PROLACTIN 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., 1960Prolactin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84516-6 1. Prolactin-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:
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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 prolactin. 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 PROLACTIN ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Prolactin........................................................................................ 7 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 75 CHAPTER 2. NUTRITION AND PROLACTIN ................................................................................... 121 Overview.................................................................................................................................... 121 Finding Nutrition Studies on Prolactin .................................................................................... 121 Federal Resources on Nutrition ................................................................................................. 126 Additional Web Resources ......................................................................................................... 127 CHAPTER 3. DISSERTATIONS ON PROLACTIN ............................................................................... 129 Overview.................................................................................................................................... 129 Dissertations on Prolactin ......................................................................................................... 129 Keeping Current ........................................................................................................................ 131 CHAPTER 4. PATENTS ON PROLACTIN .......................................................................................... 133 Overview.................................................................................................................................... 133 Patents on Prolactin................................................................................................................... 133 Patent Applications on Prolactin............................................................................................... 153 Keeping Current ........................................................................................................................ 166 CHAPTER 5. BOOKS ON PROLACTIN ............................................................................................. 169 Overview.................................................................................................................................... 169 Book Summaries: Online Booksellers......................................................................................... 169 Chapters on Prolactin ................................................................................................................ 171 CHAPTER 6. PERIODICALS AND NEWS ON PROLACTIN ................................................................ 173 Overview.................................................................................................................................... 173 News Services and Press Releases.............................................................................................. 173 Newsletter Articles .................................................................................................................... 175 Academic Periodicals covering Prolactin................................................................................... 175 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 177 Overview.................................................................................................................................... 177 U.S. Pharmacopeia..................................................................................................................... 177 Commercial Databases ............................................................................................................... 178 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 181 Overview.................................................................................................................................... 181 NIH Guidelines.......................................................................................................................... 181 NIH Databases........................................................................................................................... 183 Other Commercial Databases..................................................................................................... 185 The Genome Project and Prolactin ............................................................................................ 185 APPENDIX B. PATIENT RESOURCES ............................................................................................... 191 Overview.................................................................................................................................... 191 Patient Guideline Sources.......................................................................................................... 191 Finding Associations.................................................................................................................. 193 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 195 Overview.................................................................................................................................... 195 Preparation................................................................................................................................. 195 Finding a Local Medical Library................................................................................................ 195 Medical Libraries in the U.S. and Canada ................................................................................. 195 ONLINE GLOSSARIES................................................................................................................ 201
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Online Dictionary Directories ................................................................................................... 203 PROLACTIN DICTIONARY....................................................................................................... 205 INDEX .............................................................................................................................................. 293
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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 prolactin 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 prolactin, 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 prolactin, 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 prolactin. 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 prolactin, 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 prolactin. 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 PROLACTIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on prolactin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and prolactin, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “prolactin” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Improvement of Sexual Function in Male Patients after Parathyroidectomy for Secondary Hyperparathyroidism Source: Journal of the American College of Surgeons. 193(5): 486-492. November 2001. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: Clinically, the severity of uremia is known to be inversely proportional to sexual desire and activity in patients with chronic renal (kidney) failure. This article reports on a study of sexual function and sex hormones in male patients with symptomatic hyperparathyroidism before and 3 months after parathyroidectomy. From October 1998 to December 2000, 20 male patients with symptomatic secondary hyperparathyroidism were enrolled in this study. They underwent total
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parathyroidectomy and autotransplantation of 90 milligrams of tissue to the subcutaneous tissue of the forearm or thigh. The patients all had regular sexual partners and were sexually active. Results showed that hemoglobin, hematocrit, testosterone and LH (leutenizing hormone) were noted to have not significantly changed 3 months after surgery. Serum levels of calcium, phosphorus, alkaline phosphatase, FSH (follicle stimulation hormone), and iPTH (intact parathyroid hormone) were significantly reduced, as were the levels of prolactin. But preoperative and postoperative FSH levels were within normal limits, and 70 percent of the postoperative alkaline phosphatase levels were above normal. Sexual function increased significantly 3 months after parathyroidectomy, as did monthly frequency of attempted intercourse, satisfaction of attempted intercourse, and enjoyment of intercourse. The authors conclude that sexual function of male patients with symptomatic hyperparathyroidism can possibly be improved by parathyroidectomy and autotransplantation. An appendix reprints the individual items of the International Index of Erectile Function Questionnaire. 5 tables. 18 references. •
Reproductive Endocrinology and Pregnancy in Women on Hemodialysis Source: Seminars in Dialysis. 6(2): 105-116. March-April 1993. Summary: The prevalence and natural history of the clinical and hormonal aberrations caused by end-stage renal disease (ESRD) in women are largely unknown. In this article, the authors summarize what is known and theorized about the endocrine function of women undergoing dialysis. Topics include menstrual function, the role of gonadotropin production in the regulation of menstruation, hypothalamic and pituitary regulation of gonadotropin production, the clinical significance of menstrual irregularity, prolactin in women on dialysis, the etiology of elevated prolactin levels, the physiology of prolactin regulation, the clinical significance of hyperprolactinemia, sexual function, pregnancy in women with ESRD, infertility, the diagnosis of pregnancy and accurate pregnancy dating, pregnancy complications, pregnancy outcome in mild and moderate renal insufficiency, pregnancy outcome in hemodialysis, congenital anomalies in pregnancy in women on dialysis, dialysis in pregnant women, the use of erythropoietin (EPO) in pregnancy, therapeutic abortion, and obstetrical management.
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Lactation in Insulin-Dependent Diabetes Source: Progress in Food and Nutrition Science. Volume 14. 1990. p. 333-370. Summary: This article investigates factors that influence successful breastfeeding in women with insulin-dependent diabetes mellitus (IDDM). Topics include lactation in women with diabetes; hormonal changes in pregnancy and lactation; the role of prolactin in initiating lactation; thyroid hormones; milk synthesis; prolactin and insulin interrelationship; the role of insulin deficiency in diabetic lactation, including mammary gland metabolism; glucose transport, and RNA/DNA syntheses; insulin deficiency and breast milk of women with diabetes, including milk macronutrient composition, milk yield, hypoglycemia, breast milk macronutrient composition of women with diabetes, breast milk volume, and effect of metabolic control; maternal plasma nutrient levels, including plasma glucose, milk glucose, milk lactose, plasma lipids, postpartum lipids, and postpartum amino acids; additional factors that may influence lactation in women with IDDM, notably weight gain during pregnancy, prior lactation experience, method of delivery and feeding frequency, hospital protocol, mastitis, gestational age, fetal condition, metabolic control and insulin needs, dehydration, and maternal dietary intake; and the lactation management of women with IDDM. 1 figure. 1 table. 139 references.
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Diabetes and Erectile Dysfunction Source: Clinical Diabetes. 19(1): 45-48. February 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article provides clinicians with information on the etiology, diagnosis, and treatment of erectile dysfunction (ED). Awareness of ED as a significant and common complication of diabetes has increased in recent years. Studies suggest that the prevalence of ED in men with diabetes ranges from 35 to 75 percent versus 26 percent in the general population. Although the causes of ED are numerous, they generally fall into the categories of organic and psychogenic. The organic causes can be subdivided into the categories of vascular, traumatic/postsurgical, neurological, endocrine induced, and drug induced. Examples of psychogenic causes include depression, performance anxiety, and relationship problems. The natural history of ED in men who have diabetes is normally gradual. Both vascular and neurological mechanisms are commonly involved. Autonomic neuropathy is a major contributor to the high incidence of ED in men who have diabetes. The first step in evaluating ED is a thorough sexual and medical history and physical examination. Although few simple laboratory tests can help identify obvious causes of organic ED, initial tests should include glycosylated hemoglobin, free testosterone, thyroid function tests, and prolactin levels. Preventive measures such as improving glycemic control and hypertension, quitting smoking, reducing excessive alcohol intake, and avoiding medications that may contribute to ED may help reduce the risk of developing ED. However, once ED has developed, oral agents such as sildenafil and yohimbine are considered first line therapy. Intracavernosal injections are an acceptable alternative for men who are not candidates for oral therapy. Mechanical therapy with vacuum assisted erection devices is also effective, and penile prosthesis is a viable option. The article is accompanied by a patient information sheet.
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Clinical Efficacy of Sildenafil in Patients on Chronic Dialysis Source: Journal of Urology. 165(6): 819-821. March 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study that evaluated the clinical efficacy of sildenafil citrate (Viagra) for patients who are on chronic dialysis and who have concomitant erectile dysfunction (ED, formerly called impotence). A total of 35 men (mean age 60.7 years) on dialysis and with ED of various etiologies (causes) were administered 25 to 100 mg sildenafil for at least 6 months. The International Index of Erectile Function (IIEF) questionnaire, a global assessment question and partner satisfaction question were used to evaluate sildenafil efficacy. Patients also reported any adverse events that occurred during treatment. Treatment was effective for 28 of the 35 men (80 percent), according to the results of the IIEF and global assessment questions. Partner satisfaction correlated with the IIEF overall response and global assessment question results. No correlation was found between sildenafil failure and patient age, the etiology of ED, duration of ED, prior treatments, testosterone and prolactin blood levels, and the duration and etiology of renal (kidney) failure. In 3 of the 35 patients, sildenafil was stopped due to intolerable headaches, and in 7 others for lack of efficacy. The authors conclude that sildenafil is an effective and safe treatment for erectile dysfunction in most patients on chronic dialysis. 1 table. 15 references.
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Music Therapy Increases Serum Melatonin Levels in Patients With Alzheimer's Disease Source: Alternative Therapies. 5(6): 49-57. November 1999. Summary: This journal article describes a study of the effects of music therapy on neurotransmitters and neurohormones in patients with Alzheimer's disease (AD). Participants were 20 male patients at the Miami Veterans Administration Medical Center. The researchers took blood tests to determine the concentrations of melatonin, norepinephrine, epinephrine, serotonin, and prolactin in the patients before initiating the therapy, immediately at the end of four weeks of therapy, and at a six week followup after cessation of the therapy sessions. Melatonin concentration increased significantly after therapy and had increased further at the six week follow-up. Norepinephrine and epinephrine levels increased after four weeks of music therapy, but returned to pre-therapy levels at the follow-up. Prolactin and platelet serotonin levels were unchanged. The authors conclude that increased levels of melatonin following the therapy may have contributed to patients' relaxed and calm mood. 2 tables, 86 references.
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Hirsutism in Women Source: Postgraduate Medicine. 107(7): 93-94,99-104. June 2000. Summary: This journal article provides health professionals with information on the clinical presentation, evaluation, and management of hirsutism in women. This disorder, which is defined as excessive male pattern hair growth, commonly affects the face, neck, extremities, trunk, breasts, linea alba, lower back, upper pubic triangle, and upper inner thighs. Many drugs can induce hirsutism, including those that have androgenic activity and those that have nonandrogenic activity. Excessive androgen can also induce hirsutism. The clinical presentation of androgen excess syndrome includes seborrhea, acne, hirsutism, alopecia, obesity, and acanthosis nigricans. When hirsutism is associated with obesity and menstrual abnormalities, the source of excessive androgen is often an ovarian androgen disorder such as polycystic ovary syndrome. Hirsutism associated with normal weight and normal menses may be caused by adrenal androgens. These androgens are elevated in late onset adrenal hyperplasia, congenital adrenal hyperplasia, Cushing's syndrome, pituitary adenomas that produce excess corticotropin or prolactin, and acromegaly. Less common causes of androgen excess hirsutism include 21-hydroxylase deficiency and 3B-,11-hydroxysteroid dehydrogenase deficiency. Patient evaluation involves obtaining an extensive clinical history, performing a physical examination, and conducting laboratory tests. Treatment options include camouflaging with heavy makeup, bleaching hair, and removing it by physical methods. Thermodestruction of the hair follicle is possible with electrolysis. A new hair removal method is photothermodestruction using a laser. Obese women who have polycystic ovary syndrome and hirsutism can benefit from weight loss. Agents that may be effective in antiandrogen therapy include oral contraceptive agents, hormone replacement, cyproterone acetate, glucocorticoid agents, GnRH agonist, spironolactone, flutamide, finasteride, ketoconazole, and cimetidine. 3 figures, 2 tables, and 40 references.
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Neuroendocrine Mechanisms in Rheumatic Diseases Source: Rheumatic Disease Clinics of North America. 26(4): i-xv,693-1042. November 2000.
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Summary: This journal provides health professionals with information on neuroendocrine mechanisms in rheumatic diseases. The journal begins with an article on the reciprocal interactions between the neuroendocrine and immune systems during inflammation. This is followed by an article that explores the roles of prolactin and gonadotropin releasing hormone in affecting the hypothalamic pituitary axis and immune responses and gender differences in autoimmunity. The next article focuses on the influence of minor and major stress factors on the onset and course of various rheumatic diseases. The fourth article examines the role of the vascular endothelial system in the pathogenesis of inflammation and systemic rheumatic diseases and the way in which the neuroendocrine system influences these mechanisms. This is followed by an article that proposes an integrative physiopathogenetic concept for understanding the development of rheumatoid arthritis (RA). The next article investigates the hypothesis that abnormalities in the production and action of gonadal and sympthoadrenal hormonal mediators occur in RA and may have a role in susceptibility, severity, and progression. The seventh article focuses on the roles of androgens and estrogens in the susceptibility to autoimmune rheumatic diseases. This is followed by an article that examines the interactions of autonomic nervous, neuroendocrine, and immune systems in RA. The next article discusses the advantages and disadvantages of glucocorticoid therapy in the continuous search to optimize glucocorticoid therapy in patients with RA. The tenth article focuses on the use of sex hormone adjuvant therapy in RA. The next article reviews the multifactorial mechanisms of bone loss in RA and the effects of androgens and estrogens on bone preservation. This is followed by an article that investigates the influence of the hormonal system on pediatric rheumatic diseases. Several articles examine neuroendocrine involvement in various rheumatic diseases, including Sjogren's syndrome, systemic lupus erythematosus, ankylosing spondylitis, fibromyalgia, and chronic fatigue syndrome. The final article reviews neuroendocrine immune mechanisms in rheumatic diseases and considers promising research. 33 figures, 23 tables, and numerous references.
Federally Funded Research on Prolactin The U.S. Government supports a variety of research studies relating to prolactin. 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 prolactin. 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 prolactin. The following is typical of the type of information found when searching the CRISP database for prolactin:
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Project Title: ACCESS TO PHYSICAL ACTIVITY AND ITS RELATION TO HEALTH Principal Investigator & Institution: Alessio, Helaine M.; Physical Education, Health and Sports Stud; Miami University Oxford 500 E High St Oxford, Oh 45056 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Animal studies on mechanisms of oxidative stress, aging, and disease often include an experimental group receiving a certain intervention and a sedentary control group to which the experimental group is compared. The common use of a control group having no access to physical activity outside the cage poses a potential intervening variable that may affect results of studies investigating health and stress, in particular, oxidative stress. Animals participating in no physical activity outside of their cage may have different endogenous prooxidant and antioxidant levels, which over time may negatively affect their health. In previous studies where differences in biomarkers of oxidative stress or health were reported between control and experimental groups, investigators may have overestimated the effects of the intervention due to the hypokinetic effects of housing on the sedentary control animals. If animal studies are intended to generalize to other primate populations, including humans, then housing conditions and access to physical activity need to be carefully considered. The purpose of this study is to compare biomarkers of oxidative stress, a variety of health parameters, age and cause of death in animals that are grouped in three distinct ways: a) living solely in a standard cage with no access to physical activity outside the cage, 2) living in a standard cage with twice weekly one hour periods of physical activity in a large box, and 3) living in a standard cage with regular access to exercise on a running wheel. Cardiovascular parameters (blood pressure, heart rate, body weight, blood lipids) will be monitored weekly over the life span of the animals. Blood samples from a tail vein will be collected biannually and analyzed for antioxidants, lipids, and prolactin. Immediately after death, various tissues will be harvested and analyzed using a hematoxin and eosin staining method, and standard autopsy procedures performed by a veterinarian. Brain, ganglia, neurotrophic growth factor, pituitary gland, tumors, and organs and tissues will be analyzed for signs of pathology and differences among the three groups. Results of this study will distinguish cardiovascular parameters, morbidity, mortality, and biomarkers of oxidative stress due to different access to physical activity over the life span. These results will provide insight about the importance of housing and physical activity when designing animal experiments to study aging, selective health parameters, and oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALCOHOL AND HYPERPROLACTINEMIA Principal Investigator & Institution: Sarkar, Dipak K.; Professor Ii and Director; Animal Sciences; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 31-JAN-2008 Summary: (provided by applicant): There are several reports showing evidence for the existence of high levels of prolactin (PRL) in chronic alcoholic men and women. The study conducted by us during the past funded period provided data that suggest that chronic ethanol administration not only elevates plasma levels of PRL but also increases proliferation of pituitary lactotropes. We also found that ethanol affects the expression of estrogen-responsive hormones and polypeptides that promote growth and transformation of lactotropes. Hence, we hypothesized that, like estrogen, chronic
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ethanol might promote tumor development in lactotropes.The present proposal will address this issue by studying ethanol's in vivo and in vitro effects on lactotropic cell secretion, growth and transformation using the rat as an animal model. The proposed research will test the hypothesis that ethanol may cross-talk with estrogen receptors, an estrogen-responsive signaling cascade or estrogen-regulated cell-cell communication to control prolactin secretion and lactotropic cell proliferation. Specific proposal objectives are: (1) to evaluate the mechanisms of ethanol action on PRL gene transcription by determining the role of G protein-coupled D2 receptors and cAMP-PKA-CREB signaling, and the role of TGF-beta, estrogen receptors and p42/p44 MAP kinase; and (2) to determine the cellular action of ethanol on lactotrope proliferation by testing the role of estrogen receptors, G proteins, cAMP, PKA, PKC and MAPK in the ethanol actions. To study the mechanisms of ethanol action on lactotropes, we will pharmacologically and genetically manipulate the signal transduction systems, and measure the intracellular level of these signal transducers by histological, biochemical and molecular techniques.These studies have the potential to elucidate important cellular mechanisms underlying the ethanol effect on prolactinomas. Such knowledge will improve the understanding and management of hyperprolactinemia in alcoholic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL EFFECT ON HUMAN LACTATION AND INFANT BEHAVIOR Principal Investigator & Institution: Mennella, Julie A.; Member; Monell Chemical Senses Center 3500 Market St Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 24-SEP-1998; Project End 31-JAN-2008 Summary: (provided by applicant): The overall goal of the proposed research is to investigate the effects of maternal ethanol consumption from the perspective of both the lactating mother and her child. Research conducted during the previous grant periods revealed that: 1) the pharmacokinetics of ethanol, like a wide variety of other drugs, may be altered during lactation; 2) maternal ethanol consumption reduces milk production, disrupts milk ejection and alters the hormonal profile of the mother; 3) maternal ethanol consumption decreases milk intake and disrupts sleep-wake patterning in the breast-fed infant; 4) the ethanol that lactating mothers consume distinctly flavors human milk and such flavor changes are detected by the infant; and 5) children's hedonic response to odors of alcoholic beverages are related to the emotional context in which their parents' experience alcohol and their frequency of drinking. The proposed studies are designed to investigate the mechanisms underlying these changes, with a practical aim of providing information on a much neglected area in scientific research. To meet these objectives, research will focus on the effects of ethanol on the physiology and behavior of the lactating mother (AIMS 1 and 2) as well as her developing infant and child (AIMS 2 and 3).AIM 1: To investigate the effects of lactational state on ethanol pharmacokinetics as well as the effects of ethanol consumption on the endocrine milieu of lactating women and how such alterations impact upon lactational performance.AIM 2: To assess how ethanol consumption by the mother impacts upon her behaviors, moods and interaction with her child.AIM 3: To explore the role of early experiences with ethanol in mothers' milk and the emotional context of such experiences, on the recognition of, and preference for, the sensory properties of ethanol Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOCHEMICAL MARKERS IN THE NURSES' HEALTH STUDY COHORT Principal Investigator & Institution: Hankinson, Susan E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUN-1989; Project End 31-MAR-2004 Summary: We propose to analyze blood samples in a nested case-control manner from the 32,826 participants in the Nurses' Health Study (NHS) who provided samples in 1989-90 and were 43 to 69 years of age at that time. The samples have been stored at greater than or equal to 130 C in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed after blood collection and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected samples. We propose to build upon our recent positive findings for several plasma hormones and nutrients in relation to breast and colon cancer risk, and to address new hormonal hypotheses in relation to risk of breast, ovarian and colon cancers and myocardial infarction. Specifically, we will examine (1) plasma estrogens, androgens and prolactin levels in relation to breast cancer risk in postmenopausal women, (2) a polymorphism in the catechol-O- methyl transferase (COMT) gene and risk of breast cancer, (3) DHEA, DHEAS and 5-androstene-3beta,17beta-diol and risk of breast and ovarian cancers and myocardial infarction, (4) insulin-like growth factor I and its binding proteins 1 and 3, plasma vitamin D and polymorphisms in the vitamin D receptor, and plasma antioxidant levels - all in relation to risk of breast and colon cancers. The ongoing NHS (CA40356 and HL34594) will provide follow-up and documentation of disease outcomes in addition to providing information on important covariates (such as exogenous hormone use, diet, smoking status, among others) for the proposed study. Participation in the NHS has been high: among the 32,826 women who provided a blood sample, 98 percent continue to complete questionnaires, and vital status has been documented for 99 percent. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens provide a unique opportunity to test several hypotheses of public health importance. We also propose to collect a second blood sample from about 18,000 of the women who provided a first blood sample in 1989-90. This will increase our statistical power in future analyses, and allow us to assess in detail the temporal relationships between biomarkers and disease risk and to reduce the attenuating effects of measurement error. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAIN SEROTONIN AND ANGIOTENSIN II SYSTEMS IN MIGRAINE Principal Investigator & Institution: Terron, Jose A.; Cinvestav-Ipn Av Ipn # 2508, Col Zacatenco Mexico City, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant) Long-term objectives. The brain serotonin (5-HT) system plays an important role in cerebrovascular and neuroendocrine control. These systems have been implicated in migraine. Migraine is a low 5-HT syndrome and attacks may be triggered by a massive release of 5-HT acting on sensitized receptors. This proposal will elucidate the association between the phenomena of decreased 5-HT neurotransmission and altered cerebrovascular and neuroendocrine responsiveness. Focus will be on 5-HT receptors recently implicated in migraine pathogenesis and/or prophylactic treatment (5-HT1A, 5-HTT, 5-HT2s and 5-HT2c). As a key activator of the
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hypothalamic-pituitary-adrenal (HPA) axis, the role of the brain angiotensin II (Ang II) system will be addressed. The proposal intends to shed light into the pathophysiological mechanisms of migraine, and the mechanism of action of migraine prophylactic 5-HT and Ang II drugs. Specific aims. The following hypotheses will be challenged: 1) A decreased 5-HT transmission in the brain will cause sensitization and/or up-regulation of 5-HT receptor subtypes in the cerebral vasculature and the HPA axis; treatment with a migraine prophylactic compound that target these receptors will restore 5-HT receptor function and/or expression. This may be a useful animal model for drug screening in migraine prophylaxis. 2) The response to stress, which involves sequential activation of the brain Ang II and the HPA systems, will lead to decreased brain 5-HT levels, upregulation of 5-HT receptors, and/or amplified neuroendocrine and cerebrovascular responses to 5-HT receptor activation; treatment with an inhibitor of Ang II synthesis will restore serotonergic function. Design. 1) Cerebrovascular and neuroendocrine responses to 5-HT agonists, and expression of 5-HT receptors in the cerebral vasculature and the HPA axis, will be determined in control and 5-HT-depleted Wistar rats. It will be determined whether chronic treatment with a migraine prophylactic 5-HT antagonist restore 5-HT receptor function and/or expression. 2) Brain 5-HT content, expression of 5-HT receptors in the HPA axis, and neuroendocrine and cerebrovascular responses will be determined in control and stressed (acute and chronic isolation and restraint) Wistar rats. Reversal of stress-induced changes in these variables will be attempted by chronic treatment with the angiotensin-converting enzyme inhibitor, lisinopril (i.e. a migraine prophylactic agent). In vivo cerebrovascular reactivity will be assessed by laser- Doppler flowmetry (cortical blood flow) and the 4-iodo-[N-methyl-14C]-antipyrine method (regional cerebral blood flow). In vitro cerebrovascular reactivity will be analyzed with an arteriographic chamber system. The hormonal response (ACTH, corticosterone and prolactin) will be measured by radioimmuno assay in blood samples and 5-HT receptor expression will be determined by quantitative receptor autoradiography in tissue sections. 5-HT content will be measured by HPLC in brain homogenates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BREAST DENSITY, IGF-I, & PROLACTIN, IN FOUR POPULATIONS Principal Investigator & Institution: Maskarinec, Gertraud; Clinical Sciences; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2003; Project Start 27-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The reasons for differences in breast cancer incidence by ethnicity and geographic location are not well understood. The focus of this proposal is to identify hormonal characteristics that may explain these discrepancies. Insulin-like growth factor I (IGF-I) has been proposed as a link between nutritional factors and breast cancer, in particular among premenopausal women. Prolactin directly affects the growth of breast epithelium and has been associated with breast cancer risk among postmenopausal women. Mammographic densities, a strong predictor of breast cancer risk, appear to be associated with both hormones. The objectives of this project are to compare mammographic densities among four populations at different breast cancer risk, examine the relation of IGF-I, IGFBP-3, and prolactin with mammographic densities, and investigate the relation between these hormones and mammographic density separately by ethnicity and menopausal status. All samples and mammograms were collected as part of previous epidemiologic studies in four locations: Hawaii, Japan, Arizona, and Norway. Combining data from these diverse studies provides the opportunity to examine the consistency and strength of previously observed associations. This design will allow us to include women with a
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variety of ethnic backgrounds who have experienced different life-styles and exposures. The final analysis will include 1,520 women of different ethnicities: Caucasian women residing in all four locations, Japanese women living in two locations, Hispanic women from Arizona, and Filipino, Chinese, and Native Hawaiian women from Hawaii. The age of the subjects ranges from 40 to 80 years and approximately 60% of the women are postmenopausal. All subjects were recruited as part of previous projects, were never diagnosed with cancer, have a mammogram free of suspicious lesions, and provided information on reproductive and anthropometric characteristics. Blood samples were taken after an overnight fast, for premenopausal women during the luteal phase, and stored at -70xC. Serum samples will be analyzed in the same laboratory for IGF-I, IGFBP-3, and prolactin using an ELISA assay. After scanning the mammographic images from the four locations into the same computer, one reader will perform computer-assisted quantitative mammographic density assessment. For quality control purposes, a sample of serum samples and mammograms will be analyzed in duplicate. Because serum and mammographic analyses were partially funded by the previous projects, we are only requesting funds for 900 serum analyses and 600 mammographic density assessments. The statistical analysis will include mixed models to explore the relation between hormone levels and breast density while controlling for confounders and for clustering by study location. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAV-1 IN JAK/STAT SIGNALING, LACTATION, & BREAST CANCER Principal Investigator & Institution: Lisanti, Michael P.; Professor; Molecular Pharmacology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 23-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The long-term objective of this proposal is to understand the role of caveolin-1 in i) Jak/STAT signaling, ii) lactation, and iii) the pathogenesis of breast cancer. Caveolae function as "message centers" for regulating signal transduction. Caveolin-1 (Cav-1) is the principal structural protein of caveolae membranes that are found in most cells. We mapped human CAV-1 to a suspected tumor suppressor locus (7q31.1/D7S522). In addition, the Cav-1 gene is mutated (P132L) in up to 16% of human breast cancers. The aim of this proposal is to test the hypothesis that Cav-1 expression is important for regulating lactation via modulation of Jak/STAT signaling and that loss of Cav-1 contributes to the oncogenicity of breast cancer cells. To test this hypothesis, we will use a variety of complementary in vivo approaches, such as i) a Cav-1 null mouse model and ii) the development of transgenic mice that express dominant-negative Cav-1 (PI32L) found in human breast cancers. The three Specific Aims of the project are: 1) To determine the role of Cav-1 in negatively regulating Jak/STAT signaling. We will examine the effects of Cav-1 on the activation of Jak/STAT signaling in cultured mammary epithelial cells that are responsive to prolactin. Our preliminary results indicate that Cav-1 negatively regulates Jak/STAT5a signaling by inhibiting Jak-mediated phosphorylation of STAT5a; 2) To examine the role of Cav-1 in lactation and epithelial cell hyperplasia. Signaling from the hormone prolactin vial the Jak/STAT pathway controls normal mammary gland development. Thus, if Cav-1 were a negative regulator of Jak/STAT signaling, we would predict that a loss of Cav-1 expression leads to premature lactation. Indeed, our preliminary results show that Cav1 null mice exhibit premature lactation, as well as hyper-activation of the Jak/STAT5a signaling cascade; and 3) To determine if transgenic expression of Cav-1 (P132L) predisposes towards mammary tumor development. For this purpose, we will generate
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Cav-1 (P132L) mice that transgenically express this form of Cav-1 in the mammary gland. Our preliminary results indicate that Cav-1 (P132L) acts in a dominant-negative fashion in cultured cells. In addition, our preliminary results with Cav-1 null mice show early development of wide-spread mammary epithelial hyperplasia. We predict that this phenotype will be accelerated Cav-1 (P132L) transgenic mice. We will cross Cav-1 (P132L) transgenic mice with other well-established models of mammary tumorigenesis, such as MMTVErbB2 and MMTV-polyoma middle T mice. It is expected that these studies will contribute fundamental knowledge towards understanding the role of Cav1 in Jak/STAT signaling and mammary tumorigenesis in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTER FOR WOMEN'S HEALTH AND REPRODUCTION Principal Investigator & Institution: Fazleabas, Asgerally T.; Professor; Obstetrics and Gynecology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The objective of the Specialized Cooperate Centers Program in Reproductive Research (SCCPRR) at the University of Illinois is to conduct innovative basic and clinical research in the reproductive sciences. Four projects are proposed Projects I (Project by Fazleabas) and II (Project by Bulun) focus on the etiology and pathophysiology of endometriosis while Projects II (Project by Gibori) and IV (Project by Nowak) address important questions relating to decidualization and implantation in rodent models, however, will be directly applicable to understanding the physiology and pathobiology of human reproduction. Project I "Endometriosis in the Baboon"-will test the hypothesis that the development of endometriosis occurs in two distinct phases. The data generated will determine if ovarian steroids are necessary to first establish to first establish the disease and if local steroid biosynthesis will maintain it. This project will also establish a direct link between endometriosis and aberrations in uterine receptivity. Project II "Hormone Action in Endometriosis"will test the hypothesis that progesterone resistance in endometriotic tissue disrupts the induction of the key estradiol (E2) metabolizing enzyme 17beta- hydroxydehydrogenase (HSD) type 2. A major goal is to determine whether aberrations in nuclear receptor expression causing progesterone resistance and the absence of 17beta-HSD-2 giving rise to increased tissue 32 levels are responsible for altered cell fate in endometriosis. Project III "Cell Signaling and Gene Regulation in Decidual Development" will focus on the functional role of decidual- derived proteins. Using transgenic mice mod3els, the role and regulation of cell cycle inhibitors, activin A and prolactin in the development and maintenance of the decidua during pregnancy will be evaluated. Project IV "EMMPRIN Regulates Metalloproteinases in the Endometrium" tests the hypothesis that an inducer of metalloproteinases (EMMPRIN) that is secreted by uterine epithelial cells regulates metalloproteinase (MMP) production in the endometrium. These studies will focus on the importance of MMPs in implantation and determine if EMMPRIN expression is required for MMP production by endometriotic tissue. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula and support 7 other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of the U54 application. The U54 Center at the University of Illinois will be established within a strong interactive and collegial environment and in an institution that has a rich history in reproductive research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLOSTRUM FROM MOTHERS TREATED WITH CYCLOSPORINE Principal Investigator & Institution: Thiagarajan, Kristina D.; None; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): The candidate's long-term goal is to develop interventions that support women who require immunosuppressive therapy during their childbearing years to achieve optimal health. The immediate goal is to describe and compare the quantity of immune factors and prolactin present in colostrum from those mothers' treated with immunosuppresive agents and those mother's who are not. To achieve these goals, a focused research career development plan is proposed, including intensive study of: (1) lymphocytes, cytokines and immunoglobulins in relation to colostrum and breast milk, (2) immunsuppression in women during lactation, (3) and longiturdinal design. Increasingly, women after organ transplants and/or with autoimmune diseases who are treated with immunosuppressive drugs become pregnant and interested in breast-feeding. Over 50% of infants born to cyclosporine and tacrolimus treated mothers are low birth weight (LBW) and preterm compared to 5% in the general population. The benefits of administering colostrum to this high-risk infant population are substantial. However, since cyclosporine and tacrolimus is excreted in breast milk, breast-feeding is not recommended, despite current studies that report infants do not absorb detectable amounts of cyclosporine. No studies have described the effects of cyclosponne or tacrolimus on the immune factors of colostrum that are so valued for the infant. The purpose of the proposed study is to investigate the effects of cyclosporine and tacrolimus on specific immune factors found in breast milk (IL-1b, IL4, IL-10, IgA, IgE, IgG, and IgM) and prolactin that are known to have a direct relationship with cyclosporine and tacrolimus in the adult systemic immune system. Specific aims include measuring immune factors, prolactin and levels of cyclosporine and tacrolimus in colostrum on days 1 and 3, post partum. Mothers will be 18 to 45 yrs of age and approximately 20 treatment-subjects and 20 control-subjects will be recruited and matched according to post partum duration. We will measure immune factors and protactin by method of ELISA. Tacrolimus and cyclosporine will be quantified using HPLC method and lymphocytes utilizing flow cytometry. Data analysis will include descriptive statistics, Students' t-test to make comparisons and Pearson's Product moment for correlations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COPPER TRANSPORT IN LACTATION Principal Investigator & Institution: Linder, Maria C.; Professor of Biochemistry; Chemistry and Biochemistry; California State University Fullerton 800 N State College Blvd Fullerton, Ca 926313599 Timing: Fiscal Year 2004; Project Start 10-FEB-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Many aspects of the mechanisms by which Cu is taken up from the blood plasma by different kinds of cells (including the transporters and delivery proteins involved), and just how (after cell entry) Cu finds its way to specific secretions, remain to be defined. We have obtained evidence that lactation profoundly alters the tissue distribution of newly absorbed Cu, diverting most of it from the liver and kidney to the mammary gland, where it rapidly appears in the milk and in milk ceruloplasmin. Cu in milk ceruloplasmin may be more bio-available to the infant than the other forms of Cu in the milk, which have not been well defined. A polarized cell culture model responsive to lactational hormones has been developed for studying
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milk production by mammary epithelial cells. Mutant rodent models lacking specific proteins that could be involved in the steps required for uptake of Cu by mammary gland and its delivery to developing milk are available. The long term objective is to understand how Cu distribution and transport are regulated under normal conditions and in gestation and lactation. The immediate objectives are to determine how Cu from the exchangeable plasma pool enters mammary (and hepatic) cells, under normal conditions and in lactation, to explain the marked changes in distribution observed in the latter condition (what potential membrane transporters are involved, and how their expression and/or disposition is changed by lactation). The objectives are also to determine how, after cell entry, copper is routed to the milk and milk cemloplasmin; the role(s) of ATOX1, WND and/or MNK in this process and in regulating the copper content of the milk; and to further define the copper components of mammalian milk. Expression of potential transporters will be measured at the mRNA and protein levels, by Real Time PCR and immunoassays, respectively; and localization will be followed with immunofluorescence and confocal microscopy. Alterations in expression will be induced in the cell culture model with lactational hormones, transfection, and antisense oligos. Effects of natural and knockout mutations of specific transporters in whole animal models on copper distribution and transport will be determined. Cu uptake and its emergence in milk and milk ceruloplasmin will be followed with 67Cu/64Cu and immunoprecipitation. Effects on Cu uptake of specific antibodies against membrane transporters will be measured. Cu binding components in milk secretions will be characterized. It is expected that the proposed studies will greatly advance our knowledge of how Cu is distributed to cells from the blood and particularly how mammary epithelial cells put Cu into components of the milk that may have specific effects on the infant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECIDUAL PROLACTIN IN NORMAL AND PATHOGENIC PREGNANCIES Principal Investigator & Institution: Handwerger, Stuart; Professor of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-APR-1981; Project End 31-MAR-2008 Summary: (provided by applicant): Decidualization is critical for favorable uterine receptivity of the blastocyst during implantation and the survival of the embryo. Nevertheless, relatively little is known about the transcription factors and signaling molecules that regulate this vital process. We have demonstrated that human fibroblasts isolated from decidual tissue are precursors of decidual cells and that these cells are an excellent model system to study the regulation of decidualization. Using DNA microarray and RT-PCR analyses, we have identified and categorized many genes not previously known to be regulated during the decidualization process, including the transcription factors Ets-1, fork head in rhabdomyosarcoma (FKHR), Twist, and Id3. We subsequently showed that Ets-1 induces expression of the prolactin gene, which is a specific marker of decidualization; and others recently showed that FKHR induces prolactin gene expression. The overall goal of this proposal is to test the hypothesis that Ets-1, FKHR, Twist and Id3 are critical components of the genetic program that directs human decidualization. Our specific aims are to test the hypotheses that 1) Ets-I and FKHR, which are up regulated early during decidualization, induce a cascade of transcription factors and signaling molecules that are critical for hormone production and other biochemical processes essential for human decidualization and decidual cell function; 2) Twist and Id3, which are critical for the differentiation of several cell types,
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are important for maintaining the differentiated state of decidual cells; and 3) the expression of Ets-1, FKHR, Twist and Id3 during decidualization is coordinately regulated by cAMP and Ets-1. The first and second specific aims will utilize experiments with adenoviruses that express the transcription factors as well as antisense oligonucleotides that block their translation. The third aim will utilize transient transfections, gel shift assays, and site-directed mutagenesis. Since abnormalities of decidualization are frequent causes of spontaneous human abortion, a better understanding of the genetic program involved in decidualization may lead to the development of new drugs that will be useful in the treatment of infertility. The studies should also provide new insight into the mechanisms involved in the induction of prolactin in other extra pituitary tissues (such as lymphocytes and brain) and the genetic programs used by other human progenitor cells during differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECIDUAL SIGNALS IN THE ESTABLISHMENT OF PREGNANCY Principal Investigator & Institution: Soares, Michael J.; Professor; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The establishment and maintenance of pregnancy require the appropriate development of a specialized maternal tissue, referred to as decidua. Decidual cells arise from uterine stroma via the actions of progesterone, form intimate relationships with placental structures, and facilitate the development of the embryo. Among the important functions of decidual cells are their hormone/cytokine producing capabilities. Hormone/cytokines related to prolactin (PRL) are prominent decidual cell secretory proteins and include, decidual/trophoblast prolactin-related protein (d/tPRP). The uteroplacental PRL family contributes to the regulation of uterine inflammatory cell responses accompanying pregnancy. D/tPRP has been shown to associate with heparin containing molecules in the extracellular matrix and specifically interact with eosinophils. Eosinophils are a part of the maternal inflammatory response and must be controlled in order to ensure the establishment of pregnancy. We hypothesize that the decidual cell product, d/tPRP, participate in the modulation of maternal adaptations to pregnancy, including mediation of the anti-inflammatory actions of progesterone. In this research project, we propose to investigate decidual cell signaling. In Aim 1 we propose to identify cellular responses to d/tPRP. Aim 2 focuses on determining mechanisms underlying the interactions of d/tPRP with heparin and eosinophils. Under Aim 3 we examine d/tPRP- eosinophil interaction in vivo. The planned research utilizes cellular and molecular and in vitro and in vivo strategies. Data derived from the proposed experimentation will improve our understanding of the nature of decidua cell signaling and the role of the decidual PRL family in the regulation of viviparity. These findings will provide considerable insight into the etiology of developmental disorders associated with pregnancy failure and will also have important ramification on our understanding of the control of eosinophil functions in aberrant processes such as immune disease and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE AND IRON IN RESTLESS LEGS SYNDROME Principal Investigator & Institution: Earley, Christopher J.; Associate Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007
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Summary: (provided by applicant): Restless Legs Syndrome (RLS) is a common sensorymotor disorder whose symptoms predominans Legs Syndrome (RLS) is a common sensory-motor disorder whose symptoms predominant at night and often lead to significant sleep loss and changes in one's quality of life. Like Parkinson's disease, restless legs syndrome is exquisitely sensitive to dopamine agents and aggravated or precipitated by dopamine antagonists. Previous studies and our pilot data are consistent with an involvement of brain iron and dopamine in the pathogenesis of RLS. Based on that data we have proposed that RLS symptoms result from altered dopaminergic mechanisms, which are precipitated by a relative or absolute reduction of iron in the brain. Prior PET and SPECT studies found small decreases in D2R binding potentials and one study have reported abnormal prolactin release. These studies were all done during the day when subjects are asymptomatic and therefore the clinical relevance of the findings is in question. Prior studies have also suggested the presence of brain-ironinsufficiency state in restless legs syndrome. Although the obvious iron-dopamine relation is tyrosine hydroxylase's dependency on iron as a co-factor, animal studies suggest a more dynamic effect of CNS iron reduction on dopaminergic function. Of relevance to this Project is that iron-deficiency animals show similar CNS DA abnormalities to those observed in the limited PET studies of restless legs syndrome. This project is designed to assess abnormalities expected in the tuberoinfundibular (prolactin pulsatility), Nigrostriatal (Pet imaging of midbrain and striatum) and mesolimbic (PET imaging of nucleus accumbens) DA systems. Our general model leads to the following hypotheses to be tested in this project: (1) PET and pulsatile prolactin indices of the dopaminergic activity will be altered in RLS patients compared with controls; degree of abnormalities noted in these indices will correlate (2) with CSF and/or MRI indices of brain iron status and/or (3) with clinical symptom severity. A 4PET procedure will assess D2R binding potential and Bmax; DAT; and DA release (amphetamine challenge) in the N. Accumbens, Striatum, and Substantia Nigra of RLS and control subjects. Prolactin will be measured at 10-minute intervals to determine release and pulsatility values. Using CSF and MRI measurements of iron will assess the CNS iron status. RLS severity will be based on subjective (rating scale and diary) and objective (PSG) measurements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF SSRI THERAPY ON SPERM FUNCTION AND QUALITY Principal Investigator & Institution: Ellington, Joanna E.; Health Research & Educ Ctr; Washington State University-Spokane 601 W 1St Ave Spokane, Wa 99201 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications in the US. The majority of individuals (55%) receiving SSRIs for treatment of their depression are between the ages of 18 and 50. Thus, clinical depression commonly occurs and is treated concurrent with the reproductive years in an individual's life. Recent statistics suggest that at least 2.5 million men of reproductive age are exposed to SSRI therapy annually. In spite of the large number of individuals taking SSRIs, there is currently little information on their potential impact on sperm function, and specifically on sperm chromatin (DNA) integrity. A critical role of sperm chromatin integrity in normal reproduction has been recognized. Specifically; sperm with high levels of chromatin damage can lead to fertility disorders including: infertility, early embryonic losses spontaneous abortions, and even possible pathology in children. Recent preliminary data by the PI and others suggest a possible risk to sperm chromatin integrity for patients on SSRI therapy.
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Therefore, we hypothesize that SSRI therapy deleteriously affects sperm chromatin integrity in reproductive age men. A pilot study is proposed which aims to evaluate sperm chromatin integrity before and during SSRI therapy in clinically depressed male patients (treated group) versus depressed male patients undergoing psychotherapy alone (control group). In addition, other aspects of sperm function such as cell numbers and motility, as well as levels of sexual dysfunction and hormone concentrations will also be compared for these two groups of men. This proposal offers a unique interdisciplinary approach, combining expertise in clinical psychopharmacology and reproductive physiology to evaluate the impact of a commonly prescribed SSRI on sperm chromatin quality, and to determine if a patient profile exists for those men most at risk of such sperm chromatin damage during SSRI therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENDOCRINE REGULATION OF MATERNAL BEHAVIOR Principal Investigator & Institution: Bridges, Robert S.; Professor of Biomedical Sciences; Veterinary Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-MAY-2005 Summary: The long-term goal of this project is to identify the neural and neurochemical mechanisms underlying the regulation of maternal behavior and to elucidate potentially novel mechanisms of neural plasticity associated with the expression of maternal behavior in the adult mammal. The specific hypothesis that will be tested is that the induction, maintenance, and retention of maternal care are under endocrine regulation by a neural lactogenic system, a system that displays significant plasticity as a function of reproductive experience. The first series of studies will examine the role of the neural prolactin (PRL) receptor in the initiation of maternal behavior. Using a rat model, we will determine whether placental lactogens, like PRL, act via the PRL receptor to stimulate the onset of behavior. A second study will use the novel PRL receptor antagonist, S 179D-PRL, which will be administered centrally to test the hypothesis that activation of the PRL receptor by lactogenic hormones around the time of birth is essential for the normal onset of maternal care. The third study using ISHH will measure how pregnancy concentrations of progesterone (P) and estradiol affect expression of mRNA for neural PRL receptors. Then, central sites of P action will be examined to see how P affects the onset of maternal care and to delineate a mechanism of P's action in the initiation of maternal behavior. A second series of experiments will determine the involvement of the endocrine system in ongoing maternal care. First, the effects of exposure to PRL-secreting ectopic pituitary grafts on pup-directed maternal care and maternal aggression will be measured. Then, the effects of central administration of the PRL receptor antagonist, S179D- PRL, will be examined in lactating rats. The third set of experiments will delineate the role of the endocrine system in the retention of maternal behavior: The involvement of PRL in the opioidmediated establishment of the retention of maternal behavior will be assessed. Finally, the effects of prior maternal experience on activation of the neural lactogenic system will be measured to see whether prior maternal experience up-regulates the brain PRL system and makes the female more sensitive to her own neural hormones. The results of these investigations will delineate common endocrine and neurochemical regulators of maternal care in mammals, present a new model for examining neuroplasticity in the adult female, and provide a basis for evaluating the effects of endocrine and neurochemical imbalances on mother-young interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENDOMETRIUM DECIDUALIZATION
GENE
REGULATION
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Principal Investigator & Institution: Tseng, Linda; Professor; Ob, Gyn, and Reproductive Med; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 31-JAN-2004 Summary: The long-term goal of this study is to determine the function of transcription factors expressed during endometrial cell decidualization. We hypothesize that a handful of transcription factors regulate the downstream target gene activation to develop deciduoma receptive to the embryo and to maintain diversified biological functions during pregnancy. To pursue the proposed study, human endometrial cell culture which recapitulates the process of decidualization in vivo has been established. Using this system we have elucidated the progestin-induced production of insulin-like growth factor binding protein-1 (IGFBP-1), the major secretory protein of decidual cells. We have also identified the essential cis-elements in the promoter of the, IGFBP-1 gene. These cis-elements provide molecular tool to analyze the functions of decidual cell transcription factors. The proposed study has four specific aims: Aim 1 will identify and characterize the transcription factors that regulate the activation of the IGFBP-1 gene. The study will focus on the modes of action of the binding proteins of C/TCAAT, CRE , Sp1 and GATA motifs and progesterone receptor (PR) of PRE motif. Aim 2 will determine the functions of the transcription factors, described in aim 1, in the promoters of prolactin (PRL), PR, and fibronectin (FN) in stromal/decidual. Aim 3 will determine how these transcription factors act on the endogenous gene, IGFBP-1, PRL, PR and FN. Aim 4 will determine the effects of estrogen, progesterone and synthetic steroids, agonists/antagonists on the mRNA levels of the functional transcription factors. Results obtained from the proposed study will help us to understand how the transcription factors control the process of decidualization in the human endometrial stromal/decidual cells. This information can be applied to improving the fertility regulation, tissue-specific fertility control, treatment of implantation failure and pregnancy disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPOUNDS
EPIDEMIOLOGIC
EVALUATION
OF
PERFLUOROOCTYL
Principal Investigator & Institution: Raymer, James H.; Research Triangle Institute Box 12194, 3040 Cornwallis Rd Research Triangle Park, Nc 27709 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: This epidemiologic study will evaluate the potential endocrine and reproductive ramifications in human males of exposures to environmental concentrations of perfluourinated chemicals, including perfluourooctylsulfonate (PFOS) and perfluoroocatanoate (PFOA). Products containing these chemicals were recently withdrawn from the market by a major manufacturer amid concerns of persistence, toxicity, and widespread population exposures to these chemicals. The proposed study will focus on the semen quality and endocrine status of a potentially susceptible subpopulation, i.e., men of couples who present at a fertility clinic. It will use a casecontrol design in that the study population will include a high prevalence of men experiencing reproductive problems ("cases") as well as men with a normal fertility status ("controls"). By using a case-control design (the approach of choice for investigating rare outcomes), the study will be able to efficiently detect any important exposure-related reproductive problems. If exposure levels are associated with male
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reproductive problems, the study participants are expected to represent a range of exposure to PFOA and PFOS, which will be measured in samples of blood and semen; concentrations in these biological media will reflect the multi-route exposures to these chemicals experienced by virtually all people in our society. Semen quality will be assessed using both routine measures and a test designed to more accurately and reproducibly assess normal, motile, and fertile sperm. Measurements of Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin, Estradiol and free and total Testosterone will reflect the hormonal status of the males and will provide evidence of perturbed endocrine function. If the exposure effect is limited to a sensitive subset of the general population, our study is more likely to detect an association compared to studies that sample on PFOA/PFOS exposure status in an occupational setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTOGENS, DIETARY ENERGY AND PITUITARY TUMORIGENESIS Principal Investigator & Institution: Shull, James D.; Professor; None; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 15-AUG-1995; Project End 31-MAY-2004 Summary: Estrogens play a central role in the regulation of cell proliferation in numerous mammalian tissues and are inextricably implicated in the etiology of several major human cancers. The prolactin (PRL)-producing lactotroph of the rat anterior pituitary gland provides a valuable model for studying regulation of cell proliferation by estrogens. It is well established that estrogens stimulate lactotroph proliferation and induce development of PRL-producing pituitary tumors in several different inbred rat strains. Clinical observations indicate that estrogens act similarly in the human anterior pituitary gland. We have demonstrated that estrogens induce pituitary tumors in F344 and ACI rats by stimulating cell proliferation and inhibiting apoptosis. A 40 percent restriction of dietary energy consumption was demonstrated to virtually abolish estrogen induced pituitary tumorigenesis in the F344 rat, not by inhibiting estrogen induce cell proliferation, but by modulating the ability of estrogen to inhibit apoptosis. Interestingly, these effects of dietary energy restriction were not observed in the ACI rat strain, strongly suggesting that different molecular mechanisms regulate lactotroph proliferation and death in the F344 and ACI rat strains. Using a genetic approach, we demonstrated that the ACI alleles of at least 2 genes act in a dominant manner to confer the pituitary growth response of the ACI rat to estrogens. Herein we propose 4 specific aims to characterize further the genetic bases of estrogen induced pituitary tumor development in the ACI rat and to begin to elucidate the molecular mechanisms through which dietary energy restriction modulates, in a rat strain specific manner, the homeostatic equilibrium between proliferation and death in the lactotroph population. Specific Aim 1 is to define the genetic bases underlying estrogen induced pituitary tumor development in the ACI rat strain. Specific Aim 2 is to map quantitative trait loci (QTL)that confer the tumorigenic response of the ACI rat pituitary gland to estrogen. Specific Aim 3 is to generate congenic rat strains which carry, on the BN genetic background, ACI alleles of QTL that confer the tumorigenic response of the pituitary gland to estrogen. Specific Aim 4 is to compare the effects of dietary energy restriction on the ability of administered estrogen to induce pituitary tumor development in F344, ACI and F344/ACI FI progeny. The research proposed herein will ultimately lead to the identification of genes that are involved in the regulation of lactotroph proliferation and death by estrogens and will reveal how the actions of these genes are modulated by dietary energy consumption. We believe that this new knowledge may have broad implications for other estrogen regulated cell populations and will thereby contribute
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significantly toward our efforts to prevent and treat cancers in which estrogens are etiologic factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FETAL REGULATION
MEMBRANE
AQP
EXPRESSION/AMNIOTIC
FLUID
Principal Investigator & Institution: Ross, Michael G.; Professor and Chair; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Amniotic fluid (AF) is an essential accompaniment of normal pregnancy, necessary for fetal movement, growth and development. Excess (polyhydramnios) or deficient (oligohydramnios) AF volume is associated with significant perinatal morbidity. Despite the critical importance of AF volume, there is a lack of understanding of mechanism(s), which result in AF volume abnormalities. The intramembranous pathway of AF fluid absorption (across the amniotic membrane) has recently been recognized as a critical regulatory path for AF resorption, contributing importantly to AF volume homeostasis. Yet the underlying molecular and cellular mechanisms for water absorption across the amniotic membranes remain unknown. Aquaporins (AQPs) are cell membrane water channel proteins that greatly enhance cell membrane water permeability. Of the 11 mammalian AQPs identified to date, our studies detected the expression of three AQPs (AQP 3, 8 and 9) in human and ovine chorioamniotic membranes and placenta. In situ hybridization reveals that AQP8 is expressed in epithelial cells of human amnion and chorion, as well as trophoblasts of placenta. In addition, the investigators have demonstrated that AQP8 gene expression is maintained in a human amnion epithelial cell line, and AQP8 gene expression in amnion cells is upregulated by second messenger cAMP. In view of preliminary studies, the investigators hypothesize that AF water absorption occurs via, and is regulated by, select AQP water channels in the chorioamniotic membranes. The investigators propose to: 1) Characterize the temporal and spatial expression of water channels (AQP 3, 8 and 9) in both human and ovine fetal membranes, and correlate its change to known changes in AF volume dynamics throughout pregnancy in sheep; 2) Investigate the endocrine (oxytocin, prolactin) and second messenger camp regulation of AQPs gene expression in human amnion cell line in vitro; and 3) Explore endocrine and cAMP regulation of epithelial AQPs gene expression in vivo and determine the effect on AF volume. Our objective is to determine the regulatory mechanisms of fetal membrane AQP expression and delineate the role of AQPs in AF homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF THE DECIDUAL TISSUE Principal Investigator & Institution: Gibori, Geula; Professor; Physiology and Biophysics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-DEC-1978; Project End 31-JAN-2008 Summary: (provided by applicant): The establishment and maintenance of pregnancy requires the coordinate activity of a specialized maternal tissue, the decidua. Extensive investigation from our and other laboratories has established that decidual cells are able to produce hormones and cytokines, and to express steroidogenic enzymes. The overall objective of our research is to understand the involvement of these decidua-derived factors in the maintenance of the proper milieu for fetal development. Gene knockout strategies have revealed a crucial role for prolactin (PRL), Interleukin-11 (IL-11) and for
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decidual steroidogenic enzymes, 5alpha-reductase type 1 (5alphaR1) and 20ahydroxysteroid dehydrogenase (20alphaHSD), in the normal progress of pregnancy in rodents. The focus of this grant application is to define the role, regulation and interaction of these decidua-derived factors. The first specific aim centers on the role of decidual-PRL in the inhibition of IL-6 and caspase-3, genes involved in inflammation and cell death respectively. Using both PRL and IL-6 knockouts as well as primary decidual cells and cell lines, we propose to examine whether it is indeed IL-6 expression that leads to fetal death in the PRL (-/-) mice, whether pregnancy can be salvaged by generating double knockout mice for PRL and IL-6, and by preventing IL-6 production in the PRL null mice. We will also determine the molecular mechanism by which PRL silences the decidual expression of the IL-6 gene. Another objective of this specific aim is based on our findings that dPRL acts as a survival factor preventing the expression and activation of the cell death inducer, caspase-3, in the decidua. We will examine the mechanism by which dPRL prevents the activity of this executioner caspase, and determine whether PRL inhibition of caspase 3 is at the transcriptional level and involves the Akt/forkhead pathway. The second aim will focus on the role of decidual IL-11 in the normal progress of pregnancy and more specifically on the reason why IL11Ralpha gene deletion leads to small decidua and to uncontrolled trophoblast invasion. Finally, in the third aim, we will examine the regulation and the role of decidual steroidogenic enzymes in the maintenance of pregnancy. We will examine the mechanism by which PRL prevents decidual 20alphaHSD expression and whether PGF2a stimulates its expression at the end of pregnancy. We will also examine whether 5alphaR1 is not expressed in the IL-11Ralpha null mice causing high levels of circulating estradiol and precipitating fetal death. We will also test the hypothesis that fetal death in 5alphaReductase type 1 null mice is due to the inhibition of IL-11 signaling in the decidua by high levels of estradiol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF THE PRL RECEPTOR COMPLEX IN BREAST CANCER Principal Investigator & Institution: Clevenger, Charles V.; Associate Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 16-APR-1996; Project End 31-MAR-2007 Summary: The neuroendocrine hormone prolactin (PRL) is an important growth and differentiation factor for the human breast. The mediation of these effects of PRL on breast issues occurs through the prolactin receptor (PRLr), a Type I transmembrane receptor and member of the cytokine receptor superfamily. Within the breast, four structurally and functionally distinct PRLr isoforms (the long, intermediate, deltaS1, and PRLBP) are expressed. The extracellular binding of ligand by the PRLr isoforms initially induces receptor dimerization and phosphorylation that activates intracellular PRLrassociated signaling proteins The triggering of these PRLr associated signaling networks results in the enhanced growth and motility of human breast cancer cells. Our laboratory has demonstrated that tyrosine phosphorylation of the PRLr is necessary for these actions. PRLr action is also modulated by stimulation with extracellular matrix, indicating the presence of signaling intermediaries between the integrins and the PRLr. We have recently demonstrated that the complex of the transmembrane protein SHPS1 and the protein tyrosine phosphatases (PTP) SHP1 and SHP associate with the deltaS1 PRLr and undergo tyrosine phosphorylation following PRL stimulation. Additional data have also revealed that the SHPS1/SHP1/SHP2 complex, in turn, can modulate the
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signaling and function of associated receptors. Given these findings, it is the central hypotheses of this proposal that phosphorylation of the PRLr isoforms and their interaction with the SHPS1/SHP1/SHP2 complex contributes to the in vitro motility and in vivo progression of human breast cancer. This hypothesis will be tested by three specific aims using tissue culture and xenograft models of human breast cancer. First, the mechanism and functional significance of PRLr isoform phosphorylation will be examined through molecular approaches. Second, the phosphorylation, association, and role of the SHPS1/SHP1/SHP2 complex during the PRLr signaling will be assessed by over-expression of wild type and mutant forms of these proteins. Third, the role of the phosphorylated PRLr isoforms and the SHPS/SHP1/SHP2 complex to breast cancer motility and metastasis will be evaluated. These studies will provide insight into the function of the newly discovered PRLr isoform and the associated SHPS1 complex, further mapping the function of PRL within the breast. Such structure/function analysis of the PRLr isoforms may ultimately provide the basis for novel therapeutic strategies aimed at interrupting the function of the PRL/PRLr complex in human breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE SEQUENCES INVOLVED IN PROLACTIN ACTION Principal Investigator & Institution: Yu-Lee, Li-Yuan; Associate Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 15-MAR-1998; Project End 31-MAR-2004 Summary: The long term objective of this proposal is to understand how prolactin (PRL) regulates cell proliferation and differentiation. To study multiple components along the PRL-stimulated mitogenic pathway, we cloned and characterized the PRL receptor (PRL-R), a member of the hematopoietin/cytokine receptor superfamily, and a panel of early response genes (transcription factors, cytokines, cytokine receptors) and delayed early response genes, such as RNUDC. The structure and function of two of these genes will be analyzed: the PRL-R which mediates the mitogenic effects of PRL, and RNUDC, whose synthesis is a result of PRL-stimulated cellular proliferation. AIM number 1 analyzes PRL-R domains involved in interacting with signaling proteins. How the PRL-R intracellular domain tyrosine residues serve as docking sites for recruiting the transcription factors Stat1 and Stat5 will be examined by mutagenesis, transfection, gel sift and in vitro interaction assays. The significance of PRL-R interaction with the enzyme 2',5- oligoadenylate synthetase (OAS), which was identified as a PRL-R interacting protein by yeast two-hybrid genetics, will be addressed. PRL-R truncations will be used to determine the site of PRL-R/OAS interaction, and OAS sense and antisense constructs will be used to address potential OAS function in PRL-R signal transduction. AIM number 2 addresses RNUDC structure and function. Genetic complementation studies in Aspergillus nidulans have shown that rat RNUDC is a functional homologue of a nuclear movement protein in the fungus; however, its function in mammalian cells is unclear. Our localization of RNUDC staining to the centrosome/Golgi region suggests the exciting possibility that RNUDC may play a role in centrosome/Golgi structure and/or function. A series of biochemical, pharmacological, genetic and immunofluorescence microscopy studies are outlined to determine the cellular localization of RNUDC, and to address potential RNUDC function by sense and anti-sense strategies in mammalian cells. Finally, the identity of a 50 kDa RNUDC interacting protein will be determined by microsequencing. These combined studies should provide new insights into the signaling mechanisms, signaling molecules, and gene sequences involved in PRL regulation of cell proliferation. On a
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Prolactin
broader scale, these studies may elucidate important steps in cellular growth controls and provide insights into neuroendocrine-immune system interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF SUSCEPTIBILTY TO MMTV INDUCED MAMMARY TUMORS Principal Investigator & Institution: Ross, Susan R.; Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-MAY-1987; Project End 31-JAN-2003 Summary: All animals, including humans, show differential susceptibility to infection with viruses. Study of the genetics of susceptibility or resistance to specific pathogens is most easily studied in inbred mice. We have been using mouse mammary tumor virus (MMTV), a retrovirus that causes mammary tumors in mice, to study virus/host interactions. These studies have focused on understanding the mechanisms which determine genetic susceptibility to MMTV- induced mammary tumors and the regulation of virus gene expression in vivo. Genetic susceptibility may be determined by the ability of different mouse strains to regulate MMTV expression. Because MMTV infects both the immune system and mammary gland, it has acquired transcriptional regulatory regions that control its expression in these tissues. We will focus on 2 of these regions, the mammary gland enhancer and the STAT (Signal Transducers and Activators of Transcription) recognition element. To determine the role of the STAT family of transcription factors in mammary gland and lymphoid tissue expression of MMTV we will identify the factors that interact with the STAT consensus sequence and elucidate their in tissue-specific and cytokine-, lipopolysaccharide- or prolactinmediated regulation of MMTV transcription using transfection studies and transgenic mice. We will also identify, characterize and clone the transcription factor that controls mammary gland-specific expression. Finally, we have found a genetic locus in C3H/HeN mice that confers dominant susceptibility to MMTV infection. We will determine what step in the infection pathway is controlled by this locus, perform genetic linkage analysis using PCR-based microsatellite markers to determine its chromosomal location, establish a physical map of the region and use cloned large genomic fragments (YAC/BAC) to create transgenic mice as a functional means to test candidate loci and clone the susceptibility gene. The results obtained from these studies will greatly increase our understanding of the genetic mechanisms which viruses use to infect their hosts and how genetic resistance to such viruses in the hosts occurs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLYCOPROTEIN PROCESSING GLUCOSIDASES Principal Investigator & Institution: Vijay, Inder K.; Professor; Animal Science; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The ultimate objective of our research is to understand the structure/function relationships of the components of the biochemical machinery for protein glycosylation and the molecular basis of their gene expression during animal growth and development. The focus of investigation is on the biosynthesis and regulation of Nlinked glycoproteins in the mammary gland during its ontogeny. The biosynthesis of the precursor carbohydrate unit of these proteins is initiated by a stepwise, dolichol-linked assembly of the tri-branched Glc3Man9GlcNAC2-P-P-dolichol followed by its transfer en bloc to the nascent polypeptide in the RER. Subsequently, an extensive re-modeling
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of the oligosaccharide moiety occurs to give rise to completed glycoproteins. Glucosidases I and II are critically juxtapositioned in the post-translational maturation phase of N-linked glycoprotein synthesis since the sequential action of these two enzymes serves as a trigger for the oligosaccharide processing and polypeptide folding machinery for glycoprotein maturation in the secretory pathway of the cell. Inhibition of glucosidases I and II has been shown to interfere with normal folding, transport and egress of glycoproteins from the ER and cause accumulation and degradation of the malfolded glycoproteins. The impairment of oligosaccharide processing has been shown to affect the biological activity of many glycoproteins, transport of receptors of the cell surface, myoblast fusion, virus assembly and infectivity, reversal of the transformed phenotype of cells in vitro, and inhibition of tumor cell metastasis in vivo. Based on preliminary studies, we propose to pursue the following specific aims: 1 and 2. Identify the active site of amino acid residues and the catalytic nucleophile of glucosidases I and II by a combination of labeling with novel photoaffinity probes, conjugation with a suicide substrate and mutagenesis of selected evolutionary conserved nucleophiles and acidic residues in the enzymes; 3, Express catalytically active recombinant forms of Glucosidases I and II, and determine the crystal structure of the enzymes; 4. Investigate the significance of subunit interaction in the regulation of glucosidase II during the development and lactogenic differentiation of the mammary gland. N-linked glycoproteins, with diverse and versatile sugar moieties, represent the largest class of glycoproteins, participate in myriad biological phenomena, and are implicated in numerous pathologies, including malignancy, atherosclerosis, many genetic disorders and host-viral interaction leading to AIDS. Transgenic biotechnology can potentially provide the mammary gland as an excellent bioreactor for a 'molecular pharming' of glycoprotein pharmaceuticals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GORDON RESEARCH CONFERENCE ON PROLACTIN Principal Investigator & Institution: Melmed, Shlomo R.; Professor and Director; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 02892 Timing: Fiscal Year 2002; Project Start 27-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): We are requesting funding for three (3) Prolactin Gordon Research Conferences to be held in Ventura, California in the Winters of 2002, 2004 and 2006. These successful research meetings have been held biannually since 1982 and are dedicated to cutting-edge discussion on aspects of prolactin expression, secretion, action and pathophysiology. In recent years, the content has also included growth hormone action, especially in light of the common phylogenetic origin and signalling action of the two hormones. A program committee comprising recognized experts, is elected for each subsequent meeting by participants, as are a Chair and a Vice-Chair who assumes the Chair, thus ensuring continuity, and avoiding duplication of content. The meeting lasts from Sunday evening through Thursday evening and attracts about 130 scientists, trainees, graduate students and endocrinologists. The budget includes expenses to support speaker registration and travel, as well as trainee travel awards. Support includes Gordon Conference support, philanthropy and this NIH request. The foci of this year's meeting include pituitary development, new technologies, behaviour, pituitary regulation, novel analogs, PRL and GH physiology and signalling, and the role of PRL and GH in cancers. This request will ensure continuation of this highly regarded meeting which has contributed to the large body of new knowledge in the prolactin field that has been generated over the past 18 years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Prolactin
Project Title: GROWTH FACTOR INVOLVEMENT IN PITUITARY FUNCTION Principal Investigator & Institution: Kudlow, Jeffrey E.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-JUN-1991; Project End 31-MAY-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONAL AND DEVELOPMENTAL REGULATION OF GENE EXPRESSION Principal Investigator & Institution: Rosenfeld, Michael G.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-MAR-2006 Summary: Understanding the molecular mechanisms by which specific cell types develop from a common primordium in the anterior pituitary gland represents a basic question in molecular and developmental biology. Under this Grant, we analyzed the roles of Pit-1, cloned and characterized Prop-1 as the hypomorphic allele causing the Ames genetic dwarfism, and identified disease alleles in human pituitary combined hormone deficiency syndrome; identified the signaling molecules from ventral diencephalon and opposing signaling gradients that dictated the positional commitments of organ and cell-type determination events, and provided the initial evidence of the roles of induced transcription factors as the "molecular memory" of the transient signaling gradients. In this competitive renewal application, we propose to investigate the role of a series of transcription factors, including the members of the Six, Pax, GATA and Pitx families, and of specific co-activators, in nearly and late developmental events. The roles of specific protein-protein interactions, and coactivators and co-repressors, on their actions will be considered, and we propose to identify artificial target genes that mediate their biological actions. The role of signaling factors, including Shh, BMP, Wnt and retinoic acid, will be further explored using in vivo and in vitro approaches. The mechanism of Pit-1 lineage determination will be explored, with experiments directed at understanding the activation of the early Pit-1 gene enhancer, regulation of the Pit-1 lineage by Prop-1, and the mechanisms of control by Pit-1 of the terminal differentiation of three pituitary cell types. The allosteric effects of cognate Pit-1 DNA binding sites on these events will be explored structurally, and in vitro, and the role of co-repressor complex assembly will be investigated. This research proposal extends the approach used over the current grant period, which has been the most successful in our 22 years under this grant, combining biochemical and genetic approaches to investigate potentially important regulatory proteins, and systematically exploring the functional role of the novel proteins. We believe that these experimental approaches will provide insights into the intriguing problems of organ and cell-type differentiation, and cell-specific patterns of gene activation, with clear implications for human diseases that are caused by abnormalities of these developmental events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONAL CONTROLS OF PLACENTAL ANGIOGENESIS Principal Investigator & Institution: Linzer, Daniel I.; Professor; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-AUG-1988; Project End 31-MAY-2003
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Summary: Rapid growth of a network of blood vessels in the uterus and placenta upon implantation of the mammalian embryo is required for the exchange of nutrients and waste products between the mother and the fetus. The formation of the vasculature at this site presents several critical regulatory problems, which will be explored in the mouse. Unlike other vessels, uterine vessels that reach the placenta do not reseal at the growing end, but instead release blood into pools called blood sinuses; placental cells directly contact the maternal blood in these sinuses, enabling an efficient exchange of metabolites and gasses and the rapid distribution of placental-hormones throughout the maternal bloodstream. Another unusual feature is that vessel growth is prevented through the outer layers of the placenta; if vessels from the mother and fetus did not cross these layers, two consequences would be the exposure of the fetus to maternal immune cells (which would attack the fetus as foreign) and extensive (possibly fatal) vessel rupture and hemorrhaging at birth. our recent results suggest that we have discovered two of the key regulators of uterine-placental neovascularization in the mouse, proliferin and proliferin-related protein, which are both members of the prolactin/growth hormone family of protein hormones and are, respectively, major positive and negative regulators of blood vessel growth (angiogenesis) secreted by the placenta. This discovery makes several predictions about how the unique aspects of angiogenesis at the implantation site are regulated. Proposed experiments, using transgenic and targeted gene disruption mouse models, will test the hypothesize physiological roles of proliferin- related protein in the temporal and spatial restriction of vessel growth. Other studies will investigate the signal transduction pathways through which proliferin induces, and proliferin-related protein inhibits, angiogenesis. This research has direct implications for the management and treatment of infertility and pregnancy-related disorders, but may also provide novel insights into the process of vascularization to human disease, for example in cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL INDUCTION ANIMAL MODEL OF PROSTATE CANCER Principal Investigator & Institution: Bosland, Maarten C.; Professor; Environmental Medicine; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 12-JAN-1999; Project End 31-DEC-2003 Summary: Combined treatment with testosterone (T) + estradiol-17beta (E2) induces prostate adenocarcinomas in 100 percent of NBL rats, and T alone a 40 percent incidence. This is the only model in which steroid hormones alone produce a high prostate cancer incidence; it offers opportunities to study the mechanisms whereby steroid hormones cause prostate cancer. We hypothesize that E2, either formed endogenously from T by the enzyme aromatase or exogenously administered, acts via a genotoxic mechanism that involves the generation of reactive oxygen species to produce prostate carcinomas in the presence of T, and that estrogen receptor (ER)-mediated mechanisms are not involved. To address the hypothesis and resolve some uncertainties about the model, the following specific aims are proposed. Aim 1: To establish whether E2 is an essential factor in the hormonal induction of prostate cancer by T, and whether it acts via a mechanism that is ER-independent; we will establish whether treatment with an aromatase inhibitor reduces or eliminates prostate cancer induction by T, and to demonstrate that antiestrogen treatment does not affect the tumor response. Aim 2: To determine whether induction of oxidative DNA damage and of prostate carcinomas by T and E2 are linked and, therefore, probably causally related; we will administer antioxidant vitamins (C and E) to T+E2-treated rats, which should reduce both prostate
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Prolactin
cancer induction and prostatic oxidative DNA damage (measured by formation of 8hydroxydeoxyguanosine). Aim 3: To demonstrate that T+E2-induced carcinomas have the potential to metastasize and determine whether T+E2-induced peripheral prostate dysplasia can progress to cancer; we will determine whether lowering of the E2 dose or shortening of the E2 treatment duration, while continuing T administration, will sufficiently lower or delay pituitary tumor formation and prolong survival to allow progression of prostate carcinomas to the metastatic stage. Aim 4: To establish whether T+E2- induced prostate carcinomas are androgen-sensitive and their induction is androgen-dependent and prolactin-independent; we will test the response of prostate cancers transplanted into syngeneic rats to castration and determining the effect of castration of T+E2-treated rats at a time at which very small carcinomas have already formed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL REGULATION OF BREAST CANCER Principal Investigator & Institution: Rosen, Jeffrey; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1978; Project End 31-JAN-2007 Summary: (provided by applicant): The long-term objectives of these studies are to elucidate the mechanisms by which hormones regulate the normal development of the mammary gland and milk protein gene expression, and to determine how these regulatory mechanisms have deviated in breast cancer. This proposal addresses the question of why the same hormones, which promote growth and terminal differentiation during normal mammary gland development, result in aberrant growth in the majority of breast tumors. Specific emphasis has been placed upon studying the mechanisms by which the lactogenic hormones, prolactin and glucocorticoids, regulate the expression of milk protein genes. These studies have established that composite response elements containing multiple binding sites for several transcription factors, including CCAAT/enhancer binding protein (C/EBP) beta, nuclear factor (NF) I, signal transducers and activators of transcription (Stat)5, and the glucocorticoid receptor (GR) mediate the hormonal and developmental regulation of milk protein gene expression. Analysis of C/EBP beta knockout (KO) mice revealed alterations not only in functional differentiation, but also surprisingly in ductal morphogenesis and lobuloalveolar development. These studies led to the hypothesis that steroid hormone regulated mammary epithelial cell (MEC) proliferation occurs via paracrine/juxtacrine mechanisms mediated by local growth factors, and that a switch to an autocrine signaling mechanism is an early event in the progression to breast cancer. To test this hypothesis we propose to combine mouse genetics with the in situ analysis of signal transduction pathways. Transgenic, conditional KO and KO-transplant mouse models will be employed for these studies. The following specific aims are proposed: 1. To elucidate the mechanisms by which C/EBP beta regulates ductal morphogenesis and lobuloalveolar development. 2. To analyze steroid receptor distribution, cell proliferation and local growth factor expression in several KO mice known to affect lobuloalveolar development, including PrlR, Stat5 A & B and p27 KO mice. 3. To utilize a novel, ligand-independent, drug inducible fibroblast growth factor receptor transgenic mouse model to understand the role of local growth factors in cell proliferation and lobuloalveolar development. 4. To utilize novel transgenic and conditional mouse models to study the role of beta-catenin in mediating Wnt signaling during mammary gland development. 5. To understand the role of C/EBP beta, Stat5 and GR in hormonally regulated chromatin remodeling.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONE, CYTOKINE, AND GENETIC RISKS FOR RA IN WOMEN Principal Investigator & Institution: Karlson, Elizabeth W.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a highly disabling autoimmune disease with reduced survival that disproportionately affects women 3 to 4 times more frequently than men. Clinical, epidemiological and animal studies suggest a role and potential interaction between genetic factors, sex steroid hormones, and inflammatory cytokines on risk of RA, but these interrelationships are poorly understood. The overall goal of this study is to define the contribution of serum hormones, inflammatory markers and genetic factors in the etiology of RA in women using a prospective nested case-control design. The proposed study uses 3 ongoing cohorts, the Nurses' Health Study (NHS), the Nurses' Health Study II (NHS II), and the Women's Health Study (WHS). Blood samples were collected and archived since 1989 from 90,572 cohort participants. The study will be almost three times larger than the next largest prospective study. We will use a validated method to ascertain RA cases; we expect to confirm 1200 incident cases overall and will have archived blood samples available for 500 cases. Specifically, we hypothesize that low plasma total and free testosterone, low DHEAS, and low levels of prolactin are positively associated with subsequent risk of RA among women and men. Similarly, elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6) are prospectively associated with increased risk. We will also examine the association of genetic polymorphisms in the progesterone, estrogen, and androgen and receptors, as well as the association of polymorphisms in corticotrophin releasing hormone, CYP19, and tumor necrosis factor genes with risk of RA. The large size (>500 RA cases) and prospective nature of the proposed study, along with the availability of archived blood samples and data on other RA risk factors, provides a unique opportunity to further our understanding of the etiology of RA in women. Ultimately, this study could lead to the identification of potential targets for therapeutic interventions to treat RA or to reduce the risk of this serious autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN PROLACTIN ANTAGONIST AS A CHEMOPREVENTIVE AGENT Principal Investigator & Institution: Chen, Wen Y.; Assoiate Professor; Microbiol & Molec Medicine; Clemson University 300 Brackett Hall Clemson, Sc 296345702 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The involvement of human prolactin (hPRL) in breast cancer has been recently established based upon its autocrine/paracrine proliferative effects in mammary tumor epithelial cells. More importantly, recent evidence suggests that hPRL may constitutively activate oncogene HER2/neu through activation of JAK2 kinase. Although the molecular events involved in this cross activation is not well understood, it is believed that constitutive phosphorylation of HER2/neu contributes to poor prognosis and unsatisfactory clinical response of HER2/neu positive breast cancer to anti-HER2/neu monoclonal antibody therapy. The purpose of this two-year pilot study is to identify the alteration of gene expression in the mammary gland resulted from the interaction between hPRL and HER2/neu, more
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importantly between a hPRL antagonist (G129R) and HER2/neu, using bi-transgenic mouse models. We are especially interested to test the hypothesis that G129R can be used as a chemopreventive agent to prevent or delay the onset of HER2/neu initiated breast cancer and identify those genes involved in this process for future studies. Our specific aims are (1) to establish bi-transgenic mice by cross-breeding male mouse metallothionein I promoter (MT) hPRL transgenic mice (MT/hPRL) and MT/G129R transgenic mice with female MMTV/neu transgenic mouse to generate bi-transgenic lines (MT/PRL+MMTV/neu and MT/G129R+MMTV/neu), (2) to monitor the rate of breast tumor formation in bi-transgenic mice to determine the role of hPRL in HER2/neu induced breast tumor and the efficacy of potential chemopreventive effects of G129R, (3) to use commercial cDNA microaray services to identify alterations in gene expression in the mammary tissue of the bi-transgenic mice to identify genomic signatures of hPRL, G129R and HER/neu interaction. We hope that the results from this pilot study will not only contribute to a better understanding of the HER2/neu positive breast cancer but also lay a solid foundation for further studies to define therapeutic targets for HER2/neu positive breast cancer as well as to develop HER2/neu specific tumor inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOPITUITARISM: CHARACTERIZATION
CLINICAL
&
MOLECULAR
Principal Investigator & Institution: Radovick, Sally M.; Section Chief; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAR-2005 Summary: Pituitary development and hormone expression in mammals is controlled by pituitary-specific transcription factors including: Rpx, Lhx3, Prop-1 and Pit-1. These factors initiate a cascade of development events resulting in mature pituitary cell-types and mutation or deletion of the genes encoding these factors have been shown to result in anterior pituitary hormone deficiency in mammals. A consistent feature of these animal models is GH deficiency associated with either TSH and/or prolactin deficiency. Many patients have been described with complete or partial deficiency of hormone secretion from these cell types. However, in many cases, the pituitary function has not been carefully evaluated and patients are frequently diagnosed as having 'idiopathic' GH deficiency. My laboratory and others have described a genetic basis for combined pituitary hormone deficiency (CPHD) in man due to point mutations in the Pit-1 and Prop-1 genes. We and others have also discovered Pit-1 and Prop-1 mutations in patients with presumed idiopathic GH deficiency. These observations demonstrate that mutations in these genes may be a frequent cause of not only CPHD, but also 'isolated' GH deficiency. In addition, mutation or deletion of other pituitary developmental factors (Rpx, also 'isolated' GH deficiency. In addition, mutation or deletion of other pituitary developmental factors (Rpx, Ptx2 and Lhx3) has been associated with pituitary hormone deficiencies. This proposal will clinically characterize patients with hypopituitarism and investigate the structure of candidate genes. Study of mutations in pituitary transcription factors and their diverse pathophysiological mechanisms should increase our understanding of anterior pituitary gland development and gene regulation in normal and disease states. The candidate is an Associate Professor of Pediatrics at Harvard Medical School and an Associate Physician at Children's Hospital, Boston, where she is the director of the reproductive endocrine unit and endocrine clinical laboratories. She has independent support to study GnRH gene expression (RO1-HD34551) and Pit-1 gene function (R01-DK53977) in mammals. She also directs a
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CRC protocol to evaluate and categorize patients with hypopituitarism. She actively mentors four BE/BC pediatric endocrinologists, a BE obstetrician-gynecologist, two of whom are funded by the intramural Endocrine training grant (T32HD07277), one funded by a mentored grant (K11DK02329), one by a Janeway fellowship award from Children's Hospital mentoring success, in an environment rich with academic opportunities, this award will allow her to increase her mentoring activities and to enhance her own commitment to patient- oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGICAL ASPECTS OF HEMORRHAGE Principal Investigator & Institution: Chaudry, Irshad H.; Professor, Professor, Vice Chairman & Di; Surgery; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-MAR-2003 Summary: Our recent studies indicate that proestrus female mice [with cycle- increased levels of estrogen and prolactin (PRL)] have improved immune responses after traumahemorrhage as opposed to markedly depressed responses in males. Moreover, the survival rate of proestrus females following sepsis after trauma-hemorrhage was significantly higher than age-matched males. In contrast to young proestrus mice, aged females (defined by lowered estradiol levels) show marked immunosuppression after trauma. Our hypothesis, therefore, is that it is the high estradiol or a high estradiol: androgen ratio which directly (receptor- mediated) or indirectly (receptor-independent) enhance immune functions in proestrus females, and the loss of these estrogenic effects may contribute to the failure to maintain immune responses in aged females after trauma-hemorrhage. Studies are proposed to determine the mechanism of regulation of estradiol and estrone by hypothalamic/pituitary factors adrenals and aromatase activity and determine how differences in estradiol levels or the estradiol: androgen ratio due to the estrus cycle, ovariectomy (OVX, in middle aged mice to reduce estrogen), and age affect immune responses after trauma. Sex steroids (SS) receptor- mediated and receptor-independent gene activation mechanisms will be studied in T-cells and macrophages (Mphi). Since activation of AF-1 and AF-2 regions of estrogen receptor (ER) is critical for agonist and antagonist effects, activation of the ER agonist regions by estrogens in T-lymphocytes will be evaluated by transfection studies. Moreover, since SS non-ligand response also involve [Ca2+]i mobilization, T cells and Mphi will be examined for Ca2+ signal transduction and the expression and translocation of PKC isoforms. The release of TH1 and TH2 cytokines and IL-6 and the effects of PRL on their release in proestrus, OVX, aged, ER-, and PRL-knockout mice will also be evaluated. Additionally, the effect of SS on PRL and TH1 and TH2 cytokine-induced JAK-STAT expressions will be evaluated. Analysis of bone marrow for lymphoblastoid/myeloblastoid cell composition, and the effect of SS on the population of these cells will be determined. We will evaluate if administration of beta-estradiol, Raloxifene or PRL in vivo after trauma-hemorrhage improves the depressed immune responses in estrogen deficient mice. If a single dose is ineffective, multiple doses of these drugs with or without gonadotropin releasing hormone (GnRH) or flutamide (androgen receptor antagonist) will be administered to determine whether synergistic beneficial effects on immune responses are produced and whether the susceptibility to sepsis after trauma is decreased. Detailed mechanistic studies of T cell and Mphi functions using molecular biological techniques to determine why low estradiol fails to maintain immune functions in aged females after trauma and the use of estradiol, Raloxifene, PRL, GnRH or flutamide to restore immune functions should yield novel
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Prolactin
information and provide an innovative approach for improving the immune responses and reducing mortality from sepsis following trauma-hemorrhage in postmenopausal as well as in surgically OVX patients with low estrogen activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOSUPPRESSANT MODULATION OF DRUG METABOLISM Principal Investigator & Institution: Brunner, Lane J.; Pharmaceutics; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: (Verbatim from Investigator's Abstract): Immunosuppressants, such as cyclosporine, are widely administered to transplant patients to prevent organ rejection. The clinical use of cyclosporine is hampered by significant toxicity to the CNS, liver and kidney. While these toxicities are related to circulating cyclosporine concentrations, they are not always predictable. Although dosing regimens exist, large inter- and intrapatient variability in pharmacokinetic parameters may complicate predicting therapeutic cyclosporine blood concentrations. The toxicity may be related to changes in hepatic or intestinal drug metabolism. Cyclosporine is known to alter its own hepatic metabolism which may be responsible for the large variability in clinical responses. The objective of the proposal is to investigate possible mechansims of immunosuppressantinduced alterations in drug metabolism, using cyclosporine as the prototype drug. The hypothesis being tested is that chronic immunosuppressive therapy causes a modulation in pituitary function leading to altered circulating levels of growth hormone and prolactin which results in decreased drug metabolism. In addition, chronic immunosuppressive therapy causes an increase in circulating transforming growth factor Beta-1 or TGF Beta-1 which results in suppressed drug metabolism. These changes, alone or in concert with one another, may explain the changes in drug metabolism seen previously with immunosuppressive therapy. In order to investigate the role of growth hormone, rats will be administered cyclosporine along with growth hormone. These studies will determine the role of growth hormone and whether or not cyclosporine changes growth hormone levels. Next the proposed studies will examine the role of prolactin. Along with cyclosporine, rats will be administered exogenous prolactin or a prolactin antagonist to determine the effects of cyclosporine on the circulating levels of this pituitary hormone. Finally, rats will be given cyclosporine and TGF beta1 to determine whether or not this cytokine has a significant role in immunosuppressant-induced changes in drug metabolism. These studies will provide information how cyclosporin and other immunosuppressive drugs may regulate hepatic and intestinal drug metabolism. This information will have direct application to transplant patients and give clinicians needed information regarding the relationship between immunosuppressive therapy and the prediction of toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPACT OF A LITTERMATE ON PSYCHOLOGICAL STRESS IN RATS Principal Investigator & Institution: Wilson, Janie H.; Psychology; Georgia Southern University Statesboro, Ga 30460 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Generally known for its reproductive role, the hormone prolactin is now known to be released in response to stress. Acute psychological stress reliably increases prolactin and affects behaviors in adult male rats;
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however, responses of adult females and juvenile males and females remain to be explored. In the proposed experiments, four psychological stressors will be examined: novel open field, noise, the conditioned-emotional- response (CER) paradigm, and nonpainful exposure to a cat. As a second component, the present slate of experiments will examine the impact of a conspecific on responses to psychological stressors by testing animals in the presence of a same-sex littermate. A third component, pretreatment with 1 mg/kg i.p. injection of the oxytocin antagonist 1-deamino-2-D-Try(Oet)-4-Thr-8-Om-oxytocith will examine the possible role of oxytocin in social buffering as measured by prolactin levels. Prolactin and individual as well as social behaviors in the stressful environments will be recorded. It is hypothesized that adult male and female rats tested alone in the chamber will have lower levels of prolactin than those tested alone in the chamber with a stressor. Low levels of prolactin are also expected in females exposed to a stressor in the presence of a conspecific, and the oxytocin antagonist is expected to block oxytocin in the pre-treated conspecific females, resulting in high levels of prolactin comparable to those found in animals tested alone with a stressor. Conversely, adult males may not experience social buffering and are expected to have high levels of prolactin in the social condition; therefore, pre-treatment with an oxytocin antagonist will not cause higher levels of prolactin as compared with the nontreated social animal. Among juvenile males and females, no such sex X treatment condition interaction is expected. Juveniles are expected to respond to stress, social buffering, and the oxytocin antagonist in a pattern similar to adult females (above). Each animal model will serve as a foundation to build an understanding of responses to stress and social buffering, particularly in nonverbal populations such as children, the aged, and adults with brain injuries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLUENCE OF LACTATION ON POSTPARTUM STRESS AND IMMUNITY Principal Investigator & Institution: Groer, Maureen W.; None; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): The long-term objectives of the research are to understand the regulation of neuroendocrine and immunological responses to naturalistic stress in postpartum women, and to determine if lactational state is associated with significant differences in these variables. It is known from animal studies that lactation confers stress resistance, which may be accompanied by immunologic protection during stress. Clinical benefits of lactating may therefore include a maternal health-protecting effect. Most of the research studies on postpartum women do not distinguish lactational state, yet all animal studies naturally are of lactating organisms. Since many women do not lactate, it is essential that knowledge of the neuroendocrinology, stress responses, immune parameters, and health effects of lactating and non-lactating women be explored to determine if any differences of importance do exist. The study will analyze relationships between lactational state and stress, hormones, immune function, and symptoms of infection. The data will provide new information about whether a lactational stress resistance exists in the human species, and if lactation confers any immunological or health benefit to the mother. The specific aims of this study are to 1) To analyze perceived stress, stressful life events, mood states, levels of stress-associated hormones, and relationships among these variables in lactating compared to non-lactating women; 2) To analyze immune variables and occurrence and severity of symptoms of common infection in lactating
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Prolactin
compared to non-lactating women; 3) To analyze relationships between stress, and mood, variables, immune variables, and incidences and severity of symptoms of common infection in lactating and non-lactating women. Maternal health, and immunity will be examined at 4-6 weeks postpartum. Stress will be measured as both life events stress and perceived stress. Mood states are determined by scores on the Profile of Mood States. Stress-associated hormones are analyzed in serum and include prolactin, oxytocin and cortisol, while immune function is assayed through cytokines, T-cell proliferation, immunoglobulin level, neopterin levels and CD markers. Symptoms of infection are measured by the Carr SCL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS AND PREVENTION OF SURGERY-INDUCED METASTASIS Principal Investigator & Institution: Ben-Eliyahu, Shamgar; Associate Professor; Tel Aviv University Ramat-Aviv Tel Aviv, Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAY-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF DEVELOPMENTAL TOXICITY OF BISPHENOL-A Principal Investigator & Institution: Soto, Ana M.; Professor; Anatomy and Cellular Biology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-AUG-2005 Summary: The increase of the incidence of malformation of the genital tract and hormone-related cancers is a main health problem in the industrialized world. Environmental estrogens are suspected to be the casual agent. The long- term goal of this proposal is to understand the mechanisms underlying the toxicity of the environmental estrogen Bisphenol-A (BPA) on the female reproductive system and mammary gland. During the first period of funding, we found evidence that perinatal exposure to low- environmentally relevant doses of BPA produces irreversible alterations in the structure and function of estrogen-target tissues in female rodents. Increased body weight, changes in morphology of the ovary, uterus and mammary gland, and alterations in pattern of estrus cyclicity suggested that perinatal exposure to BPA may decrease reproductive success, and increase the risk of mammary gland cancer. Given the similarity of toxic effects of the synthetic estrogen diethylstilbestrol in rodents and humans, our results raise concern the exposure to BPA may put human health at risk. The overall hypothesis to be tested is that perinatal exposure to BPA results in morphological and functional alterations of the hypothalamus and/or pituitary as well as estrogen sensitive peripheral organs (i.e. mammary gland) by an ERmediated process. These effects of BPA in development would in turn result in an altered response to ovarian and pituitary hormones in adulthood. The following complementary Specific Aims are proposed: Aim1: To assess the hypothesis that perinatal exposure to BPA alters a) sexual differential of the brain and b) the functionality of the circuitry involved in the luteinizing hormone and prolactin surges thus altering permanently the hormonal milieu of peripheral organs (i.e. mammary gland). Aim 2: To assess the hypothesis that in utero exposure to BPA directly affects the prenatal development of the mammary gland anlage by altering the expression of ER and downstream homeobox genes Msx2, Wnt10b). Aim 3: To assess the hypothesis that the morphological changes observed in the mammary glands are due to an altered
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response to gonadal and pituitary hormones. The responsiveness to various sex hormones will be assessed in ovariectomized mice following in utero exposure to BPA. The following techniques will be used: immunocytochemistry, in sit hybridization, quantitative PCR, morphometry, radioimmunoassays. The information obtained from these studies will considerably advance our understanding of the mechanisms underlying the developmental and reproductive toxicity of BPA. These data are needed to develop biomarkers and research strategies to apply these data to assess the toxic impact of xenoestrogens on human development and reproduction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ORDERED BINDING OF LACTOGENS AND RECEPTORS Principal Investigator & Institution: Brooks, Charles L.; Associate Professor; Veterinary Biosciences; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Human lactogenic hormones, including growth hormone (hGH), placental lactogen (hPL) and prolactin (hPRL), all bind the human lactogen receptor. Current data suggests that lactogen and receptor bind with a 1:2 ratio and the two binding reactions have affinities that differ by at least an order of magnitude. Current information suggests lactogens may be similar to hGH and the somatotropin receptor where binding is an ordered process. The ordered hGH mechanism was demonstrated by mutagenic studies, where mutation of Site 1 eliminated binding at Site 2, but mutation of Site 2 had no effect of Site 1 binding. These results documented a uni-directional interaction between the two somatotrophic sites of hGH. Similar studies have been difficult to perform with lactogens because of the low affinity of Site 2. In fact, until examined by surface plasma resonance techniques, binding at Site 2 has been difficult to consistently document. No detailed structural mechanism has been described that will account for the interaction between Sites 1 and 2 in any lactogen. Using biological assays for lactogenic activity, we have recently described a series of contiguous hydrophobic residues in hGH that may be the motif by which Site 1 interacts with Site 2. Mutation of these residues, which span from Site toward Site 2, severely reduced the activity at Site 2. The main goal of this application is to determine if this motif is responsible for the interaction between Sites 1 and 2 in hGH, hPL and hPRL. Specific Objective 1 will characterize and compare the nature of lactogen/receptor binding; determining if the two binding sites interact and the nature and degree of interaction. Characterization of the binding mechanism of hGH, hPL and hPRL must be completed before studies probing the structural motif can be interpreted. Specific Objective 2 will determine the physical nature of the motif that apparently conducts the communication between Sites 1 and 2 of hGH. These studies will determine the size of the motif and characterize the role of each member residue in the communication between the two receptor binding sites. Specific Objective 3 will determine the same or a similar motif is conserved and operation in hPL and hPRL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF ORPHANIN'S EFFECTS ON PROLACTIN RELEASE Principal Investigator & Institution: Janik, James M.; Zoology; Miami University Oxford 500 E High St Oxford, Oh 45056 Timing: Fiscal Year 2000; Project Start 01-SEP-2000; Project End 31-AUG-2004
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Prolactin
Summary: The hypothesis to be tested is that Orphanin FQ (OFQ) is involved in the physiological regulation of prolactin secretion and that this peptide's mechanism of action is at the hypothalamic level. Specifically, OFQ inhibits the activity of the tuberoinfundibular and tuberohypophyseal dopaminergic (TIDA and THDA, respectively) neurons, which produces a stimulatory effect on prolactin secretion. Furthermore, OFQ plays a physiological role in prolactin regulation and is involved in the suckling-induced prolactin increase. The hypothesis will be tested using several approaches in male and females rats. First, the mechanism of action will be examined by determining the neurochemical response to OFQ administration. DOPA accumulation will be used as index of dopaminergic activity and 5-hydroxytryptophan as an index of serotonergic activity in specific regions of the brain involved in prolactin regulation. Second, pharmacological specificity of the stimulatory effects of OFQ on prolactin release will be demonstrated by blocking this response with Acetyl-RYYRIK-NH2, an OFQ antagonist that has been shown to have antagonist activity in rat brain. Third, double-label immunocyto-chemical studies will determine the specific dopaminergic neurons in the arcuate nucleus that are inhibited by OFQ. Simultaneous expression of tyrosine hydroxylase and c-fos will be examined. Finally, the role of OFQ in mediating the suckling-induced prolactin increase will be determined by pretreated post-partum, lactating female rats with Acetyl-RYYRIK-NH2 prior to a suckling bout. The sucklinginduced prolactin increase, as well as the suckling-induced inhibition of TIDA and THDA neurons and activation of serotonergic neurons, will be quantified. The long term objectives of this research are to understand the neural regulation of prolactin release and the interaction between the prolactin releasing and inhibiting factors in different physiological states, such as lactation, as well as gender differences in the regulation of this hormone. Prolactin has many important physiological roles. It can affect reproductive functions (e.g. hyperprolactinemia is associated with oligomenorrhea) and prolactin levels are affected by stress and exercise, which influences reproductive cyclicity. In order to understand reproductive disorders or disorders due to stress, it its important to understand the nature of the connections between the various and numerous factors regulating prolactin secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LACTATION
MECHANISMS
OF
SKELETAL
RECONSTITUTION
AFTER
Principal Investigator & Institution: Miller, Scott C.; Research Professor; Radiation Oncology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2005 Summary: Maternal efficiency during reproduction is essential for species propagation. The mammalian skeleton provides mineral for the fetal skeleton during pregnancy and milk production during lactation. Dramatic changes occur in the maternal skeleton during the reproductive cycle and some may serve to protect skeletal integrity. The post-lactation period is particularly 'anabolic', but mechanistically not understood. To further define the maternal skeletal adaptations and mechanisms that occur during and after the reproductive cycle, the following aims are proposed. 1). To determine the cellular and tissue events in the skeleton during the transition from late pregnancy to lactation. We hypothesize that the increases in resorption in late pregnancy and sustained during lactation are the result of an increased rate of osteoclast formation, prolongation of lifespan and a decrease in apoptosis. 2) To determine the cellular and tissue events in the skeleton that occur during the transition from lactation to postweaning. The hypothesis is that increases in bone formation are associated with an
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increased rate of osteoblast formation but decreased resorption is the result of decreased osteoclast activity, decreased formation but increased apoptosis. 3) To determine if the post-weaning increase in calcitonin (CT) levels is correlated with decreased osteoclastic functions, and establishes the "milieu" for the post-lactational recovery phase. We suspect correlation with decreases in prolactin, but increased estrogen and initiation of estrus. 4) Is there a change in the remodeling period during the reproductive cycle in mammals? This will be determined from archived materials from a species that has intracortical bone remodeling. 5) Does moderate skeletal loading improve bone mass, structure, strength and dynamics during the post-lactation 'recovery' phase? Our hypothesis is that skeletal loading will have synergistic effects on skeletal mass and structure during this period. These studies will provide new knowledge on perhaps the most dynamic and "anabolic" period in the life of the adult female skeleton and may provide new insights into treatments of diseases after reproductive capacity has ended. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS REGULATING UTERINE MORPHOGENESIS Principal Investigator & Institution: Spencer, Thomas E.; Assistant Professor; None; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 06-APR-2001; Project End 31-MAR-2005 Summary: (Scanned from the applicant's abstract) Human infertility, pregnancy loss and intrauterine growth retardation represent major public health problems. A large number of reproductive age women experience these problems, which may be due to uterine dysgenesis, dysplasia and/or dysfunction. Long-term objectives are to understand the hormonal, cellular and molecular mechanisms regulating uterine morphogenesis. The proposed research specifically focuses on mechanisms regulating endometrial gland differentiation and development or adenogenesis. Adenogenesis is a critical period of uterine morphogenesis that occurs in the fetus in humans, but in the neonate after birth in ungulates and rodents. Studies in sheep and rodents indicate that uterine glands are unequivocally required for conceptus survival, growth and implantation. Thus, success of developmental mechanisms regulating uterine morphogenesis dictates the embryotrophic potential and functional capacity of the adult uterus. Our studies indicate that: neonatal ovine endometrial adenogenesis occurs during the first eight weeks after birth and is associated with increased levels of serum prolactin (PRL) and estradiol-17b (E2-17b); proliferating and morphogenetically active endometrial glands in the neonatal uterus express short and long prolactin receptors (PRL-R), insulin like growth factor one receptors (IGF1R), and high levels of estrogen receptor alpha (ER-a); and stromal cells surrounding the developing glands express IGF-I, IGF-II and ER-a. Both the IGF1R and the short and long PRL-Rs stimulate the mitogen activated protein kinase (MAPK) signaling cascade. In other systems, stimulation of the IGF1R can lead to activation of ER-a in a ligand independent manner by MAPK. Our central hypothesis is that PRL, E2-17b and IGFs regulate endometrial adenogenesis by activation of the MAPK signaling pathway and ER-a through ligand-dependent (E2-17b) and ligandindependent (PRL, IGFs) mechanisms. Using a multidisciplinary, collaborative approach, in vivo and organ culture systems will be used to test the central hypothesis using the neonatal ovine uterus as model system. Accomplishment of these research goals is expected to significantly advance our understanding of the developmental aspects of uterine biology, determinants of adult uterine function, and provide a foundation for the design of clinical therapies to prevent, identify and treat human reproductive problems, such is infertility and pregnancy loss due to endometrial gland dysgenesis, dysplasia or dysfunction.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF ERYTHROPOIESIS IN VIVO Principal Investigator & Institution: Socolovsky, Merav; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: The receptor for erythropoietin, EpoR, is a homodimeric cytokine receptor essential for the formation of red cells. In addition, it is the principal homeostatic regulator of red cell production rate, through a wide dynamic range. The molecular mechanisms that encode quantitative features of EpoR signaling are largely unknown, but may involve the control of apoptosis in early erythroid progenitors. Dysregulation of these mechanisms may lead to oncogenic transformation. The purpose of this proposal is to identify molecular mechanisms that encode the quantitative response to EpoR signaling, and whose dysregulation predisposes to leukemia. The following approaches will be taken: 1. The receptor for prolactin, PrlR, a non-hematopoietic cytokine receptor, can rescue EpoR-/- progenitors and support their full differentiation into red cells in vitro. This and similar findings suggest that homodimeric cytokine receptors signal through a similar, 'generic' program. Components of this program will be identified using in-vitro red-cell differentiation assays. These may be relevant to other cytokine- receptor regulated systems such as mammary epithelium 2. In spite of apparent functional similarity, PrlR and EpoR share little homology in their cytoplasmic signaling domains. Gene targeting in mice will be used to generate 'knock-in' models that allow stringent testing in vivo of as yet unsuspected adaptations by these. The hypothesis that these two receptors differ in their quantitative regulation of tissue homeostasis will be tested. 3. A novel flow-cytometry assay that allows analysis and separation of erythroid precursor populations at specific maturation stages from freshly explanted hematopoietic tissue is currently being developed by the applicant. Together with expression microarrays and other approaches, this will be used to identify EpoR gene targets and cellular functions that modulate erythropoietic rate. This approach was recently validated by looking at mice mutant for the EpoR-activated transcription factor Stat 5. This identify the anti-apoptotic Stat5-bcl-xL pathway in early erythroblasts as a determinant of erythropoietic rate. 4. Retroviral expression cloning will be used to identify new erythroid anti-apoptotic genes. Components of the apoptotic machinery will be assessed as candidate modulators of erythropoietic rate and/or leukemogenic transformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BASIS OF SNELL DWARF AND LITTLE LONGEVITY Principal Investigator & Institution: Papaconstantinou, John; Professor; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Experimental models of yeast, nematodes, fruit flies, and rodents indicate that aging and longevity are, in part, under genetic control. The nematode C. elegans, has provided genetic and biochemical evidence that identifies candidate genes that govern longevity. This involves attenuation of the daf-2, age-1 and daf-16 genes whose homologies to the mammalian-insulin receptor (InR) family and signaling pathway suggest that this pathway(s) may regulate metabolic characteristics that favor vertebrate longevity. The mouse dwarf mutants Snell (dw/dw), Ames (df/df) and little (lit/lit),
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live significantly longer than their normal siblings. The nature of the dwarf mutations, i.e., growth hormone (GH), thyroid stimulating hormone (TSH) and prolactin (Prl) deficiencies may result in physiological characteristics similar to those of the long-lived C. elegans mutants. Since these mice are the only vertebrate genetic models of longevity, and since the physiological characteristics of the "anti-aging" processes of the nematode and the long-lived dwarf mutants are strikingly similar, these mice provide an excellent resource to study the molecular and genetic processes that determine longevity in vertebrates. In this research program we will determine whether the physiological characteristics of the Snell and lit dwarf mice are longevity-determining factors of vertebrate aging. Specific Aims 1 will determine whether the Snell and lit mice exhibit such characteristics of delayed senescence as a reduction-of-function phenotype due to GH, insulin and IGF-I deficiency; immunological function; and regulation of stress response genes. In Specific Aim 2 we plan to use endocrine supplementation to determine the specific role of TH and Pr1 deficiencies as longevity-determining factors; In Specific Aim 3 we will determine the role GH deficiency in longevity using conditional transgenic Snell dwarf and lit mice in which GH expression is regulatable i.e., turned on or off at will. Our long-range goal is to elucidate the molecular and genetic basis of vertebrate life span by identifying the longevity-determining factors. Achieving these aims will identify pathways involving longevity and lay down foundations for understanding the mechanism by which these pathways act. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS OF BREAST DEVELOPMENT AND NEOPLASIA Principal Investigator & Institution: Weinberg, Robert A.; Member/ Professor; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (Applicant's Description) An understanding of the molecular mechanisms leading to human breast cancer development will come from insights into how the breast tissue develops normally. Such insights can be most easily obtained in the mouse breast, the development of which is governed by biochemical regulators very similar to those that operate to program human breast morphogenesis. Breast development is governed by bi-directional communication between the mammary epithelium and surrounding stroma. The present research examines three signalling pathways that appear to be essential for normal breast development and appear to be disrupted during cancer pathogenesis. First, estrogen acting through its receptor in normal mammary epithelial cells (MECs) does not appear to be mitogenic but has acquired such powers in many human breast carcinoma cells. The proposed research examines the possibility that these powers result from the inappropriate expression of a co-activator of the receptor that is not normally expressed in MECs. A second aspect of breast signalling involves the progesterone receptor, which is responsible for sidebranching of mammary ducts. The present research examines the possibility that this receptor, when activator by progesterone, causes expression of hepatocyte growth factor in nearby stroma; this factor then acts on MECs to induce ductal sidebranching. A third line of research examines the possibility that prolactin, acting through its receptor in MECs, is able to induce the production of the neuregulin growth factor in nearby stromal tissue; once released, the neuregulin causes MEC proliferation leading to the formation of alveoli. The latter pathway is often subverted in human mammary carcinoma cells that express the HER2 receptor of neuregulin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTIDISCIPLINARY PROGRAM IN FEMALE REPRODUCTION Principal Investigator & Institution: Albrecht, Eugene D.; Professor; Obstetrics and Gynecology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2004 Summary: The objective of the Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) at the University of Maryland Medical Center is to conduct innovative basic and clinical research in the reproductive sciences and to apply the knowledge gained from these studies to improve understanding of the etiology and treatment of infertility in women. A multidisciplinary experimental approach will be taken in this program to study function of the pituitary-ovarian- uterine axis as related to the central theme on cellular remodeling. In Project I (Karen A. Gregerson, PI), the physiological importance of an inwardly-rectifying, dopamine-activated pituitary K+ channel to prolactin secretion and fertility will be determined in transgenic mice in which the function of this novel membrane channel is interrupted by dominant-negative mutation. In Project II (Gerald J. Pepe, PI), the regulatory role of estrogen on fetal ovarian follicular and oocyte development and the impact on fertility will be assessed in baboons in which placental estrogen synthesis is suppressed in utero by administration of a novel aromatase inhibitor. In Project III (Robert D. Koos, PI), the physiological role of members of the fibroblast growth factor family, bFGF and keratinocyte growth factor, on ovarian and uterine function and fertility will be studied in transgenic mice in which the truncated, dominant-negative FGF receptors are spatially and temporally overexpressed. A combined clinical-basic research study is proposed in Project IV (Eugene D. Albrecht, PI), in which the roles of estrogen and progesterone, acting via vascular endothelial growth/ permeability factor and bFGF, on endometrial angiogenesis and fertility will be investigated in vivo in baboons and in vitro in the human endometrium. Each of the research projects will draw heavily upon the Cell Immunocytochemistry/In Situ Hybridization Core (Gloria E. Hoffman, PI) for the cellular localization of regulatory peptides and steroid hormone receptors. Integration of the scientific effort in this SCCPRR will be achieved through the thematic focus on cellular remodeling, common technological molecular approaches, and an established tradition of collaborative research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: N-3 FATTY ACID & BINDING PROTEIN MRG ON MAMMARY TUMOR Principal Investigator & Institution: Shi, Yuenian E.; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): There is an increasing public interest in chemoprevention by natural agents such as n-3 polyunsaturated fatty acids (PUFAs) DHA and EPA and the pregnancy-induced differentiation against breast cancer incidence. The mechanisms underlying these preventive effects are currently unknown. Little is known about the regional and developmental expression of locally acting factors in the mammary epithelium that interact with n-3 PUFA and exert differentiating effect during pregnancy. Within this content, a novel mammary derived growth inhibitor and a fatty acid binding protein (FABP) has recently been identified, characterized, and named Mammary derived growth inhibitor Related Gene (MRG). As a new member in the family of FABP, MRG has the highest binding affinity to n-3 PUFA DHA. The preliminary data indicate: (1) MRG overexpression suppresses breast cancer
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cell growth in vitro and tumorigenesis in vivo. (2) MRG induces differentiation of mammary epithelium and its expression is associated with human mammary gland differentiation. (3) MRG synergistically interacts with DHA in growth inhibition. The present application is to test the hypotheses that (a) MRG is a mediator for intracellular accumulation of n-3 PUFAs in mammary epithelial cells and mediates tumor suppressing effect of n-3 PUFAs on mammary tumors. In this regard, one of mechanisms for pregnancy-induced prevention may be mediated in part by PUFA composition change in mammary gland which favors the ratio of n-3 PUFAs to n-6 PUFAs following pregnancy and lactation; (b) MRG is mediator of the differentiating effects of pregnancy on breast epithelium and overexpression of MRG in young nulliparous mice can induce differentiation and protect the development of mammary tumors. We propose a series of studies of both in vitro and in MMTV/MRG transgenic mice to evaluate the role of MRG on mammary differentiation and tumorigenesis and its interaction with n-3 PUFA on mammary tumorigenesis. These studies will help to identify MRG as mediator for differentiation for mammary gland and for interaction with n-3 PUPA on inhibition of mammary tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROENDOCRINE ABNORMALITIES INDUCED BY SLEEP DEPRIVATIO Principal Investigator & Institution: Everson, Carol A.; Associate Professor; Neurology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): Sleep is a vital biological process necessary to maintain cognitive ability and physical health. Profound sleep disturbance/deprivation in humans is nearly always associated with disease, and sleep deprivation in patients is considered a high risk factor for mortality. In animal models of sleep deprivation, morbidity is associated with septicemia subsequent to a constellation of neuroendocrine changes, most notably hypothyroxinemia. Preliminary data have shown that neuroendocrine abnormalities extend to deficiencies in growth hormone (GH) and prolactin (PRL), and have the potential to explain most of the pathology induced by sleep deprivation. There is strong evidence that the neuroendocrine changes are centrally mediated. The following three specific aims are intended to test the main hypothesis that sleep deprivation results in hypothalamic dysfunction: Aim 1: To determine whether centrally-mediated hypothyroxinemia is due to deficient proTRH expression and TRH secretion in sleep-deprived animals. Proposed studies will determine whether TRH mRNA expression in the paraventricular nucleus and TRH content in the median eminence are suppressed and unresponsive to low T4, indicating impaired thyroid hormone regulation at the level of the hypothalamus. The pathway of T3 feedback to PVN neurons will be examined to determine the degree of up-regulation in response to low T4. Potential TRH responsiveness of thyrotrophs will be assessed by evaluating TRH receptor mRNA expression in the pituitary. Aim 2: To identify regulatory mechanisms responsible for reduced growth hormone and prolactin levels in sleep-deprived rats. Proposed studies will examine the regulation of PRL and GH in individual rats during the course of sleep deprivation by studying stimulatory and inhibitory mechanisms and response that could be responsible for the deficiency at the hypothalamic and pituitary levels. Aim 3: To delineate effects of sleep deprivation on thyroid hormone processing in the brain. Low thyroid hormone concentrations in sleepdeprived rats imply decreased T4 availability for import to the brain and ensuing centrally-mediated dysfunction common to the clinical hypothyroid state. Proposed
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studies will examine the content and regulation of iodothyronines in the sleep deprived brain. These studies will delineate the abnormalities in brain endocrine regulation resulting from sleep deprivation and determine the mechanisms responsible for peripheral endocrine changes that underlie its associated systemic pathologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROENDOCRINE EFFECTS OF OPIATES AND COCAINE Principal Investigator & Institution: Kreek, Mary J.; Professor and Head; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Heroin, cocaine, and alcohol addictions, alone and in combination, along with their medical complications, including hepatitis B and C, AIDS, and psychiatric comorbidity, remain the major medical problems confronting our nation and much of the world. Effective treatments must be based on a fundamental understanding of the biological basis of each addictive disease, including the effects of exposure to drugs of abuse. This Project will continue to explore the atypical stress responsivity of the hypothalamic-pituitary-adrenal (HPA) axis seen in specific addictive diseases. Contributions of opioid and dopaminergic pathophysiological mechanisms will also be investigated. The specific hypotheses are: 1) that chronic cocaine addiction causes alterations in stress-responsive HPA axis function; 2) that alterations in HPA axis function caused by cocaine may be further modulated by alcohol abuse and/or opiate dependence; 3) that the relationship between cocaine addiction and alterations in HPA axis function is controlled in part by the endogenous opioid system; 4) that the regulation and release of corticotropin releasing factor (CRF) and proopiomelanocortin (POMC; and its peptide fragments including ACTH and beta-endorphin) are, in part, under the control of the endogenous opioid system and that changes in the sensitivity of the CRF-R1 receptor in the anterior pituitary are central to the atypical stress responsivity seen in different stages of addiction; 5) that psychological states which are believed to be both stress-related and important in the development and maintenance of addictions, may occur through alterations in HPA axis function and the endogenous opioid system; and 6) that the observed alterations in the physiology of the endogenous opioid system and its interactions with the stress-responsive HPA axis in addictive diseases may, in part, be influenced by specific single nucleotide and other polymorphisms in genes of the endogenous opioid system. The hypotheses will be explored using standard and novel paradigms of HPA disinhibition (by metyrapone and dexamethasone) and stimulation (by ACTH and CRF) testing alone and in combination. The role of the endogenous opioid system in affecting the HPA axis will be studied with opioid antagonists alone and in combination with HPA axis testing. This work, to be performed in patients with specific addictions and normal volunteers, will complement rodent and non-human primate studies conducted in our Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROENDOCRINE HORMONES TO PROMOTE IMMUNE RECONSTITUTION Principal Investigator & Institution: Murphy, William Joseph.; Professor; Microbiology and Immunology; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008
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Summary: (provided by applicant): Immune deficiency following bone marrow transplantation or in AIDS leaves a patient highly susceptible to life threatening opportunistic infections. Recovery of the immune system, particularly T cell function, is often delayed for up to several years, especially in aged individuals. Thus far, while cytokines have been given clinically to accelerate myeloid recovery, very few agents have been demonstrated to promote multi-lineage immune cell recovery and fewer yet promote thymopoiesis and T cell recovery. Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to exert pleiotropic effects on the immune system. We have previously demonstrated that GH and PRL promote T cell function and restore thymopoiesis in neuroendocrine hormone-deficient dwarf mice. This proposal will now evaluate the effects of GH and PRL on immune recovery in several BMT models, comparing the effects in both young (less than 10 weeks) and aged (greater than18 months) mice. Use of these mice will allow for the assessment on the role of age on the outcome following BMT. Toward this goal, we have developed 5 specific aims: Specific Aim 1 will assess the effects of GH and PRL on immune recovery after syngeneic BMT in young and aged mice. Particular emphasis will be given to effects on the thymus and T cell recovery. Specific Aim 2 will use a thymic organ culture model to determine the mechanism underlying the effects of hormones on the thymus. Specific Aim 3 will evaluate the effects of GH and PRL in allogeneic BMT models using T cell depleted BMC to ascertain effects on host rejection mechanisms and subsequent engraftment. Specific Aim 4 will examine the effects of GH and PRL on allogeneic BMT models in which graft-versus-host disease (GVHD) occurs to determine whether GVHD is worsened after hormone treatment. Finally, Specific Aim 5 will use nonmyeloablative BMT models to determine the effects of GH and PRL conditioning on thymic recovery and engraftment of donor-derived cells. All of the Specific Aims will use young and aged mice to ascertain if age significantly impacts hormone responsiveness. Thus far, even though immune reconstitution in the aged remains a significant and growing concern, very few preclinical studies have addressed the role of age and potential use of neuroendocrine hormones to circumvent the hampered immune recovery associated with age. This proposal will thus address both basic science (role of hormones in immune development) and clinically useful (role of age in BMT procedures and use of hormones to promote recovery) issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW APPROACHES TO EVALUATION AND TREATMENT OF ACROMEGALY Principal Investigator & Institution: Freda, Pamela U.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2003 Summary: Acromegaly, a disorder of chronic, growth hormone excess, is associated with significant morbidity and mortality. Prevention of the long-term complications of acromegaly depends on both an accurate biochemical assessment of disease status and an understanding of the goals of therapy. The studies planned for the final two years of my K08 (DK02561) continue to examine new approaches to the evaluation and treatment of acromegaly utilizing a large cohort of patients with acromegaly and will focus on integrating the molecular, biochemical and clinical aspects of my initial studies. Studies will continue a careful biochemical assessment of this cohort with modern, sensitive techniques in order to further define the new criteria for cure suggested by our work to date. Studies will focus on a longitudinal follow up of this cohort examining detailed biochemical parameters and determining if certain patients are at risk for disease
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recurrence. Studies will now include a new direction, the assessment of a clinical marker of GH status, body composition analysis, and a correlation of this analysis with the biochemical measures. I will continue to analyze tumor specimens from this larger cohort for the presence of activating mutations in the alpha subunit of Gs and will determine if these mutations define a clinical phenotype and/or biochemical response to medical therapy. The studies in this proposal are a first step toward achieving a multifaceted understanding of the optimal biochemical and clinical goals for disease control of acromegaly and toward integrating the information from molecular analysis of these tumors into our treatment approach. The R03will proved vital added support in the final two years of my K08. The R03 funds will enable me to continue to employ a clinical research assistant whose help with my studies will allow me to devote the needed effort to broadening my clinical research projects and to developing my skills in clinical and basic research methods as well as new projects for future funding. My current environment continues to be ideally suited for achieving my goals. My collaboration with Dr. Kalmon Post, providing me with access to large numbers of both patients and pituitary tumor specimens, continues to be effective. I continue to receive instruction in the molecular techniques from Drs. Sharon Wardlaw and Streamson Chua. My new collaboration with Dr. Steven Heymsfield on the body composition studies will add an important new aspect to my studies. My sponsor, Dr. Wardlaw, continues to be committed to providing me with the guidance I need to pursue my research plans and to facilitate my transition to independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONTOGENY OF HEPATIC ION TRANSPORT Principal Investigator & Institution: Suchy, Frederick J.; Professor of Pediatrics; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-MAR-2003 Summary: This is a renewal application to further define the ontogeny of hepatic ion transport as well as define the mechanisms by which transporters are modified under conditions of cholestasis. The overall objective of this competing renewal application is further defined by the mechanisms underlying the expression of basolateral and canalicular transporters for bile acids and other organic anions during development and cholestatic liver disease. Since transcriptional activation of the liver Na+ /bile acid cotransporter gene (Ntcp) is largely responsible for the abrupt expression of transport activity in the perinatal period, the investigators propose that a change in chromating structure, reflected in an increase in DNASE I hypersensitivity and a decrease in gene methylation precedes the onset of transcription during development. Transgenic mice expressing various portions of the 5' untranslated region linked to the luciferase reporter gene will be used to define sequences that direct tissue- and developmental stagespecific expression of Ntcp. Transgenic animals will be used to show that the rapid postnatal increase in Ntcp transcription could in part be mediated by prolactin. To demonstrate the importance of the Na+/bile acid cotransporter to hepatobiliary function, the Ntcp gene will be rendered nonfunctional in mice by targeted disruption. The phenotypes of the mice with null mutations will be defined including whether liver disease (cholestasis) is induced and how the mutation alters hepatobiliary function and enterohepatic cycling of bile acids. The signaling mediating the targeting of the liver and ileal Na+/bile acid cotransporters to the plasma membrane will be determined through transfection and analysis of native transporters, truncated mutants lacking cytoplasmic tails, and chimeric transporters comprised of portions of the liver and ileal transporters.
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Finally, the development of the canalicular multi specific organic anion transporter (cMOAT/Mrp1) will be defined including a correlation of transport activity in canalicular membrane vesicles with levels of Mrp2 mRNA and protein. The investigators will determine the mechanisms underlying the effects of bile acids and the inflammatory cytokines TNF-alpha and IL-beta on expression of Ntcp and Mrp2 through transfection of chimeric promoter/reporter gene constructs into primary hepatocytes. DNA foot printing and gel mobility shift assays will determine the importance of known or novel cis-acting elements and trans-activating factors in regulating gene expression. These studies should provide insights into the biology and pathobiology of hepatic anion transporters and help explain the susceptibility of the infant to develop cholestatic liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARACRINE INTERACTIONS IN PROLACTIN SECRETION Principal Investigator & Institution: Shah, Girish V.; Basic Pharmaceutical Sciences; University of Louisiana at Monroe 700 University Ave Monroe, La 71209 Timing: Fiscal Year 1999; Project Start 01-MAY-1992; Project End 31-AUG-2004 Summary: Well-defined distribution of various pituitary cells types in the anterior pituitary (AP) gland suggest that Cell-to-Cell interactions play an important role in the development, function and proliferation of AP cells. Previous studies from this laboratory have shown that calcitonin- like immunoreactive peptide (pit-CT) is synthesized and secreted by cultured AP cells. It may affect lactotrope function because synthetic sCT is a potent inhibitor of PRL secretion and PRL gene transcription. Our recent studies have used immunohistological, cell culture and molecular approaches to demonstrate that putative pit-CT mRNA and pit-CT IR peptide is selectively expressed by gonadotropes and RC4B cells (tumor cells of gonadotropelineage), and not by alphaT-3, GH3 or AT20 cells. Temporally, pit-CT gene expression is initiated subsequent to, and not prior to, the expression of LH Beta-subunits because pit-CT mRNA could not be detected in alphaT-3 cells or fetal AP gland (embryonic day 19), but could be detected in the AP gland of day 20 fetal age. The studies in adult AP glands have shown that pitCT IR gonadotropes were surrounded by cup-shaped lactotropes, suggesting a role for pit-CT in juxtacrine inhibition of lactotrope function. Physiological significance of pit-CT action was demonstrated by the findings that passive immunization of pit- CT with antisCT serum caused a dramatic increase in PRL secretion under in vitro and in vivo conditions. Pit-CT IR content of the AP gland varied significantly in various physiological conditions. Three days of E2 treatment caused a nine-fold decline in putative pit-CT mRNA abundance and also caused four-fold decrease in pit-CT IR concentrations. In contrast, ovariectomy induced a three-fold increase in pit-CT IR content. Thus, pit-CT is a novel, physiologically relevant, gonadotrope-derived inhibitor of lactotrope function. Since we have obtained a putative pit- CT cDNA clone and the expression of putative pit-CT mRNA parallels the expression of pit-CT IR, an objective of the present proposal is to identify the precise role for pit-CT in maturation, function and proliferation of lactotropes during development and adulthood. Specific Aim of the proposal will develop RC4B-lactotrope co-culture model to test the role of endogenous pit-CT in lactotrope function and proliferation. Specific Aim 2 will study the consequence of gonadotrope-depletion or pit-CT overexpression on lactotrope function. Specific Aim 3 and 4 will further characterize the actions of gonadal steroids and other paracrine and neuroendocrine factors on pit-CT expression. These studies will provide new and significant findings towards the role of gonadotrope- lactotrope interactions in
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pituitary function. These results will make important contributions in understanding physiology of normal reproduction and pathophysiology of aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEGYLATED PROLACTIN RECEPTOR ANTAGONISTS AS CANCER DRUGS Principal Investigator & Institution: Sherman, Merry R.; Professor; Mountain View Pharmaceuticals, Inc. 3475 Edison Way, Ste S Menlo Park, Ca 94025 Timing: Fiscal Year 2002; Project Start 30-JUL-2002; Project End 30-SEP-2003 Summary: (provided by applicant): Effective management of human cancers of the breast and other prolactin-responsive tissues (e.g., prostate) is the long-term goal of this research. The first phase of this study involves the design, synthesis and in vitro testing of polymer conjugates of a novel mutein of human prolactin (hPRL) that appears to be more selective as an antagonist than those previously tested. This antagonist (PRLA), developed and provided by Charles L. Brooks, contains a deletion that interferes with the positive cooperative interactions between the two receptor-binding sites on hPRL. PRLA binds to the receptor, but inhibits the intramolecular signal transduction pathway involving phosphorylation of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. Polymer conjugates of PRLA will be synthesized containing 1-3 strands of linear or branched poly(ethylene glycols) (PEGs) of various molecular weights (10-60 kDa), linked by various chemistries. The optimal conjugates will have long half-lives in the circulation, high affinity for hPRL receptors, minimal agonist activity and minimal immunogenicity. Conjugates will be tested on human breast cancer cells in culture and grown as xenografs in immunocompromised mice. Tumor growth or shrinkage will be monitored non-invasively, using tumors derived from cells transfected to contain luciferase, in collaboration with Robert S. Negrin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PET IMAGING OF THE 5HT TRANSPORTER IN ALCOHOLISM Principal Investigator & Institution: Szabo, Zsolt; Associate Professor; Radiology and Radiological Sci; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Impaired serotonin (5-HT) function has been implicated as a possible factor in the biological vulnerability for alcoholism, but most studies of the 5-HT system have been performed in animals or, if performed in humans, they involved only indirect measurements to assess the 5-HT system in the brain. The status of the 5-HT neurons in the brain of living alcohol dependent individuals remains unknown. To investigate the 5-HT system of the brain, quantitative PET studies of the brain 5-HT transporter (5-HTT; an established marker of serotonin neuron integrity) are proposed using [11C]McN5652 as radioligand for four groups of human subjects: family history negative (FHN) controls, family history positive (FHP) controls, FHN recovering alcoholics, and FHP recovering alcoholics. The hypothesis to be tested is that radioligand binding to the 5HT transporter is significantly reduced as a function of both alcoholism and family history of alcoholism. Serotonin function will also be measured by quantification of plasma prolactin and cortisol increase in response to fluoxetine. The genetic aspect of 5HT impairment will be investigated by measuring the frequency of specific polymorphisms of the 5-HTT gene. The hypothesis is that FHP alcoholics and FHP controls will have a higher frequency of the s-variant allele, the allele which has been associated with reduced 5-HTT expression/function in in vitro studies. The frequency of
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the s- variant allele is predicted to be higher in subjects with reduced 5-HTT densities (as determined by PET) and with reduced hormonal responses to fluoxetine. The results of this project will lead to better understanding of the role of serotonin in the biological vulnerability for alcoholism and may lead to improved approaches to prevent and treat alcoholism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGY OF THE PROLACTIN RELEASING PEPTIDES Principal Investigator & Institution: Samson, Willis K.; Professor; Pharmacological & Physiol Scis; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (applicant's abstract): The focus of this proposal is to determine the roles the recently described prolactin releasing peptides (PrRPs) may play in stress-induced elevations of prolactin secretion (neuroendocrine actions in pituitary gland and neuromodulatory actions in brain) and autonomic function (neuromodulator actions in brain). We hypothesize that the PrRPs produced in brain and pituitary gland are required for the normal neuroendocrine and cardiovascular responses to stress. Specifically we hypothesize that PrRPs, either produced locally in pituitary gland or delivered to the gland via either the portal or peripheral circulations, play a role in the secretion of prolactin from the gland during stress. Furthermore, we hypothesize that the elevation in sympathetic tone during stress depends upon the actions of brainderived PrRPs and that removal of those peptides will compromise the animal's cardiovascular response to stress. We will address the following Specific Aims (Questions): 1) Will physical or anticipatory stress elevate circulating plasma levels of PrRP, tissue levels of the peptides (brain, pituitary, adrenal), or expression of the gene (mRNA levels) in brain, pituitary gland or adrenal medulla? 2) Are the PrRPs effective releasing factors in the setting of dopamine withdrawal (which occurs in stress)? 3) Will central administration of PrRP stimulate prolactin secretion in conscious animals? 4) Can the site of action of PrRP in brain be identified by site-specific injections? 5) Will compromise of endogenous PrRP alter the neuroendocrine and cardiovascular responses to stress? The studies described here are designed to further characterize the pharmacology and physiology of the PrRPs, which have been demonstrated to act in the pituitary as neuroendocrine factors and in brain as modulators of autonomic outflow. The ultimate goal is to determine their importance in the maintenance of normal endocrine and cardiovascular function, in particular during stress. These studies will also begin to examine a potentially novel confluence of endocrine and autonomic responses to stress and thereby provide insight into the coordinated responses of multiple organ systems to stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PITUITARY SPECIFIC ONCOGENE SIGNALING MECHANISMS Principal Investigator & Institution: Gutierrez-Hartmann, Arthur; Professor, Director, Mstp; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-JUN-1994; Project End 31-MAY-2007 Summary: (provided by applicant): The cytoplasmic components and nuclear effectors mediating growth factor/Ras-induced gene expression are common to all cell types. Thus, defining the precise molecular mechanisms by which ubiquitous components of growth factor/Ras signaling pathways result in cell-specific responses remains a central
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problem in biology today. Previously, we discovered an elegant and precise tri-paritite molecular code, involving the proto-oncoprotein c-Ets-1, the POUhomeodomain protein Pit-l, and a composite DNA element containing an Ets binding site (EBS) adjacent to a Pit-1 site (FPIV). Pit-l, Ets-1 and this composite site were shown to be required not only for the Ras response of the rat (r) prolactin (PRL) promoter, but also to reconstitute lactotroph-specific rPRL promoter activity. This was the first and remains the only example of a tissue-specific Ras response element (RRE). During the past funding cycle, we used NMR and GST pull-down methods to map the Ets-1/Pit-1 interaction surfaces to exact residues on the Pit-1 POUhomeodomain and to the Ets-1 RIII TAD. We reported that Ets-1 preferentially binds to the EBS in the RRE, whereas GABP preferentially binds to the BTE/EBS centered at -95. Finally, using dominant-negative and siRNA approaches, we verified that Ets factors, in particular GABP, are critical for basal and growth factor-induced rPRL promoter activity. These studies revealed that Ets-1 and GABP are critical for lactotroph-specific expression of the endogenous rPRL gene. While our previous studies have mostly used reporter gene assays, the broad mandate of this proposal is to use molecular, biochemical and transgenic approaches to dissect the physiological role of select Ets factors and Ets factor binding sites in goveming basal and Ras-regulated lactotroph-specific expression of the endogenous rPRL gene in GH4 cells and in mice. Unifying Hypothesis: We hypothesize that basal and Ras-regulated expression of the lactotroph-specific rPRL gene is governed by specific Ets factors, some acting in concert with Pit-l, whose binding to Ets binding sites on the proximal rPRL promoter is regulated by the physiological state of the cell. Specific Aims: (1) To identify Ets factor occupancy on the endogenous, proximal rPRL promoter in GH4 rat pituitary cells q oncogenic Ras. (2) To identify the oncogenie Ras-dependent protein components of Ets-1/Pit-1 transcription factor complexes. (3) To determine the functional role of basal and oncogenic Ras-regulated transcription co-regulatory molecules (4) To elucidate the physiological role of rPRL Ets binding sites and the Ets factor GABP in PRL gene expression in transgenic mice. Information gained from these studies will provide critical insights into the mechanisms by which combinatorial Ets/Pit-1 protein interactions specify cell-restricted PRL gene expression, and also provide a novel insights into the mechanisms by which Ras/MAPK regulates gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREGNANCY HOOKWORMS
INDUCED
REACTIVATION
OF
ARRESTED
Principal Investigator & Institution: Arasu, Prema; Molecular Biomedical Sciences; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Developmental arrest within a host allows many parasitic nematodes to evade adverse external conditions and action of chemotherapeutic agents, but to reactivate at opportune periods. Our long range goal is to elucidate the molecular mechanisms that trigger reactivation of arrested parasites and to identify strategies of preventing neonatally- transmitted infections as well as self-reinfections (e.g. Strongyloides in immunodeficient individuals). This study is focused on pregnancyinduced reactivation and transmammary transmission of arrested Ancylostoma larvae because hookworms infect about 1.2 billion people, and in young children, the protein loss and anemia can contribute to physical and cognitive deficiencies. We have previously shown that larval reactivation cannot be attributed to a state of generalized immunosuppression as is associated with pregnancy; rather, hormonally- induced cytokine changes appear to be critical. Using an in vitro reactivation assay, we find that
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TGF-beta stimulates larval feeding at levels comparable to that of serum stimulation. Further, the stimulatory effect of serum can be significantly neutralized with antibodies to TGF-beta. Earlier studies have shown that exogenous estrogen and prolactin stimulate a resurgence of larvae in the milk of latently-infected, lactating dogs, and more recent work indicates that these hormones specifically upregulate the levels of TGFbeta2 during late pregnancy and lactation. In addition, TGF-beta. signaling is clearly crucial to reactivation of arrested larvae of the soil nematode, Caenorhabditis elegans. The objective of this proposal is to use the mouse/A. caninum model to test the hypothesis that host-derived TGF-beta particularly the beta2 isoform which is upregulated by estrogen and prolactin, triggers the reactivation and transmammary transmission of developmentally-arrested larvae during late pregnancy and lactation. We propose to test our hypothesis with 3 specific aims: 1. Characterize the A. caninum homologues of the TGF-beta receptor and ligand to evaluate binding of mammalian TGF-beta to the parasite receptor. 2. Use the in vivo model of infection to determine TGF-beta levels, and larval status and burden in skeletal muscle versus mammary tissue during different phases of pregnancy and lactation, and determine whether larval reactivation is stimulated by estrogen and prolactin. 3. Use in vitro co-cultures of tissue larvae with muscle versus mammary cells to distinguish the differential effects of estrogen, prolactin and staged pregnancy sera on larval reactivation, and determine if neutralizing antibodies to TGF-beta inhibit reactivation. These studies will provide important results for the development of therapeutic strategies to eradicate latent parasitic infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROLACTIN AND ESTROGENS AS MITOGENS IN PROSTATE CANCER Principal Investigator & Institution: Ben-Jonathan, Nira; Professor; Cell Biol, Neurobiol/Anatomy; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (Provided by the applicant) Prolactin (PRL) and prolactin receptor (PRLR) are members of cytokine super family. Overproduction of PRL by prostate cells results in prostatic hyperplasia in mice. Elevated serum PRL levels induced by estrogens, positive regulators of PRL, or by drugs result in rodent prostatic hyperplasia and enhanced rodent prostatic tumor growth. In rodents, hyperprolactinemia and prostatic hyperplasia are also induced by bisphenol A (BPA), an environmental estrogen. Together, this provides evidence that PRL plays a critical role in rodent prostatic hyperplasia and carcinogenesis. However, our knowledge on the role of PRL in human prostatic growth is limited and the mitogenic potential of PRL in the progression of human prostate cancer remains unexplored. Our preliminary data document expression of PRL and PRLR in different prostate cancer cells, up-regulation of PRLR expression by PRL, and increased cell proliferation in response to PRL. In addition, we show a rapid phosphorylation of ERK1/2 in response to PRL, estradiol (E2) as well as BPA. Accordingly, our hypothesis is "Human prostate cancer cells produce PRL and form a functional autocrine-paracrine regulatory loop of PRL and the PRLR. The autocrineparacrine effects of PRL/PRLR as well as the combined actions of PRL and estrogens contribute to the progression of prostate cancer. Both PRL and estrogens recruit components of the MAP kinase signaling cascade." To test our hypothesis we will use DU 145 human prostate cancer cells as a model. The following specific aims will investigate the direct as well as combined effects of PRL, E2 and BPA. Specific Aim 1: To determine: a) local production of biologically-active PRL and its effects on cell
50
Prolactin
proliferation; b) the effects of exogenous PRL, E2 and BPA on PRLR and estrogen receptor (ER)-beta expression; c) the effects of exogenous PRL, E2, and BPA on cell proliferation; d) the binding parameters of PRLR in the cells; e) the ability of tamoxifen to inhibit PRL effects via PRLR. Specific Aim 2: To examine: a) PRL induced activation of STATs and their nuclear translocation; b) activation of ERK1/2 by various treatments and their nuclear translocation; c) the enzymatic activities of Raf, MEK and MAP kinases; d) the role of the MAP kinase cascade in mediating the mitogenic responses to PRL, E2, and BPA. The results of this study should provide information on the role of local PRL and the combined actions of PRL and estrogens on prostate cancer cell proliferation. The findings on BPA may reveal the potential risk associated with human exposure to environmental estrogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROLACTIN AS A LACRIMAL GLAND IMMUNOREGULATOR Principal Investigator & Institution: Schechter, Joel E.; Cell & Neurobiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-DEC-2006 Summary: (provided by applicant): Dry eye is one of the most frequently encountered problems in ophthalmology, with highest incidence in women, especially postmenopausally where atrophy and decreased tear formation are associated with chronic inflammation. It also occurs in Sjogren's syndrome, an autoimmune disease characterized by lymphocytic infiltration and loss of lacrimal acinar cells. The hormonal milieu is a critical factor in maintenance of normal lacrimal function, and androgens and prolactin (PRL) both play important roles. We have demonstrated that lacrimal fluid production in rabbits is decreased during pregnancy, and that pregnant women experience increased symptoms of dry eye, worsening with multiple pregnancies. Our studies in rabbits demonstrate dramatic changes in the concentration and distribution of PRL and growth factors within the lacrimal gland (LG) during pregnancy and lactation, increasingly being concentrated within ductal epithelial cells. These changes are accompanied by the appearance of "reactive acinar cells," which are immunopositive for MHC Class II protein and which may also be passive sources of autoantigenic stimulation, and by a marked redistribution of T and B lymphocytes from their normal periductal location to interacinar sites. We propose a new paradigm for physiological regulation of LG function, i.e., an "acinar-ductal loop." In this system, ductal epithelial cells monitor the contents of the acinar effluent, absorb and transport materials from the duct lumen to periductal immune cells, and in so doing function in transmitting immunoregulatory signals (PRL, growth factors, cytokines) that may enhance periductal immune cell activation and responses to autoantigens. We propose to approach this integrated physiological system from perspectives of endocrinology and cellular physiology, employing rabbits, and mouse models of Sjogren's syndrome to pursue the following specific aims: (1) Test the hypothesis that lacrimal acinar cells and lacrimal ductal epithelial cells represent a physiological loop, in which ductal epithelial cells monitor acinar fluid contents, absorb and transport materials from within the duct lumen, and function in local immunoregulation. (2) Test the hypothesis that artificially altering the hormonal milieu of non-pregnant rabbits will elicit responses in the LG which are identical to those observed during pregnancy and lactation. (3) Use in vitro methods to characterize the effects of pregnancy, and growth factors whose expression is increased during pregnancy, on secretory function and intracellular autoantigen traffic in lacrimal acinar cells. (4) Test the hypothesis that increased PRL, charactersitic of pregnancy and lactation, enhances activation of lymphocytes in the LG. (5) Test the
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hypothesis that pregnancy accelerates and exacerbates the progress of Sjogren's-like infiltration of the LG in mouse models of Sjogren's syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROLACTIN TRANSDUCTION
INDUCED
PHOSPHOPROTEIN
SIGNAL
Principal Investigator & Institution: Rui, Hallgeir; Associate Professor; Oncology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-JUL-2005 Summary: (provided by applicant): Breast cancer is a leading cause of death among women. Malignant breast tumors that are not cured by initial surgery typically respond poorly to traditional chemotherapy and further antiestrogen therapy. New therapeutic strategies that will inhibit growth and suppress progression of breast cancer cells need to be identified. This goal might be achieved through targeting of signaling pathways used by the most prominent peptide hormones that regulate breast cancer growth and differentiation. Based on novel preliminary data that extend the work supported by this grant, we provide compelling rationale for investigating the growth-regulatory role of the prolactin-activated Jak2 tyrosine kinase/Stat5 transcription factor pathway in normal and malignant human breast epithelial cells. Importantly, we have discovered loss of Stat5 activation during progression from normal to primary cancer and to metastatic disease. We have also discovered a novel prolatin-activated Jak1-Stat3 signaling pathway that is Jak2-independent, and appears to require the interleukin-6 signal transducer, gp130. We will use specialized molecular tools and technologies to test the following two central hypotheses: a) Prolactin inhibits growth of normal and malignant human breast epithelial cells through activation of the Jak2-Stat5 signaling pathway. b) Prolactin activates an alternative, breast cancer-specific Jak1-Stat3 pathway by a mechanism that requires the interleukin-6 signal transducer, gpl30. We are well qualified to successfully undertake the proposcd studies. We expect to establish the importance of the Jak2-Stat5 pathway in growth-suppression of untransformed and malignant breast epithelial cells, and to identify the mechanism by of aberrant prolactin activation of the Jak 1-Stat3 pathway in breast cancer cells. The research is significant and important because it will provide novel insight into the biological role and mechanisms of prolactin signal transduction in breast cancer. More effective therapeutic strategies for breast cancer could be a result. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEIN INTERACTIONS REGULATING PITUITARY SIGNALING Principal Investigator & Institution: Duval, Dawn L.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-DEC-2003 Summary: (taken from the application) Transcriptional activity is dependent not only on the binding of transcription factors to cis-acting elements, but also on the ability of those factors to recruit a complex hierarchy of proteins to stabilize the basal transcriptional machinery. Basal lactotroph specific expression of the rat prolactin (rPRL) promoter is dependent on the interaction of the proto-oncoprotein c-Ets-1, a member of the -Ets family of transcription factors, with the pituitary-specific transcription factor, Pit-1, at a composite Ets/Pit-1 DNA binding element in the rPRL promoter. While each of these factors alone is capable of activating rPRL gene transcription, the combination of these two transcription factors results in a marked synergistic response. Although the precise
52
Prolactin
mechanism for this synergy remains unknown, it is clear that physical interaction of these two factors is required. Recent studies suggest that the activity of Pit-1 and Ets-1 may be determined by the formation of co-regulatory complexes. Thus, I hypothesize that the Pit-1/Ets-1 complex mediates the synergistic response of the rPRL promoter by recruiting specific transcription regulatory proteins. The goals of this study are to map the specific amino acids of Pit-1 and Ets-1 responsible for their physical and functional interaction, and to use liquid chromatography/mass spectrometry methods to identify the protein components that are recruited to the Ets-1/Pit-1 complex. Therefore, these studies are likely to provide critical insights into the molecular mechanisms underlying combinatorial factor interactions and how they mediate synergistic responses. Finally, these studies are important to my career development, as they will allow me to gain expertise in the cutting edge field of proteomics and protein structure-function relationships, which I can then utilize to establish my career as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PUBERTY AND GENDER DIFFERENCES IN PAIN RESPONSIVITY Principal Investigator & Institution: Zeltzer, Lonnie K.; Professor; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 22-SEP-1999; Project End 31-AUG-2004 Summary: (adapted from investigator's abstract): Female predominance in certain chronic pain syndromes begins to arise in adolescence, suggesting that age or puberty may be a marker for the emergence of gender differentiation in pain. Research shows estrogen affects pain sensitivity. However, studies have not always found higher pain responsivity in the luteal phase of menses (when estrogen levels are high) compared to the follicular phase (when estrogen is relatively low). This suggests that there are other factors which modulate the effects of estrogen on pain responses. Psychological vulnerability, as manifested in heightened physiological reactivity, sensitivity to somatic sensations, and a threat-oriented attentional focus, has been linked to increased pain responsivity. A composite of these psychological vulnerability factors may interact with estrogen levels (and thus puberty status) to produce enhanced pain responsivity in late puberty females. Experimental work to test this hypothesis is lacking; the developmental trajectory for the emergence of adult chronic pain has not been studied. A gender (male vs. female) by puberty status (early: Tanner Stages I-II vs. late: Tanner Stages III-V) by psychological vulnerability (low vs. high composite score) by task type (thermal, pressure and cold pressor pain) between-within factorial design will be used to examine the role of puberty in laboratory pain responsivity among 240 health children, ages 8-17 years. The aims of the study are to: (1) examine among health children the effects of gender, puberty and psychological vulnerability on pain responsivity as measured by subjective, behavioral, autonomic, gonadal and pituitaryadrenal responses to three types of laboratory pain tasks; (2) examine interactions between gender, puberty, and psychological vulnerability in three types of pain responses (tolerance, intensity ratings and distress ratings); and (3) determine the effects of stage of menses (luteal vs. follicular) and dysmenorrhea on pain responsivity among post-menarchal females adolescents. Puberty status will be identified by self-rating pictorial questionnaires tied to Tanner staging and confirmed by hormone assays (FSH, E2, progesterone, testosterone and DHEA-S). Physiologic (ANS) behavioral (tolerance) and subjective measures (pain intensity and distress ratings) will be recorded in response to each pain task. Two finger pricks for spot blood analyses 20 minutes apart will test for stress reactivity in two systems (cortisol, prolactin). Potential psychosocial
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moderators of pain responsivity (e.g., concurrent negative life events, past experiences with pain, and adherence to traditional gender roles which emphasize passivity and helplessness among females) will also be assessed. This study is an initial step in understanding the role of puberty in the developmental trajectory of gender differences in pain responsivity from childhood to adulthood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SMC/RMUC4 TRANSCRIPTION BY CELL SIGNALING Principal Investigator & Institution: Perez, Aymee; Cell Biology and Anatomy; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The long-term research objectives of this laboratory involve elucidating the roles of the glycoprotein complex ASGP-1/ASGP-2 (SMC) in mammary cancer, in other cancers and in normal tissues. Our short-term plan focuses on the transcriptional regulation of SMC expression in the mammary gland, uterus and mammary tumors. Abnormal expression of SMC/MUC4 has been reported in rat mammary adenocarcinoma and in human breast, pancreatic, lung and colon carcinomas; particularly in cells of highly invasive tumors obtained from patient body fluids. Our recent studies described novel post-transcriptional regulatory mechanisms for the expression of SMC in mammary gland, which has important implications for breast cancer and mammary development. Thus, the overall goal of our proposed studies is to understand the functions of SMC in normal epithelial development and tumor progression, focusing particularly on the mammary gland and uterus, and the mechanisms by which regulation of its expression contribute to those functions. The hypotheses being tested in this work are: 1) SMC contributes to tumor progression, 2) SMC is regulated by a combination of transcriptional and post-transcriptional mechanisms and 3) SMC contributes to epithelial development, specifically to mammary development. Specific Aims are to: I)investigate the mechanism required for lactogenic hormone induction of SMC/rMUC4 using an in vitro model system, the Rama 37 rat mammary epithelial stem cell line, 2) study the role of PEA3 transcription factor in SMC expression in 13762 ascites cell line and rat primary mammary epithelial cells, and 3) investigate the mechanism implicated in uterine rMUC4 expression through TGFbetasignaling using rat primary uterine epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REPRODUCTIVE AND HORMONAL RISK FACTORS FOR ADENOMYOSIS Principal Investigator & Institution: Holt, Victoria L.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-JAN-2007 Summary: Adenomyosis, also known as internal endometriosis, is the progressive invasion of endometrial glands and stroma from the uterine endometrial lining down into the myometrium, the inner muscle wall of the uterus. This condition is diagnosed in over 150,000 women in the U.S. annually, can be associated with severe pelvic and menstrual pain and excessive bleeding, and almost always requires hysterectomy for definitive treatment. Clinical observations have raised the hypothesis that multiparity and excessive estrogen may increase disease risk; however, there is little epidemiologic data to confirm or deny this hypothesis. Consequently, we propose to conduct a case-
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Prolactin
control study to investigate the relationships between adenomyosis and reproductive and hormonally-related exposures, including polymorphisms in genes involved in steroid hormone synthesis and metabolism. The study will be conducted at Group Health Cooperative of Puget Sound (GHC), a health maintenance organization serving approximately 500,000 people in western Washington State. Cases will be 500 female GHC enrollees 18-59 years of age diagnosed with adenomyosis between March 1, 2001 and Feb. 28, 2006. Two control groups will be used: 1) 500 women undergoing hysterectomy during the study period who are found to have a condition other than adenomyosis, endometriosis, or leiomyoma, frequency matched to cases on age, and 2) 500 women randomly selected from computerized enrollment files, also frequency matched to cases on age. Data will be obtained from cases and controls by in-person interview, anthropometric measurement and collection of a blood sample for DNA analysis; and these data will be linked with the GHC computerized pharmacy database. Subjects will be interviewed regarding factors known or suspected to be associated with uterine trauma or steroid hormone levels (including reproductive, contraceptive, and menstrual histories; obesity; exercise; diet; cigarette smoking) as well as other potential risk factors for adenomyosis. Blood samples will be analyzed for two polymorphic genes coding enzymes active in estrogen metabolism (CYP17, COMT). Analyses comparing cases and controls with respect to reproductive and hormonal risk factors and their interactions with genetic polymorphisms will be conducted to address the specific aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRODUCTIVE CONSEQUENCES OF PUBERTAL MORPHINE ABUSE Principal Investigator & Institution: Byrnes, Elizabeth M.; Environmental/Population Hlth; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 27-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The present proposal will study the impact of opiate abuse during puberty on future reproductive health. In both the rat and human, puberty is a period during which the reproductive cycles and daily hormonal rhythms begin to emerge. Because endogenous opioids mediate some of these changes, artificially elevated levels of opioids during this period can interfere with reproductive development. While some of the acute effects of opiates like morphine, heroin, and methadone in pubertal females have been delineated, the long-term effects of opiate abuse during the tumultuous pubertal period are unknown. Recent preliminary studies indicate that administering morphine to female rats around the time of puberty results in reproductive alterations that can be observed weeks after drug withdrawal. Specifically, while these females give birth to healthy pups, the rate of growth of their offspring is reduced. Moreover, there appears to be a decrease in the suckling-induced release of prolactin. Given the positive correlation between prolactin secretion and milk yield, a reduction in prolactin secretion could underlie reduced pup growth. Using a chronic increasing dose regimen of morphine (twice daily injections from age 30 to 50 days old), the present set of studies will examine the possible neuroendocrine alterations that may subserve both the decrease [in] suckling-induced prolactin secretion and decreased pup growth. These include examination of the level of prolactin content and message in the anterior pituitary, the sensitivity of the mu-opioid and D2 dopamine receptor subtypes to modulate prolactin secretion, and the expression of prolactin receptors in the mammary gland. In addition, the longevity of alterations in sucklinginduced prolactin secretion and reduced pup growth will be examined. The long-term objective of this proposal is to use these studies as an animal model of drug addiction in
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adolescent females. Given the recent rise in the number of adolescent girls abusing heroin, these studies will provide information on some of the potential reproductive consequences that may arise in the future for girls addicted to opiates during this sensitive developmental period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: S179D PROLACTIN: INHIBITION OF PROSTATE CANCER GROWTH Principal Investigator & Institution: Walker, Ameae M.; None; University of California Riverside 900 University Ave Riverside, Ca 92521 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (Provided by the applicant) Prostate cancer is the second leading cause of cancer deaths among males in the United States. While effective treatments exist for as long as the tumors remain sensitive to androgens, there are no good therapies available once evolution to an androgen-insensitive state occurs. An evaluation of factors which contribute to the growth of these later stage tumors is crucial to the development of new therapeutic strategies. Prolactin (PRL) is one such factor. Although large quantities of PRL are produced by the pituitary, PRL also serves as an autocrine growth factor in the normal human prostate and, as we have shown, this autocrine growth loop continues to be operative in cells representative of highly metastatic, androgen-independent cancers. Using a novel PRL growth antagonist developed in our laboratory, S179D PRL, we have demonstrated that blockade of the PRL autocrine growth loop reduces both the growth of well-established tumors and tumor initiation when androgen-independent cancer cells are grown in nude mice. This PRL growth antagonist therefore has the potential to be an important new therapeutic for late stage disease. The overall aim of the proposed project is to gain a fuller understanding of the molecular and cellular mechanisms underlying S179D PRL's antagonism of prostate tumor growth so that the full potential of this therapeutic can be realized. The specific aims are 1) to determine the optimal dose of S179D PRL, 2) to establish whether S179D PRL slows or halts growth or actually reduces tumor size, 3) to determine whether resistance can develop, and 4) to determine whether any aspect of the growth inhibition involves a) the promotion of apoptosis, or b) downregulation of the growth-promoting PRL autocrine loop, or c) upregulation of the short PRL receptor. In most experiments tumor size will be monitored by the amount of a secreted transfected gene product in the urine. In this way, individual nude mice can be assessed for their response to treatment. S179D PRL will be administered by Alzet minipumps implanted subcutaneously. Molecular and cellular effects on the tumors/tumor cells will be assessed by end-labeling for apoptosis, Northern, Western and microarray analysis for gene expression and immunoprecipitation, Western and radiolabel incorporation for signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELF INJURIOUS BEHAVIOR AND PRIMATE WELL BEING Principal Investigator & Institution: Novak, Melinda A.; Professor; Psychiatry; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-JUL-2005 Summary: Primates, such as Old World monkeys, represent a crucial research resource, and major scientific advances in medicine, biology, and neuroscience can be attributed to their use. Despite the recent strides made in controlling colony diseases, in developing new housing regimens, and in modernizing facilities, some monkeys
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Prolactin
develop pathological behavior. Of particular concern is the small but persistent percentage of monkeys that develop the syndrome of self-injurious behavior (SIB). The occurrence of SIB compromises the goal of promoting the physical and psychological well-being of laboratory primates as mandated by the Animal Welfare Act (Revised 1991). It also threatens the quality of the monkey research resource, particularly because monkeys with this condition differ both behaviorally and physiologically from other monkeys in the colony. Our research has shown that monkeys with SIB are more aggressive, are more likely to have experienced early social separation, and have been exposed to more stressful events than normal monkeys. Monkeys with this disorder also show altered heart rate patterns and a dysregulation of the hypothalamic-pituitaryadrenal (HPA) axis manifested by unusually low levels of plasma cortisol. This pattern of precipitating stressors and low cortisol parallels similar observations in patients with post-traumatic stress disorder (PTSD). The continuing objective of this project is to characterize the nature of SIB in rhesus monkeys, to identify the mechanisms responsible for this behavioral pathology, and to devise effective treatment regimens. Our current focus is on the HPA and serotonergic systems, both of which may be altered in monkeys with SIB. We will use various endocrine challenges to determine whether monkeys with SIB show reduced adrenocortical responsivity and heightened sensitivity of the glucocorticoid negative feedback system as is observed in PTSD patients. We will determine whether monkeys with SIB show altered stress responses to various social situations using our newly developed procedure of noninvasive collection of salivary cortisol in unrestrained adult animals. We will investigate cardiac and HPA reactions that surround spontaneous episodes of self-directed biting in an effort to determine whether biting serves as a coping strategy to reduce arousal. Other studies will examine the role of the serotonergic system in the expression of SIB by measuring hormonal responses to a fenfluramine challenge. Finally, we will evaluate the efficacy of serotonergic drugs as potential pharmacotherapeutic agents for reducing the incidence of SIB. These studies should provide important new information concerning the pathophysiology of SIB in monkeys and should lead to the development of useful treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN FUNCTION IN PATIENTS WITH EATING DISORDERS Principal Investigator & Institution: Jimerson, David C.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2000; Project Start 30-SEP-1991; Project End 31-JAN-2005 Summary: (Adapted from the Applicant's Abstract): The eating disorders bulimia nervosa and anorexia nervosa are serious psychiatric syndromes affecting 2 to 3 percent of young women, and significant although smaller number of young men. Women with bulimia nervosa or anorexia nervosa manifest abnormalities in regulation of serotonin, a central nervous system (CNS) neurotransmitter involved in regulation of food intake, mood and impulsive/obsessional behaviors. The goal of the current project is to evaluate whether abnormalities in serotonin regulation reflection reflect trait-related characteristics present in individuals who develop an eating disorder. Recurrent dieting is a frequent precursor to bulimia nervosa and anorexia nervosa. In healthy controls, dieting decreases blood tryptophan levels, resulting in an apparent decrease in CNS serotonin synthesis. Normally, serotonergic pathways are though to respond to dieting through augmentation of post-synaptic receptor responsiveness. It is hypothesized that in women with a neurobiological predisposition to eating disorders, CNS receptors are not able to respond adequately to compensate for diet-associated decreases in serotonin
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synthesis. This deficiency could contribute to the onset of eating disorder symptoms. Study groups will include women who have recovered from bulimia nervosa, women who have recovered from anorexia nervosa, and healthy female controls. Based on a randomized, controlled, crossover design, subjects will participate in low-tryptophan and normal tryptophan eight-day study diets. In comparison to results in controls, the long-term remitted patient groups are anticipated to respond to a low-tryptophan diet with significantly impaired diet-induced augmentation of dexfenfluramine-stimulated prolactin response. Indirect measures of physiological/metabolic response to dietary changes, including blood leptin concentration, will be compared across study groups. These studies will provide important new information on the potential roles of dieting and serotonin in the development of eating disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN, DRUG USE AND MDMA INDUCED DEFICITS Principal Investigator & Institution: Moeller, Frederick G.; Associate Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The neurotoxic effects of the drug methylenedioxymethamphetamine (MDMA), popularly known as "ecstasy", have been conclusively shown in animals. Human studies on the long-term effects of MDMA have been hampered by the confounding issue that other drugs are often sold as MDMA, and the fact that MDMA users tend to use other drugs of abuse. Thus, it has been questioned whether the neurobehavioral deficits seen in MDMA users are specifically due to MDMA. Taken together, these key issues justify the need to conduct more systematic, rigorous examination of neurobehavioral effects of MDMA use in humans. Likewise, the more clear evidence that MDMA causes detrimental effects on the brain and behavior, the more likely MDMA users will consider substance abuse treatment. Since the United States has recently seen a dramatic increase in the use of MDMA, primarily by young adults, the significance of the neurotoxic effects of MDMA in humans is clear. A further understanding of the long-term neurobehavioral effects of MDMA in humans will have a direct and significant effect on treatment development. This resubmission will use multi-modal neurobehavioral measures including behavioral laboratory measures of impulsivity and functional magnetic resonance imaging to answer three key questions regarding MDMA use in humans. First, what are the specific effects of MDMA use on mood, impulsivity, memory, and brain function? Second, how are these deficits related to quantity and frequency of MDMA use? Third, are these deficits related to serotonin function in MDMA users? The Specific Aims of this proposal are: Specific Aim 1: To compare neurobehavioral measures of mood, memory, impulsivity and functional magnetic resonance imaging between heavy MDMA using subjects, matched nonMDMA using drug users, and healthy controls. Specific Aim 2: To determine whether the quantity and frequency of MDMA use are related to the neurobehavioral deficits seen in heavy MDMA users. Specific Aim 3: To determine whether neurobehavioral deficits seen in heavy MDMA users are related to serotonergic function as measured by a mCPP neuroendocrine challenge in these subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Prolactin
Project Title: SEX POSTMENOPAUSE
STEROIDS
&
MAMMOGRAPHIC
DENSITY
IN
THE
Principal Investigator & Institution: Greendale, Gail A.; Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 01-JUN-1998; Project End 31-MAR-2008 Summary: (provided by applicant): Higher mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application proposes to continue work in "Sex Steroids and Mammographic Density in the Postmenopause", a study of the effects of endogenous and exogenous sex steroids on mammographic percent-density. This study is an outgrowth of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, which randomly assigned postmenopausal women to placebo, estrogen-only, or one of three combination estrogen/progestin treatments. To date, the principal findings of the "Sex Steroids and Mammographic Density Study" are: 1) Exogenous estrogen-only treatment did not affect mean mammographic density but significant increases in mammographic density did occur in 3 groups assigned to estrogen/progestin treatments; 2) In the three estrogen/progestin groups, but not in the estrogen-only group, the degree of increase in serum estrone level on-treatment predicted the amount of increase in mammographic density; and 3) Endogenous (we-treatment) serum levels of estrone, estradiol, progesterone, and sex hormone binding globulin were positively associated with baseline mammographic density. Based on these findings, we propose to continue work in this study to gain a further understanding of variation in mammographic density, specifically: 1) What other factors are associated with baseline (pre-treatment) mammographic density? and 2) What additional factors predict increases in mammographic density during treatment? We hypothesize that hormones (in addition to those already studied), genetic polymorphisms in sex steroid biosynthetic/metabolic pathways, and genetic polymorphisms in sex steroid receptors will be related to baseline mammographic density and/or mammographic density response to treatment with hormone therapy. The proposed continuation project will last 4 years and will take place at UCLA and USC. Using stored samples, we will measure baseline and 12-month levels of prolactin and progestins. We will also extract DNA from stored samples to assess selected genetic polymorphisms. The mammographic density outcome data and all relevant covariates have already been measured during our prior work. We will quantify the relations between the hormone and genetic exposures measured in this project and mammographic density (at baseline as well as change in density between baseline and 12 months). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP AND NOCTURNAL ENDOCRINE FUNCTION IN MDMA USER Principal Investigator & Institution: Mccann, Una D.; Associate Professor of Pyschiatry; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): (+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is an increasingly popular psychoactive drug of abuse that has been shown to be a potent brain serotonin (5-HT) neurotoxin in animals. Growing evidence in
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recreational MDMA users indicates that MDMA can also lead to 5-HT damage in humans. Recent data in non-human primates suggests that some MDMA users (i.e., those who use MDMA in a "binge" regimen) may also incur brain dopamine (DA) neurotoxicity, although clinical studies to test this possibility have not yet been conducted. Functional consequences of MDMA neurotoxicity in humans have been difficult to identify. However, several studies have demonstrated altered sleep patterns and endocrine function in individuals previously exposed to MDMA. Since 5-HT and DA are involved in the regulation of sleep and endocrine function, it is possible that altered sleep and endocrine function in MDMA users is related to MDMA-induced 5-HT and/or DA neurotoxicity. Further, since sleep and circadian rhythms influence hormonal secretion (and vice versa), abnormalities of sleep and endocrine function in MDMA users may be inter-related. The proposed studies are intended to extend previous studies of sleep and neuroendocrine function in MDMA users, and explore possible interrelations between sleep and nocturnal neuroendocrine function in MDMA users and matched controls. The specific aims of the project are: 1) To analyze sleep patterns of 2 groups of MDMA users and 2 groups of matched control subjects using standard polysomnographic and spectral power methods. One group of MDMA users will be "bingers," whereas the second group will report never having taken more than dose of MDMA dose per 12-hour period. One control group will be matched with MDMA users for non-MDMA drug use (in addition to other demographic variables) whereas the second group of controls will have no history of illicit drug abuse. 2) To characterize the nocturnal secretion patterns of prolactin, growth hormone, and cortisol, three hormones that are modulated by 5-HT and/or DA influenced by sleep; and 3) To conduct 5-HT pharmacological challenges with m-chlorophenylpiperazine (m-CPP) in male and female MDMA users during sleep, when environmental and cognitive factors that can influence endocrine secretion are minimal. Results from the proposed studies will help better define the functional consequences of MDMA exposure in humans, and could shed light on the roles of 5-HT and DA in sleep and nocturnal endocrine function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SOCS-3 IN IGF-IR SIGNALING IN MALIGNANT CELLS Principal Investigator & Institution: Dey, Bhakta R.; Orthopedics & Rehabilitation; Creighton University 2500 California Plaza Omaha, Ne 68178 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant) The insulin-like growth factor-I receptor (IGF-IR) plays an important role in promoting the growth of cancers by stimulating malignant cell proliferation and transformation, and inhibiting apoptosis. We identified suppressor of cytokine signaling (SOCS)-3 as an intracellular binding partner of the IGF-IR. In human colon cancer Caco-2 cells, the IGF-IR and IGF-II are expressed at high levels and SOCS-3 is significantly induced by IGF-I stimulation. SOCS-3 protein is heavily phosphorylated in serine residues and this serine phosphorylation is noticed with or without IGF-I stimulation. SOCS-3 protein localized mostly in the cytoplasm and IGF-I stimulation results in both nuclear and cytoplasmic localization. Moreover, SOCS-3 protein is ubiquitinated in mammalian cells. These results suggest that SOCS-3 protein may play regulatory roles in IGF-IR signaling. SOCS-3 has been shown to be a negative regulator of interleukin (IL-2, IL-6), growth hormone, prolactin, insulin and leptin receptor signaling pathways. The primary goal of this study is to define the function of SOCS-3 in IGF-IR signaling in malignant cells. We hypothesize that SOCS-3 may play a negative regulatory role in IGF-IR signaling in malignant cells. To test this hypothesis we formulated the following specific aims: 1) to identify which signal transduction
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pathway(s) of the IGF-IR might be affected by the IGF-IR-SOCS-3 interaction, 2) to determine whether this interaction alters kinase activity or stability of the receptor, and 3) to determine the mechanisms by which IGF-IR-SOCS-3 interaction might interfere with IGF-I stimulated proliferation, invasion and inhibition of apoptosis in malignant cells. Our long-term goal is to investigate the negative regulation of the IGF-IR signaling by SOCS-3, a potentially novel mechanism for growth resistance and cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECIFIC REPRESSION OF PROLACTIN GENE EXPRESSION Principal Investigator & Institution: Day, Richard N.; Associate Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 11-JUL-1994; Project End 31-MAR-2003 Summary: (Adapted from applicant's abstract) The broad objective of this proposal will be to continue the ongoing studies to map protein protein interactions of Pit1. This study will begin to assess how cell signaling influences such interactions and, specifically, it is proposed to assess how an Ets repressor protein ERF negatively regulates prolactin gene regulation. First, the applicant proposes to identify the endogenous ERF protein and characterize its subcellular localization during critical periods within the cell cycle and in response to activation of signal transduction cascades. Second, the requirements for Pit-1 nuclear localization will be precisely identified so as to permit further protein protein analysis by FRET microscopy. Continuing on this theme, the final aim will investigate the association of Pit-1 and its protein partners with the nuclear matrix. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEM CELLS AND PERINATAL FACTORS FOR BREAST CANCER RISK Principal Investigator & Institution: Hsieh, Chung-Cheng; Professor of Medicine; Cancer Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-JAN-2006 Summary: (provided by applicant): This study proposes to examine whether hormone levels in human umbilical cord blood are associated with measurements of stem cell potential and expression of Bcl-2 family proteins indicating levels of apoptotic activity. Measurements of stem cells and Bcl-2 apoptosis will be further examined to see if they correlate with birth weight as an indicator of fetal growth. The study is based on the hypothesis that cancer risk can be influenced in part by the hormonal environment in utero and that cancer risk is proportional to the number of primitive proliferating stem cells. Umbilical cord blood from 300 donors will be obtained from singleton birth, fullterm, and low-risk deliveries at hospitals affiliated with the American Red Cross Cord Blood Program. Hormones and other growth factors including estradiol, estriol, progesterone, prolactin, sex-hormone binding globulin (SHIBG), testosterone, insulinlike growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3) will be assayed in cord blood samples. We will measure the total number of nucleated cells, number of cells per volume expressing CD34 protein on the cell surface as well as CD34+/CD38, CD34+/c-kit, and CD45/GlyA sub-population cells, and the number of colony-formingunit granulocytes and macrophages (CFU-GM) as laboratory parameters for primitive proliferating stem cells. Among Bcl-2 family proteins we will measure the expression of Bcl-2, Bcl-xL, Bax, and Bad to construct an overall apoptotic index. We will apply
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regression analysis treating as outcome variables each measurement of stem cell potential and Bcl-2 apoptotic index and as predictor variables hormone levels, controlling for maternal and neonatal characteristics. Stem cell measurements and index of Bcl-2 apoptotic expressions will be further examined as predictors of birth weight. The study seeks to obtain information on parameters of perinatal cell proliferation relevant to intervening steps between intrauterine hormone exposure and subsequent cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE INVOLVEMENT OF THE VMH IN MATERNAL BEHAVIOR IN RATS Principal Investigator & Institution: Mann, Phyllis E.; Veterinary Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant): Based on new evidence from our laboratory, which has discovered an important inhibitory role of the ventromedial nucleus of the hypothalamus (VMH) in maternal behavior, the objective of this grant proposal is to elucidate the involvement of the VMH in the onset of maternal behavior. The experiments described in the present grant proposal will use behavioral, molecular, and anatomical approaches to identify the possible mechanisms of action of the VMH on the inhibition of maternal behavior. The hypothesis underlying the present proposal is that under normal physiological conditions the VMH inhibits the display of maternal behavior in virgin and late-pregnant rats by inhibiting the actions of the medial preoptic area (MPOA, an area considered to be crucially involved in the display of maternal behavior). The specific aim of the first three experiments will be to examine the role of the VMH in the regulation of maternal behavior in estradiol-primed, virgin rats. Experiment 1 will analyze the timing of neurotoxin administration into the VMH and subsequent maternal behavior stimulation. Experiment 2 will determine if infusions of the sodium channel blocker, tetrodotoxin, will stimulate short-latency maternal behavior, while experiment 3 will examine the role of GABA infusions into the VMH and subsequent maternal behavior. The second specific aim is to determine the changes in receptor gene expression of the key pregnancy hormones, estrogen, progesterone, and prolactin, in estradiol-primed, virgin rats. Experiments 4,5 and 6 will use in situ hybridization histochemistiy (ISHH) to determine the changes in estrogen, progesterone, and prolactin receptor gene expression, respectively, in the VMH and MPOA following estradiol stimulation in virgin rats. These 3 experiments will also investigate the changes in receptor gene expression in the MPOA following neurotoxic lesions to the VMH. The third specific aim is to determine, using anatomical, tracktracing methods, whether neurons in the VMH that are activated in the presence of pups project to the MPOA (experiment 7). Experiment 8 will determine the neurotransmitter involved in the regulation of the MPOA by the VMH. Together, these studies will help elucidate the role of the VMH in maternal behavior in virgin rats and identify the neural basis of parental care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT Principal Investigator & Institution: Freemark, Michael S.; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-MAY-1988; Project End 31-MAY-2008
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Summary: (provided by applicant): Prolactin (PRL) and placental lactogen (PL) stimulate fat deposition, weight gain, and leptin production in rodents and humans, suggesting that lactogens play roles in maternofetal lipid metabolism and obesity. The mechanisms by which lactogens promote fat storage and weight gain are unknown. We hypothesize: (a) that lactogens promote fat deposition through induction of adipogenesis, the process of differentiation of adipocytes from stromal precursors; (b) that adipogenic effects of lactogens are mediated through induction of transcription factors including PPARkhi-2; (c) that PPARkhi-2 induction is mediated through activation of Stat5; and (d) that adipogenic effects of lactogens are modulated by insulin, IGF-1, glucocorticoids, and sex steroids. To test these hypotheses we will examine effects of exogenous PRL and PL on adipogenesis in 3T3-L1 preadipocytes, primary mouse preadipocytes and embryonic fibroblasts and the effects of constitutive expression of PL in a novel 3T3-L1 cell line. To determine if lactogenic signaling is required for preadipocyte differentiation, we will compare rates of adipogenesis in preadipocytes of PRL receptor (PRLR)-deficient mice with rates of adipogenesis in cells of wild-type littermates. To characterize effects of lactogens on PPARkhi expression we will examine effects of PRL and PL on PPARkhi1 and 2 mRNA and protein levels in 3T3-L1 cells, primary preadipoyctes, mouse embryonic fibroblasts and will compare PPARkhi expression in tissues of PRLR deficient mice with that in wild-type littermates, We will examine effects of lactogens on transcriptional activation of the human and mouse PPARkhi-2 promoters expressed in 3T3-L1 cells and will compare the time course of expression of PPARkhi1I and 2 mRNAs in PRL-treated cells with that of ADD1 and c/EBPs beta, delta, and alpha. To test the hypothesis that induction of PPARkhi-2 is mediated through activation of Stat5, we will determine if lactogens induce binding of STAT 5 to consensus binding sites in the human and mPPAR c-2 promoters. We will examine the effect of mutating PPARkhi-2 Stat5 consensus sequences on lactogendependent activation of PPAR gamma2 transcription, and the effect of a dominantnegative STAT5 construct on the induction of PPARkhi mRNA and protein levels in 3T3-L1 cells. Finally, to test the hypothesis that the adipogenic effects of the lactogens are modulated by sex steroids, we will examine the effects of progesterone and estradiol on the adipogenic effects of PRL in 3T3-L 1 cells and the effects of progesterone supplementation on fat deposition and leptin production in PRLR-deficient mice. The results of our studies should provide new insist into the roles of pituitary and placental hormones in adipose development and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTION ENHANCER FACTOR CONTROL OF PLACENTAL GENES Principal Investigator & Institution: Jiang, Shi-Wen; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Syncytiotrophoblasts are a major placental component responsible for feto-maternal exchange and secretion of pregnancy-specific hormones. Syncytia formation is a hallmark of placental cell differentiation, accompanied by dramatic activation of the chorionic somatomammotropin (CS) gene. CS, growth hormone, and prolactin comprise a gene family required for normal growth, metabolism, and reproduction. We demonstrated that placental-specific human CS gene I expression is mediated by cooperative action of enhancers (CSEn) located downstream of each of the three CS genes. These enhancers stimulate the CS promoter in placental cells, but silence the promoter in pituitary cells. Members of the transcription enhancer
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factor (TEF) family bind to several GT-IIC and Sphl/Sphll elements in CSEn and mediate the CS enhancer/silencer functions. We isolated two differential splicing isoforms TEF-1beta and TEF-1gamma, and found that their limited sequence divergence is associated with stronger CSEn binding and trans-repression function than TEF-la. We cloned a new TEF family member, TEF-5, that trans-activates CSEn in placental cells. We are now addressing TEF actions on endogenous hCS gene expression and placental cell differentiation using primary cultures of human placental trophoblasts. We discovered that fusogenic membrane glycoprotein (FMG)-mediated fusion of choriocarcinoma cells (BeWo) results in activation of CSEn, providing another possible physiologic model that will facilitate the study of TEF regulation on placental cell function. Using these cell models and the newly developed TEF antibodies, we will define the function of individual TEF members by hCS/TEF expression correlation, TEF antisense experiments, and chromatin immunoprecipitation assays (Aim 1). Our preliminary studies demonstrate several fundamental insights with direct bearing on the mechanism of TEF action: 1) TEF control of GT-IIC enhancer is subject to PKC phosphorylation regulation; 2) TEF molecules bind cooperatively to direct repeats of GT-IIC sequences separated by 3 nucleotides, suggesting that TEF homo- and hetero-dimerization may be involved in their action; 3) two TEF-5 differentially spliced cDNA clones containing gross structural alterations are present in placenta and may play distinct roles in CSEr regulation. We will perform mechanistic studies on how PKC phosphorylation (Aim 2) and homo- and hetero-dimerization (Aim 3) regulate TEF DNA binding and transcriptional activities in cellular environments. We will determine TEF-5 isoform expression levels in placenta and examine their roles in CSEn function (Aim 4). The proposal addresses specific hypotheses that will enhance our understanding of TEFmediated placental gene expression and trophoblast differentiation that are important for human fetal development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF EARLY ONSET SCHIZOPRENIA SPECTRUM (TEOSS) Principal Investigator & Institution: Frazier, Jean A.; Director; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 19-SEP-2001; Project End 31-AUG-2006 Summary: (Adapted from the Applicant?s Abstract): Objectives: This is one of four identical revised applications of a collaborative R01 proposal being conducted at the University of Washington, Seattle, WA, University of North Carolina (UNC), Chapel Hill, NC, Harvard Medical School, Boston, MA and Case Western University, Cleveland, Ohio. The study will examine the long-term effectiveness of three different antipsychotic medications in the treatment of early onset schizophrenia and schizoaffective disorder: risperidone (RIS), olanzapine (OLA), the molindone (MOL) over a one year period. Specific Aims: 1) To determine the efficacy of MOL, RIS, and OLA in reducing psychotic symptoms in youth with schizophrenia and related disorders; 2) To determine the ability to sustain treatment over one year with each of these agents; 3) To examine the effects of treatment on adaptive and neurocognitive functioning; and 4) To examine the safety and tolerability of these agents in the pediatric population, particularly potential effects on neuropyramidal symptoms and weight gain. Research Design: 168 youths (ages 8-19 years) with schizophrenia, schizophreniform disorder or schizoaffective disorder and active psychotic symptoms will be recruited across four sites. Subjects will be randomly assigned to double-blind treatment with one of the three study medications. Standard dosage schedules will be
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followed, with modifications allowed dependent on the clinical status of subjects. Antipsychotic agents will be cross-tapered over the first week of the study to prevent exacerbation of psychotic symptoms. Symptom ratings and neurocognitive testing will be performed at baseline and repeated at specific intervals. The acute phase of treatment will last 8 weeks. Subjects with clinically significant improvement and without intolerable side effects, will continue maintenance therapy for an additional 44 weeks. Tolerance of the study medications will be systematically monitored with assessments for extrapyramidal side effects and weight gain. Revision of treatment algorithms, reliability testing and data analysis will be coordinated between the four sites. Randomization, preparation of study medications, and overall management of the database will be centralized at UNC. Revisions: To address reviewers concerns, the revised proposal has added a fourth site (Harvard), revised the data management and analysis plan, and adjusted some of the primary outcome measures. Significance: There are very few controlled studies to inform clinical practice for the treatment of youth with psychotic disorders. This study will provide information about the comparative effectiveness of the most commonly used and representative antipsychotic drugs in youth with schizophrenia spectrum disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “prolactin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for prolactin in the PubMed Central database: •
A bacterial cell that synthesizes a protein containing the antigenic determinants of rat prolactin. by Erwin CR, Maurer RA, Donelson JE.; 1980 Jun 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324100
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A BgIII RFLP at the human prolactin gene locus on chromosome 6 (PRL). by Myal Y, DiMattia GE, Gregory CA, Friesen HG, Hamerton JL, Shiu RP.; 1991 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333824
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A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. by Schmidhauser C, Casperson GF, Myers CA, Sanzo KT, Bolten S, Bissell MJ.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=275624
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A Single Phosphotyrosine Residue of the Prolactin Receptor is Responsible for Activation of Gene Transcription. by Lebrun J, Ali S, Goffin V, Ullrich A, Kelly PA.; 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42096
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Absolute requirement of glucocorticoid for expression of the casein gene in the presence of prolactin. by Ganguly R, Ganguly N, Mehta NM, Banerjee MR.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350201
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Activation of JAK2 Tyrosine Kinase by Prolactin Receptors in Nb2 Cells and Mouse Mammary Gland Explants. by Campbell GS, Argetsinger LS, Ihle JN, Kelly PA, Rillema JA, Carter-Su C.; 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43968
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Activation of Mitogen-Activated Protein Kinases by Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Capillary Endothelial Cells is Inhibited by the Antiangiogenic Factor 16-kDa N-Terminal Fragment of Prolactin. by D'Angelo G, Struman I, Martial J, Weiner RI.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41520
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Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma. by Barker CS, Bear SE, Keler T, Copeland NG, Gilbert DJ, Jenkins NA, Yeung RS, Tsichlis PN.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=240173
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Adenosine acts by A1 receptors to stimulate release of prolactin from anteriorpituitaries in vitro. by Yu WH, Kimura M, Walczewska A, Porter JC, McCann SM.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22760
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Analysis of prolactin-modulated gene expression profiles during the Nb2 cell cycle using differential screening techniques. by Bole-Feysot C, Perret E, Roustan P, Bouchard B, Kelly PA.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15026
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cDNA Cloning of Somatolactin, a Pituitary Protein Related to Growth Hormone and Prolactin. by Ono M, Takayama Y, Rand-Weaver M, Sakata S, Yasunaga T, Noso Y, Kawauchi H.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54103
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Central Prolactin Infusions Stimulate Maternal Behavior in Steroid-Treated, Nulliparous Female Rats. by Bridges RS, Numan M, Ronsheim PM, Mann PE, Lupini CE.; 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54880
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Characterization of BCE-1, a Transcriptional Enhancer Regulated by Prolactin and Extracellular Matrix and Modulated by the State of Histone Acetylation. by Myers CA, Schmidhauser C, Mellentin-Michelotti J, Fragoso G, Roskelley CD, Casperson G, Mossi R, Pujuguet P, Hager G, Bissell MJ.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121460
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Cloning and Expression of Stat5 and an Additional Homologue (Stat5b) Involved in Prolactin Signal Transduction in Mouse Mammary Tissue. by Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41061
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Cloning and nucleotide sequence of an ovine prolactin cDNA. by Adams TE, Baker L, Brandon MR.; 1989 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331561
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Comparison of long and short forms of the prolactin receptor on prolactin-induced milk protein gene transcription. by Lesueur L, Edery M, Ali S, Paly J, Kelly PA, Djiane J.; 1991 Feb 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50906
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Conformational Similarity of Ovine Prolactin and Bovine Growth Hormone. by Aloj SM, Edelhoch H.; 1970 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283125
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Construction and analysis of recombinant DNAs containing a structural gene for rat prolactin. by Gubbins EJ, Maurer RA, Hartley JL, Donelson JE.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=327742
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Construction and characterization of a cDNA clone containing a portion of the bovine prolactin sequence. by Nilson JH, Thomason AR, Horowitz S, Sasavage NL, Blenis J, Albers R, Salser W, Rottman FM.; 1980 Apr 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324017
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Context effects on N6-adenosine methylation sites in prolactin mRNA. by Narayan P, Ludwiczak RL, Goodwin EC, Rottman FM.; 1994 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=307810
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Cortisol rapidly reduces prolactin release and cAMP and 45Ca2+ accumulation in the cichlid fish pituitary in vitro. by Borski RJ, Helms LM, Richman NH 3rd, Grau EG.; 1991 Apr 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51318
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d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. by Naylor LH, Clark EM.; 1990 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330531
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d24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone and testosterone in male rats subjected to social isolation. by Esquifino AI, Chacon F, Jimenez V, Reyes Toso CF, Cardinali DP.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=373458
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Detection of two chromatin proteins which bind specifically to the 5'-flanking region of the rat prolactin gene. by White BA, Preston GM, Lufkin TC, Bancroft C.; 1985 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=369108
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Diagnosis and management of hyperprolactinemia. by Serri O, Chik CL, Ur E, Ezzat S.; 2003 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=191295
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Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth. by Chun TY, Gregg D, Sarkar DK, Gorski J.; 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19333
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DNA recognition element required for PUF-I mediated cell-type-specific transcription of the rat prolactin gene. by Sharp ZD, Helsel S, Cao ZD, Barron EA, Sanchez Y.; 1989 Apr 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317652
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Dual functions of a cis-acting element within the rat prolactin gene promoter. by Barron EA, Cao Z, Schneider BG, Kraig E, Carrillo AJ, Sharp ZD.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362659
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Effects of deletion of the prolactin receptor on ovarian gene expression. by Grosdemouge I, Bachelot A, Lucas A, Baran N, Kelly PA, Binart N.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151786
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Evidence for a physiological role of hypothalamic gastrin-releasing peptide to suppress growth hormone and prolactin release in the rat. by Kentroti S, Dees WL, McCann SM.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279675
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Expression Cloning of a cDNA Encoding a Fish Prolactin Receptor. by Sandra O, Sohm F, Luze AD, Prunet P, Edery M, Kelly PA.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41637
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Expression of the Xenopus laevis Prolactin and Thyrotropin Genes During Metamorphosis. by Buckbinder L, Brown DD.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46397
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Galanin regulates prolactin release and lactotroph proliferation. by Wynick D, Small CJ, Bacon A, Holmes FE, Norman M, Ormandy CJ, Kilic E, Kerr NC, Ghatei M, Talamantes F, Bloom SR, Pachnis V.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22889
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Genomic organization of rat prolactin and growth hormone genes. by Chien YH, Thompson EB.; 1980 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349888
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Identification and Functional Activity of Prolactin Receptors in Thymic Epithelial Cells. by Dardenne M, Kelly PA, Bach J, Savino W.; 1991 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52786
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Identification and sequence analysis of a second form of prolactin receptor by molecular cloning of complementary DNA from rabbit mammary gland. by Edery M, Jolicoeur C, Levi-Meyrueis C, Dusanter-Fourt I, Petridou B, Boutin JM, Lesueur L, Kelly PA, Djiane J.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286858
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Identification of a distal regulatory element in the 5' flanking region of the bovine prolactin gene. by Wolf JB, David VA, Deutch AH.; 1990 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331977
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Identification of an estrogen-responsive element from the 5'-flanking region of the rat prolactin gene. by Maurer RA, Notides AC.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=368106
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Identification of Prolactin and Growth Hormone Binding Proteins in Rabbit Milk. by Postel-Vinay M, Belair L, Kayser C, Kelly PA, Djiane J.; 1991 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52153
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Increased level of prolactin gene sequences in bromodeoxyuridine treated GH cells. by Biswas DK, Hanes SD.; 1982 Jul 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=320773
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Induction of prolactin-deficient variants of GH3 rat pituitary tumor cells by ethyl methanesulfonate: reversion by 5-azacytidine, a DNA methylation inhibitor. by Ivarie RD, Morris JA.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346329
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Inhibition of Gonadotropin Hormone-Releasing Hormone Release by Prolactin from GT1 Neuronal Cell Lines Through Prolactin Receptors. by Milenkovic L, D'Angelo G, Kelly PA, Weiner RI.; 1994 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43133
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Interaction of basal positive and negative transcription elements controls repression of the proximal rat prolactin promoter in nonpituitary cells. by Jackson SM, Keech CA, Williamson DJ, Gutierrez-Hartmann A.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=364465
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Interferon-regulatory factor 1 is an immediate-early gene under transcriptional regulation by prolactin in Nb2 T cells. by Yu-Lee LY, Hrachovy JA, Stevens AM, Schwarz LA.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360673
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Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad /estrogen receptor crosstalk. by Paez-Pereda M, Giacomini D, Refojo D, Nagashima AC, Hopfner U, Grubler Y, Chervin A, Goldberg V, Goya R, Hentges ST, Low MJ, Holsboer F, Stalla GK, Arzt E.; 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=298721
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Isolation and characterization of two peptides with prolactin release-inhibiting activity from porcine hypothalami. by Schally AV, Guoth JG, Redding TW, Groot K, Rodriguez H, Szonyi E, Stults J, Nikolics K.; 1991 May 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51487
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Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. by Schuff KG, Hentges ST, Kelly MA, Binart N, Kelly PA, Iuvone PM, Asa SL, Low MJ.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151153
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Low-calorie diet prevents the development of mammary tumors in C3H mice and reduces circulating prolactin level, murine mammary tumor virus expression, and proliferation of mammary alveolar cells. by Sarkar NH, Fernandes G, Telang NT, Kourides IA, Good RA.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347427
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Mechanism of induction of prolactin synthesis in GH cells. by Biswas DK, Hanes SD, Brennessel BA.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345662
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Membrane modification differentially affects the binding of the lactogenic hormones human growth hormone and ovine prolactin. by Bhattacharya A, Vonderhaar BK.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348835
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Modulations of prolactin and growth hormone gene expression and chromatin structure in cultured rat pituitary cells. by Levy-Wilson B.; 1983 Feb 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325755
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Molecular cloning of a prolactin-related mRNA expressed in bovine placenta. by Schuler LA, Hurley WL.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298920
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More about hyperprolactinemia. by Kovacs CS.; 2004 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=315510
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More about hyperprolactinemia. by Parmar MS.; 2004 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=315509
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N6-methyladenosine residues in an intron-specific region of prolactin pre-mRNA. by Carroll SM, Narayan P, Rottman FM.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=361031
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Neonatal administration of prolactin antiserum alters the developmental pattern of Tand B-lymphocytes in the thymus and spleen of BALB/c female mice. by Russell DH, Mills KT, Talamantes FJ, Bern HA.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282195
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Nerve Growth Factor in the Anterior Pituitary: Localization in Mammotroph Cells and Cosecretion with Prolactin by a Dopamine-Regulated Mechanism. by Missale C, Boroni F, Sigala S, Buriani A, Fabris M, Leon A, Toso RD, Spano P.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39519
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Nerve Growth Factor Suppresses the Transforming Phenotype of Human Prolactinomas. by Missale C, Boroni F, Losa M, Giovanelli M, Zanellato A, Toso RD, Balsari A, Spano P.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47267
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Nucleotide sequence of carp prolactin cDNA. by Chao SC, Pan FM, Chang WC.; 1988 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338723
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Nucleotide sequence of porcine preprolactin cDNA. by Schulz-Aellen MF, Schmid E, Movva RN.; 1989 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317735
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Nucleotide sequence of turkey prolactin. by Karatzas CN, Zadworny D, Kuhnlein U.; 1990 May 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330859
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Opposing actions of intact and N-terminal fragments of the human prolactin /growth hormone family members on angiogenesis: An efficient mechanism for the regulation of angiogenesis. by Struman I, Bentzien F, Lee H, Mainfroid V, D'Angelo G, Goffin V, Weiner RI, Martial JA.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15448
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Ovine prolactin: equilibrium characteristics of the recombinant molecule formed by noncovalent interaction of two fibrinolysin fragments by fluorescence polarization. by Jibson MD, Li CH, Glaser CB.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319451
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Pituitary Ets-1 and GABP bind to the growth factor regulatory sites of the rat prolactin promoter. by Schweppe RE, Gutierrez-Hartmann A.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29733
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Pituitary-specific chromatin structure of the rat prolactin distal enhancer element. by Willis SD, Seyfred MA.; 1996 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145752
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Prolactin Activates the Interferon-Regulated p91 Transcription Factor and the Jak2 Kinase by Tyrosine Phosphorylation. by David M, Petricoin EF III, Igarashi K, Feldman GM, Finbloom DS, Larner AC.; 1994 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44361
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Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat beta-casein gene promoter constructs in a mammary epithelial cell line. by Doppler W, Groner B, Ball RK.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286412
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Prolactin Effects on the Dietary Regulation of Mouse Mammary Tumor Virus Proviral DNA Expression. by Hamada N, Engelman RW, Tomita Y, Chen R, Iwai H, Good RA, Day NK.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54611
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Prolactin Increases CD4/CD8 Cell Ratio in Thymus-Grafted Congenitally Athymic Nude Mice. by Gaufo GO, Diamond MC.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39505
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Prolactin induces release of a factor from membranes capable of stimulating [beta]casein gene transcription in isolated mammary cell nuclei. by Teyssot B, Houdebine LM, Djiane J.; 1981 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349123
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Prolactin inhibits epidermal growth factor (EGF)-stimulated signaling events in mouse mammary epithelial cells by altering EGF receptor function. by Fenton SE, Sheffield LG.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=300991
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Prolactin is not a juvenile hormone in Xenopus laevis metamorphosis. by Huang H, Brown DD.; 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26639
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Prolactin modulates the naive B cell repertoire. by Peeva E, Michael D, Cleary J, Rice J, Chen X, Diamond B.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151869
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Prolactin Synthesized and Secreted by Human Peripheral Blood Mononuclear Cells: An Autocrine Growth Factor for Lymphoproliferation. by Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Arkins S, Kooijman R, Kutz L, Kelley KW, Malarkey WB.; 1992 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49781
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Prolactin upstream factor I mediates cell-specific transcription. by Cao ZD, Barron EA, Sharp ZD.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=365646
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Prolactin-deficient variants of GH3 rat pituitary tumor cells: linked expression of prolactin and another hormonally responsive protein in GH3 cells. by Ivarie RD, Morris JA, Martial JA.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=369771
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Prolactin-Immunoglobulin G Complexes from Human Serum Act as Costimulatory Ligands Causing Proliferation of Malignant B Lymphocytes. by Walker AM, Montgomery DW, Saraiya S, Ho TW, Garewal HS, Wilson J, Lorand L.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42149
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Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland. by Djiane J, Houdebine LM, Kelly PA.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349284
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Prostaglandin I2 modifies both prolactin binding capacity and fluidity of mouse liver membranes. by Dave JR, Knazek RA.; 1980 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350333
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Purification of a prolactin receptor. by Liscia DS, Vonderhaar BK.; 1982 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347024
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Radioimmunoreactivity and receptor-binding activity of the recombined molecule obtained by complementation of two fibrinolysin fragments of ovine prolactin. by Wong TM, Cheng CH, Li CH.; 1981 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318995
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Rapid activation of protein kinase C in isolated rat liver nuclei by prolactin, a known hepatic mitogen. by Buckley AR, Crowe PD, Russell DH.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282517
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Rapid glucocorticoid inhibition of vasoactive intestinal peptide-induced cyclic AMP accumulation and prolactin release in rat pituitary cells in culture. by Rotsztejn WH, Dussaillant M, Nobou F, Rosselin G.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349313
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Receptor to Nucleus Signaling by Prolactin and Interleukin 2 Via Activation of Latent DNA-Binding Factors. by Gilmour KC, Reich NC.; 1994 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44295
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Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormonereleasing hormone and somatostatin. by Kadar T, Redding TW, Ben-David M, Schally AV.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279662
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Reconstitution of cell-type-specific transcription of the rat prolactin gene in vitro. by Cao ZD, Barron EA, Carillo AJ, Sharp ZD.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=367990
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Regulation of Interleukin 2-Driven T-Lymphocyte Proliferation by Prolactin. by Clevenger CV, Russel DH, Appasamy PM, Prystowsky MB.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54554
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Regulatory elements controlling pituitary-specific expression of the human prolactin gene. by Peers B, Voz ML, Monget P, Mathy-Hartert M, Berwaer M, Belayew A, Martial JA.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=361059
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Role of Nitric Oxide in Control of Prolactin Release by the Adenohypophysis. by Duvilanski BH, Zambruno C, Seilicovich A, Pisera D, Lasaga M, DIaz MdC, Belova N, Rettori V, McCann SM.; 1995 Jan 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42839
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Selective transcription and DNase I protection of the rat prolactin gene by GH3 pituitary cell-free extracts. by Gutierrez-Hartmann A, Siddiqui S, Loukin S.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298824
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Site-specific methylation of the rat prolactin and growth hormone promoters correlates with gene expression. by Ngo V, Gourdji D, Laverriere JN.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231318
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Somatotropic actions of the homologous growth hormone and prolactins in the euryhaline teleost, the tilapia, Oreochromis mossambicus. by Shepherd BS, Sakamoto T, Nishioka RS, Richman NH III, Mori I, Madsen SS, Chen TT, Hirano T, Bern HA, Grau EG.; 1997 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20044
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Src Family Kinases Are Required for Prolactin Induction of Cell Proliferation. by Vara JA, Caceres MA, Silva A, Martin-Perez J.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55670
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Stoichiometric Structure-Function Analysis of the Prolactin Receptor Signaling Domain by Receptor Chimeras. by Chang WP, Ye Y, Clevenger CV.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108801
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Stress-induced release of prolactin: blockade by dexamethasone and naloxone may indicate beta-endorphin mediation. by Rossier J, French E, Rivier C, Shibasaki T, Guillemin R, Bloom FE.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348336
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TaqI and RsaI RFLP's at the prolactin inducible protein (PIP) locus on chromosome 7. by Myal Y, Gregory CA, Karpan C, Hamerton JL, Shiu RP.; 1989 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318240
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The effect of anandamide on prolactin secretion is modulated by estrogen. by Scorticati C, Mohn C, De Laurentiis A, Vissio P, Fernandez Solari J, Seilicovich A, McCann SM, Rettori V.; 2003 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149971
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The intranuclear prolactin /cyclophilin B complex as a transcriptional inducer. by Rycyzyn MA, Clevenger CV.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124481
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The Prolactin Gene is Expressed in the Hypothalamic-Neurohypophyseal System and the Protein is Processed Into a 14-kDa Fragment with Activity Like 16-kDa Prolactin. by Clapp C, Torner L, Gutierrez-Ospina G, Alcantara E, Lopez-Gomez FJ, Nagano M, Kelly PA, Mejia S, Morales MA, de la Escalera GM.; 1994 Oct 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45024
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The rat prolactin gene contains at least six poly(dT-dG).poly(dC-dA) repeats. by McFarlane D, Farrance I, Hall I, Morris J, Ivarie R.; 1986 Oct 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311799
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The Role of Endogenous Atrial Natriuretic Peptide in Resting and Stress-Induced Release of Corticotropin, Prolactin, Growth Hormone, and Thyroid-Stimulating Hormone. by Franci CR, Anselmo-Franci JA, McCann SM.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50556
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The signaling domain of the erythropoietin receptor rescues prolactin receptormutant mammary epithelium. by Brisken C, Socolovsky M, Lodish HF, Weinberg R.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137868
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Thyrotropin-releasing hormone exerts rapid nuclear effects to increase production of the primary prolactin mRNA transcript. by Potter E, Nicolaisen AK, Ong ES, Evans RM, Rosenfeld MG.; 1981 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349109
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Transcriptional and posttranscriptional regulation of the rat prolactin gene by calcium. by Preston GM, Billis WM, White BA.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360809
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Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release. by Vijayan E, Carraway R, Leeman SE, McCann SM.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282882
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Variation in the polyadenylylation site of bovine prolactin mRNA. by Sasavage NL, Smith M, Gillam S, Woychik RP, Rottman FM.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345698
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with prolactin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “prolactin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for prolactin (hyperlinks lead to article summaries): •
A case of macroprolactinoma with subclinical growth hormone production. Author(s): Kageyama K, Nigawara T, Kamata Y, Takahashi T, Anzai J, Suzuki S, Osamura YR, Suda T. Source: Endocrine Journal. 2002 February; 49(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008749
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A clinical study of taxotere versus taxotere plus the antiprolactinemic agent bromocriptine in metastatic breast cancer pretreated with anthracyclines. Author(s): Lissoni P, Bucovec R, Malugani F, Ardizzoia A, Villa S, Gardani GS, Vaghi M, Tancini G. Source: Anticancer Res. 2002 March-April; 22(2B): 1131-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12168912
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A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma. Author(s): Acquati S, Pizzocaro A, Tomei G, Giovanelli M, Libe R, Faglia G, Ambrosi B. Source: Journal of Neurosurgical Sciences. 2001 June; 45(2): 65-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11533529
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A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced? Author(s): Dinan TG, Mahmud N, Rathore O, Thakore J, Scott LV, Carr E, Naesdal J, O'Morain CA, Keeling PW. Source: Alimentary Pharmacology & Therapeutics. 2001 October; 15(10): 1613-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564001
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A luteinizing hormone-, alpha-subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies. Author(s): Saveanu A, Morange-Ramos I, Gunz G, Dufour H, Enjalbert A, Jaquet P. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2001 July; 145(1): 35-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11415850
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A molecular mimic of phosphorylated prolactin markedly reduced tumor incidence and size when DU145 human prostate cancer cells were grown in nude mice. Author(s): Xu X, Kreye E, Kuo CB, Walker AM. Source: Cancer Research. 2001 August 15; 61(16): 6098-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11507059
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A preliminary study of buspirone stimulated prolactin release in generalised social phobia: evidence for enhanced serotonergic responsivity? Author(s): Condren RM, Dinan TG, Thakore JH. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 August; 12(4): 349-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126875
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A preliminary study of dopamine-mediated prolactin inhibition in generalised social phobia. Author(s): Condren RM, Sharifi N, Thakore JH. Source: Psychiatry Research. 2002 August 5; 111(1): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140123
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A rare cause of hyperprolactinemia: persistent trigeminal artery with stalk-section effect. Author(s): Ekinci G, Baltacioglu F, Kilic T, Cimsit C, Akpinar I, Pamir N, Erzen C. Source: European Radiology. 2001; 11(4): 648-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11354761
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A retrospective hormonal and immunohistochemical evaluation of 47 acromegalic patients: prognostic value of preoperative plasma prolactin. Author(s): De Marinis L, Zuppi P, Valle D, Mancini A, Bianchi A, Lauriola L, Pasquini P, Anile C, Maira G, Giustina A. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 March; 34(3): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972303
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A serum prolactin-binding protein: implications for growth hormone. Author(s): Dannies PS. Source: Trends in Endocrinology and Metabolism: Tem. 2001 December; 12(10): 427-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701331
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A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. Author(s): Vigano D, Lissoni P, Rovelli F, Roselli MG, Malugani F, Gavazzeni C, Conti A, Maestroni G. Source: Neuroendocrinol Lett. 2001 April; 22(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11335890
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A woman with isolated prolactin deficiency. Author(s): Douchi T, Nakae M, Yamamoto S, Iwamoto I, Oki T, Nagata Y. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 April; 80(4): 368-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264615
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Absence of orgasm-induced prolactin secretion in a healthy multi-orgasmic male subject. Author(s): Haake P, Exton MS, Haverkamp J, Kramer M, Leygraf N, Hartmann U, Schedlowski M, Krueger TH. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2002 April; 14(2): 133-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979330
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ACTH, cortisol and prolactin in active rheumatoid arthritis. Author(s): Zoli A, Lizzio MM, Ferlisi EM, Massafra V, Mirone L, Barini A, Scuderi F, Bartolozzi F, Magaro M. Source: Clinical Rheumatology. 2002 August; 21(4): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189455
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Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site. Author(s): Kline JB, Moore DJ, Clevenger CV. Source: Molecular Endocrinology (Baltimore, Md.). 2001 May; 15(5): 832-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328862
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Aggregation of human wild-type and H27A-prolactin in cells and in solution: roles of Zn(2+), Cu(2+), and pH. Author(s): Sankoorikal BJ, Zhu YL, Hodsdon ME, Lolis E, Dannies PS. Source: Endocrinology. 2002 April; 143(4): 1302-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897686
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An Ets motif in the proximal decidual prolactin promoter is essential for basal gene expression. Author(s): Brar AK, Kessler CA, Handwerger S. Source: Journal of Molecular Endocrinology. 2002 August; 29(1): 99-112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200232
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An unusual form of big, big (macro) prolactin in a pregnant patient. Author(s): Diver MJ, Ewins DL, Worth RC, Bowles S, Ahlquist JA, Fahie-Wilson MN. Source: Clinical Chemistry. 2001 February; 47(2): 346-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11159789
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Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus. Author(s): Blanco-Favela F, Chavez-Rueda K, Leanos-Miranda A. Source: Lupus. 2001; 10(10): 757-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721703
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Androgen suppression and clinical improvement with dopamine agonists in hyperandrogenic-hyperprolactinemic women. Author(s): Hagag P, Hertzianu I, Ben-Shlomo A, Weiss M. Source: J Reprod Med. 2001 July; 46(7): 678-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499189
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Anti-prolactin autoantibodies in paediatric systemic lupus erythematosus patients. Author(s): Blanco-Favela F, Quintal MaG, Chavez-Rueda AK, Leanos-Miranda A, Berron-Peres R, Baca-Ruiz V, Lavalle-Montalvo C. Source: Lupus. 2001; 10(11): 803-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11789490
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Antiprolactin autoantibodies in systemic lupus erythematosus: frequency and correlation with prolactinemia and disease activity. Author(s): Leanos-Miranda A, Pascoe-Lira D, Chavez-Rueda KA, Blanco-Favela F. Source: The Journal of Rheumatology. 2001 July; 28(7): 1546-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469460
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Antipsychotic drugs and obesity: is prolactin involved? Author(s): Baptista T, Lacruz A, Meza T, Contreras Q, Delgado C, Mejias MA, Hernandez L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 November; 46(9): 829-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761634
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Antipsychotic induced hyperprolactinaemia: a series of illustrative case reports. Author(s): Haddad PM, Helleweil JS, Wieck A. Source: Journal of Psychopharmacology (Oxford, England). 2001 December; 15(4): 293-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11769824
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Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder. Author(s): Canuso CM, Goldstein JM, Wojcik J, Dawson R, Brandman D, Klibanski A, Schildkraut JJ, Green AI. Source: Psychiatry Research. 2002 August 5; 111(1): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140115
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Antipsychotic-induced hyperprolactinemia and sexual dysfunction. Author(s): Compton MT, Miller AH. Source: Psychopharmacology Bulletin. 2002 Winter; 36(1): 143-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397853
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Antipsychotics: impact on prolactin levels. Author(s): Goodnick PJ, Rodriguez L, Santana O. Source: Expert Opinion on Pharmacotherapy. 2002 October; 3(10): 1381-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387684
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Apparently complete restoration of normal daily adrenocorticotropin, cortisol, growth hormone, and prolactin secretory dynamics in adults with Cushing's disease after clinically successful transsphenoidal adenomectomy. Author(s): Veldman RG, Frolich M, Pincus SM, Veldhuis JD, Roelfsema F. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4039-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11095430
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Association between high serum prolactin levels and concomitant infections in HIVinfected patients. Author(s): Montero A, Bottasso OA, Luraghi MR, Giovannoni AG, Sen L. Source: Human Immunology. 2001 February; 62(2): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11182231
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Associations between side effects of nemonapride and plasma concentrations of the drug and prolactin. Author(s): Kondo T, Ishida M, Tokinaga N, Mihara K, Yasui-Furukori N, Ono S, Kaneko S. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 February; 26(2): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817505
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Atrial natriuretic hormone, vessel dilator, long acting natriuretic hormone, and kaliuretic hormone decrease circulating prolactin concentrations. Author(s): Vesely DL, San Miguel GI, Hassan I, Schocken DD. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 May; 34(5): 245-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063637
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Augmentation of prolactin secretion by estrogen in hypogonadal women. Author(s): Yen SS, Ehara Y, Siler TM. Source: The Journal of Clinical Investigation. 1974 February; 53(2): 652-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344580
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Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroidstimulating hormone, prolactin and alpha-subunit. Author(s): Idiculla JM, Beckett G, Statham PF, Ironside JW, Atkin SL, Patrick AW. Source: Annals of Clinical Biochemistry. 2001 September; 38(Pt 5): 566-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11587139
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Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma. Author(s): Seiler L, Braune S, Borm K, Magerkurth C, Talazko J, Peters T, Reincke M. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2002 October; 110(7): 3649. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397537
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Basal, pulsatile, entropic, and 24-hour rhythmic features of secondary hyperprolactinemia due to functional pituitary stalk disconnection mimic tumoral (primary) hyperprolactinemia. Author(s): Veldman RG, Frolich M, Pincus SM, Veldhuis JD, Roelfsema F. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 April; 86(4): 1562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11297584
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Beta-human chorionic gonadotropin and prolactin assays in cervicovaginal secretions as a predictor of preterm delivery. Author(s): Guvenal T, Kantas E, Erselcan T, Culhaoglu Y, Cetin A. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 December; 75(3): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728482
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Biologic activity and plasma clearance of prolactin-IgG complex in patients with systemic lupus erythematosus. Author(s): Leanos-Miranda A, Chavez-Rueda KA, Blanco-Favela F. Source: Arthritis and Rheumatism. 2001 April; 44(4): 866-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315926
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Biphasic action of prolactin in the regulation of murine Leydig tumor cell functions. Author(s): Manna PR, El-Hefnawy T, Kero J, Huhtaniemi IT. Source: Endocrinology. 2001 January; 142(1): 308-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145594
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Bone mineral density and prolactin associations in patients with chronic schizophrenia. Author(s): Abraham G, Halbreich U, Friedman RH, Josiassen RC. Source: Schizophrenia Research. 2003 January 1; 59(1): 17-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413637
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Bromocriptine and the expression of c-myc and c-fos in human prolactinomas. Author(s): Burdman JA, Guerra LN, Calabrese MT, Basso A. Source: Neurological Research. 2001 October; 23(7): 721-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11680511
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Cabergoline influences ovarian stimulation in hyperprolactinaemic patients with polycystic ovary syndrome. Author(s): Papaleo E, Doldi N, De Santis L, Marelli G, Marsiglio E, Rofena S, Ferrari A. Source: Human Reproduction (Oxford, England). 2001 November; 16(11): 2263-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11679501
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Changes in prolactin and testosterone levels induced by acute physical exertion in young female athletes. Author(s): Kochanska-Dziurowicz A, Gawel-Szostek V, Gabrys T, Kmita D. Source: Fiziol Cheloveka. 2001 May-June; 27(3): 100-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11548414
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Characterization of a novel and functional human prolactin receptor isoform (deltaS1PRLr) containing only one extracellular fibronectin-like domain. Author(s): Kline JB, Rycyzyn MA, Clevenger CV. Source: Molecular Endocrinology (Baltimore, Md.). 2002 October; 16(10): 2310-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351696
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Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus. Author(s): Stevens A, Ray D, Alansari A, Hajeer A, Thomson W, Donn R, Ollier WE, Worthington J, Davis JR. Source: Arthritis and Rheumatism. 2001 October; 44(10): 2358-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11665977
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Chemokines, prolactin and parasite interactions. Author(s): Pearson RD. Source: Trends in Parasitology. 2002 September; 18(9): 386. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377252
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Ciliary neurotrophic factor, a gp130 cytokine, regulates preovulatory surges of luteinizing hormone and prolactin in the rat. Author(s): Watanobe H, Habu S. Source: Neuroendocrinology. 2001 November; 74(5): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694760
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Circulating anti-prolactin auto-antibodies must be considered in the differential diagnosis of hyperprolactinaemia in adolescents. Author(s): Vanbesien J, Schiettecatte J, Anckaert E, Smitz J, Velkeniers B, De Schepper J. Source: European Journal of Pediatrics. 2002 July; 161(7): 373-6. Epub 2002 June 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111188
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Clinical features and medical treatment of male prolactinomas. Author(s): Asano S, Ueki K, Suzuki I, Kirino T. Source: Acta Neurochirurgica. 2001; 143(5): 465-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11482696
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Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas. Author(s): Ma W, Ikeda H, Yoshimoto T. Source: Cancer. 2002 July 15; 95(2): 258-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12124824
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Coitus-induced orgasm stimulates prolactin secretion in healthy subjects. Author(s): Exton MS, Kruger TH, Koch M, Paulson E, Knapp W, Hartmann U, Schedlowski M. Source: Psychoneuroendocrinology. 2001 April; 26(3): 287-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11166491
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Comparison of clozapine and haloperidol on some autonomic and psychomotor functions, and on serum prolactin concentration, in healthy subjects. Author(s): Pretorius JL, Phillips M, Langley RW, Szabadi E, Bradshaw CM. Source: British Journal of Clinical Pharmacology. 2001 September; 52(3): 322-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560566
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Comparison of prolactin concentrations between haloperidol and bromperidol treatments in schizophrenic patients. Author(s): Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Kaneko S, Otani K. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 April; 26(3): 575-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999910
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Comparison of prolactin concentrations between haloperidol and risperidone treatments in the same female patients with schizophrenia. Author(s): Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Kaneko S. Source: Psychopharmacology. 2002 June; 162(1): 63-6. Epub 2002 April 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12107619
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Comparison of the effects of cabergoline and bromocriptine on prolactin levels in hyperprolactinemic patients. Author(s): Sabuncu T, Arikan E, Tasan E, Hatemi H. Source: Intern Med. 2001 September; 40(9): 857-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579944
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Comparison of the effects of ketamine and memantine on prolactin and cortisol release in men. a randomized, double-blind, placebo-controlled trial. Author(s): Hergovich N, Singer E, Agneter E, Eichler HG, Graselli U, Simhandl C, Jilma B. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 May; 24(5): 590-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282259
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Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization. Author(s): Hu ZZ, Zhuang L, Meng J, Tsai-Morris CH, Dufau ML. Source: Endocrinology. 2002 June; 143(6): 2139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021177
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Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report. Author(s): Cattaneo FA, Fahie-Wilson MN. Source: Journal of Neurosurgery. 2001 August; 95(2): 334-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780906
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Control of unremitting rheumatoid arthritis by the prolactin antagonist cabergoline. Author(s): Erb N, Pace AV, Delamere JP, Kitas GD. Source: Rheumatology (Oxford, England). 2001 February; 40(2): 237-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257171
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Cooperation of pituitary hormone prolactin with interleukin-2 and interleukin-12 on production of interferon-gamma by natural killer and T cells. Author(s): Matera L, Mori M. Source: Annals of the New York Academy of Sciences. 2000; 917: 505-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11268378
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Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine. Author(s): Alfaro CL, Wudarsky M, Nicolson R, Gochman P, Sporn A, Lenane M, Rapoport JL. Source: Journal of Child and Adolescent Psychopharmacology. 2002 Summer; 12(2): 8391. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12188977
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Current management of prolactinomas. Author(s): Nomikos P, Buchfelder M, Fahlbusch R. Source: Journal of Neuro-Oncology. 2001 September; 54(2): 139-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11761431
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Cyclosporine A-induced mammary hyperplasia and hyperprolactinemia in New Zealand White rabbits. Author(s): Petraitiene R, Petraitis V, Bacher J, Das SR, Parlow AF, Walsh TJ. Source: Comp Med. 2001 October; 51(5): 430-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11924803
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Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes. Author(s): Dogusan Z, Hooghe R, Verdood P, Hooghe-Peters EL. Source: Journal of Neuroimmunology. 2001 November 1; 120(1-2): 58-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694320
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Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection. Author(s): Parra A, Ramirez-Peredo J, Larrea F, Cabrera V, Coutino B, Torres I, Angeles A, Perez-Romano B, Ruiz-Arguelles G, Ruiz-Arguelles A. Source: Clinical Endocrinology. 2001 June; 54(6): 731-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422107
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Decreased nocturnal levels of prolactin and growth hormone in women with fibromyalgia. Author(s): Landis CA, Lentz MJ, Rothermel J, Riffle SC, Chapman D, Buchwald D, Shaver JL. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 April; 86(4): 1672-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11297602
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Depot medroxyprogesterone acetate and basal serum prolactin levels in lactating women. Author(s): Ratchanon S, Taneepanichskul S. Source: Obstetrics and Gynecology. 2000 December; 96(6): 926-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084179
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Detection of macroprolactin causing hyperprolactinemia in commercial assays for prolactin. Author(s): Fahie-Wilson MN. Source: Clinical Chemistry. 2000 December; 46(12): 2022-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106347
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Detection of macroprolactinemia with the polyethylene glycol precipitation test in systemic lupus erythematosus patients with hyperprolactinemia. Author(s): Leanos-Miranda A, Pascoe-Lira D, Chavez-Rueda KA, Blanco-Favela F. Source: Lupus. 2001; 10(5): 340-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403264
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Determination of endometrial prolactin in vivo as a marker for endometrial development in spontaneous ovulatory cycles and in vitro fertilization cycles. Author(s): Dekker JJ, Martens F, Schoemaker J. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2001 June; 15(3): 210-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11447733
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Disorders of prolactin secretion. Author(s): Molitch ME. Source: Endocrinology and Metabolism Clinics of North America. 2001 September; 30(3): 585-610. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11571932
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Does normalization of prolactin levels result in weight loss in patients with prolactin secreting pituitary adenomas? Author(s): Yermus R, Ezzat S. Source: Clinical Endocrinology. 2002 April; 56(4): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966752
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Dopamine as a prolactin (PRL) inhibitor. Author(s): Ben-Jonathan N, Hnasko R. Source: Endocrine Reviews. 2001 December; 22(6): 724-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739329
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Dopamine receptor agonists for treating prolactinomas. Author(s): Colao A, di Sarno A, Pivonello R, di Somma C, Lombardi G. Source: Expert Opinion on Investigational Drugs. 2002 June; 11(6): 787-800. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036422
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Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Author(s): Doknic M, Pekic S, Zarkovic M, Medic-Stojanoska M, Dieguez C, Casanueva F, Popovic V. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 July; 147(1): 77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088923
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Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses. Author(s): Melkersson KI, Hulting AL, Rane AJ. Source: British Journal of Clinical Pharmacology. 2001 April; 51(4): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318766
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Ectopic production of prolactin by colorectal adenocarcinoma. Author(s): Bhatavdekar JM, Patel DD, Chikhlikar PR, Shah NG, Vora HH, Ghosh N, Trivedi TI. Source: Diseases of the Colon and Rectum. 2001 January; 44(1): 119-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805572
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Effect of bicalutamide therapy on prolactin response to L-dopa in metastatic prostate cancer patients. Author(s): Lissoni P, Malugani F, Casu M, Bukovec R, Egardi R, Bordin V, Fumagalli E, Mengo S, Gardani G. Source: Neuroendocrinol Lett. 2002 February; 23(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11880864
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Effect of branch chain amino acids supplemented with tryptophan on tyrosine availability and plasma prolactin. Author(s): Scarna A, Gijsman HJ, Harmer CJ, Goodwin GM, Cowen PJ. Source: Psychopharmacology. 2002 January; 159(2): 222-3. Epub 2001 November 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862353
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Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells. Author(s): Matera L, Mori M, Galetto A. Source: Lupus. 2001; 10(10): 728-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721699
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Effect of risperidone dose on serum prolactin level. Author(s): Daniels GH, Hayden DL, Goff DC, Kearns AE. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 May-June; 7(3): 224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421571
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Effect of seizures and antiepileptic drugs on prolactin secretions. Author(s): Wang MF. Source: Di Yi June Yi Da Xue Xue Bao. 2002 August; 22(8): 742-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376268
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Effect of the CYP2D6 genotype on prolactin concentration in schizophrenic patients treated with haloperidol. Author(s): Yasui-Furukori N, Kondo T, Suzuki A, Mihara K, Tokinaga N, Inoue Y, Otani K, Kaneko S. Source: Schizophrenia Research. 2001 October 1; 52(1-2): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595402
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Effect of transitory hyperprolactinemia on in vitro fertilization of human oocytes. Author(s): Mendes MC, Ferriani RA, Sala MM, Moura MD, Carrara HH, de Sa MF. Source: J Reprod Med. 2001 May; 46(5): 444-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396370
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Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitaryadrenal axis hormones, beta-endorphin and prolactin in human adults of both sexes. Author(s): Frias J, Torres JM, Miranda MT, Ruiz E, Ortega E. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2002 March-April; 37(2): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11912073
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Effects of long-lasting raloxifene treatment on serum prolactin and gonadotropin levels in postmenopausal women. Author(s): Lasco A, Cannavo S, Gaudio A, Morabito N, Basile G, Nicita-Mauro V, Frisina N. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 October; 147(4): 461-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370106
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Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients. Author(s): Esel E, Basturk M, Saffet Gonul A, Kula M, Tayfun Turan M, Yabanoglu I, Sofuoglu S. Source: Psychoneuroendocrinology. 2001 August; 26(6): 641-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403983
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Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone. Author(s): Kim KS, Pae CU, Chae JH, Bahk WM, Jun TY, Kim DJ, Dickson RA. Source: The Journal of Clinical Psychiatry. 2002 May; 63(5): 408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019665
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Effects of prolactin on hematopoiesis. Author(s): Welniak LA, Richards SM, Murphy WJ. Source: Lupus. 2001; 10(10): 700-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721696
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Effects of prolactin on HLA-DR and CD40 expressions by human thyrocytes. Author(s): Li J, Teng W, Shan Z. Source: Chinese Medical Journal. 2001 November; 114(11): 1151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729509
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Effects of prolactin on intracellular calcium concentration and cell proliferation in human glioma cells. Author(s): Ducret T, Boudina S, Sorin B, Vacher AM, Gourdou I, Liguoro D, Guerin J, Bresson-Bepoldin L, Vacher P. Source: Glia. 2002 May; 38(3): 200-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11968058
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Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. Author(s): Hooghe R, Dogusan Z, Martens N, Velkeniers B, Hooghe-Peters EL. Source: Lupus. 2001; 10(10): 719-27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721698
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Effects of sertraline treatment on plasma cortisol, prolactin and thyroid hormones in female depressed patients. Author(s): Sagud M, Pivac N, Muck-Seler D, Jakovljevic M, Mihaljevic-Peles A, Korsic M. Source: Neuropsychobiology. 2002; 45(3): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979064
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Effects of short and long-term lithium treatment on serum prolactin levels in patients with bipolar affective disorder. Author(s): Basturk M, Karaaslan F, Esel E, Sofuoglu S, Tutus A, Yabanoglu I. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2001 February; 25(2): 315-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11294478
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Effects of stress on serum prolactin levels in patients with systemic lupus erythematosus. Author(s): Dostal C, Marek J, Moszkorzova L, Lacinova Z, Musilova L, Zvarova J. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114279
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Effects of the gp130 cytokines ciliary neurotropic factor (CNTF) and interleukin-11 on pituitary cells: CNTF receptors on human pituitary adenomas and stimulation of prolactin and GH secretion in normal rat anterior pituitary aggregate cultures. Author(s): Perez Castro C, Carbia Nagashima A, Paez Pereda M, Goldberg V, Chervin A, Carrizo G, Molina H, Renner U, Stalla GK, Arzt E. Source: The Journal of Endocrinology. 2001 June; 169(3): 539-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375124
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Efficacy of monochemotherapy with docetaxel (taxotere) in relation to prolactin secretion in heavily pretreated metastatic breast cancer. Author(s): Lissoni P, Vaghi M, Ardizzoia A, Fumagalli E, Tancini G, Gardani G, Conti A, Maestroni GJ. Source: Neuroendocrinol Lett. 2001; 22(1): 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11335876
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Elevated bioactive prolactin levels in systemic lupus erythematosus--association with disease activity. Author(s): Pacilio M, Migliaresi S, Meli R, Ambrosone L, Bigliardo B, Di Carlo R. Source: The Journal of Rheumatology. 2001 October; 28(10): 2216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11669159
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Elevated levels of serum prolactin in patients with advanced multiple myeloma. Author(s): Gado K, Rimanoczi E, Hasitz A, Gigler G, Toth BE, Nagy GM, Paloczi K, Domjan G. Source: Neuroimmunomodulation. 2001; 9(4): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11847486
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Elevated prolactin to cortisol ratio and polyclonal autoimmune activation in Hashimoto's thyroiditis. Author(s): Legakis I, Petroyianni V, Saramantis A, Tolis G. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 October; 33(10): 585-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11607877
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Elevation of prolactin levels by atypical antipsychotics. Author(s): Turrone P, Kapur S, Seeman MV, Flint AJ. Source: The American Journal of Psychiatry. 2002 January; 159(1): 133-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11772702
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Elk-1, C/EBPalpha, and Pit-1 confer an insulin-responsive phenotype on prolactin promoter expression in Chinese hamster ovary cells and define the factors required for insulin-increased transcription. Author(s): Jacob KK, Stanley FM. Source: The Journal of Biological Chemistry. 2001 July 6; 276(27): 24931-6. Epub 2001 May 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11340077
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Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity. Author(s): Jacobi AM, Rohde W, Ventz M, Riemekasten G, Burmester GR, Hiepe F. Source: Lupus. 2001; 10(8): 554-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530997
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Estrogen, prolactin, and autoimmunity: actions and interactions. Author(s): McMurray RW. Source: International Immunopharmacology. 2001 June; 1(6): 995-1008. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407318
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Evidence of prolactin immunoreactivity in the bone marrow of untreated multiple myeloma patients. Author(s): Gado K, Nagy G, Hasitz A, Toth BE, Rimanoczi E, Domjan G. Source: Neuroimmunomodulation. 2001; 9(2): 95-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549891
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Exercise increases prolactin-receptor expression on human lymphocytes. Author(s): Dohi K, Kraemer WJ, Mastro AM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 February; 94(2): 51824. Epub 2002 October 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391112
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Expression and one-step purification of intracellular human prolactin in insect cells. Author(s): Strokovskaya L, Bartoszewicz Z, Szolajska E, Kikhno I, Solomko A, Michalik J. Source: Protein Expression and Purification. 2001 July; 22(2): 242-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11437600
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Expression of dominant-negative STAT5 inhibits growth hormone- and prolactininduced proliferation of insulin-producing cells. Author(s): Galsgaard ED, Friedrichsen BN, Nielsen JH, Moldrup A. Source: Diabetes. 2001 February; 50 Suppl 1: S40-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11272198
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Expression of ovarian prolactin receptor in relation to hormonal changes during induction of ovulation in the rat. Author(s): Kinoshita H, Yasui T, Ushigoe K, Irahara M, Tanaka M, Nakashima K, Aono T. Source: Gynecologic and Obstetric Investigation. 2001; 52(2): 132-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11586043
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Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. Author(s): Gill S, Peston D, Vonderhaar BK, Shousha S. Source: Journal of Clinical Pathology. 2001 December; 54(12): 956-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729217
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Expression of prolactin-releasing peptide and its receptor in the human adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas and neuroblastomas. Author(s): Takahashi K, Totsune K, Murakami O, Sone M, Noshiro T, Hayashi Y, Sasano H, Shibahara S. Source: Peptides. 2002 June; 23(6): 1135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126742
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Expression of prolactin-releasing peptide and its receptor in the human decidua. Author(s): Reis FM, Vigano P, Arnaboldi E, Spritzer PM, Petraglia F, Di Blasio AM. Source: Molecular Human Reproduction. 2002 April; 8(4): 356-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11912284
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Expression of prolactin-releasing peptide in human placenta and decidua. Author(s): Yasui Y, Yamaguchi M, Jikihara H, Yamamoto T, Kanzaki T, Murata Y. Source: Endocrine Journal. 2001 June; 48(3): 397-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11523913
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False hyperprolactinemia corrected by the use of heterophilic antibody-blocking agent. Author(s): Sapin R, Simon C. Source: Clinical Chemistry. 2001 December; 47(12): 2184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719493
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Fibroblast growth factor receptor 4 (FGFR4) mediates signaling to the prolactin but not the FGFR4 promoter. Author(s): Yu S, Zheng L, Asa SL, Ezzat S. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 September; 283(3): E490-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169442
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Free prolactin determinations in hyperprolactinemic men with suspicion of macroprolactinemia. Author(s): Sapin R, Gasser F, Grucker D. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 February; 316(1-2): 33-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750272
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Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women. Author(s): Pascoe-Lira D, Duran-Reyes G, Contreras-Hernandez I, Manuel-Apolinar L, Blanco-Favela F, Leanos-Miranda A. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 924-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158068
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From prolactin cell to prolactinoma. Author(s): Velkeniers B. Source: Verh K Acad Geneeskd Belg. 2001; 63(6): 561-73; Discussion 574-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11813510
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Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Author(s): Montero A, Bottasso OA, Luraghi MR, Giovannoni AG, Sen L. Source: Lancet. 2001 February 10; 357(9254): 473-4; Author Reply 475. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273087
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Gamma knife radiosurgery as a primary treatment for prolactinomas. Author(s): Pan L, Zhang N, Wang EM, Wang BJ, Dai JZ, Cai PW. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 10-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11143223
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Gamma knife radiosurgery for prolactinomas. Author(s): Landolt AM, Lomax N. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 14-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11143231
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Gender-related differences in prolactin secretion in pituitary prolactinomas. Author(s): Nishioka H, Haraoka J, Akada K, Azuma S. Source: Neuroradiology. 2002 May; 44(5): 407-10. Epub 2002 April 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012125
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Giant prolactinomas presenting as skull base tumors. Author(s): Minniti G, Jaffrain-Rea ML, Santoro A, Esposito V, Ferrante L, Delfini R, Cantore G. Source: Surgical Neurology. 2002 February; 57(2): 99-103; Discussion 103-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904200
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Giant prolactinomas: clinical management and long-term follow up. Author(s): Shrivastava RK, Arginteanu MS, King WA, Post KD. Source: Journal of Neurosurgery. 2002 August; 97(2): 299-306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186457
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Growth hormone and prolactin expression in the immune system. Author(s): Kooijman R, Gerlo S, Coppens A, Hooghe-Peters EL. Source: Annals of the New York Academy of Sciences. 2000; 917: 534-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11268381
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Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women. Author(s): Cunha-Filho JS, Gross JL, Vettori D, Dias EC, Passos EP. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 September; 33(9): 536-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11561213
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Growth hormone- and prolactin-induced proliferation of insulinoma cells, INS-1, depends on activation of STAT5 (signal transducer and activator of transcription 5). Author(s): Friedrichsen BN, Galsgaard ED, Nielsen JH, Moldrup A. Source: Molecular Endocrinology (Baltimore, Md.). 2001 January; 15(1): 136-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145745
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Growth potential of female prolactinomas. Author(s): Nishioka H, Ito H, Haraoka J, Hirano A. Source: Surgical Neurology. 2001 April; 55(4): 213-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358591
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Human skin expresses growth hormone but not the prolactin gene. Author(s): Slominski A, Malarkey WB, Wortsman J, Asa SL, Carlson A. Source: The Journal of Laboratory and Clinical Medicine. 2000 December; 136(6): 476-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128749
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Hyperprolactinaemia and its clinical significance. Author(s): Rajasoorya C. Source: Singapore Med J. 2001 September; 42(9): 398-401. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11811604
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Hyperprolactinaemia and prolactine binding in benign intracranial tumours. Author(s): Ciccarelli E, Razzore P, Gaia D, Todaro C, Longo A, Forni M, Ghe C, Camanni F, Muccioli G, Faccani G, Lanotte MM. Source: Journal of Neurosurgical Sciences. 2001 June; 45(2): 70-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11533530
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Hyperprolactinaemia caused by antipsychotic drugs. Author(s): Wieck A, Haddad P. Source: Bmj (Clinical Research Ed.). 2002 February 2; 324(7332): 250-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823343
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Hyperprolactinaemia during prolonged exercise in the heat: evidence for a centrally mediated component of fatigue in trained cyclists. Author(s): Pitsiladis YP, Strachan AT, Davidson I, Maughan RJ. Source: Experimental Physiology. 2002 March; 87(2): 215-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11856966
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Hyperprolactinaemia in patients with heart failure: clinical and immunogenetic correlations. Author(s): Limas CJ, Kroupis C, Haidaroglou A, Cokkinos DV. Source: European Journal of Clinical Investigation. 2002 February; 32(2): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895452
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Hyperprolactinemia and luteal insufficiency in infertile patients with mild and minimal endometriosis. Author(s): Cunha-Filho JS, Gross JL, Lemos NA, Brandelli A, Castillos M, Passos EP. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 April; 33(4): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11383925
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Hyperprolactinemia complicating juvenile granulosa cell tumor of the ovary. Author(s): Santala M, Suvanto-Luukkonen E, Kyllonen A, Ruokonen A, Puistola U. Source: Gynecologic Oncology. 2001 August; 82(2): 389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11531301
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Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women. Author(s): Imrich R, Rovensky J, Cervenakova Z, Ksinantova L, Kvetnansky R, Koska J. Source: Int J Tissue React. 2002; 24(2): 73-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182236
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Identification and characterization of the prolactin-binding protein in human serum and milk. Author(s): Kline JB, Clevenger CV. Source: The Journal of Biological Chemistry. 2001 July 6; 276(27): 24760-6. Epub 2001 May 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11337493
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Identification of a decidua-specific enhancer on the human prolactin gene with two critical activator protein 1 (AP-1) binding sites. Author(s): Watanabe K, Kessler CA, Bachurski CJ, Kanda Y, Richardson BD, Stanek J, Handwerger S, Brar AK. Source: Molecular Endocrinology (Baltimore, Md.). 2001 April; 15(4): 638-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11266514
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Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebocontrolled study. Author(s): Dinan TG, Scott LV, Thakore J, Naesdal J, Keeling PW. Source: Psychoneuroendocrinology. 2001 October; 26(7): 751-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11500255
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Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans. Author(s): Maccario M, Veldhuis JD, Broglio F, Vito LD, Arvat E, Deghenghi R, Ghigo E. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 March; 146(3): 310-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888836
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Implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target-of-rapamycin pathway in prolactin receptor signalling. Author(s): Boudreau RT, Sangster SM, Johnson LM, Dauphinee S, Li AW, Too CK. Source: The Journal of Endocrinology. 2002 June; 173(3): 493-506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065239
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In polymyalgia rheumatica serum prolactin is positively correlated with the number of typical symptoms but not with typical inflammatory markers. Author(s): Straub RH, Georgi J, Helmke K, Vaith P, Lang B. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 423-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961173
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In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells. Author(s): Ramamoorthy P, Sticca R, Wagner TE, Chen WY. Source: International Journal of Oncology. 2001 January; 18(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115535
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In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy. Author(s): Ferone D, Pivonello R, Lastoria S, Faggiano A, Del Basso de Caro ML, Cappabianca P, Lombardi G, Colao A. Source: Clinical Endocrinology. 2001 April; 54(4): 469-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318782
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In vivo studies of the anti-tumor effects of a human prolactin antagonist, hPRLG129R. Author(s): Chen NY, Holle L, Li W, Peirce SK, Beck MT, Chen WY. Source: International Journal of Oncology. 2002 April; 20(4): 813-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11894130
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Increase of serum prolactin during combined high-dose estrogen and progestin treatment in girls with constitutional tall stature. Author(s): Houdijk EC, Delemarre-van de Waal HA. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 December; 89(12): 1504-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195249
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Increased demand for steroid therapy in hyperprolactinemic patients with rheumatoid arthritis. Author(s): Rovensky J, Bakosova J, Payer J, Lukac J, Raffayova H, Vigas M. Source: Int J Tissue React. 2001; 23(4): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11771778
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Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Author(s): Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Source: The American Journal of Psychiatry. 2001 February; 158(2): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11156818
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Induction of preprotachykinin-I and neurokinin-1 by adrenocorticotropin and prolactin. Implication for neuroendocrine-immune-hematopoietic axis. Author(s): Maloof PB, Joshi DD, Qian J, Gascon P, Singh D, Rameshwar P. Source: Journal of Neuroimmunology. 2001 January 1; 112(1-2): 188-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108948
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Influence of midluteal serum prolactin on outcome of pregnancy after IVF-ET: a preliminary study. Author(s): Ozaki T, Takahashi K, Kurioka H, Miyazaki K. Source: Journal of Assisted Reproduction and Genetics. 2001 July; 18(7): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499323
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Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300. Author(s): Manfroid I, Martial JA, Muller M. Source: Molecular Endocrinology (Baltimore, Md.). 2001 April; 15(4): 625-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11266513
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Interferon-gamma modulates prolactin and tissue factor expression in differentiating human endometrial stromal cells. Author(s): Christian M, Marangos P, Mak I, McVey J, Barker F, White J, Brosens JJ. Source: Endocrinology. 2001 July; 142(7): 3142-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416037
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Isolated adrenocorticotropic hormone deficiency, thyroid autoimmunity, and transient hyperprolactinemia. Author(s): Gurlek A, Nar A, Gedik O. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 March-April; 7(2): 1025. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421554
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Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. Author(s): Hu ZZ, Meng J, Dufau ML. Source: The Journal of Biological Chemistry. 2001 November 2; 276(44): 41086-94. Epub 2001 August 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518703
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Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. Author(s): Leslie H, Courtney CH, Bell PM, Hadden DR, McCance DR, Ellis PK, Sheridan B, Atkinson AB. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 June; 86(6): 2743-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397880
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Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients. Author(s): Siegrist C, Benedetti C, Orlando A, Beltran JM, Tuchscherr L, Noseda CM, Brusco LI, Cardinali DP. Source: Journal of Pineal Research. 2001 January; 30(1): 34-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168905
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Latent prolactinoma on MRI-selective venous sampling and trans-sphenoidal microsurgical treatment. Author(s): Nakagawa H, Iwatsuki K, Yamada M, Hagiwara Y, Moriuchi S, Kadota T. Source: Neurological Research. 2001 October; 23(7): 691-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11680507
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Leukaemia inhibitory factor and interleukin 6 inhibit secretion of prolactin and growth hormone by rat pituitary MtT/SM cells. Author(s): Tomida M, Yoshida U, Mogi C, Maruyama M, Goda H, Hatta Y, Inoue K. Source: Cytokine. 2001 May 21; 14(4): 202-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448119
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Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels. Author(s): Schlosser R, Grunder G, Anghelescu I, Hillert A, Ewald-Grunder S, Hiemke C, Benkert O. Source: Neuropsychobiology. 2002; 46(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207145
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Long-term follow-up of 246 hyperprolactinemic patients. Author(s): Touraine P, Plu-Bureau G, Beji C, Mauvais-Jarvis P, Kuttenn F. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 February; 80(2): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167213
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Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. Author(s): Passos VQ, Souza JJ, Musolino NR, Bronstein MD. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3578-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161478
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Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia. Author(s): Maes M, van West D, De Vos N, Westenberg H, Van Hunsel F, Hendriks D, Cosyns P, Scharpe S. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 January; 24(1): 37-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106874
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Lower prolactin bioactivity in unmedicated schizophrenic patients. Author(s): Warner MD, Walker AM, D'Souza DC, Lee D, Nasseri D, Peabody CA. Source: Psychiatry Research. 2001 July 24; 102(3): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11440775
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Macroprolactin and the Roche Elecsys prolactin assay: characteristics of the reaction and detection by precipitation with polyethylene glycol. Author(s): Fahie-Wilson M, Brunsden P, Surrey J, Everitt A. Source: Clinical Chemistry. 2000 December; 46(12): 1993-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106334
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Macroprolactinaemia, the major unknown in the differential diagnosis of hyperprolactinaemia. Author(s): Cattaneo F, Kappeler D, Muller B. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2001 March 10; 131(9-10): 122-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416967
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Macroprolactinemia is clinically important. Author(s): Olukoga AO. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4833-4; Author Reply 4834. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364483
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Macroprolactinemia revisited: a study on 106 patients. Author(s): Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A, Martin PM, Jaquet P, Brue T. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 February; 87(2): 581-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836289
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Macroprolactinoma associated with Cushing's disease, successfully treated with cabergoline. Author(s): T'Sjoen G, Defeyter I, Van De Saffele J, Rubens R, Vandeweghe M. Source: J Endocrinol Invest. 2002 February; 25(2): 172-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929090
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Male prolactinoma with pituitary apoplexy concomitant with intracerebral hemorrhage--case report. Author(s): Abe T, Kawamura N, Ozawa H, Shimazu M, Izumiyama H, Matsumoto K. Source: Neurol Med Chir (Tokyo). 2002 March; 42(3): 125-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936054
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Maternal prolactin concentrations and lactational behaviour in the early postpartum period in women with lactational amenorrhoea. Author(s): Tennekoon KH. Source: Ceylon Med J. 2001 March; 46(1): 6-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570005
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Maternal prolactin secretion during labor. The role of dopamine. Author(s): Stefos T, Sotiriadis A, Tsirkas P, Messinis I, Lolis D. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 January; 80(1): 34-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167186
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Mechanisms for storage of prolactin and growth hormone in secretory granules. Author(s): Dannies PS. Source: Molecular Genetics and Metabolism. 2002 May; 76(1): 6-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12175775
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Milk prolactin, feed volume and duration between feeds in women breastfeeding their full-term infants over a 24 h period. Author(s): Cregan MD, Mitoulas LR, Hartmann PE. Source: Experimental Physiology. 2002 March; 87(2): 207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11856965
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Molecular characterization of prostate hyperplasia in prolactin-transgenic mice by using cDNA representational difference analysis. Author(s): Dillner K, Kindblom J, Flores-Morales A, Pang ST, Tornell J, Wennbo H, Norstedt G. Source: The Prostate. 2002 July 1; 52(2): 139-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111705
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Molecular heterogeneity of prolactin in the plasma of patients with systemic lupus erythematosus. Author(s): Cruz J, Avina-Zubieta A, Martinez de la Escalera G, Clapp C, Lavalle C. Source: Arthritis and Rheumatism. 2001 June; 44(6): 1331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407692
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Mood, prolactin and cortisol responses following intravenous L-tryptophan challenge: evidence for serotonergic vulnerability in first-degree relatives of bipolar patients. Author(s): Sobczak S, Honig A, van Duinen MA, Maes M, Riedel WJ. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2002 September; 5(3): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366878
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Mosquito larvae proteins modulate luteinizing hormone and prolactin release in pituitary cells of normal and estrogenized rats. Author(s): Bolognani F, Goya RG, Ronderos JR. Source: Cell Biology International. 2001; 25(2): 139-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11237418
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MR imaging of pituitary adenomas treated with the prolactin inhibitor quinagolide. Author(s): Ilkko E, Tikkakoski T, Salmela P, Pyhtinen J, Kurunlahti M. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2002 March; 43(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010287
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Multiple intracranial recurrent tumors with hyperprolactinemia combined with a parasellar malignant fibrous histiocytoma long after transfrontal surgery and irradiation to a pituitary adenoma. Author(s): Fujikawa M, Okamura K, Sato K, Shiratsuchi M, Yao T, Mizokami T, Fujishima M. Source: J Endocrinol Invest. 2001 June; 24(6): 448-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434670
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Murine prolactin-like protein E synergizes with human thrombopoietin to stimulate expansion of human megakaryocytes and their precursors. Author(s): Lefebvre P, Lin J, Linzer DI, Cohen I. Source: Experimental Hematology. 2001 January; 29(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11164105
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Ni(II)-based immobilized metal ion affinity chromatography of recombinant human prolactin from periplasmic Escherichia coli extracts. Author(s): Ueda EK, Gout PW, Morganti L. Source: J Chromatogr A. 2001 July 13; 922(1-2): 165-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486861
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No detectable prolactin in human saliva. Author(s): Thijssen JH, Matute LM, Van Goozen SH, Van Engeland H, Blankenstein MA. Source: Biological Psychiatry. 2001 November 15; 50(10): 817-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720702
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Ontogenesis of prolactin receptors in the human fetus: roles in fetal development. Author(s): Freemark M. Source: Biochemical Society Transactions. 2001 May; 29(Pt 2): 38-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356123
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Orbital invasion with prolactinoma: a clinical review of four patients. Author(s): Karcioglu ZA, Aden LB, Cruz AA, Zaslow L, Saloom RJ. Source: Ophthalmic Plastic and Reconstructive Surgery. 2002 January; 18(1): 64-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910327
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Orgasm-induced prolactin secretion: feedback control of sexual drive? Author(s): Kruger TH, Haake P, Hartmann U, Schedlowski M, Exton MS. Source: Neuroscience and Biobehavioral Reviews. 2002 January; 26(1): 31-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11835982
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p21-activated protein kinase gamma-PAK in pituitary secretory granules phosphorylates prolactin. Author(s): Tuazon PT, Lorenson MY, Walker AM, Traugh JA. Source: Febs Letters. 2002 March 27; 515(1-3): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943200
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Peripheral WBC count and serum prolactin level in various seizure types and nonepileptic events. Author(s): Shah AK, Shein N, Fuerst D, Yangala R, Shah J, Watson C. Source: Epilepsia. 2001 November; 42(11): 1472-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879352
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Physiological role of salsolinol: its hypophysiotrophic function in the regulation of pituitary prolactin secretion. Author(s): Toth BE, Bodnar I, Homicsko KG, Fulop F, Fekete MI, Nagy GM. Source: Neurotoxicology and Teratology. 2002 September-October; 24(5): 655-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200196
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Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter. Author(s): Quentien MH, Manfroid I, Moncet D, Gunz G, Muller M, Grino M, Enjalbert A, Pellegrini I. Source: The Journal of Biological Chemistry. 2002 November 15; 277(46): 44408-16. Epub 2002 September 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223489
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Postoperative hyperprolactinemia could predict longer disease-free and overall survival in node-negative breast cancer patients. Author(s): Mandala M, Lissoni P, Ferretti G, Rocca A, Torri V, Moro C, Curigliano G, Barni S. Source: Oncology. 2002; 63(4): 370-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417792
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Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery. Author(s): Amar AP, Couldwell WT, Chen JC, Weiss MH. Source: Journal of Neurosurgery. 2002 August; 97(2): 307-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186458
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Preparation and expression of biologically active prolactin and growth hormone receptors and suppressor of cytokine signaling proteins 1, 2, 3, and 6 tagged with cyan and yellow fluorescent proteins. Author(s): Ben-Yair L, Slaaby R, Herman A, Cohen Y, Biener E, Moran N, Yoshimura A, Whittaker J, De Meyts P, Herman B, Gertler A. Source: Protein Expression and Purification. 2002 August; 25(3): 456-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182826
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Prolactin and beta-endorphin serum elevations after ECT in manic patients. Author(s): Chaudhry HR, Hofmann P, Loimer N, Kotter M, Quehenberger F, Fueger G. Source: Acta Psychiatrica Scandinavica. 2000 November; 102(5): 386-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11098811
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Prolactin and growth hormone secretion after thyrotrophin-releasing hormone infusion and dopaminergic (DA2) blockade in infertile patients with minimal/mild endometriosis. Author(s): Cunha-Filho JS, Gross JL, Lemos NA, Dias EC, Vettori D, Souza CA, Passos EP. Source: Human Reproduction (Oxford, England). 2002 April; 17(4): 960-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11925390
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Prolactin and IgG-prolactin complex levels in patients with rheumatic arthritis. Author(s): Leiderman S, Gurfinkiel M, Damilano S, Lago RA, Martins S, Rosman F, Hamaui A, Maccagno A. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 252-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114280
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Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia. Author(s): Meaney AM, O'Keane V. Source: Life Sciences. 2002 July 19; 71(9): 979-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088758
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Prolactin and zinc in dialysis patients. Author(s): Castro AV, Caramori J, Barretti P, Baptistelli EE, Brandao A, Barim EM, Padovani CR, Aragon FF, Brandao-Neto J. Source: Biological Trace Element Research. 2002 July; 88(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117261
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Prolactin as an autocrine/paracrine growth factor in human cancer. Author(s): Ben-Jonathan N, Liby K, McFarland M, Zinger M. Source: Trends in Endocrinology and Metabolism: Tem. 2002 August; 13(6): 245-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12128285
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Prolactin but not ACTH increases during sodium lactate-induced panic attacks. Author(s): Otte C, Kellner M, Arlt J, Jahn H, Holsboer F, Wiedemann K. Source: Psychiatry Research. 2002 March 15; 109(2): 201-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927145
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Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. Author(s): Maguire GA. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 4: 56-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11913677
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Prolactin elevation with quetiapine. Author(s): Alexiadis M, Whitehorn D, Woodley H, Kopala L. Source: The American Journal of Psychiatry. 2002 September; 159(9): 1608-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202292
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Prolactin induces ERK phosphorylation in epithelial and CD56(+) natural killer cells of the human endometrium. Author(s): Gubbay O, Critchley HO, Bowen JM, King A, Jabbour HN. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2329-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994384
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Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells. Author(s): Chughtai N, Schimchowitsch S, Lebrun JJ, Ali S. Source: The Journal of Biological Chemistry. 2002 August 23; 277(34): 31107-14. Epub 2002 June 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060651
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Prolactin influences proliferation and apoptosis of a human IgE secreting myeloma cell line, U266. Author(s): Gado K, Pallinger E, Kovacs P, Takacs E, Szilvasi I, Toth BE, Nagy G, Domjan G, Falus A. Source: Immunology Letters. 2002 July 3; 82(3): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036601
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Prolactin is a component of the human synovial liquid and modulates the growth and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. Author(s): Ogueta S, Munoz J, Obregon E, Delgado-Baeza E, Garcia-Ruiz JP. Source: Molecular and Cellular Endocrinology. 2002 April 25; 190(1-2): 51-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11997178
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Prolactin levels in cerebrospinal fluid of patients with infantile spasms. Author(s): Aydln GB, Kose G, Degerliyurt A, Din N, Camurdanoglu D, Cakmak F. Source: Pediatric Neurology. 2002 October; 27(4): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12435564
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Prolactin modulation of immune and inflammatory responses. Author(s): Yu-Lee LY. Source: Recent Progress in Hormone Research. 2002; 57: 435-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12017556
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Prolactin receptor expression in human testis and accessory tissues: localization and function. Author(s): Hair WM, Gubbay O, Jabbour HN, Lincoln GA. Source: Molecular Human Reproduction. 2002 July; 8(7): 606-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087074
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Prolactin receptor in human endometriotic tissues. Author(s): Martinez LB, Leyva MZ, Romero IC. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 January; 81(1): 5-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11942880
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Prolactin responses to acute clomipramine and haloperidol of male schizophrenic patients in a drug-free state and after treatment with clozapine or with olanzapine. Author(s): Markianos M, Hatzimanolis J, Lykouras L, Christodoulou GN. Source: Schizophrenia Research. 2002 July 1; 56(1-2): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084414
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Prolactin secretion is not a core dimension of “atypicality”. Author(s): Grunder G, Benkert O. Source: Psychopharmacology. 2002 June; 162(1): 93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141276
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Prolactin stimulation in multiple sclerosis--an indicator of disease subtypes and activity? Author(s): Heesen C, Gold SM, Bruhn M, Monch A, Schulz KH. Source: Endocrine Research. 2002 February-May; 28(1-2): 9-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12108793
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Prolactin up-regulates cathepsin B and D expression in minor salivary glands of patients with Sjogren's syndrome. Author(s): Steinfeld S, Maho A, Chaboteaux C, Daelemans P, Pochet R, Appelboom T, Kiss R. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2000 November; 80(11): 1711-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11092531
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Prolactin/cortisol ratio in rheumatoid arthritis. Author(s): Zoli A, Ferlisi EM, Lizzio M, Altomonte L, Mirone L, Barini A, Scuderi F, Bartolozzi F, Magaro M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 508-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114312
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Prolactinomas in children and adolescents--consequences in adult life. Author(s): Duntas LH. Source: J Pediatr Endocrinol Metab. 2001; 14 Suppl 5: 1227-32; Discussion 1261-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964017
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Prolactin-producing pituitary adenoma and carcinoma with neuronal components--a metaplastic lesion. Author(s): Scheithauer BW, Horvath E, Kovacs K, Lloyd RV, Stefaneanu L, Buchfelder M, Fahlbusch R, von Werder K, Lyons DF. Source: Pituitary. 1999 May; 1(3-4): 197-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081198
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Prolactin-producing pituitary adenoma associated with prolactin cell hyperplasia. Author(s): Vidal S, Horvath E, Syro LV, Uribe H, Cohen S, Kovacs K. Source: Endocrine Pathology. 2002 Summer; 13(2): 157-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165665
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Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes betacasein gene expression in the rat mammary gland. Author(s): Kuo CB, Wu W, Xu X, Yang L, Chen C, Coss D, Birdsall B, Nasseri D, Walker AM. Source: Cell and Tissue Research. 2002 September; 309(3): 429-37. Epub 2002 July 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195299
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Quantification of prolactin receptor mRNA in multiple human tissues and cancer cell lines by real time RT-PCR. Author(s): Peirce SK, Chen WY, Chen WY. Source: The Journal of Endocrinology. 2001 October; 171(1): R1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11572805
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Quinagolide in the management of prolactinoma. Author(s): Schultz PN, Ginsberg L, McCutcheon IE, Samaan N, Leavens M, Gagel RF. Source: Pituitary. 2000 December; 3(4): 239-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788012
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Rapid detection of macroprolactin in the form of prolactin-immunoglobulin G complexes by immunoprecipitation with anti-human IgG-agarose. Author(s): Schiettecatte J, De Schepper J, Velkeniers B, Smitz J, Van Steirteghem A. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2001 December; 39(12): 1244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11798085
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Rapid re-expansion of a macroprolactinoma after early discontinuation of bromocriptine. Author(s): Orrego JJ, Chandler WF, Barkan AL. Source: Pituitary. 2000 November; 3(3): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11383485
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Re: Prolactin levels and adverse events in patients treated with risperidone. Author(s): Denisov MF. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 538-40; Author Reply 540-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352286
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Reactivity of macroprolactin in common automated immunoassays. Author(s): Schneider W, Marcovitz S, Al-Shammari S, Yago S, Chevalier S. Source: Clinical Biochemistry. 2001 September; 34(6): 469-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11676976
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Recovery of growth hormone secretion following cabergoline treatment of macroprolactinomas. Author(s): George LD, Nicolau N, Scanlon MF, Davies JS. Source: Clinical Endocrinology. 2000 November; 53(5): 595-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106920
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Regulated, adenovirus-mediated delivery of tyrosine hydroxylase suppresses growth of estrogen-induced pituitary prolactinomas. Author(s): Williams JC, Stone D, Smith-Arica JR, Morris ID, Lowenstein PR, Castro MG. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 December; 4(6): 593-602. Erratum In: Mol Ther 2002 February; 5(2): 211. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11735344
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Regulation of bcl-2 gene expression in human breast cancer cells by prolactin and its antagonist, hPRL-G129R. Author(s): Beck MT, Peirce SK, Chen WY. Source: Oncogene. 2002 August 1; 21(33): 5047-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140755
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Regulation of prolactin secretion during pregnancy and lactation. Author(s): Voogt JL, Lee Y, Yang S, Arbogast L. Source: Prog Brain Res. 2001; 133: 173-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589129
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Relapse of hyperprolactinemia after transsphenoidal surgery for microprolactinoma: lessons from long-term follow-up. Author(s): Thomson JA, Gray CE, Teasdale GM. Source: Neurosurgery. 2002 January; 50(1): 36-9; Discussion 39-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844232
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Relationship between prolactin responses to ECT and dopaminergic and serotonergic responsivity in depressed patients. Author(s): Markianos M, Hatzimanolis J, Lykouras L. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 August; 252(4): 166-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242577
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Relationship between serum prolactin levels and histology of benign and malignant breast lesions: a detailed study of 153 consecutive cases. Author(s): Nicol M, Willis C, Yiangou C, Sinnett D, Shousha S. Source: The Breast Journal. 2002 September-October; 8(5): 281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199755
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Relationship between Taq1 A dopamine D2 receptor (DRD2) polymorphism and prolactin response to bromperidol. Author(s): Mihara K, Suzuki A, Kondo T, Yasui-Furukori N, Ono S, Otani K, Kaneko S, Inoue Y. Source: American Journal of Medical Genetics. 2001 April 8; 105(3): 271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11353448
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Relationship of temperament and behaviour measures to the prolactin response to fenfluramine in depressed men. Author(s): Mulder RT, Joyce PR. Source: Psychiatry Research. 2002 April 15; 109(3): 221-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959359
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Relationships between psychotropic drug dosage, plasma drug concentration, and prolactin levels in nursing home residents. Author(s): Cohen-Mansfield J, Taylor L, Woosley R, Lipson S, Werner P, Billig N. Source: Therapeutic Drug Monitoring. 2000 December; 22(6): 688-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128236
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Relative localization of the prolactin receptor binding sites for lactogenic hormones. Author(s): Longhi SA, Blank VC, Roguin LP, Cristodero M, Retegui LA. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2001 October; 11(5): 324-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11735251
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REM sleep and prolactin in patients with non-affective psychoses. Author(s): Appelberg B, Katila H, Rimon R. Source: Psychoneuroendocrinology. 2002 August; 27(6): 661-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084659
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Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. Author(s): Di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R, Di Somma C, Faggiano A, Lombardi G, Colao A. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 November; 86(11): 5256-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701688
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Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Author(s): Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA, Murray JC, Sabo KM. Source: Blood. 2002 October 15; 100(8): 2687-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351372
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Retention of dopamine 2 receptor mRNA and absence of the protein in craniospinal and extracranial metastasis of a malignant prolactinoma: a case report. Author(s): Winkelmann J, Pagotto U, Theodoropoulou M, Tatsch K, Saeger W, Muller A, Arzberger T, Schaaf L, Schumann EM, Trenkwalder C, Stalla GK. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 January; 146(1): 81-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11751072
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Retest reliability of prolactin response to dl-fenfluramine challenge in adults. Author(s): Flory JD, Manuck SB, Muldoon MF. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 February; 26(2): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11790522
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Reversed-phase high-performance liquid chromatography method for the determination of prolactin in bacterial extracts and in its purified form. Author(s): Soares CR, Camargo IM, Morganti L, Gimbo E, Ezequiel de Oliveira J, Legoux R, Ferrara P, Bartolini P. Source: J Chromatogr A. 2002 May 10; 955(2): 229-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12075926
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Reversible galactorrhea and prolactin elevation related to fluoxetine use. Author(s): Peterson MC. Source: Mayo Clinic Proceedings. 2001 February; 76(2): 215-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213313
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Risperidone added to clozapine: impact on serum prolactin levels. Author(s): Henderson DC, Goff DC, Connolly CE, Borba CP, Hayden D. Source: The Journal of Clinical Psychiatry. 2001 August; 62(8): 605-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11561931
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Risperidone-associated hyperprolactinemia. Author(s): Kearns AE, Goff DC, Hayden DL, Daniels GH. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2000 November-December; 6(6): 425-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11155212
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Risperidone-induced increase in serum prolactin is correlated with positive symptom improvement in chronic schizophrenia. Author(s): Zhang XY, Zhou DF, Yuan CL, Zhang PY, Wu GY, Shen YC. Source: Psychiatry Research. 2002 April 15; 109(3): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959366
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Role of body temperature in exercise-induced growth hormone and prolactin release in non-trained and physically fit subjects. Author(s): Vigas M, Celko J, Koska J. Source: Endocrine Regulations. 2000 December; 34(4): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11137977
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Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression. Author(s): Yamashita H, Nevalainen MT, Xu J, LeBaron MJ, Wagner KU, Erwin RA, Harmon JM, Hennighausen L, Kirken RA, Rui H. Source: Molecular and Cellular Endocrinology. 2001 October 25; 183(1-2): 151-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11604235
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Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion. Author(s): Murakami Y, Koshimura K, Yamauchi K, Nishiki M, Tanaka J, Kato Y. Source: Endocrine Journal. 2001 April; 48(2): 123-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11456257
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Roles of prolactin and gonadotropin-releasing hormone in rheumatic diseases. Author(s): Walker SE, Jacobson JD. Source: Rheumatic Diseases Clinics of North America. 2000 November; 26(4): 713-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084941
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Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis. Author(s): Corbacho AM, Martinez De La Escalera G, Clapp C. Source: The Journal of Endocrinology. 2002 May; 173(2): 219-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010630
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Screening for macroprolactinaemia and pituitary imaging studies. Author(s): Hauache OM, Rocha AJ, Maia AC, Maciel RM, Vieira JG. Source: Clinical Endocrinology. 2002 September; 57(3): 327-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201824
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Screening for prolactin isoforms in the follicular fluid of patients undergoing in vitro fertilization. Author(s): Romao GS, Ferriani RA, Moura MD, Martins AR. Source: Gynecologic and Obstetric Investigation. 2002; 54(1): 46-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297718
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Secretion of growth hormone and prolactin during progression of the luteal phase in healthy dogs: a review. Author(s): Kooistra HS, Okkens AC. Source: Molecular and Cellular Endocrinology. 2002 November 29; 197(1-2): 167-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431809
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Serotonin transporter promoter polymorphism is associated with attenuated prolactin response to fenfluramine. Author(s): Reist C, Mazzanti C, Vu R, Tran D, Goldman D. Source: American Journal of Medical Genetics. 2001 May 8; 105(4): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378851
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Serum cortisol and prolactin response to surgical stress in infants and children. Author(s): Chana RS, Chattopadhyay D, Varshney R, Ahmad J. Source: J Indian Med Assoc. 2001 June; 99(6): 303, 305, 320. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678617
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Serum prolactin and response to treatment among cocaine-dependent individuals. Author(s): Patkar AA, Hill KP, Sterling RC, Gottheil E, Berrettini WH, Weinstein SP. Source: Addiction Biology. 2002 January; 7(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11900622
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Serum prolactin concentrations in male patients with rheumatoid arthritis. Author(s): Seriolo B, Ferretti V, Sulli A, Fasciolo D, Cutolo M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12114281
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Serum prolactin concentrations in patients infected with human immunodeficiency virus. Author(s): Collazos J, Ibarra S, Martinez E, Mayo J. Source: Hiv Clinical Trials. 2002 March-April; 3(2): 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11976991
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Serum prolactin in breastfeeding: state of the science. Author(s): Hill PD, Chatterton RT Jr, Aldag JC. Source: Biological Research for Nursing. 1999 July; 1(1): 65-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225299
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Serum prolactin is associated with apoptosis in men with human immunodeficiency virus infection. Author(s): Parra A, Ramirez-Peredo J, Larrea F, Perez-Romano B, Cabrera V, Torres I, Reyes-Nunez V, Ruiz-Arguelles G, Ruiz-Arguelles A. Source: Immunology and Cell Biology. 2001 June; 79(3): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380682
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Serum prolactin levels in Parkinson's disease and multiple system atrophy. Author(s): Winkler AS, Landau S, Chaudhuri KR. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 October; 12(5): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12420085
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Severe erectile dysfunction is a marker for hyperprolactinemia. Author(s): Johri AM, Heaton JP, Morales A. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2001 June; 13(3): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11525317
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Severe lymphocytic adenohypophysitis with selective disappearance of prolactin cells: a histologic, ultrastructural and immunoelectron microscopic study. Author(s): Horvath E, Vidal S, Syro LV, Kovacs K, Smyth HS, Uribe H. Source: Acta Neuropathologica. 2001 June; 101(6): 631-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515793
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Significance of heme oxygenase in prolactin-mediated cell proliferation and angiogenesis in human endothelial cells. Author(s): Malaguarnera L, Pilastro MR, Quan S, Ghattas MH, Yang L, Mezentsev AV, Kushida T, Abraham NG, Kappas A. Source: International Journal of Molecular Medicine. 2002 October; 10(4): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239590
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Spinal epidural lipomatosis associated with pituitary macroprolactinoma. Author(s): Fujisawa H, Hasegawa M, Tachibana O, Yamashita J. Source: Acta Neurochirurgica. 2002 February; 144(2): 213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862525
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Spontaneous remission in idiopathic hyperprolactinemia. Author(s): Zargar AH, Wani AI, Laway BA, Masoodi SR, Salahuddin M. Source: J Assoc Physicians India. 1998 May; 46(5): 485-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273299
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Stimulation of interferon regulatory factor-1 by prolactin. Author(s): Yu-Lee L. Source: Lupus. 2001; 10(10): 691-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721695
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Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. Author(s): Liu C, Tyrrell JB. Source: Pituitary. 2001 August; 4(3): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12138991
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Surgical treatment of prolactin-secreting pituitary adenomas: early results and longterm outcome. Author(s): Losa M, Mortini P, Barzaghi R, Gioia L, Giovanelli M. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12107221
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Synergistic action of prolactin (PRL) and androgen on PRL-inducible protein gene expression in human breast cancer cells: a unique model for functional cooperation between signal transducer and activator of transcription-5 and androgen receptor. Author(s): Carsol JL, Gingras S, Simard J. Source: Molecular Endocrinology (Baltimore, Md.). 2002 July; 16(7): 1696-710. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089361
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Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Author(s): Costello LC, Franklin RB. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 August; 34(8): 417-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198595
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The actions of prolactin in the brain during pregnancy and lactation. Author(s): Grattan DR. Source: Prog Brain Res. 2001; 133: 153-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589128
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The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin. Author(s): Beinfeld MC, Bittencourt JC, Bridges RS, Faris PL, Lucion AB, Nasello AG, Weller A, Felicio LF. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2001 November; 34(11): 1369-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668345
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The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering. Author(s): Lin SH, Arai AC, Wang Z, Nothacker HP, Civelli O. Source: Molecular Pharmacology. 2001 November; 60(5): 916-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641419
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The decline in serum choline concentration in humans during and after surgery is associated with the elevation of cortisol, adrenocorticotropic hormone, prolactin and beta-endorphin concentrations. Author(s): Ozarda Ilcol Y, Ozyurt G, Kilicturgay S, Uncu G, Ulus IH. Source: Neuroscience Letters. 2002 May 10; 324(1): 41-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11983290
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The effect of mifepristone on the expression of insulin-like growth factor binding protein-1, prolactin and progesterone receptor mRNA and protein during the implantation phase in human endometrium. Author(s): Qiu X, Sun X, Christow A, Stabi B, Gemzell-Danielsson K. Source: Molecular Human Reproduction. 2002 November; 8(11): 998-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397212
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The effect of prolactin and bromocriptine on human peripheral immune status. Author(s): Kadioglu P, Acbay O, Demir G, Gazioglu N, Gundogdu S. Source: J Endocrinol Invest. 2001 March; 24(3): 147-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11314742
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The effect of the menopause on prolactin levels in patients with hyperprolactinaemia. Author(s): Karunakaran S, Page RC, Wass JA. Source: Clinical Endocrinology. 2001 March; 54(3): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298080
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The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamicpituitary-gonadal axis. Author(s): Smith S, Wheeler MJ, Murray R, O'Keane V. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910254
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The High Mobility Group A2 gene is amplified and overexpressed in human prolactinomas. Author(s): Finelli P, Pierantoni GM, Giardino D, Losa M, Rodeschini O, Fedele M, Valtorta E, Mortini P, Croce CM, Larizza L, Fusco A. Source: Cancer Research. 2002 April 15; 62(8): 2398-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956103
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The 'hook effect' on serum prolactin estimation in a patient with macroprolactinoma. Author(s): Unnikrishnan AG, Rajaratnam S, Seshadri MS, Kanagasapabathy AS, Stephen DC. Source: Neurology India. 2001 March; 49(1): 78-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11303248
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The neurosurgical management of prolactinomas. Author(s): Gokalp HZ, Deda H, Attar A, Ugur HC, Arasil E, Egemen N. Source: Journal of Neurosurgical Sciences. 2000 September; 44(3): 128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11126446
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The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. Author(s): Gillam MP, Middler S, Freed DJ, Molitch ME. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4447-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364416
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The possible role of prolactin in preeclampsia: 2001, a hypothesis revisited a quarter of century later. Author(s): Parra A, Ramirez-Peredo J. Source: Medical Hypotheses. 2002 October; 59(4): 378-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208175
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The prolactin releasing peptides: RF-amide peptides. Author(s): Taylor MM, Samson WK. Source: Cellular and Molecular Life Sciences : Cmls. 2001 August; 58(9): 1206-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11577979
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The prolactin response to sulpiride in major depression: the role of the D2 receptor in depression. Author(s): Verbeeck WJ, Berk M, Paiker J, Jersky B. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 June; 11(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11418281
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The role of VIP and somatostatin in the control of GH and prolactin release in anorexia nervosa and in obesity. Author(s): Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Roguski K, Borowiec M. Source: Annals of the New York Academy of Sciences. 2000; 921: 443-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11193873
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The turkey transcription factor Pit-1/GHF-1 can activate the turkey prolactin and growth hormone gene promoters in vitro but is not detectable in lactotrophs in vivo. Author(s): Weatherly KL, Ramesh R, Strange H, Waite KL, Storrie B, Proudman JA, Wong EA. Source: General and Comparative Endocrinology. 2001 September; 123(3): 244-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589626
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Thyroid function and serum prolactin levels in patients with juvenile systemic lupus erythematosus. Author(s): Ronchezel MV, Len CA, Spinola e Castro A, Sacchetti S, Lourenzi VM, Ajzen S, Tufik S, Hilario MO. Source: J Pediatr Endocrinol Metab. 2001 February; 14(2): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11305794
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Time course of serum prolactin and sex hormones following successful renal transplantation. Author(s): Saha MT, Saha HH, Niskanen LK, Salmela KT, Pasternack AI. Source: Nephron. 2002; 92(3): 735-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372970
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Transforming growth factor-beta regulation of estradiol-induced prolactinomas. Author(s): Hentges S, Sarkar DK. Source: Frontiers in Neuroendocrinology. 2001 October; 22(4): 340-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11587556
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Transnasal surgery for prolactin-secreting pituitary adenomas in childhood and adolescence. Author(s): Abe T, Ludecke DK. Source: Surgical Neurology. 2002 June; 57(6): 369-78; Discussion 378-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176193
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Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children. Author(s): Cohen LG, Biederman J. Source: Journal of Child and Adolescent Psychopharmacology. 2001 Winter; 11(4): 43540. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838826
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Treatment versus no treatment of transient hyperprolactinemia in patients undergoing intracytoplasmic sperm injection programs. Author(s): Doldi N, Papaleo E, De Santis L, Ferrari A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2000 December; 14(6): 437-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228065
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Unusual case presentation of lichen simplex chronicus, Hodgkin's lymphoma, and nonpuerperal hyperprolactinemia-galactorrhea. Author(s): Win PK, Popescu I, Nicoloff R. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 September-October; 7(5): 388-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11585377
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Upregulation of IFN-gamma and soluble interleukin-2 receptor release and altered serum cortisol and prolactin concentration during general anesthesia. Author(s): Brand JM, Schmucker P, Breidthardt T, Kirchner H. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2001 October; 21(10): 793-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710990
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Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead. Author(s): Leite EM, Leroyer A, Nisse C, Haguenoer JM, de Burbure CY, Buchet JP, Bernard A. Source: Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals. 2002 January-February; 7(1): 49-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101784
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Use of CA15-3, CEA and prolactin for the primary diagnosis of breast cancer and correlation with the prognostic factors at the time of initial diagnosis. Author(s): Arslan N, Serdar M, Deveci S, Ozturk B, Narin Y, Ilgan S, Ozturk E, Ozguven MA. Source: Ann Nucl Med. 2000 October; 14(5): 395-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108173
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Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders. Author(s): Tollin SR. Source: J Endocrinol Invest. 2000 December; 23(11): 765-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11194712
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CHAPTER 2. NUTRITION AND PROLACTIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and prolactin.
Finding Nutrition Studies on Prolactin The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “prolactin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on prolactin: •
Milk-borne hormones: regulators of development in neonates. Author(s): Pennsylvania State University Source: Ellis, L.A. Picciano, M.F. Nutrition-today (USA). (October 1992). volume 27(5) page 6-14.
Additional consumer oriented references include: •
New insights on prolactin function. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. October 1991. volume 49 (10) page 320-321. 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “prolactin” (or a synonym): •
Analysis of the role of the mitogen-activated protein kinase in mediating cyclicadenosine 3',5'-monophosphate effects on prolactin promoter activity. Author(s): Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA. Source: Kievit, P Lauten, J D Maurer, R A Mol-Endocrinol. 2001 April; 15(4): 614-24 08888809
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Anti-tumoral action of octreotide and bromocriptine on the experimental rat prolactinoma: anti-proliferative and pro-apoptotic effects. Author(s): Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Lodz, Sterling Str. 3, 91-425 Lodz, Poland. Source: Gruszka, A Pawlikowski, M Kunert Radek, J Neuroendocrinol-Lett. 2001 October; 22(5): 343-8 0172-780X
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Differential induction of transcription factors and expression of milk protein genes by prolactin and growth hormone in the mammary gland of rabbits. Author(s): Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrze biec, 05-552 Wolka Kosowska, Poland. Source: Malewski, T Gajewska, M Zebrowska, T Zwierzchowski, L Growth-Horm-IGFRes. 2002 February; 12(1): 41-53 1096-6374
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Effect of a low tryptophan diet on the prolactin responses to the 5-HT2A agonist DOI in the rat. Author(s): University Department of Psychiatry, Warneford Hospital, Headington, Oxford.
[email protected] Source: Franklin, M Cowen, P J Pharmacopsychiatry. 2001 July; 34(4): 147-9 0176-3679
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Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats. Author(s): Department of Pharmacology, Jawaharlal Institute of Post-Graduate Medical Education & Research, Pondicherry, India. Source: Asad, M Shewade, D G Koumaravelou, K Abraham, B K Balasinor, N Ramaswamy, S J-Pharm-Pharmacol. 2001 November; 53(11): 1541-7 0022-3573
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Effect of prolactin inhibition on thermoregulation, water and food intakes in heatstressed fat-tailed male lambs. Source: Salah, M.S. AlShaikh, M.A. Al Saiadi, M.Y. Mogawer, H.H. Anim-sci. Penicuik, [Scotland] : British Society of Animal Science, 1995-. February 1995. volume 60 (pt.1) page 87-91.
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Effect of repeated L-histidine administration on plasma prolactin and growth hormone levels in rats. Author(s): Department of Pharmacology and Toxicology, University of Kuopio, Finland. Source: Lozeva, V Tuominen, R K Mannisto, P T Tuomisto, L Inflamm-Res. 2002 April; 51 Suppl 1: S44-5 1023-3830
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Effect of serotonin depletion by p-chlorophenylalanine on serum prolactin levels in estrogen-treated ovariectomized rats: insights concerning the serotoninergic, dopaminergic and opioid systems. Author(s): Division of Endocrinology, Hospital de Clinicas de Porto Alegre, Brazil. Source: Mallmann, E S Ribeiro, M F Spritzer, P M Horm-Metab-Res. 2001 June; 33(6): 337-42 0018-5043
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Effects of an alcoholic extract of fescue grass on plasma prolactin levels in cattle. Source: Sheeler, L.Volume Amoss, M.S. Bratton, G.R. PR-Tex-Agric-Exp-Stn. College Station, Tex. : The Station. December 1986. (4496) page 72-73. 0099-5142
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Effects of cocaine on basal and pulsatile prolactin levels in rhesus monkeys. Author(s): Department of Obstetrics-Gynecology, The University of Texas Health Science Center, San Antonio, Texas 78284-7836, USA. Source: Honore, G M King, T S Samuels, M H Moreno, A Siler Khodr, T M Eddy, C A Schenken, R S J-Soc-Gynecol-Investig. 2001 Nov-December; 8(6): 351-7 1071-5576
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Effects of diethylstilbestrol on the cytogenesis of prolactin cells in the pars distalis of the pituitary gland of the mouse. Author(s): Department of Anatomy, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Source: Matsubara, M Harigaya, T Nogami, H Cell-Tissue-Res. 2001 November; 306(2): 301-7 0302-766X
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Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats. Author(s): Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., 4365-1 Kashiwabara, Hotaka-machi, Minamiazumi-gun, Nagano 399-8304, Japan. Source: Moro, M Inada, Y Miyata, H Komatsu, H Kojima, M Tsujii, H Clin-ExpPharmacol-Physiol. 2001 August; 28(8): 651-8 0305-1870
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Effects of fescue seed extract on hypophysial prolactin in the rat: an immunocytochemical and ultrastructural study. Source: Manning, W.S. Bratton, G.R. Amoss, M.S. PR-Tex-Agric-Exp-Stn. College Station, Tex. : The Station. December 1986. (4495) page 72. 0099-5142
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Effects of oral cadmium exposure through puberty on plasma prolactin and gonadotropin levels and amino acid contents in various brain areas in pubertal male rats. Author(s): Laboratorio de Toxicologia, Facultad de Ciencias, Universidad de Vigo, Orense, Spain.
[email protected] Source: Lafuente, A Esquifino, A I Neurotoxicology. 2002 July; 23(2): 207-13 0161-813X
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Effects of weaning and suckling on gamma-casein and prolactin receptor mRNA levels in the mouse mammary gland during lactation. Author(s): Tokyo Univ. (Japan) Source: Kim, J.Y. Mizoguchi, Y. Kuraishi, T. Yamaguchi, H. Enami, J. Aoki, F. Imakawa, K. Sakai, S. Animal-Science-and-Technology (Japan). (August 1998). volume 69(8) page 728-733. mice mammary glands messenger rna casein prolactin hormone receptors lactation 0918-2365
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Efficacy and safety of bromocriptine in the treatment of macroprolactinomas. Author(s): Department of Endocrinology, Hopital Militaire de Tunis, Montfleury-Tunis, Tunisie. Source: Essais, O Bouguerra, R Hamzaoui, J Marrakchi, Z Hadjri, S Chamakhi, S Zidi, B Ben Slama, C Ann-Endocrinol-(Paris). 2002 December; 63(6 Pt 1): 524-31 0003-4266
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Evidence for the biosynthesis of a prolactin-releasing factor from the ovine pars tuberalis, which is distinct from thyrotropin-releasing hormone. Author(s): Molecular Neuroendocrinology Group, Rowett Research Institute, Bucksburn, Aberdeen, UK. Source: Graham, E S Webster, C A Hazlerigg, D G Morgan, P J J-Neuroendocrinol. 2002 December; 14(12): 945-54 0953-8194
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G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells. Author(s): Ottawa Health Research Institute, Department of Neuroscience, University of Ottawa, Ottawa, Canada K1H-8M5.
[email protected] Source: Albert, P R Mol-Endocrinol. 2002 August; 16(8): 1903-11 0888-8809
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Growth and carcass characteristics and serum growth hormone, insulin and prolactin in lambs supplemented with AmaFerm. Source: Herring, M.A. Hallford, D.M. Sheep-Res-J. Englewood, Colo. : Sheep Industry Development Program. Spring 1990. volume 6 (2) page 5-10. 1057-1809
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Initial studies on the administration route of prolactin. Author(s): Department of Applied Pharmacy and Drug Technology, Silesian Medical Academy, Sosnowiec, Poland. Source: Ryszka, F Dolinska, B Boll-Chim-Farm. 2001 May-June; 140(3): 169-71 0006-6648
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Modulation of prolactin hormone and intersequence pause days in domestic chickens. Author(s): Animal Physiology, National Institute of Animal Nutrition and Physiology, Adugodi, Bangalore, India. Source: Reddy, J David, C G Sarma, P V Singh, K Vet-Rec. 2001 November 10; 149(19): 590-2 0042-4900
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Pergolide as primary therapy for macroprolactinomas. Author(s): Department of Surgery, University of Michigan Medical Center and Department of Veterants Affairs Medical Center, Ann Arbor 48109, USA. Source: Orrego, J J Chandler, W F Barkan, A L Pituitary. 2000 December; 3(4): 251-6 1386-341X
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Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to endotoxin after damage of the anterior hypothalamic area. Author(s): Department of Anatomy, University of South Florida, College of Medicine, Tampa, FL 33612-4799, USA.
[email protected] Source: Phelps, C P Dong, J M Chen, L T Menzies, R A Neuroimmunomodulation. 2001; 9(6): 340-51 1021-7401
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Prolactin activation of mammary nitric oxide synthase: molecular mechanisms. Author(s): Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA.
[email protected] Source: Bolander, F F Jr J-Mol-Endocrinol. 2002 February; 28(1): 45-51 0952-5041
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Prolactin induces calcium influx and release from intracellular pools in human T lymphocytes by activation of tyrosine kinases. Author(s): Departamento de Farmacologia, Facultad de Veterinaria, USC (Univ. Santiago de Compostela) 27002, Lugo, Spain. Source: Alfonso, A Botana, M A Vieytes, M R Botana, L M Cell-Signal. 2001 November; 13(11): 819-26 0898-6568
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Prolactin levels in Behcet's disease: no correlation with disease manifestations and activity. Author(s): Department of Internal Medicine, La Rabta University Hospital, 1007 Tuni, Tunisia. Source: Houman, H Ben Ghorbel, I Lamloum, M Feki, M Khanfir, M Mebazaa, A Miled, M Ann-Med-Interne-(Paris). 2001 April; 152(3): 209-11 0003-410X
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Prolactin signalling to milk protein secretion but not to gene expression depends on the integrity of the Golgi region. Author(s): Faculte des Sciences, UCD, El Jadida, Maroc. Source: Lkhider, M Petridou, B Aubourg, A Ollivier Bousquet, M J-Cell-Sci. 2001 May; 114(Pt 10): 1883-91 0021-9533
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Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Author(s): Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Source: Gallego, M I Binart, N Robinson, G W Okagaki, R Coschigano, K T Perry, J Kopchick, J J Oka, T Kelly, P A Hennighausen, L Dev-Biol. 2001 January 1; 229(1): 163-75 0012-1606
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Prolactin-stimulated polymerization of acetyl-CoA carboxylase in explants of midpregnant rat mammary gland. Source: Oben, J.E. Dils, R.R. J-dairy-res. Cambridge : Cambridge University Press, 1929. August 2001. volume 68 (3) page 351-355. 0022-0299
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Promotion of cathepsin L activity in newt spermatogonial apoptosis induced by prolactin. Author(s): Department of Materials and Life Science, Graduate School of Science and Technology, Kumamoto University, Japan. Source: Fujimoto, Kenta Yamamoto, Takashi Kitano, Takeshi Abe, Shin Ichi FEBS-Lett. 2002 June 19; 521(1-3): 43-6 0014-5793
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Recombinant human prolactin improves antitumor effects of murine natural killer cells in vitro and in vivo. Author(s): School of Life Sciences, University of Science and Technology of China, Hefei City, China. Source: Sun, R Wei, H Zhang, J Li, A Zhang, W Tian, Z Neuroimmunomodulation. 20022003; 10(3): 169-76 1021-7401
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Relationship between norepinephrine release in the hypothalamic paraventricular nucleus and circulating prolactin levels in the Siberian hamster: role of photoperiod and the pineal gland. Author(s): Psychology Department/Behavioral Neuroscience Division, University at Buffalo, NY 14260, USA. Source: Imundo, J Bielefeld, E Dodge, J Badura, L L J-Biol-Rhythms. 2001 April; 16(2): 173-82 0748-7304
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Schistosomiasis (mansoni) has a negative impact on serum levels of estradiol, progesterone and prolactin in the female baboon (Papio cynocephalus anubis). Author(s): SLU, Uppsala (Sweden) Source: Farah, I.O. Andersson, E. Mwenda, J. Wango, E. Hau, J. Scandinavian-Journalof-Laboratory-Animal-Science (Denmark). (2001). volume 28(4) page 193-199. monkeys schistosoma mansoni oestrogens progesterone prolactin laboratory animals 0901-3393
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Stimulatory effects of hyperprolactinemia on aldosterone secretion in ovariectomized rats. Author(s): National Taipei College of Nursing, Taiwan, Republic of China. Source: Kau, Mei Mei Chang, Ling Ling Kan, Shu Fen Ho, Low Tone Wang, Paulus S JInvestig-Med. 2002 March; 50(2): 101-9 1081-5589
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Terguride attenuates prolactin levels and ameliorates insulin sensitivity and insulin binding in obese spontaneously hypertensive rats. Author(s): Institute of Experimental Neurosurgery, Hradec Kralove, Czech Republic. Source: Golda, V Fickova, M Pinterova, L Jurcovicova, J Macho, L Zorad, S Physiol-Res. 2001; 50(2): 175-82 0862-8408
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The morphometric parameters of adrenal cortex in sows: in normal condition and after prolactin infusion. Author(s): Department of Animal Physiology, University of Warmia and Mazury, Olsztyn, ul. Oczapowskiego 5, 10-718 Olsztyn, Poland.
[email protected] Source: Opalka, M Kaminska, B Doboszynska, T Dusza, L Folia-Morphol-(Warsz). 2001 November; 60(4): 317-22 0015-5659
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Zinc may regulate pituitary prolactin secretion. Source: Judd, A.M. MacLeod, R.M. Login, I.S. The Neurobiology of zinc : proceedings, symposium, Society for Neuroscience, Boston, Massachusetts, November 4-6, 1983 / editors, C.J. Frederickson, G.A. Howell, E.J. Kasarskis. New York : A.R. Liss, c1984. volume 11A page 91-104. ISBN: 0845127977
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to prolactin; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Bromocriptine Alternative names: Parlodel Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com
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CHAPTER 3. DISSERTATIONS ON PROLACTIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to prolactin. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “prolactin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on prolactin, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Prolactin ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to prolactin. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Acute and Chronic Effects of Exercise on Plasma Concentrations of Prolactin and Hematological Parameters in Women Runners Age 18-37 by Cavanaugh, D. Joy, PhD from The Ohio State University, 1982, 145 pages http://wwwlib.umi.com/dissertations/fullcit/8300219
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Adrenal Modulation of Prolactin and Pseudopregnancy and Inputs of the Noradrenergic System by Cameron, Nicole; PhD from Boston University, 2003, 174 pages http://wwwlib.umi.com/dissertations/fullcit/3083825
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Biochemical and Immunological Characterization of the Prolactin Receptor by Katoh, Masao; PhD from McGill University (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31210
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Biochemical and Physiological Studies with Salmon Prolactin by Fargher, Robert Charles; PhD from Simon Fraser University (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL48716
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Characterization of Pituitary Tumorigenesis in the Prolactin-Deficient Female Mouse by Cruz-Soto, Martha Elena; PhD from University of Cincinnati, 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3092094
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Human Prolactin: Its Purification and Radioimmuno-Assay with Applications to Physiology and Medicine by Hwang, Peter Lam Hum; PhD from Mcgill University (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15879
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Influence of Prolactin Level on Burn-Induced Immune Alterations by Dugan, Amy Louise; PhD from University of Cincinnati, 2003, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3092097
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Molecular Characterization of Two Estrogen Receptor (er) Alpha Subtype Cdnas from Goldfish (Carassius auratus) and Cross-Talk between Eralpha and ProlactinActivated Signal Transducers and Activators of Transcription (STAT) 5A by Wang, Ying; PhD from Chinese University of Hong Kong (People's Republic of China), 2003, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3099315
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Neuroanatomical Relationship between Hypothalamic Dopamine and Vasoactive Intestinal Peptide in the Regulation of Prolactin: Immunocytochemical and TractTracing Studies by Al-Zailaie, Khaled A.; PhD from University of Minnesota, 2003, 221 pages http://wwwlib.umi.com/dissertations/fullcit/3095446
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Photoperiod and the Anterior Pituitary Hormones in Growth and Development of the Atlantic Salmon, Salmo salar L., with Particular Emphasis on Growth Hormone and Prolactin by Komourdjian, Martin Paul; PhD from University of Ottawa (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK33705
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Prolactin Action and Mechanism of Action in NB2 Limphoma Cells by Elsholtz, Harry Paul; PhD from The University of Manitoba (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK57575
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Prolactin Regulation of Glycosylation-Dependent Cell Adhesion Molecule 1 Expression in Mouse Mammary Epithelial Cells by Hou, Zhaoyuan; PhD from University of Cincinnati, 2003, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3103318
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Proliferin and the Prolactin Family of Hormones in Pregnancy and Disease by Toft, Daniel Joseph; PhD from Northwestern University, 2003, 177 pages http://wwwlib.umi.com/dissertations/fullcit/3087989
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Regulation of BAX and BCL-2 Levels by a Prolactin Antagonist (HPRL-G129R) in Human Breast Cancer Model Systems by Peirce, Susan Kitchell; PhD from Clemson University, 2003, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3093219
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Relationships between Prolactin and Reproductive Function in Female Turkeys by Zadworny, David; PhD from University of Guelph (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL28994
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Structure and Sequence Variation of the Mink Prolactin Gene by Vardy, Tanya Laurel; MSc from Dalhousie University (Canada), 2003, 102 pages http://wwwlib.umi.com/dissertations/fullcit/MQ79503
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Subcellular Localization, Characterization and Regulation of Prolactin Receptors Studies on the Rat Liver and the Rabbit Mammary Gland by Ferland, Louis H; PhD from McGill University (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL31099
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Testosterone Modulation of Plasma Gonadotropin and Prolactin Patterns by Grosser, Peter M; PhD from McGill University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL46101
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The Mechanism of Lactogen Receptor Binding by Human Prolactin by Sivaprasad, Umasundari; PhD from The Ohio State University, 2003, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3093698
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The Properties and Purification of a Prolactin Receptor and the Development of a Radioreceptor Assay for Lactogenic Hormones by Shiu, Pak-Chung; PhD from McGill University (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20819
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The Role of Prolactin in Osmotic and Ionic Regulation of the Marine Form, Trachurus of the Threespine Stickleback, Gasterosteus aculeatus L. in Fresh Water by Lam, T. J.; ADVDEG from The University of British Columbia (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK03719
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 4. PATENTS ON PROLACTIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “prolactin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on prolactin, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Prolactin By performing a patent search focusing on prolactin, 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
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on prolactin: •
Accelerated release composition containing bromocriptine Inventor(s): Cincotta, Jr.; Manuel (Tiverton, RI), Cincotta; Anthony H. (Andover, MA), Pelloni; Christopher Louis (Louisville, CO), Runice; Christopher Eric (Denver, CO), Tigner; Sandra Louise (Broomfield, CO) Assignee(s): Ergo Science, Incorporated (charlestown, Ma), Geneva Pharmaceuticals, Inc. (broomfield, Co) Patent Number: 5,679,685 Date filed: June 2, 1995 Abstract: Disclosed herein is a solid oral dosage form comprising bromocriptine and one or more pharmaceutically acceptable excipients. The oral dosage form has a dissolution rate in excess of 90% in 5 minutes in 500 ml of 0.1N HCl aqueous medium at 37 C and is useful for adjusting the plasma prolactin profile of a patient. Excerpt(s): This invention relates to compositions and solid oral dosage forms containing bromocriptine and providing a substantially faster dissolution profile than prior art bromocriptine dosage forms. In another aspect, the invention relates to methods for using these compositions in solid oral dosage forms. Solid oral bromocriptine preparations have long been commercially available as bromocriptine mesylate (PARLODEL.RTM.) in tablet and capsule form containing 2.5 and 5 mg of bromocriptine, respectively. These preparations are approved in the United States for use in the treatment of certain hyperprolactinemia-associated dysfunctions and acromegaly, in the prevention of physiological lactation, and in the treatment of Parkinson's disease and prevention of tolerance to Levodopa therapy for Parkinson's disease. In these indications, the objective is to administer effective amounts of bromocriptine that will suppress prolactin throughout a 24-hour period. In fact, it has been reported that a 2.5 mg daily dose of bromocriptine is effective in suppressing prolactin to substantially uniform low levels throughout a 24-hour period. Web site: http://www.delphion.com/details?pn=US05679685__
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Administration of pirenzepine, methyl scopolamine and other muscarinic receptor antagonists for treatment of lipid metabolism disorders Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Baton Rouge, LA), Wilson; John M. (Charlestown, MA) Assignee(s): The Board of Supervisors of Louisiana State University and Agricultural (baton Rouge, La), The General Hospital Corporation (boston, Ma) Patent Number: 5,668,155 Date filed: June 20, 1994 Abstract: Disclosed are methods for improving various aberrant metabolic indices in mammals including humans by administration of muscarinic (particularly M1) receptor antagonists alone or in combination with prolactin inhibiting compounds. Preferably the administration takes place at a predetermined time (or, if a combination of muscarinic receptor antagonist and prolactin inhibitor is used, at different predetermined times) during a 24-hour period when the administration is effective (or
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its effect more pronounced). The invention has application in the treatment of lipid and glucose metabolism disorders. Excerpt(s): This invention relates to methods for the reduction in a subject, vertebrate animal or human, of at least one of the following indices of metabolism: body fat and more generally lipid stores, insulin resistance, hyperinsulinemia, hyperlipidemia, hyperlipoprotein-emia (such as chylomicrons, VLDL and LDL), and/or the increase in said subject of plasma HDL, and, more generally, the improvement of metabolism disorders, especially those associated with obesity, atherosclerosis and Type II diabetes. The methods comprise administration or timed administration of pirenzepine, methyl scopolamine, and other muscarinic M1 receptor antagonists, alone or in combination with a prolactin inhibitor, preferably a prolactin inhibitor that is also a dopamine agonist. In humans obesity can be defined as a body weight exceeding 20% of the desirable body weight for individuals of the same sex, height and frame (Salans, L. B., in Endocrinology & Metabolism, 2d Ed., McGraw-Hill, New York 1987, pp. 1203-1244; see also, R. H. Williams, Textbook of Endocrinology, 1974, pp. 904-916). In other animals (or also in humans) obesity can be determined by body weight patterns correlated with prolactin profiles given that members of a species that are young, lean and "healthy" (i.e., free of any disorders, not just metabolic disorders) have daily plasma prolactin level profiles that follow a regular pattern that is highly reproducible with a small standard deviation. Obesity, or excess fat deposits, correlate with and may trigger the onset of various lipid metabolism disorders, e.g. hypertension, Type II diabetes, atherosclerosis, etc. Web site: http://www.delphion.com/details?pn=US05668155__ •
Compositions, kits, and methods for modulating survival and differentiation of multi-potential hematopoietic progenitor cells Inventor(s): Cohen; Isaac (Wilmette, IL), Lefebvre; Phil (Chicago, IL), Lin; Jiandie (Evanston, IL), Linzer; Daniel (Evanston, IL) Assignee(s): The Board of Trustees of Northwestern University (evanston, Il) Patent Number: 6,261,841 Date filed: June 23, 2000 Abstract: The invention includes compositions, kits, and methods for modulating survival and differentiation of mammalian multi-potential hematopoietic progenitor cells using a placental glycoprotein hormone of the murine prolactin family, namely either murine prolactin-like protein E or murine prolactin-like protein F. The compositions, kits, and methods described herein can be used, for example, for in vitro or ex vivo expansion of hematopoietic precursor cells or to treat a disorder associated with aberrant hematopoiesis (e.g., pre-eclampsia and thrombocytopenia). Excerpt(s): The invention relates generally to the field of maintaining and expanding populations of hematopoietic cells ex vivo. Blood cells of all types derive from hematopoietic progenitor cells, which are multipotential (i.e., capable of differentiating into any of a variety of types of blood cells) at early stages of development. At later stages of development, a hematopoietic progenitor cell can become one of only certain types of cells, depending on the developmental path the cell has undergone. By way of example, a hematopoietic stem cell can differentiate to become either a myelo-erythroid progenitor cell or a lymphoid stem cell. If the cell becomes a myelo-crythroid progenitor cell, it can become an erythroid progenitor (and subsequently an erythrocyte) or a
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myeloid progenitor cell. A myeloid progenitor cell, in turn, can differentiate to become a megakaryocyte (MK), or one of several other types of blood cells. Platelets are derived from MKs. Thus, MKs and the physiological processes by which hematopoietic progenitor cells differentiate into MKs are involved in disorders associated with aberrant formation and activation of platelets. Many pregnancy-associated diseases (e.g., pregnancy-induced hypertension, pre-eclampsia, and diabetes) result from aberrant modulation of maternal physiology. For example, although the platelet count has been observed to decrease slightly during human pregnancy in some studies (Fay et al., 1983, Obst. Gynecol. 61:238-240), the rate of platelet production apparently increases to compensate for the dramatic increase in blood volume during pregnancy (Davison et al., 1989, Baillieres Clin. Endocrinol. Metab. 3:451-472). Aberrantly high rates of platelet activation in plasma have been clinically associated with pre-eclampsia, and antiplatelet treatment is widely used to treat pregnant women afflicted with this disorder (Beaufils et al., 1985, Lancet 1:840-842; Steyn et al., 1997, Lancet 350:1267-1271; Konijnenberg et al., 1997, Am. J. Obst. Gynecol. 176:461-469). Disorders associated with aberrantly low rates of platelet production include thrombocytopenia (e.g., that associated with leukemia and alcohol-induced thrombocytopenia). Web site: http://www.delphion.com/details?pn=US06261841__ •
High efficiency translation of mRNA molecules Inventor(s): Andrews; David W. (Hamilton, CA), Hughes; Martin John Glenton (Hamilton, CA), Vassilakos; Akaterini (Toronto, CA) Assignee(s): Mcmaster University (hamilton, Ca) Patent Number: 5,807,707 Date filed: February 12, 1996 Abstract: An increased level of translation of a selected mRNA molecule is effected by coupling specific nucleotide sequences at the 5'- and 3' -ends of a nucleic acid molecule transcribable to or which itself is the mRNA molecule. The nucleotide sequence at the 5'end is effective to increase the rate of translation initiation of the mRNA molecule in a cell while the nucleotide sequence at the 3'-end is effective to increase the period of translation of the mRNA molecule in a cell. The nucleotide sequence of the 3'-end is provided by a 3'-untranslated region (3'-UTR) of a gene, particularly that of.beta.prolactin, or an effective fragment thereof. A polyadenylation sequence preferably is provided at the 3'-end of the 3'-UTR sequence. The 3'-UTR sequence provides mRNA stabilization independent of the poly A tail. Excerpt(s): The present invention relates to the translation of messenger RNA (mRNA) molecules in cells and, in particular, to improvements in the efficiency thereof. The translational efficiency of mRNA has been shown to be due to several factors, including the 5' cap structure, the 5' leader sequence and sequences immediately surrounding the initiation codon (refs. 1 to 3--Throughout this specification, various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure). These sequences largely determine both the rate and the fidelity of initiation of translation in vitro and in vivo. More recently sequences in the coding region have also been implicated in translational efficiency (refs. 4 to 12). The relative abundance of an mRNA coding for a given gene product can also influence the amount of protein synthesized. The
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abundance of a specific mRNA species is determined both by the rate of transcript synthesis, processing and transport, as well as the translational half-life of the molecule within the cytoplasm (ref. 13). The translational half-life of an mRNA is determined by the kinetics of both mRNA inactivation (masking and unmasking) and degradation (chemical stability). The 3' untranslated region (UTR) of RNA molecules consists of a stretch of nucleotides usually containing methylation and polyadenylation sites. In most active cell systems, the RNA's are capped at the 3' end with a poly (A) stretch or tail. The UTR is thought to play several roles in translational regulation, including the control of translational initiation, control of translation during growth and differentiation of cells and RNA stability (ref. 14). In particular, the poly A tail, found on most eukaryotic mRNA species, has been shown to be a determinant of stability for many mRNAs (refs. 15 to 17). While there is evidence from involvement of polyadenylation in stabilizing transcripts in Xenopus oocytes, recent evidence also suggests that the poly A tail together with poly A binding protein may also be involved in increasing the efficiency of initiation for some mRNAs (refs. 15, 18 and 19). In addition, recent evidence suggests that polyadenylation and de-adenylation mechanisms are involved in the activation and inactivation of mRNA translation in oocytes (ref. 20). Web site: http://www.delphion.com/details?pn=US05807707__ •
Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin Inventor(s): Allaudeen; HameedSulthan S. (Durham, NC), Ekwuribe; Nnochiri Nkem (Cary, NC), Radhakrishnan; Balasingam (Chapel Hill, NC), Ramaswamy; Muthukumar (Cary, NC) Assignee(s): Protein Delivery, Inc. (durham, Nc) Patent Number: 6,191,105 Date filed: October 27, 1997 Abstract: A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to
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insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications. Excerpt(s): The present invention relates to microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents, and to methods of making and using same. The compositions of the invention may comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs, precursors, derivatives, and intermediates thereof. In the field of pharmaceutical therapeutic intervention, and the treatment of disease states and physiological conditions, a wide variety of therapeutic agents have come into use, including various proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs precursors, derivatives, and intermediates of the foregoing. For example, the use of polypeptides and proteins for the systemic treatment of specific diseases is now well accepted in medical practice. The role that the peptides play in replacement therapy is so important that many research activities are being directed towards the synthesis of large quantities by recombinant DNA technology. Many of these polypeptides are endogenous molecules which are very potent and specific in eliciting their biological actions. Other non-(poly)peptidyl therapeutic agents are equally important and pharmaceutically efficacious. Web site: http://www.delphion.com/details?pn=US06191105__ •
Ligand antagonists for treatment of breast cancer Inventor(s): Fuh; Germaine (San Francisco, CA), Wells; James A. (Burlingame, CA) Assignee(s): Genentech, Inc. (south San Francisco, Ca) Patent Number: 6,429,186 Date filed: September 19, 1994 Abstract: We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described. Methods for inhibiting the growth of breast cancer cells are also described. Excerpt(s): This invention relates to the field of polypeptide ligand and receptor interactions. In particular, it relates to the use of antagonists for treating breast cancer. Ligand induced receptor oligomerization has been proposed as a mechanism of signal transduction for the large family of tyrosine kinase receptors that contain an extracellular ligand binding domain (for reviews see Yarden et al. Ann. Rev. Biochem. 57:443 (1988); Ullrich et al. Cell 61:203 (1990)). In these models binding of one hormone molecule (or subunit) (H) per receptor (R) is thought to induce formation of an H.sub.2 R.sub.2 complex. For example, crosslinking and non-dissociating electrophoretic studies
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suggest that epidermal growth factor (EGF) promotes dimerization of the EGF receptor followed by receptor autophosphorylation and activation of the intracellular tyrosine kinase (Shector et al. Nature 278:835 (1979); Schreiber et al. J. Biol. Chem. 258: 846 (1983); Yarden et al. Biochemistry 26:1434 (1987); Yarden et al. Biochemistry 26:1443 (1987)). Studies of other tyrosine kinase receptors including the insulin receptor (Kahn et al. Proc. Natl. Acad. Sci. U.S.A. 75:4209 (1978); Kubar et al. Biochemistry 28:1086 (1989); Heffetz et al. J. Biol. Chem. 261:889 (1986), platelet derived growth factor (PDGF) receptor (Heldin et al. J. Biol. Chem. 264:8905 (1989); Hammacher et al. EMBO J. 8:2489 (1989); Seifert et al. J. Biol. Chem. 264:8771 (1989)) and insulin-like growth factor (IGF-I) receptor (Ikari et al. Mol. Endocrinol. 2:831), indicate that oligomerization of the receptor is tightly coupled to the biological effect. Other groups have recently crystallized a polypeptide hormone in complex with its extracellular binding domain (Lambert et al. J. Biol. Chem. 264:12730 (1989); Gunther et al. J. Biol. Chem. 265:22082 (1990)). However, more detailed analyses of the structural perturbations and requirements for ligand induced changes in these or other receptors have been hampered because of the complexities of these membrane associated systems and the lack of suitable quantities of highly purified natural or recombinant receptors. When purified receptors were available the assay procedures were often structured so that the nature of the hormonereceptor complex was not recognized. In U.S. Pat. No. 5,057,417, hGH binding assays were conducted using.sup.125 I-hGH competition with cold hGH for binding to the extracellular domain of recombinant hGH receptor (hGHbp), or hGH binding protein; the resulting complex was treated with antibody to the hGHbp, plus polyethylene glycol, to precipitate the complex formed. These immunoprecipitation assays suggested that hGH formed a 1:1 complex with hGHbp. This immunoprecipitation assay correctly detected the amount of.sup.125 I-hGH bound, but it incorrectly indicated a 1:1 molar ratio. Web site: http://www.delphion.com/details?pn=US06429186__ •
Method for inhibiting neoplastic disease in mammals Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Baton Rouge, LA) Assignee(s): The Board of Supervisors of Louisiana State University and Agricultural (baton Rouge, La), The General Hospital Corporation (boston, Ma) Patent Number: 5,792,748 Date filed: June 7, 1995 Abstract: This invention relates to a method for inhibiting the growth of neoplasms, in a mammal having a prolactin profile. This method involves comparing the prolactin profile of the afflicted mammal to a standard prolactin profile for healthy mammals of the same species and sex and adjusting the prolactin profile of the afflicted mammal to conform to or approach the standard prolactin profile for a mammal of the same species and sex of the afflicted mammal, thereby inhibiting the neoplastic growth. Excerpt(s): This invention relates to methods for inhibiting neoplasms and their metastases. More particularly, this invention relates to methods employing the alteration of circadian prolactin rhythms to inhibit or ablate neoplasms and their metastases. Research has demonstrated that circadian rhythms play important roles in regulating prolactin activities and vice versa. Publications such as Meier, A. H., Gen. Comp. Endocrinol. 3(Suppl 1):488-508, 1972; Meier, A. H., Trans. Am. Fish. Soc. 113:422431, 1984; Meier, A. H. et al., Current Ornithology II (ed Johnston R. E.) 303-343, 1984; Cincotta, A. H. et al., J. Endocrinol. 120:385-391, 1989; Meier, A. H., Amer. Zool. 15:905-
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916, 1975; Meier, A. H., Hormonal Correlates of Behavior (eds. Eleftherton and Sprott) 469-549, 1975 illustrate how circadian rhythms regulate prolactin activities. The resulting daily variations in responsiveness of various cell types to prolactin have a primary role in regulating numerous physiological processes, including fat storage, lipogenic responsiveness to insulin, migratory behavior, metamorphosis, reproduction, growth, pigeon cropsac development and mammary development (Meier, A. H., Gen. Comp. Endocrinol. 3(Suppl 1):488-508, 1972; Meier, A. H., Amer. Zool. 15:905-916, 1975; Meier, A. H. et al., Science 173:1240-1242, 1971). In regulating one of the foregoing physiological activities, prolactin may be observed to produce a stimulatory or an inhibitory effect on a given activity, or to have no effect on it. These varying effects have recently been shown in animals to be a function of the time of the daily endogenous peak (i.e. acrophase) of the rhythm of plasma prolactin concentration or a function of the time of daily injection of exogenous hormone (or of a substance that increases prolactin levels) or of the relation between endogenous peak and any induced peak. Furthermore, high levels of prolactin restricted to a discrete daily interval have a much greater physiologic (e.g. metabolic) effect in animals than do constant high levels throughout a day (Cincotta, A. H. et al., Horm. Metab. Res. 21:64-68, 1989; Borer, K. T. in The Hamster: Reproduction and Behavior (ed. Siegel, H. I.) 363-408, 1985). Such findings demonstrate the existence of daily response rhythms to prolactin by certain types of cells. Web site: http://www.delphion.com/details?pn=US05792748__ •
Method for treatment of obesity using prolactin modulators and diet Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Andover, MA) Assignee(s): Ergo Research Corporation (walkefield, Ri), The Board of Supervisors of Louisiana State University and Agricultural (baton Rouge, La) Patent Number: 5,744,477 Date filed: January 7, 1994 Abstract: The present invention is directed to an improvement in a method of weight and/or body-fat reduction comprising a (preferably moderate) reduction in the caloric intake of a subject in need of such treatment in combination with administration to said subject of a prolactin inhibitor. Additionally, the present invention is directed to an improvement in a method for altering and/or resetting prolactin profiles (and thereby controlling one or more metabolic disorders such as obesity, excessive body fat, hyperlipidemia, hyperlipoproteinemia, hyperglycemia, hypercholesterolemia, hyperinsulinemia, insulin resistance, glucose intolerance, and Type II diabetes) comprising administration to a subject in need of such treatment of a prolactin inhibitor at a predetermined time or times during a 24-hour period in combination with a (preferably moderate) reduction of the caloric intake of said subject. Excerpt(s): This invention relates to an improved method for the reduction in a subject, vertebrate animal or human, of weight and/or body fat stores. This method involves a reduction in caloric intake, in combination with the administration of a prolactin inhibitor. In another aspect, this invention relates to an improved method for altering and/or resetting prolactin profiles of a vertebrate subject (including a human), by administering to such subjects a prolactin inhibitor in combination with restricting the caloric intake of the subject, thereby effecting an amelioration in abnormal metabolic indices of said subject. The reduction of body weight and/or fat stores in man is of significant benefit, both cosmetically and physiologically. Whereas controlled diet and
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exercise can produce modest results in the reduction of weight and body fat deposits, these results are often unsatisfactory due to the substantial reduction in metabolic rate which accompanies a reduced calorie diet. Further, although a loss in body weight is seen with reduced caloric intake, this loss is often temporary and/or due to a reduction in lean body weight (as opposed to loss of fat). Various studies have shown that most calorie restriction diets result in weight loss approximately 40% of which is body fat lost and the remainder is lean body mass loss. Web site: http://www.delphion.com/details?pn=US05744477__ •
Method of producing a 19P2 ligand Inventor(s): Masato; Suenaga (Hyogo, JP), Osamu; Nishimura (Hyogo, JP), Takeo; Moriya (Osaka, JP), Yoko; Tanaka (Kyoto, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 6,103,882 Date filed: June 26, 1998 Abstract: The method of the present invention is suitable for the commercial high-level production of a protein or peptide which can be used as a prophylactic and therapeutic drug for various diseases such as senile dementia, cerebrovascular dementia (dementia arising from cerebrovascular disorders), dementia associated with genealogical retroplastic diseases (e.g. Alzheimer's disease, Parkinson's disease, Pick's disease, Huntington's disease, etc.), dementia associated with infectious diseases (e.g. Creutzfeldt-Jakob's and other virus diseases), dementia associated with endocrine or metabolic disease or toxicosis (e.g. hypothyroidism, vitamin B12 deficiency, alcoholism, intoxication by drugs, metals, and organic compounds), dementia associated with tumorigenic diseases (e.g. brain tumor), dementia associated with traumatic diseases (e.g. chronic subarachnoidal hemorrhage), and other types of dementia, depression, hyperactive child syndrome (microencephalopathy), and disturbance of consciousness. Additionally, the ligand polypeptide of the present invention has prolactin secretionstimulating and inhibiting activities. Excerpt(s): The present invention relates to a method of producing a 19P2 ligand (19P2L) or an amide thereof or a salt thereof which comprises preparing a fusion protein or peptide and subjecting said fusion protein or peptide to a peptide bond cleavage reaction. In the production of a protein or peptide by recombinant DNA technology, it is more or less common practice to have the protein or peptide expressed in the form of a fusion protein in view of the liability of the protein or peptide to be decomposed within living cells. For excision of the objective protein or peptide from the fusion protein, a chemical method for cleavage using cyanogen bromide (Itakura et al., Science, 198,1056, 1977) and an enzymatic method using factor Xa (Nagai et al., Methods in Enzymology, 153, 46, 1987) are known. Furthermore, as a method for cleavage of a peptide bond in a protein, cleavage of the acylcysteine bond with 2-nitro-5-thiocyanobenzoic acid is known [Seikagaku Jikken Koza 1, Tanpakushitsu-no-Kagaku II (Biochemical Experiment Series 1, Protein Chemistry II), Japanese Society of Biochemistry (ed.), Tokyo Kagaku Dojin, 247-250, 1976]. However, there is no disclosure on the excision of an objective protein or peptide from a protein. Web site: http://www.delphion.com/details?pn=US06103882__
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Method of regulating immune function Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Andover, MA) Assignee(s): The Board of Supervisors of Louisiana State University and Agricultural (boston, Ma), The General Hopital Corporation (baton Rouge, La) Patent Number: 6,075,020 Date filed: December 3, 1998 Abstract: Disclosed herein is a method of treating an immune system dysfunction in a mammal by administering a prolactin reducer and a prolactin enhancer at a predetermined time or times. Excerpt(s): This invention relates to methods for rectifying or ameliorating abnormal responses of the mammalian immune system, and modifying normal responses of the mammalian immune system. More particularly, this invention relates to methods employing the alteration of prolactin rhythms as a method of adjusting mammalian immune response. The importance of neuroendocrine regulation of immunity has become increasingly evident during the past decade (Besedovsky, H. O. et al., J. Immunol. 135:750s-754s, 1985; Blalock, J. E., Physiol. Rev. 69: 1-54, 1989; Berozi, I., Dev. Comp. Immunol. 13:329-341, 1989). Much of this interest has focused on the anterior pituitary hormone prolactin, which has been reported to have potent, albeit inconsistent and often conflicting, effects on immune activity (Gala, R. R., Proc. Soc. Exp. Biol. Med. 198:5-13, 1991; Nicoletti, J. et al., Reprod. Immunol. 15:113-121, 1989; Vidaller, A., et al., Clin. Immunol. Immunopathol. 38:337-343, 1986; Gerli, R. et al., Clin. Immunol. 7:463470, 1987). Other lines of evidence reveal an association between hyperprolactinemia (i.e. elevated levels of circulating endogenous prolactin) which is due to natural, pathological, pharmaceutical, or stress conditions, and states of immune dysfunction, such as immunosuppression or autoimmune diseases. The autoimmune diseases for which exacerbative associations with prolactin have been observed in the past include rheumatoid arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis. Nicoletti, J. et al., Reprod. Immunol. 15:113-121, 1989; Vidaller, A., et al., Clin. Immunol. Immunopathol. 38:337-343, 1986; Gerli, R. et al., Clin. Immunol. 7:463-470, 1987; McMurray, R. et al., J. Immunol. 147:3780, 1991. Web site: http://www.delphion.com/details?pn=US06075020__
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Method of treating hyperprolactinemia and prolactinomas Inventor(s): Culler; Michael D. (Hopkinton, MA), Melmed; Shlomo (Los Angeles, CA), Shimon; Ilan (Beverly Hills, CA) Assignee(s): Cedars-sinai Medical Center (los Angeles, Ca) Patent Number: 5,972,893 Date filed: May 6, 1997 Abstract: A method of treating hyperprolactinemia in an animal, including a human, administers one or more somatostatin type-5 receptor agonist(s) to, for example, lower abnormally high levels of prolactin in the blood of the animal. A method of treating a subject, including a human, afflicted by a prolactinoma, administers one or more type-5 receptor selective agonist(s) to, for example, lower prolactin secretion and/or decrease tumor size in the subject.
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Excerpt(s): This invention relates to the field of hyperprolactinemias, and prolactinomas. More specifically, this invention relates to the treatment of a subject afflicted with either condition, and the lowering of prolactin levels and/or the size of the tumor by administration of a selected family of pharmaceuticals. Prolactin hypersecretion, or hyperprolactinemia, may have anyone of a number of functional causes, including various neurogenic causes such as thoracic sensory nerve stimulation, stress, and psychogenic causes, various hypothalamic causes such as diffuse processes, granulomatous diseases, neoplasms, stalk section, empty sella, non-lactotropic cell pituitary tumors, and prostradiation treatment to sella, various pituitary causes such as prolactinomas and pituitary lactotropic cell hyperplasia, and various endocrine causes such as pregnancy, estrogen administration, hypothyroidism, and adrenal insufficiency. Prolactin hypersecretion may also be caused by the administration of drugs which impair dopamine secretion, such as psychotropic drugs, antihypertensive drugs, antiemetic drugs, H.sub.2 -receptor blockers, and opiates, among others. Prolactinomas are pituitary tumors, in fact, the most common pituitary tumors, which are almost five times more common in women than in men. Some prolactinomas respond to, and may be treated with, the dopamine agonist, Bromocriptine. One-third of the patients afflicted with prolactinomas, however, do not respond to, and are therefore not treatable with, this drug. The latter are usually referred for pituitary surgery and/or, rarely, irradiation. Web site: http://www.delphion.com/details?pn=US05972893__ •
Methods for the determination and adjustment of prolactin daily rhythms Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Baton Rouge, LA) Assignee(s): Ergo Research Corporation (wakefield, Ri), The Board of Supervisors of Louisiana State University and Agricultural (baton Rouge, La) Patent Number: 5,830,895 Date filed: June 1, 1995 Abstract: Methods for detecting abnormalities in prolactin daily rhythms of a subject are provided. Prolactin levels of a subject are compared to levels of healthy subjects and based on the comparison a determination is made of the adjustments necessary to normalize the subject's daily prolactin rhythm. Also provided are methods for normalizing a subject's daily prolactin rhythm. Excerpt(s): This invention relates to improved methods for the reduction in a subject, vertebrate animal or human, of body fat stores, and reduction of at least one of insulin resistance, hyperinsulinemia, hyperlipidemia, hyperglycemia, and other metabolic diseases, especially those associated with Type II diabetes. In particular the present invention is directed to methods for: (i) normalizing the daily prolactin rhythms of a human or vertebrate animal; (ii) diagnosing aberrant daily prolactin rhythms of a human or vertebrate animal; and (iii) determining the appropriate adjustments that need to be made to normalize such aberrant prolactin rhythms. Such adjustments include the daily administration to the subject of at least one of a prolactin stimulator and/or a prolactin inhibitor at a predetermined time of day (if only one is administered) or at different predetermined times of day (if both are administered). This therapy typically results in the long-term adjustment of aberrant or abnormal prolactin rhythms so that they conform to or simulate normal prolactin cycles, at which point the therapy may be discontinued, while the adjustment permits. This invention is also directed to improved methods for adjusting the neural oscillator (or oscillators) of which the daily prolactin rhythm is an expression or marker. The adjustment of daily prolactin rhythms
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and the daily rhythms of key neural oscillators results in reduction and control over an extended time period of various metabolic or other disorders. Web site: http://www.delphion.com/details?pn=US05830895__ •
Methods of identifying compounds for controlling absence seizures in a mammal relating to prolactin-releasing peptide(PrRP) Inventor(s): Civelli; Olivier (Irvine, CA), Lin; Steven (Upland, CA) Assignee(s): The Regents of the University of California (oakland, Ca) Patent Number: 6,383,764 Date filed: April 28, 2000 Abstract: The invention provides a substantially pure Prolactin Releasing Peptide (PrRP) functional analog which suppresses absence seizures in a mammal, and related pharmaceutical compositions. The invention also provides a method of controlling absence seizures in a mammal, by administering to a mammal susceptible to absence seizures an effective amount of PrRP or a PrRP functional analog. Also provided are methods of identifying a compound that modulates AMPA receptor signaling in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to modulate AMPA receptor signaling. The invention also provides methods of identifying a compound for controlling absence seizures in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to control absence seizures in a mammal. Also provided are pharmaceutical compositions for controlling absence seizures in a mammal. The compositions and related methods contain a compound identified by the methods of the invention as a compound that modulates AMPA receptor signaling or as a compound that controls absence seizures. Excerpt(s): The present invention relates generally to the field of medicine and, more specifically, to therapeutic compositions and methods relating to Prolactin Releasing Peptide (PrRP). Absence seizures are generalized non-convulsive seizures characterized by a brief period of unresponsiveness to environmental stimuli and cessation of activity, that can occur as frequently as several hundred times a day, primarily during quiet wakefulness, inattention and the transition between sleep and waking. In patients with absence seizures, generalized tonic-clonic seizures (GTCS) or "grand mal seizures" occasionally develop. Currently available drugs to control absence seizures are often associated with adverse side effects, including gastrointestinal symptoms, tremors, sedation, temporary hair loss, dizziness, incoordination, rashes, and drug interaction complications. More seriously, potentially fatal hepatic and hematopoietic complications, as well as teratogenicity (e.g. neural tube birth defects), have been associated with absence seizure medications. Additionally, while currently available drugs are effective in many individuals, certain individuals are resistant to all known treatments. Web site: http://www.delphion.com/details?pn=US06383764__
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Prolactin production inhibitory agent Inventor(s): Furuya; Shuichi (Ibaraki, JP), Matsumoto; Hirokazu (Ibaraki, JP), Suzuki; Nobuhiro (Ibaraki, JP) Assignee(s): Takeda Chemical Industries, Ltd. (osaka, Jp) Patent Number: 5,977,132 Date filed: December 9, 1996 Abstract: The prolactin production inhibition agent of the present invention containing a condensed cyclic compound, which is characterized by containing a condensed bicyclic structure of an optionally substituted homo or hetero 5- to 7-membered ring with an optionally substituted homo or hetero 5- to 7-membered ring, or a salt thereof, can be used, as a medicine, for the prophylaxis or therapy of diseases accompanied with an excess prolactin production or diseases having enhanced reactivity with prolactin, or is useful for inhibiting puerperal lactation, and also useful as a prophylactic or therapeutic agent of galactorrhea, hyperprolactinemic ovulation disturbance, amenorrhea-galactorrhea syndrome, prolactinoma, and besides, interbrain tumor, and acromegaly, pituitary gigantism. Excerpt(s): This application claims priority to Japanese Patent Application Japan 3450461995, filed Dec. 8,1995. The present invention relates to a prolactin production inhibitory composition containing a condensed cyclic compound, especially containing at least a condensed bicyclic structure, or a salt thereof; a method for treating a mammal suffering from hyperprolactinemia; and a use of a condensed cyclic compound for producing a prolactin production inhibitory composition for treating a mammal suffering from hyperprolactinemia. Prolactin, which is produced and secreted from anterior lobe of the pituitary gland, shows a variety of actions including the actions on mammary glands to play an important role for starting and maintenance of lactation, the actions on waterelectrolyte metabolism, the actions on reproductive glands, the actions on the immune system and the actions on brain function. The prolactin-producing cells of the pituitary gland are recognized to have clearly characteristic properties. For example, peptide hormones so far known as various pituitary hormone secretion/production stimulating hormones secreted from hypothalamus are clearly observed to act preferentially and specifically on specified pituitary hormone secretion/production cells of the anterior lobes of the pituitary gland. Typically, while gonadotropic hormone releasing hormone, sometimes referred to as GnRH (gonadotropin releasing hormone): lutenizing hormonereleasing hormone (LH-RH), acts preferentially and specifically on the cells which secrete/produce, for example, follicle stimulating hormone (FSH) and lutenizing hormone (LH) in the anterior lobe of pituitary, no observational studies have been reported that the GnRH acts on the cells which produce/secrete prolactin, also known as an anterior pituitary hormone, to cause secretion of prolactin. Therefore, cells which produce/secrete gonadotropins and prolactin are considered to have, among anterior pituitary hormone secreting/producing cells, entirely different characteristic features. From the viewpoints as above, for controlling the prolactin production/secretion, the drug to be used therefor should at least act on pituitary prolactin-producing cells which can be clearly distinguished from other peptide hormone secretion/production cells of pituitary. Web site: http://www.delphion.com/details?pn=US05977132__
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Prolactin receptor gene as a genetic marker for increased litter size in pigs Inventor(s): Rothschild; Max F. (Ames, IA), Tuggle; Christopher K. (Ames, IA), Vincent; Amy L. (Jewell, IA) Assignee(s): Iowa State University Research Foundation, Inc. (ames, Ia) Patent Number: 5,935,784 Date filed: March 6, 1997 Abstract: Disclosed herein are genetic markers for pig litter size, methods for identifying such markers, and methods of screening pigs to determine those more likely to produce larger litters and preferably selecting those pigs for future breeding purposes. The markers are based upon the presence or absence of certain polymorphisms in the pig prolactin receptor gene. Excerpt(s): This invention relates generally to the detection of genetic differences for reproductive efficiency among pigs and particularly use of a genetic marker prolactin receptor gene which is indicative of the heritable trait of increased litter size. Reproductive efficiency, which can be defined as the number of pigs produced per breeding female, is the major limiting factor in the efficient production of pork. The number of pigs born alive in the United States averages approximately 9.5 pigs per litter. Heritability for litter size is low (10%-15%), and standard genetic methods of selecting breeding females on the basis of past litter size have not been effective. Therefore, there is a need for an approach that deals with selection for reproduction at the cellular or DNA level. Chinese breeds are known for reaching puberty at an early age and for their large litter size. American breeds are known for their greater growth rates and leanness. Thus, it would be desirable to combine the best characteristics of both types of breeds, thereby improving the efficiency of U.S. pork production. These efforts would be greatly assisted by the discovery of genes or genetic markers that are associated with increased litter size in pigs. Web site: http://www.delphion.com/details?pn=US05935784__
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Prolactin regulatory element binding protein and uses thereof Inventor(s): Bancroft; F. Carter (Huntington, NY), Clelland; Catherine L. (New York, NY), Fliss; Maikiko (Columbia, MD) Assignee(s): The Mt. Sinai School of Medicine of New York University (new York, Ny) Patent Number: 6,586,581 Date filed: March 23, 2000 Abstract: The present invention relates to isolated nucleic acid molecules encoding Prolactin Regulatory Element Binding protein (PREB) and recombinant proteins encoded thereby. The nucleic acid sequences are useful in the production of recombinant PREB, as probes, and in the control of gene expression, and in particular, in the control of prolactin gene expression. In particular embodiments of the invention, PREB nucleic acid sequences are used to detect transcripts of the gene in astrocytomas, to detect trisomy and to detect a propensity of a subject to develop osteoporosis. In other embodiments of the invention, the PREB nucleic acid sequences, or the products thereof, are used for preventing or controlling osteoporosis in a subject. Excerpt(s): The present invention relates to isolated nucleic acids encoding Prolactin Regulatory Element Binding (PREB) protein and recombinant proteins encoded thereby.
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The nucleic acid sequences are useful in the production of recombinant PREB, as probes, and in the control of prolactin gene expression. In particular embodiments of the invention, PREB nucleic acid sequences are used to detect transcripts of the gene in astrocytomas. The PREB protein is associated with the kinase-mediated hormonal regulation of prolactin gene expression, and may be used as a trans-acting control of transcription. Prolactin (PRL) is an anterior pituitary hormone that is part of a family of hormones. Prolactin was discovered in 1928 based on the ability of pituitary extracts to cause lactation in pseudo-pregnant rabbits. Cooke, N. E., and Leibhaber, S. A., 1995, Vitamins and Hornones 50:385-459. Accumulated data now suggest a very broad spectrum of roles for PRL. PRL is linked to over three-hundred separate actions in vertebrates including effects on water and salt balance, growth and development, metabolism, brain behavior, reproduction, and immune regulation and protection. BoleFeysot C. et al.,1998, Endocr. Rev. June; 19(3):225-268. Additionally, a number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL. Bole-Feysot C. et al., 1998, Endocr. Rev. June; 19(3):225-268. Studies have shown that female transgenic mice overexpressing the rat PRL gene all develop mammary carcinomas at 11-15 months of age and male transgenic mice over-expressing PRL develop dramatic enlargement of the prostate gland. Wennbo H. et al., 1997, J Clin. Invest. December 1; 100 (11):2744-2751. The effect of PRL on cell proliferation was studied in a mouse mammary tumor cell line. The results of the study indicated that PRL antiserum is able to inhibit cell growth by 70% suggesting that PRL may be acting as a local growth factor that stimulates the proliferation of mammary tumors. Mersho, J. et al., 1995, Endocrinology. August; 136(8):3619-3623. Similarly, human breast cancer cells synthesize and secrete biologically active PRL and there is evidence to support that PRL may be involved in an autocrine/paracrine stimulatory loop within breast tissues that may play a role in the pathogenesis of breast cancer. Clevenger C. V. et al., 1995, Am. J Pathol. March; 146(3):695-705. Web site: http://www.delphion.com/details?pn=US06586581__ •
Sleep quality improvement using a growth hormone secretagogue Inventor(s): Copinschi; Georges (Brussels, BE), Van Cauter; Eve (Chicago, IL) Assignee(s): Arch Development Corporation (chicago, Il) Patent Number: 6,313,133 Date filed: January 27, 2000 Abstract: Methods for re-establishing normal sleep patterns in adults with age-related sleep disorders are provided. In particular, methods are disclosed wherein a compound that stimulates growth hormone and/or prolactin secretion is orally administered to subjects just prior to retiring. Excerpt(s): The present invention relates to the fields of sleep medicine, gerontology and hormonal disorders. In particular, the invention addresses sleep deficiencies that are associated with depressed levels of growth hormone and prolactin. In young adults, sleep is associated with marked hormonal changes, including increased release of growth hormone (GH) and prolactin (PL). A pulse of GH occurs shortly after sleep onset in association with the first episode of slow-wave sleep (SWS) and often represents 50-100% of the total daily GH output. Sleep onset is associated with a marked increase in PL secretion. PL levels return to low daytime values after morning awakening. There is good evidence to indicate that the nocturnal release of GH and PL contributes to the
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maintenance and quality of sleep. In older adults, sleep is disturbed with more awakenings, less SWS and less rapid eye movement (REM) sleep. The most dramatic change is the decrease in SWS, which often represents less than 5% of the sleep period time or, sometimes, disappears entirely in aged individuals. Simultaneously, growth hormone secretion also is markedly decreased, both during sleep and wakefulness. Since sleep-related GH secretion represents the major part of total GH secretion, the reduction or absence of SWS in the elderly plays a major role in contributing to the overall decline in GH secretion. The absence of activation of the GHRH-GH axis in early sleep also may be involved in the fragmentation, shallowness and reduced duration of mid and late sleep. Nocturnal prolactin release also is markedly decreased in old age and this alteration may play an important role in diminished sleep quality. Web site: http://www.delphion.com/details?pn=US06313133__ •
Soluble human prolactin receptors Inventor(s): Kelly; Paul A. (Paris, FR), Nagano; Makoto (Philadelphia, PA) Assignee(s): Applied Research Systems Ars Holding N.v. (curacao, An), Inserm (paris, Fr) Patent Number: 6,083,714 Date filed: February 26, 1997 Abstract: Soluble polypeptides of human prolactin receptor, corresponding to products expressed from differentially spliced mRNA and obtainable from various human tissues, are reported and recombinant molecules containing nucleic acid sequences encoding the soluble polypeptides of human prolactin receptor can be constructed and inserted into expression vectors for production in transformed host cells. Excerpt(s): The invention relates to polypeptides corresponding to soluble isoforms of human prolactin receptor and functional derivatives thereof. The invention also relates to recombinant DNA molecules encoding soluble human prolactin receptors, expression vectors carrying the recombinant DNA molecules and host cells carrying such expression vectors and capable of expressing a soluble human prolactin receptor. Two of the adenohypophysial peptide hormones, prolactin (PRL) and growth hormone (GH), are thought to have evolved from a common ancestral gene (Kelly et al., Recent Prog. Horm. Res. 48: 123-164, 1993). The receptors for PRL and GH (PRLR and GHR) show high homology to each other and belong to the GH/PRL/cytokine receptor superfamily. Thus, they are also thought to be cognates of a common ancestral gene (Kelly et al., 1993, supra). The signaling pathways of PRL and GH have been recently reported to involve a receptor-associated tyrosine kinase. The common structural features of the members of this superfamily are two pairs of cysteines and the tryptophan-serine (WS) motif in the extracellular domain. In the case of PRLR, there are five cysteines in the extracellular domain, and two pairs of cysteines and the WS motif have been shown to be important for ligand binding (Rozakis-Adcock et al., J. Biol. Chem. 266: 16472-16477, 1991; J. Biol. Chem. 267: 7428-7433, 1992). The primary structure of the mature human GH receptor is a polypeptide of 620 amino acids (aa) with an extracellular hormone-binding domain of 246 aa, a single transmembrane region, and a cytoplasmic domain of 350 amino acid residues. The extracellular domain contains seven cysteine residues and five potential N-linked gylcosylation sites (Kelly et al., 1993, supra). While the structure of the mature PRL receptor from rat liver was deduced from CDNA to contain 291 amino acids with an extracellular region of 210 aa having five cysteine residues and three potential N-linked glycosylation sites, a single
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transmembrane region of 24 aa, and a relatively short cytoplasmic domain of 57 aa (Boutin et al, Cell 53: 69-77, 1988 represents a first class of receptor (short form), the structure of mature human PRLR containing 598 amino acid residues represents a second class of receptor (long form) (U.S. Pat. No. 4,992,378). Like mature rat liver GHR, this long form human PRLR has an extracellular region of 210 aa and a single transmembrane region, but a long cytoplasmic region. Web site: http://www.delphion.com/details?pn=US06083714__ •
Therapeutic package for the long term reduction of body fat stores insulin resistance hyperinsulinemia and hyperglycemia in vertebrates Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Baton Rouge, LA) Assignee(s): Ergo Research Corporation (wakefield, Ri), The Board of Supervisors of Louisiana State University and Agricultural (baton Rouge, La) Patent Number: 5,854,255 Date filed: April 21, 1997 Abstract: A therapeutic package for dispensing to, or for use in dispensing to, a vertebrate being treated for a metabolic condition selected from the group consisting of obesity, insulin resistance, hyperinsulinemia, and hyperglycemia comprising one or more unit doses of bromocriptine and labeling directing the use of the package in the treatment of the metabolic condition in a dosage regimen under which the delivery of the bromocriptine is confined to the period during the day near the time of day at which the serum prolactin concentration of a lean, insulin sensitive vertebrate of the same sex is low, and further directing the use of said package in conjunction with the concomitant administration to the vertebrate of one or more unit doses providing a therapeutically effective amount of a prolactin stimulator in a dosage regimen under which the delivery of the prolactin stimulator is confined to the period during the day after the time at which the serum prolactin concentration of a lean, insulin-sensitive vertebrate of the same sex reaches its lowest point and prior to the time of day when the prolactin concentration rises to a peak in lean, insulin-sensitive vertebrates of the same sex. Excerpt(s): This invention relates to an improved process for the reduction in vertebrates, animals or humans, of body fat stores, and reduction of insulin resistance, hyperinsulinemia, which is often associated with insulin resistance, and hyperglycemia, or reduction of plasma glucose. In particular, it relates a process requiring the timed daily administrations of a dopamine agonist and a prolactin stimulator at appropriate preselected times of day, and preferably also a thyroid hormone, to reduce and control over an extended period the stated pathologies which, with obesity, are pathologies characteristic of the onset of noninsulin dependent, or Type II diabetes. In U.S. Pat. No. 4,659,715, which issued Apr. 21, 1987 to Albert H. Meier and Anthony H. Cincotta, there is disclosed a method for the reduction in vertebrate animals of body fat stores, without concomitant decrease in muscle mass, via the administration of multiple daily doses over prescribed periods of a prolactin-inhibiting, or dopamine compound. This method, which is associated with an altered lipid metabolism, offers hope to those suffering with obesity; a serious worldwide health problem. In pending U.S. application Ser. No. 463,327, supra, there is disclosed a method, or process, for the long term modification and regulation of lipid metabolism in a vertebrate, animal or human, not only to reduce obesity, but also to reduce insulin resistance, and hyperinsulinemia or hyperglycemia, or both, by administration to a subject of a prolactin-inhibiting compound, or dopamine agonist. The role of prolactin in a vertebrate species to control these pathologies (the
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hallmarks of noninsulin dependent, or type II diabetes), it was found, was crucial| The level of prolactin in the blood of a species is time-of-day, dependent, and cyclic, its level in the blood rising and falling at different times of day dependent on the amount of fat deposited in the body of the subject. The phrase relationships between the rise and fall of prolactin which appears in the blood streams of obese and lean subjects, respectively, are different. Administration of the dopamine agonist, it is disclosed, is made over a limited period at a time of day dependent on the normal circadian rhythm of fat and lean members, respectively, of a similar species based on the result to be achieved. Where, e.g., it is desired to reduce the body fat of a subject, decreases in body fat deposits are produced by treatment of the obese species on a timed daily sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean members of a similar species. A person, whether lean or obese, showing the effects of insulin resistance, or hyperinsulinemia and/or hyperglycemia, or both insulin resistance and hyperinsulinemia and/or hyperglycemia, treated with the dopamine agonist or prolactin-inhibiting compound, in the same manner as a person suffering with obesity, it was found would become more sensitive to insulin, and the effects of hyperinsulinemia and/or hyperglycemia would be reduced on a long term basis. Thus, insulin resistance, and hyperinsulinemia or hyperglycemia, or both, like obesity, can be controlled in humans on a long term basis by treatments corresponding to that for the treatment of obesity to lower fat deposits in the body of the subject. Web site: http://www.delphion.com/details?pn=US05854255__ •
Transgenically produced prolactin Inventor(s): Echelard; Yann (Brookline, MA), Wilburn; Brian (Boston, MA) Assignee(s): Genzyme Transgenics Corporation (framingham, Ma) Patent Number: 6,210,736 Date filed: June 15, 1998 Abstract: Transgenically produced prolactin and methods of making and using transgenically produced prolactin are disclosed. Excerpt(s): The invention relates to transgenic prolactin, and methods of making and using transgenic prolactin. A growing number of recombinant proteins are being developed for therapeutic, diagnostic, agricultural, veterinary, nutritional and other applications; however, many of these proteins may be difficult or expensive to produce in a functional form in the substantial quantities using conventional methods. Conventional methods often involve inserting the gene responsible for the production of a particular protein into host cells such as bacteria, yeast, or mammalian cells. The cells are grown in culture medium and the desired protein is recovered from the cells or the culture medium. Traditional bacteria or yeast systems are sometimes unable to produce a complex protein in finctional form. While some mammalian cells can reproduce complex proteins, they are often difficult and expensive to grow, and produce only protein in relatively low amounts. In addition, non-secreted proteins are relatively difficult to purify from procaryotic or mammalian cells, as they are often not secreted into the culture medium. Web site: http://www.delphion.com/details?pn=US06210736__
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Use of a prolactin receptor or growth hormone receptor intracytoplasmic domain for achieving protein secretion Inventor(s): Cahoreau; Claire (Montpellier, FR), Cerutti; Martine (Saint-Christol-lezAles, FR), Devauchelle; Gerard (Saint-Christol-lez-Ales, FR), Garnier; Laurence (Norieres-les-Avignon, FR) Assignee(s): Centre National DE LA Recherche Scientifique (cnrs) (paris, Fr), Institut National DE LA Recherche Agronomique (inra) (paris, Fr) Patent Number: 6,169,172 Date filed: March 16, 1998 Abstract: The use of a prolactin receptor intracytoplasmic domain or a growth hormone receptor intracytoplasmic domain, or of a fragment of either one of said domains, for achieving the secretion of a protein of interest produced in a eukaryotic host cell, is disclosed. Excerpt(s): The invention relates to polypeptides which enable proteins which are produced in eukaryotic cells to be secreted directly. In recent years, the baculovirus/insect cell system has been used successfully for expressing various genes of interest. In this system, as, in a more general manner, in the different systems which are known for producing recombinant proteins in host cells, it is desirable to have available means for exporting the said recombinant proteins into the medium in which the cells are cultured. This is because exporting these proteins makes it easier to harvest and purify them. Generally, the approach is to attempt to use the standard secretion pathway, which involves the endoplasmic reticulum and the Golgi apparatus, in order to achieve the export of a recombinant protein from a eukaryotic host cell. Web site: http://www.delphion.com/details?pn=US06169172__
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Utilization of prolactin for preventing and/or treating the expression of brooding behavior in birds Inventor(s): Guemene; Daniel (Mettray, FR), Karatzas; Costas (Quebec, CA), Zadworny; David (Quebec, CA) Assignee(s): Institute National DE LA Recherche Agronomique () Patent Number: 6,114,305 Date filed: April 28, 1997 Abstract: A pharmaceutical composition for preventing and/or treating the expression of brooding behavior in a bird is disclosed, wherein the composition is comprised of a pharmaceutically acceptable vehicle in combination with one of the following: (a) an active ingredient comprising a hybrid construct comprising a carrier group and a protein, wherein said protein comprises at least one antigenic determinant for bird prolactin; (b) a microorganism which expresses the hybrid construct at its surface, or which excretes the hybrid construct; and (c) antibodies directed against at least one bird prolactin antigen site. Excerpt(s): The present invention concerns new pharmaceutical compositions intended to prevent and/or treat the expression of brooding behavior in birds, and more particularly in the turkey. The invention also relates to the procedures for the preparation of these pharmaceutical compositions. The brooding or incubation period is one of the major phases in the natural reproductive cycle of birds. However, the
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aptitude for brooding, far from being considered a quality of breeders, is instead an unfavorable factor, inasmuch as all of the eggs to be hatched are incubated artificially. Brooding behavior still persists among several species of domestic birds, particularly among chickens, ducks, and turkeys. This behavior leads to a notable reduction in the number of incubatable eggs and thus to a very significant loss of income for the breeders. The observation and understanding of this behavior have made it possible to develop the first ways to combat broodiness on breeding farms. Web site: http://www.delphion.com/details?pn=US06114305__ •
Variants of human prolactin and human placeatal lactogen Inventor(s): Cunningham; Brian C. (Piedmont, CA), Wells; James A. (Burlingame, CA) Assignee(s): Genentech, Inc. (south San Francisco, Ca) Patent Number: 5,955,346 Date filed: June 7, 1995 Abstract: The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide. The method comprises substituting a scanning amino acid for one of the amino acid residues within the active domain of the parent polypeptide and assaying the residue-substituted polypeptide so formed with a target substance. The invention further provides polypeptide variants comprising segmentsubstituted and residue-substituted growth hormones, prolactins and placental lactogens. Excerpt(s): The invention is directed to methods for identifying the active domains and amino acid residues in polypeptides. It is also directed to hormone variants. Polypeptides, i.e., peptides and proteins, comprise a wide variety of biological molecules each having a specific amino acid sequence, structure and function. Most polypeptides interact with specific substances to carry out the function of the polypeptide. Thus, enzymes, such as subtilisin, amylase, tissue plasminogen activator, etc., interact with and hydrolyze specific substrates at particular cleavage sites whereas proteinaceous hormones such as human growth hormone, insulin and the like interact with specific receptors to regulate growth and metabolism. In other cases, the interaction is between the polypeptide and a substance which is not the primary target of the polypeptide such as an immunogenic receptor. Many polypeptides are pluripotential in that they contain discrete regions which interact with different ligands or receptors, each of which produces a discrete biological effect. For example, human growth hormone (hGH) is diabetogenic and lypogenic in adults and induces long bone growth in children. Efforts have been made to modify the primary functional properties of naturally occurring polypeptides by modifying amino acid sequence. One approach has been to substitute one or more amino acids in the amino acid sequence of a polypeptide with a different amino acid. Thus, protein engineering by in vitro
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mutagenesis and expression of cloned genes reportedly has been applied to improve thermal or oxidative stability of various proteins. Villafranca, J. E., et al. (1983) Science, 222, 782-788; Perry, L. J., et al. (1984) Science 226, 555-557; Estell, D. A., et al. (1985) J. Biol. Chem. 260, 6518-6521; Rosenberg, S., et al. (1984) Nature (London) 312, 77-80; Courtney, M., et al. (1985) Nature (London) 313, 149-157. In addition, such methods have reportedly been used to generate enzymes with altered substrate specificities. Estell, D. A., et al. (1986) Science 223, 655-663; Craik, C. S., et al. (1985) Science 228, 291297; Fersht, A. R., et al. (1985) Nature (London) 314, 235-238; Winther, J. R., et al. (1985) Carlsberg Res. Commun. 50, 273-284; Wells, J. A., et al. (1987) Proc. Natl. Acad. Sci. 84, 1219-1223. The determination of which amino acid residue should be modified has been based primarily on the crystal structure of the polypeptide, the effect of chemical modifications on the function of the polypeptide and/or the interaction of the polypeptide with various substances to ascertain the mode of action of the polypeptide. In some cases, an amino acid substitution has been deduced based on the differences in specific amino acid residues of related polypeptides, e.g. difference in the amino acid sequence in substrate binding regions of subtilisins having different substrate specificities. Wells, J. A., et al. (1987) Proc. Natl. Acad. Sci. USA 84, 5767. In other cases, the amino acid sequence of a known active region of a molecule has reportedly been modified to change that sequence to that of a known active region of a second molecule. Wharton, R. P., et al. (1985) Nature 316, 601-605, and Wharton, R. P., et al. (1984) Cell 38, 361-369 (substitution of recognition helix of phage repressor with recognition helix of different repressor); Jones, P. T., et al. (1986) Nature 321, 522-525 (substitution of variable region of a mouse antibody for corresponding region of human myeloma protein). While this approach may provide some predictability with regard to the properties modified by such substitutions, it is not a methodical procedure which would confirm that all regions and residues determinative of a particular property are identified. At best, empirical estimates of the energetics for the strengths of the molecular contacts of substituted residues may be ascertained. In this manner, the strengths of hydrogen bonds (Fersht, A. R., et al. (1985) Nature 314 , 235; Bryan, P., et al. (1986) Proc. Natl. Acad. Sci, USA 83, 3743; Wells, J. A., et al. (1986) Philos. Trans. R. Soc. London A. 317, 415), electrostatic interactions (Wells, J. A., et al. (1987) Proc. Natl. Acad. Sci. USA 84, 1219; Cronin, C. N., et al. (1987) Ja.Am. Chem. Soc. 109, 2222), and hydrophobic and steric effects (Estell, D. A., et al. (1986) Science 233, 659; Chen, J. T., et al. (1987) Biochemistry 26, 4093) have been estimated for specific modified residues. These and other reports (Laskowski, M., et al. (1987) Cold Spring Harbor Symp. Quant. Biol. 52, 545; Wells, J. A., et al. (1987) Proc. Natl. Acad. Sci. USA 84, 5167; Jones, P. T., et al. (1986) Nature 321, 522; Wharton, R. P., et al. (1985) Nature 316, 601) have concluded that mutagenesis of known contact residues causes large effects on binding whereas mutagenesis of non-contact residues has a relatively minor effect. Web site: http://www.delphion.com/details?pn=US05955346__
Patent Applications on Prolactin As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to prolactin: 9
This has been a common practice outside the United States prior to December 2000.
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Amphiphilic oligomers Inventor(s): Ekwuribe, Nnochiri Nkem; (Cary, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030229006 Date filed: May 30, 2003 Abstract: A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Didesoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications. Excerpt(s): The present invention relates to microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents, and to methods of making and using same. The compositions of the invention may comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhymics, anti-coagulants, etc., and prodrugs, precursors, derivatives, and intermediates thereof. In the field of pharmaceutical therapeutic intervention, and the treatment of disease states and physiological conditions, a wide variety of therapeutic agents have come into use, including various proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, antiarrhythmics, anti-coagulants, etc., and prodrugs precursors, derivatives, and intermediates of the foregoing. For example, the use of polypeptides and proteins for the systemic treatment of specific diseases is now well accepted in medical practice. The role that the peptides play in replacement therapy is so important that many research activities are being directed towards the synthesis of large quantities by recombinant DNA technology. Many of these polypeptides are endogenous molecules which are very potent and specific in eliciting their biological actions. Other non-(poly)peptidyl therapeutic agents are equally important and pharmaceutically efficacious. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Bi-functional cancer treatment agents Inventor(s): Chen, Wen Y.; (Simpsonville, SC), Wagner, Thomas E.; (Greer, SC) Correspondence: Charles F. Schill; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20020068043 Date filed: March 23, 2001 Abstract: A novel fusion protein, comprising a receptor-antagonizing domain and a positive immunomodulator domain, characterized, for example, by its ability to block apoptosis and/or inhibit endocrine response, is useful in treating cancer. For example, a human prolactin antagonist-interleukin 2 (hPRLA-IL-2) fusion protein combines apoptosis induction and immuno-therapy to combat cancer in the breast or prostate. Excerpt(s): The present invention relates generally to the methodology of preparing and using fusion molecules to treat cancer. Human breast cancer is the predominant malignancy and the leading cause of cancer death in women from Western society, as reported by Miller et al., (eds) BIOLOGY OF FEMALE CANCERS, 31-42 (CRC Press, 1997). According to recent estimation by the American Cancer Society, one in every eight U.S. women will have breast cancer and the disease will kill 43,500 women in 1998. Several lines of evidence have strongly linked prolactin (PRL) to breast cancer development. It has been reported that the expression level of prolactin receptors (PRLR) is higher in human breast cancer cells compared to normal breast epithelial cells (Reynolds et al., 1997), as well as in surgically removed breast cancer tissues (Touraine, Martini P. et al., Increased Expression Of Prolactin Receptor Gene In Human Breast Tumors Versus Continguous Normal Breast Tissues, (Abstract) 79.sup.th Annual Meeting of Endocrine Society, p.113, (1997)). The PRLR levels in malignant breast tissue can be five folds higher over its surrounding normal tissue (see Touraine et al. (1997), supra, making these cells highly sensitive to the stimulation of hPRL. Additionally, it has been suggested that one mechanism of the mitogenic action of estrogen in breast may influence the production and secretion of human prolactin (hPRL), since there is a positive correlation between PRLR, estrogen receptors (ER) or progesterone receptor levels (Sirbasku, 1978; Dixon and Lippman 1986; Lippman an Dickson, 1989). Taken together, these findings lead to a hypothesis that hPRL serves as an autocrine/paracrine growth factor that plays an important role in mammary carcinogenesis (Clevenger, et al., Am. J. Pathology, 146:695-705 (1995); Ginsburg, E. et al., Cancer Res., 55:2591-2595 (1995)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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COMP/TSP-1, COMP/TSP-2 and other TSP chimeric proteins Inventor(s): Lawler, John W.; (Swampscott, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20020137679 Date filed: July 30, 2001 Abstract: Tumors attract blood vessels in order to grow by a process called angiogenesis. The relative quantity of stimulators and inhibitors is an important determining factor for the initiation of angiogenesis. Thrombospondins-1 and -2 are adhesive glycoproteins
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that have the ability to inhibit angiogenesis. This inhibiting activity has been mapped to the type 1 repeats of TSP-1 and TSP-2. The invention includes chimeric proteins that contain anti-angiogenic portions of TSP-1, TSP-2, endostatin, angiostatin, platelet factor 4, or prolactin, linked to a portion of the N-terminal region of human cartilage oligomeric matrix protein (COMP) that allows formation of pentamers. Also described herein are the nucleic acid molecules, vectors, and host cells for expressing and producing these chimeric proteins. Further embodiments of the invention include methods to treat humans or other mammals with anti-angiogenic proteins to reduce tumor size or rate of growth. Since the type 1 repeat region of TSP-1 and TSP-2 reportedly inhibits HIV infection, chimeric proteins comprising these repeats may also be used for this purpose, as well as to inhibit angiogenesis. Excerpt(s): This application is a continuation of International Application No. PCT/US00/02482, which designated the United States and was filed Feb. 1, 2000, published in English, which claims the benefit of U.S. Provisional Application No. 60/118,053 filed Feb. 1, 1999. The entire teachings of the above applications are incorporated herein by reference. Thrombospondins are a family of calcium-binding multifunctional glycoproteins that are secreted by various cell types and are developmentally regulated components of the extracellular matrix (Bornstein, P., FASEB J., 6:3290-3299, 1992; Bornstein, P., J. Cell Biol., 130:503-506, 1995). Among their functions are modulating cell attachment, migration and proliferation. One member of this family, cartilage oligomeric matrix protein (COMP) is a pentamer in which multimerization appears to be directed by.alpha.-helical segments situated (in the amino acid sequence) either before or after the cysteine residues that form the interchain disulfide bonds. COMP has been purified (Prochownik, E. V. et al., J. Cell Biol. 109:843-852 (1989)). Individuals affected with pseudoachondroplasia, who have considerably shortened stature as a result of premature cessation of bone growth, have been shown to have mutations in exon 17B of the COMP protein (Nature Genetics 10:325-329 (1995)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition and method for modulating somatolactogenic function Inventor(s): Clevenger, Charles V.; (Merion Station, PA), Kline, J. Bradford; (Blue Bell, PA) Correspondence: Licatla & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20020119154 Date filed: December 21, 2001 Abstract: A human prolactin-binding protein and compositions and methods using this protein are provided. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application Serial No. 60/258,285 filed Dec. 22, 2000. Prolactin and growth hormone receptors are members of the cytokine receptor superfamily. Both the prolactin receptor (PRLR) and growth hormone receptor (GHR) are single chain transmembrane proteins composed of an extracellular, transmembrane and intracellular domain. The hormones prolactin (PRL) and growth hormone (GH) exert their effects at the molecular level by inducing the homodimerization of their respective receptors, initiating the activation of receptor-associated kinases and signaling cascades. Until the last few decades, it was believed that peptide hormones circulated freely, but experimental evidence has now proven otherwise. While PRL was found to associate with serum IgG, (Walker et al. 1995
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Proc. Natl Acad. Sci. USA 92: 3278-3282) a GH-binding factor was initially identified in the serum of pregnant mice, (Peeters et al. 1977 Endocrinology 101: 1164-1183) and subsequently discovered in rabbit (Ymer et al. 1985 Mol. Cell. Endocrinol. 41: 153-161) and human sera. (Baumann et al. 1986 J. Clin. Endocrinol. Metab. 62: 134-141). With subsequent cloning of the GHR cDNA, a GH-binding protein (GHBP) was found to have amino acid sequence identity with the extracellular domain of the membranebound GHR. (Leung et al. 1987 Nature 330: 537-543) The GHBP is a 246 residue glycoprotein with a molecular weight of 50-60 kDA. The generation of GHRBP occurs via two separate mechanisms in mammals. In the mouse and rat, alternative splicing of a primary RNA transcript generates a truncated receptor in which the transmembrane domain is replaced by a short hydrophilic sequence (Smith et al. 3: 984-990; Baumbach et al. 1989 Genes Dev. 3: 1199-1205; Barnard et al. 1997 J. Endocrinol 153: 1-14). In other species, such as man and rabbits, a full length GHR is expressed, but GHBP is generated by proteolytic cleavage of the extracellular domain (Leung et al. 1987 Nature 330: 537543; Trivedi et al. 1988 Endocrinology 123: 2201-2206; Sotiropoulos et al. 1993 Endocrinology 132: 1863-1865). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
GROWTH INHIBITION AND ERADICATION OF SOLID TUMORS USING NEUROENDOCRINE RESETTING THERAPY AND PHOTODYNAMIC THERAPY Inventor(s): CINCOTTA, ANTHONY H.; (CHARLESTOWN, MA), CINCOTTA, LOUIS; (ANDOVER, MA) Correspondence: Darby & Darby; 805 Third Avenue; New York; NY; 10022 Patent Application Number: 20010049350 Date filed: November 6, 1998 Abstract: A method of ablating the growth of or eradicating tumors in mammals having prolactin, growth hormone, and melatonin daily rhythms by adjusting one or more of the prolactin, growth hormone, and melatonin profiles of the mammal to conform to or approach the corresponding normal profile for healthy members of the same species and sex as said mammal, contacting the cells of the tumor with a photoactive photosensitizer, and, exposing the photosensitizer-contacted tumor cells to light of a predetermined wavelength, power density, and energy level. Excerpt(s): (c) exposing the contacted tumor cells to light of a predetermined wavelength, power density, and energy level. It is well known in the art to inhibit the growth of tumors by using cytotoxic compositions or ionizing radiation. A major drawback of ionizing radiation as a therapeutic modality is that it often results in injury or damage to healthy tissue in the vicinity of, or in contact with, the malignant tumor cells. Cytotoxic compositions have the even greater drawback of often causing systemic toxicity, i.e. damaging tissues at loci distal to the tumor. (iii) prolonged retention of these photosensitizers in the skin leads to dermal photosensitization that can persist for months. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for Identifying Fast- Growing Fish Inventor(s): Kocher, Thomas David; (Durham, NH), Streelman, Jeffrey Todd; (Durham, NH) Correspondence: Devine, Millimet & Branch, P.A.; 111 Amherst Street; Box 719; Manchester; NH; 03105; US Patent Application Number: 20030047143 Date filed: July 3, 2002 Abstract: Methods of selecting fish for breeding and optimum growth in conditions of various salinity are disclosed. Fish are selected for growth in specific salinity based on their prolactin 1 genotype. A simple sequence repeat polymorphism (microsatellite) in the tilapia prolactin (prl 1) promoter is associated with differences in prl 1 expression and differences in growth in "salt-challenged" or "salt-effected" fishes. This discovery suggests that dinucleotide microsatellites may represent an under-appreciated source of genetic variation for regulatory evolution, and belie the textbook interpretation that non-coding microsatellite length variation lacks functional consequences. Thus, the methods of the invention include determining or selecting the salinity of the environment in which the fish will be grown; determining the prolactin genotype of at least one male and at least one female fish being considered for breeding; breeding male and female fish having the desired genotype(s) to result in offspring having known, predictable genotypes; and raising the fish in a salinity environment compatible with the fishes' genotype(s). Excerpt(s): This application claims the benefit of Serial No. 60/315,156 which was filed on Aug. 27, 2001. A portion of the disclosure of this patent document contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the United States Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. The invention relates to selection of fish for optimum growth. More particularly the invention relates to methods of selecting fish, in particular tilapia, for optimum growth in water of differing salinity. Most particularly the invention relates to using a polymorphism in the tilapia prolactin gene to select and then breed fish, based on genotype, for optimum growth in water of differing salinity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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METHOD FOR SCREENING AND TRANSGENIC MODEL Inventor(s): ISAKSSON, OLLE; (GOTEBORG, SE), KINDBLOM, JON; (GOTEBORG, SE), NORSTEDT, GUNNAR; (BROMMA, SE), TORNELL, JAN; (VASTRA FROLUNDA, SE), WENNBO, HAKAN; (GOTEBORG, SE) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020073440 Date filed: September 9, 1999 Abstract: A method for the screening and identification of low molecular weight compounds which interact with lactogenic/somatogenic receptors is claimed. The method is characterized by the use of isolated tissues for in vitro cultivation as organ
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culture, primary cells, immortalized or transformed cells from transgenic animal that over-express hormones/receptors belonging to the somatic or lactogenic family. Also a transgenic non-human animal that over-express prolactin which cause phenotypic alterations notably in the prostate and/or mammary gland and use thereof is claimed. Excerpt(s): The present invention relates to a method for the screening and identification of low molecular weight compounds which interact with lactogenic/somatogenic receptors and which is characterized by the use of isolated tissues for in vitro cultivation as organ culture, primary cells, immortalized or transformed cells from a transgenic non-human animal that over-express hormones/receptors belonging to the somatogenic or lactogenic family, e.g. prolactin (Pr1) and growth hormone (GH) receptors. The invention also relates to a transgenic non-human animal that over-express prolactin which cause phenotypic alterations notably in the prostate and mammary gland and human e.g. growth hormone (GH) receptors and the use of the transgenic animal in the screening and identification method. Transgenic animals represent an important scientific tool to explore functions of specific genes in a physiological environment. Several examples exist where transgenic animals have been made that serve as useful models for human disease. The use of transgenic animals also include research in endocrinology and it has been well established that over-expression of growth hormone provides a model for acromegaly. In the creation of transgenic animals one can sometimes reveal more unexpected findings. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modified pituitary gland development in offspring from expectant mother animals treated with growth hormone releasing hormone therapy Inventor(s): Draghia-Akli, Ruxandra; (Houston, TX), Khan, Amir; (Houston, TX) Correspondence: T. Ling Chwang; Jackson Walker, L.L.P.; Suite 600; 2435 N. Central Expressway; Richardson; TX; 75080; US Patent Application Number: 20040038918 Date filed: February 6, 2003 Abstract: The intramuscular electroporated injection of a protease-resistant growth hormone-releasing hormone ("GHRH") cDNA into rat dams at 16 days of gestation resulted in the enhanced long-term growth of the F1 offspring. The offspring were significantly heavier by one week of age and the difference was sustained to 10 weeks of age. Consistent with their augmented growth, plasma IGF-I concentration of the F1 progeny was increased significantly. The pituitary gland of the offspring was significantly heavier, and contained an increased number of somatotropes (cells producing GH) and lactotrophs (prolactin-secreting cells), and is indicative of an alteration in cell lineages. These unique findings demonstrate that enhanced GHRH expression in pregnant dams can result in intergenerational growth promotion, by altering development of the pituitary gland in the offspring. Excerpt(s): This application claims priority to U.S. Provisional Patent Application, Serial No. 60/355,566, entitled "MODIFIED PITUITARY GLAND DEVELOPMENT IN OFFSPRING FROM EXPECTANT MOTHER ANIMALS TREATED WITH GROWTH HORMONE RELEASING HORMONE THERAPY," filed on Feb. 07, 2002, the entire content of which is hereby incorporated by reference. The present invention pertains to a plasmid-meditated gene supplementation to alter pituitary development, and to increase prolactin levels, in an offspring of a female subject. More specifically, the
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present invention pertains to administering to a female subject a nucleic acid expression construct that encodes growth hormone releasing hormone ("GHRH") to alter the pituitary development and pituitary hormone secretion (e.g. prolactin) in the offspring from the female subject. The pituitary gland is an important link between the nervous system and the endocrine system. The pituitary gland is known to release many hormones that affect growth, sexual development, metabolism (e.g. protein, lipid and carbohydrate), glucocorticoids and the reproductive system. The pituitary gland has also been shown to release hormones that affect bone growth and regulate activity in other hormone secreting glands. This invention relates a method for altering pituitary gland development in offspring from female subjects that have been treated with a nucleic acid construct that encodes a growth hormone releasing hormone ("GHRH") or functional biological equivalent. The expression of the GHRH or biological equivalent thereof is regulated by a tissue specific promoter (e.g. a myogenic promoter). When female subjects are treated with the nucleic acid construct that encodes GHRH, many physiological changes occur in the female subject directly. However, when female subjects are treated with the GHRH construct prior to, or during a gestation period, the offspring from these treated female subjects undergo similar physiological changes. For example, the subsequent expression and ensuing release of GHRH or biological equivalent thereof by the modified cells in the female subject results in the altered development of the pituitary gland in their offspring. Additionally, hormones secreted by the pituitary gland are increased in offspring from treated female subjects when compared to the offspring from control treated female subjects. More specifically, the pituitary gland is increased in sized and the levels of the multifunctional hormone prolactin is elevated utilizing this method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multimeric ligands with enhanced stability Inventor(s): Chen, Wen Yuan; (Clemson, SC) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20040033948 Date filed: April 22, 2003 Abstract: The present invention provides compositions and methods for making multimeric proteins to increase stability over their monomer. For example, more stable growth hormone and prolactin receptor agonists are provided. Excerpt(s): The present invention relates generally to compositions and methods of preparing multimeric ligands with enhanced stability. Prolactin (PRL) is a neuroendocrine polypeptide hormone primarily produced by the lactotrophs of the anterior pituitary gland in all vertebrates. Human prolactin (hPRL) is a 23 kDa protien that binds the prolactin receptor. Human growth hormone (hGH) differs from human prolactin at about 25% of its residues. Wallis et al., supra. hGH participates in much of the regulation of normal human growth and development. This 22,000 dalton pituitary hormone regulates a multitude of biological effects including linear growth (somatogenesis), lactation, activation of macrophages, insulin-like effects and diabetagenic effects among others. See Chawla, R. K. (1983) Ann. Rev. Med. 34, 519; Edwards, C. K., et al. (1988) Science 239, 769; Thorner, M. O., et al. (1988) J. Clin. Invest. 81, 745.
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Non-natural galanin receptor ligands Inventor(s): Bartfai, Tamas; (La Jolla, CA), Langel, Ulo; (Stockholm, SE), Saar, Kulliki; (Stockholm, SE) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030055000 Date filed: May 24, 2002 Abstract: Compounds which are non-natural galanin receptor ligands are disclosed. The ligands are of small size, have agonist or antagonist galanin activity and may cross the blood-brain barrier to displace galanin from galanin receptors. The ligands are useful as medicaments for treatment of convulsions (e.g. in epilepsy), diseases and disorders related to endocrinology (e.g., growth hormone, insulin or prolactin release), tumors expressing galanin receptors, feeding disorders pain, allodynia, psychiatric disorders such as depression (involving e.g., noradrenaline or serotonin), cognitive disorders (e.g. Alzeimer's disease), and the like. Excerpt(s): The present invention relates to non-natural galanin receptor ligands which can function as agonists and antagonists of galanin and can be used to treat diseases or conditions in which galanin plays a role. Galanin.sup.1 is a 29/30 amino acid long neuroendocrine peptide that potently affects seizure activity, cognition, mood, feeding, and pain threshold.sup.2-6. Galanin-overexpressing mice have increased resistance to status epilepticus, while galanin knockout mice have lowered seizure threshold.sup.6. These results indicate that endogenous galanin is an important determinant of hippocampal excitability and of seizure threshold. The importance of galanin agonists for seizure control may arise from their ability to act at both pre- and postsynaptic sites to reduce excitability, to inhibit glutamate but not GABA release.sup.7, and to hyperpolarize both dentate granule cells and CA1-CA3 pyramidal cells by opening K+channels.sup.8, dampening seizure activity. Although intracerebroventricularly injected galanin blocks seizures.sup.5 in mice, this large peptide is unable to cross the bloodbrain barrier and is rapidly degraded. To date, there are only two reports on nonpeptide ligands for galanin receptors, which behave as antagonists: spirocoumaranon.sup.9 (Sch 202596; IC50 of 1.4.mu.M at human GalR1) and dithiipin1,1,4,4-tetroxide.sup.10(IC50 of 0.17.mu.M at human GalR1), despite extensive random screening efforts at six large pharmaceutical companies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel antiangiogenic peptide agents and their therapeutic and diagnostic use Inventor(s): Bentzien, Frauke; (San Francisco, CA), Martial, Joseph A.; (Modave, BE), Struman, Ingrid; (Boncelles, BE), Taylor, Robert; (San Francisco, CA), Weiner, Richard I.; (Muir Beach, CA) Correspondence: Karl Bozicevic; Bozicevic, Field & Francis, Llp; 200 Middlefield Road, Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030186382 Date filed: March 27, 2001
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Abstract: The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormone, human placental lactogen, human growth hormone variant hGH-V, and prolactin, and their use in inhibiting angiogenesis and in the diagnosis of diseases of human pregnancy involving abnormalities of placental vascularization. Excerpt(s): This application claims the benefit of the priority date of and is a continuation of U.S. application Ser. No. 09/076,675, filed May 12, 1998, which claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application No. 60/046,394, filed May 13, 1997. A growing number of serious, debilitating and often fatal diseases are associated with angiogenesis. These diseases are cumulatively called angiogenic diseases. Under normal physiological conditions, angiogenesis in mammals is endogenously controlled throughout the lifetime and neovascularization rarely occurs except during embryonic development, the reproductive cycle, and wound healing. Examples of the pathological conditions leading to development of angiogenic diseases are, among others, arthritis, rheumatoid arthritis, atherosclerotic plaques, corneal graft neovascularization, wound healing, hypertrophic or keloid scars, proliferative retinopathy, diabetic retinopathy, macular degeneration, granulations, neovascular glaucoma and uveitis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel process and intermediates for production of cabergoline and related compounds Inventor(s): Gutman, Arie L.; (Haifa, IL), Nisnevich, Gennadiy; (Haifa, IL), Pertsikov, Boris; (Nesher, IL), Rukhman, Igor; (Kyriat Yam, IL), Tishin, Boris; (Haifa, IL), Vilensky, Alex; (Haifa, IL) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020177709 Date filed: April 16, 2001 Abstract: A process for preparation of N-(ergoline-8.beta.-carbonyl)ureas of the formula [I] their stereoisomers as well as acid addition salts thereof which process comprises silylating an ergoline-8.beta.-carboxamide of the formula [2], 1their stereoisomers as well as metal or ammonium salts or acid addition salts thereof and reacting the resultant product with an isocyanates R.sup.1N.dbd.C.dbd.O [5]wherein R.sup.1 is selected from alkyl having from 1 to 4 carbon atoms, cyclohexyl, phenyl, and dimethylamino alkyl group --(CH.sub.2).sub.nNMe.s- ub.2 in which n is an integer,R.sup.2 is selected from hydrogen, alkyl having from 1 to 4 carbon atoms, cyclohexyl, phenyl, dimethylamino alkyl group --(CH.sub.2).sub.nNMe.sub.2 in which n is an integer, pyridyl, pyrimidyl pyrazinyl, pyridazinyl, thiazolyl or thiadiazolyl,R.sup.3 represent a hydrocarbon group having from 1 to 4 carbon atoms, andR.sup.4 is selected from hydrogen, halogen, methylthio and phenylthio group; followed by desilylation.This novel approach provides an efficient method for preparation of N-(ergoline- 8.beta.-carbonyl)ureas of the formula [I] which can be useful as anty-Parkisons drugs and prolactin inhibitors. One of the most potent antiprolactinic agent of the class of compounds prepared according to the present invention is CabergolineSilylated ergolines, which are obtained as intermediates in the process of the present invention, are novel compounds and represent a further aspect of the invention.
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Excerpt(s): This invention relates to a new process for the preparation of dopamine agonists such as Cabergoline, to some novel intermediates used in this process and to their preparation. wherein R.sup.1 represents an alkyl group having from 1 to 4 carbon atoms, a cyclohexyl group or a phenyl group or a dimethylamino alkyl group -(CH.sub.2).sub.nNMe.sub.2 in which n is an integer, R.sup.2 represents any of the groups which R.sup.1 may represent, or a hydrogen atom or a pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazolyl or thiadiazolyl residue, R.sup.3 represents a hydrocarbon group having from 1 to 4 carbon atoms, R.sup.4 represents a hydrogen or a halogen atom or a methylthio or phenylthio group and R.sup.5 represents a hydrogen atom or a methyl group; have shown potent dopamine agonist properties and have been useful as anti-Parkinson drugs and as prolactin inhibitors (U.S. Pat. No. 5,382,669 and Eur, J. Med. Chem., 1989, v. 24, 421). In this case both regioisomers [1a] and [8] were obtained and the yield of the isolated Cabergoline [1a] is low as a consequence of isolation difficulties. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PROLACTIN ANTAGONISTS AND USES THEREOF Inventor(s): WALKER, AMEAE M.; (RIVERSIDE, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20010036662 Date filed: April 23, 1998 Abstract: Recombinant nucleotide sequences encoding mutated prolactin are described. Expression of the sequences result in mimics of a phosphorylated prolactin corresponding to a selected species. A particularly preferred mimic is mutated at serine 179 (corresponding to human PRL) where serine is substituted by an aspartate residue. This aspartate mutant is a very effective antagonist and shows no ability to stimulate Nb2 to cell proliferation. Excerpt(s): The present application is a continuation-in-part of co-pending PCT/US97/01435, WO 97/27865, filed Jan. 30, 1997, which is a continuation-in-part of co-pending U.S. patent application Ser. No. 08/594,809, filed Jan. 31, 1996. The entire texts of the above-referenced disclosures are specifically incorporated by reference herein. The present invention relates generally to the field of biologically active peptides and proteins that function as prolactin antagonists, and uses of these proteins/peptides in compositions for regulating prolactin and growth hormone related functions. More particularly, the invention concerns recombinant nucleotide sequences encoding a mutated prolactin, which is a mimic of human phosphorylated prolactin and is capable of antagonizing a prolactin receptor. The inventive mimic antagonizes the growth promoting effects of non-phosphorylated prolactin. Prolactin (PRL) is a polypeptide hormone produced by the anterior pituitary. This hormone is important in a number of physiological events, including maintaining normal reproductive functions, osmoregulation, growth, and immunoregulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Prolactin induced increase in neural stem cell numbers Inventor(s): Shingo, Tetsuro; (Aoe, JP), Weiss, Samuel; (Calgary, CA) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030054998 Date filed: August 30, 2002 Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions. Excerpt(s): This application claims the benefit of U.S. Provisional Applications Serial No. 60/322,514, filed Sep. 14, 2001, and Serial No. 60/386,404, filed Jun. 7, 2002. The entire disclosure of each of these priority applications is hereby incorporated by reference. The present invention relates to methods of increasing neural stem cell numbers, neurogenesis or new olfactory neuron numbers by using prolactin, as well as methods for treating or ameliorating neurodegenerative diseases or conditions. U.S. Patent Application Publication No. 20020098178 A1. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Prolactin receptor gene as a genetic marker for increased litter size in animals Inventor(s): Gladney, Christy; (Berkeley, CA), Mileham, Alan; (Berkeley, CA), Plastow, Graham; (Cambridge, GB), Rothschild, Max F.; (Ames, IA), Sargent, Carole; (Cambridge, GB), Southwood, Olwen; (Abingdon, GB), Tuggle, Christopher K.; (Ames, IA), Vincent, Amy L.; (Jewell, IA) Correspondence: Mckee, Voorhees & Sease, P.L.C.; 801 Grand Avenue; Suite 3200; Des Moines; IA; 50309-2721; US Patent Application Number: 20020160372 Date filed: July 6, 2001 Abstract: Disclosed herein are genetic markers for animal litter size, methods for identifying such markers, and methods of screening animals to determine those more likely to produce larger litters and preferably selecting those animals for future breeding purposes. The markers are based upon the presence or absence of certain polymorphisms in the prolactin receptor gene. Excerpt(s): This invention relates generally to the detection of genetic differences for reproductive efficiency among pigs and particularly use of a genetic marker prolactin receptor gene which is indicative of the heritable trait of increased litter size. Reproductive efficiency, which can be defined as the number of pigs produced per breeding female, is the major limiting factor in the efficient production of pork. The number of pigs born alive in the U.S. averages approximately 9.5 pigs per litter. Heritability for litter size is low (10%-15%), and standard genetic methods of selecting
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breeding females on the basis of past litter size have not been effective. Therefore, there is a need for an approach that deals with selection for reproduction at the cellular or DNA level. Chinese breeds are known for reaching puberty at an early age and for their large litter size. American breeds are known for their greater growth rates and leanness. Thus, it would be desirable to combine the best characteristics of both types of breeds, thereby improving the efficiency of U.S. pork production. These efforts would be greatly assisted by the discovery of genes or genetic markers that are associated with increased litter size in pigs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Therapeutic compositions and methods relating to prolactin releasing peptide (PrRP) Inventor(s): Civelli, Olivier; (Irvine, CA), Lin, Steven; (Upland, CA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20030171270 Date filed: March 12, 2002 Abstract: The invention provides a substantially pure Prolactin Releasing Peptide (PrRP) functional analog which suppresses absence seizures in a mammal, and related pharmaceutical compositions. The invention also provides a method of controlling absence seizures in a mammal, by administering to a mammal susceptible to absence seizures an effective amount of PrRP or a PrRP functional analog. Also provided are methods of identifying a compound that modulates AMPA receptor signaling in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to modulate AMPA receptor signaling. The invention also provides methods of identifying a compound for controlling absence seizures in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to control absence seizures in a mammal. Also provided are pharmaceutical compositions for controlling absence seizures in a mamma. The compositions and related methods contain a compound identified by the methods of the invention as a compound that modulates AMPA receptor signaling or as a compound that controls absence seizures. Excerpt(s): The present invention relates generally to the field of medicine and, more specifically, to therapeutic compositions and methods relating to Prolactin Releasing Peptide (PrRP). Absence seizures are generalized non-convulsive seizures characterized by a brief period of unresponsiveness to environmental stimuli and cessation of activity, that can occur as frequently as several hundred times a day, primarily during quiet wakefulness, inattention and the transition between sleep and waking. In patients with absence seizures, generalized tonic-clonic seizures (GTCS) or "grand mal seizures" occasionally develop. Currently available drugs to control absence seizures are often associated with adverse side effects, including gastrointestinal symptoms, tremors, sedation, temporary hair loss, dizziness, incoordination, rashes, and drug interaction complications. More seriously, potentially fatal hepatic and hematopoietic complications, as well as teratogenicity (e.g. neural tube birth defects), have been associated with absence seizure medications. Additionally, while currently available drugs are effective in many individuals, certain individuals are resistant to all known treatments. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of anti-prolactin agents to treat proliferative conditions Inventor(s): Chen, Wen Y.; (Simpsonville, SC), Wagner, Thomas E.; (Greer, SC) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030022833 Date filed: May 8, 2002 Abstract: The present invention relates to variant forms of human prolactin which act as antagonists at the prolactin receptor, and to the use of such variants in the treatment of human cancers and proliferative disorders, including both benign and malignant diseases of the breast and prostate. Excerpt(s): The present invention relates to methods and compositions for inhibiting the cell proliferation-promoting effects of prolactin on its receptor. The methods and compositions of the invention may be used in the treatment of benign as well as malignant conditions which involve unwanted cell proliferation. Prolactin ("PRL") is a 23-kDa neuroendocrine hormone which is structurally related to growth hormone and, to a lesser degree, to members of the interleukin family (Reynolds et al., 1997, Endocrinol. 138:5555-5560, Cunningham et al., 1990, Science 247:1461-1465; Wells et al., 1993, Recent Prog. Horm. Res. 48:253-275). Acting via the prolactin receptor, it is required for the proliferation and terminal differentiation of breast tissue (Mani et al., 1986, Cancer Res. 46:1669-1672; Malarkey et al., 1983, J. Clin. Endocrinol. Metab. 56:673677; Biswas and Vonderhaar, 1987, Cancer Res. 47:3509-3514), promoting the growth and differentiation of the ductal epithelium, proliferation and differentiation of lobular units, and initiation and maintenance of lactation (Kelly et al., 1993, Recent Prog. Horm. Res. 48:123-164; Shiu et al., 1987, recent Pro. Horm. Res. 43:277-303). A diversity of other effects have been attributed to PRL, including roles in reproduction and the immune response (Wennbo et al., 1997, Endocrinol. 138:4410-4415; Nicoll, 1974, in Handbook of Physiology, Knobil and Sawyer, eds., American Physiological Society, Washington, D.C.; Shiu and Friesen, 1980, Annu. Rev. Physiol. 42:83-96). The prolactin receptor ("PRLR") is a member of the cytokine receptor superfamily and binds a group of hormones, including not only PRL but also placental lactogens and primate growth hormone ("GH"), to produce a mitogenic effect (Ormandy et al., 1997, J. Clin. Endocrinol. Metab. 82:3692-3699; Horseman, 1995, Endocrinol. 136:5249-5251; Clevenger et al., 1990, Proc. Natl. Acad. Sci. U.S.A. 87:6460-6464; Buckley et al., 1985, Life Sci. 37:2569-2575; Costello et al., 1994, Prostate 24:162-166). PRLR is homologous to the receptor for GH ("GHR", also referred to as the somatogen receptor) and both belong to the cytokine receptor superfamily (Kelly et al., 1991, Endocrin. Rev. 12:235-251; Kelly et al., 1993, Recent. Prog. Horm. Res. 48:123-164; Horseman and Yu-Lee, 1994, Endocrin. Rev. 15:627-649). 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 prolactin, 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:
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Under “Issued Patents,” click “Quick Search.” Then, type “prolactin” (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 prolactin. You can also use this procedure to view pending patent applications concerning prolactin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON PROLACTIN Overview This chapter provides bibliographic book references relating to prolactin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on prolactin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “prolactin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “prolactin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “prolactin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Actions of Prolactin on Molecular Processes by James A. Rillema (Editor); ISBN: 0849353769; http://www.amazon.com/exec/obidos/ASIN/0849353769/icongroupinterna
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Central and peripheral regulation of prolactin function; ISBN: 0890044899; http://www.amazon.com/exec/obidos/ASIN/0890044899/icongroupinterna
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Comparative Endocrinology of Prolactin by D. M. Ensor; ISBN: 0470263946; http://www.amazon.com/exec/obidos/ASIN/0470263946/icongroupinterna
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Comparative endocrinology of prolactin; ISBN: 0306390809; http://www.amazon.com/exec/obidos/ASIN/0306390809/icongroupinterna
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Control of Growth Hormone and Prolactin Release by Angiotensin Peptides in Reaggregate Cell Cultures of the Rat Pituitary by W. Robberecht; ISBN: 9061863716; http://www.amazon.com/exec/obidos/ASIN/9061863716/icongroupinterna
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Experimental modification of rat pituitary prolactin cell function during and after spaceflight (SuDoc NAS 1.26:205105) by NASA; ISBN: B00010ZCTS; http://www.amazon.com/exec/obidos/ASIN/B00010ZCTS/icongroupinterna
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Growth Hormone, Prolactin and Igf-I As Lymphohemopoietic Cytokines (Molecular Biology Intelligence Unit) by Elisabeth Hooghe-Peters, Robert Hooghe; ISBN: 1570592500; http://www.amazon.com/exec/obidos/ASIN/1570592500/icongroupinterna
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Human prolactin : proceedings of the International Symposium on Human Prolactin, Brussels, June 12-14, 1973; ISBN: 0444150617; http://www.amazon.com/exec/obidos/ASIN/0444150617/icongroupinterna
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Local Author Progress in Prolactin by R.J. Pepperell (Editor), et al (Editor); ISBN: 1850703442; http://www.amazon.com/exec/obidos/ASIN/1850703442/icongroupinterna
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Progress in Prolactin Physiology and Pathology: Proceedings of the International Symposium on Prolactin Held in Nice, France, 20-23 October, 1977 by Nice, France, 1977. International Symposium on Prolactin; ISBN: 0444800387; http://www.amazon.com/exec/obidos/ASIN/0444800387/icongroupinterna
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Prolactin; ISBN: 0444005552; http://www.amazon.com/exec/obidos/ASIN/0444005552/icongroupinterna
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Prolactin by M. L'Hermite (Editor), P. Jaquet (Editor); ISBN: 3805542372; http://www.amazon.com/exec/obidos/ASIN/3805542372/icongroupinterna
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Prolactin (Endocrine Updates, Volume 12) by Nelson D. Horseman (Editor); ISBN: 0792372905; http://www.amazon.com/exec/obidos/ASIN/0792372905/icongroupinterna
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Prolactin and human reproduction; ISBN: 0121983455; http://www.amazon.com/exec/obidos/ASIN/0121983455/icongroupinterna
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Prolactin and Lesions in Breast, Uterus, and Prostate by Hiroshi Nagasawa (Editor); ISBN: 0849368367; http://www.amazon.com/exec/obidos/ASIN/0849368367/icongroupinterna
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Prolactin and prolactinomas; ISBN: 0890048045; http://www.amazon.com/exec/obidos/ASIN/0890048045/icongroupinterna
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Prolactin Basic and Clinical Correlates (Fidia Research Series, Vol 1) by R.M. MacLeod (Editor), et al; ISBN: 0387155945; http://www.amazon.com/exec/obidos/ASIN/0387155945/icongroupinterna
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Prolactin Gene Family and Its Receptors: Molecular Biology to Clinical Problems (International Congresses Series, No 819) by Kazumasa Hoshino (Editor); ISBN: 0444810447; http://www.amazon.com/exec/obidos/ASIN/0444810447/icongroupinterna
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Prolactin Response to Neuroleptics: Clinical and Theoretical Implications by Rolf A. A. Axelsson; ISBN: 0387816054; http://www.amazon.com/exec/obidos/ASIN/0387816054/icongroupinterna
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Prolactin Secretion: A Multidisciplinary Approach by Flavio Mena, Carlos Valverder (Editor); ISBN: 0124906206; http://www.amazon.com/exec/obidos/ASIN/0124906206/icongroupinterna
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Prolactin: Physiology and Clinical Significance by D.F. Horrobin; ISBN: 0852000650; http://www.amazon.com/exec/obidos/ASIN/0852000650/icongroupinterna
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Prolactin: Physiology, Pharmacology and Chemistry by Fluckiger; ISBN: 0387110712; http://www.amazon.com/exec/obidos/ASIN/0387110712/icongroupinterna
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Prolactinomas by Jerrold M. Olefsky, Richard J. Robbins (Editor); ISBN: 0443084068; http://www.amazon.com/exec/obidos/ASIN/0443084068/icongroupinterna
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Prolactinomas : an interdisciplinary approach; ISBN: 0899250394; http://www.amazon.com/exec/obidos/ASIN/0899250394/icongroupinterna
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Prolactinomas: An Interdisciplinary Approach by G. Leb (Editor), et al; ISBN: 311010153X; http://www.amazon.com/exec/obidos/ASIN/311010153X/icongroupinterna
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Role of Prolactin in Human Reproduction by H. Mori, et al; ISBN: 3805547862; http://www.amazon.com/exec/obidos/ASIN/3805547862/icongroupinterna
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Sex hormones, effects on prolactin cells by M. F. El Etreby; ISBN: 8774941062; http://www.amazon.com/exec/obidos/ASIN/8774941062/icongroupinterna
Chapters on Prolactin In order to find chapters that specifically relate to prolactin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and prolactin 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 “prolactin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on prolactin: •
Metabolic Disorders: Treatment Strategies for Diabetes, Prolactinoma Source: in Newman, A.J. Beyond Viagra: Plain Talk About Treating Male and Female Sexual Dysfunction. Montgomery, AL: Starrhill Press. 1999. p. 58-63. Contact: Available from Black Belt Press. P.O. Box 551, Montgomery, AL 36101. (800) 959-3245 or (334) 265-6753. Fax (334) 265-8880. PRICE: $13.95 plus shipping and handling. ISBN: 1573590142. Summary: Endocrine disorders can be grouped into three general categories: diabetes mellitus, elevated prolactin levels (hyperprolactinemia), and a third group including a number of chronic disorders, most of which suppress testosterone, thereby resulting in decreased libido with secondary erectile dysfunction. This chapter covers treatment strategies for diabetes and prolactinoma (a benign pituitary tumor that results in prolactinemia). It is from a book that discusses the drug sildenafil (Viagra) in the context of a larger discussion about sexuality and sexual dysfunction. Diabetes is the number one single cause of male erectile dysfunction, accounting for about 40 percent of all impotence cases. The author discusses erectile dysfunction in men with diabetes, noting the role of strict blood glucose (sugar) control in the prevention and control of this problem. Other endocrine, or hormonal, causes are far less common, accounting for only about 4 percent of all cases of male erectile dysfunction. However, when these other cases are properly recognized and properly treated, the result is often a marked
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improvement without any further treatment. Prolactinomas sometimes require surgery and radiation; however, medical therapy is highly effective using Bromocriptine. In addition, it is important to understand that a large number of chronic illnesses and medications can contribute to elevated blood prolactin levels. The chapter is written in nontechnical language but includes enough medical information to be of use to medical professionals wishing to learn more about sexuality and sexual dysfunction. 2 tables.
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CHAPTER 6. PERIODICALS AND NEWS ON PROLACTIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover prolactin.
News Services and Press Releases One of the simplest ways of tracking press releases on prolactin is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “prolactin” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to prolactin. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “prolactin” (or synonyms). The following was recently listed in this archive for prolactin: •
Serum prolactin linked to severity of celiac disease Source: Reuters Medical News Date: March 12, 2004
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Cabergoline can be safely withdrawn in some patients with hyperprolactinemia Source: Reuters Industry Breifing Date: November 19, 2003
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Hyperprolactinemia in schizophrenics often resolves after switch to olanzapine Source: Reuters Medical News Date: August 06, 1999
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Prolactin levels linked to postmenopausal breast cancer risk Source: Reuters Medical News Date: April 09, 1999
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Prolactin hormone linked to breast cancer Source: Reuters Health eLine Date: April 09, 1999
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OC use safe in hyperprolactinemic women Source: Reuters Medical News Date: September 18, 1998
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Bromocriptine prevents some cases of hyperprolactinemic recurrent miscarriage Source: Reuters Medical News Date: September 04, 1998 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “prolactin” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or
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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “prolactin” (or synonyms). If you know the name of a company that is relevant to prolactin, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “prolactin” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “prolactin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on prolactin: •
Hormones and SLE Source: Minnesota Lupus News. 23(5): 5,8. October/November 1999. Contact: Available from Minnesota Chapter, Lupus Foundation of America, Inc. International Market Square, 275 Market Street, Suite C19, Minneapolis, MN 55405-1620. (800) 645-1131 or (612) 375-1131. Summary: This newsletter article provides people who have lupus with information on the role of sex hormones in this disease. An investigation of the hormones that affect lupus begins with an examination of the gland that produces them. The pituitary gland is responsible for all of the hormone shifts in the bodies of both men and women. One hormone secreted from the pituitary that has been studied extensively is called prolactin. Researchers outside the United States have found that many patients with lupus have elevated blood levels of prolactin and that suppression of prolactin with drugs results in clinical improvement. Sex steroid function in patients with lupus has been of particular interest to researchers, but investigation of this part of the endocrine system and its relationship to the immune system has not provided any definitive results. Other research has focused on understanding how and why lupus predominantly affects women.
Academic Periodicals covering Prolactin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to prolactin. In addition to these sources, you can search for articles covering prolactin that have been published by any
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of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for prolactin. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with prolactin. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to prolactin: Bromocriptine •
Systemic - U.S. Brands: Parlodel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202094.html
Cabergoline •
Systemic - U.S. Brands: Dostinex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203584.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “prolactin” (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 41934 577 65 18 156 42750
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “prolactin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Prolactin In the following section, we will discuss databases and references which relate to the Genome Project and prolactin. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “prolactin” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for prolactin: •
Preproprolactin-releasing Peptide Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602663
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Prolactin Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176760
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Prolactin Deficiency with Obesity and Enlarged Testes Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264120
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Prolactin Deficiency, Isolated Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264110
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Prolactin Receptor Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176761
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Prolactin Regulatory Element-binding Protein Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606395
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Prolactin-inducible Protein Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176720
•
Prolactinoma, Familial Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600634 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease,
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glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html •
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
•
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
•
PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
•
Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “prolactin” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. 22
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “prolactin” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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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 prolactin 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 prolactin. 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. 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 prolactin. 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 “prolactin”: Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html
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Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.html Preventing Disease and Staying Healthy http://www.nlm.nih.gov/medlineplus/preventingdiseaseandstayinghealthy.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to prolactin. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to prolactin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with prolactin. 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 prolactin. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “prolactin” (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 “prolactin”. 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 “prolactin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “prolactin” (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.24
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
24
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)25: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
25
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on prolactin: •
Basic Guidelines for Prolactin Prolactin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm Prolactinoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000336.htm
•
Signs & Symptoms for Prolactin Abnormal milk flow from the breast Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003154.htm Cessation of menses Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003149.htm Decreased sexual interest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003164.htm
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Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Gynecomastia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003165.htm Impotence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003164.htm •
Diagnostics and Tests for Prolactin Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Cranial CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm Cranial MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Dopamine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003561.htm Prolactin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm Prolactin level Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm Testosterone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003707.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm
•
Nutrition for Prolactin Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm
•
Background Topics for Prolactin Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Anterior Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002232.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm
Online Glossaries 203
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 Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.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
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PROLACTIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine
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with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] 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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Hyperplasia, Congenital: A group of inherited disorders of adrenal steroidogenesis, the physical expression of which varies with the sex of the patient, the severity of the congenital enzyme defect, and the age at which the defect makes its presence felt. The most common form, the simple virilizing form, is due to a 21-hydroxylase deficiency. There is also a salt-losing form (a more complete 21-hydroxylase deficiency), a hypertensive form (11-hydroxylase deficiency), a 17-hydroxylase deficiency form, a desmolase deficiency form, and a 3-beta-hydroxysteroid deficiency form. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [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
Dictionary 207
complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] 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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH]
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Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] 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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and
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kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH]
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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] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthracyclines: Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. [NIH] Antiandrogen therapy: Treatment with drugs used to block production or interfere with the action of male sex hormones. [NIH] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH]
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Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome,
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and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aptitude: The ability to acquire general or special types of knowledge or skill. [NIH] Aqueous: Having to do with water. [NIH] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]
Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]
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Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight peptides derived from a common precursor and secreted by the heart atria. All these peptides share a sequence of about 20 amino acids. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH]
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Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
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Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [NIH]
Bilateral: Affecting both the right and left side of 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [NIH] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [NIH] Biological Phenomena: Biological functions and activities at the organic and molecular levels in humans, animals, microorganisms, and plants. For biochemical and metabolic processes, biochemical phenomena is available. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast,
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pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]
Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [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 Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells,
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megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder)
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and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [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] Caloric intake: Refers to the number of calories (energy content) consumed. [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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] 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] 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] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH]
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Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell
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division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH]
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Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [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] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] 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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choriocarcinoma: A malignant tumor of trophoblastic epithelium characterized by secretion of large amounts of chorionic gonadotropin. It usually originates from chorionic products of conception (i.e., hydatidiform mole, normal pregnancy, or following abortion), but can originate in a teratoma of the testis, mediastinum, or pineal gland. [NIH]
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Chorion: The outermost extraembryonic membrane. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Coagulants: Exogenous substances used to promote blood coagulation. The endogenous blood coagulation factors are considered to be coagulants only when administered as drugs. [NIH]
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] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations
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which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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] Colorectal: Having to do with the colon or the rectum. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]
Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete
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response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU]
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Consumption: Pulmonary tuberculosis. [NIH] Contraceptive Agents: Chemical substances that prevent or reduce the probability of conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to
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angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption
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maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] 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] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively
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persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] 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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dexfenfluramine: The S-isomer of fenfluramine. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diethylstilbestrol: DES. 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] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders.
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[NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Dolichol: Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated. [NIH]
Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. [NIH]
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Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dosage schedule: A scheme set up to determine and regulate size, frequency and number of doses. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]
Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]
Dysgenesis: Defective development. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological
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disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH]
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Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] 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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH]
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Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [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] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethyl Methanesulfonate: An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams,
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salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [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] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [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 Movement: Motion of the fetus perceived by the mother and felt by palpation of the abdomen. [NIH]
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Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the
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emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicular Fluid: A fluid consisting of sex steroid hormones, plasma proteins, mucopolysaccharides, and electrolytes that is present in the vesicular ovarian follicle (Graafian follicle) surrounding the ovum. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
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Gastrin-Releasing Peptide: Neuropeptide and gut hormone that helps regulate gastric acid secretion and motor function. Once released from nerves in the antrum of the stomach, the neuropeptide stimulates release of gastrin from the G cells. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic 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 Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] 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] Gestation period: The period of development of the young from the time of conception until birth. [NIH] 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] Gigantism: The condition of abnormal overgrowth or excessive size of the whole body or
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any of its parts. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] 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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most
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multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] 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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulosa Cell Tumor: An ovarian tumor originating in the cells of the primordial membrana granulosa of the graafian follicle. It may be associated with excessive production of estrogen. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [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] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [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
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other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic tissue: Tissue in which new blood cells are formed. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhaging: A copious discharge of blood from the blood vessels. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]
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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hookworms: A parasitic infection that may affect workers exposed to warm moist soil in which the larvae of the worm lives. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic
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acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydatidiform Mole: A trophoblastic disease characterized by hydrops of the mesenchymal portion of the villus. Its karyotype is paternal and usually homozygotic. The tumor is indistinguishable from chorioadenoma destruens or invasive mole ( = hydatidiform mole, invasive) except by karyotype. There is no apparent relation by karyotype to choriocarcinoma. Hydatidiform refers to the presence of the hydropic state of some or all of the villi (Greek hydatis, a drop of water). [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [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] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypophyseal: Hypophysial. [EU]
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Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FSH; somatotropin; and corticotropin). This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH]
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Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]
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Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important
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processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-11: Lymphohematopoietic cytokine that has the ability to modulate antigenspecific antibody responses, potentiate megakaryocytes, and regulate bone marrow adipogenesis. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH]
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Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isocyanates: Organic compounds that contain the -NCO radical. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH]
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Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Larva: Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]
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Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] 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] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [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] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipomatosis: A disorder consisting of the accumulation of abnormal localized, or tumor-like fat in the tissues. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other
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material, used for carrying an injured or disabled person. [NIH] Litter Size: The number of offspring produced at one birth by an animal. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [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] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH]
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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [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 fibrous histiocytoma: A sarcoma that usually begins in soft tissue. It usually appears as an enlarging, painful mass that can cause fracture due to destruction of the bone by a spreading tumor. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Maternal Behavior: The behavior patterns associated with or characteristic of a mother. [NIH]
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Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Eminence: Raised area on the infundibular hypothalamus at the floor of the third ventricle of the brain which contains the primary capillary network of the hypophyseal portal system. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [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] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH]
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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 Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] 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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Messenger RNA: The RNA molecule that conveys from the DNA the information that is to be translated into the structure of a particular polypeptide molecule. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metamorphosis: The ontogeny of insects, i. e. the series of changes undergone from egg, through larva and pupa, or through nymph, to adult. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular
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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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Ejection: Reflex in which tactile stimulation of nipples causes release of oxytocin which causes myoepithelial cells surrounding mammary alveoli to contract and expel the milk. Applies to humans and animals. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA,
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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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [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] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH]
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Music Therapy: The use of music as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natriuretic Hormone: A low-molecular weight substance, possibly from the hypothalamus, which is released due to plasma volume expansion. It causes natriuresis in part by inhibiting sodium potassium ATPase. The development of hypertension may be the consequence of an abnormality in volume regulation induced by a defect in the renal response to the natriuretic effect of the natriuretic hormone. Do not confuse with atrial natriuretic factor or cardionatrin which is a different, well characterized hormone. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]
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Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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] Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH]
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Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nipples: The conic organs which usually give outlet to milk from the mammary glands. [NIH]
Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Node-negative: Cancer that has not spread to the lymph nodes. [NIH]
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Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nulliparous: Having never given birth to a viable infant. [EU] Nymph: The immature stage in the life cycle of those orders of insects characterized by gradual metamorphosis, in which the young resemble the imago in general form of body, including compound eyes and external wings; also the 8-legged stage of mites and ticks that follows the first moult. [NIH] Obsessional: Neurosis characterized by the repetitive intrusion into the mind, against volition, of ideas, numinations and phobias, often associated with compulsive actions. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats,
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waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oleandomycin: Antibiotic substance produced by Streptomyces antibioticus. [NIH] Oligohydramnios: Presence of less than 300 ml of amniotic fluid at term. Principal causes include malformations of fetal urinary tracts, intra-uterine growth retardation, high maternal blood pressure, nicotine poisoning, and prolonged pregnancy. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH]
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Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] 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] Ovariectomy: The surgical removal of one or both ovaries. [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] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [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] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Palsies: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior
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abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parathyroidectomy: Excision of one or both of the parathyroid glands. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of
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tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatric Endocrinologist: A doctor who sees and treats children with problems of the endocrine glands; diabetes is an endocrine disorder. [NIH] Pedophilia: A sexual disorder occuring in a person 16 years or older and that is recurrent with intense sexually arousing fantasies, sexual urges, or behaviors involving sexual activity with a prepubescent child (generally age 13 or younger). (from APA, DSM-IV, 1994). [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penile Prosthesis: Rigid, semi-rigid, or inflatable cylindric hydraulic devices, with either combined or separate reservoir and pumping systems, implanted for the surgical treatment of organic impotence. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete 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] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH]
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Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Photosensitization: The development of abnormally heightened reactivity of the skin to sunlight. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH]
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Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pirenzepine: An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as cimetidine and ranitidine. It is generally well tolerated by patients. [NIH] Pituitary Apoplexy: Sudden hemorrhage or ischemic necrosis involving the pituitary gland which may be associated with acute visual loss, severe headache, meningeal signs, cranial nerve palsies, panhypopituitarism, and rarely coma. The most common cause is hemorrhage (intracranial hemorrhages) related to a pituitary adenoma. Ischemia, meningitis, intracranial hypertension, and other disorders may be associated with this condition. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Hormones: Hormones secreted by the anterior and posterior lobes of the pituitary gland and the pars intermedia, an ill-defined region between the two. Their secretion is regulated by the hypothalamus. [NIH] Pituitary Neoplasms: Neoplasms which arise from or metastasize to the pituitary gland. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (adenoma, basophil; adenoma, acidophil; and adenoma, chromophobe). Pituitary tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. [NIH]
Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH]
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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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched
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or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polyhydramnios: Excess of amniotic fluid greater than 2,000 ml. It is a common obstetrical complication whose major causes include maternal diabetes, chromosomal disorders, isoimmunological disease, congenital abnormalities, and multiple gestations. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system. [NIH] Post partum: After childbirth, or after delivery. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] 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] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH]
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Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] 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] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
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Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Proestrus: Phase of the estrous cycle preceding estrus during which the Graafian follicle undergoes maturation. Applies to animals. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Proliferative Retinopathy: A disease of the small blood vessels of the retina of the eye. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]
Prospective study: An epidemiologic study in which a group of individuals (a cohort), all
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free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [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] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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 Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH]
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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH]
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Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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] Pulmonary hypertension: Abnormally high blood pressure in the arteries of 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]
Pupa: An inactive stage between the larval and adult stages in the life cycle of insects. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]
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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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH]
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Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by
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specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticulocytes: Immature erythrocytes. In humans, these are erythroid cells that have just undergone extrusion of their cell nucleus. They still contain some organelles that gradually decrease in number as the cells mature. ribosomes are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the endoplasmic reticulum), hence the name reticulocytes. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH]
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Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts. [NIH] Schistosoma mansoni: A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis. [NIH] Schistosomiasis mansoni: Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an
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anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seborrhea: Hypersecretion of sebum with excessive oily secretion from the sweat glands. [NIH]
Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Self-Injurious Behavior: Behavior in which persons hurt or harm themselves without the motive of suicide or of sexual deviation. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence
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(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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH]
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Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Skull Base: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [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]
Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Lactate: The sodium salt of racemic or inactive lactic acid. It is a hygroscopic agent used intravenously as a systemic and urinary alkalizer. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH]
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Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphenoidal: Relating or belonging to the sphenoid bone. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH]
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Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] 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] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Subthalamus: A transition zone in the anterior part of the diencephalon interposed between the thalamus, hypothalamus, and tegmentum of the mesencephalon. Components of the
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subthalamus include the subthalamic nucleus, zona incerta, nucleus of field H, and the nucleus of ansa lenticularis. The latter contains the entopeduncular nucleus. [NIH] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]
Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] 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] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces
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tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] 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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenicity: The power to cause abnormal development. [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 in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases,
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palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth
Dictionary 287
of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tilapia: A freshwater fish used as an experimental organism and for food. This genus of the family Cichlidae inhabits Central and South America (one species extends north into Texas), West Indies, Africa, Madagascar, Syria, and coastal India. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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]
288
Prolactin
Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU]
Dictionary 289
Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH]
290
Prolactin
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] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]
Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU]
Dictionary 291
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [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] Volition: Voluntary activity without external compulsion. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH]
292
Prolactin
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
293
INDEX 5 5-Hydroxytryptophan, 36, 205 A Abdomen, 205, 236, 248, 252, 264, 265, 277, 282, 283 Abdominal, 205, 206, 264, 277 Aberrant, 16, 28, 51, 134, 135, 136, 143, 205 Ablate, 139, 205 Ablation, 205, 245 Abortion, 4, 16, 205, 221, 270 Acanthosis Nigricans, 6, 205 Acetylcholine, 205, 221, 260 Acne, 6, 205, 227 Adaptability, 205, 219, 220 Adaptation, 205, 268 Adenine, 205, 274 Adenocarcinoma, 53, 86, 205 Adenoma, 76, 80, 102, 108, 205, 267 Adenosine, 65, 66, 122, 137, 154, 205, 266 Adenosine Deaminase, 137, 154, 205 Adenovirus, 109, 206 Adenylate Cyclase, 112, 206 Adipocytes, 62, 206, 250 Adjunctive Therapy, 206, 258 Adjustment, 143, 205, 206 Adjuvant, 7, 206 Adjuvant Therapy, 7, 206 Adolescence, 52, 119, 206 Adrenal Cortex, 126, 206, 207, 226, 227, 235, 271 Adrenal Glands, 92, 206 Adrenal Hyperplasia, Congenital, 6, 206 Adrenal insufficiency, 143, 206 Adrenal Medulla, 47, 206, 219, 234, 261 Adrenergic, 206, 210, 212, 230, 234, 284, 292 Adverse Effect, 206, 223, 280 Afferent, 206, 250 Affinity, 35, 40, 46, 103, 206, 207, 223, 251, 255, 281 Affinity Chromatography, 103, 207 Agar, 207 Agarose, 108, 207 Agoraphobia, 207, 266 Air Sacs, 207, 208 Akathisia, 207, 212 Aldosterone, 126, 207 Algorithms, 64, 207, 216
Alimentary, 75, 207, 264 Alkaline, 4, 207, 208, 218, 285 Alkaline Phosphatase, 4, 207 Alkaloid, 207, 214, 217, 223, 257, 260, 278, 292 Allantois, 207, 236 Alleles, 20, 26, 207 Allergen, 207, 279 Allogeneic, 43, 207 Allograft, 208, 259 Alopecia, 6, 208 Alpha Particles, 208, 274 Alternative medicine, 174, 208 Alternative Splicing, 98, 157, 208, 272 Alveolar Process, 208, 276 Alveoli, 39, 208, 256 Ameliorating, 142, 164, 208 Amenorrhea, 84, 145, 208, 210, 217, 268 Amino Acid Motifs, 208, 225 Amino Acid Sequence, 138, 152, 156, 157, 208, 210, 215, 225, 236, 239, 271 Amino Acid Substitution, 153, 208 Ammonia, 206, 208, 284, 289 Amnion, 21, 208, 236 Amniotic Fluid, 208, 239, 262, 269 Amphetamine, 17, 209, 229 Ampulla, 209, 221 Amylase, 152, 209 Anabolic, 36, 209, 230 Anaesthesia, 209, 246 Anal, 209, 234, 237 Analgesic, 209, 233, 257, 262 Analog, 144, 152, 165, 209 Analogous, 152, 209, 288 Anaphylatoxins, 209, 224 Anaplasia, 209 Anatomical, 61, 209, 213, 246, 259, 278 Androgenic, 6, 209 Androgens, 6, 7, 10, 50, 55, 206, 209, 213, 227 Anemia, 48, 111, 187, 209, 218, 242, 257 Anesthesia, 120, 209, 210, 250 Anesthetics, 209, 234 Angiogenesis, 27, 40, 70, 113, 115, 155, 162, 209, 233 Angiogenesis inhibitor, 209, 233 Animal model, 9, 11, 15, 30, 33, 41, 54, 210 Anions, 44, 210, 249, 284
294
Prolactin
Anisotropy, 210, 237 Anode, 210 Anomalies, 4, 210 Anorexia, 56, 118, 210 Anorexia Nervosa, 56, 118, 210 Anovulation, 123, 210, 268 Antagonism, 55, 210, 223 Anthracyclines, 75, 210 Antiandrogen therapy, 6, 210 Antiandrogens, 210, 215 Antiangiogenic, 65, 161, 162, 210 Anti-Anxiety Agents, 210, 270, 273, 288 Antibacterial, 210, 282 Antibiotic, 210, 262, 265, 270, 282 Antibodies, 15, 49, 63, 72, 82, 138, 151, 210, 212, 214, 241, 244, 245, 252, 267 Antibody therapy, 29, 211 Anticoagulant, 211, 272 Antidepressant, 17, 205, 211, 238 Antidepressive Agents, 211, 273 Antiemetic, 143, 211, 212, 255 Antiepileptic, 87, 205, 211 Antifungal, 211, 250 Antigen, 87, 151, 207, 210, 211, 212, 224, 228, 237, 243, 244, 245, 246, 247, 248, 254, 279 Antigen-Antibody Complex, 211, 224 Antigen-presenting cell, 211, 228 Antihypertensive, 143, 211 Anti-inflammatory, 16, 211, 227, 229, 240 Antimetabolite, 211, 217 Antineoplastic, 138, 154, 211, 217, 227, 235 Antineoplastic Agents, 138, 154, 211 Antioxidant, 8, 10, 27, 211, 263 Antipsychotic, 63, 78, 79, 84, 95, 105, 117, 211, 212, 223, 231, 259, 278, 288 Antipsychotic Agents, 212, 231, 288 Antiseptic, 212, 219 Antiserum, 70, 74, 147, 212 Antispasmodic, 212, 262, 279 Antiviral, 138, 154, 212, 217, 248, 265 Antiviral Agents, 138, 154, 212 Anus, 209, 212, 224 Anxiety, 5, 207, 210, 212, 264, 266 Anxiolytic, 212, 218 Apoptosis, 20, 36, 38, 55, 59, 60, 106, 114, 125, 155, 212, 219, 227 Aptitude, 152, 212 Aqueous, 134, 212, 214, 228, 232, 244 Arcuate Nucleus, 36, 212 Arginase, 137, 154, 212 Arginine, 137, 154, 209, 212, 260, 289, 290
Aromatase, 27, 31, 40, 118, 213 Aromatic, 213, 222, 255, 266 Arterial, 213, 217, 220, 226, 244, 248, 272, 284 Arteries, 213, 216, 220, 226, 255, 258, 274, 289 Arterioles, 213, 216, 218 Arteriovenous, 213, 220 Arteritis, 213, 269 Artery, 76, 213, 220, 226, 232, 274, 289 Arthritis, Rheumatoid, 162, 213 Articular, 213 Aseptic, 213, 262, 283 Asparaginase, 137, 154, 213 Aspartate, 163, 213, 250 Assay, 10, 11, 12, 38, 48, 100, 130, 131, 139, 213 Astringent, 213, 219 Asymptomatic, 17, 213 Ataxia, 187, 213, 285 Atrial, 74, 80, 213, 226, 258, 288 Atrial Natriuretic Factor, 213, 258 Atrioventricular, 213, 226 Atrium, 213, 226, 288, 290 Atrophy, 50, 114, 187, 213, 259 Atropine, 214, 278 Attenuation, 38, 214, 275 Atypical, 42, 90, 214, 223, 278 Autoantibodies, 78, 93, 214 Autoantigens, 50, 214 Autoimmune disease, 14, 29, 50, 142, 147, 214, 257 Autoimmunity, 7, 90, 98, 214 Autonomic, 5, 7, 47, 52, 80, 83, 114, 205, 212, 214, 261, 265 Autopsy, 8, 214 Autoradiography, 11, 214 Axons, 214, 229, 262, 274 B Bactericidal, 214, 235 Bacterium, 214, 225 Basal Ganglia, 212, 213, 214, 221, 261 Basal Ganglia Diseases, 213, 214, 221 Base, 205, 214, 228, 235, 239, 249, 268, 274, 285 Basement Membrane, 214, 236 Basophils, 214, 241, 251 Benign, 91, 95, 110, 166, 171, 205, 214, 237, 241, 250, 259, 275 Benzodiazepines, 215, 218 Beta-Endorphin, 42, 73, 88, 104, 116, 215 Bicalutamide, 87, 215
Index 295
Bilateral, 215, 268 Bile, 44, 215, 238, 252, 283 Bile Acids, 44, 215, 283 Bile Acids and Salts, 215 Biliary, 215, 221 Binding Sites, 26, 28, 35, 46, 48, 62, 96, 110, 215 Bioassay, 215 Biochemical, 9, 15, 23, 24, 26, 38, 39, 43, 48, 103, 120, 129, 141, 207, 211, 215, 237, 240, 280 Biochemical Phenomena, 215 Biological Assay, 35, 215 Biological Phenomena, 25, 215 Biological response modifier, 215, 248 Biological therapy, 215, 241 Biomarkers, 8, 10, 35, 120, 215 Biopterin, 216, 259 Biotechnology, 25, 64, 75, 174, 183, 185, 186, 187, 188, 216 Bivalent, 216, 255 Bladder, 216, 246, 257, 259, 272, 290 Blastocyst, 15, 216, 225, 232, 263, 267, 289 Blood Cell Count, 216, 242 Blood Coagulation, 216, 218, 223, 286 Blood Coagulation Factors, 216, 223 Blood Glucose, 171, 216, 242, 247 Blood Platelets, 216, 254, 280, 286 Blood pressure, 8, 202, 211, 216, 221, 244, 245, 257, 262, 274, 281 Blood Volume, 136, 216 Blood-Brain Barrier, 161, 216, 251 Body Composition, 44, 216 Body Fluids, 53, 215, 216, 231, 259, 281, 289 Bone Marrow, 31, 43, 91, 106, 216, 217, 227, 235, 239, 241, 245, 248, 252, 254, 257, 281, 283 Bone Marrow Cells, 216, 254 Bone Marrow Transplantation, 43, 217 Bone Remodeling, 37, 217 Bone Resorption, 217 Brachytherapy, 217, 248, 249, 274, 292 Bradykinin, 217, 260, 268 Brain Injuries, 33, 217 Brain Ischemia, 217, 220 Brain Stem, 217, 220 Branch, 87, 199, 217, 252, 264, 274, 282, 285 Breeding, 30, 122, 146, 152, 158, 164, 217 Bromodeoxyuridine, 68, 217 Bronchi, 217, 234, 288 Bronchioles, 208, 217
Buccal, 217, 252 Bulimia, 56, 217 Buspirone, 75, 76, 96, 218 C Cadmium, 123, 218 Cadmium Poisoning, 218 Calcitonin, 37, 45, 137, 154, 218 Calcium, 4, 74, 88, 125, 156, 217, 218, 224, 264, 280, 285 Caloric intake, 140, 218 Capillary, 65, 217, 218, 254, 269, 291 Capsules, 218, 231 Carbohydrate, 24, 160, 218, 227, 240, 269, 280 Carbon Dioxide, 218, 237, 267, 276, 290 Carcinogen, 218, 235 Carcinogenesis, 49, 155, 218, 221 Carcinogenic, 218, 247, 262, 271, 283, 289 Carcinoma, 39, 108, 218, 227 Cardiac, 56, 218, 226, 234, 236, 258, 283 Cardiovascular, 8, 47, 209, 218, 267, 280, 290 Case report, 79, 84, 101, 111, 218, 223 Case series, 218, 223 Caspase, 22, 219 Castration, 28, 219 Catechol, 10, 219 Catecholamine, 211, 219, 229, 230 Caudal, 219, 229, 245, 261, 269 Caudate Nucleus, 214, 219, 261 Causal, 219, 234 Cause of Death, 8, 51, 219 Caveolae, 12, 219 Caveolins, 219 Celiac Disease, 173, 219 Cell Adhesion, 130, 219, 247 Cell Communication, 9, 219 Cell Death, 22, 212, 219 Cell Differentiation, 38, 62, 219, 280 Cell Division, 186, 214, 219, 220, 241, 248, 256, 267, 271 Cell Lineage, 159, 219 Cell membrane, 21, 219, 228, 249, 266 Cell Membrane Structures, 219 Cell motility, 219, 242 Cell proliferation, 9, 20, 23, 28, 34, 49, 59, 61, 88, 115, 147, 163, 166, 219, 280 Cell Size, 220, 237 Cell Survival, 220, 241 Cellulose, 220, 238, 267 Centrifugation, 220, 242 Centrosome, 23, 220, 256
296
Prolactin
Cerebellar, 213, 220, 276 Cerebellum, 217, 220, 276 Cerebral, 11, 213, 214, 216, 217, 220, 221, 228, 234, 273, 274, 281, 286 Cerebral Cortex, 213, 220, 274 Cerebral hemispheres, 214, 217, 220, 221 Cerebral Infarction, 220 Cerebrospinal, 106, 220 Cerebrospinal fluid, 106, 220 Cerebrovascular, 10, 141, 214, 220, 285 Cerebrovascular Disorders, 141, 220, 285 Cerebrum, 220, 221, 267, 289 Cervix, 205, 221, 276 Chemoprevention, 40, 221 Chemopreventive, 30, 221 Chemoreceptor, 212, 221 Chemotactic Factors, 221, 224 Chemotherapeutic agent, 48, 221 Chemotherapy, 51, 206, 221 Chimeric Proteins, 155, 156, 221 Chlorophyll, 221, 238 Cholecystokinin, 116, 221 Cholestasis, 44, 221 Cholesterol, 215, 219, 221, 222, 244, 275, 283, 285 Choline, 116, 221 Cholinergic, 212, 221, 260 Chondrocytes, 221, 237 Chorea, 211, 221 Choriocarcinoma, 63, 221, 244 Chorion, 21, 222, 236 Chromaffin System, 222, 232 Chromatin, 17, 28, 63, 67, 69, 70, 212, 222, 260, 261 Chromosomal, 24, 222, 268, 269, 277 Chromosome, 64, 73, 222, 225, 251, 289 Chronic Fatigue Syndrome, 7, 222 Chronic renal, 3, 222, 268 Chylomicrons, 135, 222 Chymopapain, 222, 264 Chymotrypsin, 137, 154, 222 Cicatrix, 222, 249 Cicatrix, Hypertrophic, 222, 249 Ciliary, 82, 89, 222, 290 Cimetidine, 6, 222, 267 Circadian, 59, 139, 150, 222 Circadian Rhythm, 59, 139, 150, 222 Circulatory system, 222, 232 CIS, 19, 45, 51, 67, 222, 277 Clear cell carcinoma, 222, 229 Clinical Medicine, 94, 223, 270 Clinical study, 75, 223
Clinical trial, 7, 183, 223, 226, 227, 231, 273, 275 Clone, 24, 45, 66, 223 Clonic, 144, 165, 223 Cloning, 38, 65, 66, 67, 68, 69, 157, 216, 223 Clozapine, 83, 84, 97, 107, 112, 223 Coagulants, 138, 154, 223 Coca, 223 Cocaine, 42, 114, 123, 223 Codon, 136, 223, 239 Coenzyme, 223, 237 Cofactor, 223, 272, 286 Cognition, 161, 223, 259 Cohort Studies, 223, 234 Collagen, 208, 213, 214, 224, 237, 249, 268 Colon, 10, 53, 59, 86, 186, 224 Colorectal, 86, 224 Colostrum, 14, 224 Combinatorial, 48, 52, 224 Comorbidity, 42, 224 Complement, 42, 209, 224, 239, 247, 268, 279 Complementation, 23, 72, 224 Complete remission, 224, 276 Computational Biology, 183, 185, 225 Conception, 205, 221, 225, 226, 237, 239, 270, 283 Concomitant, 5, 79, 84, 101, 149, 225 Conduction, 225, 285 Confounding, 57, 225 Congestion, 212, 225 Conjugated, 215, 225, 227, 277 Conjugation, 25, 137, 138, 154, 225 Conjunctiva, 225, 288 Connective Tissue, 216, 224, 225, 229, 237, 238, 249, 252, 255, 277, 278, 283, 284 Consciousness, 141, 209, 210, 225, 228, 230, 273, 282 Consensus Sequence, 24, 62, 208, 225 Conserved Sequence, 208, 225 Constipation, 212, 225 Constitutional, 97, 225 Consumption, 9, 20, 99, 226, 276 Contraceptive Agents, 6, 226 Contraindications, ii, 226 Control group, 8, 18, 54, 59, 226 Controlled study, 75, 96, 226 Convulsion, 215, 226 Convulsive, 144, 165, 226 Coordination, 220, 226, 257 Cor, 6, 42, 74, 226, 245, 271 Cornea, 226, 278, 283, 290
Index 297
Coronary, 226, 255, 258 Coronary Thrombosis, 226, 255, 258 Corpus, 226, 252, 265, 267, 271, 286, 291 Corpus Luteum, 226, 252, 271 Cortex, 226, 243, 276 Cortical, 11, 226, 259, 274, 279, 285 Corticosteroid, 226, 283 Cortisol, 34, 46, 52, 56, 59, 66, 77, 79, 83, 89, 90, 96, 100, 102, 107, 113, 116, 120, 227 Cortisone, 227, 229 Cranial, 202, 220, 227, 241, 249, 265, 267, 282, 288 Cross-Sectional Studies, 227, 234 Cultured cells, 13, 227 Curative, 227, 260, 286 Cutaneous, 227, 252, 264 Cyanogen Bromide, 141, 227 Cyclic, 72, 122, 145, 150, 206, 219, 227, 241, 260 Cyclosporine, 14, 32, 84, 227 Cyproterone, 6, 227, 238 Cyproterone Acetate, 6, 227 Cysteinyl, 227, 255 Cytochrome, 213, 222, 227 Cytokine, 16, 22, 23, 24, 31, 32, 38, 48, 49, 59, 82, 84, 99, 104, 120, 148, 156, 166, 228, 248 Cytoplasm, 59, 137, 212, 214, 219, 228, 234, 241, 255, 260, 278 Cytoskeleton, 228, 247 Cytotoxic, 157, 228, 275, 280 D Decidua, 13, 16, 21, 92, 96, 228, 256, 267 Defense Mechanisms, 228, 248 Degenerative, 228, 242, 253, 257 Dehydration, 4, 228 Deletion, 30, 46, 67, 212, 228, 239 Delirium, 211, 228 Dementia, 141, 211, 212, 228, 229 Dendrites, 228, 259, 274 Dendritic, 87, 228, 254 Dendritic cell, 87, 228 Density, 11, 58, 81, 157, 220, 228, 237, 262, 269, 275 Depolarization, 228, 280 Depressive Disorder, 228, 251 Deprivation, 41, 229 Dermal, 157, 229 Dermis, 229, 249, 284 DES, 125, 209, 229 Deuterium, 229, 244
Developmental Biology, 26, 122, 229 Dexamethasone, 42, 73, 229 Dexfenfluramine, 57, 229 Dextroamphetamine, 209, 229 Diabetes Mellitus, 171, 229, 240, 242 Diabetic Retinopathy, 162, 229 Diagnostic procedure, 133, 174, 229 Dialyzer, 229, 242 Diastolic, 229, 244 Diencephalon, 26, 220, 229, 234, 245, 271, 283, 285, 286 Diethylstilbestrol, 34, 123, 229 Diffuse Axonal Injury, 217, 229 Digestion, 207, 215, 230, 231, 248, 252, 283 Dihydrotestosterone, 227, 230, 276 Dihydroxy, 207, 230, 235 Dilatation, 205, 230 Dilator, 80, 230 Dimerization, 22, 63, 139, 230 Diploid, 224, 230, 267, 289 Direct, iii, 13, 14, 27, 32, 44, 49, 57, 63, 177, 219, 223, 230, 272, 276 Discrete, 140, 152, 217, 230, 252 Disinfectant, 230, 235 Disposition, 15, 230 Dissociation, 206, 230, 249 Distal, 68, 70, 157, 230, 250, 273 Dizziness, 144, 165, 230, 291 Docetaxel, 89, 230 Dolichol, 24, 230 Dopa, 87, 230, 251 Dopamine Agents, 17, 230 Dopamine Agonists, 78, 120, 163, 231 Dopamine Antagonists, 17, 231 Dosage Forms, 134, 231 Dosage schedule, 63, 231 Double-blind, 63, 75, 83, 96, 231 Drive, ii, vi, 48, 103, 121, 231, 249, 251 Drug Interactions, 178, 231 Drug Tolerance, 231, 287 Duct, 50, 209, 231, 236, 278, 284 Duodenal Ulcer, 122, 231, 267 Duodenum, 215, 222, 231, 260, 264, 283 Dwarfism, 26, 231 Dysgenesis, 37, 231 Dyskinesia, 212, 231 Dysmenorrhea, 52, 231 Dyspepsia, 75, 231 Dysplasia, 28, 37, 187, 231 Dystonia, 212, 231 Dystrophy, 187, 231
298
Prolactin
E Eating Disorders, 56, 231 Eclampsia, 136, 232, 270 Ectopic, 18, 86, 232 Edema, 229, 232, 249, 250, 270 Effector, 205, 224, 232, 250 Efficacy, 5, 30, 56, 63, 89, 124, 218, 232 Ejaculation, 232, 279 Electrolysis, 6, 210, 232 Electrolyte, 145, 207, 227, 228, 232, 256, 269, 281 Electroplating, 219, 232 Embolus, 232, 247, 248 Embryo, 15, 16, 19, 27, 205, 208, 216, 219, 232, 236, 246, 255, 257, 270, 282, 289, 292 Embryo Transfer, 232, 270 Empirical, 153, 232 Emulsion, 214, 232, 237 Endocrine Glands, 232, 264, 265 Endocrine System, 18, 160, 175, 232, 259 Endocytosis, 219, 232 Endometrial, 19, 37, 40, 53, 85, 98, 233, 263 Endometriosis, 13, 53, 95, 105, 233 Endometrium, 13, 40, 106, 117, 228, 233, 254, 256, 289 Endopeptidases, 233, 272 Endorphin, 215, 233, 238 Endostatin, 156, 233 Endothelial cell, 115, 216, 233, 237, 286 Endothelium, 233, 260 Endothelium-derived, 233, 260 Endotoxic, 233, 251 Endotoxin, 124, 233, 289 End-stage renal, 4, 222, 233, 268 Energy balance, 233, 250, 266 Enhancer, 24, 26, 28, 62, 64, 65, 70, 96, 142, 233, 277 Enkephalin, 215, 233, 271 Enterohepatic, 44, 233 Enteropeptidase, 233, 289 Environmental Exposure, 120, 233, 262 Environmental Health, 182, 184, 233 Enzymatic, 50, 137, 141, 154, 208, 218, 224, 234, 243, 264, 277 Eosinophil, 16, 234 Eosinophilic, 234 Ependyma, 212, 234, 286 Epidemiologic Studies, 11, 234 Epidemiological, 29, 234 Epidermal, 71, 125, 139, 234, 254 Epidermal Growth Factor, 71, 125, 139, 234
Epidermis, 229, 234 Epidural, 115, 234, 249 Epinephrine, 6, 206, 230, 234, 260, 261, 289 Epithalamus, 229, 234 Epithelial Cells, 12, 13, 15, 21, 29, 39, 41, 50, 51, 53, 68, 71, 116, 130, 155, 234, 242, 250 Epithelium, 11, 38, 39, 40, 74, 166, 214, 221, 233, 234 Erectile, 4, 5, 114, 171, 234, 265 Erection, 5, 234 Ergot, 217, 234 Erythroblasts, 38, 235 Erythrocyte Volume, 216, 235 Erythrocytes, 209, 216, 235, 276, 277, 279 Erythroid Progenitor Cells, 235 Erythropoiesis, 111, 235 Erythropoietin, 4, 38, 74, 137, 154, 235 Essential Tremor, 187, 235 Estradiol, 13, 18, 20, 22, 27, 31, 37, 49, 58, 60, 61, 62, 99, 119, 126, 235 Estriol, 60, 235 Estrogen receptor, 9, 27, 31, 37, 50, 67, 69, 155, 235 Estrone, 31, 58, 235 Ethanol, 8, 9, 235 Ethyl Methanesulfonate, 68, 235 Ethylene Glycol, 46, 235 Eukaryotic Cells, 151, 235, 246, 261, 262 Excipients, 134, 235 Excitability, 161, 236 Excitation, 221, 236, 237, 260 Exhaustion, 210, 236 Exocrine, 221, 236, 263 Exogenous, 10, 32, 49, 50, 58, 62, 140, 223, 231, 233, 236, 272 Exon, 98, 156, 208, 236 External-beam radiation, 236, 249, 274, 292 Extracellular, 16, 22, 64, 65, 81, 138, 148, 156, 225, 232, 236, 237, 247, 281, 285 Extracellular Matrix, 16, 22, 64, 65, 156, 225, 236, 237, 247 Extracellular Space, 236 Extrapyramidal, 64, 207, 212, 230, 236 Eye Infections, 206, 236 F Fallopian tube, 236, 276 Family Planning, 183, 236 Fatigue, 95, 222, 236, 242 Fenfluramine, 56, 110, 111, 113, 229, 236 Fertilization in Vitro, 236, 270
Index 299
Fetal Death, 22, 236 Fetal Development, 21, 63, 103, 236 Fetal Membranes, 21, 236 Fetal Movement, 21, 236 Fetus, 27, 37, 103, 205, 235, 236, 237, 267, 270, 282, 283, 289, 290 Fibrin, 216, 237, 268, 286, 287 Fibroblast Growth Factor, 28, 40, 65, 237 Fibroblasts, 15, 62, 237, 248 Fibroid, 237, 250 Fibrosis, 187, 237, 278 Finasteride, 6, 237 Fixation, 237, 279 Flow Cytometry, 14, 237 Fluorescence, 70, 237, 238 Fluorescence Polarization, 70, 237 Fluorescent Dyes, 237 Fluoxetine, 46, 112, 238 Flutamide, 6, 31, 238 Fold, 45, 238 Follicular Fluid, 113, 238 Follicular Phase, 52, 238 Forearm, 4, 216, 238 Free Radicals, 211, 230, 238 Functional magnetic resonance imaging, 57, 238 Fungi, 211, 225, 236, 238, 256, 292 Fungus, 23, 234, 238 G Galanin, 67, 161, 238 Gallbladder, 205, 215, 221, 238 Gamma-Endorphin, 238 Ganglia, 8, 205, 214, 238, 259, 265 Gas, 208, 218, 238, 244, 258, 260, 275, 276, 290 Gastric, 122, 222, 231, 234, 238, 239, 243, 265, 267, 275 Gastrin, 67, 222, 238, 239, 243 Gastrin-Releasing Peptide, 67, 239 Gastrointestinal tract, 235, 237, 239, 250, 280, 281, 289 Gene Deletion, 22, 239 Gene Therapy, 109, 206, 239 Genetic Code, 239, 261 Genetic Engineering, 216, 223, 239 Genetic Markers, 146, 164, 165, 239 Genetics, 23, 24, 28, 38, 98, 101, 110, 113, 122, 125, 156, 206, 225, 239 Genital, 34, 222, 239 Genotype, 87, 158, 239, 266 Germ Cells, 239, 262, 263, 281, 285, 292
Gestation, 15, 159, 160, 239, 265, 267, 270, 282 Gestation period, 160, 239 Gestational, 4, 239 Gestational Age, 4, 239 Gigantism, 145, 239 Glioma, 88, 240 Glucocorticoid, 6, 7, 28, 56, 65, 71, 72, 229, 240, 256 Glucose, 4, 135, 140, 149, 187, 216, 220, 229, 240, 242, 247, 278 Glucose Intolerance, 140, 229, 240 Glucose tolerance, 240 Glucose Tolerance Test, 240 Glucosidases, 25, 240 Glucuronic Acid, 240, 242 Glutamate, 161, 240 Glutamic Acid, 240, 260 Gluten, 219, 240 Glycine, 208, 215, 240, 260, 280 Glycoprotein, 25, 53, 63, 135, 157, 235, 240, 241, 286, 289 Glycosidic, 210, 240 Glycosylation, 24, 130, 148, 240 Gonad, 240, 241 Gonadal, 7, 35, 45, 52, 88, 117, 241, 283 Gonadotropic, 145, 241 Gonadotropin, 4, 7, 31, 68, 80, 88, 113, 123, 131, 145, 221, 241 Governing Board, 241, 270 Gp120, 241, 265 Graft, 43, 162, 241, 243 Grafting, 241, 246 Graft-versus-host disease, 43, 241 Granule, 161, 241, 278 Granulocytes, 60, 241, 251, 280, 291 Granulosa Cell Tumor, 95, 241 Growth, 6, 8, 10, 11, 19, 20, 21, 22, 24, 25, 27, 28, 32, 35, 37, 39, 40, 41, 43, 46, 47, 49, 50, 51, 54, 55, 59, 60, 62, 65, 66, 67, 68, 69, 70, 71, 73, 74, 75, 77, 79, 85, 91, 92, 94, 96, 99, 101, 104, 105, 106, 108, 109, 110, 112, 113, 117, 118, 119, 122, 123, 124, 125, 130, 137, 138, 139, 140, 146, 147, 148, 151, 152, 155, 156, 157, 158, 159, 160, 161, 162, 163, 165, 166, 169, 170, 187, 206, 209, 210, 211, 212, 216, 219, 220, 229, 231, 233, 234, 236, 237, 241, 242, 243, 247, 248, 250, 253, 259, 262, 267, 279, 282, 286, 289 Growth factors, 28, 50, 60, 241 Guanylate Cyclase, 241, 260
300
Prolactin
H Haemorrhage, 205, 241 Half-Life, 137, 241 Hallucinogens, 241, 273 Haptens, 207, 241 Headache, 241, 267 Heart failure, 95, 242, 251 Hematocrit, 4, 216, 242 Hematopoiesis, 88, 135, 242 Hematopoietic tissue, 38, 216, 242 Heme, 115, 227, 242, 263 Hemiparesis, 217, 242 Hemodialysis, 4, 229, 242, 250 Hemoglobin, 4, 5, 209, 216, 235, 242, 250 Hemoglobinuria, 187, 242 Hemorrhage, 31, 101, 141, 241, 242, 267, 291 Hemorrhaging, 27, 242 Hemostasis, 242, 248, 280 Heparin, 16, 137, 154, 242 Hepatic, 15, 32, 44, 72, 144, 165, 228, 240, 242, 269 Hepatitis, 42, 242 Hepatocyte, 39, 221, 242 Hepatocyte Growth Factor, 39, 242 Hereditary, 242, 257, 259, 277 Heredity, 239, 243 Heterodimers, 243, 247 Heterogeneity, 102, 207, 243 Hiccup, 231, 243 Hippocampus, 243, 274 Hirsutism, 6, 227, 243, 244 Histamine, 209, 212, 222, 243, 275 Histidine, 123, 243 Histology, 110, 243 Homeobox, 34, 243 Homeostasis, 21, 38, 217, 243 Homologous, 73, 166, 207, 216, 239, 243, 279, 284 Hookworms, 48, 243 Hormone therapy, 58, 159, 206, 243 Host, 24, 25, 43, 48, 148, 150, 151, 156, 243, 245, 277, 278, 291 Human Development, 35, 182, 243 Human growth hormone, 69, 152, 160, 162, 243, 281 Humoral, 243, 286 Hybrid, 23, 151, 223, 243, 244 Hybridization, 21, 35, 243 Hybridomas, 244, 248 Hydatidiform Mole, 221, 244
Hydrogen, 153, 162, 163, 214, 218, 229, 244, 251, 256, 260, 261, 263, 273, 284 Hydrogen Peroxide, 244, 251, 284 Hydrolysis, 205, 212, 244, 249, 265, 266, 273, 289 Hydrophilic, 137, 154, 157, 244 Hydrophobic, 35, 153, 244 Hydroxyproline, 208, 224, 244 Hypercholesterolemia, 140, 244 Hyperglycemia, 140, 143, 149, 244 Hyperlipidemia, 135, 140, 143, 244 Hyperplasia, 6, 12, 49, 84, 101, 108, 143, 244 Hypersecretion, 143, 244, 279 Hypersensitivity, 44, 207, 234, 244, 277, 279 Hypertension, 5, 135, 136, 244, 249, 251, 258, 270 Hypertrichosis, 243, 244 Hypertrophy, 226, 244, 288 Hypoglycemia, 4, 95, 244 Hypophyseal, 244, 254 Hypophysis, 245, 279 Hypopituitarism, 30, 245 Hypotension, 212, 245, 260 Hypothalamic, 4, 7, 11, 31, 36, 41, 42, 56, 67, 74, 95, 117, 124, 126, 130, 137, 143, 154, 245, 282 Hypothyroidism, 80, 141, 143, 245 Hypoxia, 217, 220, 228, 245, 285 Hysterectomy, 53, 245 I Id, 127, 186, 192, 198, 200, 245 Idiopathic, 30, 115, 245 Ileal, 44, 245 Ileum, 245, 260 Illusion, 245, 291 Immune function, 31, 33, 142, 245 Immune response, 7, 31, 142, 166, 206, 211, 214, 227, 241, 245, 246, 279, 283, 291 Immune Sera, 245 Immunity, 34, 142, 245, 246, 248, 288 Immunization, 45, 245, 279 Immunocompromised, 46, 245 Immunodeficiency, 85, 114, 186, 246 Immunofluorescence, 15, 23, 246 Immunogenic, 152, 246, 251 Immunoglobulin, 34, 72, 108, 210, 246, 257 Immunologic, 33, 221, 239, 245, 246, 275 Immunology, 42, 79, 106, 114, 206, 207, 238, 246 Immunomodulator, 155, 246
Index 301
Immunosuppressant, 32, 246 Immunosuppressive, 14, 32, 240, 246, 285 Immunosuppressive therapy, 14, 32, 246 Impairment, 25, 46, 213, 220, 221, 228, 231, 236, 246, 255, 273 Implant radiation, 246, 248, 249, 274, 292 Implantation, 13, 15, 19, 27, 37, 117, 225, 246, 263 Impotence, 5, 77, 114, 171, 202, 234, 246, 265, 292 In situ, 21, 28, 61, 164, 246 In Situ Hybridization, 40, 61, 246 Incision, 246, 249 Incontinence, 246, 279 Incubated, 152, 246 Incubation, 151, 246 Incubation period, 151, 246 Indicative, 146, 159, 164, 169, 246, 264, 290 Induction, 13, 16, 18, 27, 53, 62, 68, 69, 73, 91, 97, 122, 155, 209, 211, 246, 250, 271 Infarction, 10, 217, 220, 245, 247 Infertility, 4, 16, 17, 27, 37, 40, 191, 217, 247 Infiltration, 50, 247 Infusion, 105, 126, 247 Ingestion, 218, 240, 247, 268, 285 Initiation, 18, 37, 55, 136, 155, 166, 247, 271, 288 Initiator, 215, 247, 248 Inlay, 247, 277 Inotropic, 230, 247 Insight, 8, 16, 23, 47, 51, 86, 247 Insulator, 247, 257 Insulin-dependent diabetes mellitus, 4, 247 Insulin-like, 10, 11, 19, 59, 60, 117, 139, 160, 247 Integrins, 22, 247 Interferon, 68, 71, 84, 98, 115, 120, 137, 154, 248 Interferon-alpha, 248 Interleukin-1, 21, 84, 89, 124, 248 Interleukin-11, 21, 89, 248 Interleukin-12, 84, 248 Interleukin-2, 84, 120, 248 Interleukin-6, 29, 51, 248 Internal Medicine, 60, 100, 125, 232, 248 Internal radiation, 248, 249, 274, 292 Interphase, 220, 248, 261 Interstitial, 217, 236, 248, 249, 292 Intestinal, 32, 219, 221, 233, 240, 248, 250, 253, 278, 290, 292
Intestinal Mucosa, 219, 221, 248, 290, 292 Intestine, 215, 233, 248, 275, 281 Intoxication, 88, 141, 228, 248, 291 Intracellular, 9, 22, 23, 41, 50, 59, 88, 91, 125, 139, 156, 247, 248, 254, 260, 269, 275, 280 Intracranial Embolism, 220, 248 Intracranial Embolism and Thrombosis, 220, 248 Intracranial Hemorrhages, 249, 267, 285 Intracranial Hypertension, 241, 249, 267 Intramuscular, 159, 249, 264 Intravenous, 102, 247, 249, 264 Intrinsic, 207, 214, 249 Invasive, 53, 244, 245, 249, 253 Involuntary, 214, 221, 226, 235, 249, 258, 282 Ion Transport, 44, 249, 256 Ionization, 249 Ionizing, 157, 208, 233, 249, 253, 275 Ions, 214, 230, 232, 244, 249 Irradiation, 102, 143, 249, 292 Ischemia, 213, 217, 249, 267 Isocyanates, 162, 249 J Joint, 213, 249, 269, 284 K Kb, 182, 249 Keloid, 162, 222, 249 Keratinocyte growth factor, 40, 250 Ketamine, 83, 250 Ketoconazole, 6, 250 Kidney Cortex, 250, 255 Kidney Disease, 125, 182, 187, 250 Kidney Failure, 233, 250 Killer Cells, 250 Kinetic, 249, 250 L Labile, 224, 250 Lacrimal, 50, 250 Lacrimal gland, 50, 250 Larva, 250, 255 Latency, 61, 250 Latent, 49, 72, 99, 250, 270 Least-Squares Analysis, 250, 276 Leiomyoma, 54, 237, 250 Leptin, 57, 59, 62, 250 Lethargy, 245, 250 Leucine, 215, 250, 265 Leucocyte, 234, 251 Leukemia, 38, 65, 136, 186, 239, 251
302
Prolactin
Leukocytes, 84, 214, 216, 221, 241, 248, 251, 260, 289 Levodopa, 134, 230, 251 Libido, 171, 209, 251 Library Services, 198, 251 Life cycle, 230, 238, 250, 251, 261, 274 Ligament, 236, 251, 272 Ligands, 72, 138, 152, 160, 161, 247, 251 Likelihood Functions, 251, 276 Linear Models, 251, 276 Linkage, 24, 210, 239, 251 Lipid, 62, 134, 135, 149, 160, 219, 221, 247, 251, 257, 263 Lipid A, 135, 160, 251 Lipid Peroxidation, 251, 263 Lipomatosis, 115, 251 Lipophilic, 137, 154, 251 Lipopolysaccharide, 24, 251 Lisinopril, 11, 251 Lithium, 89, 211, 251 Litter, 146, 164, 251, 252 Litter Size, 146, 164, 252 Lobe, 145, 220, 243, 252, 271 Localization, 15, 23, 40, 59, 60, 70, 107, 110, 131, 252 Localized, 59, 217, 237, 243, 244, 247, 251, 252, 267, 289 Logistic Models, 252, 276 Loop, 49, 50, 55, 147, 252 Luciferase, 44, 46, 252 Lumen, 50, 252 Lupus, 78, 85, 87, 88, 89, 90, 115, 175, 252, 284 Luteal Phase, 12, 52, 113, 252, 256 Lutein Cells, 252, 271 Lymph, 222, 233, 252, 260, 283 Lymph node, 252, 260 Lymphatic, 233, 247, 252, 255, 281, 282, 286 Lymphatic system, 252, 281, 282, 286 Lymphocyte, 73, 211, 250, 252, 254 Lymphocytic, 50, 115, 252 Lymphoid, 24, 135, 210, 251, 252, 253 Lymphoma, 120, 186, 253 Lysine, 253, 289 M Macrophage, 248, 253 Macula, 253 Macula Lutea, 253 Macular Degeneration, 162, 253 Magnetic Resonance Imaging, 57, 253 Maintenance therapy, 64, 253
Malabsorption, 187, 219, 253 Malformation, 34, 253 Malignancy, 25, 155, 205, 253 Malignant fibrous histiocytoma, 102, 253 Malignant tumor, 157, 221, 253, 257, 277 Malnutrition, 213, 253, 257 Mammogram, 12, 253 Mandible, 208, 253, 276 Mania, 253 Manic, 104, 211, 251, 253, 273 Manifest, 56, 253 Man-made, 219, 253 Mannans, 238, 253 Mastication, 253, 288 Mastitis, 4, 253 Maternal Behavior, 18, 61, 65, 253 Medial, 61, 254, 262, 282 Median Eminence, 41, 254 Mediate, 26, 28, 52, 54, 63, 230, 250, 254, 275 Mediator, 41, 221, 230, 248, 254, 280 MEDLINE, 183, 185, 187, 254 Medroxyprogesterone, 85, 254 Medroxyprogesterone Acetate, 85, 254 Megakaryocytes, 102, 217, 248, 254, 286 Melanin, 254, 266, 289 Melanocytes, 254 Melanoma, 186, 254 Melanosis, 205, 254 Memantine, 83, 254 Membrane Proteins, 219, 254 Memory, 26, 57, 210, 228, 254 Meningeal, 254, 267 Meninges, 220, 254 Meningitis, 254, 267 Menopause, 117, 254, 269, 270 Menstrual Cycle, 238, 252, 254, 271 Menstruation, 4, 208, 228, 231, 238, 252, 254, 255, 262 Mental Disorders, 255, 273 Mental Health, iv, 7, 182, 184, 255, 274 Mentors, 31, 255 Mercury, 237, 255 Mesenchymal, 106, 213, 234, 244, 255 Mesoderm, 255, 289, 292 Mesolimbic, 17, 212, 255 Messenger RNA, 124, 255, 278 Metabolic disorder, 135, 140, 255 Metabolite, 235, 255, 271 Metallothionein, 30, 255 Metamorphosis, 67, 71, 140, 255, 261 Metastasis, 23, 25, 111, 255
Index 303
Metastasize, 28, 255, 267, 279 Metastatic, 28, 51, 55, 75, 87, 89, 245, 255, 279 Methionine, 215, 255, 271 Metoclopramide, 94, 111, 255 MI, 104, 203, 255 Microbe, 255, 287 Microbiology, 24, 42, 205, 214, 256 Microorganism, 151, 223, 256, 264, 291 Microscopy, 13, 15, 23, 60, 214, 256, 261 Mifepristone, 117, 256 Migration, 156, 256 Milk Ejection, 9, 256 Mineralocorticoids, 206, 227, 256 Miscarriage, 174, 256 Mitosis, 212, 220, 256, 282 Mitotic, 220, 230, 256, 257 Mitotic Spindle Apparatus, 220, 256 Mobility, 45, 117, 256 Mobilization, 31, 256 Modeling, 24, 256, 272 Modification, 69, 149, 170, 208, 239, 256, 274 Monitor, 30, 50, 257, 261 Monoamine, 209, 211, 229, 257 Monoclonal, 29, 244, 249, 257, 274, 292 Monocyte, 87, 257 Mononuclear, 71, 84, 257, 289 Monophosphate, 122, 257 Morphine, 54, 257, 258, 262 Morphogenesis, 28, 37, 39, 257 Morphological, 34, 232, 238, 254, 257 Morphology, 34, 257 Morula, 216, 257 Motility, 18, 22, 257, 267, 280 Motion Sickness, 257, 258, 279 Motor Activity, 257 Movement Disorders, 211, 257, 285 Mucins, 257, 278 Mucosa, 252, 257, 271, 283 Multiple Myeloma, 90, 91, 257 Multiple sclerosis, 107, 142, 257 Muscle Fibers, 257 Muscular Atrophy, 187, 257 Muscular Dystrophies, 231, 257 Music Therapy, 6, 258 Mutagen, 235, 258 Mutagenic, 35, 258 Mydriatic, 258, 279, 292 Myelin, 257, 258 Myeloma, 106, 153, 258
Myocardial infarction, 10, 212, 226, 255, 258 Myocardium, 255, 258 Myometrium, 53, 258 Myotonic Dystrophy, 187, 258 N Naive, 71, 258 Naloxone, 73, 215, 258 Narcotic, 257, 258 Natriuresis, 258 Natriuretic Hormone, 80, 258 Natural killer cells, 106, 125, 248, 258 Nausea, 211, 212, 231, 258, 289 NCI, 1, 181, 222, 258 Need, 3, 8, 44, 51, 57, 140, 143, 146, 165, 171, 175, 193, 222, 258, 287 Neonatal, 37, 61, 70, 258 Neoplasia, 186, 259 Neoplasm, 259, 278 Neoplastic, 139, 209, 244, 253, 259 Neopterin, 34, 259 Nephropathy, 250, 259 Nerve, 70, 143, 206, 209, 213, 214, 228, 254, 257, 259, 260, 262, 267, 269, 277, 278, 283, 288 Nervous System, 56, 160, 187, 205, 206, 209, 220, 221, 223, 229, 238, 240, 241, 251, 254, 257, 259, 260, 265, 267, 278, 280, 284 Networks, 22, 259 Neural, 18, 36, 61, 143, 144, 164, 165, 206, 243, 259, 271 Neurobehavioral Manifestations, 217, 229, 259 Neurodegenerative Diseases, 164, 214, 259 Neuroendocrine, 6, 7, 10, 22, 24, 33, 41, 43, 45, 47, 54, 57, 59, 97, 142, 160, 161, 166, 259 Neuroendocrinology, 33, 82, 119, 124, 259 Neurogenic, 143, 259 Neuroleptic, 207, 211, 223, 259 Neurologic, 210, 217, 259 Neuromuscular, 205, 259, 285 Neuronal, 68, 108, 259 Neurons, 36, 41, 46, 61, 164, 223, 228, 230, 238, 251, 259, 260, 274, 284 Neuropathy, 5, 259 Neuropeptide, 239, 259 Neurosecretory Systems, 232, 260 Neurosis, 260, 261, 266 Neurotensin, 74, 260 Neurotoxic, 57, 61, 260
304
Prolactin
Neurotoxicity, 59, 260 Neurotoxin, 58, 61, 260 Neurotransmitter, 56, 61, 205, 208, 217, 219, 230, 238, 240, 243, 260, 261, 280, 281, 283, 290 Neutrons, 208, 249, 260, 274 Neutrophils, 241, 251, 260 Niacin, 260, 289 Nicotine, 260, 262 Nipples, 256, 260 Nitric Oxide, 73, 125, 260 Nitrogen, 10, 207, 209, 237, 260, 289 Node-negative, 104, 260 Nonverbal Communication, 261, 273 Norepinephrine, 6, 126, 206, 230, 260, 261 Nuclear, 13, 23, 28, 47, 50, 59, 60, 74, 106, 214, 225, 235, 253, 261, 285 Nuclear Matrix, 60, 261 Nuclear Pore, 261 Nucleates, 220, 261 Nuclei, 71, 72, 208, 225, 234, 239, 253, 256, 260, 261, 268, 273 Nucleic acid, 136, 146, 148, 156, 160, 239, 244, 246, 260, 261, 274 Nucleic Acid Hybridization, 244, 261 Nucleolus, 261, 278 Nucleus Accumbens, 17, 261 Nulliparous, 41, 65, 261 Nymph, 255, 261 O Obsessional, 56, 261 Ocular, 261, 267 Ointments, 231, 261 Oleandomycin, 137, 154, 262 Oligohydramnios, 21, 262 Oligomenorrhea, 36, 262, 268 Oncogene, 29, 109, 186, 242, 262 Oncogenic, 38, 48, 248, 262 Oocytes, 87, 137, 262 Opacity, 228, 262 Operon, 262, 271, 276 Ophthalmology, 50, 237, 262 Opiate, 42, 54, 215, 233, 257, 258, 262 Opioid Peptides, 262 Opium, 257, 262 Opportunistic Infections, 43, 262 Optic Chiasm, 245, 262, 267, 270 Optic Disk, 229, 253, 262 Organ Culture, 37, 43, 159, 262, 287 Organelles, 220, 228, 254, 262, 277 Orgasm, 77, 82, 103, 232, 262 Orthostatic, 212, 263
Osteoclasts, 218, 263 Osteoporosis, 146, 217, 263, 275 Ovarian Follicle, 226, 238, 263 Ovariectomy, 31, 45, 263 Ovaries, 213, 263, 268, 276, 280, 285 Ovary, 6, 34, 90, 95, 226, 235, 240, 263, 283 Overall survival, 104, 263 Ovulation, 91, 145, 210, 238, 252, 263 Ovum, 226, 228, 238, 239, 251, 257, 263, 271, 289, 291, 292 Ovum Implantation, 263, 289 Oxidation, 211, 227, 251, 263 Oxidative Stress, 8, 263 Oxygenase, 115, 263 Oxytocin, 21, 33, 34, 256, 263 P Paediatric, 78, 263 Pain Threshold, 161, 263 Palliative, 227, 263, 286 Palpation, 236, 263 Palsies, 263, 267 Pancreas, 205, 216, 222, 247, 263, 264, 281, 289 Pancreatic, 53, 186, 221, 222, 264 Pancreatic cancer, 186, 264 Pancreatic Juice, 222, 264 Panic, 105, 264 Papain, 137, 154, 264 Paralysis, 242, 264, 285 Parasite, 49, 82, 264, 278 Parasitic, 48, 243, 264 Parathyroid, 4, 137, 154, 264, 285 Parathyroid Glands, 264 Parathyroid hormone, 4, 137, 154, 264 Parathyroidectomy, 3, 264 Parenteral, 137, 154, 264 Paresthesia, 264, 285 Parkinsonism, 212, 251, 264 Paroxysmal, 187, 264 Partial remission, 264, 276 Parturition, 264, 271 Pathogen, 246, 264 Pathogenesis, 7, 10, 12, 17, 39, 69, 147, 264 Pathologic, 212, 226, 244, 264, 276, 290 Pathologic Processes, 212, 264 Pathologies, 25, 42, 149, 265 Pathophysiology, 13, 25, 46, 56, 265 Pediatric Endocrinologist, 31, 265 Pedophilia, 100, 265 Pelvic, 53, 233, 265, 272 Pelvis, 205, 263, 265, 290 Penicillin, 210, 265
Index 305
Penile Prosthesis, 5, 265 Penis, 232, 265, 276 Pepsin, 222, 265 Pepsin A, 222, 265 Peptide Fragments, 42, 265 Peptide T, 141, 161, 265 Perfusion, 245, 265, 287 Pericardium, 265, 284 Perinatal, 21, 34, 44, 61, 265 Peripheral Nervous System, 259, 260, 263, 265, 281, 283, 290 Peripheral stem cells, 241, 265 Pharmaceutical Solutions, 231, 266 Pharmacokinetic, 32, 266 Pharmacologic, 209, 241, 266, 287 Phenotype, 13, 25, 39, 44, 70, 90, 224, 239, 266 Phenyl, 162, 163, 266 Phenylalanine, 265, 266, 289 Phobia, 76, 266 Phobic Disorders, 266 Phospholipases, 266, 280 Phospholipids, 236, 266 Phosphorus, 4, 218, 264, 266 Phosphorylated, 23, 59, 76, 163, 223, 266 Phosphorylates, 103, 266 Phosphorylation, 12, 22, 29, 46, 49, 59, 63, 71, 106, 112, 266 Photodynamic therapy, 266 Photoperiod, 126, 130, 266 Photosensitization, 157, 266 Photosensitizer, 157, 266 Physical Examination, 5, 6, 239, 267 Physiologic, 52, 63, 140, 207, 230, 236, 241, 254, 255, 267, 275, 276 Physiology, 4, 9, 13, 18, 21, 25, 42, 46, 47, 50, 91, 92, 95, 101, 124, 125, 126, 130, 136, 166, 170, 171, 205, 232, 267 Pilot study, 18, 29, 267 Pineal Body, 234, 267 Pineal gland, 126, 221, 267 Pirenzepine, 134, 135, 267 Pituitary Apoplexy, 101, 245, 267 Pituitary Gland, 8, 20, 26, 30, 47, 123, 145, 159, 160, 175, 226, 237, 245, 267, 271 Pituitary Hormones, 34, 130, 267 Pituitary Neoplasms, 245, 267 Placenta, 21, 27, 63, 69, 92, 213, 235, 267, 271, 289 Plants, 207, 214, 215, 217, 218, 221, 223, 240, 257, 261, 267, 269, 278, 288 Plasma cells, 210, 257, 258, 267
Plasma protein, 238, 268 Plasmid, 159, 268 Plasmin, 268, 287, 290 Plasminogen, 268, 287, 290 Plasticity, 18, 268 Platelet Activation, 136, 268, 280 Platelet Aggregation, 209, 260, 268 Platelet Count, 136, 268 Platelets, 136, 260, 268, 286 Platinum, 252, 268 Pleomorphic, 261, 268 Pneumonia, 226, 268 Point Mutation, 30, 268 Poisoning, 218, 228, 234, 248, 255, 258, 262, 268, 279 Polycystic, 6, 81, 187, 268 Polycystic Ovary Syndrome, 6, 81, 268 Polyethylene, 85, 98, 100, 139, 268 Polyhydramnios, 21, 269 Polymerase, 212, 269, 271, 276 Polymorphic, 54, 221, 269 Polymorphism, 10, 82, 110, 113, 158, 269 Polymyalgia Rheumatica, 96, 269 Polysaccharide, 207, 211, 220, 269 Polyunsaturated fat, 40, 269 Portal System, 254, 269 Post partum, 14, 269 Posterior, 209, 213, 220, 234, 263, 267, 269, 278, 282 Postmenopausal, 10, 11, 32, 58, 88, 174, 263, 269, 275 Postnatal, 44, 269, 282 Postoperative, 4, 104, 269 Postsynaptic, 161, 269, 280 Post-synaptic, 56, 269 Post-translational, 25, 269 Post-traumatic, 56, 217, 257, 269 Post-traumatic stress disorder, 56, 269 Potassium, 207, 256, 258, 269 Potentiate, 248, 270 Potentiating, 215, 270 Potentiation, 270, 280 Practice Guidelines, 184, 270 Precancerous, 221, 270 Precipitation, 85, 98, 100, 270 Preclinical, 43, 270 Predisposition, 56, 270, 285 Preeclampsia, 118, 270 Pre-Eclampsia, 135, 136, 270 Pre-eclamptic, 232, 270 Pregnancy Complications, 4, 270 Pregnancy Outcome, 4, 270
306
Prolactin
Pregnancy Tests, 239, 270 Premedication, 270, 279 Premenopausal, 11, 270 Prenatal, 34, 232, 270 Preoperative, 4, 76, 270 Preoptic Area, 61, 270 Presynaptic, 260, 271 Prevalence, 4, 5, 19, 111, 271 Prodrug, 271 Proestrus, 31, 271 Progeny, 20, 159, 225, 271 Progesterone, 13, 16, 18, 19, 29, 39, 40, 52, 58, 60, 61, 62, 117, 126, 155, 256, 271, 283 Prognostic factor, 120, 271 Progression, 7, 23, 28, 49, 51, 53, 113, 210, 271 Progressive, 53, 219, 222, 228, 231, 241, 257, 258, 259, 268, 271 Projection, 228, 261, 271, 274, 276 Proliferative Retinopathy, 162, 271 Promoter, 19, 30, 45, 48, 51, 62, 65, 67, 68, 70, 71, 78, 83, 90, 92, 98, 104, 106, 113, 122, 158, 160, 271 Promotor, 271, 277 Pro-Opiomelanocortin, 238, 262, 271 Prophase, 216, 262, 271, 284 Prophylaxis, 11, 145, 212, 270, 271 Proportional, 3, 60, 271 Prosencephalon, 229, 271 Prospective study, 29, 271 Prostaglandins, 256, 272 Prostaglandins F, 256, 272 Prostate, 27, 46, 49, 55, 72, 76, 87, 101, 116, 147, 155, 159, 166, 170, 186, 216, 272, 276, 289 Prostate gland, 147, 272 Prostatic Hyperplasia, 49, 237, 272 Protease, 93, 159, 272, 287 Protease Inhibitors, 93, 272 Protein Binding, 272, 287 Protein C, 48, 52, 64, 141, 151, 155, 208, 223, 272, 289 Protein Conformation, 208, 272 Protein Engineering, 152, 272 Protein Isoforms, 208, 272 Protein S, 52, 125, 136, 151, 187, 188, 212, 216, 225, 239, 243, 272, 278 Proteinuria, 257, 270, 273 Proteolytic, 157, 224, 233, 264, 268, 273, 287, 290 Protocol, 4, 31, 273 Protons, 208, 244, 249, 273, 274
Protozoa, 225, 256, 273 Proximal, 48, 68, 78, 230, 250, 269, 271, 273 Psychiatric, 42, 56, 161, 255, 273, 281 Psychiatry, 55, 57, 58, 76, 78, 79, 83, 88, 89, 90, 97, 100, 103, 105, 106, 110, 112, 122, 237, 273 Psychic, 251, 255, 260, 273, 279 Psychoactive, 58, 273, 291 Psychogenic, 5, 143, 273 Psychomotor, 83, 228, 259, 273 Psychopharmacology, 18, 79, 83, 84, 87, 89, 107, 109, 117, 119, 273 Psychosis, 211, 212, 239, 273 Psychotherapy, 18, 273 Psychotomimetic, 209, 229, 273 Psychotropic, 110, 143, 273 Psychotropic Drugs, 143, 273 Puberty, 52, 54, 123, 146, 165, 274 Public Health, 10, 37, 184, 274 Public Policy, 183, 274 Pulmonary, 216, 226, 234, 250, 274, 276, 290 Pulmonary Artery, 216, 274, 290 Pulmonary hypertension, 226, 274 Pulse, 147, 257, 274 Pupa, 255, 274 Purines, 274, 280 Pyramidal Cells, 161, 274 Pyramidal Tracts, 236, 274 Pyrimidines, 274, 280 Q Quality of Life, 17, 274 Quaternary, 272, 274, 278 R Race, 230, 256, 274, 281 Racemic, 230, 274, 281 Radiation, 36, 157, 172, 203, 206, 214, 233, 236, 237, 238, 245, 248, 249, 253, 274, 275, 292 Radiation therapy, 203, 206, 236, 248, 249, 274, 292 Radioactive, 214, 241, 244, 246, 248, 249, 253, 261, 262, 274, 275, 289, 292 Radiography, 239, 275 Radiolabeled, 249, 274, 275, 292 Radiotherapy, 217, 249, 274, 275, 292 Raloxifene, 31, 88, 275, 279 Randomized, 57, 83, 232, 275 Ranitidine, 267, 275 Rape, 269, 275 Rarefaction, 213, 275 Reactivation, 48, 275
Index 307
Reactive Oxygen Species, 27, 275 Reagent, 227, 252, 275 Receptivity, 13, 15, 275 Receptors, Serotonin, 275, 280 Recombinant, 25, 66, 70, 103, 125, 138, 139, 141, 146, 148, 150, 151, 154, 163, 275 Recombinant Proteins, 146, 150, 151, 275 Recombination, 225, 239, 275 Reconstitution, 43, 73, 275 Rectum, 86, 212, 224, 238, 246, 272, 275 Recurrence, 44, 221, 222, 267, 276 Red blood cells, 235, 263, 276, 278 Red Nucleus, 213, 276 Reductase, 22, 213, 237, 276 Refer, 1, 217, 224, 230, 237, 238, 252, 253, 258, 259, 260, 273, 276, 288 Refraction, 210, 276, 282 Regeneration, 237, 275, 276 Regimen, 54, 59, 149, 232, 276 Regression Analysis, 61, 276 Reliability, 64, 111, 276 Remission, 115, 253, 276 Repressor, 26, 60, 153, 262, 276 Reproduction Techniques, 270, 276 Reproductive system, 34, 160, 272, 276 Resorption, 21, 36, 217, 263, 276 Respiration, 218, 221, 236, 257, 276 Respiratory System, 207, 276, 290 Response Elements, 28, 276 Restless legs, 17, 277 Restoration, 79, 275, 277, 292 Reticulocytes, 235, 277 Retina, 229, 253, 262, 271, 277, 290 Retinal, 229, 262, 277 Retinoblastoma, 186, 277 Retroperitoneal, 206, 277 Retrospective, 76, 277 Retrovirus, 24, 277 Reversion, 68, 277 Rhabdomyosarcoma, 15, 277 Rheumatic Diseases, 6, 7, 113, 277 Rheumatism, 81, 82, 102, 277 Rheumatoid, 7, 29, 77, 84, 97, 107, 114, 142, 277 Rheumatoid arthritis, 7, 29, 77, 84, 97, 107, 114, 142, 277 Ribonuclease, 137, 154, 277 Ribonucleoproteins, 261, 277 Ribose, 205, 277 Ribosome, 278, 288 Risk factor, 29, 41, 54, 58, 234, 252, 272, 278
Risperidone, 63, 83, 87, 88, 109, 112, 119, 120, 278 S Saliva, 103, 278 Salivary, 56, 107, 264, 267, 278, 283 Salivary glands, 107, 278 Saponins, 278, 283 Sarcoma, 253, 278 Schistosoma, 126, 278 Schistosoma mansoni, 126, 278 Schistosomiasis mansoni, 278 Schizoid, 278, 291 Schizophrenia, 63, 77, 79, 81, 83, 86, 87, 88, 105, 107, 112, 212, 278, 291 Schizotypal Personality Disorder, 278, 291 Sclera, 225, 278, 290 Sclerosis, 187, 257, 278 Scopolamine, 134, 135, 278 Screening, 11, 65, 113, 146, 158, 159, 161, 164, 223, 279 Seborrhea, 6, 279 Sebum, 279 Secondary tumor, 255, 279 Secretion, 9, 25, 30, 36, 40, 41, 45, 47, 54, 59, 62, 74, 77, 80, 82, 86, 89, 93, 94, 96, 99, 101, 103, 104, 105, 107, 109, 112, 113, 124, 126, 141, 142, 143, 145, 147, 151, 155, 160, 170, 206, 217, 221, 222, 227, 231, 234, 239, 243, 244, 245, 247, 250, 256, 257, 267, 275, 279 Secretory, 16, 19, 25, 50, 79, 101, 103, 245, 279 Sedentary, 8, 279 Sedimentation, 220, 269, 279 Seizures, 87, 144, 161, 165, 228, 264, 279, 282 Selective estrogen receptor modulator, 275, 279, 285 Self-Injurious Behavior, 56, 279 Sella, 143, 267, 279 Semen, 19, 232, 272, 279 Semisynthetic, 217, 279 Senescence, 39, 279 Senile, 141, 212, 263, 279 Sensitization, 11, 279 Sepsis, 31, 279 Septicemia, 41, 279 Sequence Analysis, 68, 279 Sequence Homology, 265, 280 Serine, 59, 112, 148, 163, 222, 233, 280, 284, 287, 289
308
Prolactin
Serotonin, 6, 10, 17, 46, 56, 57, 58, 113, 123, 161, 205, 212, 218, 223, 229, 236, 238, 260, 275, 278, 280, 289 Serous, 224, 233, 280 Sertraline, 89, 280 Sex Characteristics, 206, 209, 274, 280, 285 Sex Determination, 187, 280 Sexual Partners, 4, 280 Shock, 280, 288 Side effect, 64, 79, 144, 165, 177, 206, 207, 212, 215, 280, 287 Signal Transduction, 9, 12, 23, 27, 28, 31, 46, 51, 59, 60, 66, 89, 138, 219, 280 Signs and Symptoms, 276, 280 Skeletal, 36, 49, 209, 231, 257, 281, 282 Skeleton, 36, 217, 249, 281 Skull, 93, 281, 285 Skull Base, 93, 281 Sleep Deprivation, 41, 281 Small intestine, 222, 231, 243, 245, 248, 281, 289 Smooth muscle, 209, 237, 243, 250, 257, 258, 272, 281, 282, 283 Social Behavior, 33, 281 Social Environment, 274, 281 Social Isolation, 66, 278, 281 Sodium, 61, 105, 207, 256, 258, 281, 284 Sodium Lactate, 105, 281 Soft tissue, 216, 253, 281 Solid tumor, 209, 233, 281 Solvent, 235, 266, 281 Soma, 274, 281 Somatic, 52, 159, 206, 243, 256, 265, 281 Somatostatin, 72, 76, 97, 118, 137, 142, 154, 281 Somatotropin, 35, 137, 154, 245, 282 Soybean Oil, 269, 282 Spasm, 212, 226, 243, 282, 285 Spatial disorientation, 230, 282 Specialist, 193, 282 Specificity, 36, 207, 233, 282, 284, 287 Spectrum, 64, 147, 250, 282 Sperm, 17, 20, 119, 209, 222, 282 Sphenoid, 279, 282 Sphenoidal, 99, 282 Spinal cord, 217, 220, 221, 234, 254, 259, 265, 274, 282 Spleen, 70, 252, 278, 282 Spondylitis, 7, 282 Spontaneous Abortion, 17, 270, 282 Sporadic, 259, 277, 282 Stabilization, 136, 282
Staging, 52, 282 Status Epilepticus, 161, 282 Stem Cells, 60, 106, 164, 235, 265, 282, 289 Sterile, 213, 264, 283 Sterility, 247, 283 Steroid, 13, 27, 28, 29, 40, 54, 58, 65, 97, 175, 213, 215, 227, 238, 278, 283 Steroid therapy, 97, 283 Stillbirth, 270, 283 Stimulant, 209, 229, 243, 283 Stimulus, 231, 236, 250, 266, 283, 286 Stomach, 205, 215, 238, 239, 240, 243, 258, 265, 281, 282, 283 Stool, 224, 246, 283 Striatum, 17, 261, 283 Stroma, 16, 39, 53, 283 Stromal, 19, 37, 39, 62, 98, 216, 233, 283 Stromal Cells, 37, 98, 216, 283 Subacute, 247, 283 Subclinical, 75, 247, 279, 283 Subcutaneous, 4, 96, 206, 232, 250, 264, 283 Submaxillary, 234, 283 Subspecies, 282, 283 Substance P, 255, 262, 275, 279, 283 Substrate, 25, 153, 283 Subthalamus, 229, 283 Subtilisin, 152, 284 Superoxide, 137, 154, 284 Superoxide Dismutase, 137, 154, 284 Supplementation, 39, 62, 159, 284 Suppression, 51, 78, 175, 227, 284 Survival Rate, 31, 263, 284 Sweat, 229, 279, 284 Sweat Glands, 229, 279, 284 Sympathomimetic, 209, 229, 230, 234, 261, 284 Symphysis, 272, 284 Symptomatic, 3, 210, 284 Synaptic, 260, 280, 284 Synergistic, 31, 37, 51, 116, 271, 284 Synovial, 106, 213, 284 Synovial Membrane, 213, 284 Systemic disease, 213, 279, 284 Systemic lupus erythematosus, 7, 78, 81, 82, 85, 89, 90, 102, 119, 142, 284 Systolic, 244, 284 T Tacrolimus, 14, 284 Tamoxifen, 50, 279, 285 Tardive, 212, 285 Telangiectasia, 187, 285 Temperament, 110, 285
Index 309
Temporal, 10, 21, 27, 243, 253, 269, 285 Teratogenicity, 144, 165, 285 Teratoma, 221, 285 Terminator, 223, 285 Testicular, 213, 285 Testis, 107, 221, 235, 285 Testosterone, 4, 5, 20, 27, 29, 52, 60, 66, 81, 116, 118, 131, 171, 202, 237, 276, 285 Tetany, 264, 285 Tetrodotoxin, 61, 285 Thalamic, 213, 234, 285 Thalamic Diseases, 213, 285 Thalamus, 229, 234, 283, 285 Therapeutics, 75, 178, 285 Thermal, 52, 153, 210, 230, 260, 286 Thermoregulation, 123, 266, 286 Thigh, 4, 286 Third Ventricle, 212, 234, 245, 254, 267, 285, 286 Thoracic, 143, 286, 291 Threonine, 265, 280, 286 Threshold, 161, 236, 244, 286 Thrombin, 237, 268, 272, 286 Thrombocytes, 268, 286 Thrombocytopenia, 135, 136, 286 Thrombomodulin, 272, 286 Thrombopoietin, 102, 286 Thrombosis, 248, 272, 286 Thrombus, 226, 247, 268, 286 Thymidine, 217, 286 Thymoma, 65, 286 Thymus, 43, 70, 71, 245, 252, 286 Thyroid, 4, 5, 39, 41, 74, 80, 89, 98, 119, 137, 149, 154, 218, 245, 264, 286, 287, 289 Thyroid Gland, 264, 286, 287 Thyroid Hormones, 4, 89, 286, 287, 289 Thyroiditis, 90, 286 Thyrotropin, 67, 74, 124, 245, 286 Thyroxine, 266, 287 Tilapia, 73, 158, 287 Tissue Culture, 23, 287 Tissue Distribution, 14, 287 Tissue Plasminogen Activator, 152, 287 Tolerance, 52, 64, 134, 205, 240, 287 Tone, 47, 85, 86, 126, 287 Tonic, 144, 165, 287 Tonus, 287 Topical, 213, 235, 244, 264, 287 Torsion, 247, 287 Toxaemia, 270, 287 Toxic, iv, 34, 214, 225, 233, 245, 259, 260, 287, 288
Toxicity, 19, 32, 34, 157, 231, 255, 287 Toxicology, 123, 184, 287 Toxin, 233, 285, 287, 288 Trachea, 217, 286, 288 Tranquilizing Agents, 273, 288 Transcriptase, 277, 288 Transcription Factors, 15, 19, 23, 24, 26, 28, 30, 51, 62, 122, 277, 288 Transduction, 280, 288 Transfection, 15, 23, 24, 31, 44, 216, 239, 288 Transfer Factor, 245, 288 Transferases, 240, 288 Translation, 16, 136, 208, 288 Translational, 136, 288 Translocation, 31, 50, 106, 288 Transmitter, 205, 230, 254, 261, 288 Transplantation, 119, 123, 164, 222, 232, 245, 288 Trauma, 31, 54, 214, 217, 228, 241, 285, 288 Tricuspid Atresia, 226, 288 Trigeminal, 76, 288 Trigger zone, 212, 288 Trisomy, 146, 289 Trophoblast, 16, 22, 63, 216, 289 Trypsin, 137, 154, 222, 233, 289 Tryptophan, 56, 87, 102, 122, 148, 224, 280, 289 Tubercle, 261, 289 Tuberous Sclerosis, 187, 289 Tumor marker, 216, 289 Tumor Necrosis Factor, 29, 289 Tumorigenic, 20, 141, 289 Tyrosine, 17, 22, 23, 36, 51, 65, 71, 77, 87, 109, 125, 138, 148, 230, 289 U Ulcer, 75, 231, 267, 289 Ultrasonography, 239, 289 Umbilical Arteries, 289 Umbilical Cord, 60, 207, 289 Umbilical cord blood, 60, 289 Unconscious, 209, 228, 245, 289 Urea, 212, 284, 289 Uremia, 3, 250, 289 Urethra, 265, 272, 290 Urinary, 120, 246, 262, 267, 279, 281, 287, 289, 290 Urinary Plasminogen Activator, 287, 290 Urinary tract, 262, 290 Urine, 55, 102, 216, 234, 235, 242, 246, 258, 273, 290 Uterine Contraction, 205, 263, 290
310
Prolactin
Uvea, 290 Uveitis, 162, 290 V Vaccine, 206, 273, 290 Vagina, 221, 229, 255, 276, 290 Vascular, 5, 7, 40, 65, 220, 229, 233, 247, 260, 263, 267, 286, 290 Vasculitis, 220, 290 Vasoactive, 72, 130, 290 Vasoactive Intestinal Peptide, 72, 130, 290 Vasoconstriction, 234, 290 Vasodilator, 217, 230, 243, 290 Vein, 8, 213, 249, 261, 289, 290 Venous, 99, 213, 216, 220, 248, 268, 272, 288, 290 Venous blood, 216, 220, 268, 290 Venter, 290 Ventral, 26, 212, 245, 261, 290 Ventricle, 213, 219, 226, 243, 261, 274, 284, 286, 288, 290 Ventricular, 226, 288, 290 Venules, 216, 218, 291 Vertebrae, 282, 291 Vertigo, 80, 291 Vesicular, 238, 291 Veterinary Medicine, 183, 291 Vial, 12, 291 Villous, 219, 291 Viral, 25, 212, 259, 262, 277, 288, 289, 291 Virulence, 215, 287, 291 Virus, 24, 25, 65, 69, 71, 85, 114, 141, 212, 233, 239, 241, 248, 288, 291 Virus Diseases, 141, 212, 291
Vitreous, 229, 277, 291 Vitreous Hemorrhage, 229, 291 Vitro, 9, 11, 16, 21, 23, 25, 26, 38, 40, 41, 45, 46, 48, 50, 53, 65, 66, 73, 76, 85, 87, 97, 113, 118, 125, 135, 136, 152, 158, 159, 164, 215, 232, 239, 242, 246, 285, 287, 291 Vivo, 9, 11, 12, 16, 19, 21, 23, 24, 25, 26, 31, 37, 38, 40, 41, 45, 49, 76, 85, 97, 118, 125, 135, 136, 137, 154, 164, 215, 239, 242, 246, 285, 291 Volition, 249, 261, 291 W Wakefulness, 144, 148, 165, 228, 291 War, 269, 291 Weight Gain, 4, 62, 63, 291 White blood cell, 210, 224, 246, 251, 252, 253, 257, 258, 267, 291 Windpipe, 286, 291 Withdrawal, 47, 54, 99, 228, 291 Womb, 276, 290, 291 Wound Healing, 162, 222, 237, 248, 292 X Xenograft, 23, 210, 292 X-ray, 237, 249, 253, 258, 261, 274, 275, 292 X-ray therapy, 249, 292 Y Yeasts, 238, 266, 292 Yohimbine, 5, 292 Yolk Sac, 236, 292 Z Zygote, 225, 292 Zymogen, 222, 272, 292
Index 311
312
Prolactin
