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

CALCITONIN A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

CALCITONIN 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., 1960Calcitonin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00196-9 1. Calcitonin-Popular works.I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on calcitonin. 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 CALCITONIN ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Calcitonin.................................................................................... 10 E-Journals: PubMed Central ....................................................................................................... 68 The National Library of Medicine: PubMed ................................................................................ 72 CHAPTER 2. NUTRITION AND CALCITONIN ................................................................................. 121 Overview.................................................................................................................................... 121 Finding Nutrition Studies on Calcitonin .................................................................................. 121 Federal Resources on Nutrition ................................................................................................. 123 Additional Web Resources ......................................................................................................... 124 CHAPTER 3. ALTERNATIVE MEDICINE AND CALCITONIN ........................................................... 125 Overview.................................................................................................................................... 125 National Center for Complementary and Alternative Medicine................................................ 125 Additional Web Resources ......................................................................................................... 140 General References ..................................................................................................................... 141 CHAPTER 4. DISSERTATIONS ON CALCITONIN ............................................................................. 143 Overview.................................................................................................................................... 143 Dissertations on Calcitonin ....................................................................................................... 143 Keeping Current ........................................................................................................................ 144 CHAPTER 5. PATENTS ON CALCITONIN ........................................................................................ 145 Overview.................................................................................................................................... 145 Patents on Calcitonin................................................................................................................. 145 Patent Applications on Calcitonin............................................................................................. 154 Keeping Current ........................................................................................................................ 171 CHAPTER 6. BOOKS ON CALCITONIN ........................................................................................... 173 Overview.................................................................................................................................... 173 Book Summaries: Federal Agencies............................................................................................ 173 Book Summaries: Online Booksellers......................................................................................... 174 Chapters on Calcitonin .............................................................................................................. 175 CHAPTER 7. PERIODICALS AND NEWS ON CALCITONIN .............................................................. 179 Overview.................................................................................................................................... 179 News Services and Press Releases.............................................................................................. 179 Newsletter Articles .................................................................................................................... 181 Academic Periodicals covering Calcitonin................................................................................. 182 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 183 Overview.................................................................................................................................... 183 U.S. Pharmacopeia..................................................................................................................... 183 Commercial Databases ............................................................................................................... 184 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 187 Overview.................................................................................................................................... 187 NIH Guidelines.......................................................................................................................... 187 NIH Databases........................................................................................................................... 189 Other Commercial Databases..................................................................................................... 191 APPENDIX B. PATIENT RESOURCES ............................................................................................... 193 Overview.................................................................................................................................... 193 Patient Guideline Sources.......................................................................................................... 193 Finding Associations.................................................................................................................. 198 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 201 Overview.................................................................................................................................... 201

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Preparation................................................................................................................................. 201 Finding a Local Medical Library................................................................................................ 201 Medical Libraries in the U.S. and Canada ................................................................................. 201 ONLINE GLOSSARIES................................................................................................................ 207 Online Dictionary Directories ................................................................................................... 208 CALCITONIN DICTIONARY .................................................................................................... 209 INDEX .............................................................................................................................................. 299

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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 calcitonin 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 calcitonin, 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 calcitonin, 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 calcitonin. 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 calcitonin, 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 calcitonin. 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 CALCITONIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on calcitonin.

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

Building a Better Mousetrap: Toward an Understanding of Osteoporosis Source: JADA. Journal of the American Dental Association. 130(11): 1632-1636. November 1999. Summary: In this article, the author reviews osteoporosis, with a eye toward the implications of osteoporosis for oral health. Osteoporosis is the most common human bone disease; it weakens bones slowly and steadily over time until they break under stresses that should not cause fractures. The author discusses risk factors, including differences in incidence by gender; the economic effects of osteoporosis; osteoporosis treatments, including estrogen therapies, calcitonin, alendronate, raloxifen, and treatments under investigation; the genetics of osteoporosis, current National Institutes of Health (NIH) research on osteoporosis and related bone diseases; and risk factors, including female gender, inadequate calcium intake, and lack of weight bearing

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exercise. The author concludes by encouraging health professionals to focus on osteoporosis and its prevention. One sidebar offers a list of organizations to contact for further information (including web sites). 21 references. •

Gastrointestinal Hormones Source: Current Opinion in Gastroenterology. 7(6): 906-912. December 1991. Summary: Investigation of gastroduodenal regulatory peptide gene expression and subsequent peptide processing and release has resulted in a series of important contributions to the literature. This review article covers articles that direct attention to the importance of luminal factors and paracrine mechanisms in regulation of gastrointestinal hormone synthesis and secretion. The author emphasizes the application of molecular biology to expanding knowledge of gastrointestinal physiology. Topics include gastrin synthesis and posttranslational processing, gastrin and enterochromaffin-like cells, gastrin release, cholecystokinin, somatostatin, and calcitonin gene-related peptide. 2 figures. 53 annotated references. (AA-M).

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Strategy for Osteoporosis in Gastroenterology Source: European Journal of Gastroenterology and Hepatology. 10(8): 689-698. August 1998. Contact: Available from Lippincott Williams and Wilkins, 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Summary: Osteoporotic fractures are a major public health problem that results not only in considerable morbidity and mortality, but also in increased costs, including acute hospital care and long-term care in the home or nursing home. Gastroenterologists see many patients at risk of osteoporosis, particularly those with celiac disease and inflammatory bowel disease (IBD). In this article, the authors review the extent of this problem and outline a strategy of investigation and treatment. The authors first review methods of screening for osteoporosis, particularly the methods for measuring bone mineral density (BMD), the primary means of determining osteoporosis. The mechanism of osteoporosis in celiac disease is likely to be related to calcium malabsorption, which leads to increased parathormone secretion. This in turn increases bone turnover and cortical bone loss. The authors note that studies of osteoporosis in IBD are less consistent than in celiac disease; This finding is not surprising given the great variation in site, extent, and severity of disease, as well as the use or non-use of steroid drugs in patients with IBD. The authors outline a strategy for preventing and treating osteoporosis that includes patient education, particularly about dietary and lifestyle risks; the timing of densitometry (to measure BMD); the role of hormone replacement therapy, biphosphonates, and calcitonin; the duration of treatment; and the use of steroids and combination treatment. For patients on steroids, the authors recommend 800 units of vitamin D daily for the duration of therapy. BMD should be measured and repeated every year in which steroids are given. If osteoporosis is found, the care plan would include a biphosphonate, usually in addition to vitamin D. The appendix summarizes the recommended strategies for different patient populations (based on age, gender, and presence of other risk factors and diseases). The article is published with the opinions of the referees who commented on the text during the peer review process; the editor explains that this was done in light of the general importance of this article and the discussion it had generated. 1 appendix. 80 references. (AA-M).

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Management of Acute Hypercalcemia Source: New England Journal of Medicine. 326(18): 1196-1203. April 30, 1992. Summary: This article discusses the management of acute hypercalcemia, a relatively frequent medical problem. The author focuses on the care of patients with hypercalcemia who require immediate treatment in the hospital. Topics include the pathophysiologic mechanisms of acute hypercalcemia; the decision to treat; treatment of hypercalcemia, notably measures to correct dehydration, to enhance the renal excretion of calcium, to inhibit accelerated bone resorption, and to treat the underlying disorder; the use of loop diuretic agents, biphosphonates, plicamycin, calcitonin, gallium nitrate, glucocorticoids, and phosphate; and choosing a therapeutic agent. 1 figure. 1 table. 102 references.

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Preventing and Managing Osteoporosis Source: American Journal of Nursing. AJN. 97(1):16B-16D. January 1997. Summary: This article discusses the prevention and treatment of osteoporosis, including its assessment, hormone strategies, and pharmacological and non-pharmacological management options. Osteoporosis is not curable, however, advances in treatment have been made to stabilize bone loss. Part of assessing patient risk is exploring the common factors such as being female, family history, small-framed body, sedentary lifestyle, excessive use of alcohol, and smoking. Biochemical markers of bone turnover can also be measured to diagnosis or track the disease's progress. Prevention strategies include calcium and vitamin D (calciferol) intake, and prevention efforts during adolescence may significantly reduce the incidence of osteoporosis in the elderly. Additionally, patients of any age may gain benefit from regular weight-bearing activities and other exercise. Estrogen replacement therapy may be prescribed to postmenopausal women to prevent osteoporosis, and for men, testosterone replacement therapy may also be appropriate, although long-term effects are unknown. Currently, calcitonin, fluoride, and a class of drugs called bisphosphonates are available. Nonpharmacologic measures include physical therapy, counseling, and home environment safety adjustments. 9 references.

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Finally, There's Real Help for Women with Osteoporosis, and a Good Reason for Doctors to Find Out Who Else Is At Risk Source: Hippocrates. 67-69. May 1996. Summary: This article discusses two new, FDA approved, drug treatments for osteoporosis, alendronate and calcitonin in nasal-spray form, and a slightly risky, nonFDA approved, slow-release sodium fluoride that can rebuild bones. The author also provides advice on using bone scans to help physicians and their patients decide on treatment options; explores the question of whether younger women just entering menopause can or should use these drugs as a preventive measure; highlights the advantages of estrogen usage and the benefits and problems associated with slowrelease sodium fluoride; and examines the nutritional and lifestyle considerations for combating the condition, including taking vitamin D and calcium supplementation.

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What You Should Know About Osteoporosis Source: Diabetes Self-Management. P. 38-42. September-October 1993. Summary: This article explains simple preventive strategies for avoiding the problems of osteoporosis, as well as some helpful treatments for those who have already

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developed osteoporosis. Topics include assessing bone mass with bone densitometry; controlling risk factors for osteoporosis, including the role of calcium, vitamin D, exercise, and estrogen replacement therapy; treatments for osteoporosis, including calcitonin, and phosphate derivatives; and falls and fractures. The authors focus on prevention of osteoporosis as the best approach, especially for women with diabetes. The article concludes with the contact information for the National Osteoporosis Foundation. •

Dermal Neurovascular Dysfunction in Type 2 Diabetes Source: Diabetes Care. 24(8): 1468-1475. August 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reviews evidence for a relationship between dermal neurovascular dysfunction and other components of the metabolic syndrome of type 2 diabetes. Heat and gravity have been shown to have specific neural, nitrergic, and independent mediators to regulate skin blood flow. Skin blood flow can be measured by laser Doppler techniques. This tool identifies dermal neurovascular dysfunction in the majority of people who have type 2 diabetes. The defect in skin vasodilation is detectable before the development of diabetes and is partially correctable with insulin sensitizers. This defect is associated with C fiber dysfunction and coexists with variables of the insulin resistance syndrome. The defect most likely results from an imbalance among the endogenous vasodilator compound nitric oxide, the vasodilator neuropeptides substance P and calcitonin gene related peptide, and the vasoconstrictors angiotensin II and endothelin. Hypertension per se increases skin vasodilation and does not impair the responses to gravity, which is opposite to that of diabetes, suggesting that the effects of diabetes override and counteract those of hypertension. The article concludes that observations suggest that dermal neurovascular function is largely regulated by peripheral C fiber neurons and that dysregulation may be a component of the metabolic syndrome associated with type 2 diabetes. 3 figures. 87 references. (AAM).

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Long Term Transplant Issues Source: Renalife. 14(3): 16, 18. Fall 1998. Contact: Available from American Association of Kidney Patients (AAKP). 100 South Ashley Drive, Suite 280, Tampa, FL 33602. (800) 749-AAKP or (813) 223-7099. E-mail: [email protected]. Website: www.aakp.org. Summary: This article, from a magazine for people with kidney disease, discusses long term kidney transplantation issues. The author notes that kidney transplantation is a successful treatment for renal failure; 92 percent of kidneys from living related donors and 87 percent of kidneys from cadaver donors are working at least 1 year after the transplant. Long term, half of the kidneys from a living donor are functioning more than 14.5 years after the transplant and about 8 years after a cadaver transplant. Acute rejection remains a major problem after a kidney transplant; however, current antirejection medicines are very effective in treating acute rejection. Medicines given to treat acute rejection can lower the resistance to infection, however, and patients treated for acute rejection may develop infections several weeks later. And immunosuppressive agents have side effects, including hypertension, hyperlipidemia, diabetes, metabolic bone disease, and increased malignancies. The most frequent cause of death in renal transplant patients is cardiovascular disease. Diabetes occurs in up to 40 percent of

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patients after a transplant, with the highest incidence in African Americans and Hispanics. Renal transplant patients usually have soft bones before transplantation; after transplant, most patients resolve the hyperparathyroid bone disease that they had when they were on dialysis. There are several new drugs, including nasal spray calcitonin, alendronate, and raloxifene, that are being used to prevent bone loss. Skin cancers and lymphomas are increased in transplant patients. The author concludes by hoping that newer immunosuppressive medicines will increase long term transplant function and have fewer side effects. •

Current Treatment Options for Osteoporosis Source: Journal of Rheumatology. 23(Supplement 45):11-14. 1996. Summary: This for physicians examines various approaches to preventing and treating of osteoporosis, including increasing calcium intake and use of drug and hormone therapies. It indicates that the goals for treating patients with osteoporosis are to maintain normal bone and to prevent the deterioration of normal bone to osteoporotic bone. Achievement of these goals, combined with a successful approach for preventing falls, may substantially decrease the incidence and risk of fractures. Using drug therapy to stimulate bone formation (e.g., fluoride, anabolic steroids), and drugs to inhibit bone resorption (e.g., estrogen replacement therapy, calcitonin, bisphosphonates) are recommended. 14 references.

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Corticosteroid-Induced Osteoporosis: Access the Risk, Protect Your Patient Source: Journal of Musculoskeletal Medicine. 14(1):43-44,46, 53-55; January 1997. Summary: This journal article for health professionals reviews the pathophysiology of corticosteroid-induced osteoporosis, identifies the at-risk population, and discusses management strategies. Long-term corticosteroid therapy causes a rapid loss of trabecular bone through disruption of calcium homeostasis, inhibition of bone formation, and reduction in sex hormone levels. Pharmacologic doses of corticosteroids inhibit the synthesis or action of several growth factors having anabolic effects on bone. It is reasonable to measure bone mineral density and to start preventive care as soon as possible in patients beginning long-term corticosteroid therapy. Calcium supplements, vitamin D, sex hormone replacement, and a weight-bearing exercise program are suitable first-line therapies to counteract bone loss. Thiazide diuretics and sodium restriction are useful in reducing hypercalciuria. Other agents, such as bisphosphonates, calcitonin, or fluoride, may be indicated for patients who cannot take hormones or in whom initial interventions do not retard bone loss. Agents that stimulate bone formation in the presence of corticosteroids may become available in the future. 11 references, 2 figures, and 1 table. (AA-M).

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Boning Up Source: Arthritis Today. 37-38,40-41; November-December 1997. Summary: This journal article for individuals with arthritis reports on important news about osteoporosis. It identifies risk factors for osteoporosis, including gender, body structure, ethnicity, genetics, inflammatory disease, and corticosteroid use. In addition, it discusses ways individuals can reduce their risk of osteoporosis, including reducing alcohol and tobacco use; consuming more calcium and vitamin D; considering the use of hormone replacement therapy, bisphosphonates, and calcitonin; and beginning an exercise program.

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Osteoporosis Prevention and Treatment Source: American Family Physician. 54(3): 986-992. September 1, 1996. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article for physicians examines the preventive strategies, evaluation, and treatment options for osteoporosis. The author indicates that bone fragility resulting from osteoporosis places a significant percentage of elderly women and other patient groups at risk for bone fracture. Risk factors for osteoporosis include hypogonadal states (particularly menopause), smoking, low calcium intake, lack of weight-bearing exercise, family history and use of certain medications. Preventive strategies are based on achieving and maintaining optimal bone mass through diet, exercise, appropriate use of hormone replacement therapy and avoidance of adverse influences, particularly smoking and certain medications. Laboratory investigations are of limited use in the detection and assessment of osteoporosis, but new techniques may help physicians identify patients with accelerated bone metabolism. Currently, the most precise method of radiologically assessing osteoporosis is dual-energy x-ray absorptiometry. Many new agents for the treatment of osteoporosis are being examined. First-line therapies currently include alendronate and calcitonin. The choice of therapy must be individualized and combined with advice about nutrition and exercise, both to optimize bone density and to minimize the risk of trauma. 2 tables, and 31 references.

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Osteoporosis: It's Not Inevitable Source: Female Patient. 11-15; 1996. Summary: This journal article for the general public presents an overview of osteoporosis. The process of bone mass loss in women after the age of 35 is explained. The risk factors for osteoporosis are outlined, and its symptoms are presented. The use of bone mineral density tests to diagnose osteoporosis in its early stages, that is, before fractures occur, is discussed. Ways of preventing osteoporosis are suggested, including consuming adequate amounts of calcium and vitamin D, making some form of weightbearing exercise part of one's daily routine, and quitting smoking. In addition, therapies that can help slow the progression of osteoporosis and make bone fractures less likely are highlighted, including using estrogen replacement therapy, hormone replacement therapy, calcitonin nasal spray, and alendronate. 1 figure and 2 tables.

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Management of Corticosteroid-Induced Osteoporosis Source: Seminars in Arthritis and Rheumatism. 29(4): 228-251. February 2000. Summary: This journal article provides health professionals with information on the pathophysiology of corticosteroid induced osteoporosis, the assessment methods used to evaluate this condition, and the results of clinical trials of drugs. In addition, the article explores a practical approach to the management of corticosteroid induced osteoporosis based on data collected from published articles. The cause of corticosteroid induced osteoporosis is multifactorial and occurs in addition to normal age and menopause associated bone loss. There are two purported abnormalities in bone metabolism that develop in patients with this condition. The first is a reduction in bone formation, and the second is an increase in bone resorption. Risk factors that should be examined in patients receiving corticosteroids include family history, hormonal status, fracture history, age, other medications that may interfere with normal bone

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metabolism, and lifestyle habits. Measurements of urinary calcium concentrations are helpful in assessing calcium balance, susceptibility to secondary hyperparathyroidism, and possible treatment options for corticosteroid treated patients. Distinctive characteristics of corticosteroid induced osteoporosis may be observed on radiographs. Early changes in bone mineral density can be observed in the lumbar spine and femoral neck using dual x-ray energy absorptiometry or quantitative computed tomography. Therapeutically, the use of alternative therapy or early discontinuation of corticosteroids is the best means of preventing corticosteroid induced osteoporosis. Several interventions have been proposed in the management of corticosteroid induced bone loss. Bisphosphonate (diphosphonate) therapy is beneficial in both the prevention and treatment of corticosteroid induced osteoporosis. Data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Although calcium and vitamin D and its analogs appear to have weak positive effects on bone in those receiving corticosteroids, they may not be potent enough to be used alone. As such, they should be administered in combination with other agents. The article concludes that bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid induced osteoporosis. 2 figures, 6 tables, and 146 references. (AA-M). •

Corticosteroid-Induced Osteoporosis: Prevention and Management Source: Journal of Musculoskeletal Medicine. 17(2): 68-70,76-81. February 2000. Summary: This journal article, the first in a special series on the prevention, diagnosis, and management of osteoporosis, provides health professionals with information on the pathophysiologic mechanisms that contribute to corticosteroid induced osteoporosis and its diagnosis and management. The benefits of corticosteroids are offset by the significant bone loss that occurs within the first 3 to 6 months of therapy and is never fully regained. This effect occurs in men and women of all ages. One mechanism by which corticosteroids interfere with normal bone remodeling is through their influence on gonadal hormone levels. Corticosteroids directly inhibit ovarian and testicular production of estrogen and testosterone and disrupt the hypothalamic pituitary gonadal axis. Corticosteroids may also decrease calcium absorption from the gut and increase urinary calcium secretion. Further, corticosteroids inhibit bone formation through mechanisms that include the direct inhibition of osteoblast replication, decreased synthesis of bone collagen by osteoblasts, and attachment to bone matrix. Patients starting corticosteroids at 7.5 milligrams per day or more for at least 3 months are candidates for osteoporosis prevention. In these patients, the physician should rule out secondary causes of osteoporosis and obtain a baseline bone mineral density measurement. Weight bearing exercise and adequate calcium and vitamin D intake are important, but drugs are usually needed. Estrogen and testosterone replacement are recommended for postmenopausal and hypogonadic patients. Calcitonin stabilizes bone mineral density in the spine but not the hip. Bisphosphonates act directly on osteoclasts to decrease bone resorption, and they have proven efficacy for both prevention and treatment of corticosteroid induced osteoporosis. 2 figures, 4 tables, and 41 references. (AA-M).

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Osteoporosis in Men: A Serious but Under-Recognized Problem Source: Journal of Musculoskeletal Medicine. 18(6): 310-316. June 2001. Summary: This journal article, the second in a special series on diagnosis and management of osteoporosis, provides health professionals with information on the

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epidemiology, etiology, diagnosis, and management of osteoporosis in men. Osteoporosis can produce profound morbidity and mortality in men, much as it can in women. Although osteoporosis is often asymptomatic, its end result, fragility fracture, creates a heavy medical and financial burden for society. Each year in the United States, between 850,000 and 1.5 million fractures occur in people who are at least 65 years old. Of these fractures, 20 percent are sustained by men. Abnormalities affecting the factors involved in normal bone turnover constitute primary and secondary causes of osteoporosis. Primary factors are usually related to aging or genetic factors, whereas secondary factors are external and can usually be avoided and corrected. Most men have secondary contributors to osteoporosis. Male hypogonadism, or testosterone deficiency, is a secondary cause of osteoporosis in up to 30 percent of men. Hypogonadism contributes to osteoporosis in men by blunting calcitonin secretion and osteoblastic activity. Estrogen deficiency may also contribute to osteoporosis in some men. Bone density studies are recommended for men older than 70 and earlier in the presence of osteoporosis risk factors. Once the diagnosis has been confirmed, management focuses on adequate calcium and vitamin D intake, regular exercise, prevention of falls, and administration of alendronate. Testosterone replacement may hold promise. 4 tables and 38 references. (AA-M). •

Pathogenesis of NIDDM: A Balanced Overview Source: Diabetes Care. 15(3): 318-368. March 1992. Summary: This lengthy review article examines the pathogenesis of NIDDM in detail. Topics include fasting insulin concentrations; glucose-stimulated insulin secretion; firstphase insulin secretion; pulsatile insulin secretion; proinsulin; the etiology of insulin deficiency in NIDDM; the site of insulin resistance; hepatic glucose production (HGP); splanchnic (gastrointestinal plus hepatic) glucose uptake; peripheral (muscle) glucose uptake; glucose disposal during oral glucose tolerance testing (OGTT); fasting hyperglycemia in NIDDM; dynamic interaction between insulin action and insulin secretion in NIDDM; cellular mechanisms of insulin resistance; glucose transport; glycogen synthesis; glucose oxidation; lipid oxidation and insulin resistance; determinants of insulin action, including skeletal muscle capillary density fiber type, blood flow and endothelial transport; amylin and calcitonin gene-related peptide (CGRP); hyperglycemia and glucose toxicity; primary cellular defects in insulin resistance; and primary insulin secretory defects. 34 figures. 7 tables. 445 references.

Federally Funded Research on Calcitonin The U.S. Government supports a variety of research studies relating to calcitonin. 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.

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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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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 calcitonin. 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 calcitonin. The following is typical of the type of information found when searching the CRISP database for calcitonin: •

Project Title: ACUPUNCTURE FOR HOT FLASHES IN PROSTATE CANCER PATIENTS Principal Investigator & Institution: Beer, Tomasz M.; Associate Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 14-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Up to 80% of men treated with androgen deprivation for prostate cancer suffer from hot flashes. Insomnia, fatigue, and irritability are often associated with hot flashes and adversely affect the quality of life for these patients. Several pharmacologic interventions can reduce hot flash frequency and intensity but have the potential for adverse effects. Acupuncture, a 23 centuries-old treatment modality, has been reported to substantially reduce hot flash frequency in 7 men treated with androgen deprivation for prostate cancer in Sweden. The study proposed here will apply validated methodology to assess the impact of acupuncture on hot flash frequency and intensity as well as hot flash related quality of life in an adequately powered phase Ii study. To extend current understanding of the physiologic changes associated with hot flashes and with acupuncture, the impact of acupuncture on serotonin and its metabolites, metabolites of brain norepinephrine, and circulating calcitonin gene-related peptide (CGRP) will be evaluated. All three of these systems have been implicated in the pathophysiology of thermoregulatory instability associated with hot flashes. Serotonin and norepinephrine are amongst the targets of western pharmacologic treatment for hot flashes. Preliminary data suggest that acupuncture may mediate changes in circulating serotonin and CGRP. Promising results in this pilot trial will lead to randomized studies of acupuncture compared to pharmacologic therapy and pilot studies of acupuncture combined with western treatment. The overall goal is to provide prostate cancer patients an effective, low toxicity, non-pharmacologic treatment modality for hot flashes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADVANCING MENTORING AND RESEARCH IN MOUSE PATHOBIOLOGY Principal Investigator & Institution: Nikitin, Alexander Y.; Assistant Professor of Pathology; Biomedical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Candidate has a long-term interest in the pathobiology of genetically modified mice. His training in human pathology and extensive experience in murine pathobiology permit for a comprehensive biomedical evaluation of novel mouse models, and constitute strong qualifications for the training of beginning mouse pathobiologists. The Award will free 50 percent of the Candidate's effort, thereby allowing him to: 1) increase his mentoring of beginning investigators; and

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Calcitonin

2) conduct ongoing research projects in the most effective manner. The immediate beneficiaries of this increase in the Candidate's mentoring are seven pathology residents at the department, as well as three postdoctoral fellows, one graduate, and five undergraduate students in the Candidate's laboratory. Additionally, the PI will extend his active training of beginning investigators to a number of collaborating laboratories. He will establish a training program in contemporary pathobiology of genetically modified mice at the College of Veterinary Medicine (CVM) at CU, and actively participate in national training forums. In his research, the Candidate will extend testing his earlier hypothesis that inactivation of the Rb results in preferential formation of neoplasms with neuroendocrine differentiation in mice. Towards this goal, the following Specific Aims are proposed: 1) to test the hypothesis that selective prevention of neoplasia in the pituitary and thyroid glands will result in preferential formation of other spontaneous tumors with neuroendocrine differentiation; 2) to test the hypothesis that targeted homozygous deletion of Rb in mouse tissues will preferentially result in neoplasia with neuroendocrine differentiation; and 3) to evaluate the hypothesis that Rb inactivation may have both synergistic and antagonistic effects on progression of neoplasia as a function of target cell type. These studies shall lead to our better understanding of mechanisms defining cell type-specific roles of Rb, lay a solid foundation for developing valid mouse models of neuroendocrine neoplasia associated with Rb deficiency, and provide numerous opportunities for training of beginning investigators. Taken together, freeing the Candidate's time from unrelated duties will greatly facilitate his efforts towards mentoring and productive research in the pathobiology of genetically modified mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANABOLIC SKELETAL AGENTS FOR OSTEOPOROSIS Principal Investigator & Institution: Stewart, Andrew F.; Professor; American Society for Bone & Mineral Res 2025 M St Nw, Ste 800 Washington, Dc 20036 Timing: Fiscal Year 2004; Project Start 24-MAY-2004; Project End 25-MAY-2004 Summary: (provided by applicant): Osteoporosis is an enormous and continually growing public health problem. It leads to a large societal burden of bone pain, skeletal fracture, mortality and reduction in the quality of life. It affects men and women, and is increasing in incidence as the population ages. The annual cost of osteoporosis in the US is in the range of $30 billion in women alone. Osteoporosis can be primary (postmenopausal and senile osteoporosis) or can be secondary (for example in patients with rheumatic disease and emphysema on glucocorticoid therapy). To date, the mainstays of therapy have been directed at nutrition (calcium and vitamin D) and at preventing further bone loss through the blockade of osteoclastic bone resorption using a family of so called "anti-resorptive" drugs such as estrogen, selective estrogen receptor modulators, bisphosphonates and calcitonin. The recent and marked reduction in the use of estrogens following the release of the interim results of the Women's Health Initiative has left millions of women in the US "unprotected" against osteoporosis. In the past year, the FDA has approved parathyroid hormone, the first effective drug in a new class of skeletal anabolic agents. This event, together with rapid and extensive advances in the understanding of osteoblastic bone formation, with the explosion in identification of a myriad of new potential signaling molecules and transcriptional targets for anabolic skeletal agents, has revolutionized the field of osteoporosis therapy. The American Society for Bone and Mineral Research is the world's largest and premier society for the study and advancement of basic and clinical research in disorders relating to the skeleton. We have worked effectively in the past with the NIH in conference

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development. The considerations described above make it very clear that this is the time for senior thought leaders, mid-career investigators, and young investigators to meet in a small meeting setting, with NIH Institute staff, to review the current status of the field, to think collectively about the direction(s) in which the field should move, and to try to prioritize areas in which future clinical and basic research should be focused. Thus, the Aim of this proposal is to develop a meeting at the NIH Lister Hill center focused on advances in Skeletal Anabolic Agents and the Treatment of Osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANIMAL HYPERTENSION

MODELS

FOR

STUDYING

THE

GENETICS

OF

Principal Investigator & Institution: Smithies, Oliver; Excellence Professor of Pathology; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2007 Summary: (provided by applicant): The long term objective of the research proposed in this continuation remains to help unravel the genetic complexities of essential hypertension. For the coming grant period, we have chosen three aims:Specific aim (i) will complete or extend our quantitative analyses to include titrations of the genes coding for: renin (Ren-1), aldosterone synthase (Cyp11b2), adrenomedullin (Adm) and its receptor (Ca/cr1). the calcitonin receptor like receptor. Blood pressures will be determined and quantitative RT-PCR will be used to assess the degree to which homeostatic compensations have been induced. The effects of environmental changes, such as dietary salt and pregnancy, will be investigated. Our expectation is that these analyses will identify additional genes predicted to cause changes in blood pressure or its homeostasis if their expression varies as a result of genetic polymorphisms in humans.Specific aim (ii) will explore a new problem--how blood pressure and its homeostasis are affected by combining high expressing and low expressing genetic variants within the same physiologic system (for example Agt & Agtr1a) and in different systems (for example Agt & Npr1). We will breed currently available animals to give four combinations (high & high, high & low, low & high and low & low) for each pair of genes. We will develop computer simulations that include interactions between different systems, and will compare them with experimental data. Any inadequacies revealed will facilitate improvement of the models. This to-and-fro process is expected to greatly increase current understanding of why some combinations of genetic variations are detrimental and others beneficial.Specific aim (iii) will investigate the mechanisms underlying highly significant gender-related differences that we have found occur (a) in the expression and responses of more than 10 genes related to the control of blood pressure; (b) in the relationship between blood pressure and variations in the liver expression of Agt that are unrelated to gene copy number, and (c) between kidney expression of Agtr1a and Kiki, the gene coding for kallikrein. All three of these gender effects have direct relevance to humans, and we expect that their analysis will reveal some previously unknown causes underlying the differences in cardiovascular risk factors in males and pre-menopausal females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ARP2/3 COMPLEX AND OSTEOCLAST BONE RESORPTION Principal Investigator & Institution: Hurst, Irene R.; Orthodontics; University of Florida Gainesville, Fl 32611

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Calcitonin

Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This grant proposal outlines a five-year training program required for the pursuit of an academic and research career in biomedical and dental sciences. The principal investigator is currently pursuing a PhD in Biomedical Sciences through the University of Florida College of Medicine and concomitantly will be beginning an orthodontic residency program through the College of Dentistry in the summer of 2003. This program will allow the principal investigator to gain competence in the areas of virology, genetics, molecular cell biology and biochemistry, by technical training in protein expression and purification, cell culture, mRNA inhibition, plasmid construction, viral vector use, and cell transduction. The immediate goals of this proposal are to 1) increase biological literacy, 2) gain skills in advanced techniques, and 3) stimulate critical thinking skills, with the ultimate goal being the preparation of Dr. Hurst for an independent career in academia and biomedical research. Dr. L. Shannon Holliday, PhD, an Assistant Professor in the Department of Orthodontics, will mentor the principal investigator in her research. Dr. Holliday studies the molecular and cellular biology of osteoclast activation, has expertise in the techniques involved in this study, and has numerous publications in the field of osteoclast biology. The extensive research community at the UF Health Science Center provides all of the necessary components, collaborative and physical, required to complete this proposal and allow the principal investigator to gain independence in research. Bone resorption by specialized cells called osteoclasts is required for normal physiology. However, enhanced bone resorption can cause severe disease, including osteoporosis and metastatic bone tumors. Although osteoclast-mediated diseases often do not share common etiologies, in each case, osteoclasts must form an acidic extracellular compartment to degrade bone. This project focuses on a region of tight contact between the osteoclast and bone, the sealing zone, which segregates this acidic compartment. Sealing zone formation is indispensable for bone resorption. As described in the research plan, a new hypothesis for how the Arp2/3 complex is involved in sealing zone formation has evolved from the principal investigator's studies. This project is designed to test this novel hypothesis and has three specific aims: first, to determine the requirement of Arp2/3 for the formation of the sealing zone in vivo; second, to characterize the Arp2/3 regulatory protein, cortactin; third, to characterize phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a regulatory protein of the Arp2/3 complex, in response to calcitonin and determine its effects on actin ring formation. By studying the structural, regulatory and functional roles of the Arp2/3 complex in the sealing zone, identification of new targets for gene therapy or conventional pharmaceuticals to inhibit resorptive bone diseases may be possible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER OUTLET OBSTRUCTION INDUCED NEUROPLASTICITY Principal Investigator & Institution: Zvara, Peter; Surgery; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Benign prostatic hyperplasia (BPH) is the most common cause of bladder outflow obstruction (BOO). This condition is commonly associated with uninhibited urinary bladder contractions. Irritative voiding symptoms, a consequence of uninhibited bladder contractions are very bothersome to a large population of aging men, adversely affecting their quality of life. The overall hypothesis for this research proposal is that the marked changes in the neural control of voiding function that occur following BPH are mediated by multiple factors, including: (1)

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changes in the properties of urinary bladder afferent neurons induced by peripheral organ (bladder) dysfunction and (2) changes in the properties of interneuronal populations in the spinal cord. Thus, we propose that reorganization of spinal micturition circuitry occurs in response to changes in neural-target organ interactions. We plan to examine the effects of BOO on the neurochemical, organizational and morphological properties of afferent and spinal neurons involved in the micturition reflex pathway. This research proposal aims to provide a more thorough understanding of the wiring diagram for lower urinary tract reflexes and the functions of neurotransmitters in these reflexes. In the first part of our study we will assess neurochemical changes in neurons involved in the micturition reflex that project to the periphery following BOO. Peripheral and spinal neurons projecting to the bladder will be identified following injection of the tracer into the urinary bladder. Subsequently, immunohistochemical techniques will be used to determine changes in the expression of neuroactive compounds in these neurons. A second group of experiments will use pharmacological techniques to evaluate the role of neuroactive compounds in the central micturition pathway following chronic BOO. The effect of selective inhibitors of these neuroactive compounds on the micturition reflexes following BOO and in shamoperated controls will be determined with the use of the cystometrography (recording pressure changes in the urinary bladder during filling and micturition). In the third part of this research project, we propose to determine the organization of urinary bladder interneurons and parasympathetic preganglionic neurons in the. lumbosacral spinal cord. Changes in connectivity between the various spinal elements will be assessed following BOO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN STEM MECHANISMS MEDIATING THE NOCICEPTIVE PRESSOR RESPONSE Principal Investigator & Institution: Felder, Robert B.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2002 Summary: The goal of this proposal is to determine the role of the lateral parabrachial nucleus (LPBN) in mediating the cardiovascular responses to pain. Noxious stimulation typically elicits increases in arterial blood pressure and heart rate. These responses are mediated by nociceptive and cardiovascular centers in the brain stem. Recent anatomical and electrophysiological studies point to the LPBN as the major projection site for nociceptive inputs from lamina I and lamina II neurons in the spinal cord and the spinal trigeminal sensory nucleus in medulla. Moreover calcitonin gene-related peptide (CGRP) and substance P (SP), neuropeptides prominently involved in sensory afferent and nociceptive pathways, are present in LPBN and have been implicated in ascending pain pathways. These studies will use single cell electrophysiological recording techniques, recordings of arterial pressure, heart rate and sympathetic nerve activity, and functional neuroanatomy (c-fos) to determine the role of the LPBN in mediating the nociceptive pressor response by stimulating the trigeminal afferent system which has a discrete termination site in caudal medulla and well defined projection pathways to LPBN. The influence of the solitary tract nucleus (NTS) will also be examined, though existing data suggest a secondary role for NTS in this process. Finally, the interactions of baroreceptor afferent signals with noxious inputs will be determined at LPBN and at the rostral ventrolateral medulla (RVLM), the medullary sympathetic outflow site for the pressor response. The trigeminal afferent system mediates a number of important clinical pain syndromes, including migraine headache,

16

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the headache of arachnoid hemorrhage, trigeminal neuralgia, temporal mandibular joint pain and corneal and oral cavity pain. Thus, a better understanding of the central neural mechanisms mediating cardiovascular responses to noxious trigeminal stimulation may ultimately lead to new management strategies for patients with these clinical syndromes. In addition, these findings will contribute to the basic understanding of the central link between nociceptive afferent signals and cardiovascular regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAINSTEM GUSTATORY PROCESSING Principal Investigator & Institution: Smith, David V.; Professor; Anatomy and Neurobiology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 30-JUN-2003 Summary: (Adapted from investigator's abstract): Anatomical, electrophysiological and pharmacological data on gustatory and visceral pathways suggest several testable hypotheses about the functional organization of the nucleus of the solitary tract (NST). The PI's laboratory has shown that taste cells in the NST are driven by peripheral taste fibers via excitatory amino acids, that these cells are tonically inhibited by GABA and that taste-responsive cells in the NST are excited and sometimes inhibited by the neuropeptide, substance P. The current application will extend these findings by addressing three specific aims. First, the mechanisms of inhibition in the NST and its role in shaping the responsiveness of gustatory neurons will be further investigated. Initial experiments will determine if GABAB and glycine receptors contribute to inhibition in the NST and if inhibition sharpens the breadth of tuning of NST neurons to gustatory stimuli. Additional experiments will determine if there are differences in inhibitory control between gustator neurons that relay information to the parabrachial nuclei (relay neurons) and those that do not (nonrelay neurons). The second aim is to determine the influence of descending inputs from the gustatory neocortex and the central nucleus of the amygdala on NST taste neurons. Initial experiments will examine the hypothesis that descending inputs from the neocortex and amygdala produce excitatory and inhibitory modulation of NST cells. Subsequent experiments will test the hypotheses that the excitatory inputs are mediated by excitatory amin acids and the inhibitory inputs by inhibitory amino acids. The final set of experiments in this aim will evaluate the hypothesis that relay neurons are modulated differently by central inputs than nonrelay neurons. The final specific aim will address the question of modulation of NST taste responses by neuropeptides, and in particular, the apparent preferential excitation of NaCl-best neurons by substance P. The effects of met-enkephalin on NST taste neurons and the possible differential modulation of neuropeptide effects on relay and nonrelay neurons will also be examined. These in vivo experiments ar designed to reveal how the synaptic interactions in the NST and the connection to and from this nucleus control responses of NST neurons to gustatory inputs. These studies will provide important new information for our understanding of the functional organization of the central gustatory system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CA CHANNELS IN TRIGEMINAL NEUROPATHIC PLASTICITY & PAIN Principal Investigator & Institution: Westenbroek, Ruth E.; Pharmacology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 30-JUN-2004

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Summary: (adapted from applicant's abstract): Peripheral tissue damage or nerve injury to somatosensory neurons in rats results in functional and cytochemical changes in sensory neurons and pain behaviors that resemble clinical neuropathic states. The longterm objectives of our research are to understand the role of voltage-gated calcium channels in the peripheral and central mechanisms associated with neuropathic pain. The proposed studies offer several unique opportunities. First, the studies will examine the normal pattern of expression and localization of voltage-gated calcium channels in the trigeminal ganglion and in teeth. Second, changes in the expression of these channels will be assessed in two models of neuropathic pain. The first model is coronal pulp exposure, which leads to pulpal necrosis and chronic inflammation and the second model is unilateral inferior alveolar nerve crush. Use of these two models will allow comparisons to be made between tissue and nerve damage. Each experiment will also assess changes in calcium channels compared to terminal marker proteins (syntaxin and synaptotagmen) as well as several neuropeptides (substance P and calcitonin generelated peptide) at various post-operative time points. Our hypotheses are that discrete changes in calcium channels will occur and will differ for the two models. Behavior tests will allow us to determine whether or not those changes have behavioral correlates. The trigeminal system provides an ideal model system in which to investigate these changes since its somatotopic organization is well known and changes which are known to occur following lesions of the trigeminal system differ from those of injured segmental nerves. The studies outlined in this proposal will lead to a greater understanding of the changes in calcium channels that occur after trigeminal sensory nerve injury and will have important implications for future drug therapies for inflammatory and neuropathic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCITONIN GENE-RELATED PEPTIDE IN HYPERTENSION Principal Investigator & Institution: Dipette, Donald J.; Professor and Chair; Internal Medicine; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Recent data has demonstrated that sensory nerves have the capacity to act in an efferent manner. This efferent function is mediated by the release of neuropeptides, such as CGRP and substance P (SP). Despite the observation that CGRP and SP are potent vasodilators, their role in the long-term regulation of cardiovascular function and hypertension is unknown. Recent evidence, largely generated in our laboratory shows that; 1) neuronal expression and/or vascular reactivity to CGRP and SP is increased in experimental hypertension, 2) CGRP and SP receptor blockade significantly increases the BP in several models of experimental hypertension, 3) CGRP KO mice have higher basal BP, lower coronary flow, and greater ischemic cardiac injury; and 4) CGRP KO mice have greater cardiac and renal injury secondary to DOC-salt hypertension. These observations have led to a central hypothesis that states that the sensory nervous system, through the actions of CGRP and SP plays a major role in the long-term modulation of cardiovascular function and the pathophysiology of hypertension. To test this hypothesis, we will determine whether decreased CGRP or SP function (by studying CGRP KO and SP receptor (NK1) KO mice) alters the ability of the sensory nervous system to modulate BP in the absence or presence of hypertension induced by DOC-salt and subtotal-nephrectomy (SN)-salt. These mice will also be subjected to neuronal release of neuropeptides from sensory nerves by capsaicin. In vivo changes in BP in response to specific receptor antagonists of these peptides, systemic and regional hemodynamics (via microspheres), and cardiac

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Calcitonin

function (via Doppler echocardiography) will also be determined. In addition we will determine whether a- CGRP KO or NK-1 KO mice have reduced coronary flows and increased myocardial damage following ischemia/reperfusion injury. This will be accomplished in vitro by studying isolated-perfused hearts from a- CGRP KO mice and NK-1 KO mice. Finally, we will determine whether a-CGRP KO and NK-1 KO mice have greater cardiac and renal injury, independent of BP, secondary to DOC-salt hypertension. Studies investigating the mechanism (ie oxidative stress) of this enhanced tissue injury will also be performed. Taken together, these studies will use a novel experimental paradigm to define the role of the sensory nervous system, through CGRP and SP, in the long-term regulation of cardiovascular function, including the pathogenesis of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCITONIN IN PROSTATE GROWTH AND NEOPLASIA Principal Investigator & Institution: Shah, Girish V.; Pharmaceutical Sciences; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2002; Project Start 26-SEP-2001; Project End 31-AUG-2003 Summary: (Provided by the applicant) Cell-to Cell interactions are known to play a critical role in morphogenesis and pathogenesis of the prostate gland. Neuroendocrine (NE) cells secrete numerous peptide hormones which induce mitogenesis in proliferation-competent cells. Recent studies by the PI suggest that primary human prostate epithelial cells secrete immunoreactive calcitonin (CT-I) in culture, and its secretion from prostate carcinoma (PC)-derived cells is several-fold greater than that from the cells-derived from benign prostatic hypertrophy(BPH). In situ hybridization and immunohistochemistry studies of tumors have shown that 1) CT mRNA, CT-I and CT-R mRNA are localized in the basal layer of benign prostate gland. In contrast, CT mRNA, CT-I, CT-R mRNA and CT binding sites are localized in luminal layers of malignant prostate epithelium, and their expression increases with tumor progression. Poorly differentiated PC-3M cells and undifferentiated NRP-152 cells co-express CT and CT-R mRNAs and well-differentiated LnCaP cells express only CT-R. Exogenously added CT stimulates DNA synthesis of primary PC cells, LnCaP and PC-3M cells; and anti-sCT inhibits this growth. CT also inhibited TGF-b and TGF-b receptor immunoreactivity in prostate cells. Considered with the role of TGF-b in cell differentiation and apoptosis, it is conceivable that CT promotes tumor progression by arresting differentiation, and increasing the growth of transformed cells. Specific Aim 1 will test the effect of manipulation of CT and CT-R expression on proliferative, invasive and tumorigenic activities of prostate cancer cells. Specific Aim 2 will delineate mitogenic signaling pathway activated by CT in these cells. Specific Aim 3 will examine the effect of CT on transdifferentiation and TGF-b expression in these cell lines. The proposed studies will define the role for prostatic CT in regulation of growth and differentiation in malignant human prostate gland. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CALCITONIN RECEPTOR GENE EXPRESSION Principal Investigator & Institution: Goldring, Steven R.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 30-APR-2004 Summary: Our initial application proposed to study the mechanism of action and regulation of the calcitonin receptor (CTR) gene. Although the ultimate goal was to use

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this information to gain insights into the control of osteoclast differentiation and function, we have broadened the scope our studies to include investigation of the regulation and mechanism of action of the CTR in organs and tissues not directly involved in mineral ion homeostasis. We have established that the human CTR gene encodes multiple CTR isoforms that are functionally distinct and are expressed in a tissue- and cell-specific fashion. These observations have provided insights into the diversity of the biological activities of calcitonin (CT). In the competing renewal, we will continue to focus attention on the osteoclast CTR, but will also investigate the receptor in other CT-responsive tissues. The Aims are as follow: 1. Utilize the reverse transcriptase/polymerase chain reaction (RT-PCR) and cloning techniques to complete the sequencing and characterization of the structural properties of the human CTR isoforms. The corresponding genomic structure will be identified and the tissue and cellspecific distribution of the isoforms established using in situ hybridization, Northern blot analysis and RNase protection. 2. Complete the characterization of cells in specific bone lesions, e.g. Paget's disease of bone and other granulomatous diseases and tumors in which the phenotype of the giant cells and their relationship to osteoclasts is not well established. This will help to define the phenotypic relationship between bone resorbing cells in physiological and pathological remodeling and identify the structural features of the osteoclast-associated CTR. 3. Because the CTR family of receptors exhibit structural features that are different from other members of the G protein-coupled receptor superfamily, the structure/function relationships for these receptors are of particular interest. We propose to utilize the different CTR cDNAs presently available, as well as additional CTR isoforms that we have recently identified, to define the unique signaling properties and binding kinetics of the human CTR isoforms. 4. In the final Specific Aim, we propose to clone and characterize the human CTR gene and to define the specific and potentially unique regulatory sequences responsible for expression of the CTR in osteclasts and other CTR-expressing cells and tissues. Constructs of the CTR 5'-region containing the putative promoter sequences of the CTR gene will be linked to reporter gene(s) and screened for the capacity to induce CTR expression using transfection in human mononuclear cell lines or other cell types that constitutively express the CTR (e.g. kidney). This will define the structural basis of CTR gene regulation and permit identification of potentially unique factors that regulate the CTR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONS

CALCITONIN

REGULATION

OF

OSTEOCLAST

INTEGRIN

Principal Investigator & Institution: Horne, William C.; Research Scientist; Orthopedics and Rehabilitation; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-APR-2008 Summary: (provided by applicant): The importance of the cytoskeleton and integrin signaling in osteoclast (OC) function has been established by ourselves and others. Loss of proteins that connect integrin-dependent attachment structures (podosomes) and the cytoskeleton, such as Src and Pyk2, results in impaired bone resorption. The potent inhibition of OCs by calcitonin (CT) is also well known. CT induces a rapid cytoskeletal change, resulting in OC retraction and loss of motility. We previously showed that CT affects the activities and phosphorylation state of several proteins that associate with the cytoskeleton or cell attachment structures or are involved in integrin signaling. Furthermore, dephosphorylation of Pyk2 by CT and ionomycin suggest that CT may be activating tyrosine phosphatase-lB via calpain, implicating two proteins that play key

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roles in regulating cell motility. Finally, yeast two-hybrid screening with the C-terminal domain of the CTR also yielded cytoskeletal proteins, reinforcing the idea that regulation of cytoskeletal function may be an important function of the CTR. This proposal presents a specific innovative perspective on elucidating how CT inactivates bone resorption, asking if CT indeed affects integrin signaling and cytoskeletal integrity, thereby leading to alterations in OC adhesion and motility. The Specific Aims of this application are: (1) Characterize the effects of CT on podosome proteins (the Pyk2/Src/Cbl complex, paxiilin, Cas family members) in osteoclasts and the mechanisms involved in cross-talk between integrin signaling and CTR signaling. (2) Determine if the CTR-induced activation of calpain contributes to the modulation of cytoskeletal organization and cell adhesion and motility, identify the mechanisms by which it acts, and explore the functional role of some calpain-specific substrates, i.e., PTPIB and filamin; and (3) Characterize the interaction of the CTR with filamin, and determine how that interaction affects the CTR regulation of OC attachment and motility. Thus, this proposal can be expected to reveal as yet unappreciated features of the molecular mechanisms of osteoclast attachment and motility and bone resorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CAN OSTEOPOROSIS

PTH

REVERSE

GLUCOCORTICOID

INDUCED

Principal Investigator & Institution: Lane, Nancy E.; Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 22-FEB-1995; Project End 30-JUN-2004 Summary: (Adapted From Investigator's Abstract) Glucocorticoid- induced bone loss is the most common cause of drug-related osteoporosis. It is especially severe in patients over 50 years of age and in those women who are postmenopausal. The important antiinflammatory and immunosuppressive properties of this class of drugs have prompted their extensive use; however, side effects are many and bone loss resulting in vertebral fractures is the most incapacitating. Glucocorticoid excess produces bone loss by two primary mechanisms: (1) suppression of osteoblast function and (2) inhibition of intestinal calcium absorption leading to secondary hyperparathyroidism and increased bone resorption by osteoclasts. Attempts to treat glucocorticoid- induced osteoporosis include calcium, vitamin D3 replacement and anti-resorptive agents that include bisphosphonates, calcitonin and estrogen. All of these therapies seem to slow further bone loss but none have been able to increase bone mass. Recently, studies in vivo in humans and animals have shown that parathyroid hormone (PTH) administered intermittently in relatively low doses stimulates bone formation. This is in contrast to its well established ability to stimulate bone resorption when it is given in high doses continuously. The mechanisms of these paradoxical effects of PTH on bone are poorly understood, but recent studies in vitro suggest that the anabolic effects may be related to the ability of PTH to stimulate osteoblasts to produce insulin-like growth factor (IGF-I). The purpose of the proposed investigation is to determine if treatment with synthetic human parathyroid hormone fragment, 1-34, (hPTH1-34) will reverse glucocorticoidinduced osteoporosis in patients with rheumatic disease on chronic low dose glucocorticoid treatment. The osseous effects of PTH 1-34 will be monitored with conventional dual energy x- ray absorptiometry measurements of the spine, hip and forearm (mid- radius), quantitative computed tomography of the lumbar spine, and other outcome measurements which will include serial measurements of bone biochemical markers (including serum alkaline phosphatase, osteocalcin, urine calcium, and pyridinoline cross- links).

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER SUPPRESSION BY THE RETINOBLASTOMA GENE Principal Investigator & Institution: Lee, Wen-Hwa K.; Donald Bren Professor; Molecular Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 01-MAY-1992; Project End 31-AUG-2003 Summary: We have previously demonstrated the potential of RB-mediated tumor suppression. Direct test of the hypothesis that RB gene therapy is effective in the context of the whole organism is hindered by the lack of suitable animal models that faithfully mimic human RB-deficient cancers. In particular, RB plus/minus mice die prematurely due to brainstem compression by melanotroph tumors. Such tumors are extremely rare in humans. To resolve this difficulty and to explore the efficacy of RB therapy, we intend to generate mouse models that closely parallel human cancer by refining current model systems and by creating new ones. Three specific aims are proposed: Aim 1 is to modify the spectrum of tumors that spontaneously develop in RB plus/minus mice by expressing an RB transgene under the control of the proopiomelanocortin and/or calcitonin promoters that are specific, respectively, for the pituitary melanotroph and thyroid C-cell lineages. Prevention of the rapidly progressing melanotroph or C-cell neoplasia will extend the life span of the mice, thus permitting a complete development of other tumors, including hematogenous metastasis to lungs and liver, which are more relevant to human diseases. Aim 2 is to test the hypothesis that targeted homozygous deletion of RB in a temporal, spatial, and cell-type specific manner will result in nonneuroendocrine neoplasia that mimic human cancers. Toward this end, novel models will be generated using Cre-loxP regulatory systems. Aim 3 is to test the hypothesis that the expression of RB abrogates progression and metastasis of RB-deficient tumors. Clinically feasible approaches for RB gene therapy will be applied to the animal models developed in Aims 1 and 2. We expect that the proposed studies will further substantiate the general theory of tumor suppression in immunocompetent animals. Thus, firm grounds for clinical trials on a significant subset of advanced human cancers will be established. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANNABINOID MODULATION OF HYPERALGESIA Principal Investigator & Institution: Simone, Donald A.; Associate Professor; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 03-FEB-2000; Project End 31-JAN-2005 Summary: (Adapted from the Investigator's Abstract) Persistent pain and cutaneous hyperalgesia are associated with many painful syndromes. Traditional pain management approaches, such as with narcotics, are problematic due to their adverse side effects such as tolerance and addition. Analgesic properties of cannabinoid drugs have been acknowledged for many years but it is only recently that the underlying neural mechanisms are being elucidated. Although cannabinoids have been traditionally believed to produce their antinociceptive properties through actions in the central nervous system, recent evidence suggests that cannabinoids may produce antinociception peripherally. Moreover, low doses of cannabinoids may be very effective in relieving hyperalgesia. The proposed studies will investigate the peripheral neural mechanisms that contribute to cannabinoid-mediated antinociception. Our preliminary data suggest that 1) cannabinoid receptors are located on dorsal root

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Calcitonin

ganglion (DRG) neurons that contain calcitonin gene-related peptide (CGRP); 2) intraplantar and intrathecal injection of cannabinoids prevent the development of hyperalgesia produced by capsaicin; 3) cannabinoids decrease evoked release of GCRP from cultured DRG neurons. To further investigate peripheral mechanisms of cannabinoid antinociception, we propose: to determine antihyperalgesic properties of intarplantar and intrathecal cannabinoids using the capsaicin and carrageenan models of inflammation (Aim 1); to determine whether cannabinoids reduce sensitization of cutaneous nociceptors produced by capsaicin and carrageenan (Aim 2); and to determine whether cannabinoids decrease transmitter release from primary afferent fibers in vitro and in vivo, and investigate underlying mechanisms. These studies will provide new information on the mechanisms by which cannabinoids produce antinociception. Moreover, results will have direct clinical significance if cannabinoids attenuate hyperalgesia through peripheral mechanisms. Peripheral cannabinoids may be very effective for managing certain chronic pains without undesirable side effects associated with traditional therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CAPSAICIN INSENSITIVE NOCICEPTORS OF THE DRG Principal Investigator & Institution: Cooper, Brian Y.; Associate Professor; Oral and Maxillofacial Surgery; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 30-JUN-2005 Summary: The development and maintenance of chronic inflammatory and neuropathic pain are often associated with functional changes in the excitability of peripheral afferents. Electrophysiological recordings on dissociated cells offer the greatest opportunity to study the mechanisms responsible for events that lead to changes in excitability. However, specific nociceptive populations in the DRG are not readily identifiable in vitro. Capsaicin sensitivity can broadly identify heat sensitive nociceptors but there is no means to readily identify subpopulation of capsaicin sensitive or capsaicin insensitive (CI) nociceptive populations of the DRG. In vivo, it has been shown that afterhyperpolarization duration (AHP) can distinguish nociceptive subpopulations from non-nociceptive populations. In our proposed investigations we will determine whether AHP distributions, observed in vivo, are maintained in vitro, and we will specifically examine and contrast the properties of CI cells with capsaicin insensitive groups with different AHPs. The experiments described we will use whole cell patch recordings on adult dissociated DRG cells. The studies have the following goals: 1) Characterization and modulation of proton activated currents in CI cells, including: an ASIC/DRASIC form of proton activated current and a TASK-like (TASK-1) current; 2) An examination of the reactivity of CI cells to heat and cold; 3) Determination of the histochemical phenotype of CI cells (IB4, SP, CGRP); and 4) To contrast the electrophysiological and immunohistochemical properties of CI and capsaicin sensitive cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOPULMONARY SURGERY RESEARCH Principal Investigator & Institution: Hyman, Albert L.; Pharmacology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 20-JUL-2000; Project End 30-JUN-2004 Summary: The long-term objective of the research proposed in this application is to improve the current understanding of regulation of the pulmonary circulation by

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humoral factors, including vasoactive peptides. Calcitonin gene-related peptide (CGRP) is an endogenous lung peptide which has been shown to have potent vasodilator activity. It has been hypothesized that CRGP may play a role in the regulation of the pulmonary circulation and that blockade of CGRP receptors exacerbates the increase in pulmonary arterial pressure in chronically hypoxic rats whereas CGRP infusion has a beneficial effect in treating pulmonary hypertension. These observations suggest that strategies that increase lung CGRP levels may be useful in the treatment of pulmonary hypertensive disorders. The transfer of genes that code for the production of vasoactive peptides represents a new potential strategy for the treatment of cardiovascular diseases. It has been shown that gene transfer to the lung can decrease pulmonary vascular resistance and responses, suggesting that gene transfer technology may be applicable to the treatment of pulmonary hypertensive disorders. The investigators therefore hypothesize that adenovirally-mediated transfer of the gene coding for preproCGRP (ADRSVCGRP) may reduce pulmonary vascular resistance and responses to vasoconstrictor agents and may have a beneficial action in a model of pulmonary hypertension. In recent studies they have been able to show that adenovirally-mediated transfer of prepro CGRP increases lung CGRP levels, alters vascular responses, and has a beneficial effect in a model of hypoxia-induced pulmonary hypertension in the mouse. The experiments proposed in this revised application will determine if in vivo delivery of prepro CGRP will alter pulmonary vascular resistance and responses 3, 5, 7, 14, and 21 days after transfection with ADRSVCGRP. The effects of transfection with ADRVSCGRP will be compared in wild type control mice and in CGRP knockout mice. The studies with the CGRP knockout mice will determine if CGRP is playing a role in regulating baseline tone and responses in the pulmonary vascular bed of the mouse. To further test the hypothesis that CGRP has a modulatory role in the response to hypoxia, the experiments in the A2 version of the grant will test the hypothesis that CGRP has a beneficial role in the response to hypoxia by comparing responses to hypobaric hypoxia in wild type control and CGRP knockout mice. It is anticipated that the results of these studies will provide new information on the potential use of in vivo adenovirallymediated transfer of the gene coding for prepro CGRP in the treatment of, pulmonary hypertensive disorders which are managed with vasodilator therapy and lung transplantation but are often fatal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR BASIS OF CRANIOFACIAL BONE DISORDERS Principal Investigator & Institution: Osdoby, Philip A.; Professor; Biology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: Normal bone development and remodeling require complex humoral, cellcell, and cell-matrix interactions. The integration of humoral and local signals is necessary to permit proper development, maintain mineral homeostasis, insure mechanical strength, and support haematopoeisis. There is now good evidence that osteoblasts can orchestrate osteoclast development and modulate osteoclast activity via paracrine signals. Information is just beginning to emerge that osteoclasts themselves synthesize and release factors that may influence bone remodeling. We therefore hypothesize that osteoclast-derived signals may function as autocrine effectors of osteoclast development and activity and therefore influence normal and pathological osteoclastogenesis and osteoclast-mediated bone resorption. We have shown that osteoclasts produce small proinflammatory molecules known as chemokines, such as IL8 and GRO alpha and that such molecules can act to modulate osteoclast precursor

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Calcitonin

recruitment, development, and activity. Therefore, to further investigate and define osteoclast autocrine regulation we propose the following specific aims: 1) Identify a profile of chemokines produced by human and mouse OC and determine which exhibit autocrine effects on OC function (bone resorption, motility, free radical production, TRAP, cathepsin K, and carbonic anhydrase II expression). The regulation of this subset of chemokines by select known modulators of OC function will be analyzed. Included here will be studies employing selective chemokine and chemokine receptor antagonists, chemokine neutralizing antibodies, and mouse OC-like cells formed in vitro from bone marrow obtained from IL-8 receptor knockout mice. 2) Identify and characterize the profile of chemokine receptors expressed on OC as a function of OC physiology, and pathophysiology. As part of this aim we will begin to elucidate the intracellular signal transduction pathways involved in chemokine modulation of OC activity. 3) Examine the potential role of chemokines in OC precursor recruitment and differentiation in vitro, in vivo, and in ovo. 4. Examine spatial and temporal aspects of chemokine and chemokine receptor expression in normal and pathological bone tissue by in situ hybridization and immunohistochemistry. Included here are mouse IL-8 receptor knockout studies. All of the above studies will use a combination of in vivo and in vitro approaches, and model systems including the mouse calvarial injection model for histomorphometric studies, human tissue sections for in situ hybridization and immunohistochemical analysis, isolated human and avian Ocs, human Oc-like cells, the mouse Oc-like cell developmental model, and cells obtained from an IL-8 receptor knockout mouse. Oc- chemokine production, mRNA steady state levels and regulation will be assessed by RT-PCP, RNAse protection assay, chemokine ELISA, and in situ hybridization techniques. Osteoclast development and activity will be evaluated based on functional, biochemical and molecular markers of the osteoclast phenotype, including bone resorption, osteoclast antigen expression tartarate-resistant acid phosphatase activity, and calcitonin receptor levels. Such studies are anticipated to reveal new aspects of normal bone remodeling mechanisms such as tooth eruption and have potential to lend insight into skeletal pathologies such as periodontal disease, implant loosening, osteoarthritis, other inflammatory skeletal disorders, and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR CALCIUM TRANSPORT IN URINARY EPITHELIA Principal Investigator & Institution: Friedman, Peter A.; Professor; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-MAR-2003 Summary: The long-term objective of our work is directed toward a complete understanding of the cellular mechanisms and regulation of calcium transport by renal tubular epithelial cells. Although most calcium absorption proceeds in proximal tubules, distal tubules are the site of the physiological regulation of calcium transport by parathyroid hormone (PTH), calcitonin and vitamin D3. The specific aims of the present proposal are to: 1) characterize the mechanism of calcium entry across apical plasma membranes of distal convoluted tubule (DCT) cells; 2) evaluate the participation and regulation of Na+/Ca2+ exchange in mediating calcium efflux; and, 3) define the signaling pathways activated by PTH and calcitonin in DCT cells, and to examine the coordinate regulation of PTH-dependent calcium transport by 1,25(OH)2 vitamin D3 and estradiol. We identified and partially characterized a novel calcium channel that mediates calcium entry. To acquire additional information about these channels we will: 1) characterize the properties of these channels with regard to their ion selectivity,

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pharmacologic sensitivity and voltage- dependence; 2) determine the regulation of these calcium channels by protein kinases; 3) define the participation of G-proteins in regulating calcium entry channels; and, 4) identify and clone calcium channel transcripts. Extrusion of calcium across basolateral plasma membranes of distal tubules is mediated by Na+/Ca2+ exchange and by /ca2+-ATPase. Pilot studies suggest that Na+/Ca2+ exchange is the dominant efflux mechanism in DCT cells. We will: 1) Test the hypothesis that thiazide diuretics can inhibit Na+/Ca2+ exchange; and 2) Characterize the stimulatory effects of PTH on Na+/Ca2+ exchange. Calcium transport in distal nephrons is regulated by PTH, calcitonin and 1,25(OH)2 vitamin D3. The following studies will evaluate the mechanism mediating the hormonal regulation of calcium transport in DCT cells. The goals of these experiments are to: 1) Characterize the signaling pathways with particular regard to the phospholipases responsible for activating PKA and PKC and characterize the temporal sequence in which PKA and PKC are activated. We will test the hypothesis that PTH and calcitonin activate PKC via phospholipase D. 2) Identify the mechanism by which PTH activates C1- channels, a primary event in membrane hyperpolarization and stimulation of calcium transport in DCT cells. We will test the hypothesis that these chloride channels are regulated by the PKA limb of the PTH-activated signaling pathway. 3) Examine the regulation of vitamin D3 and estradiol accelerate PTH dependent calcium transport by up-regulating PTH receptor expression. The specific aims will be achieved by applying single cell fluorescence, patch clamp, tracer flux measurements, biochemical and molecular techniques to a DCT cell line that we developed, which expresses an appropriate phenotype. In selected studies, primary cell cultures of proximal or distal tubule cells will be used to verify results in transformed cells or as controls. All procedures are established in our lab. Results from the proposed experiments will provide new information on the mechanism and regulation of calcium transport in the kidney under normal conditions, but also in calcium-wasting syndromes including hyperparathyroidism, renal failure, osteoporosis and malignancy- associated hypercalcemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR ELECTROPHYSIOLOGY OF VASCULATURES IN INNER EAR Principal Investigator & Institution: Jiang, Zhi-Gen; Otolaryngology Head & Neck Surgery; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Strong evidence suggests that blood circulation disturbances contribute to hearing losses in loud sound induced trauma, aging, Meniere's disease, ototoxic drugs and some forms of sudden deafness. To understand and treat these hearing conditions, knowledge of inner ear vascular physiology is a prerequisite. Little is known about the regulating mechanisms of cochlear vessels. The long-term objective of this proposal is to increase our understanding of the cellular and subcellular physiology of these vessels and how they differ from vessels of other vascular beds. Specifically, this proposal aims to: 1) determine the membrane channels and mechanisms that cause two distinct levels of resting potentials in smooth muscle cells of cochlear spiral modiolar artery (SMA); 2) determine the actions of candidate neurotransmitters and neuropeptides on the ion channels, the responsible receptors and the intracellular signaling pathways; 3) identify the nature of neuromuscular transmission in the SMA; 4) determine how the contractile and cellular properties of the SMA differ from small arteries of the brain and intestine. These goals will be achieved

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Calcitonin

by experiments using conventional and whole-cell current- and voltage-clamp recording methods on in vitro smooth muscle cells in segments of the SMA, as well as single-cell labeling and vasotone measurements. Comparative studies of contractile and membrane properties between the SMA and the arterioles from the brain and intestine will be conducted to evaluate the heterogeneity among the vessel beds. With these studies, we expect to describe the unique contractile and membrane properties, key ionchannel features, functional neuromuscular transmitters and related receptors, and mechanisms by which these functioning properties are regulated in the SMA; in addition, we expect to understand how these mechanisms of the SMA differ from those of other vessel beds. The knowledge obtained will improve our understanding of how cochlear blood flow is uniquely regulated, thus contributing to the understanding of circulation-related hearing losses and leading to prevention and treatment of these hearing conditions. The acquired knowledge should also be of significance in broad areas of cardiovascular physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CGRP, DYSFUNCTION

NO,

AND

SEPSIS

INDUCED

MICROVASCULAR

Principal Investigator & Institution: Arden, Warwick A.; Veterinary Clinical Medicine; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 29-SEP-2003 Summary: (Adapted from the applicant's abstract) The broad and long-term objectives of this proposal are to define the mechanisms of peripheral vascular and microvascular dysfunction in trauma, ischemia, and circulatory shock. The investigator focuses on the role of the potent vasoactive neuropeptide calcitonin gene-related peptide (CGRP) in resistant artery dysfunction in endotoxin-induced circulatory shock. The fundamental hypothesis to be addressed is that in vivo exposure of the vasculature to LPS results in release of CGRP from sensory nerve terminals, enervating the vasculature and that CGRP in combination with enhanced vascular NO production contributes to the observed vasodilatation and diminished resistance vascular responsiveness. This investigation has two principal inter-related objectives: 1) to further define the cellular mechanisms of action of CGRP on resistance artery smooth muscle cell and specifically define interactions between CGRP and NO; 2) to establish whether a cause and effect relationship exists between augmented perivascular CGRP release during septic shock and progressive microvascular dysfunction. These hypotheses and objectives will be subjected to a rigorous examination using a combination of methodologies including systemic hemodynamic recordings in anesthetized rats, in vivo video microscopy of the cremaster muscle microcirculation, assessment of the functional state of isolated cannulated cremaster arterioles, and digital fluorescence ratio imaging of vascular smooth muscle calcium responses in intact cremaster arterioles. These techniques will allow the investigator to determine whether changes in vascular responses correlate with changes in intracellular calcium-mediated directly or indirectly by CGRP and/or NO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF THE NEUROINFLAMMATORY CGRP RECEPTOR Principal Investigator & Institution: Porter, James E.; University of North Dakota 264 Centennial Drive Grand Forks, Nd 58202

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Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term goal for this research is the development of alternate therapeutic strategies that prevent the inflammatory changes associated with neurodegeneration. The immediate goal of this project is to characterize the molecular mechanisms of calcitonin gene-related peptide (CGRP) receptor activation that initiates signaling networks leading to increased production of proinflammatory compounds. The neuroactive peptide, CGRP is released from peripheral and central nerve terminals upon sensory activation caused by damaged tissue. CGRP potently initiates vascular changes that are a hallmark of neurogenic inflammation. However, CGRP released from sensory nerve endings are suggested to initiate more than just a direct vasodilator effect on vascular smooth muscle during an inflammatory event. Increasing evidence suggests that neurogenic inflammation orchestrated in part by microglial cells, is a major pathophysiological component of neurodegenerative disease. An increased expression of cyclooxygenase-2 (COX-2) by CGRP has been shown in vitro using the human microglia progenitor cell line, THP-1. Selective generation of prostaglandins by COX-2 has been demonstrated to cause a hypersensitive response in neurons. Moreover, chronic induction of inflammatory cytokines (e.g., TNFa) has been implicated in the pathophysiology of neurodegeneration. Conversely, application of CGRP to LPS activated THP-1 cells inhibits the production of TNF-a suggesting an anti-inflammatory role for CGRP. These opposing observations implicate CGRP as an important modulator of selective neuroinflammatory signaling possibly initiated through distinct receptor subtypes. However, the bioavailability and protease sensitivity of receptor ligands limits exploration and characterization of CGRP effects in vivo. This research is guided by the hypothesis that detailed insights, into the molecular mechanisms of ligand dependent receptor signaling will provide information for the rational development of CGRP receptor mediated therapeutics. Aim one will describe the CGRP mediated signal transduction pathways that lead to production of inflammatory compounds. Aim two will characterize the structure-function relationships of CGRP receptor activation from which a working molecular model of the receptor can be developed. Aim three will challenge this molecular model using altered CGRP ligands to authenticate binding contacts and to categorize functions of specific CGRP receptor amino acids. Completion of these specific aims will further our understanding of molecular signaling mechanisms initiated by CGRP receptor activation that participate in selective inflammatory responses implicated in the pathophysiology of neurodegenerative diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--SYNTHETIC CORE FACILITY Principal Investigator & Institution: Hruby, Victor J.; Regents Professor; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The major goals of the Synthetic Core Facility, which was renovated by the University of Arizona specifically for this Program Project Grant, are to synthesize, purify and perform necessary analytical work on 100 mg to 10 g quantities of bioactive peptides, novel amino acids and peptide mimetics that are needed for the extensive biochemical, pharmacological, biophysical and biological studies that are part of this Program Project Grant. Of specific importance will be the development of proper asymmetric synthetic methodology, other synthetic methods, purification methods, and analytical methodologies that are needed for the various research projects and protocols. The Specific Aims are: 1) To prepare 1 g to 5 g quantities of biphalin, substance P

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Calcitonin

antagonists, and CGRP fragment antagonists for biological studies. 2) To develop and establish all necessary synthetic methodologies, purification protocols, and analytical procedures that are needed for preparing any ligands that are needed by investigators in the Program Project Grant. 3) To prepare by asymmetric synthesis quantities (1 g to 10 g) of novel amino acids and peptide mimetics that are needed for the preparation of ligands for the Program Project. 4) To prepare up to gram quantities of potent bioactive peptides, glycopeptides, peptidomimetics, and peptide conjugates that will be needed for biological and/or biophysical studies, and 5) To prepare any other peptides, peptide mimetics or other ligands that are needed by investigators in this Program Project Grant for further biological and biophysical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCITONIN

DEGRADABLE

HYDROGELS

FOR

ORAL

DELIVERY

OF

Principal Investigator & Institution: Kopecek, Jindrich N.; Distinguished Professor and Chairman; Pharmaceutics/Pharmaceutl Chem; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-DEC-2003 Summary: Osteoporosis is a major cause of morbidity and mortality in postmenopausal women. In an United States, an estimated 13% to 18% of women have osteoporosis. The financial burden is substantial, with an estimated yearly cost of $10 billion in the United States alone. The lifetime risk for osteoporotic fractures in Caucasian women 50 years of age is about 30-40%. Between 13-19% of postmenopausal women who have a hip fracture die within the following year. We propose to use a combination of human calcitonin (hCT) and polymer-bound cathepsin K inhibitor (CKI) as a novel treatment of osteoporosis. The rationales for hCT use in osteoporosis therapy are the stimulation of osteoblasts, specific inhibition of bone resorption by osteoclasts, and prevention of fusion of osteoclast precursors. Clinical studies have shown that a significant gain in bone mass can be achieved by administration of CT. An osteoclast-specific cysteine proteinase, cathepsin K, plays a specialized role in the resorption of organic bone matrix. It was shown that cathepsin K inhibitors (CKI) are effective in reducing osteoclastmediated bone resorption both in vitro and in vivo. The binding of CKI to a macromolecular carrier will change the mechanism of CKI internalization by osteoclasts from diffusion (CKI) to endocytosis (polymer-bound CKI). Consequently, the polymerbound CKI will localize in the sealed zones of the ruffled border (resorption lacuna), i.e. exactly in the place where bone resorption mediated by cathepsin K occurs. We hypothesize that the combination of the actions of hCT and CKI will produce cures which cannot be achieved with hCT or CKI alone. Establishing an oral delivery system for hCT and CKI is of great importance because it is expected that for treatment of chronic disorders in non-life threatening situations, such as postmenopausal osteoporosis, parenteral administration will lead to poor patient compliance and thus restricted utility. hCT is an excellent candidate for the development of alternate delivery routes due to its size and wide therapeutic index. The size of CKIs will be modified with semitelechelic poly[(N-2- hydroxypropyl)methacrylamide] (ST-PHPMA) chains to achieve comparable hydrodynamic volumes of CT and of the ST-PHPMA-CK conjugate, which will simplify the design of the delivery system and have beneficial biological consequences. Novel hydrogels were designed in the first period of research; they contain azoaromatic crosslinks, susceptible to degradation by bacterial enzymes in the colon and hydrolyzable side-chains, which control the kinetics of swelling in the small intestine. The structure and properties of biodegradable hydrogels will be optimized. A

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new macromolecular CKI will be synthesized. Its efficacy will be evaluated in an osteoclast culture in vitro as well as on an animal model in vivo. The effect of combination therapy will be compared with individual therapies. The bioavailability of hCT and ST-PHPMA-CKI conjugates in rabbits and dogs using hydrogel based delivery devices and a penetration enhancer will be determined. The efficacy and biocompatibility of an hCT and CKI delivery device in an animal model of osteoporosis will be studied. Based on in vivo animal data criteria will be studied. Based on in vivo animal data criteria will be established for the design of an oral hCT and CKI delivery system for the treatment of postmenopausal osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DESENSITIZATION AND DOWN REGULATION OF CALCIUM RECEPTORS Principal Investigator & Institution: Shoback, Dolores M.; Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 31-OCT-2004 Summary: CaRs sense changes in the [Ca2+] and activate downstream effectors. Evidence indicates that the expression of adequate numbers of CaRs is necessary for precise Ca2+-sensing in tissues like the parathyroid and kidney. Patients heterozygous for 1 abnormal CaR gene have mild hypercalcemia and hypocalciuria, while homozygotes are severely affected with life-threatening hypercalcemia and hyperparathyroidism supporting a gene-dosage effect. CaR protein expression is reduced in parathyroid glands from patients with primary hyperparathyroidism. Either excessive receptor degradation or reduced biosynthesis could explain this finding. Desensitization and downregulation of receptors are mechanisms for regulating target cell responses to agonists. Internalization often accompanies these events and serves to remove active signaling receptors from the cell surface. We found that treating parathyroid cells and Xenopus oocytes expressing CaR cRNA with protein kinase C agonists desensitizes these cells to subsequent challenge with high [Ca2+] -- in terms of parathyroid hormone (PTH) release and high [Ca2+] -regulated signal transduction. We will test the hypothesis that CaR agonists promote receptor desensitization and internalization; that sequences in the CaR's carboxy-terminal tail are involved in these pathways; and that levels of CaR protein expression are critical in determining cellular responses to [Ca2+]. Three aims will address the hypothesis. (1) We will determine whether CaR agonists promote desensitization and internalization of CaRs by assessing PTH secretion and signaling responses after treating cells with agonists and by quantifying internalization of CaRs using a surface biotinylation assay. Intracellular trafficking of CaRs will be followed in HEK-293 cells expressing green fluorescent protein-tagged CaRs by confocal microscopy. (2) We will assess the role of the CaR's Cterminal tail in desensitization and internalization using tail-truncation mutants and site-directed mutagenesis to identify putative positive or negative endocytic motifs. The role of intact signaling pathways in internalization will be addressed. (3) Internalizationdefective mutants will be expressed in fibroblasts and calcitonin-secreting cells and the effects on high (Ca2+] -regulated calcitonin secretion and cell proliferation will be tested. Our studies should provide insights into mechanisms underlying CaR responsiveness in secretion and growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHIBITORS

DEVELOPMENT

OF

TOPICAL

NEUROINFLAMMATORY

Principal Investigator & Institution: Sachdeva, Mandip S.; Professor; Division of Basic Pharmaceutical Scis; Florida Agricultural and Mechanical Univ 400 Foote Hilyer Administration Center Tallahassee, Fl 32307 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-MAY-2006 Summary: (taken from the application?s abstract): There is increasing evidence that through the release of neuropeptides the cutaneous sensory neurological system plays an important role in the pathogenesis of inflammatory skin disorders. Certain skin diseases such as psoriasis, contact dermatitis and atopic dermatitis may have a significant neurogenic component. The hypothesis to be tested by the proposed research is that certain topically-delivered neuromodulators will prove to be effective therapeutic agents for the treatment of a wide range of inflammatory skin diseases. Thus, the longterm objective is to develop topical agents with novel anti-inflammatory activities. Specifically, agents such as calcitonin-gene-related peptide (CGRP), alpha-melanocyte stimulating hormone (alpha-MSH), substance P receptor (SPR) antagonists such as spantide II (peptide molecule) and SR 140333 (a non-peptide), which have antiinflammation properties or inhibit various aspects of neurogenic inflammation will be utilized as topical compounds to treat well-defined models of cutaneous inflammation. The specific aims of this research proposal are: Aim #1) The preparation of topical formulations (gels, creams and lotions) of neuromodulatory agents using prototype topical vehicles and screening these formulations for antiinflammatory effects in an animal model of cutaneous inflammation. Studies designed under this aim include formulation of topical agents (gels, creams and lotions) of neuromodulators and screening of these formulations for anti-inflammatory activity in a murine contact hypersensitivity model; Aim #2) The development, evaluation and optimization of various topical neuromodulatory formulations, which have shown promise in Specific Aim #1) Development of topical formulations includes compatibility and stability of neuromodulators in topical vehicles. The stable formulations will be optimized by ex vivo skin absorption and distribution studies in hairless mouse skin using Franz diffusion cells and; Aim #3) To determine the effectiveness of topically applied neuromodulatory agents to inhibit cutaneous inflammation. This will be accomplished by utilizing well-defined murine models of cutaneous inflammation such as allergic contact dermatitis, irritant contact dermatitis and acute photodermatitis. The effect of topical formulations on cutaneous inflammation will be compared with that of intravenous administration of these peptides. The results of these studies are intended to provide the basic information required for the development of novel skin disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIAGNOSTIC CHALLENGES IN IC (AND MALE CPPS) Principal Investigator & Institution: Dimitrakov, Jordan D.; Queen's University at Kingston Kingston K7l 3N6, Canada Kingston, On Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The etiology and pathogenesis of interstitial cystitis (IC) and its related condition in men, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has remained elusive. This has hampered development of mechanistic treatment strategies for these common, chronic and distressing medical conditions. We believe that IC and perhaps CP/CPPS are a spectrum of complex but inter-related genetic and acquired diseases resulting from the interaction of several genes regulating

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immune/inflammatory and neurogenic parameters and environmental factors/circumstances or exposure, culminating in the combination of pain, frequency, urgency and sexual specific symptoms. New research has delineated the dynamic and powerful association of the immune and neurogenic system in pain activation. An immune-modulated neurogenic model of IC illuminating the action of immune derived substances and pain related substances might be important in discovering the determinants of pain, voiding dysfunction and gender specific sexual problems. This inter-related dynamic model of IC disease pathogenesis could be explored for potential avenues leading to novel diagnostic and treatment strategies. We plan to identify and evaluate the sensitivity and specificity of several novel nerve and inflammation related markers in the diagnosis and follow up of IC (and CP/CPPS). By correlating the levels of urine immune and pain related substances to disease mechanisms, severity and progression, we may be able to create a human disease specific model for diagnosis and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISPROPORTIONATE DWARFISM IN THE MOUSE MUTANT RHIZOMELIA Principal Investigator & Institution: Bergstrom, David E.; Research Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The vertebrate skeleton is an important anatomical system providing structural support for a motile body, protection for vital internal organs, and a hospitable environment for the hematopoetic system. The set of processes by which these bony structures develop is known as skeletal morphogenesis. Defects in skeletal morphogenesis are manifested as osteochondrodysplasias, a large group of statural disorders affecting more than 1 person in 5000 in the human population and observed in nearly one percent of perinatal deaths. These conditions range in seriousness from relatively mild to severe. The more mild conditions may affect such quality of life issues as stature, mobility, activity and sexuality. Moderate conditions may include neurological and orthopedic complications. The most severe cases can result in perinatal lethality. The purpose of this proposal is to study the molecular genetic basis of disproportionate dwarfism seen in mice carrying the rhizomelia (rzm) mutation, rzm is a novel, transgene-induced mutation that causes skeletal growth aberrations in both the axial and appendicular skeleton including shortened humeri and femora, narrowed thoracic cavity, shortened tail, and craniofacial defects. The specific aims of this proposal are focused at understanding the molecular genetic basis of the rzm phenotype. First, experiments will be performed to determine whether the rzm phenotype results from a gain-of-function (GoF) or loss-of-function (LoF) mechanism. Using an embryonic stem (ES) cell-based approach, a deletion (delta) will be constructed which spans the rzm locus. After creating deletion-bearing mice, genetic crosses will be used to place rzm in trans to the encompassing deletion (rzm/A). Assessment of the resulting phenotype should allow one to discriminate between the GoF and LoF hypotheses. Second, molecular studies will be performed to clone the genomic region flanking the transgene insertion and to assess the expression of linked candidate genes and other critical players implicated in skeletal morphogenesis. The ultimate goal of this and subsequent studies is to use this unique animal and the molecular tag provided by the transgene itself as a means of entry into the network of structural and regulatory genes that coordinate skeletal development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Calcitonin

Project Title: DYNORPHIN MODULATES CGRP RELEASE VIA PKC Principal Investigator & Institution: Wang, Zaijie; Pharmaceutics/Pharmacodynamics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's Abstract) Dynorphin plays an important functional role in many aspects of neuropathic pain. This application aims to further explore the link between dynorphin and neuropathic pain by studying the cellular mechanism for the action of the non-opioid peptide, des-Tyr-dynorphin A on activation of spinal protein kinase C (PKC) and release of excitatory transmitters from primary afferent fibers. Considerable evidence has linked PKC with the abnormal pain seen following nerve injury. Both dynorphin and activation of PKC were found to augment capsaicin-evoked calcitonin gene-related peptide (CGRP) release, characteristic of activation of primary afferent fibers. It is possible therefore that dynorphin and PKC are part of a spinal signaling pathway that promotes sensory hyperexcitability. For these reasons, this application will test the hypothesis that (a) dynorphin potentiates the activity of PKC, or specific isoforms of PKC, via a non-opioid mechanism; and (b) that dynorphin facilitates capsaicin-evoked CGRP release through PKC activation. To test this hypothesis, Aim l will examine the modulation of basal and stimulated-CGRP release by dynorphin A (117), or by its des-Tyr fragments which do not interact with opioid receptors. These experiments will be done using a spinal cord minced preparation as well as dorsal root ganglion cells in culture. The structure-activity relationship for dynorphin and its fragments will also be determined in these experiments. The second aim will establish the modulation of PKC and its isozymes by dynorphin A (2-17) using both in vitro and in vivo approaches. Temporal and anatomical correlation between activation of PKC by dynorphin in vivo will be established with development of hyperalgesia. Aim 3 will examine whether blockade of PKC, or relevant isoform(s), will prevent dynorphin A (217) enhancement of capsaicin-evoked CGRP release in spinal cord preparations. Specific inhibitors of PKC will be used in conjunction with antisense oligodeoxynucleotides (ODN) to "knock-down" expression of selective isoforms. Appropriate controls such as mismatch ODN, time-related actions and reversibility, and the quantitative analysis of the target proteins will be emphasized. Finally, the knockdown of relevant PKC isoforms will be tested against dynorphin A (2-17)-induced pain in vivo. These studies will elucidate the underlying cellular mechanisms for the role of dynorphin in pathological pain states and may offer insight into rational approaches to manage such pain. The University of Arizona Health Science Center provides a unique environment and opportunity for the candidate to broaden his background in the area of pain pharmacology under the guidance of Drs. Frank Porreca and Josephine Lai. This award is consistent with the long-term career goal of the candidate to become an independent investigator contributing to the basic research of pain and opioid pharmacology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF O2 RADICALS AND PERIVASCULAR NERVES IN TRAUMA Principal Investigator & Institution: Dewitt, Douglas S.; Professor; Anesthesiology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-JAN-2004 Summary: (Verbatim from the Applicant's Abstract) Traumatic brain injury (TBI) increases cerebral vascular resistance, damages cerebral vascular endothelial cells and the blood brain barrier and reduces cerebral vasodilatory responses to hypotension,

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hypoxia and hemodilution. Our overall hypothesis is that traumatic brain injury increases superoxide anion radicals which react with increased NO to form OONO-, impairing the function of cerebral vascular smooth muscle and perivascular nerves. Aim 1 is to determine the association between NO, O2-, and CBF decreases after traumatic brain injury. NO, superoxide, and CBF will be measured in rats after moderate traumatic brain injury. Studies will be done to see if arginine supplementation restores CBF despite increases in O2- production. Immunohistochemical staining for nitrotyrosine will be used to determine if TBI and L-arginine treatment increases OONO- production. Aim 2 is to determine if traumatic brain injury reduces the activity of eNOS and/or increases the potentially damaging iNOS and nNOS isoforms, using arginine to citrulline conversion assays with specific inhibitors and mRNA expression studies. Aim 3 is to determine if traumatic brain injury affects the cerebral vascular responses to endothelium-dependent vasodilator ACh, activators of ATP-sensitive potassium channels like aprikalim, or reduced perfusion pressure, using arteries harvested following traumatic brain injury. Aim 4 is to determine the effects of TBI and OONO- exposure on perivascular vasodilatory neurotransmitters CGRP, ACh, and anadamide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AFFERENTS

EFFERENT

INNERVATION

OF

IDENTIFIED

VESTIBULAR

Principal Investigator & Institution: Lysakowski, Anna; Associate Professor; Anatomy and Cell Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-JUL-2005 Summary: The purpose of this grant is to investigate the efferent innervation of the peripheral vestibular apparatus. Knowledge of the neurotransmitters and the projections from the brainstem efferent neurons to the peripheral labyrinth will help us understand the role of the vestibular efferent system in health and disease. Recent studies have suggested that neurons in the vestibular efferent nucleus are heterogeneous in their transmitter composition and in their peripheral targets. Such heterogeneity changes our long-held view that vestibular efferents are a nonspecific system. The goal of this study is to define subpopulations of efferent neurons in the chinchilla based upon their brain stem locations, their projection patterns, their peripheral endings, their neurotransmitters, and their receptor subtypes. Specific aims are: 1) to characterize anatomical and neurochemical subpopulations of brainstem efferent neurons by combining retrograde and anterograde tracers with transmitter immunohistochemistry, and 2) to determine details of the morphological terminations of efferents in the periphery, at both the light and electron microscopic levels, and details of their neurochemistry at the molecular level by determining their transmitter receptor subtypes. Efferent neurons in the brainstem are identified by means of retrograde tracer injections into the peripheral vestibular apparatus. They are simultaneously characterized immunohistochemically with antibodies to several putative neurotransmitters (acetylcholine, calcitonin gene- related peptide, nitric oxide synthase, met-enkephalin, adenosine triphosphate, and others). In the periphery, the distribution of receptor sub-types for peptidergic, purinergic and muscarinic transmission will be examined in an attempt to specifically understand the slow response of afferents to efferent stimulation. Vestibular afferents are identified by means of extracellular horseradish peroxidase injections or calretinin immunohistochemistry. The innervation patterns of efferent terminals in the periphery is determined by injections of biotinylated

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dextran amine centrally. Electron microscopic immunohistochemical methods are used to characterize chemically distinct efferent boutons according to their terminations in the sensory epithelium, that is, by the class of afferents (calyx, dimorphic or bouton) and by the region (central or peripheral zones) that they innervate. The intent is to produce a body of knowledge about the structural basis of the efferents, and their relationship to the afferents, from which physiologically and pharmacologically testable hypotheses can be derived. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EICOSANOID INFLAMMATION

MECHANISMS

INITIATING

NEUROGENIC

Principal Investigator & Institution: Vasko, Michael R.; Professor of Pharmacol.; Pharmacology and Toxicology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 30-NOV-2004 Summary: (Adapted from the Investigator's Abstract) Increasing evidence suggests that a major component of the inflammatory actions of prostaglandins is through augmenting the activity of small diameter sensory neurons. This activation and the subsequent release of neuropeptides from these neurons results in neurogenic inflammation and enhanced pain sensation. The studies outlined in this proposal will determine which prostaglandin receptor subtypes mediate sensitization of sensory neurons. The investigators will also examine the effects of inflammation and long-term exposure to inflammatory mediators on the expression and function of prostaglandin receptor subtypes. Finally, studies will elucidate the role of calcium/calmodulin dependent protein kinase in mediating sensitization after acute and long term exposure to prostaglandins. Alterations in receptor expression and function will be studied using two experimental models, 1) rat sensory neurons grown in culture and 2) spinal cord slices and dorsal root ganglia(DRGs) from rats with unilateral inflammation. The former model provides a unique opportunity to examine the mechanisms of eicosanoid action on sensory neurons without significant interference from other types of cells, whereas the latter affords the opportunity to study eicosanoid actions at the level of sensory input to the spinal cord during chronic inflammation. To assess receptor expression real time PCR detection, radioligand binding and immunoblotting will be used. To establish a causal relationship between activation of receptor subtypes and the sensitizing actions of prostaglandins, antisense technology will be used to reduce expression of specific receptor subtypes. The ability of prostaglandins to augment evoked release of substance P and calcitonin gene-related peptide from sensory neurons and to increase cAMP will be used as indices of sensitization. These studies will provide basic information as to the mechanisms of eicosanoid actions on sensory neurons and establish which prostaglandin receptor subtypes are important in altering neuronal sensitivity during inflammation. This knowledge is critically important for understanding the process of neurogenic inflammation and in ultimately designing new drug therapies for the management of inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATING REVERSIBLE SPINAL FIXATION IN BIPED RATS Principal Investigator & Institution: Henderson, Charles N.; Research and Development; Palmer Chiropractic Universtiy 1000 Brady St Davenport, Ia 52803 Timing: Fiscal Year 2003; Project Start 10-SEP-2001; Project End 28-FEB-2005

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Summary: (provided by applicant): We propose to develop and evaluate a novel bipedal rat model of the manipulable spine lesion (the subluxation). Well-designed animal models is of this spine lesion are sorely needed to evaluate outcomes that are predicted by current theoretical models explaining the mechanism of spinal manipulation. Our group has recently designed and collected data on a quadruped rat model of the manipulable lesion that is providing very interesting information. Although the quadruped model has been useful, the degree to which information gained from such a model can be applied to the biped human is a question that remains unanswered. We propose to merge the unique biomechanical features of the bipedal rat with our reversible spinal fixation approach developed in the quadruped rat. This new combined model will allow us to develop a better understanding of anatomic and physiologic differences that occur largely on the basis of the bipedal stance. The resulting increased understanding of the effects of spinal fixation on the bipedal spine should increase our ability to extrapolate information gained in the animal study to clinical trials research and clinical practice. Therefore, in the proposes study, specially designed spinal attachment units (SAUs) will be surgically attached to the L4, L5, and L6 lumbar spinous processes of rats that have been prepared and, raised to walk with a bipedal stance. After post-surgical recovery, the SAUs will be externally linked for 8 weeks. The links will be applied to "fix" the vertebrae in a neutral position in one-half of the linked animals and in a flexed position in the other half. Other animals will have the links attached for 8 weeks and then removed for 8 weeks (the model permit easy "unlinking" of the spinal attachment units). Unlinking will permit us to study the effects of reestablishing motion following fixation. Three age-matched controls will be used: 1) animals with the SAUs applied but not linked, 2) animals that undergo a sham SAU surgery, and 3) animals that have no spinal surgery at all. Biomechanical testing will evaluate relative spine stiffness in all animals: All animals will be euthanized and the zygapophysial joints will be studied macroscopically for degeneration (osteophyte development, articular surface roughing, pitting, elevations, and remodeling). Lastly, the spinal cord will be examined for changes in two neuropeptides substance P and calcitonin gene related peptide. Pending the results of the proposed study, we will submit an R0I grant application to evaluate the effectiveness of spinal manipulation as a treatment for segmental spine stiffness, joint degeneration, and neurophysiologic changes using the bipedal spinal fixation model. This progressive plan of study will permit evaluation of biological mechanisms thought to link the manipulable lesion (subluxation) with spinal manipulation and the chiropractic clinical experience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FEMALE REPRODUCTIVE ORGANS AND THEIR INNERVATION Principal Investigator & Institution: Papka, Raymond E.; Neurobiology; Northeastern Ohio Universities Coll Med P.O. Box 95 Rootstown, Oh 44272 Timing: Fiscal Year 2003; Project Start 15-SEP-1988; Project End 30-JUN-2007 Summary: (provided by applicant): Two important problems in obstetrics are control of uterine body contractions and cervical dilatation. The long-term goal of this research is to understand neural mechanisms for integration of uterine cervical information and how these play a role in cervical ripening and parturition (act of giving birth) particularly as this relates to pre-term or protracted labor, spinal cord-injured females and autonomic dysreflexia. Rationale for these studies is that birthing problems are critical obstetric problems; pre-term labor occurs in 5-10 percent of pregnancies in North America. Within this context, the aims of this proposal are to elucidate the sensory neural substrate of the uterine cervix and how this substrate relates to physical changes

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Calcitonin

in the cervix during cervical ripening and parturition. We propose that this substrate involves sensory nerves, neurotransmitters, receptors, the hormone estrogen, and controlled neurogenic inflammation and leads to the hypothesis: sensory neurons and transmitters innervating the uterine cervix are estrogen responsive, plastic, and are critical components participating in tissue rearrangements occurring at cervical ripening and parturition. Specific aims will determine: 1) if there is enhanced synthesis and release of neurotransmitters by sensory neurons innervating the uterine cervix, specifically at cervical ripening & parturition; 2) if there are specific neurochemically identifiable sensory neurons of lumbosacral spinal ganglia activated expressly at cervical ripening and parturition; 3) if estrogen, working through estrogen receptors, influences levels of neurotransmitters in sensory ganglionic neurons innervating the cervix during pregnancy, parturition, and early postpartum; 4) if cervical ripening and parturition entail a controlled neurogenic inflammatory process; and 5) if specific subclasses of small C-type (peptidergic and non-peptidergic) neurons have identifiable roles in cervical ripening and parturition. These studies will utilize in situ hybridization, RT-PCR, Western blots, immunohistochemistry, nerve transections and neurotoxins. Health benefits from understanding involvement of neural mechanisms in the uterine cervix include an increased basic understanding of neuroendocrine coordination of gestational events including pregnancy, cervical ripening and parturition and the possibility of remediating problems such as pre-term labor, protracted labor, and autonomic dysreflexia. Finally, knowledge of estrogen responsive sensory neurons has important implications for understanding neuropathic pain syndromes influenced by estrogen levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF UTERINE CALCITONIN DURING IMPLANTATION Principal Investigator & Institution: Bagchi, Indrani C.; Associate Professor; Veterinary Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 30-JUN-2004 Summary: The long-term objective of this research proposal is to explore the molecular basis of the regulation of embryonic implantation by calcitonin (CT), a peptide hormone that regulates calcium homeostasis. The expression of CT is induced in the glandular epithelium of rat uterus in the preimplantation phase of gestation and is switched off once implantation is completed. CT expression in human endometrium is restricted to the mid- secretory phase (days 19-24) of the menstrual cycle, with closely overlaps with the putative window of implantation. These findings suggest that CT may function as an important regulatory signal in the uterus during implantation. The specific aims of this proposal are: 1. To determine the functional event(s) regulated by CT during implantation. Administration of antisense oligodeoxynucleotides (ODNs), targeted against CT mRNA, into the preimplantation phase uterus results in marked suppression of the steady-state level of uterine CT mRNA. This intervention is also accompanied by a severe reduction in the number of implanted embryos. These results suggest that the impairment of implantation could be a direct phenotypic consequence of the blockade of CT gene expression by the antisense ODN. The effect of antisense ODN-induced CT deficiency on (a) uterine receptivity and (b) the ability of the embryo to implant will be examined by embryo transfer experiments. 2. To elucidate the signal transduction pathway(s) of CT in transformed human endometrial cell line Ishikawa and in primary cultures of human endometrial epithelial cells. CT acts on target cells through specific cell surface receptors. The expression of the CT receptor is also markedly elevated in the

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preimplantation endometrial epithelium. The second messenger pathways that are activated by CT via its receptor will be investigated in Ishikawa and primary cultures of endometrial epithelial cells. 3. To identify the genes that mediate the cellular actions of CT. CT stimulates the expression of c-fos mRNA while it inhibits the expression of osteopontin mRNA in human endometrial cells. To further understand how CT influences the embryo-uterine interactions, additional genes whose expression in the target cells is modulated in response to this hormone will be identified by subtractive cloning and their spatio-temporal expression in human endometrium during the menstrual cycle will be determine. The proposed study will provide valuable insights into the molecular mechanisms underlying the chain of events that link the transient expression of CT in the uterine glands to the control of embryo-endometrial interactions during implantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HU PROTEINS AS NOVEL SPLICING REGULATORS IN NEURONS Principal Investigator & Institution: Lou, Hua; Genetics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): The long-term goal of this project is to investigate a novel function of the Hu family of paraneoplastic neurological disease (PND) antigens in neurons as alternative splicing regulators. Hu proteins belong to a group of neuronal RNA-binding proteins that were cloned using antiserum from PND patients and are antigens of the Hu syndrome triggered by small cell lung carcinomas. Similar to their closest Drosophila homolog ELAV, Hu proteins were shown to be required for neuronal differentiation in the mammalian nervous system. However, the function of Hu proteins as RNA-binding proteins is not understood. Except for a handful of examples indicating that they bind to the AU-rich element of 3'-untanslated region of mRNA to regulate mRNA stability and translation, the in vivo targets of Hu proteins are largely unknown. Recently we have identified two RNA targets for Hu proteins and provided compelling evidence for a prominent role of these proteins as alternative splicing regulators. To characterize the novel function of Hu proteins as splicing regulators in neurons, we propose three specific aims. In aims I and II, we will study the mechanisms that control the neuron-specific alternative RNA processing of the two newly identified Hu targetcontaining pre-mRNAs by Hu proteins. Specific hypotheses regarding the function of Hu proteins will be generated and tested with both in vitro and in vivo experiments. In aim III, we will identify additional neuronal targets bound by Hu proteins using both in silico database screening and genomic SELEX approaches. The identification of these novel targets will provide the basis for future work that will focus on universality of the principle developed in the proposed studies. These studies will provide not only significant insights into the role of Hu proteins in the development and function of neurons, but also important hints of pathogenesis of the PND disease, the Hu syndrome. Finally, these studies will also greatly increase our understanding of the mechanisms controlling alternative splicing in neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN FETOPLACENTAL VASCULATURE AND CGRP Principal Investigator & Institution: Dong, Yuan-Lin; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2006

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Calcitonin

Summary: (provided by applicant): The maintenance of adequate blood flow to the placenta is essential for a successful pregnancy. Increased fetoplacental vascular resistance and reduced blood flow seen in intrauterine growth restriction (IUGR) and/or preeclampsia is associated with increased fetal and neonatal morbidity and mortality. Calcitonin gene-related peptide (CGRP) has been demonstrated to be involved in the regulation of blood pressure and myometrial contractility during pregnancy via its potent smooth muscle relaxant property, but its role as a vasodilator in physiological and pathological fetoplacental circulation is poorly understood. We have new evidence that CGRP receptors are present in the rat placenta and progressively increase as gestation advances. In addition, CGRP peptide is present in fetal plasma at a higher concentration than that in maternal circulation in late pregnancies. CGRP mRNA is abundantly expressed in the fetal dorsal root ganglia (DRG) and progressively enhanced at term. In humans, CGRP relaxes umbilical, chorionic, and stem villous arteries in a dose-dependent fashion indicating that endogenous CGRP may help maintain low fetoplacental vascular tone during pregnancy. To assess the role of CGRP in the control of human fetoplacental vascular tone, we have proposed the following Specific Aims: Specific Aim 1: To characterize CGRP receptors in the human fetoplacental vasculature. We will identify the cellular location and distribution of CGRP receptor component CRLR and RAMP1 in fetoplacental vessels, and assess radio ligand CGRP binding affinities and capacities. Specific Aim 2: To assess the vasodilatory effects of CGRP on fetoplacental vessels, and determine if they are altered with advancing gestation and modulated by steroid hormones. Specific Aim 3: To determine the post-receptor signaling pathway of CGRP-induced fetoplacental vascular relaxation. Specific Aim 4: To determine the role of CGRP in altered fetoplacental vascular reactivity in IUGR and/or preeclampsia, and evaluate whether insufficient CGRPrelated vasodilator mechanisms were involved in the pathophysiology of IUGR and/or preeclampsia. Our long-term goal is to define the role of CGRP in the regulation of fetoplacental circulation and vascular adaptation during pregnancy. This proposal will have important basic science and clinical implications. Our results may indicate that CGRP has vasodilatory effects on human fetoplacental vasculature and is regulated by sex steroid hormones, as well as elucidate the role of CGRP in IUGR and/or preeclampsia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADDUCTS

IDENTIFICATION

OF

SITES

OF

MDA-ACETALALDEHYDE

Principal Investigator & Institution: Kearley, Mark L.; Associate Professor and Chair; Chemistry; Sonoma State University 1801 E Cotati Ave Rohnert Park, Ca 94928 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): A common result of prolonged alcohol consumption is liver damage. There is a considerable body of evidence that implicates the first metabolite of ethanol oxidation, acetaldehyde (AA), and malondialdehyde (MDA), a byproduct of lipid peroxidation, as the precursors to hepatotoxicity. When proteins are incubated with MDA and AA, hybrid protein adducts, designated as MAA adducts, are generated. To date we have determined the structures of two MAA adducts. One adduct is the fluorescent 1,4-dihydopyridine 3,5-dicarboxaldehyde, formed by a Hantzsch reaction. The other is the nonfluorescent 2-formyl-3-alkylamino-butanal, which results from a Mannich reaction. Both adducts can form on a protein via the t-amino group of lysine or the N-terminus whereas the Mannich adduct can also form on a histidine residue. The research proposed here will focus on identifying the specific sites of MAA

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modifications on proteins. First, each adduct will be synthesized on model peptides and their mass spectra studied to determine the characteristic fragmentation patterns of each adduct. Next we will MAA-modify human alpha-calcitonin gene-related peptide, a 37 residue peptide that has 2 lysines and 1 histidine, and use mass spectrometry to identify the sites of MAA adduct formation. Finally, the proteins ribonuclease A (RNase A) and soybean trypsin inhibitor (STI) will be used in similar experiments. Both proteins have been extensively studied and their structures are well characterized. In addition, each protein has only 10 lysine residues and thus, mass spectrometry should be able to determine the sites of adduct formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATION, AIRWAYS REACTIVITY AND ASTHMA Principal Investigator & Institution: Gelfand, Erwin W.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 30-JUN-2006 Summary: Asthma is a complex illness involving genetic and environmental interactions targeting the lower airways. Worldwide, its incidence has increased at an alarming rate despite significant therapeutic advances. Although heterogeneity between patients exists at several levels, central to the asthma phenotype airway hyperreponsiveness and inflammation The continuing theme of this program is that immune responses in the chemokines, and eicosanoids released from activated cells, profoundly impact the recruitment, activation, and survival of these inflammatory cells in particular (but not solely) eosinophils, which affect large/central and small/peripheral airway function. As part of these responses, T-cell derived cytokines target glucocorticoid receptors on different cell types, creating a state of corticosteroid resistance. The precise mechanisms by which cytokines alter glucocorticoid responsiveness will be defined. The continuing theme of this program is that immune responses in the lung, triggered by allergen exposure and orchestrated by T cells, result in allergic inflammation. Cytokines, chemokines, and eicosanoids released from activated cells, profoundly impact the recruitment, activation, and survival of these cells, in particular (but not solely) eosinophils, which affect large/central and small/peripheral airway function. As part of these responses, T-cell derived cytokinbes target glucocorticoid receptors on different cell types, creating a state of corticosteroid resistance. The precise mechanisms by which cytokines alter glucocorticoid responsiveness will be defined. Using a murine model of allergen- induced airway inflammation and hyperreponsiveness to address critical issues that cannot early be addressed in humans is a focal point of the program. The role of individual T-cell populations in triggering allergic inflammation will be examined, with emphasis on distinct pathways affecting central vs. peripheral airway function. Calcitonin gene related peptide is depleted during an inflammatory response in the lung. It's role in the maintenance of normal related peptide is depleted during an inflammatory response in the lung. Its role in the maintenance of normal airway tone will be determined. Resolution of eosinophilic inflammation through apoptosis and clearance will be analyzed in vitro, in the murine model, and human tissue. In the model of allergen-induced lung inflammation and in human samples, the formation and activity of lipid- derived chemotactic compounds, 5-oxygenated eicosanoids and their metabolites will be analyzed. These questions will be addressed through use of the combined techniques of biochemistry, experimental pathology, and cellular and molecular biology, interwoven throughout the program and provide a framework for acquiring novel insights into the pathogenesis of asthma and strategies for innovative therapies.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSECT DIURETIC HORMONSES: STRUCTURES AND FUNCTION Principal Investigator & Institution: Schooley, David A.; Professor; Biochemistry; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2004 Summary: Insects have low pressure circulatory systems and require diuretic hormones (DH) to control rate of urine production by Malpighian tubules. There are 13 similar DH related to CRF, but with far more diverse structures than the CRF superfamily. It has become apparent during this project that many species have two DH which are related but belong to sub-families of paralogues. We plan to continue investigating to continue investigating what appears to be two members of this family of DH in the disease vector Rhodnius prolixus. The kinins are another family of small peptides that control diuresis. They share rather conserved C-terminal pentapeptide motif and have been found to have synergistic effects with the CRF-like DH in several species of insect. We propose to identify kinins from R. prolixus and Manduca sexta; these insects represent species with disparate dietary habits, the former being an obligate blood feeder and the latter being phytophagous. We plan to study the interactions of these peptides on Malpighian tubules of the two species and their molecular mode of action. The kinins are another family of small peptides that control diuresis. They share a rather conserved C-terminal pentapeptide motif and have been found to synergistic effects with the CRF-like DH in several species of insect. We propose to identify kinins from R. prolixus and Manduca sexta; these insects represent species with disparate dietary habits, the former being an obligate blood feeder and the latter being phytophagous. We plan to study the interaction of this obligate blood feeder and the latter being phytophagous. We plan to study the interactions of these peptides on Malpighian tubules of the two species and their molecular mode of action. During the prior grant period a particularly novel DH was identified from a cockroach, Diploptera punctata, along with a CRF-like DH. This new DH proved to be structurally and functionally related to calcitonin in vertebrates. The peptide (Dippu-DH31) and the CRF-like DH from the same species have strongly synergistic effects. Due to the high potency of this peptide on related species have strongly synergistic effects. Due to the high potency of this peptide on related species of insects, it may well constitute an additional important family of DH. The existence of homologues of this DH will be investigated in other species, including R. prolixus. Studies of the effects of such peptides on the target tissue will be pursued at the molecular level. It is probable that M. sexta has at least 2 receptors for its 2CRF-like DH; one receptor has been identified and efforts to characterize other receptors will be pursued. The ligand binding site on the identified receptor will be approached by protein cross-linking and molecular biological approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIGNALING

LANGERHANS

CELLS

AND

NERVES:

BIDIRECTIONAL

Principal Investigator & Institution: Granstein, Richard D.; Professor; Dermatology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-AUG-2004 Summary: The overall goal of this application is to evaluate and define the bidirectional signaling between epidermal Langerhans cells (LC) and nerves This work is based on the following observations made in the initial funding period: (1) LC are

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anatomically-associated with calcitonin gene-related peptide (CGRP)-containing nerves, (2) CGRP regulates LC function, (3) LC express receptors for several other neuropeptides, as well as beta-adrenergic receptors, and some of these agonists regulate aspects of LC function including cytokine expression and antigen presenting function, and (4) LC are capable of producing neurotrophins. Thus, we hypothesize that bidirectional signaling occurs between nerves and LC with nerves influencing LC by production of neuron-derived signals while LC influence nerve cells by production of neurotrophins. This signaling allows regulation of immune function by neurons and may promote the formulation of the close association between nerves and LC that promotes this functional regulation. In Aim 1, we will test this hypothesis by examining LC for responses to neuropeptides and neuro-transmitters (effects on cytokine expression, co- stimulatory molecule expression and antigen presentation) and production of neurotrophins. Complementary in vivo experiments will test the physiological importance of neuropeptides and neurotransmitters in both induction and elicitation of immunity. Cytokine-deficient ("knock-out") mice will be used to test the involvement of certain cytokines in neural factor effects. In Aim 2, we will study the influence of primary neurons and neuropeptides on the migration of LC cells. Conversely, we will study the factors released by nerve cells that induce migration of LC towards nerve cells. The proposed studies will define an important locus of interaction between the nervous system and the immune system. The results obtained may provide a greater understanding of how the nervous system influences immunity within the skin, and how the association between the neural and immune systems in the skin is formed. These studies may lead to currently unforseen new therapeutic approaches to treat immunologic derangements, ranging form psoriasis to skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF CANNABINOID ANTINOCICEPTIVE ACTION Principal Investigator & Institution: Welch, Sandra Commonwealth University Richmond, Va 232980568

P.;

Professor;

Virginia

Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2003 Summary: Cannabinoids and morphine produce antinociceptive effects in combination, which are far greater in magnitude than the effects of either drug alone. Cannabinoidinduced release of endogenous opioids results in antinociceptive effects of the cannabinoids and enhancement of morphine, A low dose combination of delta9-THC (THC) and morphine produces antinociception without the development of tolerance, while antinoceptive doses of THC and morphine alone produce tolerance. Tolerance to THC or morphine is accompanied by change sin opioid receptor protein levels that may underlie tolerance. However, no change in receptor proteins is observed with the low dose combination of THC and morphine. Thus, prevention of behavioral tolerance results in prevention of biochemical correlates of behavioral tolerance. Similarly, we have implicated c-AMP dependent protein kinase (PKA) in the actions of both cannabinoids and opioids. A PKA inhibitor has been shown to reverse tolerance to both THC and to morphine. Reversal of tolerance to THC with the PKA inhibitor restores THC-induced release of dynorphin. Therefore, reversal of behavioral tolerance results in reversal of the correlated biochemical events associated with tolerance. Thus, our proposed work is designed to answer several pertinent questions raised by our studies. We have yet to answer the important question of how the activation of the BC1 receptor modulates opioid release. We will determine if the THC/morphine interaction involves an interaction with common G-proteins using agonist-stimulated [35S]GTPgammaS binding and determine the role of G proteins in tolerance to the drugs. In addition, we

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Calcitonin

will evaluate down-stream effectors in nociceptive pathways distal to and modulated by opioid release, such as Substance P and CGRP. We hypothesize that opioid-induced decreases in the release of Substance P and CGRP are a contribute to THC/morphine enhancement. Thus, our Specific Aims are designed to capitalize upon the cannabinoid/opioid synergy in order understand the response (plasticity) of neuronal substrates to both THC and opioid tolerance. The ability to better define those processes involved in tolerance may enable us to produce long term antinociceptive effects with the THC/morphine combination, while preventing the neuronal biochemical changes that accompany tolerance. 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 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: MENTORED DEVELOPMENT AW

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Sandroni, Paola; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005

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Summary: Pathophysiology of Pure Autonomic Failure and Idiopathic Autonomic Neuropathy The primary hypothesis is that pure autonomic failure (PAF) and idiopathic autonomic neuropathy (IAN), two disabling and together, relatively common disorders, are different clinically, pathogenetically and pathophysiologically. We posit that PAF is a progressive selective postganglionic autonomic neuropathy, whereas IAN is a monophasic immune-mediated multifocal small fiber neuropathy, affecting both somatic and autonomic fibers. The two disorders are often confused. We will undertake a prospective study to develop a predictive prognostic model of PAF and IAN to evaluate their differentiation, course and outcome. It will be possible to generate insights into the pathophysiologies of IAN and PAF with the availability of the ganglionic antibody (positive in IAN selectively), a validated instrument to evaluate the severity and distribution of autonomic symptoms, new techniques to undertake laboratory evaluation of the systemic, splanchnic-mesenteric and cerebrovascular vasoregulation and the ability to measure muscle sympathetic nerve activity directly using microneurography. Dr. Sandroni will acquire the necessary training to undertake microneurographic, superior mesenteric blood flow, and cerebral blood flow recordings and apply them to autonomic studies on IAN and PAF. It is also possible to study the sympathetic supply to eccrine sweat gland and unmyelinated somatic fiber innervation of the skin (positive in IAN, negative in PAF) using punch skin biopsies. She will acquire training in morphometry of skin innervation, labeled with tile panaxonal marker PGP 9.5 and antibodies to tyrosine hydroxylase (autonomic fibers) and sensory neuropeptidic fibers (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide). Finally, she will undertake a double-blind, randomized, 4-way crossover study of pyridostigmine in the treatment of neurogenic orthostatic hypotension of PAF and IAN. This strategy of acetylcholinesterase inhibition to improve ganglionic transmission could improve orthostatic hypotension without complicating supine hypertension. This research is set up to create a balance in research and clinical responsibility. The planned training in autonomic techniques and specific pathophysiologic studies will provide Dr. Sandroni with the necessary conceptual development, publications track record and investigational tools to effectively compete as an independent investigator in autonomic disorders in future years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METHYLATION OF THE CALCITONIN GENE IN HUMAN TUMORS Principal Investigator & Institution: Baylin, Stephen B.; Professor of Oncology; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-1986; Project End 31-MAY-2004 Summary: An increasing body of data suggest that aberrant DNA methylation of selected clusters of CpG dinucleotides ("CpG Islands") may act as a "mutation" which can silence gene expression and participate In chromosome changes critical to neoplastic progression. Also, increased cellular capacity to methylate DNA, via increases in DNA methyltransferase gene expression, is a very early change in experimental and native tumor progression models. Our proposal seeks to validate, further, interaction between the above events and their direct role in the evolution of human cancer. The molecular and cell phenotype consequences of two discrete CpG island methylation events are under study. We have Identified, through analysis of a hypermethylated CpG island at 17p13.3, a new gene with excellent features for being a candidate tumor suppressor residing telomeric to p53. The potential suppressor role and molecular function of this gene will be determined. Also, aberrant methylation of a 5' CpG island associated with the estrogen receptor (ER) gene on 6q has been found in virtually all samples of human

44

Calcitonin

and murine colon neoplasms and leukemias tested and also in cultured ER negative human breast cancer cells. The role of this change will be studied in the hematopoietic cell system. We have tightly linked loci of aberrant CpG island methylation, especially that above at 17p13.3, with timing and incidence of allelic losses for different types of human cancer (colon, brain, renal, lung). We will determine how the CpG Island changes might Influence chromosome function to predispose to structural abnormalities. Hypermethylated CpG Islands are known to be associated with delayed DNA replication timing on the Inactive X-chromosome, and at the fragile-X gene locus. We will determine whether such delays may be the case for domains around methylated CpG islands in neoplastic cells. Finally, we will expand our recent findings that overexpression of an exogenous DNA methyl transferase (DNA-MTase) gene causes hypermethylation and transformation of NIH 3T3 cells. We will attempt to use this maneuver to model selected human tumor progression steps. We will also evaluate the phenotypic consequences of general, and tissue specific, overexpresslon of an exogenous DNAMTase gene In transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR AND CELL BIOLOGY CORE Principal Investigator & Institution: Berg, Kelly; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The purpose of the Molecular and Cell Biology Core is to consistently provide high quality biochemical and cellular resources to the Sub-Projects. Primary trigeminal ganglion cultures will be derived from both rat and baboon trigeminal ganglia. These primary cultures will be used to study opioid receptor-mediated signaling (subproject #1), and the effects of integrin receptor activation (subproject #2). This Core facilitates these research programs by ensuring quality control, by achieving economies of scale and by permiting project scientists to concentrate on experiments rather than preparation and maintenance of cultures. Quality control issues are particulady important in primary neuronal cell cultures which must be optimized with respect to reagents and culture conditions in order to achieve high quality and consistent results. Our quality control program includes assessment of functional (i.e, central repository and analysis of all control data (eg., PGE2-evoked cAMP accumulation) from all sub-projects) and immunological (e.g., immunostaining for marker proteins) measures to ensure consistency of culture conditions across SubProjects and over time. This Core will also perform various radioimmunoassays (RIA) for each of the subprojects. Release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) will be used as a readout for opioid receptor signaling in all four subprojects, Opioid receptor-mediated inhibition of cAMP accumulation will also be a common read-out for opioid receptor signaling (subprojects 1, 2, and 3). Therefore, RIAs for SP, CGRP and cAMP will be done by the Core on a routine basis. These services are necessary to conduct the experiments proposed in the subprojects in an efficient way and guarantee the necessary quality control and consistency across the program project. In addition to performing a service, starting in year 3, the Core will be responsible for the development and implementation of transfection protocols for expression of foreign DNA in primary rat and baboon TG ganglia cultures. The goal will be to provide suitably transfected cultures with a given signaling molecule gene of interest (e.g., dominant negative strategies) to the individual subprojects in order to delineate specific signaling molecules involved in opioid receptor function as well as real time measures in single cells. Overall, the Core is designed to

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45

maximize efficient use of resources to generate consistent high quality data, and to prepare new technologies for the evolving needs of the Sub-Projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF VESTIBULAR EFFERENT FUNCTION Principal Investigator & Institution: Wackym, P. Ashley.; Professor and Chairman; Otolaryngology and Commun Scis; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 30-JUN-2005 Summary: Description (adapted from the PI abstract): The long term objective is to understand fundamental molecular organization of the projection of the vestibular efferent neurons to the vestibular periphery. The proposal addresses 4 questions: 1) what are the topographic distributions of expressed genes and proteins for transmitter signaling in the rat and human vestibular end-organs and primary afferent ganglia; 2) what are the full length cDNA sequences encoding the mRNAs subserving the efferent/afferent interaction in the vestibular periphery; 3) what is the chromosome location and genomic sequence for each of these genes and how are they processes to yield these cDNAs; and 4) what changes occur in these genes during the aging process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NERVE-TARGET MAINTENANCE

CELL

INTERACTION

IN

TASTE

BUD

Principal Investigator & Institution: Whitehead, Mark C.; Professor; Surgery; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 30-JUN-2004 Summary: The peripheral gustatory system exhibits remarkable receptoneural plasticity. Taste bud receptor cells are continuously renewed and interact dynamically with nerves. Moreover, taste nerves respond to injury by regenerating to the tongue epithelium with great effectiveness. While structural features of receptoneural plasticity in taste are known, its neurochemical substrates are poorly understood. Recently, a few molecular factors have been associated with gustatory neurotrophism. The hamster is a critical model in this approach because fungiform buds atrophy, but the buds do not disappear after denervation, allowing the residual bud cells to be assessed for their differences relative to innervated cells as well as during reinnervation. In contrast, hamster foliate buds do disappear after denervation, allowing comparison with persistent fungiform buds. Hamster fungiform buds express NCAM, NSE and CGRP in centrally located gemmal cells. In denervated buds, these cells are dramatically reduced. The identifying features of immunopositive cells in innervated and denervated buds are not known, and the process by which bud cell become reinnervated, not understood. Electron microscopy (EM) combined with immunocytochemistry (IC) in normal buds will identify NCAM-, NSE- and CGRP-immunopositive cells with respect to their type, e.g., dark or light cells, and whether immunoreactive cells synapse with nerve fibers. In chronically-denervated buds, and buds with regenerating nerves, EM similarly will identify immunopositive gemmal cell types and any receptoneural contacts. A new tetramethylrhodamine dextran amine (TRDA) iontophoretic method for labeling single taste buds and their innervation will evaluate the timing and quantity of reinnervation relative to bud IC. Recent unexpected observations of sparse CGRP-immunopositive nerve fibers near some sensory-denervated buds raise.questions about the source of these fibers and their possible trophic influence upon residual bud cells. The cell bodies

46

Calcitonin

of oigin of these fibers will be determined by TRDA labeling in chronic sensory denervated animals. To better characterize the molecular nature of fungiform taste buds during degeneration and reinnervation, markers that have proven useful in other sensory systems for evaluating cell-cell recognition, differentiating receptor cells and growing axons, will be used in addition to anti-NCAM, -NSE and -CGRP. Use of these markers will be extended to include study of hamster foliate buds after glossopharyngeal nerve section. This will permit intraspecies comparison of anterior and posterior lingual taste bud fields which have responses to denervation that are dramatically different. The possibility that this difference relates to the different embryological origin of the two taste bud fields, i.e. as ectoderm vs. endoderm derivatives, will enhance the data interpretation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL SUBSTRATES OF PEPTIDE INDUCED SATIETY Principal Investigator & Institution: Ritter, Robert C.; Professor of Physiology and Neuroscience; Vet & Comp Anat/Pharm/Physiol; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 30-NOV-2003 Summary: (Adapted From The Applicant's Abstract) This application is a revised version for a competitive renewal of a research program aimed at defining the neuromechanisms through which gastrointestinal peptides especially cholecystokinin, CCK, reduce food intake and ultimately to appreciate how these substrates are involved in the physiology and pathology of food intake. CCK is released by intestinal mucosal I cells, in response to nutrients in the intestine. We discovered that exogenous CCK and intestinally infused nutrients reduce food intake by acting on similar, if not identical, capsacin sensitive, vagal fibers. Furthermore, reduction of feeding by exogenous CCK and intestinal nutrient infusions is blocked by receptor antagonist acting at CCKA but not CCKB receptors. These results suggest that peripheral CCK receptors and small unmyelinated vagal sensory neurons participate in the reduction of food intake by exogenous CCK and intestinal nutrients. They also suggest that endogenous CCK plays an important role in reduction of food intake by intestinal nutrients. Although it is now known that capsaicin sensitive vagal fibers mediate the reduction of food intake by both CCK and intestinal nutrients, we do not know the neurotransmitter(s) used to communicate these satiety signals from vagal fibers to the brain. Furthermore, we do not know how other gastrointestinal peptides may participate in activation of vagal sensory fibers in the intestinal wall. Our recent work suggests that glutamate, acting at NMDA receptors, may be involved in transmitting satiety signals from the vagus to brain. Also, we have some evidence that the peptide, CGRP, may participate in initiating satiety signals at the intestinal end of the vagus. Finally, we have little understanding of how CCK may respond to dietary changes to alter sensitivity of satiety signals. However, our recent results suggest that adaptation to certain diets, notably high fat diets, may cause marked reduction of response to CCK and other satiety signals. Therefore, the experiments proposed are designed to: 1) use intracranial injections together with intestinal infusions to evaluate the participation of glutamatergic transmission in the reduction of food by CCK and intestinal nutrients; 2) use behavioral, pharmacological and biochemical approaches to assess participation of gut CGRP in vagal activation leading to reduction of food intake and 3) to use dietary manipulations, behavioral testing, immunohistochemical and biochemical techniques to assess the role of dietary macronutrients in altering responsiveness to exogenous CCK and to evaluate participation of endogenous CCK in alterations of responsiveness to intestinal nutrients.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROGENIC CALCIUM SIGNALS IN SMALL ARTERIES Principal Investigator & Institution: Wier, Withrow Gil.; Professor; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The research will focus on the roles and mechanisms of neurogenic Ca 2+ signals in autonomic nervous system control of arterial diameter, particularly the Ca2+ signals generated in smooth muscle cells (SMC) by the concerted action of the sympathetic 'triad' of co-transmitters, ATP, norepinephfine (NE) and neuropeptide Y (NPY). Although components of neurogenic vasoconstriction are attributable to ATP, NE and NPY, the underlying Ca 2+ signals in SMC are not known. Preliminary confocal imaging of Ca 2+ within the SMC of intact pressurized rat mesenteric small arteries during low frequency nerve stimulation has revealed novel Ca2+ transients, putatively associated with excitatory junction potentials (EJPs) and provisionally called "junctional Ca 2+ transients" (jCaTs). With higher frequency stimulation, Ca 2+ 'flashes' (may be due to SMC action potentials) and Ca 2+waves are generated. Stimulation of perivascular sensory nerves elicits vasodilation; preliminary results implicate an increase in the frequency of Ca 2+ sparks. Specific Experimental goals include: 1) Test the hypothesis that jCaTs arise from Ca 2+entering SMCs through P2X1 receptors, which are activated by the ATP contained in one or a few quanta of transmitter, 2) Test the hypothesis that neurally released ATP elicits Ca 2+ influx, but not Ca 2+ waves, 3) Test the hypothesis that neurally released NE elicits Ca 2+ waves that function to activate contraction, 4) Test the hypothesis that neurally released NPY activates the Y1 receptor on SMCS to modulate the effects of NE by changing the frequency of Ca 2+ waves, and 5) Test the hypothesis that calcitonin gene related peptide (CGRP) released from sensory nerves decrease Ca 2+ spark frequency; thus causing vasodilation. Mesenteric small arteries from rats and mice (including a P2Xzreceptor deficient transgenic mouse) will be loaded with fluo-4 and mounted on a confocal myograph for simultaneous Ca2+ imaging, recording of isometric force, and measurement of membrane potential. A real-time confocal microscope will be used to provide 2D images fast enough to resolve jCaTs, flashes and waves. The research will test a comprehensive hypothesis on sympathetic neuromuscular transmission and the control of smooth muscle contraction by the autonomic nervous system: Neurally released ATP activates P2X1 receptors. The resulting Ca 2+ influx activates a small contraction, generates EJPs and is visualized as jCaTs. EJPs may summate to trigger action potentials, visualized as Ca 2+ 'flashes' Neurally released NE and NPY (as metabotropic or G protein-lined receptors) increase the frequency of Ca 2+ waves, which activate strong contraction. By visualizing novel, physiological neurogenic Ca 2+ signals and contraction of intact arteries, the research seeks to provide new information on the concerted action of neurotransmitters in controlling arterial function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROGENIC MECHANISMS OF INTESTINAL INFLAMMATION Principal Investigator & Institution: Grady, Eileen F.; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUN-1997; Project End 28-FEB-2007 Summary: (provided by applicant): This proposal examines the general hypothesis that the neuropeptides substance P (SP) and calcitonin-gene related peptide (CGRP) act in a

48

Calcitonin

co-operative fashion to induce neurogenic inflammation of the intestine. The previous grant defined the mechanisms by which SP interacts with the neurokinin 1 receptor (NK1R) to initiate inflammation. Degradation of SP by the cell surface-enzyme neutral endopeptidase (NEP) and desensitization of the NK 1 R by Beta-arrestins, were found to terminate signaling by SP. In the current proposal, a combination of studies in transfected cell lines, endothelial cells that naturally express the receptors, and knockout mice that lack the peptides, their receptors, NEP and p-arrestins will be used to define novel mechanisms of neurogenic inflammation. Aim 1 will define whether a complex of calcitonin receptor like receptor (CRLR) and receptor activity modifying protein (RAMP) 1 form a functional CGRP receptor that mediates the proinflammatory effects of CGRP. The mechanism and function of trafficking of CRLR/RAMP1 to and from the plasma membrane will be investigated by expression of dominant negative mutants of dynamin and rab GTPases that are required for vesicular transport. The cellular distribution of CRLR and RAMP1 will be defined in the intestine to ascertain whether the proteins are suitably located to comprise a functional CGRP receptor. Aim 2 will define importance of beta-arrestins in mediating endocytosis and desensitization of NK1R and CRLR/RAMP1 in cell lines by expressing dominant negative mutants. The role of Beta-arrestins in terminating the inflammatory effects of SP and CGRP will be examined in vivo using Beta-arrestins 1 and 2 knockout animals. Aim 3 will investigate novel mechanisms that account for the potentiating proinflammatory interactions between CGRP and SR The capacity of CGRP to inhibit the degradation of SP by NEP and thereby potentiate its proinflammatory effects will be evaluated in vitro and in the intact animal. Preliminary observations have identified a novel mechanism by which the SP induces sequestration of beta-arrestins into endosomes, thereby depleting cytosolic pools of beta-arrestins and attenuating endocytosis and desensitization of other receptors. The importance of this sequestration in potentiating CGRP signaling will be examined to determine whether this process could also account for the potentiating interactions of SP and CGRP. Together, the results of these experiments will provide new insights into peptide signaling, generate novel information about mechanisms of intestinal inflammation, and suggest new strategies for therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VULVODYNIA

NEUROIMMUNOLOGY/CYTOKINE

ALTERATIONS

IN

Principal Investigator & Institution: Reed, Barbara D.; Family Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: Hundreds of thousands of women in the United States suffer from vulvodynia a chronic burning vulvar pain of unknown cause. Millions of health care dollars are spent annually for this disorder in the United States alone, not only on management, but also on the large proportion of cases that are misdiagnosed and inadequately treated. This pain, associated with allodynia and hyperpathia, has a strong genetic predelection, with African- American women rarely being affected. The broad, long-term objectives of this proposal are to assess the differences in specific neuroimmunological characteristics between women with vulvodynia and asymptomatic controls. The specific aims include: evaluation of l) the individual cytokine/neurokine production response to stimulation of peripheral blood; 2) local changes in nerve fiber, mast cell, Substance P and serotonin density in vulvar tissue; 3) the interactions of the systemic and local immunologic systems assessed in l) and 2); and 4) the multivariable assessment of these laboratory factors with historical risk factors for

Studies

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vulvodynia to explore potential pathophysiologic mechanisms accounting for the historical risk factors identified. The research design involves a case-control evaluation of 100 women with vulvodynia, 100 controls matched for ethnicity, and 100 AfricanAmerican control women, using questionnaires, physical examinations, clinical laboratory data, cytokine/neurokine levels in stimulated peripheral blood, and neuroimmunohistological assessment of vulvar biopsy specimens for nerve fiber density, mast cells, Substance P and serotonin. Results from this study will lead to improved understanding of neuroimmunologic alterations in women with vulvodynia which will direct future therapeutic strategies for this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURONAL CELL DETERMINATION IN THE PNS Principal Investigator & Institution: Hall, Alison K.; Associate Professor; Neurosciences; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 06-JUL-2000; Project End 30-APR-2004 Summary: Verbatim from applicant's abstract): Regulated development of the sensory nervous system results in the ability to feel pain and to sense body position. A major challenge has been to understand how neural crest precursor differentiation is controlled during development and how appropriate neurons are matched with target tissues in the periphery. This application focuses on the developmental regulation of the pain-sensing, calcitonin gene related peptide (CGRP)-containing sensory neurons in the dorsal root ganglion (DRG). CGRP-containing sensory neurons contact skin and gut peripheral target tissues and play pivotal roles in mediating pain sensation and local skin inflammation. This project is based on our novel observation that members of the transforming growth factor beta family -- including activins and bone morphogenetic proteins (BMPs) -- induce the pain sensing phenotype that includes CGRP expression in vitro. We hypothesize that specific TGFb family ligands from skin, blood vessel and gut target tissues induce the pain-sensing phenotype in sensory neurons during development. Studies in this application will test this hypothesis using both in vitro and in vivo functional assays. Noggin and follistatin will be used to identify classes of ligands that underlie CGRP induction by skin cell line factors. Native skin and gut will be assayed for biological activity and ligands in vitro, using assays developed with cell lines. The spatial and temporal localization of ligands and inhibitors will be carried out at critical periods of target contact to learn where and when bioactive factors are present. The role of TGFb family ligands in vivo will be tested by viral misexpression of ligand, inhibitor or BMP receptor. The long term objective of these studies is to understand the mechanisms that regulate neuronal differentiation. Even within the DRG, where relatively few neuronal types arise, little is known about what regulates how different types of neurons are generated from neural crest cells. The completion of the proposed studies will advance our understanding of the importance of target derived growth factors, and in particular the TGFb family ligands activin and bone morphogenetic proteins, in specifying sensory neuronal types from embryonic precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURONAL EXCITABILITY AND MOTILITY IN COLITIS Principal Investigator & Institution: Mawe, Gary M.; Professor; Anatomy and Neurobiology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405

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Calcitonin

Timing: Fiscal Year 2002; Project Start 12-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): The striking motor disturbances that accompany inflammatory bowel disease (IBD) reflect a dynamic interplay between inflammatory mediators and the enteric nervous system. While it is clear that inflammatory mediators trigger enteric neuronal responses, their precise targets and mechanisms of action are unknown. The proposed studies are designed to elucidate how inflammation modulates the afferent components of the reflex circuitry of the bowel, namely the enterochromaffin (EC) cells and AH neurons. We will test the hypothesis that colitis is associated with an increase in the availability of serotonin (5-HT) from EC cells and increased excitability of AH neurons, and that these changes are mediated by prostaglandins generated by cyclooxygenase 2 (COX-2). To test this hypothesis, we will use the thoroughly validated trinitrobenzene sulfonic acid (TNBS) model of colitis in the guinea pig. In the first specific aim, we will evaluate the availability of 5-HT from EC cells in the inflamed colon by quantifying the 5-HT-immunoreactive EC cell population, mucosal 5-HT levels, stimulus-induced 5-HT release, and 5-HT uptake by the mucosa of the inflamed colon. In Specific Aim 2, we will test whether colitis is associated with an increase in the excitability of AH neurons, leading to an increase in the activation of these cells in response to physiological stimuli. The excitability of AH neurons will be investigated by evaluating their electrical properties and their sensitivity to 5-HT. Furthermore, activation of AH neurons by mucosal stimulation will be evaluated (1) electrophysiologically, (2) with the activity marker, FM2-10, (3) by measuring release of calcitonin gene-related peptide, and (4) by measurement of propulsive motor activity. The third specific aim will test whether changes in EC cell and AH neuron function, that are induced during inflammation, are initiated by prostaglandins derived from the induction of COX-2. To accomplish this, we will test whether prostaglandins mimic the effects of inflammation on EC cells and on AH neurons, and we will test whether the neuroendocrine effects of TNBS-induced colitis are attenuated by blockade of COX-2. The results of these studies will reveal how inflammation and prostaglandins alter the function of the afferent components of enteric neural circuits. This information will advance our understanding of the mechanisms of neuro-immune integration and motility disturbances that are associated with IBD, and may lead to novel therapeutic approaches for restoring motor function to normal levels in individuals with IBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURONAL PLASTICITY RELATED TO TMD AND FIBROMYALGIA Principal Investigator & Institution: Dessem, Dean A.; Associate Professor; Oral & Craniofacial Biol Scis; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): The long term objective of this project is to elucidate the role of craniofacial primary afferent neurons in musculoskeletal disorders such as temporomandibular disorders (TMD) and fibromyalgia (FM) using animal models. Two hypotheses are proposed: Hypothesis 1) Masticatory muscle inflammation increases the number of trigeminal ganglion (TG) muscle afferent neurons that express: substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin-1 receptor (NK-lr) and CGRP receptor (CGRPr). This increase involves a phenotypic switch in which muscle primary afferent neurons that do not normally express neuropeptides express SP, CGRP, NK-1r, CGRPr following inflammation. We propose that this change contributes to muscle allodynia and hyperalgesia and can be modulated by pharmacologic manipulations thus providing insight into therapeutics for deep tissue pain. This hypothesis will be tested by quantifying the distribution of TG muscle afferent somata and peripheral axons

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containing SP, CGRP, NK-1r, CGRPr in three groups: i) control, ii) inflamed muscle, iii) inflamed muscle with intervention (anti-nerve growth factor, NK-lr and CGRPr antagonists). This hypothesis will also be tested by determining the levels ofCGRP, SP and gene expression for CGRP, SP within the TG using radioimmunoassay and reverse transcriptase polymerase chain reaction. Hypothesis 2) SP and CGRP alter the functional properties of TG muscle afferent neurons in part by evoking spontaneous activity and increasing their excitability. We predict that substantially more group II, III and IV TG muscle afferent neurons will be modulated by SP and CGRP following inflammation and that these functional alterations can be modulated pharmacologically. This hypothesis will be tested by characterizing the a) spontaneous and evoked activity and b) active and passive membrane properties of TG muscle afferent neurons prior to muscle inflammation, following muscle inflammation, and following muscle inflammation combined with pharmacological intervention. This will be achieved using intracellular electrophysiological recordings from masseter muscle afferent neurons in a trigeminal ganglion-masseter nerve in vitro preparation. Determination of soma size, axon diameter, and SP, CGRP immunoreactivity for physiologically characterized TG muscle afferent neurons will also test Hypothesis 1. Because a gender difference is reported for TMD and FM, both hypotheses will be tested in males, estrous females and diestrous females. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITRIC OXIDE CONTROL OF CGRP IN TRIGEMINAL NEURONS Principal Investigator & Institution: Durham, Paul L.; Biology; Southwest Missouri State University 901 S National St Springfield, Mo 65802 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The objective of the proposed research is to understand the mechanisms by which nitric oxide (NO) regulates calcitonin generelated peptide (CGRP) gene expression in trigeminal neurons. Serum levels of CGRP are elevated in alt forms of vascular headaches, including migraine. The neuropeptide CGRP is known to play a critical role in the underlying pathology of migraine due to its ability to regulate cerebral blood flow, mediate neurogenic inflammation, and relay nociceptive information to the CNS. Another agent implicated in migraine pathology is nitric oxide (NO). Glyceryl trinitrate, an exogenous NO donor, triggers migraine attacks, while blockade of NO synthesis aborts acute migraine attacks. The cerebrovascular affect of NO is thought to be mediated by the local release of neuropeptides from trigeminal neurons. In this proposal, I will test the hypothesis that NO directly stimulates CGRP gene expression and determine whether serotonergic anti-migraine drugs can repress the effect of NO. Studies proposed in the first specific aim will determine the effect of NO alone or in combination with other inflammatory mediators on CGRP release from trigeminal neurons and whether the anti-migraine drug sumatriptan can repress this effect. The second aim will focus on identifying the basal and NO-responsive regulatory sites in the CGRP promoter. Primary trigeminal ganglia cultures will be transiently transfected with CGRP-luciferase reporter DNA and reporter activity measured. The effect of sumatriptan on basal and NO-stimulated CGRP promoter activity will be determined. The third aim will elucidate the pathways involved in NO signaling in trigeminal neurons. Initially, specific cyclase and kinase inhibitors and activators will be used to identify the major pathway(s) involved in regulating the synthesis and release of CGRP. Further studies of individual pathways will utilize phosphospecific antibodies and signaling pathway detection kits. The effect of sumatriptan on NO-activated pathways will be determined. The overall goal of these

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studies is to gain insight into basal and NO regulation of CGRP gene expression in trigeminal neurons that may lead to the development of novel therapeutic strategies for migraine and other diseases involving neurogenic inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PAIN AND INFLAMMATION Principal Investigator & Institution: Willis, William D.; Chairman; Marine Biomedical Institute; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-FEB-1974; Project End 31-JUL-2006 Summary: The application is fore renewal of a long-standing Program Project. The focus of the currently funded grant and that of the renewal is on the role of the peripheral nervous system and the spinal cord in pain mechanisms. Animal modes of human pain states are used so that experimental manipulations can be employed to provide evidence for pathophysiological mechanisms of pain of potential improvements in therapy. The theme of the Program Project is the role of inflammation in a number of clinically in a number of clinically important pain states. These include visceral, arthritic, peripheral neuropathic and central neuropathic pain. Multi-disciplinary approaches are taken in each project. Project 1 investigates the role of a newly described visceral nociceptive pathway in the dorsal column in mediating genitourinary, as well as gastrointestinal pain. Sensitization of primary visceral afferents and ventral viscerosensitive postsynaptic dorsal column and spinothalamic tract cells will be studied in vivo and in vitro. Project 2 examines the contribution of glutamate to neurogenic inflammation in the knee joint. The effects of glutamate in releasing cytokines and chemokines will be studied in vivo and also in vitro, using cultures of synoviocytes. Project 3 considers dual roles of the sympathetic nervous system in neuropathic pain. Up-regulation of adrenoreceptors, purinoceptors and NPY receptors on axotomized afferents on non-axotomized primary afferents will be investigated. The role of inflammation will be examined. Project 4 is concerned with changes in neuropeptide expression in a model of spinal cord injury, hemisection of the cord. Peptides that change include galanin, substance P, and calcitonin gene-related peptide. These are regulated in opposite directions by leukemia inhibitory factor and nerve growth factor, and so the effects of manipulations of these substances on peptide expression and nociception will be examined. The projects will be supported by 4 cores. Core A is an Administrative Core and will provide coordination of the budgets and of interactions amongst the group, consultant help with statistics and experimental design, and computer services. Core B is an Electronics Core and will provide assistance with equipment failures and with the design and construction of electronic devices that are not commercially available. Core C is an Imaging core and will support the projects by providing assistance with confocal microscopy and image analysis. C is an Imaging core and will support the projects by providing assistance with confocal microscopy and image analysis. Core D is a Neurochemistry/Molecular Biology Core and will help the projects with standardized chemical and molecular biological assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PAIN, NOCICEPTION AND THE AMYGDALA Principal Investigator & Institution: Neugebauer, Volker E.; Associate Professor; Anatomy and Neurosciences; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555

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Timing: Fiscal Year 2004; Project Start 01-JUL-1999; Project End 28-FEB-2008 Summary: (provided by applicant): Arthritic pain is significantly associated with negative affect, such as depression and anxiety. The amygdala plays a key role in emotionality and affective disorders. In the previous grant period we delineated the laterocapsular part of the central nucleus of the amygdala (CeA) as the "nociceptive amygdala". We showed that in a model of arthritic pain multireceptive neurons in the CeA develop nociceptive plasticity, which is mediated by and dependent on the enhanced function of glutamate receptors: nociceptive transmission is enhanced through presynaptic metabotropic glutamate receptors of the mGluR1 subtype and neuronal excitability is increased through protein kinase A (PKA)-dependent phosphorylation of postsynaptic N-methyl-D-aspartate (NMDA) receptors in the CeA. The mechanism of PKA activation, however, is unknown. The proposed studies will analyze the role of two major non-opioid neuropeptides, calcitonin gene-related peptide (CGRP) and corticotropin releasing factor (CRF), in the amygdala in our kaolin/carrageenan arthritis pain model. CGRP and CRF are present at particularly high levels in the amygdala and their G-protein-coupled receptors are directly linked to the PKA signal transduction pathway. We will use an innovative and integrative pharmacological approach that combines behavioral tests and in vivo and in vitro electrophysiology to define, at the systems and cellular levels, the role of CGRP, CRF and their receptors in nociceptive processing and pain-related plasticity in the CeA. We will measure spontaneous exploratory behavior and audible and ultrasonic vocalizations in awake rats and use extracellular single-unit recordings in anesthetized rats in vivo and whole-cell patchclamp in rat brain slices in vitro to test the hypotheses that: 1. CGRP produces pronociceptive effects through CGRP1 receptors and is required for nociceptive plasticity in the CeA in arthritis pain. 2. CRF has anti-nociceptive effects through CRF1 receptors and pro-nociceptive effects through CRF2 receptors in the CeA. The pro-nociceptive, but not anti-nociceptive, actions are enhanced and required for nociceptive plasticity in the CeA in arthritis pain. Specific aims are: 1. To analyze arthritis pain-related behavioral (a), electrophysiological in vivo (b) and in vitro (c) changes of CGRP receptor agonist and antagonist effects and their signal transduction mechanisms. 2. To define pro and antinociceptive effects and signal transduction mechanisms of CRF1 and CRF2 receptor agonists and antagonists on pain behavior (a) and electrophysiological in vivo (b) and in vitro (c) measures of nociceptive plasticity in the arthritis model. These studies will provide important new information on the role of non-opioid neuropeptides in pain mechanisms in the amygdala, a brain area that plays a key role in affective disorders, which are significantly associated with arthritic pain. The innovative and integrative behavioral and electrophysiological in vivo and in vitro approach will also contribute valuable insight into the potential therapeutic value of central non-opioid neuropeptide receptors as novel targets for pain relief. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PERIPHERAL INFLAMMATION

CANNABINOIDS

AND

NEUROGENIC

Principal Investigator & Institution: Hargreaves, Kenneth M.; Professor; Endodontics; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002; Project Start 15-JUL-1998; Project End 31-MAY-2004 Summary: (Applicant's Abstract) The management of pain and inflammation are too often unpredictable, with many patients reporting little-to-no relief with most available drugs. Therefore, research into novel drug mechanisms may offer potentially new clinically useful therapeutic agents. We propose to evaluate the hypothesis that

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cannabinoids, known to have central antinociceptive actions, also act in the periphery to modulate the activity of terminals of certain nociceptors. Such peripheral actions of cannabinoids would be physiologically and clinically significant, since inhibition of nociceptive primary afferent neurons could alter both peripheral secretion of neuropeptides (reducing neurogenic inflammation), and, possibly, membrane depolarization (inhibiting hyperalgesia). Specifically, we will test the hypothesis that cannabinoids modulate the development of neurogenic inflammation by inhibiting activation of peripheral terminals of capsaicin-sensitive primary afferent fibers, as measured by peripheral release of the pro-inflammatory neuropeptide calcitonin generelated peptide (CGRP). Our research strategy takes advantage of a uniquely innervated tissue: dental pulp. Application of any physiologic stimulus to human dental pulp, including thermal, osmotic, chemical or mechanical, produces only a pain sensation. Thus, virtually all sensory neurons which innervate pulp appear to be nociceptors. Accordingly, application of drugs to pulpal sensory neurons targets a population of sensory neurons consisting predominantly of nociceptors. Our specific aims will: 1. Characterize the pharmacological effects of cannabinoids to modulate the development of neurogenic inflammation, as measured by inhibition of iCGRP secretion from superfused dental pulp. 2. Evaluate the molecular basis for cannabinoids to directly modulate iCGRP release via interaction with receptors expressed on peptidergic trigeminal sensory neurons. 3. Determine whether cannabinoid inhibition of iCGRP release is mediated by a direct mechanism (i.e., activation of sensory neuronal cannabinoid receptors), by an indirect mechanism (i.e., activation of receptors expressed on autonomic fibers or non-neuronal cells in pulp), or by a combination of the two. Since dental pulp is innervated primarily by nociceptors and is frequently involved with inflammation and healing, this tissue is a relevant biomedical model system. Moreover, the use of specific pharmacological, immunological and molecular probes for cannabinoids should contribute to an understanding on a biochemical level for the effects of cannabinoids on sensory neurons and open new avenues of research on the peripheral actions of these compounds. This knowledge base may provide a rationale for developing peripherally-selective cannabinoid analgesics with minimal CNSmediated side-effect liability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOLOGY OF NEUROTRANSMITTERS IN HAIR CELL ORGANS Principal Investigator & Institution: Sewell, William F.; Associate Professor; Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-DEC-1990; Project End 30-NOV-2005 Summary: The hair cell and its afferent and efferent synapses provide a remarkable system for studying neurotransmitters. The innervation patterns are relatively simple and well defined, yet the processes mediated by these neurotransmitters challenge the limits of our understanding of neurobiology. To accomplish our long-term goal of understanding afferent and efferent transmission in hair cell organs, we have taken a pharmacological approach to characterize molecular and cellular processes in the intact Xenopus lateral line organ and guinea pig cochlea. With this approach we have made significant progress toward understanding the action of two efferent neurotransmitters (acetylcholine (ACH) and calcitonin gene-related peptide (CGRP)) and in identifying the hair cell afferent transmitter. In the previous project period, we found that CGRP acts like ACH to decrease sensitivity to mechanical stimulation, but differs from ACH in increasing spontaneous discharge. In the coming project period, we will follow up this

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finding to determine the actions and interactions of CGRP and ACH as efferents transmitters and will complete work to identify a hair cell afferent neurotransmitter candidate we have purified from retina and inner ear. Specifically, we will 1) determine the mechanism of CGRP'S action as an efferent neurotransmitter in the lateral line organ; 2) determine the mechanism of ACH's action as an efferent neurotransmitter in the lateral line organ and its interaction with CGRP; 3) determine he action of CGRP in the mammalian cochlea; and 4) identify the neurotransmitter released by the hair cell to excite afferent nerve fibers. The development of an understanding of neurotransmitters in hair cells organs will continue to provide insight into basic neurobiological mechanisms. The development of an understanding of neurotransmitters in hair cells organs will continue to provide insight into basic neurobiological mechanisms. For instance, the identification of our "new" neurotransmitter candidate can serve as a probe for all of neurobiology. As we advance our understanding of the role of CGRP as an efferent transmitter and consider its interactions with ACH, we should enhance the ability to probe cochlear function and pave the way for future analysis of these complexities at the biophysical and molecular levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGY OF CALCIUM APPETITE Principal Investigator & Institution: Tordoff, Michael G.; Member; Monell Chemical Senses Center 3500 Market St Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 30-JUN-2003 Summary: (Adapted From The Applicant's Abstract): This is the second revision of a competitive renewal seeking 4 years of support for a program aimed at identifying the physiological basis of a specific calcium appetite. Scant attention has been paid to the role of calcium intake and calcium homeostasis. This is a critical omission in light of the low calcium intake of most Americans, and the involvement of low calcium intake in many chronic diseases (e.g., osteoporosis, kidney disease, heart disease, and hypertension). In this project, it is proposed to take advantage of the biopsychological methods developed to study other ingestive behaviors to elucidate the physiological processes underlying the motivation to drink calcium. Three specific aims are proposed. First, the hypothesis will be tested that circulating concentrations of calcium mediate calcium intake. This will be done by measuring calcium intake in rats given intracerebral ventricular infusions of calcium or calcium antagonists. Second, the hypothesis will be tested that one or more of the calcium regulatory hormones has direct effects on calcium intake. The contribution of each of the three hormones involved (parathyroid hormone, calcitonin, and 1,25-dihydroxy vitamin D) will be assessed by measuring the effect on calcium intake of 1,25-dihydroxy vitamin D infused into rats with plasma concentration of parathyroid hormone and calcitonin held constant. Third, the question of why calcium deprived rats drink sodium chloride and various other taste solutions will be addressed. It is hypothesized that calcium deprived rats ingest these solutions because they increase plasma calcium concentrations, which in turn, reinforces subsequent intake. This will be tested by a) screening a large number of compounds to determine whether they influence plasma calcium concentrations and b) using the electronic esophagus preparation to investigate whether rats find manipulations that increase plasma calcium rewarding. These studies will provide a solid foundation for understanding the physiological controls of calcium intake. This information from studies with rats will help identify the reasons for the low calcium intake of Americans, and provide strategies to help rectify this problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RAMP INVOLVEMENT IN PTH REGULATION OF BONE METABOLISM Principal Investigator & Institution: Nervina, Jeanne M.; Orthodontics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 17-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The goal of this proposed study is to provide the Principal Investigator, Jeanne M. Nervina, DMD, PhD, with the opportunity to develop as an independent researcher to complement her clinical training in orthodontics. Her training will be conducted under the guidance of the project's sponsors, Dr, Sotirios Tetradis and Dr. Harvey Herschman. Dr. Nervina's career goal is to pursue an academic career and establish herself as an independent dentist scientist conducting molecular biology research, mentoring students at all levels, and practicing orthodontics. Bone quality and quantity are important indicators of orofacial pathology and are predictors of outcome success for many dental surgical procedures. Uncoupled activity of bone forming osteoblasts and bone resorbing osteoclasts produce significant changes in bone metabolism. Our rationale is that understanding the molecular mechanisms of bone metabolism will greatly impact medicine and dentistry. Parathyroid hormone (PTH) has significant anabolic effects on bone, yet we do not understand the molecular mediators of these effects. We have identified receptor activity modifying protein 3 (RAMP3) as a PTH-induced primary gene in mouse osteoblasts. In preliminary studies we found that PTH also regulates RAMP1, but not RAMP2, mRNA levels in mouse osteoblasts. RAMP1, 2, and 3 are critical coactivators of calcitonin and calcitonin receptor-like receptors. Ligands for these receptors have significant anabolic effects on bone. We hypothesize that RAMP proteins participate in PTH's anabolic effect on osteoblasts. To test our hypothesis we propose three Specific Aims. (1) We will characterize PTHinduced RAMP1 and RAMP3 gene expression in mouse osteoblasts in vitro and in vivo. (2) Adenoviruses expressing RAMP1 and RAMP3 will be generated to assess the role of these genes in regulating osteoblast phenotype. (3) RAMP1 and RAMP3 transgenic mice will be generated using the COL1A1 promoter to target transgene expression to osteoblasts. Each mouse line will be studied for changes in bone phenotype at the gross, cellular, and molecular levels. These studies will help us understand the mechanisms of PTH-induced RAMP1 and RAMP3 gene expression and they will unveil the impact of these genes on osteoblast function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION CALCITONIN/CGRP

OF

ALTERNATIVE

PROCESSING

OF

Principal Investigator & Institution: Berget, Susan M.; Professor of Biochemistry; Biochem and Molecular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 30-JUN-2005 Summary: This project is aimed at understanding the mechanism whereby alternative pre-mRNA processing is used to generate tissue-specific RNAs coding for different proteins. The gene under study is that coding for the peptide hormones calcitonin (CT) and calcitonin-gene-related peptide (CGRP). The two peptides are produced from a single pre-mRNA to include an alternative 3' terminal exon, exon 4, to produce CT or exclude exon 4 to produce CGRP. Calcitonin and mRNA including exon 4 are produced mainly in thyroid C cells; CGRP and mRNA excluding exon 4 are produced mainly in neuronal cells. Malignant thyroid C cells and small lung cell carcinomas express both

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RNAs and peptides, presumably due to a loss of processing regulation. We have identified an intriguing intron enhancer that regulates this processing choice by altering polyadenylation cleavage efficiency of the alternative 3'-terminal exon. This enhancer is located downstream of the regulated exon and is the only known distal tissue-specific enhancer known to regulate polyadenylation. In previous work we have shown that the enhancer has a CORE resembling a pseudo exon and binds splicing factors, including U1 snRNPs, SR proteins (ASF/SF2 and SRp20), and PTB. In addition, we have shown that the enhancer contains additional sequences important for both inclusion and exclusion of exon 4 that bind unknown factors that may be important for exon skipping in neuronal and malignant cells. This proposal contains experiments to further characterize the enhancer in both normal and malignant cells. Experiments are directed at the mechanism whereby the enhancer facilitates polyadenylation and exon inclusion in most cells, or exon exclusion in neuronal and malignant cells. In addition, the proposal contains experiment directed at the role pseudo exon intron elements might play in more generalized splicing events. Specific aims include: 1) Identify new factors involved in enhancer function, 2) Determine the role of these factors in tissue-specific inclusion and exclusion of exon 4; and 3) Determine the role of the enhancer in general and regulated splicing. The overall goal of these experiments is to understand how an enhancer resembling an exon participates in both polyadenylation and splicing of neighboring exons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF B CELL DEVELOPMENT BY NEUROPEPTIDES Principal Investigator & Institution: Mcgillis, Joseph P.; Associate Professor; Microbiology Immunology, and Molecular Genetics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: The objective of this project is to understand how the nervous system influences the production of new B cells in the bone marrow. B cells produce antibodies following vaccination or exposure to a pathogen. The function of the immune system requires that new white blood cells (leukocytes), including B cells, be produced at controlled rates. Under or overproduction of leukocytes could lead to a reduced capacity to fight infectious disease or to leukemia, autoimmunity or other disease states. For this reason it is critical that the rate of production of leukoctyes is maintained at levels that insure sufficient numbers for their proscribed protective functions without risk of overproduction. The focus of this project is on the role of the neuropeptide calcitonin- gene related peptide (CGRP) in regulating early B cell differentiation. Cells in the immune system have CGRP receptors and CGRP influences the activity of mature lymphocytes, macrophages and granulocytes. CGRP and another sensory neuropeptide, substance P, play a role in regulating the differentiation of distinct leukocyte populations. CGRP is found in nerve endings in bone marrow, hematopoietic cells have CGRP receptors, CGRP induces production of B cell regulatory cytokines and inhibits B cell progenitor responses to IL-7. The specific aims of this project are to show that administration of CGRP reduces the number of B cell progenitors, to identify CGRP receptor expressing cells in the B cell lineage, to examine how specific stages in early B cell development are influenced by CGRP, and to study the cellular mechanisms by which CGRP blocks B cell differentiation. The in vivo studies will determine the number of pre-B CFUs following CGRP treatment. CGRP receptor expressing cell populations will be identified by CGRP receptor mRNA analysis and by functional responses to CGRP. The role of CGRP in B cell differentiation will be studied using short term in

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vitro studies with cells derived from bone marrow. These studies will examine the effect of CGRP on proliferation and differentiation of distinct populations of B cell precursors present in bone marrow. Preliminary studies suggest that CGRP inhibits early B cell differentiation by cellular mechanisms involving events influenced by IL-7 and by activation of NFkappa-B. Studies will determine how CGRP inhibits NFkappa-B activation in a pre-B cell line and will examine how CGRP inhibits IL-7 responses in normal B cell progenitors. A better understanding of CGRP's role in B cell development may offer new avenues for new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CARDIAC NEURONS BY MAST CELLS AND PEPTIDES Principal Investigator & Institution: Hardwick, Jean C.; Biology; Ithaca College Ithaca, Ny 14850 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF OSTEOCLASTIC BONE RESORPTION Principal Investigator & Institution: Baron, Roland E.; Orthopedics and Rehabilitation; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-1977; Project End 31-DEC-2003 Summary: The research described in this application is aimed at understanding of the molecular mechanisms by which bone resorption is regulated. Bone resorption is performed by the osteoclast and acidification of the extracellular bone resorbing compartment constitutes one of the major physiological constraint on the osteoclast. Agents that regulate the differentiation and/or function of the osteoclast affect, albeit not exclusively, the ion transporters and attachment molecules involved in the acidification process. Investigation f the mechanisms by which peptide and steroid hormones affect these processes will therefore help refine our understanding of their regulation. Furthermore, to try to elucidate the mechanisms in which the non-receptor tyrosine kinase c-src is involved and so critically needed for normal osteoclast function may open new avenues for therapeutic intervention. The overall aim of this proposal is to further characterize the specific isoforms of the ion transporters involved in osteoclast-mediated acidification and the mechanisms by which their expression and/or function in bone resorption are regulated. This will include examples of the three main regulatory pathways, i.e., steroid hormones, peptide hormones and the tyrosine kinase signal transduction pathway. This proposal will address the following specific aims: (1) Further analyze the mechanisms by which the peptide hormone calcitonin regulates the processes of acidification by kidney cells and osteoclasts and compare them to the action of PTHrP 107-111 and RGD-containing peptides; (2) Further elucidate the mechanisms by which c-src regulates the function of the osteoclast and, possibly, some of the processes involved in acidification. (3) Further analyze the role of the steroid hormones 1,25- dihydroxyvitamin D3 and estrogens in the regulation of the expression of the various genes required for acidification by the osteoclast; This research program is particularly relevant to health related issues since a detailed analysis of the molecular mechanisms of bone resorption and its regulation can provide more specific and, thereby, more efficient, means to regulate these processes in vivo, whether to therapeutically activate osteoclasts in diseases involving a reduced rate of bone

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resorption (osteopetrosis, growth deficiencies for instance) or to inactivate osteoclasts in diseases involving an increased bone resorption (osteoporosis, osteoarthritis, periodontal disease, Paget's disease, etc.). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RENORENAL REFLEXES Principal Investigator & Institution: Kopp, Ulla C.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: (Verbatim from the application): Increased renal pelvic pressure from acute ureteral obstruction or high urine flow rate stretches the renal pelvic wall and activates renal pelvic mechano sensitive neurons leading to increases in afferent renal nerve activity (ARNA) and urinary sodium excretion, a renorenal reflex. The renorenal reflexes are impaired in hypertension. Long-term Objectives: To study (1) the renorenal reflex-mediated control of water and Na+ excretion during changes in dietary Na+ in rats and mice lacking the genes encoding mediators involved in the activation of renal sensory neurons, (2) the interaction among cyclooxygenase-2 (COX-2), angiotensin and nitric oxide (NO) in the activation of rena] mechanosensory neurons and (3) the essential role of substance P (SP). Specific Aim#1. Mechanisms involved in the increased responsiveness of renal mechanosensitive neurons during high Na+ diet: (a). Is the enhanced responsiveness of the renal mechano sensitive neurons during increased Na+ diet due to increased release/activation of bradykinin, COX-2, PGE2 and/or SP? (b). Does the renin-angiotensin system modulate the activation of renal mechanosensitive neurons? Specific Aim#2. Role of NO as an inhibitory neurotransmitter in the activation of renal mechanosensory neurons: (a). Does NO alter renal pelvic contractility and/or renal pelvic release of PGE2, SP and calcitonin gene-related peptide (CGRP)? (b). Does NO desensitize renal pelvic bradykinin B2 and/or SP receptors? Specific Aim#3. Characterization of renorenal reflexes in mutant mice lacking the gene encoding SP. (a). Is substance P essential foi activation of renal mechanosensitive neurons? (b). Are substance P receptors located on substance P containing neurons and/or sympathetic neurons in the renal pelvis? Renal mechanosensitive neurons will be stimulated b3 increasing renal pelvic pressure in anesthetized mice and rats and ARNA will be recorded. Release of SP, PGE2 anc CGRP will be measured from the renal pelvis by ELISA. Immunohistochemistry will be used to localize the various mediators involved. Identifying the mechanisms involved in the activation of the renal sensory neurons during changes in dietary Na+ in rats and mice may further our understanding of the renal mechanisms contributing to hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF NONCLASSICAL TRANSMITTERS IN CARDIAC GANGLIA Principal Investigator & Institution: Hoover, Donald B.; Pharmacology; East Tennessee State University Box 70565 Johnson City, Tn 37601 Timing: Fiscal Year 2002; Project Start 09-JUL-1997; Project End 30-JUN-2005 Summary: Abnormal neural regulation of the heart plays a prominent role in the pathophysiology of cardiac arrhythmias, congestive heart failure and sudden cardiac death. Mechanism of neural dysfunction at the end organ level are poorly understood. The central hypothesis of this renewal application is the intrinsic cardiac ganglia are major targets where sensory neuropeptides and paracrine mediators act to disrupt

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neural regulation of the heart. Specific Aims 1 3 focus on the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) and their role as mediators in intracardiac reflexes. In Aim 1 we use neuroanatomical techniques to map collateral nerve projection that link the ventricular myocardium with the intrinsic cardiac ganglia. Experiments to evaluate the presence of AP and CGRP in these collaterals are an important element of this Aim. Aim 2 focuses on identifying stimuli that trigger intracardiac reflexes mediated by SP and CGRP and defining mechanisms underlying cardiac responses. The following questions are addressed in studies using the isolated heart preparation and anesthetized guinea pigs: Are SP/CGRP-containing afferents activated by mechanical stimuli as well as chemical stimuli? In Aim 3 a cellular approach is used to evaluate the impact of SP on cholinergic neurotransmission in the intrinsic cardiac ganglia and determine whether SP and CGRP interact in affecting intracardiac neurons. Intracellular recording methods will be used to quantify responses of intracardiac neurons to applied peptides, acetylcholine and vagal stimulation? Do SP and CGRP interact in stimulating intracardiac neurons? If so, does the mechanism of interaction require activation of CGRP receptors? Aim 4 is conceptually similar to the preceding work but focuses on the hypothesis that proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) function as paracrine mediators in the intrinsic cardiac ganglia. Intracellular recording techniques and in vivo physiological measurements will be used to address two basic questions. Do PAMP and ADM affect intracardiac neurons of their response to acetylcholine? Do PAMP and ADM inhibit release of SP and CGRP and cardiac afferents? Results from these studies will improve our understanding of neural mechanisms that operate within the heart and their importance in cardiac pathophysiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ANGIOGENESIS

OF

THE

NEUROLOGIC

SYSTEM

IN

CUTANEOUS

Principal Investigator & Institution: Ansel, John C.; Professor and Chair; Dermatology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 30-JUN-2005 Summary: (Adapted from the applicant's abstract) - This is a resubmission of a competitive renewal of a previous proposal that examined the role of the neurological system in cutaneous wound healing. During the previous funding period, it was demonstrated that the cutaneous sensory neurological system and released neuropeptides were capable of modulating a number of important components of inflammation and wound healing responses in the skin. This application will test the general hypothesis that the sensory nervous system is capable of regulating a number of essential aspects of cutaneous angiogenesis by the release of neuropeptides such as substance P (SP) and calcitonin gene related peptide (CGRP). The released neuropeptides activate specific dermal microvascular endothelial cell (DMEC) neuropeptide receptors to promote angiogenesis. This interaction might play a key role in modulating normal and pathological processes in the skin. The specific aims of this application are: 1) Determine the capacity of specific sensory neuropeptides to modulate DMEC angiogenic responses directly; 2) determine the capacity of activated neurites to modulate DMEC angiogenic responses directly; 3) determine the capacity of the cutaneous neurological system to modulate angiogenesis in the skin; and 4) determine the capacity of the cutaneous neurological system to modulate angiogenesis in wound healing of the skin. The role of specific neuropeptides and their respective receptors in modulating angiogenesis will be determined in vitro and in vivo utilizing both murine

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and human model systems. In vitro DMEC angiogenesis responses will be assessed by measuring microvascular endothelial cell (a) proliferation, (b) chemotaxis/ chemokinesis, (c) matrix metalloproteinase (MMP)/tissue inhibitor of MMP production, (d) endothelial cell derived angiogenic factor production, and (e) endothelial tube formation/sprouting. The ability of activated sensory neurons co-cultured with DMEC to induce angiogenic activities will be determined. In vivo cutaneous angiogenic responses to topical capsaicin, injected neuropeptides, in normal and during wound healing will be measured by direct vessel counts and computer-assisted image analysis after immunostaining. These studies will further basic understanding of the role of the nervous system in angiogenesis and could lead to novel therapies for a wide range of cutaneous processes including inflammation, wound healing, and neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECRETIN AND GASTRIC MOTILITY Principal Investigator & Institution: Owyang, Chung; Chief, Division of Gastroenterology; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-1990; Project End 31-MAR-2005 Summary: Duodenal acidification inhibits gastric antral contractions, promotes gastric fundic relaxation, and thereby protects the duodenum from excess acid exposure. Secretin plays an important role in this process, mediating duodenal acid-induced gastric relaxation by acting on vagal afferent neurons that activate vagal motor neurons, releasing VIP which then evokes gastric relaxation by way of prostaglandin pathways. The current proposal focuses on vagovagal circuits that are activated by secretin and duodenal acid. It is postulated that secretin activates vagal afferent fibers that release CGRP that then stimulates interneurons in the nucleus tractus solitarius. GABAergic neurons inhibit dorsal motor nucleus of the vagal cholinergic neurons which synapse with intragastric cholinergic neurons, while stimulation of glutaminergic neurons activate dorsal motor nucleus vagal neurons which synapse with intragastric VIP neurons. This provides a mechanism whereby single vagal afferents may concurrently excite and inhibit vagal efferent transmission producing dysfacilitation of cholinergic and activation of nonadrenergic and noncholinergic input to the stomach to optimize gastric relaxation. In the current proposal, the neurotransmitter coding utilized by vagal fibers possessing secretin receptors will be assessed by intracellular recording and labeling techniques. The intracellular mechanisms involved in secretin-stimulated release of CGRP from the nodose ganglia will be explored. Both morphologic and electrophysiologic characterization of duodenal acid and secretin-stimulated nucleus tractus solitarius neurons will be performed and their neurochemical phenotypes examined. In vivo, the secretin-induced release of glutamine and GABA will be quantified using radionucleotide tagging techniques. Finally, the dorsal motor neuron vagoneural circuits mediating the action of secretin and the roles of GABA and NMDA will be explored. This should provide a comprehensive characterization of the neural components of the vagovagal circuit activated by secretin to effect gastric relaxation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SENSING PH AT THE GASTRIC SURFACE Principal Investigator & Institution: Montrose, Marshall H.; Professor; Physiology and Biophysics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167

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Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: The stomach must survive HCl secreted by the gastric epithelium. This challenge is heightened by the frequent presence of compounds (e.g. non-steroidal antiinflammatory drugs) or organisms (Helicobacter pylori) which compromise the gastric barrier to acid, leading to ulcers when the barrier is breached. An alkaline juxtamucosal gel layer is the first line of gastric defense: acting to protect the gastric epithelium from back-diffusion of acid from the lumen. We have developed a unique approach to noninvasively measure pH at the gastric surface in vivo. Using confocal microscopy, we have imaged a juxtamucosal alkaline layer, which converts to an acid layer when luminal pH is changed to values found in the fed stomach. Our results suggest a new model of gastric surface pH regulation, which includes a substantial change in the transporters that control surface pH. Our objective is to define the elements regulating luminal pH sensing and surface pH regulation in the stomach. Using primarily in vivo confocal microscopy of rat or mouse stomach, our first aim will define fundamental requirements for the stomach to sense and respond to luminal pH. We will a) define the timing and location of luminal pH change required for conversion from alkali to acid secretion, and b) test the role of luminal nutrients and buffers in surface pH regulation. In the second aim, we will question which molecules are transducers of the luminal pH stimulus that mediate the integrated regulation of both gastric acid and alkali secretion. We will focus on the role of somatostatin, PGE2, and capsaicin-sensitive afferent nerves containing CGRP. The role of somatostatin will be analyzed using antagonists and agonists selective for the somatostatin type 2 receptor (SST2) with parallel studies of SST2-knockout mice. The role of prostaglandin synthesis will be approached using selective inhibitors of known cycloxygenase (COX) isoforms, with parallel studies of COX-1 and COX-2 knockout mice. Capsaicin-sensitive afferents will be analyzed using vanilloid receptor agonists, CGRP receptor agonists and antagonists, with parallel studies of chemically deafferented animals. The third aim will ask how gastric mucosal damage disrupts surface pH regulation. We will generate microscopic lesions in the gastric epithelium by two-photon microscopy. Using this new model of focal gastric damage, we will follow the disruptions in surface pH regulation and the tissue repair process in real time. We will ask if aspirin, a major cause of clinical mucosal damage, weakens the gastric barrier by disruption of luminal pH sensing and surface pH regulation in normal and COX-knockout mice. We will determine if aspirin affects the repair of focal lesions created by two-photon microscopy. Results will integrate understanding of gastric defense with regulation of acid and alkali secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX STEROID HORMONES AND CALCITONIN GENE-RELATED PEPTIDE Principal Investigator & Institution: Yallampalli, Chandrasekhar; Professor; Obstetrics and Gynecology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 20-DEC-1997; Project End 30-NOV-2005 Summary: (provided by applicant): Smooth muscle relaxant molecules are implicated in the regulation of vascular adaptations during pregnancy and in normal uteroplacental function and fetal growth. The long-term goal of our research is to define the role of potent, smooth muscle relaxant, calcitonin gene-related peptide (CGRP) in these vascular adaptations and uteroplacental function. In the previous funding period, we found that both the expression of CGRP and the vasodilatory action of CGRP are upregulated during pregnancy and by sex-steroid hormones. However, the mechanisms

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of CGRP-induced vasodilation as well as the involvement of CGRP in uterine and placental blood flow regulation are not known. Thus, the overall goal of this application is to determine the mechanisms of CGRP-induced vasorelaxation of mesenteric artery and assess the involvement of CGRP in uteroplacental blood flow in the rat. Hypotheses to be tested are: 1) that the increased CGRP-induced mesenteric artery relaxation during pregnancy is due to elevated expression of CGRP receptor components, caicitonin receptor-like receptor (CRLR) and receptor signaling modifying protein (RAMP1), and their post-receptor signaling, and 2) CGRP is involved in the regulation of uteroplacental blood flow and fetal growth. Three specific aims are proposed. Specific aim 1: to characterize CGRP receptors and post-receptor signaling in the mesenteric artery and describe the regulation of the receptors during rat pregnancy and by the sexsteroid hormones. We will measure changes in CRLR and RAMP1, post-receptor signaling and arterial relaxation of mesenteric artery, and assess CGRP-induced blood flow throughout gestation and assess their regulation by sex-steroid hormones. Specific aim 2: to examine the vasodilatory effects of CGRP on uterine artery and assess if these effects are regulated by pregnancy and sex-steroid hormones. We will measure changes in CRLR, RAMP1 and post-receptor signaling and relaxation of uterine artery, and assess CGRP-induced blood flow throughout gestation and regulation by steroid hormones. Specific aim 3: to investigate the role of CGRP in placental blood flow. We will measure changes in CRLR, RAMP1 and CGRP binding in placenta throughout late gestation and their influence by sex-steroid hormones and assess CGRP-induced blood flow through placenta. These studies would help assess the involvement of CGRP in vascular adaptations and in fetal growth during pregnancy and lay a foundation for assessing therapeutic value of CGRP in pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING PATHWAYS IN MEDULLARY THYROID CANCER Principal Investigator & Institution: Chen, Herbert; Chief, Endocrine Surgery; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Medullary thyroid cancer (MTC) is a neuroendocrine tumor derived from the calcitonin-producing thyroid C-cells and accounts for 3-5% of cases of thyroid cancer. Besides surgery, there are limited curative and palliative treatments available to patients with MTC, emphasizing the need for development of other forms of therapy. We have shown that over-expression of raf-1 markedly suppresses cellular growth and induces differentiation of human MTC cells in vitro. We have also shown that these raf-1 effects can be mediated through leukemia inhibitory factor (LIF), a soluble cytokine currently in clinical use for central nervous system disorders. However, the role of raf-1 and LIF in modulating MTC growth and differentiation in vivo has not been explored. In this proposal we will further characterize the downstream events required for raf-1-mediated MTC growth suppression and differentiation. Secondly, we will determine if raf-1 activation can inhibit in vivo MTC tumor growth in a mouse model of metastatic MTC. These studies should determine if modulation of the raf-1 signaling pathway, either by direct activation or through LIF signaling, could play a potential role in the management of patients with metastatic MTC. Because LIF has been already utilized in human subjects for treatment of central nervous system disorders, if our animal data validates our in vitro observations, clinical trials with LIF in patients with metastatic MTC could happen in the near future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIGNALS CONTROLLING OSTEOCYTE VIABILITY Principal Investigator & Institution: Bellido, Teresita M.; Associate Professor; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2003 Summary: The functional syncytium comprising osteocytes, osteoblastic cells, marrow stromal cells, and endothelial cells of the blood vessels is thought to be the mechanosensory apparatus by which bone, as an organ, detects the need for mechanical adaptation and microdamage repair and initiates the appropriate adaptive responses. Consistent with this, studies leading to this project have revealed that the increased bone fragility that results from glucocorticoid excess in mice and humans is associated with increased bone fragility that results from glucocorticoid excess in mice and humans is associated with increased osteocyte apoptosis. Conversely, bisphosphonates and intermittent PTH, two treatments that are effective in steroid-induced osteoporosis (as well as estrogens, androgens, and calcitonin) prevent osteocyte and osteoblast apoptosis in vitro and in vivo. In addition, it has been demonstrated in vitro than the antiapoptotic effect of bisphosphonates and estrogens results from rapid activation of the extracellular signal-regulated kinases (ERKs) and that mechanical signals also cause ERK activation in osteocytic cells. Collectively, these lines of evidence give credence to the hypotheses that disruption of the osteocyte network by apoptosis, resulting from hormonal or strain changes, may contribute to microdamage accumulation and increased bone fragility; whereas prevention of osteocyte viability may increase bone strength. Hormonal, pharmacological, and mechanical signals converge on common signal transduction pathways that influence the viability of osteocytes and the integrity of the lacuno-canalicular network, to orchestrate the appropriate addition or removal of bone and participate in the detection and repair of fatigue microdamage. To advance this hypothesis, the effects of pro- and anti-apoptotic agents (glucocorticoids and bisphosphonates) as well as mechanical signals on focal adhesion molecules (FAK and Pyk2), MAP kinases, intracellular calcium, and connexin channels and hemichannels will be determined in vitro. Further, the contribution of osteocyte apoptosis to mechanical strength will be studied using a murine model of glucocorticoid excess treated with bisphosphonates. These studiers should chart the signaling pathways controlling osteocyte viability and advanced our understanding of the contribution of altered prevalence of osteocyte apoptosis to bone strength. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYNAPTIC INTERACTIONS OF HYPOGLOSSAL MOTONEURONS Principal Investigator & Institution: Gatti, Philip J.; Pharmacology; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2004 Summary: The extrinsic muscles of the tongue are extremely important in the articulation of both consonants and vowels. They participate in shaping the vocal tract for normal articulation. However, little is known regarding the neural control of these muscles; specifically the central nervous system transmitters that modulate the motoneurons innervating the muscles. This project will investigate the motocircuitry of these motoneurons, utilizing a double-labeling electron microscopic technique. The styloglossus, hyoglossus, or genioglossus muscle of the cat will be injected with a retrograde neuronal tracer, cholera toxin B conjugated to horseradish peroxidase (CTBHRP). Two to three days later, animals will be perfused and histochemistry performed to locate the motoneurons labeled from each injection. Then immunohistochemistry will

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then be done to label processes containing substance P, serotonin transporter, tyrosine hydroxylase, calcitonin gene-related peptide, thyrotropin-releasing hormone, gammaaminobutyric acid, or arginine-vasopressin. It is hypothesized that the different extrinsic muscles are innervated by motoneurons that are differentially innervated by these neurotransmitters, thus allowing the coordinated activity of the muscles to correctly shape the vocal tract for speech. Rational pharmacotherapy for a variety of dysarthrias could then be developed as a result of these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED TRIGEMINOVASCULA

REGULATION

OF

CGRP

ACTIVITY

IN

Principal Investigator & Institution: Russo, Andrew F.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: The major goal of these studies is to examine the molecular control of calcitonin gene4"elated peptide (CGRP) activity in the trigeminovascular system. CGRP from trigeminal ganglia neurons is one of the most potent vasodilator mechanisms in the cercbral circulation. The importance of CGRP is highlighted by its involvement in subarachnoid hemorrhage, hypertension, and migraine. We have recently shown that viral delivery of CGRP is capable of preventing vasospasm after subarachnoid hemorrhage. To understand the mechanisms of CGRP action, we now propose to study the CGRP receptor regulatory subunits. Both presynaptic and postsynaptic receptors on the trigeminal ganglia neurons and cerebral vessels have been reported. However, the molecular mechanisms that define CGRP receptor activity are only recently becoming known. The CGRP receptor is a trimer of the calcitonin receptor-like receptor (CRLR) and two regulatory subunits called receptor activity-modifying protein 1 (RAMP1) and receptor component protein (RCP). RAMP1 is required for ligand binding activity and RCP is required for full signaling activity. We propose to test the hypothesis that gene transfer of CGRP receptor subunits can increase CGRP activity in the trigeminovascular system. Specifically, we will ask whether the RAMP1 and RCP proteins can regulate presynaptic and postsynaptic CGRP receptor function in trigeminal ganglia neurons and vascular muscle. The approach will be to use primary cell cultures and transgenic mice. First, the CGRP receptor proteins will be tested in cultured trigeminal neurons and vascular muscle. Second, CGRP-induced vasorelaxation will be measured in vitro using large arteries from RAMP1 and RCP transgenic mice and vasomotor responses will be studied in cerebral microvessels in vivo. Third, relaxation of the basilar artery will be compared in wildtype and transgenic mice in combination with CGRP gene transfer. This project builds on and continues our past studies on effects of CGRP and CGRP gene transfer in the cerebrovasculature. By coupling receptor studies with our adenoviral vector encoding CGRP we expect to lay the foundation for a combined approach of CGRP gene delivery and CGRP receptor modulation. The project will bring together expertise in cerebral circulation (Faraci and Heistad), CGRP expression (Russo), and CGRP receptor function (Dickerson). The significance of this project is that it will provide a new understanding of mechanisms of CGRP action and a potentially new perspective on therapeutic strategies for vascular disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THERAPEUTICAL PROFILES OF OPIOID DELTA RECEPTORS: NEW MODALITIES Principal Investigator & Institution: Porreca, Frank; Professor of Pharmacology and Anesthesio; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: An unexplained paradoxical clinical observation is that opioids can produce unexpected abnormal pain (i.e., hyperesthesias including hyperalgesia and allodynia) during their use for pain relief. Such opioid-induced abnormal "pain" (i.e., increased sensitivity to normally non-noxious mechanical and to noxious thermal stimuli) is also readily observed in preclinical models evaluating the effects of sustained systemic or spinal opioid exposure on sensory thresholds. Critically, manipulations which block opioid-induced pain also block the behavioral manifestation of opioid antinociceptive tolerance. Related to this idea is the observation that almost all of the substances reported to block experimental opioid antinociceptive tolerance (e.g., MK-801, CGRP antagonists) block endogenous mediators (i.e., glutamate, CGRP) which promote pain. The mechanisms by which opioids produce pain are not known. Preliminary data show that following sustained exposure to morphine, capsaicin-evoked release of CGRP from spinal tissues is enhanced. This observation may provide a physiological basis for increased excitation to the spinal cord, and the opioid-induced pain which may underlie the behavioral manifestation of opioid antinociceptive tolerance. Our goals are to understand the mechanisms by which spinal opioids produce pain and antinociceptive tolerance. We hypothesize that opioid-induced pain, and antinociceptive tolerance, results from enhanced evoked transmitter release from primary afferents. One local mechanism for such enhanced release may be the result of down-regulation of opioid receptors on primary afferent fibers. Enhanced evoked transmitter release, and pain, will result as a consequence of loss of basal inhibitory tone on the primary afferents. In support of this idea are our preliminary data which show that spinal infusion of DAMGO or "knock-down" of spinal mu opioid receptors (MOR) with antisense produces pain as well as a right shift in the antinociceptive dose-response curve (i.e., antinociceptive tolerance for DAMGO or an analogous right shift in the dose-response curve following antisense knock-down of receptors). Our Aims will evaluate the requirement for receptor down-regulation as a local mechanism of opioid-induced pain by determining the time-course of such pain in animals, receptor down-regulation and capsaicin-evoked CGRP release in spinal cord tissues or DRG cells in culture. These studies will be extended to spinal opioid antinociceptive and cellular (signal transduction) tolerance. Critically, treatments will focus on the use of spinal DAMGO and MOR receptor antisense oligodeoxynucleotides (ODNs), which produce receptor down-regulation, and morphine which does not produce receptor down-regulation in vivo. Blockade of MOR down-regulation will be evaluated to determine if this also blocks pioid-induced pain, enhanced evoked CGRP release and opioid tolerance. Data from these studies will provide new information which will bring together cellular and systems observations to identify a plausible mechanism which may underlie the decrease in spinal antinociceptive potency seen with sustained opioid administration. Clearly, spinal antinociceptive tolerance will also impact the systemic potency of opioids due to the need for supraspinal/spinal synergy. Such insights may be relevant to the use ofopioids for chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UV LIGHT AND THE CUTANEOUS NEUROSENSORY SYSTEM Principal Investigator & Institution: Glass, Jonathan D.; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: Ultraviolet (UV) light affects the neurosensory system of the skin which likely plays an important pathophysiological role in various skin diseases. Mediators released from the cutaneous neurosensory system by UV irradiation participate in the sunburn reaction and UV-induced immunosupression, and in some skin diseases (e.g. psoriasis) the therapeutic effectiveness of UV treatment may be mediated by the cutaneous neurosensory system. This proposal will investigate the effect of UV light on the neurosensory system by measuring regulation of a number of soluble mediators released in response to UV irradiation. We will use cultured dorsal root ganglia (DRG) as a model of the peripheral nervous system (PNS) to investigate direct effects of UV light on sensory nerve fibers and their respective cell bodies. Responses measured in DRG will be compared to those in the intact neurocutaneous system in hairless mice. In Aim 1 we will analyze the effects of broadband and narrowband UVB irradiation on the sensory nerves from DRG. After single or repeated UVB exposure of DRG we will assess the UV effects on (i) the neuropeptides calcitonin gene-related peptide and substance P, (ii) the intracellular calcium levels of axons and ganglia cells, (iii) the expression of c-fos as a marker of neuronal activation, and (iv) the pattern and speed of axonal outgrowth. In Aim 2 we will compare the acute and chronic UV-induced effects observed in our "DRG-in vitro model" with the effects of acute and chronic UVB exposure on sensory nerves in the skin as well as on their respective cell bodies in the DRKs in hairless mice. The comparison of in vitro and in vivo data from our experiments should give us new insight in the effects of UV light on the cutaneous neurosensory system, and increase our understanding of direct and indirect interactions between UV irradiation and cutaneous nerves. In the future this knowledge could result in the improvement of present and the development of new treatments for skin diseases with neurosensory components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: YALE CORE CENTER FOR MUSCULOSKELETAL DISORDERS Principal Investigator & Institution: Insogna, Karl L.; Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Yale Core Center for Musculoskeletal Disorders (YCCMD) will unite under a single umbrella the talents and skills of 25 investigators from Yale Medical School, Yale University and the John B. Pierce Laboratory. Development, Bone Cell Biology, Cytokines & Growth Factors, Metabolic Bone Disease and Skeletal Biomechanics. YCCMD investigators, based in multiple departments and divisions, share a common goal of understanding the fundamental mechanisms of musculoskeletal disease through the in vivo and in vitro analysis of animal models. Core facilities have been created to facilitate and support the this approach. The Molecular Core will permit the efficient design and generation of molecular regents for tissue-specific transgene over-expression or targeted gene deletions relevant to musculoskeletal disease. The core will also support molecular analysis such as in situ hybridization. The Physiology Core will support densitometric, histomorphometric and biochemical bone- marker analyses to permit detailed evaluation of skeletal homeostasis in experimental animals. The Cell Core will allow investigators to culture osteoblasts, osteoclast-like cells and prepares

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osteoclasts from animals for in vitro studies. The first period of Pilot and Feasibility proposals have been evaluated and three chosen to complement each other and to foster collaborative interactions between groups that may not have interacted previously. Submitted principally by promising young investigators, they reflect the depth of our Research Base. The first study will examine the cellular localization of the PEX protein, a novel metalloendopeptidase which is functionally deficient in X-linked dominant hypophosphatemic rickets. The application proposes a transgenic rescue of a murine model for this disease. The third study analyzes the molecular details of calcitonin signaling in osteoclasts which will help further define the biology of this critical cell type. The final study will explore the physiologic differences between the soluble and cell surface forms of CSF-1. The goals of the YCCMD are to foster collaboration between biomedical scientists and investigative clinicians and to support education, training, and scientific innovation directed at our shared goal of improving musculoskeletal health. 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 “calcitonin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for calcitonin in the PubMed Central database: •

Biological and physical properties of a model calcitonin containing a glutamate residue interrupting the hydrophobic face of the idealized amphiphilic alpha-helical region. by Green FR 3rd, Lynch B, Kaiser ET.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299538

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Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin. by Lenz HJ, Brown MR.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296382

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Characterization of rat calcitonin mRNA. by Amara SG, David DN, Rosenfeld MG, Roos BA, Evans RM.; 1980 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349860

3 4

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

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

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•

Characterization of specific receptors for calcitonin in porcine lung. by FouchereauPeron M, Moukhtar MS, Benson AA, Milhaud G.; 1981 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319696

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Characterization of the Immunochemical Forms of Calcitonin Released by a Medullary Thyroid Carcinoma in Tissue Culture. by Goltzman D.; 1978 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372556

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Cooperation of 5' and 3' processing sites as well as intron and exon sequences in calcitonin exon recognition. by Zandberg H, Moen TC, Baas PD.; 1995 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306662

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Differential effect of alpha-latrotoxin on exocytosis from small synaptic vesicles and from large dense-core vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction. by Matteoli M, Haimann C, Torri-Tarelli F, Polak JM, Ceccarelli B, De Camilli P.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282187

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Differential utilization of calcitonin gene regulatory DNA sequences in cultured lines of medullary thyroid carcinoma and small-cell lung carcinoma. by de Bustros A, Lee RY, Compton D, Tsong TY, Baylin SB, Nelkin BD.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362284

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Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography. by Bouizar Z, Rostene WH, Milhaud G.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298806

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Effects of Glucagon, Dibutyryl Cyclic 3[prime prime or minute],5[prime prime or minute]-Adenosine Monophosphate, and Theophylline on Calcitonin Secretion In Vitro. by Bell NH.; 1970 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322609

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Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. by Steinwald PM, Whang KT, Becker KL, Snider RH, Nylen ES, White JC.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29007

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Evidence for physiological importance of calcitonin in the regulation of plasma calcium in rats. by Kalu DN, Hadji-Georgopoulos A, Foster GV.; 1975 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301808

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Human calcitonin gene regulation by helix-loop-helix recognition sequences. by Ball DW, Compton D, Nelkin BD, Baylin SB, de Bustros A.; 1992 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=310334

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Identification of a New Calcitonin Gene in the Salmon Oncorhynchus gorbuscha. by Jansz H, Martial K, Zandberg J, Milhaud G, Benson AA, Julienne A, Moukhtar MS, Cressent M.; 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=37993

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Identification of a Protein that Confers Calcitonin Gene-Related Peptide Responsiveness to Oocytes by Using a Cystic Fibrosis Transmembrane Conductance Regulator Assay. by Luebke AE, Dahl GP, Roos BA, Dickerson IM.; 1996 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39630

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Immunochemical heterogeneity of calcitonin in plasma of patients with medullary thryoid carcinoma. by Sizemore GW, Hpeath H 3rd, Larson JM.; 1975 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301858

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Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. by Hoff AO, Catala-Lehnen P, Thomas PM, Priemel M, Rueger JM, Nasonkin I, Bradley A, Hughes MR, Ordonez N, Cote GJ, Amling M, Gagel RF.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151647

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Metabolic Clearance Rate of Radioiodinated Human Calcitonin in Man. by Ardaillou R, Sizonenko P, Meyrier A, Vallee G, Beaugas C.; 1970 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322735

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Model for alternative RNA processing in human calcitonin gene expression. by Bovenberg RA, van de Meerendonk WP, Baas PD, Steenbergh PH, Lips CJ, Jansz HS.; 1986 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311911

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Modified binding of proteins from calcitonin-negative tumor cells to the neuroendocrine-specific CANNTG motif of the calcitonin gene. by Peleg S.; 1993 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=310571

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Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling. by Paolocci N, Saavedra WF, Miranda KM, Martignani C, Isoda T, Hare JM, Espey MG, Fukuto JM, Feelisch M, Wink DA, Kass DA.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56983

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Physiological studies in heterozygous calcium sensing receptor (CaSR) gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo. by Fudge NJ, Kovacs CS.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=419359

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Plasma Calcitonin in Normal Man DIFFERENCES BETWEEN MEN AND WOMEN. by Heath H III, Sizemore GW.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372466

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Preand Postoperative Studies of Plasma Calcitonin in Primary Hyperparathyroidism. by Lambert PW, Heath H III, Sizemore GW.; 1979 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371994

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Regulation of Calcitonin Secretion in Normal Man by Changes of Serum Calcium within the Physiologic Range. by Austin LA, Heath H III, Go VL.; 1979 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371328

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Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics. by Reginster JY, Deroisy R, Albert A, Denis D, Lecart MP, Collette J, Franchimont P.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303786

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Renal Effects of Calcitonin and Parathyroid Extract in Man. STUDIES IN HYPOPARATHYROIDISM. by Haas HG, Dambacher MA, Guncaga J, Lauffenburger T.; 1971 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292219

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Secretion of Calcitonin in Hypocalcemic States in Man. by Deftos LJ, Powell D, Parthemore JG, Potts JT Jr.; 1973 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302586

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Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: Tailored-SELEX. by Vater A, Jarosch F, Buchner K, Klussmann S.; 2003 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=275487

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Specific Induction of cAMP in Langerhans Cells by Calcitonin Gene-Related Peptide: Relevance to Functional Effects. by Asahina A, Moro O, Hosoi J, Lerner EA, Xu S, Takashima A, Granstein RD.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41149

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The calcitonin gene is expressed in salmon gills. by Martial K, Maubras L, Taboulet J, Jullienne A, Berry M, Milhaud G, Benson AA, Moukhtar MS, Cressent M.; 1994 May 24; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43899

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The Clinical and Metabolic Effects of Porcine Calcitonin on Paget's Disease of Bone. by Shai F, Baker RK, Wallach S.; 1971 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292119

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

A brief history of calcitonin. Author(s): Colman E, Hedin R, Swann J, Orloff D. Source: Lancet. 2002 March 9; 359(9309): 885-6. Erratum In: Lancet 2002 July 13; 360(9327): 176. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897305

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A calcitonin and vasoactive intestinal peptide-producing pancreatic endocrine tumor associated with the WDHA syndrome. Author(s): Ichimura T, Kondo S, Okushiba S, Morikawa T, Katoh H. Source: International Journal of Gastrointestinal Cancer. 2003; 33(2-3): 99-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716055

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A calcium homeostasis model: orchestration of fast acting PTH and calcitonin with slow calcitriol. Author(s): Kurbel S, Radic R, Kotromanovic Z, Puseljic Z, Kratofil B. Source: Medical Hypotheses. 2003 September; 61(3): 346-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944103

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A case of spurious hypercalcitoninemia: a cautionary tale on the use of plasma calcitonin assays in the screening of patients with thyroid nodules for neoplasia. Author(s): Uwaifo GI, Remaley AT, Stene M, Reynolds JC, Yen PM, Snider RH, Becker KL, Sarlis NJ. Source: J Endocrinol Invest. 2001 May; 24(5): 361-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407657

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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 controlled trial of calcitonin therapy for the prevention of post-liver transplantation atraumatic fractures in patients with primary biliary cirrhosis and primary sclerosing cholangitis. Author(s): Hay JE, Malinchoc M, Dickson ER. Source: Journal of Hepatology. 2001 February; 34(2): 292-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281559

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A pilot study of rat brain regional distribution of calcitonin, katacalcin and calcitonin gene-related peptide before and after antipsychotic treatment. Author(s): Angelucci F, Gruber SH, Mathe AA. Source: Neuropeptides. 2001 October-December; 35(5-6): 285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030813

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A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. Author(s): Trovas GP, Lyritis GP, Galanos A, Raptou P, Constantelou E. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 March; 17(3): 521-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874243

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Adrenomedullin selectivity of calcitonin-like receptor/receptor activity modifying proteins. Author(s): Muff R, Born W, Fischer JA. Source: Hypertens Res. 2003 February; 26 Suppl: S3-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630805

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Adrenomedullin, calcitonin gene-related peptide and their receptors: evidence for a decreased placental mRNA content in preeclampsia and HELLP syndrome. Author(s): Knerr I, Dachert C, Beinder E, Metzler M, Dotsch J, Repp R, Rascher W. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2002 February 10; 101(1): 47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11905404

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Agonist-promoted internalization of a ternary complex between calcitonin receptorlike receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin. Author(s): Hilairet S, Belanger C, Bertrand J, Laperriere A, Foord SM, Bouvier M. Source: The Journal of Biological Chemistry. 2001 November 9; 276(45): 42182-90. Epub 2001 September 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535606

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Allergy to calcitonin. Author(s): Rodriguez A, Trujillo MJ, Herrero T, Baeza ML, de Barrio M. Source: Allergy. 2001 August; 56(8): 801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488691

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Amyloid fibril formation by pentapeptide and tetrapeptide fragments of human calcitonin. Author(s): Reches M, Porat Y, Gazit E. Source: The Journal of Biological Chemistry. 2002 September 20; 277(38): 35475-80. Epub 2002 July 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12095997

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Analgesic effect of calcitonin in osteoporosis. Author(s): Gennari C. Source: Bone. 2002 May; 30(5 Suppl): 67S-70S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008161

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Analgesic effects of calcitonin. Author(s): Lyritis GP, Trovas G. Source: Bone. 2002 May; 30(5 Suppl): 71S-74S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008162

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Analgesic efficacy of calcitonin for vertebral fracture pain. Author(s): Blau LA, Hoehns JD. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 564-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12659616

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Androgen receptor and calcitonin gene-related peptide in neurons of the genitofemoral nerve during testicular descent induced with human chorionic gonadotropin. Author(s): Vigueras RM, Moreno-Mendoza N, Reyes G, Merchant-Larios H. Source: Archives of Medical Research. 2003 May-June; 34(3): 166-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567394

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Assessment of the biological activity of synthetic salmon calcitonin by intranasal administration in healthy volunteers. Author(s): Fiore CE, Romagnoli A, Foti R, Coppini A. Source: Drugs Exp Clin Res. 1991; 17(10-11): 537-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1668656

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Association of calcitonin receptor gene polymorphism with early marginal bone loss around endosseous implants. Author(s): Nosaka Y, Tachi Y, Shimpuku H, Kawamura T, Ohura K. Source: Int J Oral Maxillofac Implants. 2002 January-February; 17(1): 38-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858573

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Association of the calcitonin gene (CA) polymorphism with bone mass and bone responsiveness to hormone therapy in postmenopausal Korean women. Author(s): Kim JG, Choi YM, Moon SY, Lee JY. Source: Menopause (New York, N.Y.). 2003 November-December; 10(6): 544-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627864

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Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma. Author(s): Kotzmann H, Schmidt A, Scheuba C, Kaserer K, Watschinger B, Soregi G, Niederle B, Vierhapper H. Source: Thyroid : Official Journal of the American Thyroid Association. 1999 September; 9(9): 943-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10524574

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Basal tail skin temperature elevation and augmented response to calcitonin generelated peptide in ovariectomized rats. Author(s): Kobayashi T, Ushijima O, Chen JT, Shiraki M, Ohta T, Kiyoki M. Source: The Journal of Endocrinology. 1995 September; 146(3): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7595138

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Binding of a candidate splice regulator to a calcitonin-specific splice enhancer regulates calcitonin/CGRP pre-mRNA splicing. Author(s): Coleman TP, Tran Q, Roesser JR. Source: Biochimica Et Biophysica Acta. 2003 January 27; 1625(2): 153-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531474

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Binding of filamin to the C-terminal tail of the calcitonin receptor controls recycling. Author(s): Seck T, Baron R, Horne WC. Source: The Journal of Biological Chemistry. 2003 March 21; 278(12): 10408-16. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531889

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Binding of upstream stimulatory factor and a cell-specific activator to the calcitonin/calcitonin gene-related peptide enhancer. Author(s): Lanigan TM, Russo AF. Source: The Journal of Biological Chemistry. 1997 July 18; 272(29): 18316-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9218472

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Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. Author(s): Buclin T, Cosma Rochat M, Burckhardt P, Azria M, Attinger M. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 August; 17(8): 1478-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162502

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Biochemical responses to sequential human parathyroid hormone (1-38) and calcitonin in osteoporotic patients. Author(s): Hodsman AB, Fraher LJ. Source: Bone Miner. 1990 May; 9(2): 137-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2161692

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Biological accessibility and distribution of calcitonin in rats with experimental osteoporosis. Author(s): Ryszka F, Krupej J, Dolinska B. Source: Pharmazie. 1995 September; 50(9): 636-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480104

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Biological accessibility of calcitonin and osteocalcin marked 125J for rats. Author(s): Ryszka F, Krupej J, Dolinska B, Gawronski M, Jeszka H, Ustjanycz E, SuszkaSwitek A. Source: Boll Chim Farm. 1994 November; 133(10): 659-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7865197

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Biological markers of alcohol consumption and effect of calcitonin in nonalcoholic men: a prospective, double-blind study. Author(s): Elomaa VV, Loyttyniemi E, Karkkainen P, Salaspuro M, Laitinen K. Source: Alcoholism, Clinical and Experimental Research. 1996 August; 20(5): 830-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865956

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Biological potency and radioimmunoassay of canine calcitonin. Author(s): Hazewinkel HA, Schoenmakers I, Pelling D, Snijdelaar M, Wolfswinkel J, Mol JA. Source: Domestic Animal Endocrinology. 1999 November; 17(4): 333-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628425

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Biphasic intraocular pressure response to calcitonin gene-related peptide. Author(s): Taniguchi T, Nakai Y, Karim Z, Gu ZB, Kawase K, Kitazawa Y. Source: Current Eye Research. 1999 November; 19(5): 432-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520220

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Bone densitometric and histomorphometric responses to sequential human parathyroid hormone (1-38) and salmon calcitonin in osteoporotic patients. Author(s): Hodsman AB, Steer BM, Fraher LJ, Drost DJ. Source: Bone Miner. 1991 July; 14(1): 67-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1868270

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Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin. Author(s): Roux C, Pelissier C, Listrat V, Kolta S, Simonetta C, Guignard M, Dougados M, Amor B. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1995 May; 5(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7655179

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Bone loss during gonadotropin-releasing hormone agonist treatment in girls with true precocious puberty is not due to an impairment of calcitonin secretion. Author(s): Saggese G, Bertelloni S, Baroncelli GI, Pardi D, Cinquanta L. Source: J Endocrinol Invest. 1991 March; 14(3): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1830057

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Bone loss in young women with primary hypogonadism and its prevention with calcitonin. Author(s): Biberoglu K, Yildiz A, Kandemir O. Source: Gynecologic and Obstetric Investigation. 1993; 36(2): 114-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225045

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Bone mass in totally thyroidectomized patients. Role of calcitonin deficiency and exogenous thyroid treatment. Author(s): Gonzalez DC, Mautalen CA, Correa PH, el Tamer E, el Tamer S. Source: Acta Endocrinol (Copenh). 1991 May; 124(5): 521-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2028710

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Bone remodeling during calcitonin excess: reconstruction of the remodeling sequence in medullary thyroid carcinoma. Author(s): Eriksen EF, Kudsk H, Emmertsen K, Mosekilde L, Melsen F. Source: Bone. 1993 May-June; 14(3): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8363884

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Breast cancer cell response to calcitonin: modulation by growth-regulating agents. Author(s): Lacroix M, Siwek B, Body JJ. Source: European Journal of Pharmacology. 1998 March 5; 344(2-3): 279-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600664

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Bronchoprotector properties of calcitonin gene-related peptide in guinea pig and human airways. Effect of pulmonary inflammation. Author(s): Cadieux A, Monast NP, Pomerleau F, Fournier A, Lanoue C. Source: American Journal of Respiratory and Critical Care Medicine. 1999 January; 159(1): 235-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872844

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Calcitonin for osteoporosis and bone pain. Author(s): Mehta NM, Malootian A, Gilligan JP. Source: Current Pharmaceutical Design. 2003; 9(32): 2659-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529539

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Calcitonin gene-related peptide (CGRP) and the pathophysiology of headache: therapeutic implications. Author(s): Edvinsson L. Source: Cns Drugs. 2001; 15(10): 745-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11602001

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Calcitonin gene-related peptide in Langerhans cells in psoriatic plaque lesions. Author(s): He Y, Ding G, Wang X, Zhu T, Fan S. Source: Chinese Medical Journal. 2000 August; 113(8): 747-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776062

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Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK. Author(s): Schaeffer C, Vandroux D, Thomassin L, Athias P, Rochette L, Connat JL. Source: Biochimica Et Biophysica Acta. 2003 December 7; 1643(1-3): 65-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654229

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Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. Author(s): Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM; BIBN 4096 BS Clinical Proof of Concept Study Group. Source: The New England Journal of Medicine. 2004 March 11; 350(11): 1104-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014183

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Calcitonin gene-related peptide: an endogenous mediator of preconditioning. Author(s): Li YJ, Song QJ, Xiao J. Source: Acta Pharmacologica Sinica. 2000 October; 21(10): 865-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501035

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Calcitonin is a prostate epithelium-derived growth stimulatory peptide. Author(s): Chien J, Ren Y, Qing Wang Y, Bordelon W, Thompson E, Davis R, Rayford W, Shah G. Source: Molecular and Cellular Endocrinology. 2001 July 5; 181(1-2): 69-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11476942

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Calcitonin kinetics in the early postoperative period of medullary thyroid carcinoma. Author(s): Brauckhoff M, Gimm O, Brauckhoff K, Ukkat J, Thomusch O, Dralle H. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2001 November; 386(6): 434-9. Epub 2001 October 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11735017

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Calcitonin precursor levels in human medullary thyroid carcinoma. Author(s): Bihan H, Becker KL, Snider RH, Nylen E, Vittaz L, Lauret C, Modigliani E, Moretti JL, Cohen R. Source: Thyroid : Official Journal of the American Thyroid Association. 2003 August; 13(8): 819-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558925

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Calcitonin receptor gene and breast cancer: quantitative analysis with laser capture microdissection. Author(s): Wang X, Nakamura M, Mori I, Takeda K, Nakamura Y, Utsunomiya H, Yoshimura G, Sakurai T, Kakudo K. Source: Breast Cancer Research and Treatment. 2004 January; 83(2): 109-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997041

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Calcitonin receptor gene polymorphism: a possible genetic marker for patients with calcium oxalate stones. Author(s): Chen WC, Wu HC, Lu HF, Chen HY, Tsai FJ. Source: European Urology. 2001 June; 39(6): 716-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464063

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Channel formation by salmon and human calcitonin in black lipid membranes. Author(s): Stipani V, Gallucci E, Micelli S, Picciarelli V, Benz R. Source: Biophysical Journal. 2001 December; 81(6): 3332-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720996

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Characterization of calcitonin gene-related peptide (CGRP) receptors and their receptor-activity-modifying proteins (RAMPs) in human brain microvascular and astroglial cells in culture. Author(s): Moreno MJ, Terron JA, Stanimirovic DB, Doods H, Hamel E. Source: Neuropharmacology. 2002 February; 42(2): 270-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804624

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Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. Author(s): Kuwasako K, Cao YN, Nagoshi Y, Tsuruda T, Kitamura K, Eto T. Source: Molecular Pharmacology. 2004 January; 65(1): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722252

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Circulating calcitonin and carcinoembryonic antigen m-RNA detected by RT-PCR as tumour markers in medullary thyroid carcinoma. Author(s): Bojunga J, Dragan C, Schumm-Draeger PM, Usadel KH, Kusterer K. Source: British Journal of Cancer. 2001 November 16; 85(10): 1546-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720443

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Clinical evaluation of a new sensitive calcitonin assay: study of specificity. Author(s): d'Herbomez M, Leclerc L, Vantyghem MC, Fourrier F, Proye C, Wemeau JL. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 September 25; 311(2): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11566174

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Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. Author(s): Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 April; 89(4): 151225. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070906

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Comparison of alendronate, calcitonin and calcium treatments in postmenopausal osteoporosis. Author(s): Dursun N, Dursun E, Yalcin S. Source: Int J Clin Pract. 2001 October; 55(8): 505-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695068

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Comparison of risedronate to alendronate and calcitonin for early reduction of nonvertebral fracture risk: results from a managed care administrative claims database. Author(s): Watts NB, Worley K, Solis A, Doyle J, Sheer R. Source: J Manag Care Pharm. 2004 March-April; 10(2): 142-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15032563

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Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation. Author(s): Coyle D, Cranney A, Lee KM, Welch V, Tugwell P. Source: Pharmacoeconomics. 2001; 19(5 Pt 2): 565-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11465301

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Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon. Author(s): Bunker CB, Terenghi G, Springall DR, Polak JM, Dowd PM. Source: Lancet. 1990 December 22-29; 336(8730): 1530-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1979366

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Degradation and aggregation of human calcitonin in vitro. Author(s): Lu RH, Kopeckova P, Kopecek J. Source: Pharmaceutical Research. 1999 March; 16(3): 359-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10213365

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Delimitation of the time of death by immunohistochemical detection of calcitonin. Author(s): Wehner F, Wehner HD, Subke J. Source: Forensic Science International. 2001 November 1; 122(2-3): 89-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11672961

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Determinants for calcitonin analog interaction with the calcitonin receptor Nterminus and transmembrane-loop regions. Author(s): Stroop SD, Nakamuta H, Kuestner RE, Moore EE, Epand RM. Source: Endocrinology. 1996 November; 137(11): 4752-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895343

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Development of a highly sensitive enzyme immunoassay for human calcitonin using solid phase coupled with multiple antibodies. Author(s): Isomura M, Honda N, Kawada A, Suzuki H, Ashihara Y. Source: Annals of Clinical Biochemistry. 1999 September; 36 ( Pt 5): 629-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10505214

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Development of calcitonin gene-related peptide slow-release tablet implanted in CSF space for prevention of cerebral vasospasm after experimental subarachnoid haemorrhage. Author(s): Ahmad I, Imaizumi S, Shimizu H, Kaminuma T, Ochiai N, Tajima M, Yoshimoto T. Source: Acta Neurochirurgica. 1996; 138(10): 1230-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8955444

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Different levels of sensory neuropeptides (calcitonin gene-related peptide and substance P) during and after exercise in man. Author(s): Lind H, Brudin L, Lindholm L, Edvinsson L. Source: Clinical Physiology (Oxford, England). 1996 January; 16(1): 73-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8867778

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Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus. Author(s): Nikitenko LL, Brown NS, Smith DM, MacKenzie IZ, Bicknell R, Rees MC. Source: Molecular Human Reproduction. 2001 July; 7(7): 655-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11420389

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Differential regulation of calcitonin secretion in normal and neoplastic pulmonary neuroendocrine cells in vitro. Author(s): Pu FR, Manning FC, Brannigan AE, Crosby SR. Source: Experimental Lung Research. 2001 December; 27(8): 689-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11768719

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Differential sensitivity of human nonpregnant and pregnant myometrium to calcitonin gene-related peptide. Author(s): Chan KK, Robinson G, Pipkin FB. Source: Journal of the Society for Gynecologic Investigation. 1997 January-February; 4(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9051629

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Direct inhibitory effect of adrenomedullin, calcitonin gene-related peptide, calcitonin, and amylin on cholecystokinin-induced contraction of guinea-pig isolated caecal circular smooth muscle cells. Author(s): Ochiai T, Chijiiwa Y, Motomura Y, Yasuda O, Harada N, Nawata H. Source: Peptides. 2001 June; 22(6): 909-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11390020

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Discovery of a non-peptide small molecule that selectively mimics the biological actions of calcitonin. Author(s): Katayama T, Furuya M, Yamaichi K, Konishi K, Sugiura N, Murafuji H, Magota K, Saito M, Tanaka S, Oikawa S. Source: Biochimica Et Biophysica Acta. 2001 May 3; 1526(2): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11325540

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Discovery of novel peptide/receptor interactions: identification of PHM-27 as a potent agonist of the human calcitonin receptor. Author(s): Ma JN, Currier EA, Essex A, Feddock M, Spalding TA, Nash NR, Brann MR, Burstein ES. Source: Biochemical Pharmacology. 2004 April 1; 67(7): 1279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013843

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Disordered calcium homeostasis of sepsis: association with calcitonin precursors. Author(s): Muller B, Becker KL, Kranzlin M, Schachinger H, Huber PR, Nylen ES, Snider RH, White JC, Schmidt-Gayk H, Zimmerli W, Ritz R. Source: European Journal of Clinical Investigation. 2000 September; 30(9): 823-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998084

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Distribution and colocalization of calcitonin gene-related peptide, tachykinins, and vasoactive intestinal peptide in normal and idiopathic unstable human urinary bladder. Author(s): Smet PJ, Moore KH, Jonavicius J. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1997 July; 77(1): 37-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251677

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Distribution of calcitonin-containing parafollicular cells of the thyroid in patients with chronic lymphocytic thyroiditis: a clinical, pathological and immunohistochemical study. Author(s): Lukacs G, Sapy Z, Gyory F, Toth V, Balazs G. Source: Acta Chir Hung. 1997; 36(1-4): 204-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9408347

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Distribution of substance P-immunoreactive and calcitonin gene-related peptideimmunoreactive nerves in normal human lungs. Author(s): Komatsu T, Yamamoto M, Shimokata K, Nagura H. Source: Int Arch Allergy Appl Immunol. 1991; 95(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1717382

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Distribution of vasoactive intestinal polypeptide-, calcitonin gene-related peptide-, somatostatin- and neurofilament-immunoreactivities in sympathetic ganglia of human fetuses and premature neonates. Author(s): Roudenok V, Kuhnel W. Source: Ann Anat. 2001 May; 183(3): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396789

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Diverse interactions of calcitonin gene related peptide and nitric oxide in the gastric and cutaneous microcirculation. Author(s): Holzer P, Wachter C, Heinemann A, Jocic M, Lippe IT, Herbert MK. Source: Canadian Journal of Physiology and Pharmacology. 1995 July; 73(7): 991-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846442

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DNA methylation patterns in the calcitonin gene region at first diagnosis and at relapse of acute lymphoblastic leukemia (ALL). Author(s): Leegwater PA, Lambooy LH, De Abreu RA, Bokkerink JP, van den Heuvel LP. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 July; 11(7): 971-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9204977

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Effect of +Gz on plasma levels of calcitonin gene related peptide, endothelin and renal function in pilots. Author(s): Dai Y, Ji G, Dai D, Wang X, Xiao L. Source: Space Med Med Eng (Beijing). 1998 February; 11(1): 8-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11541277

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Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive intestinal peptide on interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha production by peripheral whole blood cells from rheumatoid arthritis and osteoarthritis patients. Author(s): Hernanz A, Medina S, de Miguel E, Martin-Mola E. Source: Regulatory Peptides. 2003 August 15; 115(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873794

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Effect of calcitriol on proliferation of TT cells and on expression of calcitonin gene. Author(s): Zabel M, Gebarowska E, Drag-Zalesinska M, Wysocka T. Source: Folia Histochem Cytobiol. 2002; 40(2): 187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12056638

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Effect of electrostatic interaction on fibril formation of human calcitonin as studied by high resolution solid state 13C NMR. Author(s): Kamihira M, Oshiro Y, Tuzi S, Nosaka AY, Saito H, Naito A. Source: The Journal of Biological Chemistry. 2003 January 31; 278(5): 2859-65. Epub 2002 November 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12446725

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Effect of seminal plasma calcitonin levels on sperm mobility. Author(s): Mungan NA, Mungan G, Basar MM, Baykam M, Atan A. Source: Archives of Andrology. 2001 April-June; 47(2): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554682

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Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia. Author(s): Preas HL 2nd, Nylen ES, Snider RH, Becker KL, White JC, Agosti JM, Suffredini AF. Source: The Journal of Infectious Diseases. 2001 August 1; 184(3): 373-6. Epub 2001 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11443567

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Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development. Author(s): Cornish J, Callon KE, Bava U, Kamona SA, Cooper GJ, Reid IR. Source: Bone. 2001 August; 29(2): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502478

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Effects of histamine H(2)-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. Author(s): Itoh H, Naito T, Takeyama M. Source: The Journal of Pharmacy and Pharmacology. 2002 November; 54(11): 1559-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495560

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Effects of human recombinant calcitonin on a rat osteopenia model induced by TPTX and arotinoid. Author(s): Fukuda C, Oizumi K, Ohhata K, Kiyokawa A, Katsumata M, Ishikawa H, Miyamoto M. Source: Calcified Tissue International. 2002 July; 71(1): 80-7. Epub 2002 June 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200658

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Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism. Author(s): Casez JP, Tschopp P, Sandberg Tschopp A, Lippuner K, Zingg E, Jaeger P. Source: Hormone Research. 2003; 59(6): 263-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784089

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Effects of steroid hormones on calcitonin gene-related peptide receptors in cultured human myometrium. Author(s): Dong YL, Wimalawansa S, Yallampalli C. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 466-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592257

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Effects of the combined use of calcitonin and 1 alpha-hydroxycholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin. Author(s): Ushiroyama T, Ikeda A, Sakai M, Higashiyama T, Ueki M. Source: Maturitas. 2001 December 14; 40(3): 229-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731184

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Enhanced vasodilator responses to calcitonin gene-related peptide (CGRP) in subcutaneous arteries in human hypertension. Author(s): Lind H, Edvinsson L. Source: Journal of Human Hypertension. 2002 January; 16(1): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11840230

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Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment. Author(s): Nagano T, Takeyama M. Source: The Journal of Pharmacy and Pharmacology. 2001 December; 53(12): 1697-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804400

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ERT, HRT, raloxifine, calcitonin, or bisphosphonates for osteoporosis. Author(s): Curtiss FR. Source: J Manag Care Pharm. 2003 March-April; 9(2): 178-81. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613350

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Evaluation of circulating calcitonin: analytical aspects. Author(s): Martinetti A, Seregni E, Ferrari L, Pallotti F, Aliberti G, Coliva A, Fracassi S, Bombardieri E. Source: Tumori. 2003 September-October; 89(5): 566-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14870789

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Explaining decreased nitric oxide production in psoriatic lesions: arginase 1 overexpression versus calcitonin gene-related peptide. Author(s): Namazi MR. Source: American Journal of Pathology. 2003 December; 163(6): 2642; Author Reply 2642-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633638

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Expression and function of the calcitonin gene products. Author(s): Zaidi M, Moonga BS, Bevis PJ, Alam AS, Legon S, Wimalawansa S, MacIntyre I, Breimer LH. Source: Vitam Horm. 1991; 46: 87-164. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746162

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Expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide in human stellate ganglia after acute myocardial infarction. Author(s): Roudenok V, Gutjar L, Antipova V, Rogov Y. Source: Ann Anat. 2001 July; 183(4): 341-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11508359

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False serum calcitonin high levels using a non-competitive two-site IRMA. Author(s): Tommasi M, Brocchi A, Cappellini A, Raspanti S, Mannelli M. Source: J Endocrinol Invest. 2001 May; 24(5): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11407656

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False-positive results of basal and pentagastrin-stimulated calcitonin in non-gene carriers of multiple endocrine neoplasia type 2A. Author(s): Hernandez G, Simo R, Oriola J, Mesa J. Source: Thyroid : Official Journal of the American Thyroid Association. 1997 February; 7(1): 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9086571

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Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1bisphosphonate. Author(s): Thiebaud D, Jacquet AF, Burckhardt P. Source: Archives of Internal Medicine. 1990 October; 150(10): 2125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2222097

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Fed-batch production of recombinant human calcitonin precursor fusion protein using Staphylococcus carnosus as an expression-secretion system. Author(s): Dilsen S, Paul W, Sandgathe A, Tippe D, Freudl R, Thommes J, Kula MR, Takors R, Wandrey C, Weuster-Botz D. Source: Applied Microbiology and Biotechnology. 2000 September; 54(3): 361-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030573

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Fibrous dysplasia in the maxilla: possible mechanism of bone remodeling by calcitonin treatment. Author(s): Yasuoka T, Takagi N, Hatakeyama D, Yokoyama K. Source: Oral Oncology. 2003 April; 39(3): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618204

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First therapeutic use of calcitonin. Author(s): Milhaud G. Source: Bone Miner. 1992 March; 16(3): 201-10. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1562820

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Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction. Author(s): Djamilian M, Stief CG, Kuczyk M, Jonas U. Source: The Journal of Urology. 1993 May; 149(5 Pt 2): 1296-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8479019

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Formation of neutralizing antibodies after treatment with human calcitonin. Author(s): Grauer A, Reinel HH, Lunghall S, Lindh E, Ziegler R, Raue F. Source: The American Journal of Medicine. 1993 October; 95(4): 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8213878

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Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS. Author(s): Zaidi M, Inzerillo AM, Moonga BS, Bevis PJ, Huang CL. Source: Bone. 2002 May; 30(5): 655-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996901

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Free solution capillary electrophoresis of calcitonins and calcitonin tryptic digests. Author(s): Tagliaro F, Moffa M, Gentile MM, Clavenna G, Valentini R, Ghielmi S, Marigo M. Source: Journal of Chromatography. B, Biomedical Applications. 1994 June 3; 656(1): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7952019

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Frequency and relevance of elevated calcitonin levels in patients with neoplastic and nonneoplastic thyroid disease and in healthy subjects. Author(s): Karanikas G, Moameni A, Poetzi C, Zettinig G, Kaserer K, Bieglmayer C, Niederle B, Dudczak R, Pirich C. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 February; 89(2): 515-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764755

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From micromolar to nanomolar affinity: a systematic approach to identify the binding site of CGRP at the human calcitonin gene-related peptide 1 receptor. Author(s): Rist B, Entzeroth M, Beck-Sickinger AG. Source: Journal of Medicinal Chemistry. 1998 January 1; 41(1): 117-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438028

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Function of the rat calcitonin receptors, C1a and C1b, expressed in Xenopus oocytes. Author(s): Matsumoto M, Kaibara M, Uezono Y, Izumi F, Sumikawa K, Sexton PM, Taniyama K. Source: Biochemical and Biophysical Research Communications. 1998 January 26; 242(3): 484-91. Erratum In: Biochem Biophys Res Commun 1998 April 28; 245(3): 947. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9464242

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Functional calcitonin gene-related peptide subtype 2 receptors in porcine coronary arteries are identified as calcitonin gene-related peptide subtype 1 receptors by radioligand binding and reverse transcription-polymerase chain reaction. Author(s): Rorabaugh BR, Scofield MA, Smith DD, Jeffries WB, Abel PW. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 December; 299(3): 1086-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714898

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Functional calcitonin gene-related peptide type 1 and adrenomedullin receptors in human trigeminal ganglia, brain vessels, and cerebromicrovascular or astroglial cells in culture. Author(s): Moreno MJ, Cohen Z, Stanimirovic DB, Hamel E. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 1999 November; 19(11): 1270-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566974

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Functional expression of heteromeric calcitonin gene-related peptide and adrenomedullin receptors in yeast. Author(s): Miret JJ, Rakhilina L, Silverman L, Oehlen B. Source: The Journal of Biological Chemistry. 2002 March 1; 277(9): 6881-7. Epub 2001 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733510

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Functional expression of receptors for calcitonin gene-related peptide, calcitonin, and vasoactive intestinal peptide in the human thymus and thymomas from myasthenia gravis patients. Author(s): Marie J, Wakkach A, Coudray A, Chastre E, Berrih-Aknin S, Gespach C. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 February 15; 162(4): 210312. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973484

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Functional role of alpha-calcitonin gene-related peptide in the regulation of the cardiovascular system. Author(s): Shen YT, Pittman TJ, Buie PS, Bolduc DL, Kane SA, Koblan KS, Gould RJ, Lynch JJ Jr. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 August; 298(2): 551-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454916

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Functionally different isoforms of the human calcitonin receptor result from alternative splicing of the gene transcript. Author(s): Moore EE, Kuestner RE, Stroop SD, Grant FJ, Matthewes SL, Brady CL, Sexton PM, Findlay DM. Source: Molecular Endocrinology (Baltimore, Md.). 1995 August; 9(8): 959-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7476993

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Further development of the locus control region/murine erythroleukemia expression system: high level expression and characterization of recombinant human calcitonin receptor. Author(s): Needham M, Egerton M, Millest A, Evans S, Popplewell M, Cerillo G, McPheat J, Monk A, Jack A, Johnstone D, et al. Source: Protein Expression and Purification. 1995 April; 6(2): 124-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7606159

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G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Author(s): Offermanns S, Iida-Klein A, Segre GV, Simon MI. Source: Molecular Endocrinology (Baltimore, Md.). 1996 May; 10(5): 566-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732687

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Gastric fundectomy in the rat: effects on mineral and bone metabolism, with emphasis on the gastrin-calcitonin-parathyroid hormone-vitamin D axis. Author(s): Rumenapf G, Schwille PO, Erben RG, Schreiber M, Berge B, Fries W, Schmiedl A, Koroma S, Hohenberger W. Source: Calcified Tissue International. 1998 November; 63(5): 433-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9799830

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91

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Gastrin-releasing peptide-, calcitonin gene-related peptide-, and calcitonin-like immunoreactivity in human breast cyst fluid and gastrin-releasing peptide-like immunoreactivity in human breast carcinoma cell lines. Author(s): Weber CJ, O'Dorisio TM, McDonald TJ, Howe B, Koschitzky T, Merriam L. Source: Surgery. 1989 December; 106(6): 1134-9; Discussion 1139-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2588117

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Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs. Author(s): Nakamura H, Asano T, Haruta K, Takeda K. Source: Canadian Journal of Physiology and Pharmacology. 1995 January; 73(1): 43-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7600451

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GH response to growth hormone releasing hormone and hypoglycaemia is unaltered by high endogenous plasma calcitonin levels in patients with medullary thyroid carcinoma. Author(s): Popovic V, Micic D, Damjanovic S, Durbaba M, Petakov M, Zoric S, Djurovic M, Manojlovic D, Micic J. Source: Clinical Endocrinology. 1991 August; 35(2): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1934528

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Giant cell lesions complicating Paget's disease of bone and their response to calcitonin therapy. Author(s): Penfold CN, Evans BT. Source: The British Journal of Oral & Maxillofacial Surgery. 1993 August; 31(4): 267. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8399049

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Glycosylation is important for binding to human calcitonin receptors. Author(s): Ho HH, Gilbert MT, Nussenzveig DR, Gershengorn MC. Source: Biochemistry. 1999 February 9; 38(6): 1866-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10026267

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Glycosylation of the calcitonin receptor-like receptor at Asn(60) or Asn(112) is important for cell surface expression. Author(s): Buhlmann N, Aldecoa A, Leuthauser K, Gujer R, Muff R, Fischer JA, Born W. Source: Febs Letters. 2000 December 15; 486(3): 320-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11119727

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Granin-A, parathyroid hormone-related protein, and calcitonin gene products in neuroendocrine prostate cancer. Author(s): Deftos LJ. Source: Prostate Suppl. 1998; 8: 23-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9690660

92

Calcitonin

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High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems. Author(s): Henriksen JH, Moller S, Schifter S, Abrahamsen J, Becker U. Source: Gut. 2001 July; 49(1): 112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11413119

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High concentrations of procalcitonin but not mature calcitonin in normal human milk. Author(s): Struck J, de Almeida P, Bergmann A, Morgenthaler NG. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 August; 34(8): 460-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198603

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High level, tissue-specific expression of a modified calcitonin/calcitonin gene-related peptide promoter in a human medullary thyroid carcinoma cell line. Author(s): Messina M, Yu DM, Learoyd DL, Both GW, Molloy PL, Robinson BG. Source: Molecular and Cellular Endocrinology. 2000 June; 164(1-2): 219-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11026573

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History of calcitonin. Author(s): Chesnut CH 3rd. Source: Lancet. 2002 September 7; 360(9335): 801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12241848

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Hormonal replacement therapy affects calcitonin gene-related peptide and atrial natriuretic peptide secretion in postmenopausal women. Author(s): Spinetti A, Margutti A, Bertolini S, Bernardi F, BiFulco G, degli Uberti EC, Petraglia F, Genazzani AR. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1997 December; 137(6): 664-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9437234

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Human calcitonin receptor is directly targeted to and retained in the basolateral surface of MDCK cells. Author(s): Nussenzveig DR, Matos MD, Thaw CN. Source: The American Journal of Physiology. 1998 November; 275(5 Pt 1): C1264-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9814975

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93

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Human calcitonin receptor-like receptor for adrenomedullin: genomic structure, eight single-nucleotide polymorphisms, and haplotype analysis. Author(s): Nakazawa I, Nakajima T, Harada H, Ishigami T, Umemura S, Emi M. Source: Journal of Human Genetics. 2001; 46(3): 132-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310580

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Human calcitonin receptors exhibit agonist-independent (constitutive) signaling activity. Author(s): Cohen DP, Thaw CN, Varma A, Gershengorn MC, Nussenzveig DR. Source: Endocrinology. 1997 April; 138(4): 1400-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9075694

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Human facial nucleus: choline acetyltransferase and calcitonin gene-related peptide. Author(s): Arzberger T, Ritter E, Weindl A. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1994 December; : S403-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10774405

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Human osteoblast-like cell proliferation induced by calcitonin-related peptides involves PKC activity. Author(s): Villa I, Dal Fiume C, Maestroni A, Rubinacci A, Ravasi F, Guidobono F. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 March; 284(3): E627-33. Epub 2002 November 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556355

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Human pulp cells respond to calcitonin gene-related peptide in vitro. Author(s): Calland JW, Harris SE, Carnes DL Jr. Source: Journal of Endodontics. 1997 August; 23(8): 485-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9587316

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Human transformer 2beta and SRp55 interact with a calcitonin-specific splice enhancer. Author(s): Tran Q, Coleman TP, Roesser JR. Source: Biochimica Et Biophysica Acta. 2003 January 27; 1625(2): 141-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531473

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Hybridocytochemical detection of mRNA for calcitonin, CGRP, somatostatin and NPY in cultured cells of medullary thyroid carcinoma using immunomax technique. Author(s): Kasprzak A, Zabel M, Surdyk-Zasada J, Seidel J. Source: Folia Histochem Cytobiol. 1999; 37(2): 59-60. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10352957

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Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and during complete remission. Author(s): Thomas X, Teillon MH, Belhabri A, Rimokh R, Fiere D, Magaud JP, Archimbaud E. Source: Hematology and Cell Therapy. 1999 February; 41(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193642

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Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing. Author(s): Hakkarainen M, Wahlfors J, Myohanen S, Hiltunen MO, Eskelinen M, Johansson R, Janne J. Source: International Journal of Cancer. Journal International Du Cancer. 1996 December 20; 69(6): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8980249

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Hypermethylation of the calcitonin gene and leukemia. Author(s): Baruchel A, Sigaux F. Source: Nouv Rev Fr Hematol. 1991; 33(6): 551-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1818314

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Hypermethylation of the calcitonin gene in acute lymphoblastic leukaemia is associated with unfavourable clinical outcome. Author(s): Roman J, Castillejo JA, Jimenez A, Bornstein R, Gonzalez MG, del Carmen Rodriguez M, Barrios M, Maldonado J, Torres A. Source: British Journal of Haematology. 2001 May; 113(2): 329-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380396

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Hypermethylation of the WT1 and calcitonin gene promoter regions at chromosome 11p in human colorectal cancer. Author(s): Hiltunen MO, Koistinaho J, Alhonen L, Myohanen S, Marin S, Kosma VM, Paakkonen M, Janne J. Source: British Journal of Cancer. 1997; 76(9): 1124-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9365158

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Hypocalcaemia and calcitonin precursors in critically ill patients. Author(s): Ammori BJ. Source: Archives of Disease in Childhood. 2003 February; 88(2): 179. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538340

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Hypothalamic amenorrhea and cardiovascular hormones: changes of plasma calcitonin gene-related peptide and atrial natriuretic peptide levels. Author(s): Bernardi F, Valentini A, Margutti A, Santuz M, Degli Uberti EC, Petraglia F, Genazzani AR. Source: J Endocrinol Invest. 1998 April; 21(4): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9624600

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Identification of two distinct subpopulations in a ganglioneuroblastoma: lack of colocalization of vasoactive intestinal polypeptide and calcitonin in ganglionic cells at the ultrastructural level. Author(s): Schellscheidt J, Baas S, Schmid KW, Vormoor J, Zimmer KP. Source: Medical and Pediatric Oncology. 2003 December; 41(6): 571-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595721

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Identification, structural determination, and biological activity of bovine and canine calcitonin receptor-stimulating peptides. Author(s): Katafuchi T, Hamano K, Minamino N. Source: Biochemical and Biophysical Research Communications. 2004 January 2; 313(1): 74-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672700

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Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature. Author(s): Oliver KR, Wainwright A, Edvinsson L, Pickard JD, Hill RG. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2002 May; 22(5): 620-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973435

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Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. Author(s): Elisei R, Bottici V, Luchetti F, Di Coscio G, Romei C, Grasso L, Miccoli P, Iacconi P, Basolo F, Pinchera A, Pacini F. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 January; 89(1): 1638. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715844

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Importance of the amino terminus in secretin family G protein-coupled receptors. Intrinsic photoaffinity labeling establishes initial docking constraints for the calcitonin receptor. Author(s): Dong M, Pinon DI, Cox RF, Miller LJ. Source: The Journal of Biological Chemistry. 2004 January 9; 279(2): 1167-75. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583624

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Improving depth and maintenance of sleep with intramuscular calcitonin: A case report. Author(s): Nakajima T, Kajimura N, Kato M, Watanabe T, Nakabayashi T, Hori T, Takahashi K. Source: Psychiatry and Clinical Neurosciences. 2002 August; 56(4): 481-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109970

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In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Author(s): Linscheid P, Seboek D, Nylen ES, Langer I, Schlatter M, Becker KL, Keller U, Muller B. Source: Endocrinology. 2003 December; 144(12): 5578-84. Epub 2003 August 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960010

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In vitro characterization of a human calcitonin receptor gene polymorphism. Author(s): Wolfe LA 3rd, Fling ME, Xue Z, Armour S, Kerner SA, Way J, Rimele T, Cox RF. Source: Mutation Research. 2003 January 28; 522(1-2): 93-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517415

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Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. Author(s): Hoff AO, Catala-Lehnen P, Thomas PM, Priemel M, Rueger JM, Nasonkin I, Bradley A, Hughes MR, Ordonez N, Cote GJ, Amling M, Gagel RF. Source: The Journal of Clinical Investigation. 2002 December; 110(12): 1849-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488435

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Influence of fluor salts, hormone replacement therapy and calcitonin on the concentration of insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor-beta 1 in human iliac crest bone matrix from patients with primary osteoporosis. Author(s): Pepene CE, Seck T, Diel I, Minne HW, Ziegler R, Pfeilschifter J. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2004 January; 150(1): 81-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14713283

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Inhibitory effect of calcitonin on growth hormone response to growth hormone releasing hormone in acromegaly. Author(s): Sarno-Moraes CR, Czepielewski MA, Vieira JG, Chacra AR, Lengyel AM. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1991; 24(10): 1003-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1686733

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Interaction of bisphosphonates with calcitonin in monitoring medullary carcinoma of the thyroid. Author(s): Osborne ME, Brown RS, Hoskin PJ. Source: Clin Oncol (R Coll Radiol). 2001; 13(5): 370-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11716232

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Interaction of calcitonin-gene-related peptide with its receptors. Author(s): Conner AC, Hay DL, Howitt SG, Kilk K, Langel U, Wheatley M, Smith DM, Poyner DR. Source: Biochemical Society Transactions. 2002 August; 30(4): 451-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196113

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Interference causes false high calcitonin levels with a commercial assay. Author(s): Bieglmayer Ch, Niederle B, Vierhapper H. Source: J Endocrinol Invest. 2002 February; 25(2): 197. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929094

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Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes. Author(s): Roh J, Chang CL, Bhalla A, Klein C, Hsu SY. Source: The Journal of Biological Chemistry. 2004 February 20; 279(8): 7264-74. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615490

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International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Author(s): Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. Source: Pharmacological Reviews. 2002 June; 54(2): 233-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037140

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Intramuscular transfer of naked calcitonin gene-related peptide gene prevents autoimmune diabetes induced by multiple low-dose streptozotocin in C57BL mice. Author(s): Sun W, Wang L, Zhang Z, Chen M, Wang X. Source: European Journal of Immunology. 2003 January; 33(1): 233-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12594852

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Intranasal and intramuscular human calcitonin in female osteoporosis and in Paget's disease of bones: a pilot study. Author(s): Pontiroli AE, Pajetta E, Calderara A, Alberetto M, Pozza G, Manganelli V, Resmini G, Tessari L, Maresca V. Source: J Endocrinol Invest. 1991 January; 14(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1646250

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Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone. Author(s): Dong YL, Vegiraju S, Chauhan M, Gangula PR, Hankins GD, Goodrum L, Yallampalli C. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2004 January; 286(1): H230-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684361

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Is calcitonin an important physiological substance? Author(s): Hirsch PF, Baruch H. Source: Endocrine. 2003 August; 21(3): 201-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515002

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Katacalcin and calcitonin immunoreactivity in different types of leukocytes indicate intracellular procalcitonin content. Author(s): Oberhoffer M, Vogelsang H, Jager L, Reinhart K. Source: Journal of Critical Care. 1999 March; 14(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10102721

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Kidney: a target organ for calcitonin gene-related peptide. Author(s): Zaidi M, Datta H, Bevis PJ. Source: Experimental Physiology. 1990 January; 75(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2155624

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Lack of effect of calcitonin gene-related peptide and amylin on major markers of glucose metabolism in hepatocytes. Author(s): Pittner RA. Source: European Journal of Pharmacology. 1997 May 1; 325(2-3): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9163566

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Lack of effect of human parathyroid hormone and calcitonin on cytokine and prostaglandin secretion by blood mononuclear cells. Author(s): Zarrabeitia MT, Riancho JA, Amado JA, Gonzalez-Macias J. Source: Methods Find Exp Clin Pharmacol. 1991 October; 13(8): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1956208

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Lack of effect of nasal salmon calcitonin on cell-mediated immunity. Author(s): Thamsborg G, Moller T, Kollerup G, Sorensen OH. Source: Bone Miner. 1993 March; 20(3): 245-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8490328

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Lack of effect of salmon calcitonin on serum level of soluble form of E-selectin (CD 62E) in patients with atopic bronchial asthma. Author(s): Polanowicz U, Gina AR, Pieczyrak R, Kucharz EJ, Jonderko G, KonderaArasz Z. Source: Rom J Intern Med. 1998 January-June; 36(1-2): 113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10660976

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Lack of efficacy of calcitonin in preventing glucocorticoid-induced bone loss: comment on the American College of Rheumatology recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Author(s): Fudman EJ. Source: Arthritis and Rheumatism. 1997 August; 40(8): 1549. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259445

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Lafutidine changes levels of somatostatin, calcitonin gene-related peptide, and secretin in human plasma. Author(s): Itoh H, Naito T, Takeyama M. Source: Biological & Pharmaceutical Bulletin. 2002 March; 25(3): 379-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11913538

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Leg uptake of calcitonin gene-related peptide during exercise in spinal cord injured humans. Author(s): Kjaer M, Mohr T, Dela F, Secher N, Galbo H, Olesen H, Sorensen F, Schifter S. Source: Clinical Physiology (Oxford, England). 2001 January; 21(1): 32-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168294

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Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors. Author(s): Fujiwara S, Sposto R, Shiraki M, Yokoyama N, Sasaki H, Kodama K, Shimaoka K. Source: Radiation Research. 1994 January; 137(1): 96-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8265793

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Limitations in using peptide drugs to characterize calcitonin gene-related peptide receptors. Author(s): Waugh DJ, Bockman CS, Smith DD, Abel PW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 June; 289(3): 1419-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10336535

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Linkage between capsaicin-stimulated calcitonin gene-related peptide and somatostatin release in rat stomach. Author(s): Inui T, Kinoshita Y, Yamaguchi A, Yamatani T, Chiba T. Source: The American Journal of Physiology. 1991 November; 261(5 Pt 1): G770-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1683166

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Localization of calcitonin gene-related peptide in the rat and human pituitary gland using immunocytochemistry and in situ hybridization. CGRP expression during ontogeny and after endocrine manipulations. Author(s): Steel JH, Gon G, Giaid A, O'Halloran DJ, Emson MA, Van Noorden S, Ghatei MA, Jones PM, Amara SG, Ishikawa H, et al. Source: Annals of the New York Academy of Sciences. 1992 June 30; 657: 135-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1637080

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Localization of cholecystokinin-like and calcitonin-like peptides in infant carotid bodies: a light- and electron-microscopic immunohistochemical study. Author(s): Wang YY, Perrin DG, Cutz E. Source: Cell and Tissue Research. 1993 April; 272(1): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8481949

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Long- and short-term side effects and safety of calcitonin in man: a prospective study. Author(s): Wimalawansa SJ. Source: Calcified Tissue International. 1993 February; 52(2): 90-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8443697

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Long-term (3 years) prevention of trabecular postmenopausal bone loss with lowdose intermittent nasal salmon calcitonin. Author(s): Reginster JY, Denis D, Deroisy R, Lecart MP, De Longueville M, Zegels B, Sarlet N, Noirfalisse P, Franchimont P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1994 January; 9(1): 69-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8154311

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Long-term excess of endogenous calcitonin in patients with medullary thyroid carcinoma does not affect bone mineral density. Author(s): Wuster C, Raue F, Meyer C, Bergmann M, Ziegler R. Source: The Journal of Endocrinology. 1992 July; 134(1): 141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1354241

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Long-term exposure to SMS 201-995 inhibits proliferation and calcitonin release in neoplastic C-cells. Author(s): Mekonnen Y, Raue F, Zink A, Ziegler R. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1993 October; 25(10): 528-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8262461

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Long-term influence of anticonvulsant agents on calcitonin, parathyroid hormone and osteocalcin. Author(s): Rico H, Varela de Seijas E, Arias JA, Cabranes JA. Source: European Neurology. 1992; 32(6): 324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1490499

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Long-term treatment with calcitonin in osteoporosis. Author(s): Gennari C, Agnusdei D, Camporeale A. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1993 September; 25(9): 484-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225202

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Loss of transcriptional repression contributes to the ectopic expression of the calcitonin/alpha-CGRP gene in a human lung carcinoma cell line. Author(s): Symes AJ, Craig RK, Brickell PM. Source: Febs Letters. 1992 July 20; 306(2-3): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1633879

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Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients. Author(s): Lindh C, Liu Z, Welin M, Ordeberg G, Nyberg F. Source: Neuropeptides. 1999 December; 33(6): 517-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10657534

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Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells. Author(s): Aldecoa A, Gujer R, Fischer JA, Born W. Source: Febs Letters. 2000 April 14; 471(2-3): 156-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10767413

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Maternal plasma calcitonin gene-related peptide levels do not change during labor and are not influenced by delivery route. Author(s): Florio P, Margutti A, Apa R, Miceli F, Pezzani I, Degli Uberti EC, Petraglia F. Source: Journal of the Society for Gynecologic Investigation. 2001 May-June; 8(3): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11390251

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Mechanism of SNAP potentiating antiproliferative effect of calcitonin gene-related peptide in cultured vascular smooth muscle cells. Author(s): Wang X, Wang W, Li Y, Bai Y, Fiscus RR. Source: Journal of Molecular and Cellular Cardiology. 1999 September; 31(9): 1599-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10471344

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Mechanism of tissue-specific alternative RNA processing of the calcitonin CGRP gene. Author(s): Lou H, Gagel RF. Source: Frontiers of Hormone Research. 1999; 25: 18-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10941400

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Medullary thyroid carcinoma: role of genetic testing and calcitonin measurement. Author(s): Lips CJ, Hoppener JW, Thijssen JH. Source: Annals of Clinical Biochemistry. 2001 May; 38(Pt 3): 168-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11392493

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Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Author(s): Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Shea B, Wells G, Adachi J, Waldegger L, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 540-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202469

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Metastatic cervical carcinoma with ectopic calcitonin production presenting as a thyroid mass. Author(s): Singh R, Bibbo M, Cunnane MF, Carlson JA, de Papp AE. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2002 January-February; 8(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939761

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Migration of 3T3 and lung fibroblasts in response to calcitonin gene-related peptide and bombesin. Author(s): Yule KA, White SR. Source: Experimental Lung Research. 1999 April-May; 25(3): 261-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10352955

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Modifications to the N-terminus but not the C-terminus of calcitonin gene-related peptide(8-37) produce antagonists with increased affinity. Author(s): Smith DD, Saha S, Fang G, Schaffert C, Waugh DJ, Zeng W, Toth G, Hulce M, Abel PW. Source: Journal of Medicinal Chemistry. 2003 June 5; 46(12): 2427-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773046

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Molecular cloning and characterization of mouse calcitonin gene-related peptide receptor. Author(s): Miyauchi K, Tadotsu N, Hayashi T, Ono Y, Tokoyoda K, Tsujikawa K, Yamamoto H. Source: Neuropeptides. 2002 February; 36(1): 22-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147211

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Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells. Author(s): Aiyar N, Disa J, Ao Z, Xu D, Surya A, Pillarisetti K, Parameswaran N, Gupta SK, Douglas SA, Nambi P. Source: Biochemical Pharmacology. 2002 June 1; 63(11): 1949-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093471

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Molecular cloning of otoconin-22 complementary deoxyribonucleic acid in the bullfrog endolymphatic sac: effect of calcitonin on otoconin-22 messenger ribonucleic acid levels. Author(s): Yaoi Y, Suzuki M, Tomura H, Sasayama Y, Kikuyama S, Tanaka S. Source: Endocrinology. 2003 August; 144(8): 3287-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865304

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Molecular pharmacology of the calcitonin receptor. Author(s): Purdue BW, Tilakaratne N, Sexton PM. Source: Receptors & Channels. 2002; 8(3-4): 243-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529940

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Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate. Author(s): Spetz AC, Pettersson B, Varenhorst E, Theodorsson E, Thorell LH, Hammar M. Source: The Journal of Urology. 2001 November; 166(5): 1720-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11586209

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Multicenter collaborative study to calibrate salmon calcitonin by bioassay and highperformance liquid chromatography: establishment of the third international standard. Author(s): Rafferty B, Corran P, Bristow A. Source: Bone. 2001 July; 29(1): 84-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472896

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Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Author(s): Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, Sexton PM. Source: Molecular Pharmacology. 1999 July; 56(1): 235-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385705

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Multiple promoters regulate human calcitonin receptor gene expression. Author(s): Hebden C, Smalt R, Chambers T, Pondel MD. Source: Biochemical and Biophysical Research Communications. 2000 June 16; 272(3): 738-43. Erratum In: Biochem Biophys Res Commun 2000 July 14; 273(3): 1180. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10860825

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Multiple ramp domains are required for generation of amylin receptor phenotype from the calcitonin receptor gene product. Author(s): Zumpe ET, Tilakaratne N, Fraser NJ, Christopoulos G, Foord SM, Sexton PM. Source: Biochemical and Biophysical Research Communications. 2000 January 7; 267(1): 368-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10623626

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Mutations of the asparagine117 residue of a receptor activity-modifying protein 1dependent human calcitonin gene-related peptide receptor result in selective loss of function. Author(s): Gujer R, Aldecoa A, Buhlmann N, Leuthauser K, Muff R, Fischer JA, Born W. Source: Biochemistry. 2001 May 8; 40(18): 5392-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11331002

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Myocardial outflow of calcitonin gene-related peptide in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass. Author(s): Kallner G, Owall A, Franco-Cereceda A. Source: The Journal of Thoracic and Cardiovascular Surgery. 1999 March; 117(3): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10047646

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Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis. Author(s): Flicker L, Hopper JL, Larkins RG, Lichtenstein M, Buirski G, Wark JD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1997; 7(1): 29-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9102059

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Nasal calcitonin. Author(s): Silverman SL. Source: Endocrine. 1997 April; 6(2): 199-202. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9225136

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Nasal salmon calcitonin in osteoporosis. Author(s): Overgaard K, Riis BJ. Source: Calcified Tissue International. 1994 August; 55(2): 79-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7953983

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Neurogenic vasodilation in rabbit basilar isolated artery: involvement of calcitoningene related peptide. Author(s): Olivar T, Razzaque Z, Nwagwu M, Longmore J. Source: European Journal of Pharmacology. 2000 April 21; 395(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10781675

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Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone. Author(s): Imai S, Matsusue Y. Source: Microscopy Research and Technique. 2002 July 15; 58(2): 61-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203704

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Neuropeptide Y and the calcitonin gene-related peptide attenuate learning impairments induced by MK-801 via a sigma receptor-related mechanism. Author(s): Bouchard P, Maurice T, St-Pierre S, Privat A, Quirion R. Source: The European Journal of Neuroscience. 1997 October; 9(10): 2142-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9421174

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No need to heat bronchoalveolar lavage fluid for calcitonin measurement. Author(s): Prados C, Alvarez-Sala R, Garcia-Rio F, Blasco R, Gomez de Terreros FJ, Villamor J. Source: Int J Biol Markers. 1994 July-September; 9(3): 148-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7829895

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Nocturnal rise in markers of bone resorption is not abolished by bedtime calcium or calcitonin. Author(s): Sairanen S, Tahtela R, Laitinen K, Karonen SL, Valimaki MJ. Source: Calcified Tissue International. 1994 November; 55(5): 349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7866915

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NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Author(s): Juhasz G, Zsombok T, Modos EA, Olajos S, Jakab B, Nemeth J, Szolcsanyi J, Vitrai J, Bagdy G. Source: Pain. 2003 December; 106(3): 461-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659530

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Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses. Author(s): Redding AH, Levine SN, Fowler MR. Source: Thyroid : Official Journal of the American Thyroid Association. 2000 October; 10(10): 919-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081258

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Novel and selective calcitonin-inducing agents. Author(s): Gilbert AM, Caltabiano S, Roberts D, Sum SF, Francisco GD, Lim K, Asselin M, Ellingboe JW, Kharode Y, Cannistraci A, Francis R, TrailSmith M, Gralnick D. Source: Journal of Medicinal Chemistry. 2000 March 23; 43(6): 1223-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10737755

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Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from coexpression of calcitonin receptor with receptor activity-modifying proteins. Author(s): Kuwasako K, Kitamura K, Nagoshi Y, Eto T. Source: Biochemical and Biophysical Research Communications. 2003 February 7; 301(2): 460-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12565884

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Novel daunorubicin-carrier peptide conjugates derived from human calcitonin segments. Author(s): Krauss U, Kratz F, Beck-Sickinger AG. Source: Journal of Molecular Recognition : Jmr. 2003 September-October; 16(5): 280-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523941

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Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma. Author(s): Erdogan MF, Gullu S, Baskal N, Uysal AR, Kamel N, Erdogan G. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 March; 82(3): 897-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9062503

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On the role of tachykinins and calcitonin gene-related peptide in the spinal mechanisms of nociception and in the induction and maintenance of inflammationevoked hyperexcitability in spinal cord neurons (with special reference to nociception in joints). Author(s): Schaible HG. Source: Prog Brain Res. 1996; 113: 423-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9009749

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On the role of the C-terminus of alpha-calcitonin-gene-related peptide (alpha CGRP). The structure of des-phenylalaninamide37-alpha CGRP and its interaction with the CGRP receptor. Author(s): O'Connell JP, Kelly SM, Raleigh DP, Hubbard JA, Price NC, Dobson CM, Smith BJ. Source: The Biochemical Journal. 1993 April 1; 291 ( Pt 1): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8385932

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Oral delivery of salmon calcitonin. Author(s): Lee YH, Sinko PJ. Source: Advanced Drug Delivery Reviews. 2000 August 31; 42(3): 225-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963837

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Osteoblast numbers after calcitonin therapy: a retrospective study of paired biopsies obtained during long-term calcitonin therapy in postmenopausal osteoporosis. Author(s): Gruber HE, Grigsby J, Chesnut Ill CH. Source: Calcified Tissue International. 2000 January; 66(1): 29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10602841

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Osteoporosis by ovariectomy: calcitonin effect in an experimental model on the rat. Author(s): Gnudi S, Giardino R, Mongiorgi R, Zati A, Giavaresi GL, Bertocchi G, Gandolfi MG, Avella M. Source: Boll Soc Ital Biol Sper. 1993 September; 69(9): 563-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8155314

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Osteoporosis syndromes: patient selection for calcitonin therapy. Author(s): Avioli LV. Source: Geriatrics. 1992 April; 47(4): 58, 61-4, 67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1555780

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Osteoporosis: monitoring techniques and alternate therapies. Calcitonin, fluoride, bisphosphonates, vitamin D. Author(s): Baran DT. Source: Obstetrics and Gynecology Clinics of North America. 1994 June; 21(2): 321-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7936547

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Oxytocin does not modify glucagon- or calcitonin-induced ACTH-cortisol rise in humans. Author(s): Volpi R, Chiodera P, Bianconi L, Marcato A, Cavazzini U, Pignatti D, Capretti L, Lacroce P, Rossi G, Camellini L, et al. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1989 November; 21(11): 635-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2556340

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Persistent hypercalcitoninemia in patients with medullary thyroid cancer: a therapeutic approach based on selective venous sampling for calcitonin. Author(s): Medina-Franco H, Herrera MF, Lopez G, Tielve-Campillo M, Sierra M, Lozano-Salazar RR, Gonzalez O. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2001 May-June; 53(3): 212-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11496707

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Phosphorylation of mitogen-activated protein kinase is inhibited by calcitonin in DU145 prostate cancer cells. Author(s): Segawa N, Nakamura M, Nakamura Y, Mori I, Katsuoka Y, Kakudo K. Source: Cancer Research. 2001 August 15; 61(16): 6060-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11507054

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Plasma type 1 collagen cross-linked C-telopeptide: a sensitive marker of acute effects of salmon calcitonin on bone resorption. Author(s): Zikan V, Stepan JJ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 February; 316(1-2): 63-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750275

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Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and changes during calcitonin plus calcium therapy. Author(s): Gur A, Denli A, Nas K, Cevik R, Karakoc M, Sarac AJ, Erdogan F. Source: Rheumatology International. 2002 September; 22(5): 194-8. Epub 2002 July 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12215865

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Preparation and evaluation of proliposomes containing salmon calcitonin. Author(s): Song KH, Chung SJ, Shim CK. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2002 November 7; 84(1-2): 27-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399165

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Presurgical assessment of the tumor burden of familial medullary thyroid carcinoma by calcitonin testing. Author(s): Pomares FJ, Rodriguez JM, Nicolas F, Sola J, Canteras M, Balsalobre M, Pascual M, Parrilla P, Tebar FJ. Source: Journal of the American College of Surgeons. 2002 November; 195(5): 630-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437249

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Prevention of heterotopic ossification after total hip replacement: a prospective comparison of indomethacin and salmon calcitonin in 60 patients. Author(s): Gunal I, Hazer B, Seber S, Gokturk E, Turgut A, Kose N. Source: Acta Orthopaedica Scandinavica. 2001 October; 72(5): 467-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728072

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Production and secretion of calcitonin gene-related peptide from human lymphocytes. Author(s): Wang H, Xing L, Li W, Hou L, Guo J, Wang X. Source: Journal of Neuroimmunology. 2002 September; 130(1-2): 155-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12225897

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Production of cAMP by adrenomedullin in human oligodendroglial cell line KG1C: comparison with calcitonin gene-related peptide and amylin. Author(s): Uezono Y, Nakamura E, Ueda Y, Shibuya I, Ueta Y, Yokoo H, Yanagita T, Toyohira Y, Kobayashi H, Yanagihara N, Wada A. Source: Brain Research. Molecular Brain Research. 2001 December 16; 97(1): 59-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744163

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Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins. Author(s): Hilairet S, Foord SM, Marshall FH, Bouvier M. Source: The Journal of Biological Chemistry. 2001 August 3; 276(31): 29575-81. Epub 2001 May 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11387328

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Quantification of intracellular calcitonin gene transcripts in human medullary thyroid carcinoma (MTC) by in situ hybridization. Author(s): Noel M, Gavoille A, Lasmoles F, Kahn E, Caillou B, Gardet P, Fragu P. Source: J Endocrinol Invest. 1990 July-August; 13(7): 567-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2229929

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Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in gingival crevicular fluid associated with painful human teeth. Author(s): Awawdeh LA, Lundy FT, Linden GJ, Shaw C, Kennedy JG, Lamey PJ. Source: European Journal of Oral Sciences. 2002 June; 110(3): 185-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12120702

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Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. Author(s): Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG. Source: International Endodontic Journal. 2002 January; 35(1): 30-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11853236

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Quantitative analysis of synthetic human calcitonin by liquid chromatography-mass spectrometry. Author(s): Kobayashi N, Kanai M, Seta K, Nakamura K. Source: Journal of Chromatography. B, Biomedical Applications. 1995 October 6; 672(1): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8590932

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Quantitative autoradiography reveals higher densities of specific calcitonin-generelated peptide receptors in small intramyocardial compared with large epicardial coronary arteries. Author(s): Sun B, Davenport AP, Brown MJ. Source: Clinical Science (London, England : 1979). 1993 January; 84(1): 55-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8382135

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Randomized, double-blind, clinically controlled trial of intranasal calcitonin treatment in patients with hip fracture. Author(s): Huusko TM, Karppi P, Kautiainen H, Suominen H, Avikainen V, Sulkava R. Source: Calcified Tissue International. 2002 December; 71(6): 478-84. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370798

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Rapid growth of giant cell granuloma in pregnancy treated with calcitonin. Author(s): O'Regan EM, Gibb DH, Odell EW. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 November; 92(5): 532-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11709690

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Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells. Author(s): Aiyar N, Disa J, Pullen M, Nambi P. Source: Molecular and Cellular Biochemistry. 2001 August; 224(1-2): 123-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11693189

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Receptors for calcitonin gene-related peptide, adrenomedullin, and amylin: the contributions of novel receptor-activity-modifying proteins. Author(s): Born W, Fischer JA, Muff R. Source: Receptors & Channels. 2002; 8(3-4): 201-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529937

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Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Author(s): Durham PL, Cady R, Cady R. Source: Headache. 2004 January; 44(1): 35-42; Discussion 42-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979881

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Regulation of osteoclasts by calcitonin and amphiphilic calcitonin conjugates: role of cytosolic calcium. Author(s): Komarova SV, Shum JB, Paige LA, Sims SM, Dixon SJ. Source: Calcified Tissue International. 2003 September; 73(3): 265-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667140

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Relative bioavailability of salmon calcitonin given intramuscularly. Author(s): Chen P, Lai JM, Deng JF, Lu SB, Ku H. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 August; 63(8): 619-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10969448

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Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis. Author(s): Woo T, Adachi JD. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 469-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485341

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Role of substance P and calcitonin gene-related peptide in the regulation of interleukin-8 and monocyte chemotactic protein-1 expression in human dental pulp. Author(s): Park SH, Hsiao GY, Huang GT. Source: International Endodontic Journal. 2004 March; 37(3): 185-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15009408

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RT-PCR-based detection of circulating calcitonin-producing cells in patients with advanced medullary thyroid cancer. Author(s): Saller B, Feldmann G, Haupt K, Broecker M, Janssen OE, Roggendorf M, Mann K, Lu M. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 January; 87(1): 2926. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788662

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Salmon calcitonin treatment by nasal spray in primary hyperparathyroidism. Author(s): Torring O, Bucht E, Sjostedt U, Sjoberg HE. Source: Bone. 1991; 12(5): 311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1782100

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Sequencing of a calcitonin receptor-like receptor in salmon Oncorhynchus gorbuscha. Functional studies using the human receptor activity-modifying proteins. Author(s): Pidoux E, Cressent M. Source: Gene. 2002 October 2; 298(2): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426108

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Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin. Author(s): Yap AS, Mortimer RH, Jacobi JM, Galligan JP, Perry-Keene DA, Khafagi FA. Source: Hormone Research. 1991; 36(1-2): 70-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1814803

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Solid-phase synthesis of peptide radiopharmaceuticals using Fmoc-N-epsilon-(hynicBoc)-lysine, a technetium-binding amino acid: application to Tc-99m-labeled salmon calcitonin. Author(s): Greenland WE, Howland K, Hardy J, Fogelman I, Blower PJ. Source: Journal of Medicinal Chemistry. 2003 April 24; 46(9): 1751-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699393

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Somatostatin receptor subtype 1-selective activation reduces cell growth and calcitonin secretion in a human medullary thyroid carcinoma cell line. Author(s): Zatelli MC, Tagliati F, Piccin D, Taylor JE, Culler MD, Bondanelli M, degli Uberti EC. Source: Biochemical and Biophysical Research Communications. 2002 October 4; 297(4): 828-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359227

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SRp55 is a regulator of calcitonin/CGRP alternative RNA splicing. Author(s): Tran Q, Roesser JR. Source: Biochemistry. 2003 February 4; 42(4): 951-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549914

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Stability of a transdermal salmon calcitonin formulation. Author(s): Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK. Source: Drug Delivery. 2003 January-March; 10(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554363

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Substance P and calcitonin gene-related peptide increase IL-1 beta, IL-6 and TNF alpha secretion from human peripheral blood mononuclear cells. Author(s): Cuesta MC, Quintero L, Pons H, Suarez-Roca H. Source: Neurochemistry International. 2002 April; 40(4): 301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792459

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Substance P-containing and calcitonin gene-related peptide-containing neurons in the human trigeminal ganglion. Immunohistochemical detection, morphometric characterization, and coexistence of peptides. Author(s): Del Fiacco M, Diaz G, Floris A, Quartu M. Source: Annals of the New York Academy of Sciences. 1991; 632: 382-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1719883

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Superior local tolerability of human versus salmon calcitonin preparations in young healthy volunteers. Author(s): Wuster C, Schurr W, Scharla S, Raue F, Minne HW, Ziegler R. Source: European Journal of Clinical Pharmacology. 1991; 41(3): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1748138

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The calcitonin conundrum--is it time for routine measurement of serum calcitonin in patients with thyroid nodules? Author(s): Hodak SP, Burman KD. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 February; 89(2): 511-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764754

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The effect of adrenomedullin, amylin fragment 8-37 and calcitonin gene-related peptide on contractile force, heart rate and coronary perfusion pressure in isolated rat hearts. Author(s): Kaygisiz Z, Erksap N, Uyar R, Kabadere S, Kabadere TE, Dernek S. Source: Acta Physiol Hung. 2003; 90(2): 133-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12903912

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The effects of calcitonin on acute bone loss after pertrochanteric fractures. A prospective, randomised trial. Author(s): Karachalios T, Lyritis GP, Kaloudis J, Roidis N, Katsiri M. Source: The Journal of Bone and Joint Surgery. British Volume. 2004 April; 86(3): 350-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15125121

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The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas. Author(s): Benes L, Kappus C, McGregor GP, Bertalanffy H, Mennel HD, Hagner S. Source: Journal of Clinical Pathology. 2004 February; 57(2): 172-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747444

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The neuropeptide calcitonin gene-related peptide differently modulates proliferation and differentiation of smooth muscle cells in culture depending on the cell type. Author(s): Connat JL, Schnuriger V, Zanone R, Schaeffer C, Gaillard M, Faivre B, Rochette L. Source: Regulatory Peptides. 2001 September 15; 101(1-3): 169-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11495693

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The role of trace minerals in the pathogenesis of postmenopausal osteoporosis and a new effect of calcitonin. Author(s): Gur A, Colpan L, Nas K, Cevik R, Sarac J, Erdogan F, Duz MZ. Source: Journal of Bone and Mineral Metabolism. 2002; 20(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810415

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Three receptor-activity-modifying proteins define calcitonin gene-related peptide or adrenomedullin selectivity of the mouse calcitonin-like receptor in COS-7 cells. Author(s): Husmann K, Born W, Fischer JA, Muff R. Source: Biochemical Pharmacology. 2003 December 1; 66(11): 2107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609735

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Tissue-specific activity of the proximal human calcitonin receptor promoter is mediated by Sp1 and an epigenetic phenomenon. Author(s): Pondel MD, Partington GA, Mould R. Source: Febs Letters. 2003 November 20; 554(3): 433-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623107

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Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors. Author(s): Jiang S, Altmann A, Grimm D, Kleinschmidt JA, Schilling T, Germann C, Haberkorn U. Source: Cancer Gene Therapy. 2001 July; 8(7): 469-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11498767

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Trichorzin HA V, a member of the peptaibol family, stimulates intracellular cAMP formation in cells expressing the calcitonin receptor. Author(s): Katayama T, Miyagawa K, Kodama T, Oikawa S. Source: Biological & Pharmaceutical Bulletin. 2001 December; 24(12): 1420-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11767114

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U1 snRNP-dependent function of TIAR in the regulation of alternative RNA processing of the human calcitonin/CGRP pre-mRNA. Author(s): Zhu H, Hasman RA, Young KM, Kedersha NL, Lou H. Source: Molecular and Cellular Biology. 2003 September; 23(17): 5959-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917321

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Ultrasound parameters in osteoporotic patients treated with salmon calcitonin: a longitudinal study. Author(s): Gonnelli S, Cepollaro C, Pondrelli C, Martini S, Rossi S, Gennari C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1996; 6(4): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8883119

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Ultrastructural evaluation of calcitonin gene-related peptide immunoreactivity in the human cochlea and vestibular endorgans. Author(s): Kong WJ, Scholtz AW, Kammen-Jolly K, Gluckert R, Hussl B, von Cauvenberg PB, Schrott-Fischer A. Source: The European Journal of Neuroscience. 2002 February; 15(3): 487-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876776

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Ultraviolet B radiation induces upregulation of calcitonin gene-related peptide levels in human Finn chamber skin samples. Author(s): Sleijffers A, Herreilers M, van Loveren H, Garssen J. Source: Journal of Photochemistry and Photobiology. B, Biology. 2003 March; 69(3): 14952. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695028

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Unilateral injection of calcitonin gene-related peptide (CGRP) induces bilateral oedema formation and release of CGRP-like immunoreactivity in the rat hindpaw. Author(s): Bileviciute I, Stenfors C, Theodorsson E, Lundeberg T. Source: British Journal of Pharmacology. 1998 November; 125(6): 1304-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9863661

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Up-regulation of calcitonin gene-related peptide receptors underlying elevation of skin temperature in ovariectomized rats. Author(s): Noguchi M, Ikarashi Y, Yuzurihara M, Mizoguchi K, Kurauchi K, Chen JT, Ishige A. Source: The Journal of Endocrinology. 2002 October; 175(1): 177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379501

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Upregulation of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) expression in stellate ganglia of children with congenital cardiovascular lesions. Author(s): Roudenok V, Schmitt O. Source: Ann Anat. 2001 May; 183(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11396788

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Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate. Author(s): Wyon Y, Spetz AC, Hammar M, Theodorsson E, Varenhorst E. Source: Scandinavian Journal of Urology and Nephrology. 2001 April; 35(2): 92-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11411665

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Use of calcitonin for the treatment of an odontoid fracture. Case report. Author(s): Darakchiev BJ, Bulas RV, Dunsker SB. Source: Journal of Neurosurgery. 2000 July; 93(1 Suppl): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10879776

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Use of protease inhibitors to improve calcitonin absorption from the small and large intestine in rats. Author(s): Tozaki H, Odoriba T, Iseki T, Taniguchi T, Fujita T, Murakami M, Muranishi S, Yamamoto A. Source: The Journal of Pharmacy and Pharmacology. 1998 August; 50(8): 913-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751457

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Validation, role in perioperative assessment, and clinical applications of an immunoradiometric assay for human calcitonin. Author(s): Wimalawansa SJ, Bailey F. Source: Peptides. 1995; 16(2): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7784260

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Vascular steal mimicking compression myelopathy in Paget's disease of bone: rapid reversal with calcitonin and systemic steroids. Author(s): Yost JH, Spencer-Green G, Krant JD. Source: The Journal of Rheumatology. 1993 June; 20(6): 1064-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8350315

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Vasoactive intestinal peptide and calcitonin gene-related peptide levels and hemodynamics during human liver transplantation. Author(s): McNicol PL, Liu G, Shulkes A, Hardy KJ, Jones RM. Source: Transplantation Proceedings. 1993 April; 25(2): 1830-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8470185

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Vasodilating actions of calcitonin gene-related peptide in normal man: comparison with atrial natriuretic peptide. Author(s): Ando K, Ito Y, Ogata E, Fujita T. Source: American Heart Journal. 1992 January; 123(1): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1530893

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Vasodilator effects of parathyroid hormone, parathyroid hormone-related protein, and calcitonin gene-related peptide in the human fetal-placental circulation. Author(s): Mandsager NT, Brewer AS, Myatt L. Source: Journal of the Society for Gynecologic Investigation. 1994 January-March; 1(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9419741

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Vasodilator responses to calcitonin gene-related peptide (CGRP) and amylin in the rat isolated perfused kidney are mediated via CGRP1 receptors. Author(s): Chin SY, Hall JM, Brain SD, Morton IK. Source: The Journal of Pharmacology and Experimental Therapeutics. 1994 June; 269(3): 989-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8014885

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Venous ulcers: improved healing by iontophoretic administration of calcitonin generelated peptide and vasoactive intestinal polypeptide. Author(s): Gherardini G, Gurlek A, Evans GR, Milner SM, Matarasso A, Wassler M, Jernbeck J, Lundeberg T. Source: Plastic and Reconstructive Surgery. 1998 January; 101(1): 90-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9427920

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Visualization of the calcitonin receptor-like receptor and its receptor activitymodifying proteins during internalization and recycling. Author(s): Kuwasako K, Shimekake Y, Masuda M, Nakahara K, Yoshida T, Kitaura M, Kitamura K, Eto T, Sakata T. Source: The Journal of Biological Chemistry. 2000 September 22; 275(38): 29602-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10882736

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Vitamin D status in Paget's bone disease. Effects of calcitonin therapy. Author(s): Nunziata V, Giannattasio R, di Giovanni G, Lettera AM, Nunziata CA. Source: Clinical Orthopaedics and Related Research. 1993 August; (293): 366-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8339504

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Vitamin D, parathormone, and calcitonin profiles in persons with long-standing spinal cord injury. Author(s): Vaziri ND, Pandian MR, Segal JL, Winer RL, Eltorai I, Brunnemann S. Source: Archives of Physical Medicine and Rehabilitation. 1994 July; 75(7): 766-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8024422

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What PROOF proves about calcitonin and clinical trials. Author(s): Cummings SR, Chapurlat RD. Source: The American Journal of Medicine. 2000 September; 109(4): 330-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996586

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CHAPTER 2. NUTRITION AND CALCITONIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and calcitonin.

Finding Nutrition Studies on Calcitonin 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 “calcitonin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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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 calcitonin: •

Parathyroid hormone, 1,25-dihydroxyvitamin D3 and calcitonin in women breastfeeding twins. Source: Nutrition-reviews (USA). (October 1985). volume 43(10) page 300-301. vitamin d calcitonin suckling calcium mothers lactation mineral metabolism 0029-6643

The following information is typical of that found when using the “Full IBIDS Database” to search for “calcitonin” (or a synonym): •

Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in Ccells. Author(s): Abteilung Innere Medizin I, Universitat Heidelberg, Germany. Source: Zink, A Scherubl, H Hoflich, M Hescheler, J Raue, F Horm-Metab-Res. 1995 September; 27(9): 408-14 0018-5043

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Antidromic effect of calcitonin gene-related peptide containing nerves on cerebral arteries in rats--a possible role of sensory nerves on cerebral circulatio. Author(s): Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima City, Japan. Source: Asari, J Suzuki, K Matsumoto, M Sasaki, T Kodama, N Fukushima-J-Med-Sci. 2001 December; 47(2): 75-84 0016-2590

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Basal and calcium stimulated serum calcitonin in insulin-dependent diabetics. Source: Schmitz, O. Christensen, C.K. Christensen, S.E. Emmertsen, K. Horm-Metab-Res. Stuttgart, W. Ger. : Georg Thieme. February 1984. volume 16 (2) page 100-101. 0018-5043

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Comparison of calcitonin gene-related peptide release from rat lymphocytes and dorsal root ganglia neurons. Author(s): Institute of Vascular Medicine, Beijing Medical University, Beijing 100083, People's Republic of China. Source: Xing, Liyu Hou, Lingfei Wang, Xian Brain-Behav-Immun. 2002 February; 16(1): 17-32 0889-1591

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Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate. Author(s): Department of Obstetrics and Gynecology, Gazi University School of Medicine, Besevler, Ankara, Turkey. Source: Tiras, M B Noyan, V Yildiz, A Biberoglu, K Climacteric. 2000 June; 3(2): 92-101 1369-7137

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Conformationally constrained human calcitonin (hCt) analogues reveal a critical role of sequence 17-21 for the oligomerization state and bioactivity of hCt. Source: Kazantzis, A. Waldner, M. Taylor, J.W. Kapurniotu, A. Eur-j-biochem. Oxford, UK : Blackwell Science Ltd. February 2002. volume 269 (3) page 780-791. 0014-2956

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Effect of Brn-3a deficiency on parvalbumin-, calbindin D-28k-, calretinin- and calcitonin gene-related peptide-immunoreactive primary sensory neurons in the trigeminal ganglion. Author(s): Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. [email protected] Source: Ichikawa, H Yamaai, T Jacobowitz, D M Mo, Z Xiang, M Sugimoto, T Neuroscience. 2002; 113(3): 537-46 0306-4522

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Endothelin-1-induced vasospasms of spiral modiolar artery are mediated by rhokinase-induced Ca(2+) sensitization of contractile apparatus and reversed by calcitonin gene-related Peptide. Author(s): Anatomy and Physiology Department, Kansas State University, Manhattan, KS 66506, USA. Source: Scherer, E Q Herzog, M Wangemann, P Stroke. 2002 December; 33(12): 2965-71 1524-4628

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Regulatory effect of vitamin D3 metabolites, calcitonin and parathyroid hormone on the BGP synthesis and/or secretion in chick embryonic calvaria in vitro. Source: Tsutsumi, C. Hosoya, N. Orimo, H. Hoshiba, K. Moriuchi, S. Vitamin D : chemical, biochemical, and clinical update; proceedings of the Sixth Workshop on Vitamin D, Merano, Italy, March 1985 / editors, A.W. Norman. [et al.]. Berlin [West Ger.] : De Gruyter, 1985. page 489-490. ISBN: 3111010815

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Roles of calcitonin and parathyroid hormone on calcium and phosphorus metabolism in sheep. Source: Matsui, T. Yano, H. Kawashima, R. New strategies for improving animal production for human welfare : proceedings / the Fifth World Conference on Animal Production, August 14-19, 1983. Tokyo, Japan : Japanese Society of Zootechnical Science, 1983. volume 2 page 321-322.

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The cardioprotection of rutaecarpine is mediated by endogenous calcitonin relatedgene peptide through activation of vanilloid receptors in guinea-pig hearts. Author(s): Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, P.R. China. Source: Hu, C P Xiao, L Deng, H W Li, Y J Planta-Med. 2002 August; 68(8): 705-9 00320943

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The effect of calcitonin on osseous healing in guinea pig mandible. Author(s): Department of Endodontics, Faculty of Dentistry, Hacettepe University, Ankara, Turkey. Source: Dogan, H Ozcelik, B Gedikoglu, G Senel, S J-Endod. 2001 March; 27(3): 160-3 0099-2399

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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

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

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

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

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

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

The following is a specific Web list relating to calcitonin; 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 Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND CALCITONIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to calcitonin. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to calcitonin and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “calcitonin” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to calcitonin: •

A comparative study of the calcification-promoting action of 1,25 (OH)2D3 and calcitonin on the growth cartilage of rats with 1-hydroxyethylidene-1, 1-biphosphonic acid (HEBP)-induced rickets. Author(s): Eguchi M, Shibata K, Wada F, Kawamura H, Shimauchi T, Shiota E, Sugioka Y. Source: International Orthopaedics. 1987; 11(1): 77-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3104219

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A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. Author(s): Valimaki MJ, Kinnunen K, Volin L, Tahtela R, Loyttyniemi E, Laitinen K, Makela P, Keto P, Ruutu T. Source: Bone Marrow Transplantation. 1999 February; 23(4): 355-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10100579

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A prospective study of bone loss and turnover after cardiac transplantation: effect of calcium supplementation with or without calcitonin. Author(s): Valimaki MJ, Kinnunen K, Tahtela R, Loyttyniemi E, Laitinen K, Makela P, Keto P, Nieminen M. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 10(2): 128-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10501793

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A study of human calcitonin in an ovarian carcinoid and ovarian cancers. Author(s): Sakura H, Fujii T, Okamoto K. Source: Exp Clin Endocrinol. 1991 March; 97(1): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1713852

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A study of thyrocalcitonin secretion by direct measurement of in vivo secretion rates in pigs. Author(s): Care AD, Cooper CW, Duncan T, Orimo H. Source: Endocrinology. 1968 July; 83(1): 161-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4968975

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Ability of several cations to promote secretion of thyrocalcitonin in the pig-1-2 (38559). Author(s): Cooper CW. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1975 February; 148(2): 449-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1121494

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Acupuncture to the skin induces release of substance P and calcitonin gene-related peptide from peripheral terminals of primary sensory neurons in the rat. Author(s): Kashiba H, Ueda Y. Source: The American Journal of Chinese Medicine. 1991; 19(3-4): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1722639

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Acute effect of large doses of calcitonin on calcium, magnesium and inorganic phosphate levels in rat serum in correlation to differences in thryroid function. Author(s): Neradilova M, Blahosova A, Reisenauer R. Source: Physiol Bohemoslov. 1977 August; 26(4): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=144283

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Acute effects of chundosunbup qi-training on blood concentrations of TSH, calcitonin, PTH and thyroid hormones in elderly subjects. Author(s): Lee MS, Kang CW, Shin YS, Huh HJ, Ryu H, Park JH, Chung HT.

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Source: The American Journal of Chinese Medicine. 1998; 26(3-4): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862015 •

Amylin-induced relaxation of the perfused mesenteric arterial bed: meditation by calcitonin gene-related peptide receptors. Author(s): Westfall TC, Curfman-Falvey M. Source: Journal of Cardiovascular Pharmacology. 1995 December; 26(6): 932-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8606530

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Are calcitonins analgesic and/or hyperalgesic? Author(s): Giusti P, Carrara M, Zampiron S, Cima L, Borin G. Source: Peptides. 1985; 6 Suppl 3: 277-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3938532

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Association of low bone mass with vitamin d receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. Author(s): Masi L, Cimaz R, Simonini G, Bindi G, Stagi S, Gozzini A, Malentacchi C, Brandi ML, Falcini F. Source: The Journal of Rheumatology. 2002 October; 29(10): 2225-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12375338

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Calcitonin and reflex sympathetic dystrophy syndrome. Author(s): Gobelet C, Meier JL, Schaffner W, Bischof-Delaloye A, Gerster JC, Burckhardt P. Source: Clinical Rheumatology. 1986 September; 5(3): 382-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3536262

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Calcitonin and the human endocrine pancreas. Author(s): Giugliano D. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1984; 38(5): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6395913

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Calcitonin decreases the adherence and survival of HEK-293 cells by a caspaseindependent mechanism. Author(s): Findlay DM, Raggatt LJ, Bouralexis S, Hay S, Atkins GJ, Evdokiou A. Source: The Journal of Endocrinology. 2002 December; 175(3): 715-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475382

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Calcitonin gene-related peptide (CGRP) and transcutaneous electrical nerve stimulation (TENS) increase cutaneous blood flow in a musculocutaneous flap in the rat. Author(s): Kjartansson J, Lundeberg T, Samuelson UE, Dalsgaard CJ, Heden P.

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Source: Acta Physiologica Scandinavica. 1988 September; 134(1): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3266418 •

Calcitonin gene-related peptide immunoreactivity in familial amyotrophic lateral sclerosis. Author(s): Kato T, Hirano A, Manaka H, Sasaki H, Katagiri T, Kawanami T, Shikama Y, Seino T, Sasaki H. Source: Neuroscience Letters. 1991 December 9; 133(2): 163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1667811

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Calcitonin gene-related peptide in tension-type headache. Author(s): Ashina M. Source: Scientificworldjournal. 2002 June 7; 2: 1527-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12806133

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Calcitonin gene-related peptide produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats. Author(s): Sato A, Sato Y, Shimura M, Uchida S. Source: Neuroscience Letters. 2000 April 7; 283(2): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10739894

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Calcitonin gene-related peptide suppresses hair cell responses to mechanical stimulation in the Xenopus lateral line organ. Author(s): Bailey GP, Sewell WF. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2000 July 1; 20(13): 5163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10864973

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Calcitonin gene-related peptide treatment of flaps with compromised circulation in humans. Author(s): Jernbeck J, Dalsgaard CJ. Source: Plastic and Reconstructive Surgery. 1993 February; 91(2): 236-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8430138

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Calcitonin gene-related peptide, neurokinin A and substance P: effects on nociception and neurogenic inflammation in human skin and temporal muscle. Author(s): Pedersen-Bjergaard U, Nielsen LB, Jensen K, Edvinsson L, Jansen I, Olesen J. Source: Peptides. 1991 March-April; 12(2): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1712469

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Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse. Author(s): Buma P, Verschuren C, Versleyen D, Van der Kraan P, Oestreicher AB.

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Source: Histochemistry. 1992 December; 98(5): 327-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1283163 •

Calcitonin gene-related peptide: a potent and selective stimulator of gastrointestinal somatostatin secretion. Author(s): Dunning BE, Taborsky GJ Jr. Source: Endocrinology. 1987 May; 120(5): 1774-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2882997

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Calcitonin inhibits the increase in bone acid phosphatase activity by high dose of zinc in rats. Author(s): Yamaguchi M, Takahashi K. Source: Toxicology Letters. 1983 October-November; 19(1-2): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6658820

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Calcitonin produces hypercalcemia in leopard sharks. Author(s): Glowacki J, O'Sullivan J, Miller M, Wilkie DW, Deftos LJ. Source: Endocrinology. 1985 February; 116(2): 827-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3967631

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Calcitonin secreting property of ipriflavone in the presence of estrogen. Author(s): Yamazaki I, Kinoshita M. Source: Life Sciences. 1986 April 28; 38(17): 1535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3702590

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Calcitonin, bone-active isoflavones and vitamin D metabolites. Author(s): Gennari C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9 Suppl 2: S81-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525730

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Calcitonin: chronotherapeutic effect on osteopenia in the ovariectomized rat. Author(s): Simmons DJ, Yang C, Gundberg CM, Kidder L, Cornelissen G, Thomas M, Lozano R, Sandstead E. Source: Prog Clin Biol Res. 1990; 341A: 517-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2217271

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Capsaicin-induced release of calcitonin gene-related peptide from dorsal horn slices is enhanced in adjuvant arthritic rats. Author(s): Nanayama T, Kuraishi Y, Ohno H, Satoh M.

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Source: Neuroscience Research. 1989 August; 6(6): 569-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2797508 •

Chronic hyperoxia and hamster pulmonary neuroendocrine cell bombesin and calcitonin. Author(s): Nylen ES, Becker KL. Source: The Anatomical Record. 1993 May; 236(1): 248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8507012

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Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats. Author(s): Martin-Lacave I, Ramos F, Utrilla JC, Conde E, Hevia A, Fernandez R, Moreno AM, Fernandez-Santos JM, Galera-Davidson H. Source: J Endocrinol Invest. 1998 February; 21(2): 102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9585384

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Comparative effect of calcium and of the adrenergic system on calcitonin secretion in man. Author(s): Vora NM, Williams GA, Hargis GK, Bowser EN, Kawahara W, Jackson BL, Henderson WJ, Kukreja SC. Source: The Journal of Clinical Endocrinology and Metabolism. 1978 April; 46(4): 567-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=113423

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Comparison of antiresorptive activities of ipriflavone, an isoflavone derivative, and elcatonin, an eel carbocalcitonin. Author(s): Fujita T, Fujii Y, Miyauchi A, Takagi Y. Source: Journal of Bone and Mineral Metabolism. 1999; 17(4): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10575594

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Comparison of the effects of hange-shashin-to and rikkunshi-to on human plasma calcitonin gene-related peptide and substance P levels. Author(s): Naito T, Itoh H, Takeyama M. Source: Biological & Pharmaceutical Bulletin. 2003 August; 26(8): 1104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913259

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Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin. Author(s): Shah RB, Palamakula A, Khan MA. Source: Journal of Pharmaceutical Sciences. 2004 April; 93(4): 1070-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999743

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Dihydropyridine binding and Ca(2+)-channel characterization in clonal calcitoninsecreting cells. Author(s): Krautwurst D, Scherubl H, Kleppisch T, Hescheler J, Schultz G. Source: The Biochemical Journal. 1993 February 1; 289 ( Pt 3): 659-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8382045

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Effect of calcitonin on bone and connective tissue metabolism in hemiplegic patients: a two-year prospective study. Author(s): Uebelhart D, Hartmann DJ, Barbezat S, Mermillod B, Chantraine A. Source: Clinical Rehabilitation. 1999 October; 13(5): 384-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10498345

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Effect of calcitonin on experimental osteolathyrism. (3). Selective inhibition of collagen resorption by calcitonin. Author(s): Seyama Y, Mori Y, Niinobe S. Source: Endocrinol Jpn. 1972 February; 19(1): 35-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4625401

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Effect of early oral calcium supplementation on serum calcium and immunoreactive calcitonin concentration in preterm infants. Author(s): Sann L, David L, Chayvialle JA, Lasne Y, Bethenod M. Source: Archives of Disease in Childhood. 1980 August; 55(8): 611-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7436517

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Effect of prostaglandin E1, E2 or indomethacin on serum parathyroid hormone and calcitonin in the rat. Author(s): Shemerdiak WP, Kukreja SC, Johnson PA. Source: Prostaglandins Med. 1981 June; 6(6): 641-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7267829

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Effect of thyrocalcitonin on the blood calcium level and degree of adhesion of the hepatocytes. Author(s): Arkhipenko VI, Briskin AI, Pinskaya VM. Source: Bulletin of Experimental Biology and Medicine. 1974 September; 77(3): 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4213061

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Effects of 17beta-estradiol and the Japanese herbal medicine Keishi-bukuryo-gan on the release and synthesis of calcitonin gene-related peptide in ovariectomized rats. Author(s): Noguchi M, Ikarashi Y, Yuzurihara M, Kase Y, Takeda S, Aburada M. Source: Journal of Pharmacological Sciences. 2003 September; 93(1): 80-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501156

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Effects of calcitonin on human auditory and visual evoked brain potentials. Author(s): Pietrowsky R, Dentler M, Fehm HL, Born J. Source: Psychopharmacology. 1992; 107(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1589561

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Effects of hypercalcemia, hypercalcemia and calcitonin on glucose stimulated insulin secretion in man. Author(s): Ziegler R, Bellwinkel S, Schmidtchen D, Minne H. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1972 January; 4(1): 60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4622099

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Effects of intranasal salmon calcitonin in juvenile idiopathic arthritis: an observational study. Author(s): Siamopoulou A, Challa A, Kapoglou P, Cholevas V, Mavridis AK, Lapatsanis PD. Source: Calcified Tissue International. 2001 July; 69(1): 25-30. Epub 2001 May 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685430

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Effects of ipriflavone on calcitonin synthesis in C cells of the rat thyroid. Author(s): Watanabe K, Takekoshi S, Kakudo K. Source: Calcified Tissue International. 1992; 51 Suppl 1: S27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1422981

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Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine. Author(s): Wyon Y, Hammar M, Theodorsson E, Lundeberg T. Source: Acta Physiologica Scandinavica. 1998 April; 162(4): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9597120

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Effects of the Japanese herbal medicine Keishi-bukuryo-gan and 17beta-estradiol on calcitonin gene-related peptide-induced elevation of skin temperature in ovariectomized rats. Author(s): Noguchi M, Ikarashi Y, Yuzurihara M, Kase Y, Chen JT, Takeda S, Aburada M, Ishige A. Source: The Journal of Endocrinology. 2003 March; 176(3): 359-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630921

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Elevations in circulating calcitonin gene-related peptide correlate with hemodynamic deterioration during endotoxic shock in pigs. Author(s): Arden WA, Fiscus RR, Wang X, Yang L, Maley R, Nielsen M, Lanzo S, Gross DR.

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Source: Circ Shock. 1994 March; 42(3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8025980 •

Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin. Author(s): Body JJ, Cryer PE, Offord KP, Heath H 3rd. Source: The Journal of Clinical Investigation. 1983 March; 71(3): 572-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6402521

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Estimates of circulating monomeric calcitonin: physiological studies in normal and thyroidectomized man. Author(s): Body JJ, Heath H 3rd. Source: The Journal of Clinical Endocrinology and Metabolism. 1983 November; 57(5): 897-903. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6413526

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Evaluation of a fully automated procalcitonin chemiluminescence immunoassay. Author(s): Hubl W, Krassler J, Zingler C, Pertschy A, Hentschel J, Gerhards-Reich C, Mack M, Demant T. Source: Clin Lab. 2003; 49(7-8): 319-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908732

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Evidence for derivative control of calcitonin secretion. Author(s): West TE, O'Riordan JL, Copp DH, Bates RF, Care AD. Source: The Journal of Endocrinology. 1972 January; 52(1): 28-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4621940

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Furosemide, mithramycin, and salmon calcitonin in hypercalcemia. Author(s): Filastre JP, Humbert G, Leroy J, Maitrot J, Deshayes P, Canonne MA. Source: Eur J Intensive Care Med. 1975 December; 1(4): 185-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=130239

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Hormonal control of hypercalcemia. Historic development of the calcitonin concept. Author(s): Copp DH. Source: The American Journal of Medicine. 1967 November; 43(5): 648-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4964179

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Immunoassay for human calcitonin. II. Clinical studies. Author(s): Deftos LJ, Bury AE, Habener JF, Singer FR, Potts JT Jr.

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Source: Metabolism: Clinical and Experimental. 1971 December; 20(12): 1129-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5001933 •

Immunological stability of calcitonin in plasma. Author(s): Habener JF, Singer FR, Deftos LJ, Potts JT Jr. Source: Endocrinology. 1972 April; 90(4): 952-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4622097

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Improvement and initial in vivo application of the radioimmunoassay of rat thyrocalcitonin. Author(s): Cooper CW, Obie JF, Hsu WH. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1976 January; 151(1): 183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1250844

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Improvement of the pulmonary absorption of (Asu1,7)-eel calcitonin by various absorption enhancers and their pulmonary toxicity in rats. Author(s): Yamamoto A, Okumura S, Fukuda Y, Fukui M, Takahashi K, Muranishi S. Source: Journal of Pharmaceutical Sciences. 1997 October; 86(10): 1144-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9344172

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In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix. Author(s): Guggi D, Kast CE, Bernkop-Schnurch A. Source: Pharmaceutical Research. 2003 December; 20(12): 1989-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725364

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Induction of uPA but not NF-IL3A by calcitonin is dependent on Erk1/2 phosphorylation in porcine renal cell line LLC-PK1. Author(s): Nakamura M, Yang Q, Ozaki T, Nakamura Y, Yamasaki H, Mori I, Kakudo K. Source: Biochemical and Biophysical Research Communications. 2002 February 8; 290(5): 1483-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11820789

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Innervation of the equine mature and immature proximal sesamoid bone by calcitonin gene-related peptide and substance P-containing nerves. Author(s): Cornelissen BP, Buma P, Rijkenhuizen AB, Barneveld A. Source: Am J Vet Res. 1998 November; 59(11): 1378-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9829393

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Lack of influence of isoproterenol, propranolol, and dopamine on immunoreactive parathyroid hormone and calcitonin in normal man. Author(s): Epstein S, Heath H 3rd, Bell NH. Source: Calcified Tissue International. 1983; 35(1): 32-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6404531

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Melatonin inhibits calcitonin gene-related peptide-induced vasodilation and increase in cAMP in rat middle cerebral arteries. Author(s): Viswanathan M. Source: European Journal of Pharmacology. 2001 Mar16; 415(2-3): 247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275006

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Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis. Author(s): Cecchettin M, Bellometti S, Cremonesi G, Solimeno LP, Torri G. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1995; 49(10): 465-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8746073

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Modulation of calcitonin binding by calcium: differential effects of divalent cations. Author(s): Stroop SD, Moore EE, Kuestner RE, Thompson DL. Source: J Recept Res. 1993; 13(8): 1173-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8254582

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Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines. Author(s): Salido M, Vilches J, Lopez A. Source: Histology and Histopathology. 2000 July; 15(3): 729-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963117

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Neuropeptides bombesin and calcitonin inhibit apoptosis-related elemental changes in prostate carcinoma cell lines. Author(s): Salido M, Vilches J, Lopez A, Roomans GM. Source: Cancer. 2002 January 15; 94(2): 368-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11900223

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Parasympathetic control of parathyroid hormone and calcitonin secretion in rats. Author(s): Stern JE, Sarmiento MI, Cardinali DP. Source: Journal of the Autonomic Nervous System. 1994 June; 48(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027517

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Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. Author(s): Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T.

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Source: The Journal of Clinical Investigation. 1999 November; 104(10): 1363-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10562298 •

Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1. Author(s): Gerard Y, Hober D, Assicot M, Alfandari S, Ajana F, Bourez JM, Chidiac C, Mouton Y, Bohuon C, Wattre P. Source: The Journal of Infection. 1997 July; 35(1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9279723

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Procalcitonin in fever of unknown origin after liver transplantation: a variable to differentiate acute rejection from infection. Author(s): Kuse ER, Langefeld I, Jaeger K, Kulpmann WR. Source: Critical Care Medicine. 2000 February; 28(2): 555-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10708199

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Procalcitonin--influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Author(s): Meisner M, Tschaikowsky K, Schnabel S, Schmidt J, Katalinic A, Schuttler J. Source: Eur J Clin Chem Clin Biochem. 1997 August; 35(8): 597-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9298349

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Radioimmunoassay of calcitonin in human plasma. Author(s): Silva OL, Snider RH, Becker KL. Source: Clinical Chemistry. 1974 March; 20(3): 337-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4205033

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Radioimmunoassay of calcitonin in plasma, normal thyroid, and medullary thyroid carcinoma of the rat. Author(s): Roos BA, Deftos LJ, Roberts G, Wilson P, Bundy L. Source: The Journal of Laboratory and Clinical Medicine. 1976 August; 88(2): 173-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=822106

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Radioimmunoassay of calcitonin in the plasma of rhesus monkey and man. Author(s): Hargis GK, Reynolds WA, Williams GA, Kawahara W, Jackson B, Bowser EN, Pitkin RM. Source: Clinical Chemistry. 1978 April; 24(4): 595-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=416924

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Reduction of serum prolactin after salmon calcitonin infusion in patients with impaired renal function. Author(s): Pun KK, Varghese Z, Moorhead JF.

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Source: Acta Endocrinol (Copenh). 1987 June; 115(2): 243-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3604555 •

Release of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity from rat isolated soleus muscle by low pH, capsaicin and potassium. Author(s): Santicioli P, Del Bianco E, Geppetti P, Maggi CA. Source: Neuroscience Letters. 1992 August 31; 143(1-2): 19-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1279475

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Role of inorganic pyrophosphatase in the mechanism of action of parathyroid hormone and calcitonin. Author(s): Orimo H, Ohata M, Fujita T. Source: Endocrinology. 1971 September; 89(3): 852-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4327778

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Role of the cytoskeleton in the secretory response of the frog adrenal gland to calcitonin gene-related peptide. Author(s): Delarue C, Esneu M, Fournier A, Vaudry H. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1997 SeptemberOctober; 63(1-3): 21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9449202

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Sensory stimulation (acupuncture) increases the release of calcitonin gene-related peptide in the saliva of xerostomia sufferers. Author(s): Dawidson I, Angmar-Mansson B, Blom M, Theodorsson E, Lundeberg T. Source: Neuropeptides. 1999 June; 33(3): 244-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10657499

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Structural studies of EDTA-induced fibrillation of salmon calcitonin. Author(s): Seyferth S, Lee G. Source: Pharmaceutical Research. 2003 January; 20(1): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608539

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Suppression and stimulation of calcitonin secretion in medullary thyroid carcinoma. Author(s): Deftos LJ, Goodman AD, Engelman K, Potts JT Jr. Source: Metabolism: Clinical and Experimental. 1971 April; 20(4): 428-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4994451

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Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin. Author(s): Guggi D, Krauland AH, Bernkop-Schnurch A.

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Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2003 September 19; 92(1-2): 125-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499191 •

The assay of human thyrocalcitonin in mice. Author(s): Laljee HC, Smith RN, Dorrington KJ. Source: The Journal of Endocrinology. 1967 December; 39(4): 507-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4965435

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The calcitonin-calcium relation curve and calcitonin secretory parameters in renal patients with variable degrees of renal function. Author(s): Messa P, Mioni G, Turrin D, Guerra UP. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1995 December; 10(12): 2259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8808222

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The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets. Author(s): Eguchi M, Shibata K, Wada F, Kawamura H, Shimauchi T, Shiota E, Sugioka Y. Source: Acta Endocrinol (Copenh). 1986 September; 113(1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3094310

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The cardioprotection of rutaecarpine is mediated by endogenous calcitonin relatedgene peptide through activation of vanilloid receptors in guinea-pig hearts. Author(s): Hu CP, Xiao L, Deng HW, Li YJ. Source: Planta Medica. 2002 August; 68(8): 705-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221592

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The depressor and vasodilator effects of rutaecarpine are mediated by calcitonin gene-related peptide. Author(s): Hu CP, Xiao L, Deng HW, Li YJ. Source: Planta Medica. 2003 February; 69(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624816

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The effect of calcitonin on glucose assimilation and insulin secretion in man. Author(s): Minne H, Bellwinkel S, Ziegler R. Source: Acta Endocrinol Suppl (Copenh). 1973; 173: 162. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4199190

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The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat. Author(s): Glajchen N, Thomas S, Jowell P, Epstein S, Ismail F, Fallon M. Source: Calcified Tissue International. 1990 January; 46(1): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2104771

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The effect of hypocalcaemia on the secretion of calcitonin. Author(s): West TE, O'Riordan JL, Copp DH, Bates RF, Care AD. Source: The Journal of Endocrinology. 1973 March; 56(3): 463-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4633293

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The influence of cervical sympathetic neurons on parathyroid hormone and calcitonin release in the rat: independence of pineal mediation. Author(s): Stern JE, Esquifino AI, Garcia Bonacho M, Cardinali DP. Source: Journal of Pineal Research. 1997 January; 22(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9062864

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The influence of various enzyme inhibitors on 125I-porcine calcitonin adsorption and incubation damage. Author(s): Pento JT. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1975 September; 7(5): 444-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=810398

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The regulation of calcitonin in normal human plasma as assessed by immunoprecipitation and immunoextraction. Author(s): Parthemore JG, Deftos LJ, Bronzert D. Source: The Journal of Clinical Investigation. 1975 October; 56(4): 835-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=808561

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Tryptophan and neutral amino acid concentrations in serum of rats after salmon calcitonin injection. Author(s): Dupuy B, Peuchant E, Vitiello S, Jensen R, Baghdiantz A, Blanquet P. Source: Experientia. 1983 March 15; 39(3): 294-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6402375

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Unresponsiveness of exocrine rat pancreas to calcemic challenges (hypercalcemia, EDTA hypocalcemia or calcitonin administration) which influence stomach function. Author(s): Ziegler R, Minne H, Zwicker M, Hotz J. Source: Research in Experimental Medicine. Zeitschrift Fur Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie. 1974; 162(4): 347-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4209820

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Veratridine evokes release of calcitonin gene-related peptide from capsaicin-sensitive nerves of rat urinary bladder. Author(s): Tramontana M, Del Bianco E, Cecconi R, Maggi CA, Geppetti P. Source: European Journal of Pharmacology. 1992 March 3; 212(2-3): 137-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1376273

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to calcitonin; 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: •

General Overview Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Menopause Source: Integrative Medicine Communications; www.drkoop.com

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Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com •

Herbs and Supplements Calcitonin Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Ipriflavone Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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

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CHAPTER 4. DISSERTATIONS ON CALCITONIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to calcitonin. 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 “calcitonin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on calcitonin, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Calcitonin 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 calcitonin. 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: •

Calcium and calcitonin studies in Pacific salmon, genus Oncorhynchus and rainbow trout, Salmo gairdneri by Watts, Eric George; PhD from The University of British Columbia (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK17242

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Characterization of the gene for the calcitonin gene-related peptide (CGRP) receptor component protein (RCP), and generation of RCP +/- embryonic stem cells by Mnayer, Laila Omar; PhD from University of Miami, 2003, 145 pages http://wwwlib.umi.com/dissertations/fullcit/3090859

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Effect of calcitonin on epidermal cells and collagen synthesis in experimental wounds as revealed by electron microscopy, autoradiography and scanning electron microscopy by Lupulescu, Aurel Peter; PhD from University of Windsor (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK29187

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Factors influencing the levels of calcitonin in the plasma of the domestic fowl Gallus domesticus by Widjajakusuma, M. C. M. Reviany; PhD from University of Guelph (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20956

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Physiopathology of calcitonin experimental and clinical studies by Sturtridge, W. C; PhD from University of Toronto (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK10827

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON CALCITONIN 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 “calcitonin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on calcitonin, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Calcitonin By performing a patent search focusing on calcitonin, 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 calcitonin: •

Alpha-amidating enzyme compositions and processes for their production and use Inventor(s): Gilligan; James P. (Union, NJ), Jones; Barry N. (West Milford, NJ) Assignee(s): Unigene Laboratories, Inc. (Fairfield, NJ) Patent Number: 6,319,685 Date filed: August 14, 1987 Abstract: Purified enzymatic compositions are provided having alpha-amidating enzymes capable of catalyzing the conversion of a peptidyl compound having a Cterminal glycine residue to a corresponding peptidyl amide having an amino group in place of the C-terminal glycine. The purified compositions have specific activities above 25 mU per mg protein and are sufficiently free of proteases to allow effective catalysis of even peptidyl compounds having L-amino acids. Biologically important alpha-amidated products such as calcitonin and other regulatory hormones are efficiently produced using the alpha-amidation reaction catalyzed by the enzymes. Purification by size exclusion chromatography in combination with strong anion exchange chromatography results in homogeneous enzyme species which are used to prepare antibodies specific for the alpha-amidating enzyme. A gene capable of expressing the alpha-amidating enzyme is ligated into an expression vector and transformed into a host cell capable of expressing the gene. Excerpt(s): This invention relates to alpha-amidating enzymes, the production of alphaamidating enzymes and their use in the production of alpha-amidated products by action of the enzymes on glycine-extended substrates. In certain preferred embodiments, the alpha-amidating enzyme of the invention may be used in the production of useful alpha-amidated hormones and products for agricultural or medical use including calcitonins, growth hormone releasing factors, calcitonin gene-related peptides, and other alpha-amidated products. The intracellular processing (cleavage and/or functional group modification) of precursor forms of native proteins following their translation from nucleic acid coding sequences has been clearly documented. In general, mammalian cells and other eukaryotes can perform certain post-translational processing procedures, while prokaryotes can not. Certain prokaryotes, such as E. coli, are widely employed as hosts for the production of mammalian proteins via recombinant DNA (rDNA) technology because they can be readily grown in batch fermentation procedures and because they are genetically well-characterized. However, many mammalian proteins produced by genetic engineering technology require some type of post-translational processing, and this must often be accomplished by using complex, in vitro chemical procedures which are cost-prohibitive for large-scale production applications. Web site: http://www.delphion.com/details?pn=US06319685__

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Anti-human calcitonin monoclonal antibodies and an immunoassay utilizing said antibodies Inventor(s): Kataoka; Chiwa (Kyoto, JP), Miura; Kazunobu (Kyoto, JP), Nakamoto; Manabu (Osaka, JP), Sakaki; Junko (Kyoto, JP), Yamashita; Nobuhiko (Osaka, JP) Assignee(s): Osaka Gas Company Limited (Osaka, JP) Patent Number: 6,133,427 Date filed: December 23, 1997 Abstract: Monoclonal antibodies having a high affinity for human calcitonin, particularly monoclonal antibodies suitable for a sandwich immunoassay are disclosed. Also disclosed are hybridomas producing said monoclonal antibodies and a sandwich immunoassay utilizing said antibodies for determining human calcitonin in blood. Excerpt(s): The present invention relates to monoclonal antibodies having a high affinity for human calcitonin, particularly monoclonal antibodies suitable for a sandwich immunoassay. The monoclonal antibodies can be used to quantify the human calcitonin produced in blood in a high sensitivity, and to precisely judge the kinetic of the human calcitonin in blood for treatment or diagnosis. Calcitonin (CT) is a peptide hormone constituted of 32 amino acids and secreted from thyroid gland C-cells in mammals. Although an action to decrease calcium levels in blood by inhibiting bone absorption in bone and an action to decrease phosphorus levels in serum by accelerating excretion of inorganic phosphorus into urine in the kidney as well as other actions are known as physiological actions of this hormone, many actions are still unknown. Currently, determination of human calcitonin (hCT) in blood is carried out by a radioimmunoassay (RIA) and utilized for diagnosis of thyroid medullary carcinoma, observation of its therapeutical process, screening of familial thyroid medullary carcinoma, and diagnosis of ectopic hCT-producing tumors. However, a commercially available RIA kit utilizes an anti-hCT polyclonal antibody which is a mixture of antibodies against various epitopes. Accordingly, the kit may also determine decomposition products in blood other than the monomer hCT. Thus, it is believed that hCT in blood can not be accurately determined by the RIA method utilizing such a polyclonal antibody. In addition, its sensitivity is relatively low, in the order of 30 pg/ml, and therefore, it is not possible to accurately determine a concentration of hCT in the blood of normal people. Web site: http://www.delphion.com/details?pn=US06133427__

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Calcitonin mimetics Inventor(s): Baindur; Nand (Edmonds, WA), Beigel; Stephanie (Seattle, WA), Labroo; Virender (Banglore, WA), Martinez; Theresa (Greenbank, WA), Mckernan; Patricia A. (Woodinville, WA), Moore; Emma E. (Seattle, WA), Orme; Mark W. (Seattle, WA), Petrie; Charles R. (Woodinville, WA), Stroop; Steven (Seattle, WA) Assignee(s): ZymoGenetics, Inc. (Seattle, WA) Patent Number: 6,395,740 Date filed: July 14, 2000 Abstract: Compounds are described which act as calcitonin mimetics. These compounds are useful in the treatment of diseases which are associated with bone resorption. Included among the calcitonin mimetics of the present invention are substituted

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piperazines. The calcitonin mimetics of the present invention are also useful in libraries and in assays for the determination of calcitonin receptor activity. Excerpt(s): Bone is a dynamic tissue, and homeostasis in the adult skeleton requires a balance between bone resorption and bone formation. Osteoclasts and osteoblasts play a key role in this balance, with osteoclasts initiating bone resorption and osteoblasts synthesizing and depositing new bone matrix. Imbalances in bone homeostasis are associated with such conditions as osteoporosis, Paget's disease, and hyperparathyroidism. The activities of osteoclasts and osteoblasts are regulated by complex interactions between systemic hormones and the local production of growth factors and cytokines. Calcitonin, a peptide hormone secreted by the thyroid and thymus of mammals, plays an important role in maintaining bone homeostasis. Calcitonin inhibits bone resorption through binding and activation of a specific calcitonin receptor on osteoclasts (The Calcitonins--Physiology and Pharmacology, Azria (ed.), Karger, Basel, Su., 1989), with a resultant decrease in the amount of calcium released by bone into the serum. This inhibition of bone resorption has been exploited, for instance, by using calcitonin as a treatment for osteoporosis, a disease characterized by a decrease in the skeletal mass often resulting in debilitating and painful fractures. Calcitonin is also used in the treatment of Paget's disease where it provides rapid relief from bone pain, which is frequently the primary symptom associated with this disease. This analgesic effect has also been demonstrated in patients with osteoporosis or metastatic bone disease and has been reported to relieve pain associated with diabetic neuropathy, cancer, migraine and post-hysterectomy. Reduction in bone pain occurs before the reduction of bone resorption. Salmon calcitonin has been shown to be considerably more effective in arresting bone resorption than human forms of calcitonin. Several hypotheses have been offered to explain this observation: 1) salmon calcitonin is more resistant to degradation; 2) salmon calcitonin has a lower metabolic clearance rate (MCR); and 3) salmon calcitonin may have a slightly different conformation, resulting in a higher affinity for bone receptor sites. Web site: http://www.delphion.com/details?pn=US06395740__ •

Calcitonin receptor binding reagents Inventor(s): Bush; Larry R. (Exeter, NH), Dean; Richard T. (Bedford, NH), Lister-James; John (Bedford, NH), Pearson; Daniel A. (Bedford, NH) Assignee(s): Diatide, Inc. (Londonderry, NH) Patent Number: 6,479,032 Date filed: April 20, 2000 Abstract: This invention relates to calcitonin receptor binding reagents comprising compounds which are covalently linked to a radiometal chelator. The invention is embodied as calcitonin receptor binding peptide derivatives and analogues of calcitonin which may be radiolabeled with a suitable isotope and used as radiodiagnostic or radiotherapeutic agents. Methods and kits for making, radiolabeling and using such reagents diagnostically and therapeutically in a mammalian body are also provided. Excerpt(s): This invention relates to calcitonin receptor binding reagents which are capable of complexing with metal ions, including radioactive metal ions, and to labeled embodiments of such reagents for use in imaging sites in a mammalian body or for use in therapy, particularly for use in cancer therapy. Great strides have been made over the

Patents 149

past 60 years in reducing long-term mortality trends for some types of cancer, such as stomach cancer. However, during the same period, mortality trends for other cancers have remained stable or increased. For example, lung cancer is the most frequent cancer worldwide, representing the leading cause of cancer mortality among men and women. Breast cancer is the commonest cancer among women and the second leading cause of cancer mortality in women, and ovarian cancer mortality rates are increasing in some countries. Childhood and adult lymphatic cancers, such as leukemias and nonHodgkin's lymphomas, also continue to represent significant causes of cancer mortality. Early diagnosis and effective treatment remains a goal for all of these cancers. Several years ago, site directed diagnosis and therapy were proposed, to allow in vivo targeting of particular sites of disease within an animal's body. In general, site-directed diagnosis or therapy employs a targeting moiety, such as an antibody specific for the disease site or for the organism which caused the disease, coupled to a label in the case of a diagnostic agent or to a cytotoxic agent in the case of a therapeutic agent. A very large body of literature exists relating to radiolabeling antibodies or antibody fragments for diagnostic imaging purposes. Similarly, a number of site directed therapeutic agents employing monoclonal antibodies and a variety of radioisotopes have been proposed over the years, e.g., as set forth in U.S. Pat. Nos. 4,454,106; 4,472,509; 4,828,991; 5,246,691; 5,355,394; and 5,641,471; in EP 429624; EP 585986; WO 90/15625, and the like. Such antibody-based agents produce side effects related to the immune responses of the treated animal to the antibody, even if antibody fragments or humanized antibodies are employed as the targeting moiety. Web site: http://www.delphion.com/details?pn=US06479032__ •

Hydrophobic preparations containing medium chain monoglycerides Inventor(s): Kirby; Christopher John (Berkshire, GB), New; Roger Randal Charles (London, GB) Assignee(s): Provalis UK Limited (GB) Patent Number: 6,258,377 Date filed: December 22, 1998 Abstract: Hydrophobic preparations which are useful as, among other things, pharmaceutical delivery systems comprise: (i) an oil phase comprising one or more medium chain monoglycerides, such as Akoline MCM.TM.; (ii) at least one amphiphile, preferably including a phospholipid such as phosphatidyl choline; and (iii) a hydrophilic species, which may be a protein such as insulin or calcitonin or another macromolecule, solubilized or otherwise dispersed in the one or more glycerides. The hydrophilic species is one that is not normally soluble in the glycerides. Excerpt(s): The present invention relates to preparations of substances in hydrophobic solvents in which they would normally be soluble and to processes for obtaining these preparations. In particular, the invention relates to preparations of hydrophilic species in mixtures of medium chain monoglycerides (MCMs) and diglycerides. The invention in particular applies to hydrophilic macromolecules which would not normally be soluble in oils or other hydrophobic solvents. For many applications, e.g. in the pharmaceutical sciences, in food technology or the cosmetics industry, work with proteins and similar macromolecules presents problems because their hydrophilicity and high degree of polarity limit the extent to which they can interact with or incorporate into lipid phases. Many natural systems employ lipidic barriers (eg skin, cell membranes) to prevent access of hydrophilic molecules to internal compartments; the

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ability to disperse proteins in lipidic vehicles would open up a new route to introduction of these macromolecules into biological systems, whereby the lipid medium containing the protein can integrate with the hydrophobic constituents of barriers, instead of being excluded by them. Web site: http://www.delphion.com/details?pn=US06258377__ •

Method for treating hypercalcemia Inventor(s): Donovan; Stephen (Capistrano Beach, CA) Assignee(s): Allergan Sales, Inc. (Irvine, CA) Patent Number: 6,447,785 Date filed: November 2, 2000 Abstract: A method for treating hypothyroidism by local administration of a neurotoxin, such as a botulinum toxin, to a thyroid, thereby reducing an inhibitory effect upon thyroid hormone secretion. A method for treating hyperthyroidism by local administration of a neurotoxin, such as a botulinum toxin, to a sympathetic ganglion which innervates the thyroid, thereby reducing a stimulatory effect upon thyroid hormone secretion. Methods for treating calcium metabolism disorders by local administration of a neurotoxin to modulate calcitonin secretion are also disclosed. Excerpt(s): The present invention relates to methods for treating thyroid disorders. In particular the present invention relates to methods for treating thyroid disorders by administration of a neurotoxin to a patient. It has been estimated that at least about two hundred million people worldwide are afflicted with a thyroid disorder and women are affected disproportionaly, as compared to men, by a ratio of about ten to one. In the United States, about ten million persons, including ten percent of all women over age 45, have either overactive or underactive thyroid glands. Bayliss et al., Thyroid Disease The Facts, preface, Oxford University Press (1998). The thyroid is an endocrine gland comprised of follicle cells and non-follicular or C cells. The follicle cells are capable of making two hormones, triiodothyronine (T.sub.3) which contains three iodine atoms and thyroxine (T.sub.4) which contains four. The action of thyroid hormone is concerned principally with the regulation of metabolic rate by, for example, increasing energy production and oxygen consumption by most normal tissues. Synthesis and release of T.sub.3 and T.sub.4 by thyroid cells in influenced by thyroid stimulating hormone (TSH, also called thyrotrophin) made by the pituitary. The C cells can make calcitonin which appears to influence calcium metabolism. Significantly, calcitonin is a potent hypocalcemic agent. Disorders of the thyroid include autoimmune disorders (such as Graves' disease), thyroiditis (inflammation or infection of the thyroid), and cancer, all of which conditions can result in hypothyroidism (as can occur in Hashimoto's thyroiditis) or hyperthyroidism (thyroidtoxicosis, as can occur in Graves' disease). An enlarged thyroid (goiter) can by euthyroid, or a symptom of either hyperthyroidism (thyroidtoxicosis) or hypothyroidism. Web site: http://www.delphion.com/details?pn=US06447785__

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Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same Inventor(s): Ansari; Aslam M. (Rockville, MD), Ekwuribe; Nnochiri N. (Cary, NC), Odenbaugh; Amy L. (Morrisville, NC), Price; Christopher H. (Chapel Hill, NC) Assignee(s): Nobex Corporation (Durham, NC) Patent Number: 6,713,452 Date filed: June 4, 2001 Abstract: A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin. Excerpt(s): The present invention relates to drug-oligomer conjugates, and, more particularly, to calcitonin drug-oligomer conjugates. Calcitonin is a naturally occurring hormone with a short half-life that is believed to act directly on osteoclasts (via receptors on the cell surface for calcitonin). This action may directly inhibit osteoclastic bone resorption, which may lead to hypocalcemic and/or hypophosphatemic serum effects. Calcitonin may be use full in treating various bone disorders including, but not limited to, osteoporosis and Paget's disease. Osteoporosis is a bone disease in which bone tissue is normally mineralized, but the amount of bone is decreased and the structural integrity of trabecular bone is impaired. Cortical bone becomes more porous and thinner. This makes the bone weaker and more likely to fracture. In the United States, about 21% of postmenopausal women have osteoporosis (low bone density), and about 16% have had a fracture. In women older than 80, about 40% have experienced a fracture of the hip, vertebra, arm, or pelvis. The population of older men and women has been increasing, and therefore the number of people with osteoporosis is increasing. Web site: http://www.delphion.com/details?pn=US06713452__

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Modulation of sperm function Inventor(s): Fraser; Lynn Repsis (Rickmansworth, GB), Pondel; Marc Dean (Sutton, GB) Assignee(s): King's College London (GB) Patent Number: 6,716,812 Date filed: August 3, 2001 Abstract: The hormone calcitonin promotes fertilizing ability in mammalian sperm and is useful for treatment of conditions of low fertility in humans and animals. Human, porcine or salmon calcitonin may be formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier for topical application, e.g. as a cream or jelly containing up to 100 ng/ml or more of salmon calcitonin or up to 2.mu.g/ml or more of human calcitonin. Calcitonin may also be administered parenterally, orally, or nasally. For improving in vitro fertilization or artificial insemination methods calcitonin is added to sperm prior to use e.g. salmon calcitonin present at a concentration of from 5 to 50 ng/ml or human calcitonin at a concentration of from 20 to 200 ng/ml in the sperm preparation. Calcitonin levels in seminal plasma can also be used to diagnose infertility.

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Excerpt(s): This invention relates to the treatment of mammalian sperm to modulate sperm function. Although morphologically complete and capable of vigorous motility when they leave the male reproductive tract, mammalian sperm are not immediately able to fertilize oocytes. The acquisition of the capacity to fertilize an oocyte is termed capacitation. Once capacitated, sperm can undergo the acrosome reaction, a prerequisite for penetration of the zona pellucida and fusion with the oocyte plasma membrane; however sperm that have undergone a spontaneous acrosome reaction are nonfertilizing. A defect in these mechanisms results in a condition of infertility. At present there is no real treatment for this problem. The present invention is based on the discovery that the hormone calcitonin acts upon mammalian sperm to stimulate fertility. Throughout the following description reference is made to various publications in the literature; a full reference list of these is given at the end of this specification. Web site: http://www.delphion.com/details?pn=US06716812__ •

Nasal calcitonin formulations Inventor(s): Stern; William (Tenafly, NJ) Assignee(s): Unigene Laboratories, Inc. (Fairfield, NJ) Patent Number: 6,440,392 Date filed: February 2, 2001 Abstract: A liquid pharmaceutical composition is disclosed comprising calcitonin or an acid addition salt thereof and citric acid or salt thereof in a concentration from about to about 50 mM, said composition being in a form table for nasal administration. Excerpt(s): The present invention relates to an intranasal pharmaceutical compositions comprising calcitonin as an active ingredient and specific concentrations of citric acid or a salt thereof as a stabilizer and absorption enhancer. Calcitonins are a class of polypeptide hormones that are used in the treatment of a variety of conditions including osteoporosis, Paget's disease and malignant hypercalcemia. They are composed of amino acids and have been extracted from a number of sources including salmon, porcine, eel and human. Calcitonins with amino acid sequences identical to the natural forms have been produced by chemical synthesis as well as by recombinant technology. Given their size and chemical composition, calcitonins were originally administered by subcutaneous or intramuscular injection. Other routes of administration were technically difficult because calcitonins were poorly absorbed through tissue and were readily degraded by bodily fluids. Despite these obstacles, a formulation (U.S. Pat. No. 5,759,565) was developed that could be administered via the nasal route. The nasal formulation was designed to be stored in a multi-dose container that was stable for an extended period of time and resisted bacterial contamination. The preservative in the formulation, benzalkonium chloride, was found to enhance the absorption of salmon calcitonin. However, benzalkonium chloride was reported (P. Graf et al., Clin. Exp. Allergy 25:395-400; 1995) to aggravate rhintis medicamentosa in healthy volunteers who were given a decongestant nasal spray containing the preservative. It also had an adverse effect on nasal mucosa (H. Hallen et al., Clin. Exp. Allergy 25:401-405; 1995). Berg et al. (Laryngoscope 104:1153-1158; 1994) disclose that respiratory mucosal tissue that was exposed in vitro underwent severe morphological alterations. Benzalkonium chloride also caused significant slowing of the mucocilary transport velocity in the ex vivo frog palate test (P.C. Braga et al., J. Pharm. Pharmacol. 44:938-940; 1992). Web site: http://www.delphion.com/details?pn=US06440392__

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Oral calcitonin pharmaceutical compositions and methods of making the same Inventor(s): Ghirri; Matteo (Milan, IT), Zema; Marco (Como, IT) Assignee(s): Eurand International S.p.A. (IT) Patent Number: 6,352,974 Date filed: September 21, 1999 Abstract: The present invention relates to novel compositions, in particular to compositions comprising calcitonin or a fragment or conjugate thereof and to methods for preparing such compositions. It also relates to oral formulations comprising the compositions and to shelf stable formulations of calcitonin or a fragment or conjugate thereof. Excerpt(s): Many proteins and polypeptides have potential as pharmaceutical agents but because they are susceptible to both physical and chemical degradation they are often too unstable to be included in pharmaceutical formulations. In particular such proteins and polypeptides do not have adequate shelf life. The primary, secondary and tertiary structures of proteins and polypeptides are all vulnerable to various types of disruption. Some proteins and peptides are physically unstable as a result of, for example, adsorption, aggregation or denaturation. Others are chemically unstable as a result of, for example, oxidation, hydrolysis, deamidation, beta-elimination, racemisation or disulphide exchange (if the polypeptide contains a disulphide bridge e.g. a cystine link). Many proteins and polypeptides are susceptible to a number of these factors. Web site: http://www.delphion.com/details?pn=US06352974__

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Pharmaceutical compositions containing calcitonin in a spray dosing feeder for intranasal administration Inventor(s): Mardente; Salvatore (Turin, IT), Rotini; Leone Gabriele (Bologna, IT) Assignee(s): Alfa Wassermann S.p.A. (Alanno Scalo, IT) Patent Number: 6,149,893 Date filed: March 1, 1999 Abstract: Pharmaceutical compositions for intranasal administration containing in a spray dosing feeder calcitonin dissolved in a substantially physiological solution of sodium chloride adjusted to a pH between 3.5 and 4.5 with citrate buffer and hydrochloric acid without any preservative are the object of the present invention. Excerpt(s): The present invention relates to pharmaceutical compositions for intranasal administration containing in a spray dosing feeder calcitonin, preferably salmon calcitonin also known under the denomination of salcatonin, dissolved in a substantially physiological solution of sodium chloride adjusted to a pH between 3.5 and 4.5 with citrate buffer and hydrochloric acid and free from any preservative. The therapeutical action carried out by the calcitonin in the treatment of osteoporosis, Paget's disease and hypercalcemia is known. It is also known how the various calcitonins, having polypeptidic structure, are easily deteriorated and cannot be administered by oral route, while the administration by parenteral route shows many drawbacks including also painful reactions. Web site: http://www.delphion.com/details?pn=US06149893__

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Superpotent calcitonin analogs having greatly increased hypocalcemic action in vivo Inventor(s): Bernhagen; Jurgen (Tubingen, DE), Brunner; Herwig (Stuttgart, DE), Kapurniotu; Afroditi (Tubingen, DE) Assignee(s): Fraunhofer-Gesellschaft zur Forderung der Angewandten Forschung E.V. (Munich, DE) Patent Number: 6,617,423 Date filed: December 20, 2000 Abstract: Calcitonins and calcitonin derivatives such as are employed for therapy for, for example, osteoporosis. Paget's disease or hypercalcemia. The calcitonins and calcitonin derivatives are distinguished by a bridging of the amino acids present in the positions 17 and 21. In this case, by means of a suitable choice of the amino acids present in these positions an 18- or 19-membered ring is produced. This ring leads to an increased conformational stability and to an increased activity of the modified calcitonin. A particularly suitable hCt (human Ct) analog is the cyclo.sup.17,21 [Asp.sup.17, Orn.sup.21 ]-hCt according to the invention having a 19-membered ring structure between the lactam-bridged Asp.sup.17 and Orn.sup.21. Excerpt(s): The present invention relates to calcitonins and calcitonin derivatives having a hypocalcemic effect. Calcitonins and calcitonin derivatives of this type are employed in particular in the field of the pharmaceutical industry and in the field of medicine, for example for the treatment of osteoporosis, of Paget's disease or of hypercalcemia. Calcitonins are peptide hormones which consist of 32 amino acids. On account of their hypocalcemic effect and of the inhibition of bone destruction caused by them, they have great pharmacological importance. They are therapeutically employed for the treatment of osteoporosis, of Paget's disease or of hypercalcemia. Use is made here, in particular, of the calcitonins of man (hCt), of pig (pCt) or of ultimobranchial species, such as the salmon (sCt) or the eel (eCt). The calcitonins or their derivatives of ultimobranchial species have a 20- to 50-fold higher activity in vivo than human calcitonin. Therefore these calcitonins are preferably employed for therapeutic purposes. The calcitonins of the ultimobranchial species differ considerably, however, in their amino acid sequence from the peptide of human calcitonin. For example, salmon calcitonin differs in 16 of the 32 amino acids from human calcitonin. Nevertheless, it is used to this day, since on account of its considerably higher activity the dosage for therapeutic purposes can be kept lower. Web site: http://www.delphion.com/details?pn=US06617423__

Patent Applications on Calcitonin 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 calcitonin:

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

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Analogs of parathyroid hormone Inventor(s): Dong, Zheng Xin; (Holliston, MA) Correspondence: Jeffrey D. Hsi; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20030166836 Date filed: November 6, 2002 Abstract: The present invention is directed to peptide analogues of fragment of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP), a method of using said analogues alone or in combination with a bisphosphonate or calcitonin to treat osteoporosis and pharmaceutical compositions comprising said analogues alone or in combination with a bisphosphonate or calcitonin. Excerpt(s): This application is a continuation-in-part of co-pending U.S. application Ser. No. 09/341,217, filed Jul. 7, 1999, which is the national phase continuation application of International Application No PCT/US97/22498, filed Dec. 8, 1997, which is a continuation-in-part of co-pending U.S. application Ser. No. 08/813,534, filed Mar. 7, 1997, which is a continuation-in-part of co-pending U.S. application Ser. No. 08/779,768, filed Jan. 7, 1997, which is a continuation-in-part of U.S. application Ser. No. 08/626,186, filed Mar. 29, 1996. now issued as U.S. Pat. No. 5,723,577, which claims the benefit of priority of U.S. Provisional Application No. 60/003,305, filed Sep. 6, 1995 and U.S. Provisional Application No. 60/001,105, filed Jul. 13, 1995. Parathyroid hormone ("PTH") is a polypeptide produced by the parathyroid glands. The mature circulating form of the hormone is comprised of 84 amino acid residues. The biological action of PTH can be reproduced by a peptide fragment of its N-terminus (e.g. amino acid residues 1 through 34). Parathyroid hormone-related protein ("PTHrP") is a 139 to 173 amino acid-protein with N-terminal homology to PTH. PTHrP shares many of the biological effects of PTH including binding to a common PTH/PTHrP receptor. Tregear, et al, Endocrinol. 93:1349 (1983). PTH peptides from many different sources, e.g. human, bovine, rat, chicken, have been characterized. Nissenson. et al., Receptor, 3:193 (1993). PTH has been shown to both improve bone mass and quality Dempster, et al., Endocrine Rev., 14:690 (1993); and Riggs, Amer. J. Med. 91 (Suppl 5B):37S (1991). The anabolic effect of intermittently administered PTH has been observed in osteoporotic men and women either with or without concurrent antiresorptive therapy. Slovik, et al, J. Bone Miner. Res., 1:377 (1986); Reeve, et al., Br. Med. J., 301:314 (1990); and Hesch, R D., et al., Calcif. Tissue Int'l, 44:176 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Anti-procalcitonin antibodies and the preparation and use thereof Inventor(s): Althaus, Harald; (Wetter, DE), Walter, Gotz; (Munchhausen, DE) Correspondence: Finnegan, Henderson, Farabow, Garrett And Dunner; Franklin Square BLDG., Suite 700; 1300 I Street, N. W.; Washington; DC; 20005-3315; US Patent Application Number: 20010007022 Date filed: December 22, 2000 Abstract: The invention relates to anti-procalcitonin antibodies, their preparation and use, in particular in therapy and diagnostics. The antibodies comprise binding to procalcitonin but not to free calcitonin, free katacalcin and free N-procalcitonin.

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Excerpt(s): The invention relates to anti-procalcitonin antibodies, their preparation and use. Procalcitonin ("pCT") is a protein consisting of 116 amino acids and having a molecular weight of about 13,000 dalton. It is the prohormone of calcitonin which under normal metabolic conditions is produced and secreted by the C cells of the thyroid. pCT and calcitonin synthesis is initiated by translation of preprocalcitonin ("pre-pCT"), a precursor peptide comprising 141 amino acids. The amino acid sequence of human prepCT was described by Moullec et al. in FEBS Letters, 167:93-97 in 1984. pCT is formed after elimination of the signal peptide (first 25 amino acids of pre-pCT). In healthy people the hormone calcitonin (amino acids 60-91 of the pCT amino acid sequence), and N-procalcitonin (amino acids 1-57 of the pCT amino acid sequence) and katacalcin (amino acids 96-116 of the pCT amino acid sequence) are produced intracellularly from pCT by specific proteolysis (see also Conlan et al. (1988) Biochem. J., 256:245-250). pCT and fragments thereof were detected in increased concentrations in the serum or plasma of patients, in particular in cases of certain neoplastic diseases (Ghillani et al. (1989) Cancer Research, 49:6845-6851) and sepsis (EP-B1-0 656 121) and SIRS (systemic inflammatory response syndrome) (Snider et al. (1997) J. Investig. Med., 45:552-560). During the typical sepsis bacteria are released continuously or in phases from a focus into the bloodstream. Endotoxin or other pyrogenic and toxic substances interacting with body mechanisms cause the clinical manifestations. The acute onset triggers chills and in severe cases a shock reaction. Special forms of septic shock are WaterhouseFriderichsen syndrome and toxic shock syndrome (TSS). TSS is known as an acute clinical picture in staphylococcal infections which is caused by a specific staphylococcal toxin. A severe sepsis quite frequently develops in patients with serious primary disorders such as, for example, neoplastic diseases, serious burns and traumas. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Calcitonin drug-oligomer conjugates, and uses thereof Inventor(s): Ekwuribe, Nnochiri N.; (Cary, NC), Radhakrishnan, Balasingam; (Chapel Hill, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20040091452 Date filed: November 8, 2002 Abstract: Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed. Excerpt(s): The present invention relates to drug-oligomer conjugates, and, more particularly, to calcitonin drug-oligomer conjugates. Calcitonin is a naturally occurring hormone with a short half-life that is believed to act directly on osteoclasts (via receptors on the cell surface for calcitonin). This action may directly inhibit osteoclastic bone resorption, which may lead to hypocalcemic and/or hypophosphatemic serum effects. Calcitonin may be useful in treating various bone disorders including, but not limited to, osteoporosis and Paget's disease. Osteoporosis is a bone disease in which bone tissue is normally mineralized, but the amount of bone is decreased and the structural integrity of trabecular bone is impaired. Cortical bone becomes more porous and thinner. This makes the bone weaker and more likely to fracture. In the United States, about 21% of postmenopausal women have osteoporosis (low bone density), and about

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16% have had a fracture. In women older than 80, about 40% have experienced a fracture of the hip, vertebra, arm, or pelvis. The population of older men and women has been increasing, and therefore the number of people with osteoporosis is increasing. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Calcitonin gene related peptide receptor Inventor(s): Adamou, John; (St. David's, PA), Aiyar, Nambi; (Berwyn, PA), Bergsman, Derk; (Berwyn, PA), Elshourbagy, Nabil; (West Chester, PA), Lee, Norman H.; (Woodstock, MD), Yi, Li; (Sunnyvale, CA) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20020164707 Date filed: January 22, 2002 Abstract: A human CGRP receptor polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for identifying antagonists and agonists to such polypeptide. Antagonists against such polypeptides may be used therapeutically to treat cancer, arthrits, pain, diabetes, migraine and inflammation and agonists which may be used to treat hypercalcemia, obesity, hypertension, and disorders of bone remodelling. Diagnostic assays are also disclosed which detect the presence of mutations in the nucleic acid sequences which encode the receptor polypeptide. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is a human 7-transmembrane receptor which has been identified as a human Calcitonin Gene Related Peptide receptor, sometimes hereinafter referred to as "CGRP". The invention also relates to inhibiting the action of such polypeptides. It is well established that many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers, e.g., CAMP (Lefkowitz, Nature, 351:353354 (1991)). Herein these proteins are referred to as proteins participating in pathways with G-proteins or PPG proteins. Some example's of these proteins include the GProtein Couple Receptor (GPCR), such as those for adrenergic agents and dopamine (Kobilka, B. K., et al., PNAS, 84:46-50 (1987); Kobilka, B. K., et al., Science, 238:650-656 (1987); Bunzow, J. R., et al., Nature, 336:783-787 (1988)), G-proteins themselves, effector proteins, e.g., phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins, e.g., protein kinase A and protein kinase C (Simon, M. I., et al., Science, 252:802-8 (1991)). For example, in one form of signal transduction, the effect of hormone binding is activation of an enzyme, adenylate cyclase, inside the cell. Enzyme activation by hormones is dependent on the presence of the nucleotide GTP, and GTP also influences hormone binding. A G-protein connects the hormone receptors to adenylate cyclase. G-protein was shown to exchange GTP for bound GDP when activated by hormone receptors. The GTP-carrying form then binds to an activated adenylate cyclase. Hydrolysis of GTP to GDP, catalyzed by the G-protein itself, returns the G-protein to its basal, inactive form. Thus, the G-protein serves a dual role, as an intermediate that relays the signal from receptor to effector, and as a clock that controls the duration of the signal.

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Calcitonin gene related peptide receptor antagonists Inventor(s): Chaturvedula, Prasad V.; (Cheshire, CT), Chen, Ling; (Middletown, CT), Civiello, Rita; (Killingworth, CT), Conway, Charles Mark; (Cheshire, CT), Degnan, Andrew P.; (New Haven, CT), Dubowchik, Gene M.; (Middlefield, CT), Han, Xiaojun; (Cheshire, CT), Karageorge, George N.; (Portland, CT), Luo, Guanglin; (Madison, CT), Macor, John E.; (Guilford, CT), Poindexter, Graham; (Old Saybrook, CT), Vig, Shikha; (Durham, CT) Correspondence: Stephen B. Davis; Bristol-Myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20040063735 Date filed: May 27, 2003 Abstract: The present invention relates to compounds of Formula (I) 1as antagonists of calcitonin gene-related peptide receptors ("CGRP-receptor"), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors. Excerpt(s): This non-provisional application claims priority from provisional application U.S. S No. 60/386,138 filed Jun. 5, 2002, from provisional application U.S. S No. 60/388,617 filed Jun. 13, 2002, from provisional application U.S. S No. 60/389,870 filed Jun. 19, 2002, from provisional application U.S. S No. 60/393,200 filed Jul. 1, 2002, and from provisional application U.S. S No. 60/413,534 filed Sep. 25, 2002. The present invention relates to novel small molecule antagonists of calcitonin gene-related peptide receptors ("CGRP-receptor"), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine, cluster headache and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors. Calcitonin gene-related peptide (CGRP) is a naturally occurring 37-amino-acid peptide first identified in 1982 (Amara, S. G. et al, Science 1982, 298, 240-244). Two forms of the peptide are expressed (ACGRP and SCGRP) which differ by one and three amino acids in rats and humans, respectively. The peptide is widely distributed in both the peripheral (PNS) and central nervous system (CNS), principally localized in sensory afferent and central neurons, and displays a number of biological effects, including vasodilation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Calcitonin-like sequence expressed by gonadotropes of the anterior pituitary Inventor(s): Shah, Girish; (Amarillo, TX) Correspondence: Jones, Tullar & Cooper, P.C.; P.O. Box 2266 Eads Station; Arlington; VA; 22202 Patent Application Number: 20030114383 Date filed: November 1, 2002 Abstract: A cDNA sequence has been identified for an anterior pituitary-derived peptide (pit-CT) produced and secreted by the pituitary cells. The pit-CT has substantial sequence homology to calcitonin (CT) and has biological properties similar to salmon calcitonin (SCT). The pit-CT may be used to treat various diseases, such as osteoporosis, Pagets, and Prolactinoma. Excerpt(s): This application claims the benefit, under 35 U.S.C. 119(e), of U.S. Provisional Application No. 60/330,838 filed Nov. 1, 2001 and U.S. Provisional Application No. 60/331,398 filed Nov. 15, 2001, the contents of which are incorporated herein by reference. The present invention relates generally to the treatment of various diseases, such as osteoporosis, Pagets, and prolactinoma, using an anterior pituitary-derived peptide (herein referred to as "pit-CT") which has substantial sequence homology to calcitonin (herein referred to as "CT") and has biological properties similar to a calcitonin-like peptide derived from salmon, commonly known as salmon calcitonin (herein referred to as "SCT"). Osteoporosis is a major health problem that affects more than 25 million women in the United States alone and potentially 200 million worldwide. The disease is characterized by diminished structural integrity of the skeleton, which results in an increased risk of fracture. Osteoporosis is a condition that develops silently over a period of years, eventually progressing to a point where a fracture can easily occur causing pain and disability. The post-menopausal female population has the highest incidence of osteoporosis and the highest rate of morbidity and mortality due to this disease. The National Osteoporosis Foundation in the U.S. estimates that osteoporosis is responsible for approximately 1.5 million fractures in the U.S. alone. Hip fractures lead to the most serious consequences with one in five hip fracture patients dying of complications within a year after the fracture and one in four requiring long-term care. The National Osteoporosis Foundation in the U.S. estimates that the cost of treating osteoporosis is approximately $14 billion annually in the U.S. alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cloning and characterization of calcitonin gene related peptide receptors Inventor(s): Pisegna, Joseph R.; (Santa Monica, CA), Wank, Stephen A.; (Potomac, MD) Correspondence: Quine Intellectual Property Law Group, P.C.; P O Box 458; Alameda; CA; 94501; US Patent Application Number: 20040110170 Date filed: May 16, 2003 Abstract: This invention provides CGRP receptors (including both amino acid and nucleic acid sequences). Compositions which include these polypeptides, proteins, nucleic acids, recombinant cells, transgenic animals, and antibodies to the receptors are also provided.

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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/381,911 filed May 18, 2002, entitled "CLONING AND CHARACTERIZATION OF CALCITONIN GENE RELATED PEPTIDE RECEPTORS" and naming Joseph Pisegna et al. as the inventors. This prior application is hereby incorporated by reference in its entirety. The invention relates to the field of neuropeptide receptors. In particular, the invention relates to amino acid and nucleic acid sequences for CGRP receptors and methods for producing and isolating such sequences or molecules. The invention also provides methods for use of such molecules (e.g., for identifying, isolating, and/or purifying agonists/antagonists of CGRP receptors), compositions comprising the molecules, and homologous molecules, as well as antibodies to the molecules. The Calcitonin Gene Related Peptide (CGRP) is a 37-amino acid neuropeptide encoded as a splice variant by the calcitonin/CGRP gene. See, e.g., S. G. Amara, et al. (1982) Nature 298:240-244 and M. G. Rosenfeld, et al. (1983) Nature 204:129-135. CGRP peptides are structurally similar to members of the Adrenomedullin and Amylin families (e.g., including similar N-terminal disulfide bonds and C-terminal amide). Two biologically active forms of CGRP (.alpha.-CGRP and.beta.-CGRP) exist in both rats and humans and induce similar biological activities. CGRP receptors are highly expressed throughout the brain and gastrointestinal tract where they are involved in, e.g., regulation of pain responses and gut motility. CGRP has also been found to be involved in numerous important physiological activities, such as: vasodilatation, cardiac acceleration, inhibition of gastric acid secretion, reduction of intestinal motility, regulation of glucose metabolism, diminution of appetite, and reduction of growth hormone release, etc. See, e.g., S. J. Wimalawansa, (1997) Crit Rev in Neurobiol 11, 167-239. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for treating female sexual arousal disorder using hydrophobic-calcitonin gene related peptide Inventor(s): Rosenthal, Gary J.; (Louisville, CO), Southard, Jeffrey L.; (Olathe, KS), Yewey, Gerald L.; (Overland Park, KS) Correspondence: Steven C. Petersen; Hogan & Hartson, Llp; 1200 17th Street; Denver; CO; 80202; US Patent Application Number: 20030130183 Date filed: January 8, 2002 Abstract: The present invention provides a method and composition for the treatment of Female Sexual Arousal Disorder. Calcitonin gene-related peptide, a naturally occurring substance in the human body, is chemically conjugated to a hydrophobic agent thereby increasing its permeability across the skin membrane. When locally applied to female genitalia localized blood flow is promoted thus resulting in increased sexual arousal. Excerpt(s): The present invention relates to compositions and methods for the local administration of a therapeutic preparation for treating female sexual arousal dysfunction, and more particularly, to a preparation comprising calcitonin gene-related peptide conjugated to a hydrophobic agent and methods of use for promoting blood flow to the genital region, specifically the clitoris of a female patient. According to the Journal of the American Medical Association, more than 43% of American women (about 40 million) experience some form of sexual disorder. Other reports state that 70% of post-menopausal and 25% of pre-menopausal women experience sexual dysfunction. Any woman can experience Female Sexual Dysfunction at some point in her life. Physicians and other healthcare providers recognize Female Sexual Dysfunction as a

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medical condition. It includes a variety of disorders that are related to the desire for sex, arousal during sexual activity, problems with orgasm or pain during sexual activity. If a woman's sexual concerns are recurring in nature and cause her personal distress, she may indeed have female sexual dysfunction. Specifically, Female Sexual Dysfunction is divided into categories related to desire, orgasm, arousal and pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Electrical stimulation to increase calcitonin levels Inventor(s): Shealy, C. Norman; (Fair Grove, MO) Correspondence: Foley & Lardner; 150 East Gilman Street; P.O. Box 1497; Madison; WI; 53701-1497; US Patent Application Number: 20030220669 Date filed: May 23, 2002 Abstract: The endogenous enhancement of calcitonin in a human being has the ability to act as an analgesic and to treat osteoporosis, for example. Exogenous administration of calcitonin has disadvantages given its expense and the possible triggering of a hypersensitivity reaction and other side effects. The present invention provides the benefits of enhanced calcitonin through electrical stimulation that increases endogenous calcitonin levels without the need for exogenous administration of calcitonin. Excerpt(s): This invention pertains to a method for enhancing calcitonin levels in human beings without exogenous administration of calcitonin. Calcitonin was discovered in 1961 and has been widely used clinically for the treatment Paget's disease, hypercalcemia, osteoporosis, and the relief of bone pain. Calcitonin is a hormone produced by the thyroid gland and secreted in response to high levels of calcium in the blood. Also known as thyrocalcitonin, it lowers the level of calcium in the blood by inhibiting bone resorption, the dissolution of bony tissue. Calcitonin plays a role in pain relief and has been noted for its analgesic effects in bone metastases of primitive cancer and phantom limb pain. It can also enhance or produce recalcification, and is the subject of studies for treatment of peptic ulcers. Though a wide range of pharmacological effects have been attributed to calcitonin, discussion of calcitonin is generally associated with its effectiveness in treating pain and osteoporosis. Copp reported discovering in addition to parathyroid hormone (PTH), which plays a key role in controlling hypocalcemia by stimulating osteolysis, a second calcium-regulating hormone, calcitonin. Copp found that hypercalcemia and lowered plasma calcium, by inhibiting osteolysis, released calcitonin. Copp was involved in the isolation of salmon calcitonin, which is the form most widely used in therapy because of its high potency. In addition to inhibiting bone resorption, salmon calcitonin is a powerful analgesic agent with a potency in certain circumstances which is 30 to 50 times that of morphine. It is widely used clinically for the treatment of Paget's disease, hypercalcemia, osteoporosis, and relief of bone pain. World sales in 1992 exceeded U.S. $900 million, of which 85% was for osteoporosis. Copp, D. H., "Calcitonin: discovery, development, and clinical application," Clin. Invest. Med., Vol. 17(3), pp. 268-77 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Formulations for administering calcitonin and processes for preparing the same Inventor(s): Libbey, Miles A.; (US), McCoy, Randall E.; (US), Williams, Robert O. III; (US) Correspondence: Mathews, Collins, Shepherd & Gould, P.A.; 100 Thanet Circle, Suite 306; Princeton; NJ; 08540-3674; US Patent Application Number: 20020132757 Date filed: May 14, 2001 Abstract: The present invention provides a non-invasive method for administering polypeptides across epithelial membranes. The formulations in the present invention comprise solid polypeptide particles mixed with a permeation enhancer and excipients which are dispersed in a media for oral or intranasal administration. Also provided in the present invention is a process to prepare the formulations. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/204,308 filed on May 15, 2000 entitled "Formulations for Administering Calcitonin and Process for Preparing the Same", hereby incorporated by reference into this application. The present invention relates to formulations for non-invasive delivery of calcitonin across mucous membranes by oral or inhalant routes to patients and to processes for preparing the formulations. Effective, convenient, and comfortable delivery of calcitonin to patients is an area of major concern. A conventional mode of delivery for many drugs is by oral ingestion of pills or tablets that disintegrate into primary particles, and release the drug for absorption into the patient's bloodstream from the stomach and gastrointestinal (GI) tract. However, calcitonin is not suitable for conventional modes of delivery such as oral delivery, as it is susceptible to enzymatic degradation, and its large size and hydrophilic nature makes it ill suited for absorption through the GI tract. Saliva and/or gastrointestinal compounds tend to degrade or digest the calcitonin, rendering it ineffective. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treatment of persistent pain Inventor(s): Omoigui, Osemwota; (Tarzana, CA) Correspondence: Osemwota Omoigui MD; 4019 W. Rosecrans AVE.; Hawthorne; CA; 90250; US Patent Application Number: 20040038874 Date filed: August 22, 2002 Abstract: This invention relates to a method for treating persistent pain disorders by inhibiting the biochemical mediators of inflammation in a subject comprising administering to said subject a therapeutically effective dosage of said inhibitor. Said process for treating persistent pain disorders is based on Sota Omoigui's Law, which states: The origin of all pain is inflammation and the inflammatory response. Biochemical mediators of inflammation that are targeted for inhibition include but are not limited to: prostaglandin, nitric oxide, tumor necrosis factor alpha, interleukin 1alpha, interleukin 1-beta, interleukin-4, Interleukin-6 and interleukin-8, histamine and serotonin, substance P, Matrix Metallo-Proteinase, calcitonin gene-related peptide, vasoactive intestinal peptide as well as the potent inflammatory mediator peptide proteins neurokinin A, bradykinin, kallidin and T-kinin.

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Excerpt(s): This invention relates to a method of treatment of persistent pain by application of Sota Omoigui's Law, which states: The origin of all pain is inflammation and the inflammatory response. Irrespective of the type of pain whether it is acute pain as in a sprain, sports injury or eurochange jellyfish sting or whether it is chronic pain as in arthritis, migraine pain, back or neck pain from herniated disks, RSD/CRPS pain, migraine, Fibromyalgia, Interstitial cystitis, Neuropathic pain, Post-stroke pain etc, the underlying basis is inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. The current theories and treatment options for persistent pain are not satisfactory. The population of patients with chronic pain and disrupted lives grows constantly. According to the American Pain foundation, there are 75 million Americans who have chronic pain. Pain is the second most common reason for doctor visits. Unless we can understand how pain is generated, we cannot provide a solution. Our understanding of Pain has not advanced since the 1965 publication of the Gate Theory of Pain by Canadian psychologist Ronald Melzack and British physiologist Patrick Wall. In their paper titled "Pain Mechanisms: A New Theory".sup.1, Melzack and Wall suggested a gating mechanism within the spinal cord that closed in response to normal stimulation of the fast conducting "touch" nerve fibers; but opened when the slow conducting "pain" fibers transmitted a high volume and intensity of sensory signals. The gate could be closed again if these signals were countered by renewed stimulation of the large fibers. Sota Omoigui's Law is a dramatic and revolutionary shift from a focus on structural pathology to an understanding of the biochemical origin of Pain. Current medical theories place an over reliance on structural abnormalities to explain pain syndromes. This is not surprising because our current imaging technologies are structure based. Physicians are comfortable treating what they see. Patients who have structural abnormalities such as a herniated disk on MRI scans get operated upon often times needlessly and end up with more back or neck pain. Patients with severe pain who do not have structural abnormalities on MRI scans are dismissed as psychiatric cases. The fallacy of this approach has been confirmed in numerous published studies. In one of these studies.sup.2, the authors performed magnetic resonance imaging on sixty-seven individuals who had never had low-back pain, sciatica, or neurogenic claudication. The scans were interpreted independently by three neuro-radiologists who had no knowledge about the presence or absence of clinical symptoms in the subjects. About one-third of the subjects were found to have a substantial abnormality. Of those who were less than sixty years old, 20 per cent had a herniated nucleus pulposus and one had spinal stenosis. In the group that was sixty years old or older, the findings were abnormal on about 57 per cent of the scans: 36 per cent of the subjects had a herniated nucleus pulposus and 21 per cent had spinal stenosis. There was degeneration or bulging of a disc at least one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects. In view of these findings in asymptomatic subjects, the authors concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated. In another study, the authors examined the prevalence of abnormal findings on magnetic resonance imaging (MRI) scans of the lumbar spine in people without back pain. 52 percent of the asymptomatic subjects were found to have a bulge at least at one level, 27 percent had a protrusion, and 1 percent had an extrusion. Thirty-eight percent had an abnormality of more than one intervertebral disk. The prevalence of bulges, but not of protrusions, increased with age. The most common nonintervertebral disk abnormalities were Schmorl's nodes (herniation of the disk into the vertebral-body end plate), found in 19 percent of the subjects; annular defects (disruption of the outer fibrous ring of the

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disk), in 14 percent; and facet arthropathy (degenerative disease of the posterior articular processes of the vertebrae), in 8 percent. The findings were similar in men and women. The authors concluded that on MRI examination of the lumbar spine, many people without back pain have disk bulges or protrusions but not extrusions. The authors went further to state that given the high prevalence of these findings and of back pain, the discovery by MRI of bulges or protrusions in people with low back pain may frequently be coincidental. In another study.sup.4, which tracked the natural history of individuals with asymptomatic disc abnormalities in magnetic resonance imaging the authors stated that the high rate of lumbar disc alterations recently detected in asymptomatic individuals by magnetic resonance imaging demands reconsideration of a pathomorphology-based explanation of low back pain and sciatica. The origins of pain are the biochemical mediators of inflammation. To treat pain, we must block these mediators and block the signals they send up through the nerve cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for the modulation of neurogenic inflammatory pain and physical opiate withdrawal Inventor(s): Changeux, Jean-Pierre; (Paris, FR), Picciotto, Marina; (Guilford, CT), Salmon, Anne-Marie; (Paris, FR), Sekine, Susumu; (Kanagawa, JP) Correspondence: Finnegan Henderson Farabow Garrett & Dunner; Suite 700; 1300 I Street, N.W.; Washington; DC; 20005; US Patent Application Number: 20020162125 Date filed: March 6, 2002 Abstract: A method of screening for a compound that is an antagonist of calcitonin gene related peptide (.alpha.CGRP) is provided. The method comprises: exposing a mutant mouse to a compound. The mutant mouse has a genome that comprises a homozygous disruption of the.alpha.CGRP gene, wherein the disruption results in the mutant mouse lacking detectable levels of endogenous.alpha.CGRP as compared to a wild type mouse. The response of the mutant mouse to a nociceptive-inducing stimulus is determined. A difference in response compared to a wild type mouse is indicative of the compound functioning to alter.alpha.CGRP activity. In a preferred embodiment, the disruption comprises the insertion of a transgene. A compound identified by the method is also provided. The compound is useful for ameliorating neurogenic inflammatory pain and/or physical opiate withdrawal. Excerpt(s): This application is based on and claims the benefit of U.S. Provisional Application No. 60/273,349, filed Mar. 6, 2001 (attorney docket no. 03495.6062) The entire disclosure of this application is relied upon and incorporated by reference herein. The present invention relates to methods and compositions for the modulation of neurogenic inflammatory pain and/or physical opiate withdrawal. In a particular embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of calcitonin gene related peptide (.alpha.CGRP). Calcitonin gene related peptide (.alpha.CGRP) is expressed in a variety of cell types in both central and peripheral nervous systems and the characteristics of the gene encoding.alpha.CGRP have been disclosed (1). Among its various functions,.alpha.CGRP has been suggested to contribute to local, neurogenic inflammatory responses (2) and to nociception (3).alpha.CGRP is expressed in 40% of the sensory neurons of the dorsal ganglia, being present in both the peripheral A.delta. and C fibres and in the primary afferent nerves to the spinal cord.

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Methods and nucleic acids for the analysis of CpG dinucleotide methylation status associated with the calcitonin gene Inventor(s): Cottrell, Susan; (Seattle, WA), Mooney, Suzanne; (Seattle, WA) Correspondence: Davis Wright Tremaine, Llp; 2600 Century Square; 1501 Fourth Avenue; Seattle; WA; 98101-1688; US Patent Application Number: 20040029121 Date filed: August 8, 2002 Abstract: The disclosed invention provides methods and sequences for the analysis of methylation patterns within a novel 5' upstream CpG island of the calcitonin gene. Excerpt(s): The present invention relates to human DNA sequences that exhibit altered methylation patterns (hypermethylation or hypomethylation) in cancer patients. These novel methylation-altered DNA sequences are useful as diagnostic, prognostic and therapeutic markers for human cancer. 5-methylcytosine is the most frequent covalent base modification in the DNA of eukaryotic cells. It plays a role, for example, in the regulation of the transcription, in genetic imprinting, and in tumorigenesis. Therefore, the identification of 5-methylcytosine as a component of genetic information is of considerable interest. However, 5-methylcytosine positions cannot be identified by sequencing since 5-methylcytosine has the same base pairing behavior as cytosine. Moreover, the epigenetic information carried by 5-methylcytosine is completely lost during PCR amplification. Current use of bisulfite modification to assess CpG methylation status A relatively new and currently the most frequently used method for analyzing DNA for 5-methylcytosine is based upon the specific reaction of bisulfite with cytosine which, upon subsequent alkaline hydrolysis, is converted to uracil which corresponds to thymidine in its base pairing behavior. However, 5-methylcytosine remains unmodified under these conditions. Consequently, the original DNA is converted in such a manner that methylcytosine, which originally could not be distinguished from cytosine by its hybridization behavior, can now be detected as the only remaining cytosine using "normal" molecular biological techniques, for example, by amplification and hybridization or sequencing. All of these techniques are based on base pairing which can now be fully exploited. In terms of sensitivity, the prior art is defined by a method which encloses the DNA to be analyzed in an agarose matrix, thus preventing the diffusion and renaturation of the DNA (bisulfite only reacts with singlestranded DNA), and which replaces all precipitation and purification steps with fast dialysis (Olek A, et al., A modified and improved method for bisulphite based cytosine methylation analysis, Nucleic Acids Res. 24:5064-6, 1996). Using this method, it is possible to analyze individual cells, which illustrates the potential of the method. However, currently only individual regions of a length of up to approximately 3000 base pairs are analyzed, and a global analysis of cells for thousands of possible methylation events is not possible. Moreover, this method cannot reliably analyze very small fragments from small sample quantities. Such fragments are lost through the matrix despite the diffusion protection. An overview of art-recognized methods for detecting 5methylcytosine is provided by Rein, T., et al., Nucleic Acids Res., 26:2255, 1998. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Oral peptide pharmaceutical dosage form and method of production Inventor(s): Crotts, George; (Kintnersvill, PA), Ghebre-Sellassie, Isaac; (Morris Plains, NJ), Sheth, Ashlesh; (Randolph, NJ) Correspondence: Ostrolenk Faber Gerb & Soffen; 1180 Avenue OF The Americas; New York; NY; 100368403 Patent Application Number: 20030017203 Date filed: March 7, 2002 Abstract: A pharmaceutical composition for oral delivery of a peptide is in the form of a lamination having at least two layers. The first layer of the lamination includes at least one pharmaceutically acceptable pH-lowering agent. The second layer includes a therapeutically effective amount of the peptide. The composition also includes at least one absorption enhancer effective to promote bioavailability of the peptide, which is preferably in the second layer, and an enteric coating surrounding the lamination. In a preferred dosage form of a tablet, a water-soluble coating is applied between the lamination and enteric coating which substantially prevents contact between the pHlowering agent and the enteric coating. In a preferred embodiment, the peptide is salmon calcitonin, the pH-lowering agent is citric acid, and the absorption enhancer is lauroyl l-carnitine. Excerpt(s): The present invention relates to oral peptide pharmaceutical dosage forms, to methods of enhancing the bioavailability of orally administered peptides, and to methods of production of tableted dosage forms useful for the treatment of disorders in humans by orally administering a peptide in accordance with the invention. Salmon calcitonin is a peptide hormone that decreases uptake of calcium from bone. When used to treat bone-related diseases and calcium disorders (such as osteoporosis, Paget's disease, hypercalcemia of malignancy, and the like), it has the effect of helping maintain bone density. Many types of calcitonin have been isolated, such as human calcitonin, salmon calcitonin, eel calcitonin, elkatonin, porcine calcitonin, and chicken calcitonin. There is significant structural non-homology among the various calcitonin types. For example, there is 50% identity between the amino acids making up human calcitonin and those making up salmon calcitonin. Salmon calcitonin used in the prior art has usually been administered by injection or by nasal administration. However, these modes of administering the calcitonin are significantly less convenient than oral administration and involve more patient discomfort. Often this inconvenience or discomfort results in substantial patient noncompliance with a treatment regimen. However, the prior art is not believed to have reported an ability to achieve reproducible blood levels of peptides such as salmon calcitonin when administered orally. This is believed to be because these peptides lack sufficient stability in the gastrointestinal tract, and tend to be poorly transported through intestinal walls into the blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Peptide antagonists of CGRP-receptor superfamily and methods of use Inventor(s): Abel, Peter W.; (Omaha, NE), Saha, Shankar; (Indianapolis, IN), Smith, Derek David; (Omaha, NE) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55401; US Patent Application Number: 20020068814 Date filed: March 20, 2001 Abstract: This invention relates to antagonists of calcitonin gene related peptide and in particular the invention relates to amino terminal modifications to peptides to improve their ability to bind to a member of the CGRP-receptor superfamily. Excerpt(s): This invention relates to the field of vasoactive compounds and their antagonists. In particular, this invention relates to antagonists of the vasoactive peptide CGRP and other members of the CGRP superfamily. The calcitonin gene related peptide (CGRP) is a sensory neuropeptide with potent vasodilatory and cardiotonic action as described in U.S. Pat. No. 4,530,838 to Evans et al. The peptide exists in two forms (denoted.alpha. and.beta.).alpha.-CGRP is produced by the calcitonin gene (Amara et al. Nature 298:240-244, 1982 and Rosenfeld et al. Nature 304:129-135, 1983) while.beta.-CGRP is the product of a separate gene (Amara et al. Nature 298:240-244, 1985 and Steenbergh et al. FEBS Lett. 183:403-407, 1985). The human.beta.-form and.alpha.-form differ by three amino acids. CGRP is concentrated in those areas of the body receiving sensory input from the dorsal horn with limited amounts associated with autonomic input. The peptide is present in the brain in the nuclei of sensory and motor cranial nerves and in cell bodies in the hypothalamus, preoptic area, ventromedial thalamus, hippocampus, and the like. CGRP is found in both sensory and motor nerves of the peripheral nervous system. The peptide is found in the skin, blood vessels, heart, gastrointestinal tract, tongue, esophagus, pancreas, salivary glands, lungs, kidney and other organs (Poyner, D. Pharmac. Ther. 56:23-51, 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions for the oral delivery of pharmacologically active agents Inventor(s): Ault, Joseph M.; (Blairstown, NJ), Azria, Moise; (Basel, CH), Bateman, Simon David; (Randolph, NJ), Sikora, Joseph; (Succasunna, NJ), Sparta, Gregory; (Bridgewater, NJ), Xiao, Jie; (Randolph, NJ), Yang, Rebecca Fai-ying; (Randolph, NJ) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20020123459 Date filed: December 4, 2001 Abstract: Solid pharmaceutical compositions suitable for the oral delivery of pharmacologically active agents, e.g. peptides, comprising a therapeutically-effective amount of a pharmacologically active agent; a crospovidone or povidone; and a delivery agent for said pharmacologically active agent are disclosed. The compositions provide excellent oral bioavailability of pharmacologically active agents, particularly calcitonin. Excerpt(s): The present invention relates to oral compositions for the delivery of pharmacologically active agents, to methods of enhancing the bioavailability of orally administered pharmacologically active agents, and to methods of treating and/or

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preventing disease in mammals, particularly humans, by orally administering a pharmacologically active agent in accordance with the invention. Oral delivery of pharmacologically active agents is generally the delivery route of choice since it is convenient, relatively easy and generally painless, resulting in greater patient compliance relative to other modes of delivery. However, biological, chemical and physical barriers such as varying pH in the gastrointestinal tract, powerful digestive enzymes, and active agent impermeable gastrointestinal membranes, makes oral delivery of some pharmacologically active agents to mammals problematic, e.g. the oral delivery of calcitonins, which are long-chain polypeptide hormones secreted by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish, has proven difficult due, at least in part, to the insufficient stability of calcitonin in the gastrointestinal tract as well as the inability of calcitonin to be readily transported through the intestinal walls into the blood stream. R.sup.6 and R.sup.7 are independently hydrogen, oxygen, or C.sub.1-C.sub.4 alkyl; and hydrates and solvates thereof as particularly efficacious for the oral delivery of active agents, such as calcitonin, cyclosporin and heparin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Polypeptide-calcitonin 11 and the polynucleotide encoding it Inventor(s): Mao, Yumin; (Shanghai, CN), Xie, Yi; (Shanghai, CN) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20040038873 Date filed: June 24, 2002 Abstract: The present invention discloses a new polypeptide-calcitonin 11, the polynucleotide encoding it and a method producing the polypeptide by recombinant DNA technology. The present invention further discloses a method using the polypeptide to treat various disorders, e.g. malignant neoplasm, hematopathy, HIV infection and immunological disease and various inflammation etc. The present invention also discloses agonists of the polypeptide and their therapeutic uses. The present invention further discloses the use of the polynucleotide encoding the new calcitonin 11. Excerpt(s): The invention relates to the field of biotechnology. In particular, the invention relates to a novel polypeptide, calcitonin 11, and a polynucleotide sequence encoding the polypeptide. The invention also relates to the method for the preparation and use of the polynucleotide and polypeptide. Calcitonin, calcitonin Gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) have similarities in their structure. Calcitonin is a polypeptide hormone with 32 amino acid residues. By binding to the calcium ion, it can modulate the concentration of calcium ion in blood (Breimer, et al., 1988, Biochem. J. 255:377-390). CGRP is a polypeptide hormone with 39 amino acid residues. It can cause vasodilatation in different vessels (including coronary artery, blood vessel of brain, and the entire vascular system). IAPP is a polypeptide hormone with 37 amino acid residues. It can selectively inhibit glucose metabolism and glycogen synthesis which are induced by insulin (Nishi et al., 1990, J. Biol. Chem. 265: 4173-4176). In almost all organisms, the three proteins share a conserved structural motif: C[SAGDN]-[STN]-x (0,1)-[SA]-T-C-[VMA]-x (3)-[LYF]-x (3)-[LYF], and the two cysteines was bonded by a disulfide bond.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant preparation of calcitonin fragments and use thereof in the preparation of calcitonin and related analogs Inventor(s): Frank, Julie A.; (Lincoln, NE), Henriksen, Dennis B.; (Lincoln, NE), Holmquist, Bart; (Lincoln, NE), Partridge, Bruce E.; (Lincoln, NE), Stout, Jay S.; (Lincoln, NE), Wagner, Fred W.; (Walton, NE) Correspondence: Beth A. Burrous; Foley & Lardner; Washington Harbor; 3000 K Street, N.W, Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20010031856 Date filed: January 2, 2001 Abstract: A process for the recombinant preparation of a calcitonin fragment and the use of the fragment in the preparation of calcitonin and related analogs is provided. The process includes recombinantly forming a fusion protein which includes the calcitonin fragment linked to a carbonic anhydrase. The recombinantly formed fusion protein is subsequently cleaved to produce a polypeptide which includes the calcitonin fragment. A method for producing a calcitonin carba analog which includes condensing a desaminononapeptide with the recombinantly formed calcitonin fragment is also provided. Excerpt(s): Calcitonins and related analogs, such as Elcatonin, are known polypeptides which can be employed for treating bone atrophy (see, e.g., U.S. Pat. No. 4,086,221). Naturally occurring calcitonins, such as eel, salmon or human calcitonin, are C-terminal amidated polypeptides which consist of 32 amino acids, the first and the seventh amino acids in each case being L-cysteines whose mercapto groups are connected to each other by the formation of a disulfide bridge. The natural calcitonins can be obtained, for example, by extraction from the mammalian thyroid gland (see, e.g., U.S. Pat. No. 5,428,129). Currently, a variety of processes are known for the preparation of Elcatonin using purely chemical methods. These chemical methods involve condensation of the corresponding amino acids or peptides (see, e.g., U.S. Pat. Nos. 4,086,221 and 5,428,129). The purely chemical methods, however, all suffer from the disadvantage that, due to the elaborate purification methods required, the Elcatonin is obtained in low yield and its preparation is consequently very expensive. It would accordingly be beneficial to be able to avoid the disadvantages of the purely chemical methods in the preparation of Elcatonin through the use of a approach which includes the recombinant preparation of a portion of the molecule. This could be achieved, for example, if a simple process for the recombinant preparation of a C-terminal polypeptide fragment was available. The recombinantly synthesized C-terminal fragment could then be used as a starting peptide for the preparation of calcitonin or carba analogs such as Elcatonin. A partially recombinant strategy would also facilitate the synthesis of peptides/peptide analogs of calcitonin, Elcatonin and related analogs or derivatives which could potentially include non-natural amino acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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THERAPEUTIC/COSMETIC COMPOSITIONS COMPRISING ANTAGONISTS FOR TREATING SENSITIVE HUMAN SKIN

CGRP

Inventor(s): BRETON, LIONEL; (VERSAILLES, FR), DE LACHARRIERE, OLIVIER; (PARIS, FR) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20010051157 Date filed: October 28, 1999 Abstract: Topically applicable pharmaceutical/dermatological/cosmetic compositions well suited for the therapeutic treatment or care of sensitive human skin, hair, mucous membranes, nails and/or the scalp, in particular for reducing or avoiding the skinirritant side effects of a variety of bioactive agents, for example the.alpha.-hydroxy acids, comprise a therapeutically/cosmetically effective amount of at least one calcitonin gene related peptide ("CGRP") antagonist, e.g., CGRP 8-37 or an anti-CGRP antibody. Excerpt(s): The present invention relates to the formulation of an antagonist of CGRP (peptide derived from the calcitonin gene: Calcitonin Gene Related Peptide, or "CGRP") into topically applicable cosmetic/pharmaceutical/dermatological compositions, for the treatment of sensitive skin-types, as well as to cosmetic compositions containing a CGRP antagonist for reducing or eliminating the irritant effects elicited by certain active agents, and especially by certain bioactive agents conventionally employed in the cosmetics, pharmaceutical or dermatological field. It is known to this art that certain skin-types are more sensitive than others. The symptoms of sensitive skin-types were heretofore poorly characterized and the problem of these skin-types was, as a result, poorly defined; the exact mechanism involved in the sensitivity--nonallergic cutaneous hyperreactivity--of the skin, was unknown. In certain quarters it was believed that a sensitive skin was a skin which reacted to cosmetic products, while others believed that it concerned a skin which reacted to a variety of external factors, not necessarily associated with cosmetic products. Certain tests have been conducted in attempting to define sensitive skin-types, for example tests using lactic acid and DMSO which are known to be irritant substances: see, for example, the article by K. Lammintausta et al, Dermatoses, 36, pages 45-49 (1988); and the article by T. Agner and J. Serup, Clinical and Experimental Dermatolooy, 14, pages 214-217 (1989). However, these tests did not make it possible to characterize sensitive skin-types. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

USE OF CALCITONIN GENE-RELATED PEPTIDE IN THE PREVENTION AND ALLEVIATION OF ASTHMA AND RELATED BRONCHOSPASTIC PULMONARY DISEASES Inventor(s): CADIEUX, ALAIN; (ROCH FOREST, CA) Correspondence: Stephen A Bent; Foley & Lardner; Washington Harbour; 3000 K Street N W Suite 500; Washington; DC; 200075109 Patent Application Number: 20020037846 Date filed: December 30, 1999

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Abstract: The present invention relates to the use of calcitonin gene-related peptide (CGRP) in the prevention and alleviation of asthmatic symptoms. In contrast to other therapeutic agents now in use, CGRP combines both bronchoprotector and antiinflammatory properties. Furthermore, it prevents both early and late phase bronchial responses associated with an asthma attack and its effective dose is small enough that undesirable haemodynamic side effects are not present. Excerpt(s): The present invention teaches that calcitonin gene-related peptide (CGRP), a neurotransmitter present in sensory nerves of several mammalian species, including humans, displays potent and efficient bronchoprotector and anti-inflammatory properties. More specifically, the present invention discloses that CGRP, when administered by inhalation to mammals, is capable of reducing the accumulation of eosinophils in the bronchial walls and of preventing bronchospastic airway responses, especially reversible airway hyperreactivity such as that encountered in bronchial asthma. Bronchial asthma may be defined as a clinical syndrome characterized by outbursts of suffocation and of severe discomfort, especially when air is exhaled from the lungs. These asthma outbursts or asthma attacks often occur after exertions or during the night, are reversible either spontaneously or following treatments and are generally the result of bronchial obstructions. Three major factors contribute to these obstructions: a spasm (contraction) of the smooth muscles surrounding the airways, an inflammation of the bronchial walls accompanied by an effusion of fluid (oedema) and an hypersecretion of mucus. Although the relative contribution of each of these conditions is unknown, the net result is an increase in airway resistance, hyperinflation of the lungs and thorax, as well as abnormal distribution of ventilation and pulmonary blood flow. Thus, when an asthma attack occurs, breathing becomes difficult and may be accompanied by wheezing, coughing and dyspnea. A major feature of this disorder is the propensity of the airways of asthmatics to respond in an abnormally exaggerated way (bronchial hyperreactivity) to a large variety of apparently unrelated stimuli such as allergic triggers, cigarette smoke, dust, pollens, chemical products, irritating vapours, cold air, food substances, physical exertion, stress, etc. Because of this increase in the sensitivity of the airways (10 to 1000 times normal), asthma has for a long time been regarded as a disease of the large airways which was believed to be caused mainly by mucus secretion and extensive narrowing of the tracheobronchi which consequently made breathing difficult for asthmatics. 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 calcitonin, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “calcitonin” (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 calcitonin. You can also use this procedure to view pending patent applications concerning calcitonin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON CALCITONIN Overview This chapter provides bibliographic book references relating to calcitonin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on calcitonin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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

Boning Up on Osteoporosis: A Guide to Prevention and Treatment Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 75 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: $3.00; bulk orders available at cost. Summary: This book provides the general public and people who have osteoporosis with information on preventing and treating this disease. It is characterized by a loss of bone mass and by poor bone quality, leading to reduced bone strength and increased risk of fractures. The first section explains how bones grow and change through the process of bone remodeling. A description of risk factors for osteoporosis follows. Risk factors that people cannot change are gender, age, family history, body size, and ethnicity. Risk factors that people can change are hormone levels, diet, exercise, and lifestyle choices. A description of other factors that influence bone health and a

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discussion of osteoporosis and arthritis are included. The next section focuses on preventing bone loss at all ages. Building and maintaining strong bones involves attaining peak bone mass during childhood, adolescence, and young adulthood; maintaining peak bone mass; and preventing bone loss in later life. In addition, this section discusses the prevention of osteoporosis by consuming enough calcium and vitamin D, exercising, and taking medications such as estrogen and hormone replacement therapy and alendronate sodium. The occurrence of osteoporosis in children and men is also discussed. The third section uses a question and answer format to provide information on using bone mineral density tests to diagnose osteoporosis. In addition, this section discusses other methods of diagnosis such as detecting biochemical markers and using laboratory and other tests. The next section deals with treatment. Approved medications are estrogen, calcitonin, alendronate sodium, and etridronate. In addition, many experimental treatments may prevent bone breakdown or stimulate the formation of new bone. The section also presents strategies for recovering from fractures and managing pain, discusses osteoporosis support groups, provides tips on moving safely, and describes exercises designed to promote and maintain good posture. A final section presents suggestions on finding better fitting clothing, remaining sexually active, and preventing falls. Numerous figures, 7 tables, and 3 references.

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 “calcitonin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “calcitonin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “calcitonin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Calcitonin: Chemistry, physiology, pharmacology, and clinical aspects : proceedings of the International Symposium Calcitonin 1984, Milan, 2-4 October 1984 (International congress series); ISBN: 0444806903; http://www.amazon.com/exec/obidos/ASIN/0444806903/icongroupinterna

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Human calcitonin and Paget's disease: Proceedings of an international workshop, London, April 1976; ISBN: 3456805020; http://www.amazon.com/exec/obidos/ASIN/3456805020/icongroupinterna

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Parathormone and calcitonin radioimmunoassay in various medical and osteoarticular disorders by Paul Franchimont; ISBN: 039758184X; http://www.amazon.com/exec/obidos/ASIN/039758184X/icongroupinterna

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The CGRP Family: Calcitonin Gene-Related Peptide (CGRP), Amylin, and Adrenomedullin by David Poyner, et al; ISBN: 1587060043; http://www.amazon.com/exec/obidos/ASIN/1587060043/icongroupinterna

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

Management of Primary Biliary Cirrhosis: Osteoporosis Source: in Lindor, K.D.; Heathcote, E.J.; Poupon, R., eds. Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment. Boston, MA: Kluwer Academic Publishers. 1998. p. 92-101. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: Primary biliary cirrhosis (PBC) is a chronic cholestasic (lack of bile flow) liver disease of unknown etiology (cause), although the association with a large number of autoimmune disorders suggests that the disease may be of autoimmune origin. The disease usually affects middle aged women and progresses from asymptomatic disease with only laboratory abnormalities to a severe cholestatic disease with deep jaundice, xanthomas (fatty tumors in the skin), portal hypertension (high blood pressure), and eventually liver failure. This chapter on osteoporosis (bone thinning) is from a monograph that reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of PBC. Bone disease complicates the natural history in patients with PBC. The author discusses the incidence of bone disease in PBC, bone turnover in PBC, and the management of osteoporosis in PBC. Although bone turnover may change during the disease, it is generally accepted that osteoporosis in PBC results from impaired osteoblast function probably as the consequence of cholestasis, and is particularly related to the duration of the disease, postmenopausal condition, and intestinal calcium malabsorption. The management of osteoporosis is addressed to prevent the development of bone loss. Calcium and vitamin D supplements are mandatory, particularly in patients with severe cholestasis and in countries with a low rate of sunlight irradiation. Calcitonin has minor effects, if any, for preventing bone loss, whereas both sodium fluoride and cyclical etidronate are effective for treating trabecular osteopenia (subnormally mineralized bone). 4 figures. 1 table. 42 references.

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Why Legs Bow in Patients with Paget 's Disease Source: in A Patient's Guide to Paget 's Disease of Bone. New York, NY: The Paget 's Disease Foundation, Inc. 1994. p. 25-26. Contact: Paget Foundation For Paget 's Disease of Bone and Related Disorders. 200 Varick Street, Suite 1004, New York, NY 10014-4810. (212) 229-1582 or FAX (212) 2291502. PRICE: Free. Summary: This chapter explains that the reason legs bow in patients with Paget 's disease ( PD ) is because PD causes the leg bone to soften and become deformed. This

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softening process is due to the normal daily bone repair process of the body being too rapid or haphazard causing the bone to lose its optimum strength. No one knows if medical treatment helps prevent bowing in a patient with PD , but many believe that suppressing PD with medications such as calcitonin or bisphosphonates is a wise option. If pain is present in the joint, then arthritis interventions are recommended. If pain management or measures to stop the bowing are unsuccessful, then the option of surgically straightening the leg ( osteotomy ) may be considered. Obtaining several opinions from experienced physicians about this operation is recommended. •

Osteoporosis and Osteomalacia Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 1005-1024. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals presents an overview of osteoporosis and osteomalacia. Epidemiological data on osteoporosis are provided. Types of osteoporosis are described, including postmenopausal, age-related, idiopathic, juvenile, and endocrine- and drug-induced osteoporosis. The clinical features of osteoporosis are highlighted. Its pathogenesis is explained. The use of risk factor assessment, bone mass measurement, bone biopsy, and biochemical markers in the diagnosis of osteoporosis is discussed. The role of calcium and calcitonin supplementation, exercise, and hormone replacement therapy (HRT) in the prevention of osteoporosis is examined. Approaches to treating established osteoporosis are considered, including the use of HRT, calcitonin, bisphosphonates, testosterone and anabolic steroids, vitamin D and metabolites, sodium fluoride, and parathyroid hormone. In addition, the clinical and laboratory features and causes of osteomalacia and rickets are presented. 114 references, 12 figures, and 6 tables.

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Hormone Tests: Tracking the Body's Messengers Source: in Shaw, M., et al., eds. Everything You Need to Know About Medical Tests. Springhouse, PA: Springhouse Corporation. 1996. p. 425-482. Contact: Available from Springhouse Publishing. Attention: Trade and Textbook Department, 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477-0908. (800) 3313170 or (215) 646-4670 or (215) 646-4671. Fax (215) 646-8716. PRICE: $24.95 (as of 1995). ISBN: 0874348234. Summary: This chapter on hormone tests is from a consumer reference guide to over 400 diagnostic tests. For each test, the book covers the reasons for performing the test; what patients should know before the test; what to expect during and after the test; risk factors; the normal results; and what abnormal results mean. Tests in this chapter include tests for pituitary hormones; thyroid and parathyroid hormones; adrenal hormones; pancreas and stomach hormones; sex hormones; and pregnancy-triggered hormones. Tests specifically related to digestive diseases include the insulin tolerance test; thyroid-stimulating hormone; calcitonin; cortisol; catecholamine levels; insulin; and gastrin. Other topics include the physiology of hormone production, including thyroid hormones; the anatomy of the thyroid gland; the anatomy of the adrenal gland; the physiology of the stress reaction; and the anatomy of the pancreas.

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Hypercalcemia Source: in Mandal, A.K. and Nahman, N.S., Jr., eds. Kidney Disease in Primary Care. Baltimore, MD: Williams and Wilkins. 1998. p. 193-203. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail: [email protected]. PRICE: $39.95. ISBN: 0683300571. Summary: This chapter on hypercalcemia (high levels of calcium in the blood) is from a textbook that provides primary care physicians with practical approaches to common clinical problems of kidney diseases. The author first provides background information about hypercalcemia, including the physiology of calcium metabolism. The author then discusses the causes of hypercalcemia, including associated conditions, symptoms, diagnosis, familial benign hypercalcemia, milk alkali syndrome, treatment options (hydration, calcium diuresis), and inhibiting osteoclastic bone reabsorption. The chapter concludes with a discussion of prevention issues, the indications for referring a patient to a specialist, and the answers to a list of questions commonly asked by patients diagnosed with hypercalcemia. In general, the higher the level of serum calcium, the more likely malignancy (cancer) is the underlying cause of hypercalcemia. Good hydration is a vital preventive measure because dehydration aggravates hypercalcemia. Rehydration with intravenous infusion of isotonic saline is the essential first step of treatment of hypercalcemia, regardless of etiology. The cornerstone of therapy is inhibition of osteoclastic bone reabsorption by drug agents, including calcitonin, a biphosphonate, plicamycin (mithramycin), or corticosteroids. 1 figure. 1 table. 6 references.

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Chapter 48: Paget's Disease of Bone Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 2 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have Paget's disease of bone with information on the symptoms, diagnosis, and treatment of this chronic disorder of the skeleton. Although the disease can affect any bone, it most commonly affects the pelvis, thighbone, skull, shin, spine, collarbone, and upper arm bone. Men over age 40 most commonly get this disease in which areas of bone grow abnormally, enlarging and becoming soft. The cause of Paget's disease is unknown. It tends to run in families, but no specific genetic pattern has been discovered. Some evidence suggests that viral infection has a role. Symptoms are frequently absent in Paget's disease, and when they occur, they vary depending on which bones are affected. Bone pain may occur. The disease is often discovered accidentally when x rays or laboratory tests are performed for other reasons. The diagnosis may be suspected on the basis of symptoms and the physical examination. Tests that confirm the diagnosis include x rays and laboratory tests measuring blood levels of alkaline phosphatase. Treatment is needed only if the symptoms cause discomfort or if the risk of complications is great. Bone pain can be reduced by using aspirin, other nonsteroidal antiinflammatory drugs, and common analgesics. A bisphosphonate or calcitonin can be used to slow the progression of the disease.

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Endocrine Regulation of Calcium and Phosphate Metabolism Source: in Porterfield, S.P. Endocrine Physiology. 2nd ed. St. Louis, MO: Mosby, Inc. 2001. p. 107-129. Contact: Available from Harcourt Health Sciences. Foots Cray High Street, Sidcup, Kent DA14 5HP, United Kingdom. 020 8308 5700. Fax 020 8308 5702. E-mail: [email protected]. PRICE: $32.95 plus shipping and handling. ISBN: 0323011284. Summary: This chapter, which is part of a textbook on endocrine physiology, focuses on endocrine regulation of serum calcium and phosphate. The chapter begins with an examination of the role of calcium and phosphate in the body. This is followed by a discussion of serum calcium and phosphate levels and serum calcium and phosphate balance. The chapter then describes the role of osteoblasts, osteocytes, and osteoclasts in bone metabolism and identifies major growth factors in bone such as insulin like growth factors. These components, which are mitogenic polypeptides that resemble insulin structure and function, are present in bone matrix. They stimulate bone and cartilage growth and increase osteoblast proliferation. Insulin and growth hormone control their production. The chapter next discusses parathyroid hormone, calcitonin, and vitamin D in terms of their structure, control of secretion, and actions on bone and kidney. The actions of other hormones are also highlighted, including estrogens, glucocorticoids, and thyroid hormones. In addition, the chapter describes pathologic disorders of calcium and phosphate balance, including hyperparathyroidism, hypercalcemia of malignancy, pseudohypoparathyroidism, hypothyroidism, vitamin D deficiency, Paget's disease, and bone problems of renal failure. The chapter includes a list of key words and concepts and presents self study problems. 15 figures. 1 table. 11 references.

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CHAPTER 7. PERIODICALS AND NEWS ON CALCITONIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover calcitonin.

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

Unigene, Chinese firm form calcitonin joint venture Source: Reuters Industry Breifing Date: June 19, 2000

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•

Alendronate increases bone density better than intranasal calcitonin in osteoporotic women Source: Reuters Medical News Date: June 15, 1999

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Unigene's calcitonin approved in Europe Source: Reuters Medical News Date: January 20, 1999

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Alendronate, raloxifene, calcitonin prevent fractures in postmenopausal women Source: Reuters Medical News Date: September 15, 1998

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Unigene files nasal calcitonin product with FDA Source: Reuters Industry Breifing Date: March 06, 2003

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Preoperative calcitonin measurement may predict spread of thyroid carcinoma Source: Reuters Medical News Date: December 30, 2002

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EMEA recommends label changes for calcitonin products Source: Reuters Industry Breifing Date: November 21, 2002

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EMEA expected to rule on calcitonin this week Source: Reuters Industry Breifing Date: November 18, 2002 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 “calcitonin” (or synonyms) into the search box, and click on “Search News.” As this service is technology

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oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “calcitonin” (or synonyms). If you know the name of a company that is relevant to calcitonin, 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 “calcitonin” (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 “calcitonin” (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 calcitonin: •

Osteoporosis Revolution Source: Lupus News. 17(3):4-5; Autumn 1997. Contact: Lupus Foundation of America, Inc., 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (301) 670-9292. (301) 670-9486 (fax). Summary: This newsletter article for individuals with lupus reports on the revolution in the approach to the prevention and treatment of osteoporosis in postmenopausal women. The most important aspects of this revolution include the development of bone densitometry to measure the mineral content of the bones of the lower lumbar spine and of the upper end of the femur to help determine the risk of fracture and the use of bone markers to predict bone loss and assess the response to therapy. Another aspect of this revolution is the development of new agent drugs to inhibit bone breakdown, including bisphosphonates such as alendronate, estrogen analogs, and nasal calcitonin. Studies are also being conducted on the effectiveness of parathyroid hormone and fluoride in increasing bone formation.

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Our Strong Recommendation for Bone Density Testing Source: Health After 50. 9(8):6-7; October 1997. Contact: Johns Hopkins Medical Letter, Health After 50, 550 North Broadway, Suite 1100, Baltimore, MD 21205-2011. Summary: This newsletter article for the general public discusses the need for bone density testing among postmenopausal women. It explains how bones are constantly built up and broken down in a dynamic process known as bone remodeling. The article identifies the risk factors for osteoporosis and describes the process of bone density testing using dual energy x-ray absorptiometry. In addition, it highlights the drugs that may be useful in treating osteoporosis, including hormones, calcitonin, and alendronate. 1 figure.

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Glucocorticoid-Induced Osteoporosis: Prevention and Treatment Source: Bulletin on the Rheumatic Diseases. 49(4): 1-4. 2000. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the pathogenesis and clinical course of glucocorticoid induced osteoporosis (GIOP) and the management options for both primary prevention and treatment. Bone loss from glucocorticoids is related to dose and duration of treatment, hormonal status, genetics, and baseline bone mineral density (BMD). Glucocorticoids are associated with a decrease in gonadal hormones that can accelerate bone resorption and decrease bone formation, and they interfere with osteoblast maturation and accelerate apoptosis. In addition, they decrease calcium absorption from the gastrointestinal tract and increase renal excretion of calcium. Baseline BMD should be determined, and bone preserving therapy should begin at the initiation of glucocorticoid treatment. Patients receiving glucocorticoids should take calcium and vitamin D supplements. Other preventive measures that should be considered include treatment with bisphosphonates, calcitonin, and estrogen and testosterone replacements. The article also presents an approach to management of GIOP in patients who have normal BMD, patients who have osteopenia, and patients who have osteoporosis. 33 references.

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

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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

Nasal-Systemic - U.S. Brands: Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203482.html

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Systemic - U.S. Brands: Calcimar; Cibacalcin; Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202106.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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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

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

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

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

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

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

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

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

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

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

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

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 “calcitonin” (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 20821 95 144 33 76 21169

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 “calcitonin” (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/.

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

18 Adapted 19

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

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

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on calcitonin 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 calcitonin. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to calcitonin. 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 “calcitonin”:

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Asian-American Health http://www.nlm.nih.gov/medlineplus/asianamericanhealth.html Cancer Chemotherapy http://www.nlm.nih.gov/medlineplus/cancerchemotherapy.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Paget's Disease of Bone http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html Prostate Diseases http://www.nlm.nih.gov/medlineplus/prostatediseases.html Sinusitis http://www.nlm.nih.gov/medlineplus/sinusitis.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on calcitonin. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Questions and Answers About Paget's Disease of the Bone Source: New York, NY: Paget Foundation. 1999. [7 p.]. Contact: Available from Paget Foundation. 120 Wall Street, Suite 1602, New York, NY 10005-4001. (212) 509-5335. Fax (212) 509-8492. E-mail: [email protected]. Website: www.paget.org. Price: Single copy free plus $2.00 shipping and handling. Summary: Paget's disease of bone is a chronic disorder that typically results in enlarged and deformed bones in one or more regions of the skeleton. Excessive bone breakdown and formation can cause the bone to weaken. This brochure, written in question and answer format, answers common questions about Paget's disease. Topics include the causes of the disease, the symptoms, how the diagnosis is established, the bones affected by Paget's disease, the relationship between Paget's disease and other problems (arthritis, osteoporosis, heart disease, diabetes, kidney diseases, hearing loss), the causes

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of pain in Paget's disease, complications of the nervous system, how Paget's disease affects the teeth, the role of diet and exercise, and treatment options, including drug therapy and surgery. One chart summarizes the administration, dosage, and cost of drugs that are approved in the U.S. for the treatment of Paget's disease (biphosphonates, calcitonin). The brochure briefly identifies the Paget Foundation, an organization that provides information and programs for consumers and medical professionals for bone disorders involving abnormal bone resorption, including Paget's disease of bone, primary hyperparathyroidism, fibrous dysplasia, osteopetrosis, and cancer metastatic to bone. 1 figure. 1 table. •

Inside Look at Osteoporosis, An Source: South Deerfield, MA: Channing L. Bete Company, Inc. 2003. 15 p. Contact: Available from Channing L. Bete Company, Inc. 200 State Road, South Deerfield, MA 01372-0200. (800)628-7733. Fax: (800) 499-6464. E-mail: [email protected]. PRICE: Contact company for pricing information; available in bulk. Order Number: PS75201. Summary: This booklet discusses osteoporosis, a disease that leads to an abnormal rate of bone loss resulting in weak bones, height loss, spinal changes, and severe pain. Fractures of the hip, wrist, and spine are the most common in individuals with osteoporosis. Risk factors for osteoporosis include gender, menopause, ethnicity, a diet low in calcium and Vitamin D, smoking, and heavy alcohol use. Doctors use the individual's medical history, physical examination, x-rays, and bone mineral density (BMD) tests to diagnose osteoporosis. Many different tests and machines are used to measure BMD in the form of a T-score. The T-score measures the difference between the individual's bone density and average normal bone density of someone of the same gender. The various testing processes are described. To help prevent osteoporosis, individuals should include more calcium and vitamin D in their diet, become more physically active, have regular checkups, quit smoking, limit or avoid alcohol, and use medication. Medications used to treat osteoporosis include alendronate, risedronate, raloxifene, calcitonin, and teriparatide. In addition, the benefits and risks of hormone replacement therapy are discussed.

•

Stand Up to Osteoporosis: Your Guide To Staying Healthy and Independent Through Prevention and Treatment Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 26 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides the general public with information on preventing and treating osteoporosis, a disease characterized by a loss of bone mass that leads to reduced bone strength and increased risk of fractures. The booklet presents facts about osteoporosis, explains how bone loss occurs, and lists risk factors. Risk can be reduced by consuming enough calcium and vitamin D; exercising; and taking various medications such as estrogen replacement therapy (ERT), alendronate, and raloxifene. The booklet also discusses the diagnosis and treatment of osteoporosis. Bone mass measurement is commonly used for diagnosis, while various medications, such as ERT, calcitonin, and alendronate, may be used for treatment. Several additional medications are under investigation: bisphosphonates, selective estrogen receptor modulators, sodium fluoride, parathyroid hormone, and vitamin D metabolites. The booklet offers

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suggestions on preventing falls and speaking to one's doctor about osteoporosis. In addition, the booklet presents several osteoporosis profiles. 9 figures, 1 table, and 1 reference. •

Menopause and Osteoporosis: Choices for a Healthy Future Source: Washington, DC: National Osteoporosis Foundation (NOF). 199x. 23 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides women with information about the impact of menopause on osteoporosis, a disease characterized by a loss of bone mass and by poor bone quality, which lead to reduced bone strength and increased risk of fractures. Following menopause, production of estrogen, which has an important role in the bone renewal process, ceases. In many women, the loss of estrogen after menopause leads to rapid bone removal. The booklet lists the risk factors for osteoporosis, explains how a bone mineral density test can determine the strength of a woman's bones, and outlines steps women can take to prevent osteoporosis, among them the use of estrogen replacement therapy or hormone replacement therapy, which slows or stops bone loss in postmenopausal women. Additional medications that may be used to treat osteoporosis include calcitonin and alendronate. Other approaches include consuming enough calcium and vitamin D and exercising. The booklet also lists some questions women should ask their doctor about osteoporosis, offers suggestions for improving health and well-being, presents a list of resources, and concludes with information on the National Osteoporosis Foundation. 3 figures and 1 table.

•

Questions and Answers About Paget's Disease of Bone Source: New York, NY: The Paget's Disease Foundation, Inc. 1999. 8 p. Contact: Paget Foundation for Paget's Disease of Bone and Related Disorders. 120 Wall Street, Suite 1602, New York, NY 10005-4001. (800) 23-PAGET or (212) 509-5335. Fax (212) 509-8492. E-mail: [email protected]. Website: www.paget.org. PRICE: $2.00 postage and handling. Summary: This brochure provides answers to general questions concerning Paget 's disease, related medical conditions, the importance of diet and exercise, and treatment options. Questions answered define what PD is and its symptoms; explains who is at risk for getting the disease; describes its diagnosis; and discusses the relationship it has with other medical conditions such as arthritis, osteoporosis, heart disease, diabetes, kidney problems, and central nervous system complications. The brochure reveals there is no relationship between diet and PD, that exercise is important in maintaining skeletal health and is recommended, and that treatment of PD involves two classes of drugs, calcitonin and bisophosphonates , which suppress the abnormal bone cell activity associated with PD.

•

How Strong Are Your Bones? Find Out If You Are at Risk for Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 15 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost.

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Summary: This brochure uses a question and answer format to provide the general public with information on osteoporosis and bone density testing. Osteoporosis is a disease that causes bones to weaken and break easily. The brochure describes the normal bone remodeling process, explains how osteoporosis occurs, identifies its causes and risk factors, and discusses the medical tests available to measure bone density. The brochure presents the features of these tests, explains the information that the test provides the patient and the doctor, identifies candidates test, and explains what the results of the test mean. In addition, the brochure highlights treatments that can slow bone loss and prevent osteoporotic fractures, such as estrogen replacement therapy, alendronate, and calcitonin. 8 figures, 1 table, and 1 reference. •

Osteoporosis and Corticosteroid-Induced Osteoporosis Source: American College of Rheumatology. 2000. 3 p. Contact: American College of Rheumatology. 1800 Century Place, Suite 250, Atlanta, GA 30345. (404) 633-3777. Website: www.rheumatology.org. Email: [email protected]. Summary: This fact sheet provides information on osteoporosis, a skeletal disease characterized by abnormal decrease in bone mass and strength resulting in an increased susceptibility of bone fractures of the spine, hip, or wrist. Bone loss is normal as people age but certain factors or conditions, including menopause, cigarette smoking, lack of calcium, lack of exercise, and certain medications, can increase the risk of developing osteoporosis. Diagnosis is made using X-ray densitometry (DEXA), CT scans, and plain x-rays. Treatment for osteoporosis includes having a healthy diet emphasizing adequate calcium and vitamin D consumption, regular weight-bearing exercise, and for postmenopausal women estrogen, biphosphonates, calcitonin, and ralaxofene. Prolonged corticosteroid use can also cause osteoporosis by decreasing calcium absorption in the intestine and increasing the rate of breakdown of bone. Corticosteroidinduced osteoporosis (CIO) is diagnosed using DEXA and is treated the same way nonCIO induced osteoporosis is. If possible the dose of corticosteroids is decreased.

•

Osteoporosis: A Woman's Guide Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 12 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides women with information on reducing bone loss and preventing osteoporosis, a disease in which the skeleton becomes so weakened that the slightest injury can mean a broken bone. Osteoporosis has no early warning signs and few outward indications until a fracture occurs. Risk factors include age, gender, race, normal or early menopause, lifestyle, use of certain medications, and family history. Women can protect themselves against osteoporosis by taking estrogen, alendronate, or raloxifene; consuming enough calcium; and engaging in weight-bearing exercise. A bone mass measurement taken around the time of menopause may be helpful in deciding whether to initiate treatment. Women who already have osteoporosis may be able to slow its progress by consuming enough calcium, taking estrogen replacement drugs, and using calcitonin or alendronate. The pamphlet provides a safety checklist to help women eliminate common fracture hazards and presents information on the National Osteoporosis Foundation.

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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 calcitonin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

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

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

•

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

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

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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 “calcitonin” (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 “calcitonin”. 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 “calcitonin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “calcitonin” (or a synonym) into the search box, and click “Submit Query.”

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

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

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

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

21

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

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

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

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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)

•

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

•

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

•

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

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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/

•

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

22

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

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•

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

•

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

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Calcitonin Calcitonin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003699.htm

•

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

•

Diagnostics and Tests for Calcitonin Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm PTH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003690.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm

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X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Nutrition for Calcitonin Vitamin D Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm

•

Background Topics for Calcitonin Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm 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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CALCITONIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acrosome: Cap-like structure covering the nucleus and anterior part of the sperm head. [NIH]

Acrosome Reaction: Changes that occur to liberate the enzymes of the acrosome of spermatozoa that allow the entry of a spermatozoon into the ovum. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] 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

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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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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 Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [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] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [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] 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 Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [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] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]

Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] 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,

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organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [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] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [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]

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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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [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] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH]

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Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [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]

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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] Anethole Trithione: Choleretic used to allay dry mouth and constipation due to tranquilizers. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood

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thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] 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] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH]

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Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendicular skeleton: The framework around and within which the soft parts of the body are situated. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] 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] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthropathy: Any joint disease. [EU] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU]

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Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrial: Pertaining to an atrium. [EU] 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] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [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 Dysreflexia: That part of the nervous system concerned with the unconscious regulation of the living processes of the body. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [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] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the

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thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] 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] Base Pairing: Pairing of purine and pyrimidine bases by hydrogen bonding in doublestranded DNA or RNA. [NIH] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [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]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [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] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific

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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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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 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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotinylation: Incorporation of biotinyl groups into molecules. [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 Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a

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network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins. [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]

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Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] 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 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] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budgets: Detailed financial plans for carrying out specific activities for a certain period of time. They include proposed income and expenditures. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Cadaver: A dead body, usually a human body. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits

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and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [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] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [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] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Metabolism Disorders: Disorders in the processing of calcium in the body, including absorption, transport, storage, and utilization. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH]

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Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] 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] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]

Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH]

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Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] 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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell 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]

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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 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 division. [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] Cellular Structures: Components of a cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] 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] 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] 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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Ripening: A change in the cervix with respect to its readiness to relax. The cervix becomes softer, more flexible, more distensible, and shorter in the final weeks of pregnancy. Though naturally occurring during normal pregnancy, it can also be induced for certain cases of prolonged or high-risk pregnancy by administration of hormones. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH]

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Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [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] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [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] Chorda Tympani Nerve: A branch of the facial (7th cranial) nerve which passes through the middle ear and continues through the petrotympanic fissure. The chorda tympani nerve carries taste sensation from the anterior two-thirds of the tongue and conveys parasympathetic efferents to the salivary glands. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular

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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] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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 Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long time. [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] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Claudication: Limping or lameness. [EU] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

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Cochlear: Of or pertaining to the cochlea. [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [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] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH]

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Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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] 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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU]

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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 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyst: A sac or capsule filled with fluid. [NIH] Cyst Fluid: Liquid material found in epithelial-lined closed cavities or sacs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for

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organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [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] Decongestant: An agent that reduces congestion or swelling. [EU] 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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure.

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The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis, Irritant: A non-allergic contact dermatitis caused by prolonged exposure to irritants and not explained by delayed hypersensitivity mechanisms. [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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond

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normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] 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] 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] Disulphide: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject

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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] 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]

Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectoderm: The outer of the three germ layers of the embryo. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and

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hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endolymphatic Duct: Duct connecting the endolymphatic sac with the membranous

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labyrinth. [NIH] Endolymphatic Sac: The blind pouch at the end of the endolymphatic duct. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [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] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enterochromaffin-like Cells: Irregular-shaped argyrophilic cells which produce histamine, chromogranin A/pancreastatin, and an as yet unidentified peptide hormone. They are the predominant endocrine cell type of the oxyntic (acid-producing) mucosa of the stomach. ECL cells respond to gastrin by releasing their secretory products and this source of histamine acts as the positive paracrine stimulator of the release of hydrochloric acid from the parietal cell. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Entorhinal Cortex: Cortex where the signals are combined with those from other sensory

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systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] 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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [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] 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] Equipment Failure: Failure of equipment to perform up to standards. The failure may be due to defects or improper use. [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] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroleukemia: Cancer of the blood-forming tissues in which large numbers of immature, abnormal red blood cells are found in the blood and bone marrow. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH]

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Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

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] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [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, 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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the

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vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Exploratory Behavior: The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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 Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [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]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU]

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Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fever of Unknown Origin: Fever in which the etiology cannot be ascertained. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [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] Flexor: Muscles which flex a joint. [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] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding,

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rolling, or flowing of another with which it is in contact. [NIH] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [NIH] Gallium nitrate: A drug that lowers blood calcium. Used as treatment for hypercalcemia (too much calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioneuroblastoma: A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with Horner syndrome and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea. [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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [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.

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[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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] 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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste

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afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [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 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] 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]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [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] Goiter: Enlargement of the thyroid gland. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH]

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Gonadal: Pertaining to a gonad. [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]

Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] 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] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent

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headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [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] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

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] Hepatocyte: A liver cell. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

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

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entorhinal cortex in the hippocampal formation. [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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Humeri: A condition similar to tennis elbow involving the flexor origin at the medial epicondyle of the humerus, characterized by pain in or near the medial epicondyle of the humerus as a result of unusual strain. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydra: A genus of freshwater cnidarians, of interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals.

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[NIH]

Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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 Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [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] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [NIH]

Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [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]

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Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] Hypervitaminosis: A condition due to ingestion of an excess of one or more vitamins; called also supervitaminosis. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] 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] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterectomy: Excision of the uterus. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU]

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Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [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] Immunoradiometric Assay: Form of radioimmunoassay in which excess specific labeled antibody is added directly to the test antigen being measured. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft 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] 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] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH]

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Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] 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] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a 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] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] 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] 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

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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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-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] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] 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]

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Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [NIH]

Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [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] Ionomycin: A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes. [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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation;

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those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jellyfish: Free swimming marine cnidarians. Most of the large jellyfish are in the class Scyphozoa; the small jellyfish are in the class Hydrozoa (hydra). [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [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] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [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 Transplantation: The transference of a kidney from one human or animal to another. [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] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large

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intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lesion: An area of abnormal tissue change. [NIH] 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]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [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] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [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]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH]

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Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locus Control Region: A regulatory region first identified in the human beta-globin locus but subsequently found in other loci. The region is believed to regulate transcription by opening and remodeling chromatin structure. It may also have enhancer activity. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

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Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] 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] 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] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macronutrients: Nutrients in the diet that are the key sources of energy, namely protein, fat, and carbohydrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Malondialdehyde: The dialdehyde of malonic acid. [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] Mandibular Nerve: A branch of the trigeminal (5th cranial) nerve. The mandibular nerve carries motor fibers to the muscles of mastication and sensory fibers to the teeth and gingivae, the face in the region of the mandible, and parts of the dura. [NIH] Manic: Affected with mania. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in

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wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Maxillary Nerve: The intermediate sensory division of the trigeminal (5th cranial) nerve. The maxillary nerve carries general afferents from the intermediate region of the face including the lower eyelid, nose and upper lip, the maxillary teeth, and parts of the dura. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [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] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] 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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions

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which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [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] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Micturition: The passage of urine; urination. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU]

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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] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [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] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

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Motor Neurons: Neurons which activate muscle cells. [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] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme

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washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myograph: A recording instrument by which tracings are made of muscular contractions. [NIH]

Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [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] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [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] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephrectomy: Surgery to remove a kidney. Radical nephrectomy removes the kidney, the adrenal gland, nearby lymph nodes, and other surrounding tissue. Simple nephrectomy removes only the kidney. Partial nephrectomy removes the tumor but not the entire kidney. [NIH]

Nephrons: The functional units of the kidney, consisting of the glomerulus and the attached tubule. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in

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the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [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] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [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] Neuroendocrine tumor: A tumor derived from cells that release a hormone in response to a signal from the nervous system. Some examples of neuroendocrine tumors are carcinoid tumors, islet cell tumors, medullary thyroid carcinoma, and pheochromocytoma. These tumors secrete hormones in excess, causing a variety of symptoms. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurogenic Inflammation: Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury. [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

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normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neurophysiology: The scientific discipline concerned with the physiology of 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] Neurotrophins: A nerve growth factor. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nidation: Implantation of the conceptus in the endometrium. [EU] 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] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nodose: Having nodes or projections. [EU]

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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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] 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 -

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morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [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 Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] Orofacial: Of or relating to the mouth and face. [EU] Orthodontics: A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion). [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteochondrodysplasias: Abnormal development of cartilage and bone. [NIH]

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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] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [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] Osteotomy: The surgical cutting of a bone. [EU] Ototoxic: Having a deleterious effect upon the eighth nerve, or upon the organs of hearing and balance. [EU] 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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [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] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate

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and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH]

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Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [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] Pentagastrin: A synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid 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 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] 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] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The

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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] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Perivascular: Situated around a vessel. [EU] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] 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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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]

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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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodermatitis: Dermatitis caused or elicited by exposure to ultraviolet light, may be phototoxic or photoallergic. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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] Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Circulation: The circulation of blood, of both the mother and the fetus, through the placenta. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many

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bacteria. Plasmids are widely used as carriers of cloned genes. [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 Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Plicamycin: A tricyclic pentaglycosidic antibiotic from Streptomyces strains that inhibits RNA and protein synthesis by adhering to DNA. It is used as a fluorescent dye and as an antineoplastic agent, especially in bone and testicular tumors. Plicamycin is also used to reduce hypercalcemia, especially that due to malignancies. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH]

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Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postsynaptic: 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] 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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: 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] Povidone: A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. [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] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU]

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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] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Preimplantation Phase: The time period between fertilization and implantation. [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]

Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH]

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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] Prolactinoma: A pituitary adenoma which secretes prolactin, leading to hyperprolactinemia. Clinical manifestations include amenorrhea; galactorrhea; impotence; headache; visual disturbances; and cerebrospinal fluid rhinorrhea. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Propulsive: Tending or having power to propel; driving onward or forward; impelling to action or motion. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15-

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hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins B: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [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] Prostaglandins G: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2. [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] Prostatitis: Inflammation of the prostate. [EU] 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 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 Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [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]

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Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulposus: Prolapse of the nucleus pulposus into the body of the vertebra; necrobacillosis of rabbits. [NIH] Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyrogenic: Inducing fever. [EU] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]

Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called

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radioactive drugs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH]

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Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] 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] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] 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] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] 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

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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] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [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] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the

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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] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [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] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [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

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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] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] 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] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [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] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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,

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and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Sharks: A group of elongate elasmobranchs. Sharks are mostly marine fish, with certain species large and voracious. [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] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]

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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH]

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Spermatozoon: The mature male germ cell. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinal Stenosis: Narrowing of the spinal canal. [NIH] Spinous: Like a spine or thorn in shape; having spines. [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] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] 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]

Staphylococcal Infections: Infections with bacteria of the genus Staphylococcus. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [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] Stenosis: Narrowing or stricture of a duct or canal. [EU] 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

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hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the

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treatment of migraines. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [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] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Syncytium: A living nucleated tissue without apparent cellular structure; a tissue composed of a mass of nucleated protoplasm without cell boundaries. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of

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the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taste Buds: Small sensory organs which contain gustatory receptor cells, basal cells, and supporting cells. Taste buds in humans are found in the epithelia of the tongue, palate, and pharynx. They are innervated by the chorda tympani nerve (a branch of the facial nerve) and the glossopharyngeal nerve. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] 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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Temporal Muscle: A masticatory muscle whose action is closing the jaws; its posterior portion retracts the mandible. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tennis Elbow: A condition characterized by pain in or near the lateral humeral epicondyle or in the forearm extensor muscle mass as a result of unusual strain. It occurs in tennis players as well as housewives, artisans, and violinists. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] 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] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [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, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH]

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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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [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] Thyroid Nodule: A small circumscribed mass of differentiated tissue associated with the thyroid gland. It can be pathogenic or non-pathogenic. The growth of nodules can lead to a condition of nodular goiter. Most nodules appear between the ages of 30 and 50 years and most are benign. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth 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] 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] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired

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drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] 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] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [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] 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] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [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] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] 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]

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Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [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] 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] Triad: Trivalent. [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] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] 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] Trigeminal Ganglion: The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves. [NIH] Trigeminal Nerve: The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trophic: Of or pertaining to nutrition. [EU]

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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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [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] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] 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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH]

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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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [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] Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

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Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] 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] 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] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body,

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especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [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

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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] Zona Pellucida: The transport non-cellular envelope surrounding the mammalian 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]

299

INDEX A Abdomen, 209, 221, 238, 252, 255, 269, 270, 286, 287, 294, 296 Abdominal, 209, 258, 268, 270, 293 Aberrant, 43, 209 Acceptor, 209, 255, 267, 292 Acetaldehyde, 38, 209 Acetylcholine, 33, 54, 60, 209, 226, 264 Acetylcholinesterase, 43, 209 Acid Phosphatase, 24, 129, 209 Acrosome, 152, 209 Acrosome Reaction, 152, 209 Actin, 14, 209, 261, 262 Action Potentials, 47, 209 Acute leukemia, 94, 209 Acute lymphoblastic leukemia, 84, 209 Acute lymphocytic leukemia, 209 Adaptation, 38, 46, 64, 209, 272 Adduct, 38, 210 Adenine, 210 Adenoma, 210, 275 Adenosine, 33, 69, 122, 210, 271 Adenosine Triphosphate, 33, 210, 271 Adenylate Cyclase, 157, 210, 226 Adipose Tissue, 96, 210 Adjustment, 209, 210 Adjuvant, 129, 210 Adolescence, 5, 174, 210 Adrenal Cortex, 210, 211, 231, 238, 274, 280 Adrenal Medulla, 210, 224, 238, 242, 265 Adrenaline, 92, 210 Adrenergic, 41, 130, 157, 210, 215, 234, 238, 275, 288 Adrenergic Agents, 157, 210 Adsorption, 139, 153, 210 Adsorptive, 210 Adverse Effect, 11, 152, 210, 284 Afferent, 15, 22, 32, 45, 50, 54, 59, 61, 62, 66, 158, 164, 210, 231, 240, 286 Affinity, 89, 103, 147, 148, 210, 211, 217, 285 Agar, 211, 271 Agarose, 165, 211 Age of Onset, 211, 293 Agonist, 41, 53, 73, 77, 83, 93, 211, 234, 287 Airway, 39, 158, 171, 211, 221, 275, 296 Airway Resistance, 171, 211

Akathisia, 211, 215 Aldosterone, 13, 211 Alendronate, 3, 5, 7, 8, 10, 80, 81, 174, 180, 181, 182, 195, 196, 197, 211 Alendronate Sodium, 174, 211 Algorithms, 211, 219 Alimentary, 211, 254, 268 Alkaline, 20, 62, 165, 177, 211, 212, 213, 222, 289 Alkaline Phosphatase, 20, 177, 212 Alkaloid, 212, 223, 260 Alkylating Agents, 212, 293 Allergen, 39, 212, 233, 283 Allogeneic, 125, 212 Allogeneic bone marrow transplantation, 125, 212 Allylamine, 212 Alpha Particles, 212, 278 Alternative medicine, 180, 212 Alternative Splicing, 37, 90, 212, 276 Alveolar Process, 212, 280 Alveoli, 212, 295 Ameliorating, 164, 212 Amenorrhea, 95, 212, 275 Amine, 34, 45, 212, 247 Amino Acid Sequence, 152, 154, 156, 212, 214, 240, 243 Ammonia, 212, 213, 244, 288, 293 Amplification, 165, 213 Ampulla, 213, 226 Amygdala, 16, 53, 213, 255 Amyloid, 74, 168, 213 Anabolic, 7, 9, 12, 20, 42, 56, 155, 176, 213 Anabolic Steroids, 7, 176, 213 Anaesthesia, 213, 251 Anal, 213, 241, 256 Analgesic, 21, 74, 127, 148, 161, 213, 260, 266 Analog, 81, 154, 169, 213, 254 Analogous, 66, 213, 292 Anaphylatoxins, 213, 228 Anatomical, 15, 16, 31, 32, 33, 130, 213, 217, 230, 233, 250, 259, 282 Androgens, 64, 210, 213, 231 Anemia, 213, 220, 253, 267 Anesthesia, 211, 213, 214, 231 Anesthetics, 214, 238 Anethole Trithione, 86, 214

300

Calcitonin

Aneurysm, 214, 294 Angina, 214, 275 Angina Pectoris, 214, 275 Angiotensinogen, 214, 280 Animal model, 21, 29, 30, 35, 50, 67, 69, 214 Anions, 214, 253, 284 Annealing, 214, 272 Anomalies, 214, 266, 289 Anorexia, 214, 267 Antagonism, 158, 214, 234 Anterograde, 33, 214 Anthracycline, 214, 232 Antiallergic, 214, 231 Antibacterial, 214, 285 Antibiotic, 214, 232, 269, 272, 285 Anticoagulant, 214, 276 Anticonvulsant, 101, 215 Antiemetic, 215 Antigen, 24, 41, 211, 214, 215, 228, 247, 248, 249, 250, 251, 254, 258, 259, 278, 283 Antigen-Antibody Complex, 215, 228 Anti-infective, 215, 248, 253 Anti-inflammatory, 20, 27, 30, 62, 85, 171, 215, 216, 231, 244, 250 Anti-Inflammatory Agents, 85, 215, 216, 231 Antineoplastic, 212, 215, 231, 272 Antioxidant, 215, 267 Antiproliferative, 102, 215 Antipsychotic, 73, 215, 263 Antiserum, 37, 215 Antithrombotic, 215, 276 Antiviral, 215, 269 Anus, 213, 215, 228 Anxiety, 53, 211, 216, 275 Aorta, 216, 223, 230, 295 Aponeurosis, 216, 242 Apoptosis, 18, 39, 42, 64, 78, 135, 182, 216, 224 Appendicular skeleton, 31, 216 Aqueous, 216, 218, 231, 236, 248 Arachidonic Acid, 216, 235, 255, 275 Arginase, 87, 216 Arginine, 33, 65, 213, 216, 264, 293 Arrestin, 73, 216 Arterial, 15, 23, 47, 63, 92, 127, 136, 212, 216, 230, 248, 276, 288 Arteries, 25, 33, 38, 47, 65, 86, 89, 111, 216, 218, 219, 220, 225, 230, 261, 278, 290 Arteriolar, 216, 221, 280 Arterioles, 26, 216, 220, 223, 259, 294

Arteriovenous, 216, 259 Artery, 25, 26, 63, 105, 123, 168, 214, 216, 218, 224, 230, 241, 261, 268, 280 Arthropathy, 164, 216 Articular, 35, 164, 216, 266 Articulation, 64, 216 Ascites, 216, 265 Aspartate, 53, 216 Aspirin, 62, 177, 216 Assay, 24, 29, 70, 80, 97, 138, 216, 249, 278 Astrocytes, 217, 257, 259 Asymptomatic, 10, 48, 163, 175, 217 Atopic, 30, 99, 217 Atrial, 92, 95, 117, 217, 230, 292 Atrioventricular, 217, 230 Atrium, 217, 223, 230, 292, 295 Atrophy, 45, 169, 217, 263 Attenuated, 50, 217 Auditory, 132, 217, 245, 294 Autacoids, 217, 250 Autoimmune disease, 217 Autoimmunity, 57, 217 Autonomic Dysreflexia, 35, 217 Autonomic Nervous System, 47, 135, 217, 270, 285, 288 Autonomic Neuropathy, 43, 217 Autoradiography, 69, 111, 143, 217 Avian, 24, 217 Axons, 46, 50, 67, 217, 233, 252, 263, 266, 274, 286 B Back Pain, 163, 217 Bacterial Physiology, 210, 218 Bactericidal, 218, 239 Basal cells, 218, 289 Basal Ganglia, 215, 218, 227, 242, 255 Base, 54, 68, 165, 210, 218, 231, 232, 233, 239, 243, 254, 289 Base Pairing, 165, 218 Basilar Artery, 65, 218 Basophils, 218, 245 Benign, 14, 18, 177, 210, 218, 223, 242, 245, 262, 279, 290 Beta-pleated, 213, 218 Beta-Thromboglobulin, 218, 252 Bilateral, 116, 218 Bile, 175, 218, 242, 247, 254, 255, 274, 282, 286 Bile Acids, 218, 286 Bile Acids and Salts, 218 Bile duct, 218, 274 Bile Pigments, 218, 254

301

Biliary, 175, 218, 222, 226 Binding Sites, 18, 218 Bioassay, 104, 219 Bioavailability, 27, 29, 76, 112, 151, 166, 167, 219 Biological Assay, 52, 219 Biological therapy, 219, 245 Biological Transport, 219, 233 Biopsy, 49, 176, 219 Biopsy specimen, 49, 219 Biosynthesis, 29, 216, 219, 275, 276, 283 Biotechnology, 68, 72, 88, 168, 180, 189, 219 Biotinylation, 29, 219 Bladder, 14, 83, 140, 217, 219, 229, 231, 263, 276, 280, 293, 294 Blastocyst, 219, 236, 271 Blood Coagulation, 219, 222, 290 Blood Platelets, 219, 272, 283 Blood pressure, 13, 15, 38, 175, 207, 219, 223, 224, 226, 248, 249, 260, 273, 278, 285 Blood transfusion, 219, 246 Blood vessel, 49, 64, 167, 168, 219, 221, 223, 224, 225, 227, 230, 237, 243, 245, 254, 255, 256, 258, 269, 285, 287, 290, 294 Blood Viscosity, 220, 246 Blood Volume, 220, 273 Blot, 19, 220, 249 Blotting, Western, 220, 249 Body Fluids, 220, 235, 285 Bombesin, 103, 130, 135, 220 Bone Density, 8, 151, 156, 166, 180, 182, 195, 197, 220 Bone Development, 23, 220 Bone Marrow, 24, 57, 125, 209, 220, 238, 243, 249, 256, 287 Bone Marrow Transplantation, 125, 220 Bone metastases, 161, 220, 227, 239, 242, 278 Bone Morphogenetic Proteins, 49, 220 Bone Remodeling, 9, 23, 42, 88, 173, 182, 197, 220 Bone scan, 5, 221, 282 Bowel, 50, 213, 221, 251, 252, 287, 293 Brachytherapy, 221, 252, 253, 278, 296 Bradykinin, 59, 162, 221, 254, 264 Brain Stem, 15, 33, 221, 292 Bronchi, 221, 238, 254, 291 Bronchial, 99, 171, 221, 247, 276 Bronchial Hyperreactivity, 171, 221 Bronchitis, 221, 227 Bronchoalveolar Lavage, 106, 221

Bronchoalveolar Lavage Fluid, 106, 221 Bronchodilator, 221, 254 Buccal, 221, 256 Budgets, 52, 221 Buffers, 62, 221 C Cadaver, 6, 221 Calcifediol, 221, 222 Calcification, 125, 138, 221 Calcitriol, 72, 84, 222 Calcium, 3, 4, 5, 6, 7, 8, 9, 10, 12, 17, 20, 24, 26, 34, 36, 55, 64, 67, 69, 70, 71, 72, 79, 80, 83, 106, 109, 111, 122, 123, 124, 125, 126, 130, 131, 133, 135, 138, 143, 147, 148, 150, 151, 161, 166, 168, 174, 175, 176, 177, 178, 182, 195, 196, 197, 211, 220, 221, 222, 227, 228, 234, 239, 242, 248, 253, 257, 259, 262, 266, 267, 268, 284, 289, 296 Calcium Channels, 17, 25, 222 Calcium Metabolism Disorders, 150, 222 Calcium Oxalate, 79, 222 Calculi, 222 Calmodulin, 34, 222 Calpain, 19, 222 Cannabidiol, 222 Cannabinoids, 21, 41, 54, 222 Cannabinol, 222, 223 Capillary, 10, 88, 221, 223, 295 Capillary Permeability, 221, 223 Capsaicin, 17, 22, 32, 46, 54, 61, 62, 66, 100, 129, 137, 140, 223 Capsules, 223, 234 Carbohydrate, 223, 231, 244, 273 Carbon Dioxide, 223, 232, 241, 242, 271 Carboxy, 29, 223 Carboxy-terminal, 29, 223 Carcinoembryonic Antigen, 80, 223 Carcinogen, 210, 223, 239 Carcinogenic, 212, 223, 251, 275, 286, 293 Carcinoid, 126, 223, 263 Cardiac, 17, 59, 70, 126, 160, 212, 222, 223, 230, 238, 239, 242, 262, 286, 287 Cardiopulmonary, 105, 223, 246 Cardiopulmonary Bypass, 105, 223, 246 Cardioselective, 223, 275 Cardiotonic, 167, 223 Cardiovascular disease, 6, 23, 223 Cardiovascular Physiology, 26, 224 Cardiovascular System, 90, 217, 224 Carnitine, 166, 224 Carotid Sinus, 224, 244

302

Calcitonin

Carrier Proteins, 224, 278 Case report, 96, 117, 224 Caspase, 127, 224 Castration, 104, 117, 224 Catecholamine, 176, 224, 234, 270 Cathode, 224, 236 Cations, 126, 135, 224, 253 Cauda Equina, 224, 282 Caudal, 15, 224, 249, 273 Causal, 34, 224 Cause of Death, 6, 224 Cecum, 224, 254 Celiac Disease, 4, 224 Cell Adhesion, 20, 224 Cell Cycle, 224, 239, 246 Cell Death, 216, 224, 239, 262 Cell Differentiation, 18, 57, 224, 284 Cell Division, 218, 224, 225, 239, 245, 258, 260, 271, 275 Cell Lineage, 21, 57, 225 Cell membrane, 149, 219, 222, 224, 225, 226, 233, 240, 253, 254, 270, 273, 296 Cell motility, 20, 225 Cell proliferation, 29, 93, 225, 252, 284 Cell Survival, 225, 245 Cellular Structures, 225, 260 Central Nervous System Infections, 225, 245 Cerebral Arteries, 122, 135, 218, 225 Cerebral Cortex, 225, 239, 242, 262 Cerebral hemispheres, 218, 221, 225 Cerebrospinal, 101, 132, 225, 275 Cerebrospinal fluid, 101, 132, 225, 275 Cerebrovascular, 43, 51, 223, 225 Cerebrum, 225 Cervical, 35, 102, 139, 225, 242, 262 Cervical Ripening, 35, 225 Cervix, 35, 225, 280 Character, 214, 226, 232, 244 Chemokines, 23, 39, 52, 226 Chemoreceptor, 215, 226 Chemotactic Factors, 226, 228 Chemotaxis, 61, 226 Chiropractic, 34, 35, 226 Chloride Channels, 25, 226 Cholecystokinin, 4, 46, 82, 100, 226 Cholera, 64, 226, 295 Cholera Toxin, 64, 226 Cholestasis, 175, 226 Cholesterol, 218, 226, 230, 286 Choline, 93, 149, 209, 226 Cholinergic, 60, 61, 215, 226

Chorda Tympani Nerve, 226, 289 Chorea, 215, 226 Choroid, 227, 280 Chromatin, 216, 227, 238, 256, 257, 264, 285 Chromosomal, 213, 227, 271 Chromosome, 43, 45, 94, 227 Chronic Disease, 55, 227, 255 Chronic Obstructive Pulmonary Disease, 158, 227 Chronic prostatitis, 30, 227 Circulatory system, 40, 227, 236 Cirrhosis, 92, 175, 227, 273, 274 Clamp, 25, 26, 53, 227 Clathrin, 227, 237 Claudication, 163, 227 Clear cell carcinoma, 227, 233 Clinical Medicine, 26, 136, 227, 274 Clinical trial, 8, 11, 21, 35, 63, 118, 189, 227, 234, 269, 279 Clodronate, 122, 227 Cloning, 19, 37, 103, 159, 219, 227 Coated Vesicles, 227, 237 Cochlea, 54, 116, 227, 228, 251 Cochlear, 25, 55, 228 Cofactor, 228, 276, 290 Colitis, 50, 228 Collagen, 9, 109, 131, 143, 228, 240, 241, 257, 272, 275 Colloidal, 228, 236, 240, 284 Colon, 28, 44, 50, 223, 228, 251, 255, 293 Colorectal, 94, 228 Colorectal Cancer, 94, 228 Combination Therapy, 29, 228, 239 Complement, 56, 68, 213, 228, 229, 243, 283 Complementary and alternative medicine, 125, 141, 228 Complementary medicine, 125, 229 Complete remission, 94, 229, 279 Complete response, 229 Compliance, 92, 229 Computational Biology, 189, 229 Computed tomography, 9, 20, 220, 229, 282 Computer Simulation, 13, 229 Computerized axial tomography, 229, 282 Computerized tomography, 229 Confusion, 229, 249, 263, 293 Congestion, 215, 229, 232, 238 Congestive heart failure, 59, 229 Conjugated, 64, 151, 160, 218, 229

303

Conjunctiva, 229, 292 Connective Tissue, 131, 220, 228, 229, 233, 241, 242, 256, 281, 287, 289 Connective Tissue Cells, 229 Consciousness, 213, 229, 232, 234, 277 Constipation, 214, 215, 229 Constitutional, 230, 261 Constriction, 230, 254, 294, 296 Constriction, Pathologic, 230, 294 Contact dermatitis, 30, 230, 233 Contamination, 152, 230 Contractility, 38, 59, 230 Contraindications, ii, 230 Convulsion, 219, 230 Coordination, 36, 52, 230 Cor, 53, 230 Coronary, 17, 89, 105, 111, 114, 168, 214, 223, 230, 261 Coronary Artery Bypass, 105, 230 Coronary heart disease, 223, 230 Coronary Thrombosis, 230, 261 Cortex, 230, 231, 237 Cortical, 4, 151, 156, 231, 239 Corticosteroid, 7, 8, 9, 39, 197, 231 Cortisol, 108, 176, 231 Cranial, 167, 226, 231, 240, 243, 245, 257, 258, 263, 266, 268, 270, 292, 294 Cranial Nerves, 167, 231 Craniocerebral Trauma, 231, 245 Cultured cells, 93, 231 Curare, 231, 261 Curative, 63, 231, 281, 289 Cutaneous, 21, 30, 60, 67, 84, 127, 170, 230, 231, 253, 256 Cyclic, 69, 210, 222, 231, 245, 264, 270, 275 Cyst, 91, 231 Cyst Fluid, 91, 231 Cysteine, 28, 222, 226, 231, 234 Cystine, 153, 231, 234 Cystitis, 30, 163, 231 Cytokine, 41, 48, 63, 98, 231, 252 Cytoplasm, 216, 218, 225, 226, 231, 232, 238, 245, 257, 262, 264, 281, 288 Cytosine, 165, 231 Cytoskeletal Proteins, 20, 222, 227, 231 Cytoskeleton, 19, 137, 231, 232 Cytotoxic, 149, 223, 232, 250, 279, 284 D Daunorubicin, 107, 232 Decarboxylation, 232, 247 Decidua, 232, 271 Decongestant, 152, 232

Degenerative, 164, 232, 261, 266, 281 Dehydration, 5, 177, 226, 232 Deletion, 12, 21, 31, 70, 96, 216, 232, 243 Delirium, 215, 232 Dementia, 215, 232 Denaturation, 153, 232, 272 Dendrites, 232, 233, 263, 264 Dental Caries, 232, 285 Dentate Gyrus, 232, 246 Deoxyribonucleic, 103, 233, 281 Deoxyribonucleic acid, 103, 233, 281 Deoxyribonucleotides, 233 Depolarization, 54, 233, 284 Deprivation, 11, 233 Dermatitis, 30, 233, 271 Dermatitis, Irritant, 30, 233 Dermis, 233, 288, 291 DES, 32, 107, 213, 233 Desensitization, 29, 48, 233, 250 Deuterium, 233, 248 Diagnostic Imaging, 149, 233 Diagnostic procedure, 145, 181, 233 Dialyzer, 233, 246 Diarrhea, 233, 242 Diastolic, 233, 248 Diffusion, 28, 30, 62, 165, 219, 223, 233, 253 Digestion, 151, 211, 218, 221, 233, 252, 255, 269, 287, 294 Digestive tract, 217, 233, 284 Dihydroxy, 55, 211, 233 Dilatation, Pathologic, 233, 294 Dilation, 221, 234, 294 Diltiazem, 138, 234 Direct, iii, 4, 9, 13, 21, 22, 27, 36, 43, 49, 54, 55, 61, 63, 67, 82, 126, 183, 227, 234, 279, 288 Discrete, 15, 17, 43, 220, 234, 289 Disinfectant, 234, 239 Dissociation, 211, 234 Distal, 24, 42, 57, 230, 234, 274, 277, 281 Disulphide, 153, 234 Diuresis, 40, 177, 234 Diuretic, 5, 40, 234 Dopamine, 135, 157, 215, 234, 264, 270 Dorsal, 21, 32, 34, 38, 49, 52, 61, 67, 122, 128, 129, 164, 167, 234, 263, 273, 286 Dorsum, 234, 242 Dosage Forms, 166, 234 Dose-dependent, 38, 234 Double-blind, 43, 76, 111, 234 Drive, ii, vi, 6, 13, 26, 34, 61, 121, 181, 235, 253, 255

304

Calcitonin

Drug Interactions, 184, 235 Drug Tolerance, 235, 291 Duct, 213, 235, 236, 239, 282, 286, 288 Duodenum, 61, 218, 235, 242, 269, 282, 287 Dwarfism, 31, 235 Dyes, 213, 218, 235, 264 Dyskinesia, 215, 235 Dysplasia, 88, 195, 235 Dyspnea, 171, 235 Dystonia, 215, 235 Dystrophy, 127, 235 E Echocardiography, 18, 235 Eclampsia, 218, 235, 274 Ectoderm, 46, 235, 263 Ectopic, 101, 102, 147, 235 Edema, 230, 235, 261, 265, 274 Effector, 157, 209, 228, 235, 263, 270 Efferent, 17, 33, 45, 54, 61, 231, 235, 240, 260, 286 Efficacy, 9, 21, 29, 74, 76, 99, 235 Effusion, 171, 235 Eicosanoids, 39, 235 Elastin, 228, 236, 240 Elective, 236 Electrolysis, 214, 224, 236 Electrolyte, 211, 231, 232, 236, 260, 273, 285 Electrons, 215, 218, 224, 236, 253, 267, 278, 279 Electrophoresis, 88, 236 Embryo, 36, 219, 220, 224, 225, 235, 236, 243, 251, 267 Embryo Transfer, 36, 236 Emphysema, 12, 227, 236 Emulsion, 217, 236, 241 Endemic, 226, 236, 286 Endocrine Glands, 236, 268 Endocrine System, 236, 263 Endocytosis, 28, 48, 236 Endoderm, 46, 236 Endolymphatic Duct, 236, 237 Endolymphatic Sac, 103, 236, 237 Endometrial, 36, 237 Endometrium, 36, 232, 237, 258, 264 Endorphins, 237, 264 Endosomes, 48, 236, 237 Endothelial cell, 32, 48, 60, 64, 103, 237, 252, 290 Endothelium, 33, 237, 264 Endothelium, Lymphatic, 237 Endothelium, Vascular, 237

Endothelium-derived, 237, 264 Endotoxemia, 85, 237 Endotoxic, 132, 237 Endotoxin, 26, 156, 237, 293 Enhancer, 29, 57, 75, 76, 93, 152, 162, 166, 237, 256 Enkephalin, 16, 33, 237 Enteric Nervous System, 50, 237 Enterochromaffin-like Cells, 4, 237 Enteropeptidase, 237, 293 Entorhinal Cortex, 237, 247 Environmental Health, 188, 190, 238 Enzymatic, 146, 162, 222, 228, 232, 238, 247, 272, 280 Enzyme Inhibitors, 130, 139, 238 Eosinophilic, 39, 238 Eosinophils, 39, 171, 238, 245 Epidermal, 40, 143, 238, 254 Epidermis, 218, 233, 238, 254, 278 Epigastric, 238, 268 Epinephrine, 133, 210, 234, 238, 254, 264, 265, 293 Epithelial, 18, 24, 36, 162, 210, 219, 226, 231, 232, 238 Epithelial Cells, 18, 24, 36, 226, 238 Epithelium, 18, 34, 36, 45, 62, 79, 237, 238, 242 Equipment Failure, 52, 238 Erectile, 88, 238 Erection, 238, 271 Erythema, 230, 238 Erythrocytes, 213, 220, 222, 238, 279, 283 Erythroleukemia, 90, 238 Esophagus, 55, 167, 233, 238, 269, 270, 287 Estradiol, 24, 131, 132, 238, 239 Estrogen receptor, 36, 43, 239 Estrogen Replacement Therapy, 6, 7, 8, 195, 196, 197, 239 Estrone, 71, 239 Ethanol, 38, 239, 241 Etidronate, 175, 239 Etoposide, 135, 239 Eukaryotic Cells, 165, 231, 239, 250, 266 Evoke, 239, 287 Excipients, 162, 239 Excitability, 22, 50, 51, 53, 239 Excitation, 16, 66, 226, 239, 264 Excitatory, 16, 32, 47, 239, 244 Excitatory Amino Acids, 16, 239 Excrete, 239, 280 Exhaustion, 214, 239 Exocrine, 139, 226, 239, 268

305

Exocytosis, 69, 239, 288 Exogenous, 44, 46, 51, 77, 91, 161, 210, 236, 240, 293 Exon, 56, 69, 212, 240 Expander, 240, 273 Exploratory Behavior, 53, 240 Extensor, 240, 277, 289 External-beam radiation, 240, 253, 278, 296 Extracellular, 14, 33, 53, 58, 64, 213, 217, 229, 236, 240, 241, 257, 266, 285, 289 Extracellular Matrix, 229, 240, 241, 257, 266 Extracellular Matrix Proteins, 240, 257 Extraction, 169, 240 Extrapyramidal, 211, 215, 234, 240 F Facial, 93, 226, 240, 268, 285, 289 Facial Nerve, 240, 268, 289 Family Planning, 189, 240 Fat, 46, 210, 216, 218, 220, 230, 231, 240, 255, 257, 285 Fatigue, 11, 64, 240, 246 Fatty acids, 235, 240, 275, 290 Feces, 223, 229, 240, 287 Femoral, 9, 223, 240, 241 Femoral Artery, 223, 241 Femur, 181, 240, 241 Fermentation, 146, 241 Fetus, 220, 241, 271, 274, 294 Fever of Unknown Origin, 136, 241 Fibril, 74, 85, 241 Fibrillation, 137, 241 Fibroblasts, 29, 103, 229, 241, 252 Fibrosis, 70, 212, 241, 282 Fistula, 241, 242 Fixation, 35, 241, 283 Flexor, 240, 241, 247 Fluorescence, 25, 26, 241 Flushing, 158, 241 Fold, 18, 154, 241, 258 Food Technology, 149, 241 Foramen, 241, 246, 270 Forearm, 20, 219, 241, 289 Fovea, 241 Friction, 211, 241 G Galanin, 52, 242 Gallbladder, 209, 218, 226, 242 Gallium, 5, 242 Gallium nitrate, 5, 242

Ganglion, 22, 32, 49, 51, 150, 242, 263, 266, 292 Ganglioneuroblastoma, 95, 242 Gas, 147, 213, 223, 233, 242, 248, 264, 280, 295 Gas exchange, 242, 280, 295 Gastric, 61, 62, 84, 90, 160, 220, 224, 234, 242, 247, 248, 253, 269 Gastric Acid, 62, 160, 242, 269 Gastric Juices, 242, 269 Gastric Mucosa, 62, 242 Gastrin, 4, 90, 91, 176, 237, 242, 247, 269 Gastroduodenal, 4, 242 Gastrointestinal tract, 160, 166, 167, 168, 182, 223, 239, 242, 255, 283 Gels, 30, 242 Gene Deletion, 67, 243 Gene Expression, 4, 36, 43, 51, 56, 70, 96, 104, 115, 243 Gene Therapy, 14, 21, 115, 243 Genetic Code, 243, 265 Genetic Engineering, 146, 219, 227, 243 Genetic testing, 102, 243, 272 Genetics, 3, 7, 14, 37, 57, 93, 182, 243, 260 Genital, 160, 217, 227, 243, 294 Genitourinary, 52, 243, 294 Genotype, 243, 270 Germ Cells, 243, 258, 265, 267, 285, 289 Germ Layers, 220, 235, 236, 243 Gestation, 36, 38, 63, 243, 269, 271 Gestational, 36, 243 Gland, 18, 43, 137, 150, 168, 176, 210, 243, 256, 262, 268, 271, 276, 282, 287, 288, 290 Glomerular, 243, 279 Glomerulus, 243, 262 Glossopharyngeal Nerve, 46, 243, 289 Glucocorticoid, 12, 20, 39, 64, 99, 182, 244 Glucose, 10, 98, 132, 138, 160, 168, 244, 249, 251, 252, 271, 279, 282 Glucose tolerance, 10, 244 Glucose Tolerance Test, 10, 244 Glucuronic Acid, 244, 246 Glutamate, 46, 52, 53, 66, 68, 244, 259 Glutamic Acid, 244, 264, 275 Glutamine, 61, 244 Gluten, 224, 244 Glycine, 16, 146, 218, 244, 264, 283 Glycogen, 10, 168, 244, 271 Glycopeptides, 28, 244 Glycoprotein, 223, 244, 245, 253, 261, 290, 293 Glycosylation, 91, 110, 244

306

Calcitonin

Goiter, 150, 244, 290 Gonad, 244, 245 Gonadal, 9, 182, 245, 286 Gonadotropin, 74, 77, 245 Governing Board, 245, 273 Gp120, 245, 269 Grafting, 105, 230, 245, 250 Gram-negative, 237, 245, 295 Granulocytes, 57, 245, 255, 284, 296 Granuloma, 111, 245 Gravis, 90, 245 Growth factors, 7, 49, 148, 178, 245, 259, 263 Guanylate Cyclase, 245, 264 H Haematoma, 245 Haemorrhage, 82, 245 Hair Cells, 55, 245 Half-Life, 151, 156, 245 Haptens, 211, 245, 278 Headache, 15, 78, 111, 128, 158, 245, 249, 275, 294 Headache Disorders, 245 Heart attack, 223, 246 Heart failure, 246, 265 Heartbeat, 246, 287 Helix-loop-helix, 69, 246 Hematogenous, 21, 246 Hemicrania, 246, 294 Hemodialysis, 75, 233, 246 Hemodilution, 33, 246 Hemodynamics, 17, 117, 246 Hemoglobinopathies, 243, 246 Hemorrhage, 16, 65, 231, 245, 246, 262, 278, 287 Hemostasis, 246, 283 Heparin, 168, 246, 272 Hepatic, 10, 232, 244, 246 Hepatocyte, 226, 246 Hepatotoxicity, 38, 246 Heredity, 242, 243, 246 Herniated, 163, 246 Heterodimer, 220, 246 Heterogeneity, 26, 33, 39, 70, 211, 246 Hippocampus, 167, 232, 246, 255, 287 Histamine, 85, 162, 213, 215, 237, 247 Histidine, 38, 247 Homeostasis, 7, 13, 19, 23, 36, 55, 67, 72, 83, 148, 220, 247, 285 Homodimer, 247, 292 Homogeneous, 146, 247, 270 Homologous, 160, 243, 246, 247, 283, 288

Homozygotes, 29, 247 Hormonal, 8, 25, 64, 92, 133, 182, 217, 219, 231, 239, 247, 296 Hormone Replacement Therapy, 4, 7, 8, 9, 96, 122, 174, 176, 195, 196, 247 Hormone therapy, 75, 247 Horseradish Peroxidase, 33, 64, 247 Humeri, 31, 247 Humoral, 23, 247 Humour, 247 Hybrid, 20, 38, 247 Hybridization, 18, 24, 165, 247, 260 Hybridomas, 147, 247, 252 Hydra, 247, 254 Hydration, 177, 248 Hydrochloric Acid, 153, 237, 248 Hydrogel, 29, 248 Hydrogen, 168, 209, 212, 218, 221, 223, 232, 233, 240, 248, 255, 260, 264, 265, 267, 270, 277 Hydrogen Bonding, 218, 248, 265 Hydrogen Peroxide, 248, 255 Hydrolysis, 153, 157, 165, 209, 216, 248, 253, 270, 273, 277, 293 Hydrophilic, 149, 162, 248 Hydrophobic, 68, 149, 160, 248 Hydroxy Acids, 170, 248 Hydroxylation, 222, 248 Hydroxylysine, 228, 248 Hydroxyproline, 228, 248 Hyperalgesia, 21, 32, 50, 54, 66, 248 Hyperbilirubinemia, 248, 254 Hypercalciuria, 7, 248 Hyperglycemia, 10, 248 Hyperlipidemia, 6, 248 Hyperoxia, 130, 248 Hypersecretion, 171, 248 Hypersensitivity, 30, 161, 212, 233, 248, 255, 281, 283 Hypertension, 6, 13, 17, 23, 43, 55, 59, 65, 86, 157, 223, 245, 248, 273, 274, 275 Hyperthyroidism, 150, 249, 275 Hypertrophy, 18, 230, 249, 292 Hypervitaminosis, 130, 249 Hypoglycaemia, 91, 232, 249 Hypogonadism, 10, 77, 249 Hypotension, 32, 43, 215, 249 Hypotensive, 249, 254 Hypothalamic, 9, 95, 249 Hypothalamus, 167, 217, 237, 249, 255, 271, 274, 290 Hypothermia, 246, 249

307

Hypoxia, 23, 33, 232, 249 Hypoxic, 23, 249 Hysterectomy, 148, 249 I Idiopathic, 43, 73, 83, 127, 132, 176, 249 Imaging procedures, 249, 291 Immune response, 39, 149, 210, 215, 217, 231, 245, 249, 250, 283, 287, 294, 295 Immune system, 41, 57, 217, 219, 249, 250, 255, 257, 294, 296 Immunity, 41, 99, 249 Immunization, 249, 250, 274, 283 Immunoassay, 81, 133, 147, 249 Immunoblotting, 34, 249 Immunogenic, 249, 278 Immunohistochemistry, 18, 24, 33, 36, 59, 64, 250 Immunologic, 41, 48, 226, 249, 250, 279 Immunology, 57, 90, 97, 210, 211, 247, 250 Immunoradiometric Assay, 117, 250 Immunosuppression, 250 Immunosuppressive, 6, 20, 244, 250 Immunosuppressive Agents, 6, 250 Immunotherapy, 219, 233, 250 Impairment, 36, 77, 226, 232, 235, 250, 258, 277 Implant radiation, 250, 252, 253, 278, 296 Implantation, 36, 250, 264, 274 Impotence, 238, 250, 275 In situ, 18, 19, 24, 36, 67, 100, 110, 250 In Situ Hybridization, 19, 24, 36, 67, 100, 110, 250 In vitro, 18, 20, 22, 24, 26, 27, 28, 32, 37, 39, 48, 49, 51, 52, 53, 56, 58, 60, 63, 64, 65, 67, 81, 82, 93, 96, 123, 146, 151, 152, 219, 220, 236, 243, 250, 272, 290 Incision, 250, 253 Incubated, 38, 250 Incubation, 139, 250 Indomethacin, 109, 131, 250 Induction, 27, 41, 49, 50, 71, 107, 134, 213, 215, 251, 275 Infancy, 251, 281 Infarction, 251, 280 Infection, 6, 80, 136, 150, 168, 177, 217, 219, 226, 232, 251, 256, 264, 269, 281, 287, 296 Infertility, 151, 152, 251, 254 Inflammatory bowel disease, 4, 50, 251 Infusion, 23, 66, 69, 87, 136, 177, 251, 262 Ingestion, 162, 244, 249, 251, 289 Inhalation, 171, 251 Initiation, 42, 182, 251

Initiator, 219, 251 Inner ear, 25, 55, 251 Innervation, 33, 43, 45, 54, 134, 240, 251 Inorganic, 126, 137, 147, 251, 261, 285 Inositol, 251, 259 Inotropic, 234, 251 Insight, 24, 32, 50, 52, 53, 55, 67, 251 Insulin, 6, 10, 20, 96, 122, 132, 138, 149, 168, 176, 178, 219, 244, 251, 252, 274, 293 Insulin-dependent diabetes mellitus, 252 Insulin-like, 20, 96, 252 Interleukin-1, 84, 252 Interleukin-2, 252 Interleukin-6, 84, 162, 252 Interleukin-8, 112, 162, 252 Interleukins, 250, 252 Intermittent, 64, 100, 252, 256 Internal Medicine, 17, 59, 61, 67, 87, 252, 281 Internal radiation, 252, 253, 278, 296 Interneurons, 15, 61, 252 Interstitial, 30, 163, 221, 252, 253, 279, 296 Intervertebral, 163, 246, 252, 256, 278, 282 Intervertebral Disk Displacement, 252, 256, 278, 282 Intestinal Mucosa, 46, 224, 226, 252, 294 Intestine, 25, 46, 48, 197, 218, 221, 228, 252, 254, 259 Intoxication, 232, 252, 296 Intramuscular, 96, 97, 98, 152, 253, 268 Intramuscular injection, 152, 253 Intraocular, 77, 253 Intraocular pressure, 77, 253 Intrathecal, 22, 253 Intravenous, 30, 112, 177, 251, 253, 268 Intrinsic, 59, 95, 211, 253, 269 Intrinsic Factor, 253, 269 Invasive, 18, 162, 249, 253, 257 Involuntary, 226, 230, 241, 253, 262, 271, 279, 285 Iodine, 150, 253 Ion Channels, 25, 217, 253 Ion Transport, 58, 253, 260 Ionomycin, 19, 253 Ions, 148, 218, 221, 222, 226, 234, 236, 248, 253, 273 Irradiation, 67, 175, 253, 297 Irritants, 233, 253 Ischemia, 18, 26, 214, 217, 254, 261, 280 Isoflavones, 129, 254 Isoproterenol, 135, 254 Isotonic, 177, 254, 260

308

Calcitonin

Isozymes, 32, 254 J Jaundice, 175, 248, 254 Jellyfish, 163, 254 K Kallidin, 162, 221, 254 Kallikreins, 254 Kb, 188, 254 Keratinocytes, 252, 254 Kidney Disease, 6, 55, 177, 188, 194, 254 Kidney Transplantation, 6, 75, 254 Kinetic, 147, 254 L Labile, 228, 254 Labyrinth, 33, 227, 237, 251, 254, 283, 295 Lactation, 42, 122, 254, 275 Large Intestine, 117, 224, 228, 233, 252, 254, 279, 284 Lesion, 35, 230, 245, 255, 256, 289 Leucocyte, 255, 257 Leukaemia, 94, 255 Leukemia, 52, 57, 63, 84, 94, 243, 255 Leukotrienes, 216, 235, 255 Libido, 213, 255 Life cycle, 210, 255 Ligament, 255, 276, 286 Ligands, 27, 28, 49, 56, 255 Limbic, 213, 255 Limbic System, 213, 255 Lipid, 10, 38, 39, 79, 149, 223, 226, 252, 255, 267 Lipid Peroxidation, 38, 255, 267 Lithium, 215, 255 Liver scan, 255, 282 Liver Transplantation, 73, 117, 136, 256 Localization, 17, 49, 68, 95, 100, 250, 256 Localized, 18, 158, 160, 232, 241, 245, 251, 256, 262, 265, 271 Locus Control Region, 90, 256 Longitudinal study, 116, 256 Long-Term Care, 4, 32, 159, 256 Loop, 5, 81, 256 Low Back Pain, 164, 256 Luciferase, 51, 256 Lumbar, 9, 20, 35, 163, 181, 218, 224, 252, 256 Lung Transplantation, 23, 256 Lupus, 181, 194, 256 Lutein Cells, 256, 275 Lymph, 225, 227, 237, 247, 256, 262 Lymph node, 225, 256, 262

Lymphatic, 149, 237, 251, 256, 265, 286, 290 Lymphatic system, 256, 286, 290 Lymphoblastic, 94, 257 Lymphoblasts, 209, 257 Lymphocytes, 57, 109, 122, 215, 247, 249, 252, 255, 256, 257, 286, 290, 296 Lymphocytic, 83, 257 Lymphoid, 214, 255, 257 Lymphoma, 257 Lysine, 38, 113, 248, 257, 293 M Macroglia, 257, 259 Macronutrients, 46, 257 Macrophage, 252, 257 Magnetic Resonance Imaging, 163, 257, 282 Malabsorption, 4, 175, 224, 257 Malignancy, 25, 166, 177, 178, 257 Malignant, 18, 56, 87, 152, 168, 215, 242, 257, 262, 279 Malnutrition, 217, 257 Malondialdehyde, 38, 257 Mammary, 230, 257 Mammogram, 221, 257, 259 Mandible, 123, 212, 257, 280, 289 Mandibular Nerve, 257, 292 Manic, 215, 255, 257, 277 Mastication, 257, 292 Masticatory, 50, 257, 289 Matrix metalloproteinase, 61, 257 Maxillary, 258, 268, 292 Maxillary Nerve, 258, 292 Medial, 247, 258, 266 Mediate, 11, 34, 37, 46, 51, 55, 62, 234, 258 Mediator, 79, 162, 226, 252, 258, 272, 284 Medical Records, 258, 281 MEDLINE, 189, 258 Meiosis, 258, 288 Melanin, 258, 270, 293 Membrane Glycoproteins, 258 Meninges, 225, 231, 258 Menopause, 5, 8, 75, 140, 158, 195, 196, 197, 258, 273, 275 Menstrual Cycle, 36, 258, 274 Menstruation, 212, 232, 258 Mental, iv, 10, 188, 190, 225, 229, 232, 234, 240, 258, 274, 277, 282, 293 Mental Disorders, 258, 274, 277 Mental Health, iv, 10, 188, 190, 258, 274, 277 Mesenteric, 43, 47, 63, 127, 258, 273

309

Mesentery, 258 Mesolimbic, 215, 258 Meta-Analysis, 81, 258 Metabolic Clearance Rate, 70, 148, 259 Metabolite, 38, 221, 239, 259 Metabotropic, 47, 53, 259 Metastasis, 21, 258, 259 Metastatic, 14, 63, 102, 148, 195, 259, 282 Methyltransferase, 43, 259 Microbe, 259, 291 Microbiology, 57, 88, 210, 259 Microcalcifications, 222, 259 Microcirculation, 26, 84, 246, 259 Microglia, 27, 217, 259 Microorganism, 228, 259, 268, 296 Microscopy, 26, 29, 45, 52, 62, 105, 143, 247, 259 Microspheres, 17, 259 Micturition, 15, 259 Migration, 41, 103, 259 Milliliter, 220, 259 Mineralization, 259, 267 Mineralocorticoids, 210, 231, 260 Mitochondrial Swelling, 260, 262 Mitosis, 216, 260 Mitotic, 239, 260 Mobility, 31, 85, 260 Modification, 146, 165, 243, 260, 278 Modulator, 27, 260 Molecular Probes, 54, 260 Monitor, 223, 260, 265 Monoclonal, 147, 149, 247, 249, 253, 260, 278, 297 Monoclonal antibodies, 147, 149, 249, 260 Monocyte, 112, 260 Mononuclear, 19, 98, 113, 245, 260, 293 Morphine, 41, 66, 161, 260, 262, 266 Morphogenesis, 18, 31, 260 Morphological, 15, 33, 152, 236, 260 Motility, 19, 24, 50, 152, 160, 250, 260, 283 Motor Activity, 50, 260 Motor nerve, 167, 260, 261 Motor Neurons, 61, 261 Movement Disorders, 215, 261 Mucinous, 242, 261 Mucins, 261, 282 Mucociliary, 261, 284 Mucolytic, 221, 261 Mucosa, 50, 237, 242, 256, 261, 262, 275, 287 Mucositis, 261, 290 Mucus, 171, 261, 281, 293

Muscle Contraction, 47, 213, 221, 261 Muscle relaxant, 38, 62, 261 Muscle tension, 261 Mutagenesis, 29, 261 Mutagens, 261 Myasthenia, 90, 261 Myelin, 261, 265 Myocardial infarction, 87, 218, 230, 261, 275 Myocardial Reperfusion, 261, 280 Myocardial Reperfusion Injury, 261, 280 Myocardium, 60, 214, 261, 262 Myofibrils, 222, 262 Myograph, 47, 262 Myometrium, 82, 86, 262 Myosin, 261, 262 N Narcotic, 209, 260, 262 Nasal Cavity, 262, 268 Nasal Mucosa, 152, 262 Nasopharynx, 244, 262 Nausea, 215, 234, 262, 293 Neck Pain, 163, 262 Necrosis, 17, 216, 251, 261, 262, 280, 283 Neocortex, 16, 262 Neonatal, 38, 262 Neoplasia, 12, 21, 61, 72, 87, 262 Neoplasm, 168, 242, 262, 293 Nephrectomy, 17, 262 Nephrons, 25, 262 Nephropathy, 254, 262 Nerve Endings, 27, 57, 262, 264 Nerve Fibers, 45, 55, 67, 163, 263, 286 Nerve Growth Factor, 51, 52, 263, 264 Networks, 27, 263 Neural, 6, 14, 16, 21, 35, 41, 49, 50, 59, 61, 64, 210, 213, 222, 247, 259, 263 Neural Crest, 49, 263 Neuralgia, 16, 263 Neurites, 60, 263 Neuroblastoma, 242, 263 Neurodegenerative Diseases, 27, 263 Neuroeffector Junction, 262, 263 Neuroendocrine, 12, 18, 21, 36, 50, 63, 70, 82, 91, 130, 263 Neuroendocrine tumor, 63, 263 Neurogenic, 27, 30, 31, 34, 36, 43, 47, 48, 51, 52, 54, 105, 128, 158, 163, 164, 263 Neurogenic Inflammation, 27, 30, 34, 36, 48, 51, 52, 54, 128, 158, 263 Neuroleptic, 211, 215, 263 Neuromuscular, 25, 47, 69, 209, 264, 280

310

Calcitonin

Neuromuscular Junction, 69, 209, 264, 280 Neuronal, 17, 34, 37, 42, 44, 49, 50, 53, 54, 56, 64, 67, 105, 222, 264 Neuropathy, 43, 148, 217, 264, 282 Neuropeptide, 16, 26, 47, 51, 52, 53, 54, 57, 60, 84, 86, 105, 114, 160, 167, 222, 264 Neurophysiology, 233, 264 Neurotoxin, 150, 264 Neurotransmitter, 46, 55, 59, 61, 171, 209, 210, 220, 221, 222, 234, 239, 242, 244, 247, 253, 264, 265, 284, 287, 294 Neurotrophins, 41, 264 Neutrons, 212, 253, 264, 278 Neutrophils, 245, 252, 264 Nidation, 236, 264 Nitric Oxide, 6, 33, 51, 59, 84, 87, 162, 264 Nitrogen, 211, 212, 213, 240, 241, 244, 264, 293 Nociceptors, 22, 54, 264 Nodose, 61, 264 Norepinephrine, 11, 68, 210, 234, 264, 265 Nuclear, 218, 236, 239, 242, 255, 262, 265, 289, 293 Nuclei, 16, 167, 212, 213, 236, 243, 255, 257, 260, 264, 265, 266, 277 Nucleic acid, 146, 157, 159, 160, 165, 231, 243, 247, 250, 261, 264, 265, 281 Nucleic Acid Hybridization, 247, 265 O Observational study, 132, 265 Obstetrics, 35, 37, 62, 73, 86, 108, 122, 265 Oedema, 116, 171, 265 Ointments, 234, 265 Oligodendroglial, 110, 265 Oocytes, 29, 70, 89, 152, 265 Ophthalmic, 265, 292 Ophthalmology, 241, 265 Opiate, 164, 237, 260, 265 Opium, 260, 265 Optic Chiasm, 249, 266, 274 Optic Nerve, 266, 280 Oral Health, 3, 266 Organelles, 227, 231, 232, 266 Orgasm, 161, 266 Orofacial, 56, 266 Orthodontics, 13, 14, 56, 266 Orthostatic, 43, 215, 266 Osmosis, 266 Osmotic, 54, 260, 266, 284 Osseointegration, 220, 266 Ossification, 109, 266, 267, 281 Osteoarthritis, 24, 59, 84, 266

Osteoblasts, 9, 20, 23, 28, 56, 67, 148, 178, 266, 267 Osteocalcin, 20, 76, 101, 266 Osteochondrodysplasias, 31, 266 Osteoclasts, 9, 14, 19, 20, 23, 28, 56, 58, 68, 111, 148, 151, 156, 178, 222, 267 Osteocytes, 64, 178, 267 Osteogenesis, 194, 220, 267 Osteolysis, 161, 267 Osteomalacia, 176, 221, 267 Osteopetrosis, 59, 195, 267 Osteotomy, 176, 267 Ototoxic, 25, 267 Ovariectomy, 108, 267 Ovaries, 267, 280, 284 Ovary, 238, 244, 267, 287 Ovum, 209, 232, 243, 255, 267, 274, 275, 296, 297 Oxalic Acid, 222, 267 Oxidation, 10, 38, 153, 209, 215, 231, 234, 255, 267 Oxidative Stress, 18, 78, 267 Oxygen Consumption, 150, 267 Oxygenator, 223, 267 P Palate, 152, 244, 262, 267, 289 Palliative, 63, 268, 289 Pamidronate, 112, 268 Pancreas, 127, 139, 167, 176, 209, 251, 268, 274, 282, 293 Pancreatic, 72, 224, 226, 268 Paradoxical, 20, 66, 268 Paranasal Sinuses, 268, 284 Parathyroid Glands, 29, 155, 268, 281 Parathyroidectomy, 86, 268 Parenteral, 28, 153, 268 Parietal, 237, 268, 272 Parkinsonism, 215, 268 Parotid, 243, 268 Paroxysmal, 214, 246, 268, 294 Particle, 268, 291 Parturition, 35, 265, 268, 275 Patch, 22, 25, 53, 268, 291 Pathogen, 57, 250, 268 Pathologic, 178, 216, 219, 230, 248, 268, 277, 280 Pathologic Processes, 216, 268 Pathologies, 24, 268 Pathophysiology, 7, 8, 11, 17, 24, 27, 38, 43, 59, 78, 269 Patient Compliance, 28, 168, 269

311

Patient Education, 4, 194, 202, 204, 208, 269 Patient Selection, 108, 269 Peer Review, 4, 121, 269 Pelvic, 30, 59, 269, 276 Pelvis, 59, 151, 157, 177, 209, 256, 267, 269, 294 Penicillin, 214, 269 Pentagastrin, 75, 87, 269 Pepsin, 269, 282 Peptic, 161, 269 Peptic Ulcer, 161, 269 Peptide T, 39, 89, 123, 128, 138, 269 Perfusion, 33, 114, 249, 269 Perinatal, 31, 269 Periodontal disease, 24, 59, 269 Perioperative, 117, 269 Peripheral blood, 48, 113, 269 Peripheral Nervous System, 52, 67, 164, 167, 263, 264, 269, 274, 287, 294 Peritoneal, 216, 265, 270 Peritoneal Cavity, 216, 265, 270 Perivascular, 26, 33, 47, 222, 259, 270 Petechiae, 245, 270 PH, 14, 61, 62, 70, 77, 220, 270 Phagocytosis, 259, 270 Phallic, 241, 270 Phantom, 161, 270 Pharmaceutical Solutions, 234, 270 Pharmacologic, 7, 11, 25, 50, 213, 217, 245, 270, 291 Pharmacotherapy, 65, 74, 127, 135, 270 Pharynx, 262, 270, 289, 294 Phenotype, 19, 22, 24, 25, 31, 39, 43, 49, 56, 70, 96, 104, 243, 270 Phenylalanine, 270, 293 Phosphodiesterase, 157, 270 Phospholipases, 25, 270, 284 Phospholipids, 240, 251, 270 Phosphorus, 123, 133, 147, 222, 268, 271 Phosphorylase, 222, 271 Phosphorylated, 216, 271 Phosphorylation, 14, 19, 53, 108, 134, 271 Photodermatitis, 30, 271 Physical Examination, 49, 177, 195, 271 Physical Therapy, 5, 271 Physiologic, 11, 13, 35, 54, 68, 71, 211, 219, 233, 245, 254, 258, 271, 275, 279, 280 Piloerection, 249, 271 Pilot study, 73, 98, 271 Pituitary Gland, 100, 231, 271, 283 Pituitary Hormones, 176, 271

Placenta, 38, 63, 238, 239, 271, 274, 277 Placental Circulation, 118, 271 Plants, 212, 223, 226, 244, 265, 267, 271, 282, 291 Plaque, 78, 271 Plasma cells, 214, 271 Plasmid, 14, 271, 294 Plasticity, 42, 45, 53, 272 Platelet Activation, 272, 284 Platelet Aggregation, 213, 264, 272, 275, 290 Platelet Factor 4, 252, 272 Platelets, 218, 222, 264, 272 Pleural, 265, 272 Pleural cavity, 265, 272 Plicamycin, 5, 177, 272 Pneumonia, 230, 272 Podophyllotoxin, 239, 272 Polymerase, 19, 89, 272 Polymerase Chain Reaction, 19, 89, 272 Polymorphism, 75, 79, 96, 272 Polypeptide, 43, 84, 87, 95, 116, 118, 152, 153, 155, 157, 162, 168, 169, 212, 223, 228, 244, 247, 269, 273, 275, 276, 294, 297 Polyposis, 228, 273 Polysaccharide, 211, 215, 273 Pons, 113, 218, 221, 273 Portal Hypertension, 175, 273 Portal Vein, 273 Posterior, 46, 164, 213, 217, 218, 227, 234, 244, 262, 268, 271, 273, 282, 289 Postnatal, 273, 286 Postoperative, 71, 79, 273 Postoperative Period, 79, 273 Postsynaptic, 52, 53, 65, 263, 273, 284 Post-translational, 146, 273 Potassium, 33, 137, 211, 260, 273 Potassium Channels, 33, 273 Potentiates, 32, 252, 273 Potentiating, 48, 102, 219, 273 Potentiation, 273, 284 Povidone, 167, 273 Practice Guidelines, 190, 273 Precipitation, 165, 273 Preclinical, 66, 273 Preeclampsia, 38, 73, 274 Preimplantation Phase, 36, 274 Prenatal, 236, 274 Preoperative, 106, 180, 274 Preoptic Area, 167, 274 Presynaptic, 53, 65, 263, 264, 274, 288 Presynaptic Terminals, 263, 274, 288

312

Calcitonin

Prevalence, 64, 163, 274 Primary Biliary Cirrhosis, 73, 175, 274 Primary Prevention, 182, 274 Primary Sclerosing Cholangitis, 73, 274 Probe, 55, 274 Progesterone, 274, 275, 286 Progression, 8, 12, 18, 21, 31, 43, 177, 214, 274 Progressive, 26, 35, 43, 224, 227, 232, 235, 239, 262, 263, 266, 272, 274, 279, 293 Proinsulin, 10, 274, 278 Projection, 15, 33, 45, 60, 252, 265, 266, 274 Prolactin, 42, 136, 275 Prolactinoma, 159, 275 Proline, 228, 248, 275 Promoter, 19, 51, 56, 92, 94, 115, 275 Prophase, 265, 275, 288 Prophylaxis, 275, 294 Propranolol, 135, 275 Propulsive, 50, 275 Prospective study, 43, 86, 100, 125, 126, 131, 256, 275 Prostaglandin, 34, 61, 62, 88, 98, 131, 162, 275, 276, 290 Prostaglandin Endoperoxides, 275, 276, 290 Prostaglandins A, 50, 250, 275, 276 Prostaglandins B, 27, 276 Prostaglandins D, 50, 276 Prostaglandins F, 276 Prostaglandins G, 50, 276 Prostate, 11, 18, 79, 91, 104, 108, 117, 135, 194, 227, 254, 276, 280 Prostate gland, 18, 227, 276 Prostatic Hyperplasia, 14, 276 Prostatitis, 276 Protease, 27, 117, 228, 276 Protease Inhibitors, 117, 276 Protein C, 40, 101, 150, 156, 157, 212, 227, 266, 276, 293 Protein Conformation, 212, 276 Protein Isoforms, 212, 276 Protein Kinases, 25, 276 Protein S, 149, 157, 219, 243, 266, 272, 276, 281 Proteinuria, 274, 277 Proteolytic, 220, 228, 237, 254, 277 Protons, 212, 248, 277, 278 Proximal, 24, 115, 134, 234, 262, 274, 277 Psoriasis, 30, 41, 67, 277 Psychiatric, 163, 258, 277 Psychiatry, 21, 96, 241, 277, 295

Psychoactive, 277, 289, 296 Psychosis, 215, 243, 277 Puberty, 77, 277 Public Health, 4, 12, 190, 277 Public Policy, 189, 277 Publishing, 68, 176, 277 Puerperium, 265, 277 Pulmonary, 22, 78, 82, 130, 134, 171, 211, 219, 221, 230, 238, 255, 277, 278, 280, 295 Pulmonary Artery, 219, 277, 295 Pulmonary Circulation, 22, 278 Pulmonary hypertension, 23, 230, 278 Pulposus, 163, 252, 278 Purified Insulins, 274, 278 Purifying, 160, 278 Purpura, 245, 278 Pyrogenic, 156, 278 Q Quality of Health Care, 269, 278 Quality of Life, 11, 12, 14, 31, 278 R Race, 197, 259, 278 Radiation, 42, 99, 116, 214, 217, 240, 241, 250, 252, 253, 270, 278, 279, 282, 296 Radiation therapy, 240, 252, 253, 278, 296 Radiculopathy, 278, 282 Radioactive, 148, 217, 221, 245, 248, 250, 252, 253, 255, 260, 265, 278, 282, 289, 293, 296 Radioimmunoassay, 51, 76, 134, 136, 147, 174, 218, 250, 278 Radioisotope, 278, 291 Radiolabeled, 148, 220, 253, 278, 297 Radiopharmaceuticals, 113, 278 Radiotherapy, 221, 253, 278, 279, 297 Randomized, 11, 43, 73, 111, 235, 279 Reabsorption, 177, 279 Reagent, 248, 256, 267, 279 Receptivity, 36, 279 Receptors, Serotonin, 279, 284 Recombinant, 85, 88, 90, 146, 152, 157, 159, 168, 169, 279, 294 Recombination, 243, 279 Rectum, 215, 228, 233, 242, 251, 254, 276, 279 Red blood cells, 238, 279, 282 Refer, 1, 221, 228, 237, 241, 252, 256, 263, 264, 277, 279, 291, 295 Reflex, 15, 50, 59, 127, 279 Refraction, 279, 285 Refractory, 112, 279 Regimen, 166, 235, 269, 270, 279

313

Relapse, 84, 279 Relaxant, 62, 279 Remission, 279 Renal Circulation, 220, 279 Renal failure, 6, 25, 178, 232, 279 Renal pelvis, 59, 280 Renal tubular, 24, 280 Renin, 13, 59, 214, 280 Renin-Angiotensin System, 59, 280 Reperfusion, 18, 261, 280 Reperfusion Injury, 18, 280 Reproductive system, 276, 280 Research Design, 49, 280 Resorption, 5, 7, 8, 9, 12, 14, 19, 20, 23, 28, 42, 58, 106, 109, 131, 147, 148, 151, 156, 161, 182, 195, 220, 222, 267, 279, 280 Respiratory Paralysis, 209, 280 Respiratory Physiology, 280, 295 Respiratory System, 261, 280, 294 Retina, 55, 227, 266, 280, 281, 294, 296 Retinal, 216, 266, 280, 281 Retraction, 19, 281 Retrograde, 33, 64, 281 Retrospective, 107, 281 Retrospective study, 107, 281 Retroviral vector, 243, 281 Reverse Transcriptase Polymerase Chain Reaction, 51, 281 Rheumatoid, 84, 281 Rheumatoid arthritis, 84, 281 Rheumatology, 7, 99, 109, 112, 117, 127, 176, 197, 281 Rhinorrhea, 275, 281 Rhodopsin, 216, 280, 281 Ribonuclease, 39, 281 Ribonucleic acid, 103, 281 Ribose, 210, 281 Ribosome, 281, 292 Rickets, 68, 125, 138, 176, 221, 281, 296 Risk factor, 3, 4, 6, 7, 8, 10, 13, 48, 173, 176, 182, 195, 196, 197, 275, 281 Rod, 227, 237, 281 S Saline, 177, 221, 281 Saliva, 86, 137, 162, 259, 281, 282 Salivary, 86, 167, 226, 240, 281, 282, 296 Salivary glands, 167, 226, 240, 281, 282 Saphenous, 230, 282 Saphenous Vein, 230, 282 Saponins, 282, 286 Scans, 163, 197, 282 Scatter, 270, 282

Schizoid, 282, 296 Schizophrenia, 282, 296 Schizotypal Personality Disorder, 282, 296 Sciatica, 163, 282 Sclerosis, 128, 282 Screening, 4, 20, 30, 37, 55, 72, 107, 147, 164, 227, 282 Secondary tumor, 259, 282 Secretin, 61, 95, 99, 282 Secretory, 10, 36, 71, 137, 138, 237, 263, 283 Sedentary, 5, 283 Segmental, 17, 35, 283, 286 Segmentation, 283 Selective estrogen receptor modulator, 12, 195, 283 Sella, 234, 271, 283 Sella Turcica, 234, 271, 283 Semen, 276, 283 Semicircular canal, 251, 283 Semisynthetic, 239, 283 Senile, 12, 267, 283 Sensibility, 213, 248, 283 Sensitization, 22, 34, 52, 123, 283 Sepsis, 69, 80, 83, 136, 156, 283 Septic, 26, 156, 283 Sequence Homology, 159, 269, 283 Sequencing, 19, 94, 112, 165, 272, 283 Sequester, 283, 288 Serine, 254, 283, 293 Serologic, 249, 283 Serotonin, 11, 48, 50, 65, 106, 162, 215, 264, 270, 279, 283, 287, 293 Serous, 237, 284 Serum Albumin, 278, 284 Sex Characteristics, 210, 213, 277, 284, 289 Sharks, 129, 284 Shock, 26, 132, 133, 156, 158, 237, 284, 292 Side effect, 6, 20, 21, 100, 149, 161, 170, 171, 183, 210, 211, 215, 219, 284, 291 Signal Transduction, 24, 27, 29, 36, 53, 58, 64, 66, 157, 251, 284 Signs and Symptoms, 163, 279, 284 Sinusitis, 194, 284 Skeletal, 10, 12, 24, 31, 42, 67, 128, 148, 196, 197, 213, 227, 231, 235, 254, 262, 284, 285 Skeleton, 12, 31, 42, 148, 159, 177, 194, 197, 209, 220, 241, 275, 284 Skull, 177, 231, 284, 289 Small intestine, 28, 224, 235, 247, 252, 284, 293, 295 Social Environment, 278, 285

314

Calcitonin

Sodium, 5, 7, 55, 59, 153, 174, 175, 176, 195, 211, 260, 279, 285, 288 Sodium Fluoride, 5, 175, 176, 195, 285 Soft tissue, 220, 284, 285 Solitary Nucleus, 217, 285 Solvent, 239, 266, 270, 285 Soma, 51, 285 Somatic, 43, 210, 231, 243, 247, 255, 258, 260, 270, 285, 294 Spasm, 171, 285, 289 Specialist, 177, 198, 234, 285 Specificity, 31, 80, 211, 222, 285 Spectrum, 21, 30, 259, 285 Sperm, 85, 151, 152, 209, 213, 227, 285 Sperm Head, 209, 285 Spermatozoa, 209, 283, 285 Spermatozoon, 209, 286 Spinal Nerve Roots, 278, 282, 286 Spinal Nerves, 270, 286 Spinal Stenosis, 163, 286 Spinous, 35, 238, 254, 286 Spleen, 256, 286 Splenomegaly, 267, 286 Sporadic, 263, 286 Sprains and Strains, 256, 286 Stabilizer, 152, 286 Staging, 282, 286 Staphylococcal Infections, 156, 286 Steady state, 24, 286 Steel, 100, 227, 286 Stellate, 87, 116, 286 Stem Cells, 143, 212, 286 Stenosis, 163, 286, 287 Sterile, 268, 286 Sterility, 251, 286 Steroid, 4, 38, 58, 62, 64, 86, 137, 218, 231, 282, 286 Stimulant, 247, 254, 287 Stimulus, 50, 54, 62, 164, 221, 230, 235, 239, 251, 252, 253, 263, 279, 287, 290 Stool, 228, 255, 287 Strand, 272, 287 Stress, 105, 171, 176, 217, 224, 231, 241, 262, 267, 281, 287 Stricture, 286, 287 Stroke, 123, 163, 188, 223, 287 Stroma, 242, 287 Stromal, 64, 287 Stromal Cells, 64, 287 Structure-Activity Relationship, 32, 287 Subacute, 251, 284, 287 Subarachnoid, 65, 82, 245, 287

Subclinical, 251, 287 Subcutaneous, 86, 152, 235, 265, 268, 287 Subiculum, 246, 287 Subspecies, 285, 287 Substance P, 42, 48, 113, 259, 283, 287 Substrate, 35, 238, 287 Sudden cardiac death, 59, 287 Sumatriptan, 51, 287 Superoxide, 33, 288 Supine, 43, 288 Supplementation, 5, 33, 125, 126, 131, 176, 288 Support group, 174, 288 Suppression, 20, 21, 36, 63, 137, 231, 288 Supraspinal, 66, 288 Sweat, 43, 233, 249, 259, 288 Sweat Glands, 233, 288 Sympathetic Nervous System, 52, 217, 288 Sympathomimetic, 234, 238, 254, 265, 288 Symphysis, 276, 288 Symptomatic, 221, 288 Synapse, 45, 61, 210, 263, 264, 274, 288, 292 Synapsis, 288 Synaptic, 16, 69, 264, 284, 288 Synaptic Vesicles, 69, 288 Syncytium, 64, 288 Synergistic, 12, 40, 42, 275, 288 Systolic, 248, 288 T Tardive, 215, 289 Taste Buds, 45, 289 Technetium, 113, 289 Temporal, 16, 21, 24, 25, 32, 37, 49, 128, 213, 246, 289, 292 Temporal Lobe, 213, 289 Temporal Muscle, 128, 289 Tendon, 242, 289 Tennis Elbow, 247, 289 Teratogenic, 212, 234, 289 Testicular, 9, 74, 272, 289 Testis, 238, 289 Testosterone, 5, 9, 10, 176, 182, 213, 289 Tetany, 268, 289 Tetrahydrocannabinol, 222, 289 Thalamus, 167, 255, 289 Therapeutics, 27, 50, 89, 90, 100, 118, 184, 289 Thermal, 54, 66, 158, 234, 264, 272, 289 Thigh, 240, 241, 289 Third Ventricle, 249, 289, 290 Thoracic, 31, 105, 218, 290, 296 Threonine, 269, 283, 290

315

Threshold, 239, 248, 290 Thrombin, 272, 276, 290 Thrombomodulin, 276, 290 Thrombosis, 218, 276, 287, 290 Thromboxanes, 216, 235, 275, 276, 290 Thymidine, 165, 290 Thymus, 90, 148, 249, 256, 290 Thyroid Gland, 12, 147, 150, 161, 168, 169, 176, 244, 249, 268, 290 Thyroid Hormones, 126, 176, 178, 290, 293 Thyroid Nodule, 72, 114, 290 Thyroiditis, 83, 150, 290 Thyrotropin, 65, 290 Thyroxine, 150, 270, 290 Tissue Culture, 69, 263, 290 Tolerance, 21, 41, 66, 176, 244, 290 Tomography, 291 Tone, 23, 38, 39, 66, 98, 291 Tonic, 223, 291 Tonicity, 235, 254, 291 Tonus, 291 Tooth Preparation, 210, 291 Topical, 30, 61, 151, 239, 248, 291 Toxaemia, 274, 291 Toxic, iv, 156, 212, 231, 232, 249, 264, 272, 291 Toxicity, 10, 11, 134, 235, 291 Toxicology, 34, 129, 190, 291 Toxin, 111, 150, 156, 237, 290, 291 Tracer, 15, 25, 33, 64, 247, 291 Trachea, 221, 270, 290, 291 Traction, 227, 291 Tractus, 61, 291 Transcriptase, 19, 291 Transcutaneous, 127, 291 Transdermal, 113, 291 Transduction, 14, 53, 157, 284, 291 Transfection, 19, 23, 44, 219, 243, 292 Transferases, 244, 292 Transforming Growth Factor beta, 49, 292 Translation, 37, 146, 156, 292 Translational, 146, 292 Transmitter, 22, 33, 45, 47, 54, 66, 209, 217, 234, 239, 253, 258, 265, 288, 292 Transplantation, 6, 117, 126, 138, 236, 249, 292 Trauma, 8, 25, 26, 232, 262, 292 Triad, 47, 292 Tricuspid Atresia, 230, 292 Tricyclic, 272, 292 Trigeminal, 15, 17, 44, 50, 51, 54, 65, 89, 111, 113, 122, 257, 258, 292

Trigeminal Ganglion, 17, 44, 50, 113, 122, 292 Trigeminal Nerve, 111, 292 Trigger zone, 215, 292 Trophic, 45, 292 Trypsin, 39, 237, 293 Tryptophan, 139, 228, 283, 293 Tuberculosis, 256, 293 Tumor Necrosis Factor, 84, 162, 293 Tumorigenic, 18, 293 Tumour, 80, 242, 293 Tunica, 261, 293 Type 2 diabetes, 6, 293 Tyrosine, 19, 43, 58, 65, 105, 234, 293 U Ulceration, 269, 293 Ulcerative colitis, 251, 274, 293 Unconscious, 214, 217, 293 Uracil, 165, 293 Uranium, 289, 293 Urea, 216, 288, 293 Uremia, 279, 293 Ureters, 293 Urethra, 276, 293, 294 Urinary, 9, 14, 59, 83, 117, 140, 222, 231, 243, 293, 294 Urinary tract, 15, 293 Urine, 20, 31, 40, 59, 90, 132, 147, 219, 222, 234, 239, 248, 254, 259, 267, 277, 280, 293, 294 Urogenital, 243, 294 Uterus, 36, 82, 225, 232, 237, 249, 258, 262, 267, 274, 280, 294 Uveitis, 216, 294 V Vaccination, 57, 294 Vaccine, 210, 294 Vacuoles, 236, 266, 294 Vagal, 46, 60, 61, 294 Vagina, 225, 233, 258, 280, 294 Vagus Nerve, 285, 294 Vascular Headaches, 51, 294 Vascular Resistance, 23, 32, 38, 294 Vasoactive, 23, 26, 43, 72, 83, 84, 85, 87, 90, 95, 116, 117, 118, 162, 167, 242, 294 Vasoactive Intestinal Peptide, 72, 83, 84, 85, 90, 162, 242, 294 Vasoconstriction, 47, 238, 294 Vasoconstrictor Agents, 23, 294 Vasodilatation, 26, 160, 168, 224, 254, 294 Vasodilation, 6, 47, 63, 105, 128, 135, 158, 294

316

Calcitonin

Vasodilator, 6, 14, 23, 27, 33, 38, 65, 86, 118, 138, 221, 222, 234, 247, 261, 294 Vasomotor, 65, 239, 294 Vector, 40, 65, 146, 291, 294 Vein, 214, 216, 253, 265, 268, 273, 282, 294 Venous, 108, 118, 136, 216, 218, 265, 276, 292, 295 Venter, 295 Ventilation, 171, 280, 295 Ventral, 52, 249, 273, 286, 295 Ventricle, 213, 217, 230, 246, 277, 288, 290, 292, 295 Ventricular, 55, 60, 230, 262, 292, 295 Venules, 220, 223, 237, 259, 295 Vertebrae, 35, 164, 252, 286, 295 Vertebral, 20, 74, 86, 163, 218, 295 Vesicular, 48, 295 Vestibular, 33, 45, 116, 245, 295 Vestibule, 227, 251, 283, 295 Veterinary Medicine, 12, 189, 295 Vibrio, 226, 295 Vibrio cholerae, 226, 295 Villi, 295 Villous, 38, 224, 295 Viral, 14, 49, 65, 177, 291, 293, 295 Viral vector, 14, 295 Virulence, 217, 219, 291, 295 Virus, 225, 237, 243, 245, 271, 281, 291, 295 Viscera, 258, 285, 295, 296 Visceral, 16, 52, 217, 231, 243, 255, 294, 296 Visceral Afferents, 52, 217, 243, 294, 296

Vitamin D, 118, 122, 123, 127, 195, 208, 281, 296 Vitreous, 280, 296 Vitreous Body, 280, 296 Vitro, 22, 24, 29, 49, 52, 53, 61, 63, 64, 67, 68, 69, 246, 296 Vivo, 14, 16, 17, 20, 22, 23, 24, 26, 27, 28, 30, 32, 37, 41, 48, 49, 52, 53, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 70, 96, 126, 134, 137, 149, 152, 154, 219, 243, 246, 250, 290, 296 Voltage-gated, 17, 296 W Weight-Bearing, 5, 7, 8, 197, 296 Wheezing, 171, 296 White blood cell, 57, 209, 214, 250, 256, 257, 260, 261, 271, 296 Windpipe, 270, 290, 296 Withdrawal, 164, 232, 296 Womb, 280, 294, 296 Wound Healing, 60, 258, 296 X Xenograft, 214, 296 Xerostomia, 137, 296 X-ray, 8, 9, 182, 195, 197, 208, 220, 224, 229, 241, 253, 257, 265, 278, 279, 282, 286, 296 X-ray therapy, 253, 296 Y Yeasts, 270, 297 Z Zona Pellucida, 152, 297 Zymogen, 276, 297