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Monographs on Pathology of Laboratory Animals M'UM
Sponsored by the International Life Sciences Institute
Editorial Board
C.e. Capen, Columbus· A. Cardesa, Barcelona D.L. Dungworth, Port Townsend· J.L. Emerson, Atlanta F.M. Garner, Rockville· e.F. Hollander, Riom R.D. Hunt, Southborough· T.e. Jones, Washington, D.e. N.W. King, Jr., Southborough · Y. Konishi, Nara R. Kroes, Bilthoven . L. J. Lowenstine, Davis H. Luginbuhl, Bern· U. Mohr, Hannover P. Olsen, S0borg . J.A. Popp, Collegeville J.R. Schenken, Omaha· R.A. Squire, Baltimore J. Sugar, Budapest· B.F. Trump, Baltimore V.S. Turusov, Moscow · M.G. Valerio, Collegeville J.M. Ward, Frederick
Officers - ILSI
Alex Malaspina, Atlanta - President Peter B. Dews, Boston - Vice President Ulrich Mohr, Hannover - Vice President James W. Stanley, Valhalla - Secretary Alfred W. Wishart, Jr., Pittsburgh - Treasurer
The following volumes have appeared so far
Endocrine System 1983. 346 figures. XV, 366 pages. ISBN 3-540-U677-X
Respiratory System 1985. 279 figures. XV, 240 pages. ISBN 3-540-13521-9
Digestive System 1985. 352 figures. XVIII, 386 pages. ISBN 3-540-15815-4
Urinary System 1986. 362 figures. XVIII, 405 pages. ISBN 3-540-16591-6
Genital System 1987. 340 figures. XVII, 304 pages. ISBN 3-540-17604-7
Nervous System 1988. 242 figures. XVI, 233 pages. ISBN 3-540-19416-9
Integument and Mammary Glands 1989.468 figures. XI, 347 pages. ISBN 3-540-51025-7
Hemopoietic System 1990. 351 figures. XVIII, 336 pages. ISBN 3-540-52212-3
Cardiovascular and Musculoskeletal Systems 1991. 390 figures. XVII, 312 pages. ISBN 3-540-53876-3
Eye and Ear 1991. 141 figures. XIII, 170 pages. ISBN 3-540-54044-X
Nonhuman Primates I 1993.235 figures. XIII, 221 pages. ISBN 3-540-56465-9
0-944398-15-4
Nonhuman Primates II 1993. 264 figures. XVI, 248 pages. ISBN 3-540-56527-2
0-944398-16-2
2nd editions to follow
Respiratory System 1996. 382 figures. Approx. 440 pages. ISBN 3-540-60383-2
0-944398-69-3
T.C. Jones C.C. Capen U. Mohr (Eds.)
Endocrine System Second Edition
Completely Revised and Updated with 521 Figures and 37 Tables
Springer
Thomas Carlyle Jones, D.V.M., D.Sc. Professor of Comparative Pathology Emeritus, Harvard Medical School ILSI Research Foundation 1126 Sixteenth Street, N.W., Washington, DC 20036, USA
Charles C. Capen, D.V.M., Ph.D. Professor of Veterinary Pathobiology and Chairman, Department of Veterinary Biosciences, Professor of Endocrinology, Department of Internal Medicine, College of Medicine, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210-1093, USA
Ulrich Mohr, M.D. Professor of Experimental Pathology Medizinische Hochschule Hannover Institut fUr Experimentelle Pathologie Konstanty-Gutschow-Strasse 8 30625 Hannover, Germany
Distribution rights for North America, Canada, and Mexico by International Life Sciences Institute (ILSI) 1126 Sixteenth Street NW, Washington, DC 20036, USA
2nd Edition ISBN 978-3-642-64649-2 ISBN 978-3-642-60996-1 (eBook) DOI 10.1007/978-3-642-60996-1
Ist Edition
Library of Congress Cataloging-in-Publication Data. Endocrine system/T.e. Jones, e.e. Capen, U. Mohr eds. - 2nd ed. p. cm. - (Monographs on pathology of laboratory animals) Includes bibliographical references (p. ) and index. ISBN 3-540-59477-9 1. Laboratory animals-Diseases. 2. Veterinary endocrinology. 3. Endocrine glands- Diseases. 4. Rodents-Diseases. 5. Rodents as laboratory animals. 6. Pathology, Comparative. 1. Jones, Thomas Carlyle. II. Capen, Charles e. III. Mohr, U. (Ulrich) IV. Series. SF996.5.E5 1995616.4'027-dc20. 95-31393
This work is subject to copyright. AII rights are reserved whether the whole or part of the material is concerned, specifically the rights of translation, rcprinting, rcusc of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations arc liable for prosecution undcr the German Copyright Law.
© Springer-Verlag Berlin Heidelberg 1996
Originally published by Springer-Verlag Berlin Heidelberg 1996
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Foreword to the Second Edition
The International Life Sciences Institute (ILSI) is a nonprofit, worldwide foundation established in 1978 to advance the understanding of scientific issues relating to nutrition, food safety, toxicology, risk assessment, and the environment. By bringing together scientists from academia, government, industry, and the public sector, ILSI seeks a balanced approach to solving problems of common concern for the well-being of the general public. This volume is the first of the Second Edition of Monographs on Pathology of Laboratory Animals. The series is designed to facilitate communication among those involved in the safety testing of foods, drugs, and chemicals. The complete set covers cardiovascular, musculoskeletal, digestive, endocrine, genital, hemopoietic, nervous, respiratory and urinary systems, eye and ear, integument and mammary glands, and nonhuman primates. The series is intended for use by pathologists, toxicologists, and others concerned with evaluating toxicity and carcinogenicity studies. ILSI is committed to supporting programs to harmonize toxicologic testing, to advance a more uniform interpretation of bioassay results worldwide, to promote a common understanding of lesion classifications, and to encourage wide discussion of these topics among scientists. Scientific understanding and cooperation will be improved worldwide through the series and this international project. ILSI accomplishes its work through its branches and institutes. ILSI's branches currently include Argentina, Australasia, Brazil, Europe, Japan, Korea, Mexico, North America, Southeast Asia, and Thailand, and a focal point in China. The ILSI Health and Environmental Sciences Institute focuses on global environmental issues. ILSI Research Foundation includes the ILSI Allergy and Immunology Institute, ILSI Human Nutrition Institute, ILSI Pathology and Toxicology Institute, and ILSI Risk Science Institute.
Alex Malaspina President International Life Sciences Institute
Preface to the Second Edition
Approximately 10 years have elapsed since the first volume of the International Life Sciences Institute (ILSI) Monographs on Pathology of Laboratory Animals, Endocrine System was completed. New information of interest to pathologists has developed at a rather remarkable pace during the intervening years. Exceptional progress has been made in the routine identification of cell products in endocrine cells. A better understanding has developed of the mechanisms involved in cell metabolism, particularly involving toxins and carcinogens. Clear concepts have developed concerning the significance of some pathologic lesions in the endocrine system and their relation to human health and risk assessment. Standardized nomenclature has developed significantly during the 1O-year period since the first volume and is being utilized on an international basis. This has resulted in significant improvement in communication of pathologic data to regulatory agencies and in scientific publications worldwide. This monograph series and others sponsored by ILSI have produced a significant effect on improved communications and the international acceptance of standardized nomenclature. In this second edition, new formats have been used where more appropriate for the subjects to be covered. In many cases, the format used in the first edition still is useful. It is still necessary to recognize the morphologic features of pathologic lesions in order to identify them precisely, an essential step toward development of new insights into pathogenetic mechanisms and their use in decisions eventually applicable to public health. The role of the hypothalamus in the control of the endocrine system has been increasingly appreciated. Methods useful to pathologists will continue to develop and be applied to the pathologic lesions of the hypothalamus to understand their effect on the rest of the endocrine system. Approaches to evaluate possible xenobiotic-induced changes in the hypothalamus are presented in this edition. We are very grateful to the dedicated scientists from lands all around the world who have contributed to this volume. The authors are named in the list of contributors in the frontispiece of this volume, in the table of contents, and at the heading of each individual manuscript. The members of the editorial board are listed in the frontpiece. They are particularly to be thanked for their efforts in identifying authors and for the scientific review of individual manuscripts. The editors are especially grateful for the steadfast support of Dr. Alex Malaspina and to members of the ILSI staff and others who have helped in so many ways. We particularly wish to mention Ms. Sherri Lopez, Associate Editor and Manager of the Pathology and Toxicology Institute; Ms. Sharon Weiss, formerly the Associate Director of the Pathology and Toxicology Institute; as well as Ms. Frances DeLuca, Executive Assistant, Pathology and Toxicology Institute and Research Foundation.
VIII Preface to the Second Edition
We are grateful to Prof. Dr. Dietrich Goetze, Ms. Barbara Montenbruck, and others on the staff of Springer-Verlag for the quality of the finished book.
August 1995 T.e. Jones e.e. Capen U. Mohr
Contents
Pituitary .............................................. 1
Morphology and Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Functional and Pathologic Interrelationships of the Pituitary Gland and Hypothalamus in Animals Charles C. Capen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Histology, Ultrastructure, and Immunocytochemistry, Pituitary Gland, Rat R Yoshiyuki Osamura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Function and Morphology of the Rat Pituitary Gland, Combined Investigations by Means of an In Vitro Model Annamaria Baiocco, Claude E. Boujon, Gilberto E. Bestetti, Giovanni L. Rossi ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Hyperplasia and Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Modern Approaches to Classification of Pituitary Tumors in Human Subjects and Animals L. Stefaneanu and K. Kovacs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Histochemical Identification of Hormones in Pituitary Tumors, Rat R Yoshiyuki Osamura and Shozo Takayama. . . . . . . . . . . . . . . 66
Adenoma and Carcinoma, Pars Distalis, Anterior Pituitary Gland, Rat William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 71
Adenoma, Pars Intermedia, Anterior Pituitary, Rat William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 82
Craniopharyngioma, Pituitary Gland, Rat William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 86
Pituitary Tumors Induced by Estrogen, Rat RYoshiyuki Osamura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Pituicytoma, Neurohypophysis, Rat William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 94
Gangliocytoma, Pituitary Gland, Rat James E. Heath .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Pituitary Gland in the Human Growth-Releasing Factor Transgenic Mouse R Yoshiyuki Osamura . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
X Contents
Nonneoplastic Lesions 106
Cysts, Pituitary, Rat, Mouse, and Hamster William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 106
Inflammation, Pituitary Gland: Rat, Mouse, and Hamster William W. Carlton and Christian L. Gries. . . . . . . . . . . . . . . . . 109
Cystoid Degeneration Due to Diethylstilbestrol, Anterior Pituitary, Mouse Alexander M. Cameron and Winslow G. Sheldon. . . . . . . . . . . 110
Craniopharyngeal Derivatives in the Neurohypophysis, Rat and Hamster Eberhard Karbe and Heinrich Ernst. . . . . . . . . . . . . . . . . . . . . . . 114
Hypothalamus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Stereotaxic Map, Cytoarchitectonic and Neurochemical Summary of the Hypothalamic Nuclei, Rat Miklos Palkovits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Study of Pathologic Lesions in the Hypothalamic-Pituitary System, Rat Giovanni L. Rossi, Gilberto E. Bestetti, and Claude E. Boujon .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Hypothalamic-Pituitary Lesions Associated with Diabetes and Aging, Rat Gilberto E. Bestetti and Giovanni L. Rossi. . . . . . . . . . . . . . . . . 177
Hypothalamic-Pituitary-Adrenal Axis of Genetically Obese fa/fa Rats Gilberto E. Bestetti, Corinne Guillaume-Gentil, Fran<;oise Rohner-leanrenaud, Giovanni L. Rossi, Francesca Abramo, and Bernard leanrenaud . . . . . . . . . . . . . . . 186
Pineal Gland. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Functional Morphology of the Mammalian Pineal Gland Michal Karasek and Russell. Reiter . . . . . . . . . . . . . . . . . . . . . . 193
Tumors of the Pineal Gland, Rat Adalbert Koestner and Henk A. Solleveld 205
Thyroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Contents XI
Morphology and Function
Hormonal Imbalances and Mechanisms of Chemical Injury of Thyroid Gland
217
Charles C. Capen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Ectopic Thyroid, Mouse Charles H. Frith. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Ectopic Thyroid, Rat George A. Parker and Marion G. Valerio. . . . . . . . . . . . . . . . . . 240
Ectopic Thymus, Thyroid, Rat George A. Parker and Marion G. Valerio. . . . . . . . . . . . . . . . . . 241
Hyperplasia and Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Follicular Cell Hyperplasia, Adenoma, and Carcinoma, Thyroid, Rat Gary A. Boorman and Michael R. Elwell . . . . . . . . . . . . . . . . . . 245
Adenoma and Carcinoma, Thyroid Follicular Cell, Mouse James E. Heath ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
C-Cell Hyperplasia, C-Cell Adenoma, and C-Cell Carcinoma, Thyroid, Rat Gary A. Boorman, Ronald A. DeLellis, and Michael R. Elwell ...................................... 262
Goiter, Nodular Hyperplasia, Adenoma, and Carcinoma of the Thyroid Induced by Amitrole and Ethylenethiourea, Rat Hiroyuki Tsuda ........................................ 275
Ganglioneuroma, Thyroid Gland, Rat James W. Crissman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Nonneoplastic Lesions ................................... 287
Lymphocytic Thyroiditis, Rat George E. Sandusky and Glen C. Todd. . . . . . . . . . . . . . . . . . . . 287
Parathyroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Pathobiology of Parathyroid Gland Structure and Function in Animals Charles C. Capen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Morphology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
Anatomy, Histology, and Ultrastructure, Parathyroid, Syrian Hamster Birgit Kittel, Heinrich Ernst, and Kenji Kamino . . . . . . . . . . . . 328
XII Contents
Anatomy, Histology, and Ultrastructure, Parathyroid, Mouse Birgit Kittel, Heinrich Ernst, and Kenji Kamino . . . . . . . . . . . . 328
Anatomy, Histology, Ultrastructure, Parathyroid, Rat Birgit Kittel, Kenji Kamino, and Heinrich Ernst. . . . . . . . . . . . 330
Ectopic Parathyroid, Mouse Charles H. Frith and Judith Fetters ....................... 333
Hyperplasia and Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Hyperplasia, Parathyroid, Syrian Hamster Heinrich Ernst, Birgit Kittel, and Kenji Kamino
Hyperplasia, Parathyroid, Rat
335
Kenji Kamino, Birgit Kittel, and Heinrich Ernst . . . . . . . . . . . . 338
Adenoma, Parathyroid, Syrian Hamster Heinrich Ernst, Paul-George Germann, and Kenji Kamino . . . 345
Adenoma, Carcinoma, Parathyroid, Rat Kenji Kamino, Heinrich Ernst, and Birgit Kittel . . . . . . . . . . . . 350
Pancreatic Islets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Hyperplasia and Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Hyperplasia, Adenoma, and Carcinoma of Pancreatic Islets, Mouse Charles H. Frith and Winslow D. Sheldon ................. 361
Pancreatic Islet-Cell Hyperplasia, Golden Hamster J.K. Frenkel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
Adenoma and Carcinoma, Pancreatic Islets, Rat James E. Heath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Adrenals .............................................. 379
Embryology and Morphology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Embryology, Adrenal Gland, Mouse Bernard Sass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Histology, Adrenal Gland, Mouse Charles H. Frith. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
Accessory Adrenocortical Tissue, Mouse Bernard Sass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Accessory Adrenocortical Tissue, Rat George A. Parker and Marion G. Valerio. . . . . . . . . . . . . . . . . . 394
Contents XIII
Immunohistochemical and In Situ Hybridization Analysis of Steroidogenic Enzymes for Study of Steroid Metabolism in Endocrine Organs Hironobu Sasano . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
Hyperplasia and Neoplasia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Cell Proliferation in the Adult Adrenal Medulla: Chromaffin Cells as a Model for Indirect Carcinogenesis Arthur S. Tischler. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Hyperplasia and Pheochromocytoma, Adrenal Medulla, Rat John D. Strandberg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Adrenal Medullary Tumors, Mouse Loic E. Longeart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Ganglioneuroma, Adrenal, Rat Gerd Reznik and Paul-Georg Germann. . . . . . . . . . . . . . . . . . . . 427
Neuroblastoma, Adrenal, Rat Gerd Reznik and Paul-Georg Germann. . . . . . . . . . . . . . . . . . . . 433
Focal Hyperplasia, Adrenal Cortex; Rat John D. Strandberg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Adenoma, Adrenal Cortex, Rat John D. Strandberg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
Adenocarcinoma, Adrenal Cortex, Rat John D. Strandberg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
Adenoma and Carcinoma, Adrenal Cortex, Mouse James E. Heath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
Nonneoplastic Lesions ................................... 455
Amyloidosis, Adrenal, Mouse Bernard Sass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
Lipogenic Pigmentation, Adrenal Corex, Mouse Charles H. Frith. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Lipogenic Pigmentation, Adrenal Cortex, Rat George A. Parker and Marion G. Valerio. . . . . . . . . . . . . . . . . . 462
Subcapsular-Cell Hyperplasia, Adrenal, Mouse Dawn G. Goodman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Chemically Induced Adrenocortical Degenerative Lesions John T. Yarrington and James F. Reindel. . . . . . . . . . . . . . . . . . 467
Nodular Cortical Hyperplasia, Adrenal, Thymectomized Mouse Frantisek Zak . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Lipid Hyperplasia, Adrenal Cortex, Rat Christian Landes, Georg Krinke, and Frantisek Zak . . . . . . . . . 481
XIV Contents
Lesions Due to Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Mouse Hepatitis Viral Infection, Adrenal, Mouse Stephen W. Barthold. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Adrenovirus Infection, Adrenal, Mouse Stephen W. Barthold. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490
Murine Cytomegalovirus Infection, Adrenal, Mouse Stephen W. Barthold. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Polyoma Virus Infection, Adrenal, Mouse Stephen W. Barthold. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Lymphocytic Choriomeningitis Virus Infection, Adrenal, Mouse Stephen W. Barthold. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Adrenal Necrosis Due to Besnoitiosis, Golden Hamster 1.K. Frenkel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501
Subject Index .......................................... 505
Contributors
Francesca Abramo, D.V.M. Research Assistant, University of Pisa, Pisa, Italy
Annamaria Baiocco, D.V.M. Research Assistant, University of Bern, Bern, Switzerland
Stephen W. Barthold, D.V.M., Ph.D. Professor of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
Gilberto E. Bestetti, D.V.M. Professor of Animal Pathology, University of Bern, Bern, Switzerland
Gary A. Boorman, D.V.M., M.S., Ph.D. Chief, Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
Claude E. Boujon, D.V.M. Research Assistant, University of Bern, Bern, Switzerland
Alexander M. Cameron, D.V.M., Ph.D. R.W. Johnson, Pharmaceutical Research Institute, Spring House, Pennsylvania, USA
Charles C. Capen, D.V.M, Ph.D. Professor of Veterinary Pathobiology and Chairman, Department of Veterinary Biosciences, Professor of Endocrinology, Department of Internal Medicine, College of Medicine, The Ohio State University, 1925 Coffey Road, Columbus, Ohio, USA
William W. Carlton, D.V.M., Ph.D. Leslie Morton Hutchings Distinguished Professor of Veterinary Pathology, Emeritus Purdue University, West Lafayette, Indiana, USA
James W. Crissman, D.V.M., Ph.D. The Dow Chemical Company, Midland, Michigan, USA
Ronald A. DeLellis, M.D. Professor of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA
Michael R. Elwell, D.V.M., Ph.D. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
XVI Contributors
Heinrich Ernst, D. V. M. Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany
Judith Fetters System Analyst, National Center for Toxicological Research, Jefferson, Arkansas, USA
J.K. Frenkel, M.D., Ph.D. Professor Emeritus, University of Kansas, Adjunct Professor, University of New Mexico, Santa Fe, New Mexico, USA
Charles H. Frith, D.V.M., Ph.D. Consultant, Toxicology Pathology Associates, Little Rock, Arkansas, USA
Paul-Georg Germann, D.V.M. Institute for Pathology and Toxicology, Byk Gulden, Hamburg, Germany
Dawn G. Goodman, V.M.D. PATHCO, Inc., Ijamsville, Maryland, USA
Christian L. Gries, D.V.M., Ph.D. Department of Toxicology and Pathology, Eli Lilly and Company, Greenfield, Indiana, USA
Corinne Guillaume-Gentil, Ph.D. Research Assistant, University of Geneva, Geneva, Switzerland
James E. Heath, D.V.M. Senior Pathologist, Southern Research Institute, Birmingham, Alabama, USA
Bernard Jeanrenaud, M.D. Professor of Medicine, University of Geneva, Geneva, Switzerland
Kenji Kamino, M.D. Hannover Medical School, Hannover, Germany
Michal Karasek, M.D., Ph.D. Professor, Medical University, Lodz, Poland
Eberhard Karbe, Dr.med.vet., Ph.D. Professor, Bayer AG, Wuppertal, Germany
Birgit Kittel, Dr.med.vet. BASF AG, Abt. Toxikologie, Ludwigshafen, Germany
Adalbert Koestner, D.V.M., Ph.D. Professor and Chair, Emeritus, Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA
Contributors XVII
Kalman Kovacs, M.D., Ph.D., D.Sc, FRCP(C), FCAP, FRC(Path) Professor of Pathology, St. Michael's Hospital, Toronto, Canada
Georg J. Krinke, MVDr., C.Sc., FVH Path. Head of Experimental Pathology, CIBA GEIGY AG, Crop Protection, Basel, Switzerland
Christian Landes, Dr.med.vet., FTA Path. Senior Pathologist, Deputy Head of Toxicological Pathology, CIBAGEIGY Ltd, Crop Protection, Basel, Switzerland
Loic E. Longeart, D.V.M. Group Leader, Pathology Department, Pfizer Centre de Recherche, Amboise, France
R. Yoshiyuki Osamura, M.D. Professor of Pathology, School of Medicine Tokai University, Kanagawa, Japan
Miklos Palkovits, M.D., D.Sc., Ph.D. Professor of Anatomy, First Department of Anatomy, Semmelweis University Medical School, Budapest, Hungary, and Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland, USA
George A. Parker, D.V.M. Mountainside, New Jersey, USA
James F. Reindel, D.V.M., Ph.D. Staff Pathologist/Senior Research Associate, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co, Ann Arbor, Michigan, USA
Russel J. Reiter, Ph.D., D.Med. Professor, The University of Texas Health Science Center, San Antonio, Texas, USA
Gerd K. Reznik, D.V.M., Ph.D. Director, Institute for Pathology and Toxicology, BYK Gulden, Hamburg, Germany
Franl50ise Rohner-Jeanrenaud, Ph.D. Research Associate, University of Geneva, Geneva, Switzerland
Giovanni L. Rossi, M.D. Professor of Experimental Pathology, University of Bern, Bern, Switzerland
George E. Sandusky, Jr., D.V.M., Ph.D. Lilly Research Laboratories, Greenfield, Indiana, USA
Hironobu Sasano, M.D. Tohoku University School of Medicine, Sendai, Japan
XVIII Contributors
Bernard Sass, V.M.D.(t) Pathologist, Registry of Experimental Cancers, National Institutes of Health, Bethesda, Maryland, USA
Winslow D. Sheldon, D.V.M. National Center for Toxicological Research, Pathology Associates, Inc., Jefferson, Arkansas, USA
Henk A. Solleveld, D.V.M., Ph.D. Director, Morphologic Pathology and General Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA
Lucia Stefaneanu, Ph.D. Assistant Professor of Pathology, St. Michael's Hospital, University of Toronto, Toronto, Canada
John D. Strandberg, D.V.M., Ph.D. Director, Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Shozo Takayama, M.D. Vice Director, Cancer Institute, Tokyo, Japan
Arthur S. Tischler, M.D. Professor of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA
Glen C. Todd, V.M.D., Ph.D. Research Advisor, Retired, Crawfordsville, Indiana, USA
Hiroyuki Tsuda, M.D., Ph.D. Chief, Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan
Marion G. Valerio, D.V.M. Rhone Poulenc Rorer, Collegeville, Pennsylvania, USA
John T. Yarrington, D.V.M., Ph.D. Pathologist, Battelle Memorial Institute, Columbus, Ohio, USA
Frantisek Zak, M.D., Ph.D., FMH(Path.) Associate Professor of Pathology, Consultant in Toxicological Pathology and Pathology of Tropical Diseases, CIBA-GEIGY AG, Basel, Switzerland
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