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

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© 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