Thymic epithelial tumors are rare and mostly malignant human neoplasms charac- terized by a fascinating variety of morphological features and an unrivaled frequency of associated autoimmune diseases. As a consequence, a myriad of complex diagnostic and clinical problems ensues in patients with these tumors. Since only a few specialists in each country are familiar with these problems, this volume intends to summarize the state of the art of thymic epithelial tumor pathology and biology and treatment protocols. The vol- ume is also designed to promote the interaction between scientists from a variety of disci- plines and physicians treating thymoma patients. In the first part of the volume, morphological and immunohistological criteria are given for the various subtypes of thymic epithelial tumors. The two competing classifica- tions and nomenclature systems existing to date are jointly considered. In addition. mor- phological overlaps between organotypic and nonorganotypic thymic epithelial tumors are stressed, since they may have a major bearing on diagnostic and therapeutic strategies. The second part of the volume is devoted to recent data on normal T-cell maturation and the impact of abnormal T-cell development in thymic epithelial tumors on the development of paraneoplastic autoimmunity. Multicolor flow cytometry. the human/SCI[}-mouse system, transgenic mouse technology, and T-cell cloning techniques have greatly contributed to this fascinating field of research.

The identification and quantitation of environmental risk in humans is one of the main problems to be solved in order to improve the protection of individuals and of human populations against phys ical and chemical pollutants. Epidemiology plays a central role in the evaluation of health risk directly in human populations. In this volume are collected 33 lectures presented at the AS course on "Epidemiology and quanti tat ion of environmental risk in humans from radiation and other agents: potential and limitations," sponsored by NATO and Italian Association of Radiobiology and or ganized by ENEA. The course has been devoted to a number of aspects of environ mental risk analysis and evaluation based on epidemiological in vestigation. Basic epidemiological concepts and methods have been reviewed. Fundamentals of dosimetry and microdosimetry were presented in re lation to the contribution of epidemiology in defining the dose effect relationships for radiation carcinogenesis and its relation with age, sex and ethnicity. The mechanisms of carcinogenesis as a multi-stage process were illustrated. One of the main topics was 'cancer epidemiology' and its cor relation with: - occupational and non-occupational exposure to ra diation - diagnostic and therapeutic irradiation - cancer proneness - hereditary and familiar diseases - abnormal response to carcino gens - environmental pollution in air and water - exposure to radon in mines and in building material - atomic bomb explosion - chemo therapy - dioxin and related compounds."

In this volume are collected 30 papers, 9 round table discus sions and 11 communications presented at the ASI Course on "The use of human cells for the evaluation of risk from physical and chemical agents," sponsored by NATO and organized by ENEA. The aim of the Course was to present different scientific ap proaches and technical advices in order to get dose-effect relation ships which are the basis for risk evaluation. The scientific back ground which is behind this approach was extensively discussed. Emphasis has been given to the use of human cells or human data in order to attempt to have a correct and realistic evaluation of the damage in humans. There are many criticisms on the use of animal data for human risk evaluation because of differences between species and between strains within the same species: differences in metabolism, activa tion processes and DNA repair ability makes uncertain the extrapola tion of animal data to humans. Also data obtained using specific strains or highly inbred strains in order to reduce the variance are not applicable due to the heterogeneity of the human population connected with individual responses. In this respect only the use of human cells enable us to detect the individual variability and to identify sensitive subpopu lations that would be at greater risk. My appreciation to Pieranita and Alberto Castellani for the as sistance during the meeting and to Giuseppe Biondi for his help in some of the editorial work."

The papers collected in this volume were presented at an International Conference that, with the same heading, was held at the Verona University, Italy, in June 1986. The meeting was organized by the Institute of Forensic Hedicine and the Laboratory of Medical Research of the University in cooperation with the Italian Group for Mass Spectrometry in Biochemistry and Medicine. The aim of the symposium was bringing together people, work ing in different branches of the wide field of modern analytical sciences, for promoting inter-disciplinary discussions and exchange of experiences. Actually it was felt that most of the analytical problems that very often have to be faced in quite different fields (chem istry, pharmacology, medicine, biology) have similar solutions, that could be made much easier by closer contac'cs among researches of these disciplines. Original papers and invited rewiews presented during the 3 days of the conference by leading experts gave an up-to-date outline of the modern analytical methods applied in pharmaceuti cal, biomedical and forensic sciences and a glimpse of the future perspectives.

This book is actually a product of efforts of many people, not only of the authors. W ide investigations of marine mammals began in Russia (that time, in the former Soviet Union) in the 1960s when a few teams of enthusiasts founded in captivity experimental stations intended for keeping dolphins and seals and for performing experimental studies of these fascinating animals. It was a time when attention of many people throughout the world was attracted to dolphins and other marine mammals due to appearance of oceanariums and dolphinariums, which demonstrated unique capabilities of these animals. So scientists in many countries concentrated on studies of them. There was much to learn about the morphology, physiology, and psychology of marine mammals, and investigators spending their time and efforts on studies in this field were rewarded by a number of surprising findings. The authors of this book represent one of such research teams focused on the neuro- and sensory physiology of marine mammals. A few decades of studies naturally resulted in the idea to summarize in a book both the results of these studies and a large body of data in adjacent fields. Our goal was to synthesize the many research findings and the present knowledge on sensory capabilities and mechanisms of sensory systems of aquatic mammals. We realize, however, that the appearance of this book was made possible due to the help and assistance of many colleagues.

Our purpose is to provide understanding for appropriate use of metals in a technical society. Knowledge of metal toxicity is needed for the preven tion, prediction, diagnosis, and therapy of adverse reactions from excess metals in mammals. Metal Toxicity in Mammals is presented in two volumes. Volume 1, Physiologic and Chemical Basis for Metal Toxic ity, provides the basis for understanding the toxic actions of metals recorded in Volume 2, Chemical Toxicity of Metals and Metalloids. The details and bases for many concepts summarized in Volume I are given, with appropriate references, in Volume 2. Thus, references for specific items in Volume 2 are not generally given in Volume 1. The authors reviewed the known toxicity of several heavy metals in anticipation of their use as multinutrient markers for NASA. As more and more metals were considered, the need for a complete review became obvious. This treatise supplants onerous searches of metal-toxicity litera ture up to 1975 and reviews the toxicity of all the metals of the periodic table on the basis of available relevant data. Books on pharmacological, nutritional, medical, veterinary, or industrial toxicity contain information about selected metals. More complete data about metals of public concern, such as mercury, lead, and cadmium, may be found in numerous books and reviews. The reader should refer to general texts and basic reference works, when specific references are not given, for general information."

When first developed, chlorinated pesticides such as DDT, dieldrin, and mirex were received with open arms, quickly becoming popular as effective, economic agents against pests. But evidence began to mount that residues of these chemicals remained in the environment, not breaking down, often appearing in plants and animals. By the late seventies many pesticides had achieved a terrible notoriety and were subsequently banned in a number of countries. Of tremendous concern, then, is the persistence of pesticides in the environment. The major thrust of research and development in the area of pesticides has properly been the creation of substances that are both effective and degradable. Yet in order to successfully promote the use of biodegradable pesticides, one must fully understand the mechanism of degradation, and it is to this vital subject that we address ourselves in the present volume. According to the Biodegradation Task Force, Safety of Chemicals Com mittee, Brussels (1978), biodegradation may be defined as the molecular degradation of an organic substance resulting from the complex action of living organisms. A substance is said to be biodegraded to an environmentally acceptable extent when environmentally undesirable properties are lost. Loss of some characteristic function or property of substance by biodegradation may be referred to as biological transformation."

Pituitary Disease brings together an international panel of experts who summarize the most recent and exciting advances in the diagnosis and treatment of pituitary disease. Coverage includes pathogenesis and pathology of pituitary tumors; clinical scenarios underpinning each type of pituitary tumor as well as their diagnosis and treatment. It is a useful resource for clinicians, students or researchers with an interest in the pituitary and its disorders.

Despite recent progress in many areas of treatment and control, cancer remains a frightening threat to everyone. While scientists have known for decades that the majority of human cancers are caused by environmental agents such as radiation and the chemicals in cigarette smoke, not everyone who smokes gets lung cancer. Furthermore, many people who assiduously avoid all possible risk from smoking, diet, and pollution still succumb to some form of cancer later in life. Does this mean that there is an element of blind chance in the underlying mechanisms of human carcinogenesis? To what extent do genetic influences play a role in determining the cancer risk of individuals? A number of `cancer families', in which several closely related individuals have suffered from various specific forms of cancer, have been studied by genetic epidemiologists. However, for the majority of cancer cases, little or no discernible genetic influence or family history is found. Recent research has discovered that for many of these `sporadic' (non-familial) cancer cases, defects or aberrations in certain metabolic genes not previously associated with genetic cancer risk may contribute to either causing the disease or at least increasing the chances of developing cancer. It is therefore possible that much of what has previously passed for `bad luck' may turn out to be a new type of `bad genes'. Genetic Susceptibility to Cancer explains that this new idea of `bad genes' may contain an unexpected positive side. The carcinogenic effects of these metabolic genes, unlike those of the oncogenes and tumor suppressor genes that are responsible for the inherited cancer syndromes, can potentially be overcome or nullified. Genetic Susceptibility to Cancer will provide a valuable reference for health professionals, researchers, clinicians and biomedical scientists who are interested in the current thinking in this critically important area of cancer management.

The Color Atlas of "Xenopus laevis" Histology provides the first central source on the microscopic anatomy of cells, tissues, and major organs of the adult South African clawed frog, Xenopus laevis. For many years, X. laevis has been a highly popular experimental animal model in many areas of research. The recent development of transgenic Xenopus technology offers the promise that this animal model will be utilized more than ever before. The purpose of this book is to provide the active researcher with a central source of high quality light microscopic color images of the tissues of X. laevis, to aid in the identification of the cells and tissues of interest.

Major features of this atlas include:

*277 large, colorful, high resolution light microscopic images of cells, structures, tissues and organs;
*Clear, detailed labeling of important structures in all images;
*Concise, easy-to-read descriptions of histological organization and functions;
*Colorful three-dimensional illustrations that simplify complex structure;
*Detailed presentation of cranial structures and organization;
*Easy-to-use cross-referenced index;
*Bundled CD/ROM containing all images for easy downloading.

Male urogenital glands (also named male accessory sex glands) have received relatively little attention from electron microscopists, with the possible exception of the prostate gland. Moreover, even though comparative studies have clearly shown that these glands exhibit species-dependent features, very few studies, scattered over various publications, are available on the urogenital glands of man. This volume, the 11th of the series on Electron Microscopy in Biology and Medicine, presents an unprecedented collection of information on the functional microanatomy and cytoarchitecture of these organs in humans. Through the integration of transmission and scanning electron microscopy with a variety of modern techniques, it documents the most important aspects of the histophysiology of these glands from their development to some pathological alterations. In order to cover some key mechanisms of their cell biology, such as the action of sex hormones, the epithelio-mesenchymal interactions, and the dynamic of the secretory process, reports on human organs have been supplemented by some studies on experimental animals. The outstanding level of the contributions and the quality of the illustrations make this book, which has been compiled by some of the world authorities on the topic, a work of reference for students, scientists, and professionals interested in biomedical foundations of andrology, as well as a stimulus for future research in this exciting and relatively neglected chapter of human reproduction.

To meet the needs of an ever-growing world population for food and fiber, agriculture uses an arsenal of chemicals to control insects, weeds and other pests that compete with man in the agricultural arena. In addition to their intended effect, many of these biologically active materials affect non-target organisms including man himself. There is concern about the resulting occupational exposure of those who work in agriculture and the environmental health of those who live in rural areas. Unintended side effects from the use of agricultural chemicals are further complicated by the dispersal of these substances well beyond the area of immediate use, through food chains, atmospheric transport, irrigation runoff, percolation to and diffusion through ground water, sometimes giving rise to public health and environmental problems at a distance from the place of application. In addition to toxic substances introduced into the agro ecosystem by man, one must be concerned about naturally occurring agents including mfcotoxins, plant poisons, infective biological agents and the levels of certain heavy metals. The formation of toxic substances, many of them mutagenic, during cooking and other processing of food is a related problem. While acute effects are more immediate and somewhat readily discerned, chronic and genetic effects tend to be more obscure and sometimes surface in a crisis situation long after substantial damage has been sustained. Genotoxicity assays and epidemiological studies play increasing roles in predicting and evaluating long term effects of low-level exposure to toxic materials."

In Volume 1 of this series, attention was focused on neuropoisons of animal origin. In the present volume, attention has been shifted to poisons of plant origin. In both cases, we have attempted to identify those poisons for which there is a large measure of clinical or research interest. Our efforts in compiling the series have been aided by three groups of individuals. First, we are grateful to the investigators who contributed chapters. Their labors are the substance of this two-volume work. Second, we are pleased to acknowledge the support of Mr. Seymour Weingarten and Plenum Press in our project. And third, we have been immeasurably aided by our assistants, Mrs. Ruby Hough in New York City and Mrs. Helena Walsh in Canberra. To all these persons, we are indebted. Dr. Lance L. Simpson Dr. David R. Curtis New York City Canberra vii Contents Chapter 1 Reserpine 1 by Theodore A. Slot kin I. Introduction .......................................... .

During the past two decades, research on animal, plant, and microbial toxins has expanded rapidly, and new and exciting information has appeared to clarify both the clinical and therapeutic aspects of intoxication and, even more impor tant, to help us understand more exactly the structure and the mode of action of toxins on a molecular basis. Because of the interdisciplinary nature of toxin research, it is of vital impor tance that workers specializing in its different aspects should make a particular effort to exchange and keep up with new developments in this rapidly-expanding field. This has been one of the main purposes of the series of international meetings that have been held over the past ten years. The increasing interest in the results of toxin research can be explained partly by the growing general preoccupation with pollution and its toxic effects, which means that more anq more specialists in other fields are finding it necessary to keep in touch with current research into naturally occurring toxins. The papers in these volumes were presented at the Fourth International Symposium on Animal, Plant and Microbial Toxins, organized by the Inter national Society on Toxicology, held in Tokyo in September, 1974. The editors have decided to include both original reports and review articles, arranged according to disciplines. Editing has been kept to the minimum necessary for adequate comprehension of the materials.

Im Vergleich zum Humansport ist der tierische Athlet im Reitsport als gleichberechtigter Sportpartner den kunstlichen Leistungssteigerungen ohne Mitspracherecht ausgesetzt. In Anbetracht der erheblichen Zunahme von Dopingfallen im nationalen und internationalen Reitsport mussten sich die Pferdesportverbande unter Berucksichtigung des World-Anti-Doping Codes materiell- und verfahrensrechtlich neu positionieren. Ziel dieser Arbeit ist es zu beleuchten, inwieweit die Regeln des WADA- und NADA-Codes, die in erster Linie fur den Humansport konzipiert wurden und fur den Pferdeport nur rudimentare Regelungen enthalten, durch den nationalen und internationalen Pferdesportverband unter Beachtung des jeweils geltenden Rechts umsetzbar sind und inwieweit langen sowie kostenintensiven Dopingverfahren vor den staatlichen Gerichten zugunsten der Sportgerichtsbarkeit ein Ende gesetzt werden kann. Vor diesem Hintergrund gilt es einen internationalen Entscheidungseinklang in der sportrechtlichen Anti-Doping Rechtsprechung mithilfe der Sportschiedsgerichtsbarkeit weiter zu fordern und zu foerdern.

Ensuring the well-being of animals is a primary concern for every veterinary practice. Split into easily accessible sections, part one of this book outlines the origin of animal behavior and how this has adapted to the domestic environment. Part two focuses on the role of the veterinary practice in preventing undesirable behavior, such as practice design, socialization classes and communication with owners. Part three gives practical advice for handling dangerous animals, discussing options such as euthanasia and working with referral veterinarians. Behavioral problems remain the number one cause of companion animal euthanasia; this book seeks to improve the situation for all involved.

The Symposium on Organ and Species Specificity in Chemical Carcinogenesis was held March 1981 in Raleigh, North Carolina. Dr. James Miller concluded this Symposium with these remarks: "Without a doubt all of us would agree this has been a very successful symposium in illustrating a very wide range of chemical, stereochemical, biochemical, metabolic, molecular, and biological factors in chemical carcinogenesis. I think it is noteworthy that many of the discussions have dealt with pharmacodynamic, or toxicodynamic, factors that can influence the biological activities of the extremely wide range of structures that we choose to call chemical carcinogens. I sincerely hope that after this symposium everyone here will realize the very great need we have for further information on these agents in the species we profess to be working for, the human species. We badly need an adequate data base on human organs, human tissues, human cells, human subcellular preparations, and human body fluids. I don't think we can rely on extrapolations of data on chemical carcinogenesis from experimental animals to humans, no matter how sophisticated or plausible these extrapolations may seem, until we know far more about chemical carcinogenesis in humans. Now, I'd like to add a somewhat personal note. As many of you know, my wife and I have shared a joint career of some 40 years in this field, and I'd like to emphasize in these closing remarks the factor of youth.

Concern is often expressed that our environment may include an increasingly large variety of mutagens, but the extent of the potential hazard they pose has yet to be fully evaluated. A variety of empirical procedures has been devised with which to estimate the mutagenic potency of suspect agents, and the relative merits of different tests are currently under debate. Although such tests are of great value, and are indeed indispensable, they are not, nevertheless, sufficient. In the long term, accurate estimation of hazard will also require a better understanding of the various mechanisms of mutagenesis, and in many instances these remain remarkably elusive. Our knowledge and appreciation of the problem has increased substantially over the last few years, but the precise way in which many mutagens cause mutations is not yet known. The aims of this conference were therefore two-fold. The first was to survey present information about mutagenic mechanisms, drawing together data from work with various experimental approaches and organisms, in order to discern the principles governing the action of different mutagens. The second was to examine the implications of such principles for the execution and evaluation of test procedures, and critically assess the research areas that need further attention in order to improve the interpretation of test results. Chris Lawrence v ACKNOWLEDGEMENT We gratefully acknowledge the support provided for this Conference by the U., S. Department of Energy, The Foundation for Microbiology, Exxon Corporation and the University of Rochester

During the past two decades, research on animal, plant, and microbial toxins has expanded rapidly, and new and exciting information has appeared to clarify both the clinical and therapeutic aspects of intoxication and, even more impor tant, to help us understand more exactly the structure and the mode of action of toxins on a molecular basis. Because of the interdisciplinary nature of toxin research, it is of vital impor tance that workers specializing in its different aspects should make a particular effort to exchange and keep up with new developments in this rapidly-expanding field. This has been one of the main purposes of the series of international meetings that have been held over the past ten years. The increasing interest in the results of toxin research can be explained partly by the growing general preoccupation with pollution and its toxic effects, which means that more and more specialists in other fields are finding it necessary to keep in touch with current research into naturally occurring toxins. The papers in these volumes were presented at the Fourth International Symposium on Animal, Plant and Microbial Toxins, organized by the Inter national Society on Toxinology, held in Tokyo in September, 1974. The editors have decided to include both original reports and review articles, arranged according to disciplines. Editing has been kept to the minimum necessary for adequate comprehension of the materials.

There is general agreement that increased environmental pollution poses a potential health hazard to humans and that effective control of such genetic injury requires monitoring the exposed individuals for genetic damage and identifying chemicals that may cause mutation or cancer. Tests available for identifying mutagens or carcinogens range from relatively simple, rapid assays in prokaryotes and test systems utilizing mammalian cells in tissue culture to highly elaborate tests in intact animals. No single test can provide data for an unequivocal assessment of the mutagenicity of a given chemical and the risk it might pose to human health. A tier approach, therefore, was suggested for mutagenicity testing in which the suspected agents would be initially evaluated with simple, inexpensive tests that would give qualitative results. Chemicals found to be positive in the first-tier testing would then be evaluated with more complex tests, including those based on mammalian cells in culture. Testing in the final tier requires whole-animal studies, and is expensive and time-consum ing, and even the results from these studies need to be extrapolated for human risk assessment. The mutation systems based on whole animals require scoring large num bers of animals, and therefore are not practical for the routine testing of muta gens. As an alternative to monitoring the pedigree, cells from exposed individ uals may be considered for screening for point mutations through the use of an appropriate marker protein."

Two questions could not be avoided in the avant-propos of this book; (i) what is the importance to man of ruminant livestock, and (ii) what results of practical relevance in the growing mountain of scientific verbiage could be found in the Proceedings of this Symposium. Herbivores are an integral and critical part of the natural ecosystem which must be preserved because of their impact on human welfare. Wh at makes ruminants especially important to man is that they can thrive on fibrous forage and are thus the only viable enterprise over much of the earth's surface where crop growing is impracti cable. They contribute a wide array of products in addition to 50000 000 tonnes ofmeat (1977) and represent a 'capital reserve' that can be drawn upon in times of emergency: milk for example (450000000 tonnes) can make the difference between subsistence and starvation. About 60% of the world's meat and 80 % of the milk are produced by one third of the world ruminant population in the developed regions and as much as 99 % of the power for agriculture is provided by the ruminant population in developing countries. For the next two decades, a probable increase by 30 % for . cattle and buffalo and more than 40 % for sheep and goats is expected by improving health, fertility, nutrition and genetic potential rather than feed resources."

Poisons are topics of multidisciplinary concern. The clinician and the pathologist are sensitive to instances of human poisoning. The laboratory researcher, whether pharmacologist, physiologist, or biochemist, is oriented toward molecular modes of poison action. Both clinician and researcher are eager to learn of poisons that can be used as therapeutic agents or methodological tools. This volume is an attempt to underscore the multidisciplinary charac ter of neuropoisons. Six poisons of animal origin which are receiving considerable clinical and research attention are discussed. Each poison is presented first as a clinical entity, then as a topic of investigative research, and finally as an agent useful to the study of nerve function. Because no single volume on neuropoisons can be exhaustive, an attempt at balance is offered as compensation. Two snake venoms, two marine poisons, and two bacterial toxins are presented in detail. In the sequel to this volume, attention will be focused on representative neuro poisons of plant origin."

This publication contains the proceedings of a seminar held in Brussels on November 8-9, 1988. The title of the seminar was "Reducing the costs of disease by improving resistance through genetics." The seminar was held as an activity of the Community Programme for the Coordination of Agricultural Research, 1984-1988. Costs of disease depend on losses caused by morbidity, mortality and production decreases and on the costs of preventive measures including vaccination and medication. Production losses often contribute a major portion to the total costs. To reduce costs of disease preventive measures like vaccination, preventive medication and hygienic procedures are applied. Genetic resistance is an attractive preventive measure because of its consistent nature in the next generations, because it precludes veterinary services and because there are no side-effects. Constraints are the long term investment, relatively slow progress per generation (in combination with production traits) and the considerable lack of knowledge about inheritance of resistance mechanisms in farm animals.

This third volume of articles dealing with advances in animal welfare science and philosophy covers a wide variety of topics. Major areas of discussion include the ethics and use of animals in biomedical research, farm animal behavior and welfare, and wildlife conservation. Three articles dealing with aspects of equine behavior and welfare cover new ground for this companion species. An in-depth study of the destruction of Latin America's tropical rain forests links the need for conservation and wildlife protection with the devastating impact of the international beef (hamburger) industry, and also highlights serious welfare problems in the husbandry of cattle in the tropics. Papers from a recent symposium at Moorhead State University, Animals and Humans: Ethical Perspectives have been included in this volume. Many of these are "benchmark" papers presenting the most up-to-date and documented evidence in support of animal welfare and rights. Articles oppos ing these position papers are included since they were part of the symposium, and because they provide the reader with a deeper understanding of the arguments given in support of various forms of animal exploitation. While there is no intent to endorse these views by publishing them, it should be acknowledged that without an open and scholarly exchange of opposing of constructive exchange and conflict resolution will views, the possibility remain remote."

Toph's in Chemical Mutagenesis is a new series dedicated to studies in the areas of environmental chemical mutagenesis and genetic toxicology. In this series we will explore some of many topics that are emerging in these rapidly developing fields. The purpose of the present volume is to attempt to organize and compare the genotoxic properties of the N-nitroso compounds. This is a particularly interesting class of compounds because of the problems encountered with the Salmonella assay of Ames in generating both false positive and false negative results. The battery approach using a number of assay systems seems more appropriate to evaluate chemicals in this class. Topics to be discussed in other volumes in this series include single-cell mutation monitoring systems, the detection of genetic damage in mammalian germ cells, the mutagenicity of pesticides, problems in monitoring human populations in genetic toxicology, and a glossary of terms in genetic toxicology. All of these books are in various stages of development and should appear within the next few years. Frederick J. de Serres Series Editor vii Preface During the past ten years there has been an explosive development in the number of short-term tests to predict the biological risks, especially risks of cancer, in exposure to xenobiotic chemicals. The number of published articles in this area has reached many thousands a year and there are several new journals devoted almost entirely to the presentation of the results obtained in these tests.