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.

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.

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.

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.

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."

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.

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."

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."

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.

Approximately five years have elapsed since the Conference on "Tick-borne Diseases and their Vectors" (Wilde, 1978, University of Edinburgh) was held at the Centre for Tropical Veterinary Medicine in Edinburgh. Theileriosis was one of the main topics at that Conference and some 20 scientific presentations were given. Also in the same year a Workshop on "Theileriosis" was held at the Kenyatta Conference Centre in Nairobi (Henson & Campbell, 1977, IDRC, Ottawa). Both of these meetings provided a valuable up dating of theilerial diseases, and the Proceedings have been a constant source of reference for scientists in the ensuing years. The meetings played a significant role in setting the scene for a number of important advances which have been made since then. In February of this year, attention was focused on these advances when nearly 200 scientists from over 30 countries were assembled at the International Laboratory for Research on Animal Diseases in Nairobi for the international conference on "Advances in the Control of Theileriosis." The interest and concern shown in this subject has now grown to the extent that more than 70 scientific presentations were given over the course of a very busy week. An important facet of the Conference was the attention given to the control of Theileriosis, since this must be the ultimate aim of all those involved with the disease. Control will be difficult."

This second volume of papers dealing with scientific and ethical aspects of animal welfare covers a variety of topics and areas of inves tigation. It will be of particular interest to those readers seeking more insight into such subjects as farm animal welfare and humane husbandry systems; animal experimentation, especially in the field of psychology; and pain in animals, notably its recognition and alleviation. Several of our selections deal with very specific subjects that are germane to animal welfare: the use of T-61 for euthanizing cats and dogs, a new humane method of stunning for livestock and poultry, an innovative alternative to killing animals for rabies diagnosis, alterna tives to aversive procedures in teaching experimental psychology, and the need for improved theoretical modeling in animal experimentation and research design. Following the precedent set in the first volume of Advances in Animal Welfare Science, we have included several papers dealing with people's attitudes toward animals. These papers range from a consider ation of cultural influences and veterinary ethics to an examination of anthropomorphism, to a discussion of the linkage between the environ mental politics and perceptions of the Green Movement and animal welfare and rights. We wish to express our gratitude to the Manuscript Review Commit tee for the excellent work they have done and to the twenty contributors to this volume which we believe will do much to advance the science of animal welfare, and the well-being of animals under man's dominion."

This seminar referred to latent herpes virus infections in veterinary medicine, with emphasis on the domestic animals. The phenomenon of latency is of particular importance in veterinary medicine because it can jeopardize the successful control and eradication of diseases such as Aujeszky's disease and infectious bovine rhinotracheitis, diseases which are often the cause of great economic losses. For this reason, the Commission of the European Communities (CEC) realized the importance of summarizing the present state of knowledge on latent herpes virus infections in veterinary medicine. A seminar was therefore organized by the Federal Research Institute for Animal Virus Diseases in Ttibingen, Federal Republic of Germany, from September 21 to 23, 1982, as a part of the 'Animal Pathology Programme' of the CEC. The seminar was attended by 50 participants not only from the countries of the CEC, and 38 papers were selected for presentation. In veterinary medicine, more intensive investigations on the latency of animal herpes viruses have only relatively recently been initiated. In contrast, great efforts have been made for many years to elucidate latency in human and primate herpes viruses, and consequently the most considerable advances have been made in this field. Some of the most experienced scientists working on both systems were therefore invited. As a result, this seminar was the first occasion on which scientists from different countries and faculties investigating herpes virus latency had the opportunity to present and exchange their latest results. The.

Up to about twenty-five years ago, virtually the entire field of microscopy could be overseen and even practized by any active research worker. The rapid evolution which microscopy in its broadest sense has since undergone and which has contributed greatly to our insight in many fields of biological science and medicine has, however, lead to a progressive specialisation. Both experienced investigators in clinical and biological laboratories and post graduate students, confronted with a limited number of microscopic tech niques in their daily research work, have increasing difficulty in keeping (or obtaining) a general idea of the many time-honoured and new possibilities which microscopy has to offer. This book has been written with the aim of presenting general informa tion on light microscopic techniques, at a level somewhere in between booklets like those provided by microscope manufacturers (which are often too much focussed on the production program of a particular make) and very advanced treatises with a thorough mathematical treatment of all phenomena concerned. The physically oriented texts moreover often do not sufficiently take into account the practical situation in a medical or biolog ical laboratory; on the other hand, the value of really understanding what one is doing in using a microscopic technique is often underestimated. At tempt has been made, therefore, to present sufficient background informa tion necessary for a rational application of the different microscopical tech niques in their mutual relationship."

J.F. Crul The topic Legal Aspects of Anaesthesia is still rarely treated in book publications, but deserves increasing attention as more cases of litigation occur each year and anaesthetists also become more aware of the legal structure within which they practice their profession. I am happy to have been able to obtain the cooperation of experts in this field from various European countries. The contributing authors in this book come from both the anaesthesia and surgery side as well as from the jurisprudential background. As these two fields have their own professional jargon we have been very careful in using definitions, avoiding that a specific term might lead to misunderstanding and confusion. The international authorship did not facilitate this task. The subject of this book was also the topic of a meeting of the European Academy of Anaesthesiology held at the French Study Center, La Suquette, Saint Vincent Ie Palue~ held three years before publication of this book. The organizers G. Barrier, J.F. Crul, and J. Lassner felt the need for a book publication presenting the state of the art of anaesthesia and the law in European countries. With the present book this plan has been realized. During the meeting many subjects were thoroughly discussed and the editor considered a number of them as very informative and therefore these were included in this book.

This book, the first in an annual series, written by academicians scientists, philosophers and others-is not intended exclusively for an imal welfarists and conservationists. Since it is written* by scholars, it will appeal to a wide range of academic and professional readers who are involved with animals for scientific, economic, altruistic, and other reasons. While this first volume cannot cover the entire spectrum of animal welfare science-related topics, it does, in its diversity of con tributions, demonstrate the multi-faceted and interdisciplinary nature of the subject of this new series. Indeed, animals are as much an integral part of society as we are dependent upon them. The many interfaces between us and the billions of animals under our dominion (as well as the environment upon which the welfare of human and non-human animals alike is ultimately de pendent) have their separate features: trapping and wildlife manage ment; laboratory animal research; whaling and fishing; veterinary practice; agriculture and farm animal husbandry; horse racing and the ownership of animal companions; the propagation of captive wildlife and their preservation in the wild; the use of animals as companions and for the purposes of vicarious entertainment."

4* Doody's Review! Ideal for veterinary students, residents and clinicians, the fourth edition of this bestselling textbook has been fully updated in line with developments in research and teaching. The logical chapter progression reflects the stages in a clinical case work-up and how epidemiological concepts and methods contribute. This new edition provides guidelines for improving patient and population health outcomes, and detecting emerging diseases through systematic evaluation of patient encounters and electronic medical records incorporates new methodologies and concepts drawn from the recent veterinary practice literature updates chapter content including expanded coverage of risk, statistical and economic analyses, and surveillance for emerging diseases more than 60 examples of clinical research drawn from the international veterinary practice literature presented as structured abstracts; follow-up questions invite the reader to participate in the analysis of results online links to full text versions of more than half of structured abstracts and more than 40% of the book's 174 literature citations updates the listing and review of public and private online resources, including guidelines for online literature searching and critical evaluation of clinical reports. Today's veterinary curricula places greater emphasis on experiential/problem-based learning versus discipline-oriented instruction. This fourth edition is ideally suited to introduce epidemiologic concepts and methodologies to veterinary students in the context of the patient encounter, and should be of use at any point in the veterinary curriculum.

This book is a direct result of a symposium held in December 1988, in Washington, DC, honoring Professor Emeritus Miodrag Ristic for his contributions to rickettsial disease research, in general, and, to ehrlichiosis, in particular. He and his colleagues in the United States Army Medical Research Unit brought to the world's attention an epidemic of ehrlichiosis, that occurred in German shepherd dogs during the Vietnam War. The group was able to culture the microorganism Ehrlichia canis and to fulfill Koch's postulates. They eventually developed an indirect immunofluorescent antibody (IFA) test which has been adopted internationally. The same group joined a national effort to decipher another mysterious disease known as Potomac horse fever (PHF). They used the same technology developed by Nyindo in Dr. Ristic's laboratory to isolate, characterize, and again develop a similar IFA test for PHF. Today PHF has been diagnosed, at least serologically, practically across the entire United States, in some provinces of Canada, and reports are beginning to trickle in of its occurrence in European countries. Thus, the etiologic agent of PHF, now named after Professor Ristic, Ehrlichia risticii, historically places this scientist side by side with the other 2 "R's", i. e. , Ricketts and da Rochalima. Ehrlichiosis is not limited to domestic animals. Sennetsu rickettsiosis, long known by Japanese scientists as an imitator of "infectious mononucleosis," was subsequently shown to be caused by an ehrlichial agent, through collaborative efforts among the United States Army, the University of Illinois, and Dr.

Recent advances in electron microscopy have opened up new dimensions and perspectives in the field of morphology, and these are presently being integrated with biochemical and physiopathological phenomena occurring in cells, tissues, and organs. Methods such as freeze-fracture, freeze-etching, scanning, and high-voltage electron microscopy have contributed immensely to this progress, as well as to the study of smooth muscle tissue and contractile cells in general. The articles composing this book have been selected and edited with the purpose of updating and reviewing the most important aspects of smooth muscle cells as revealed by the integration of these submicroscopic techniques. The chapters of this volume have been prepared by some of the most authoritative experts in the discipline. Therefore each article not only offers the reader a concise review of the specific topic, but also seeks to highlight areas that require further investigation. Much of the volume is presented in an illustrative format so as to emphasize the remarkable results obtainable by the combination of the aforementioned methods, which allow a better appreciation of smooth muscle structure and ultrastructure. This volume, like others in the series, is intended not only for researchers in the field, but also for graduate students of histology, embryology, anatomy, physiology, and pathology in both medical and veterinary colleges. My hope is that this book will prove to be a valuable academic resource to the audience of the world in this fascinating and expanding field.

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.

In the past half century, filamentous fungi have grown in commercial importance not only in the food industry but also as sources of pharmaceutical agents for the treatment of infectious and metabolic diseases and of specialty proteins and enzymes used to process foods, fortify detergents, and perform biotransformations. The commercial impact of molds is also measured on a negative scale since some of these organisms are significant as pathogens of crop plants, agents of food spoilage, and sources of toxic and carcinogenic compounds. Recent advances in the molecular genetics of filamentous fungi are finding increased application in the pharmaceutical, agricultural, and enzyme industries, and this trend promises to continue as the genomics of fungi is explored and new techniques to speed genetic manipulation become available. This volume focuses on the filamentous fungi and highlights the advances of the past decade, both in methodology and in the understanding of genomic organization and regulation of gene and pathway expression.

The last half-century has shown a dramatic increase in the standard of living of millions of people in Europe, North America and many parts of the Third World. This has, in many ways been brought about by scientific and technical developments which were initiated in the 1940s and 1950s. Promises were then made that nuclear energy would provide electricity so cheap that it would not need metering, pesticides would end malnutrition throughout the world and plastics and other synthetic chemicals would revolutionise our manufacturing industry and our way of life. Whilst some of these promises have been fulfilled, the problems of long-term health risks to humans and wildlife arising from the use, production and disposal of these products were either unknown or deliberately understated. Nuclear power is rendered economically unviable when the real cost of decommissioning and storage of waste for several millenia is included, and the effects on health of both humans and wildlife of early pest eradication programmes with organochlorine pesticides were well documented in Rachel Carson's "Silent Spring." Evidence of the effects of aerosols and refrigerants on depletion of the ozone layer has led to restriction on the use of CFCs, and there is now increasing evidence of climate change resulting from our profligate use of fossil fuels.

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