With the growing incidence of fragility fractures in Europe and North America over the last three decades, bone loss and osteoporosis have become active areas of research in skeletal biology. Bone loss is associated with aging in both sexes and is accelerated in women with the onset of menopause. However, bone loss is related to a suite of complex and often synergistically related factors including genetics, pathology, nutrition, mechani cal usage, and lifestyle. It is not surprising that its incidence and severity vary among populations. There has been increasing interest to investigate bone loss and osteoporosis from an anthropological perspective that utilizes a biocultural approach. Biocultural approaches recognize the inter-relationship between biological, cultural, and environmental variables. Anthropological studies also highlight the value of evolutionary and population approaches to the study of bone loss. These approaches are particularly suited to elucidate the multifactorial etiology of bone loss. The idea for this volume came out of a symposium organized by the editors at the 70th annual meeting of The American Association of Physical Anthropologists in Kansas City, Missouri. Many of the symposium participants, along with several additional leading scientists involved in bone and osteoporosis research, are brought together in this volume. Each chapter focuses on a different aspect of bone loss and fragility with a fresh and stimulating perspective.

The best protection against environmental mutagens is to identify them before they ever come into general use. But it is always possible that some substance will escape detection and affect a large number of persons without this being realized until later generations. This article considers ways in which such a genetic emergency might be promptly detected. A mutation-detecting system should be relevant in that it tests for effects that are as closely related as possible to those that are feared. It should be sensitive enough to detect a moderate increase in mutation rate, able to discover the increase promptly before more damage is done, responsive to various kinds of mutational events, and designed in such a way as to maxi mize the probability that the Gause of an increase can be found. Methods based on germinal mutation necessarily involve enormous numbers of persons and tests. On the other hand, with somatic mutations the individual cell becomes the unit of measurement rather than the in dividual person. For this reason, I think that somatic tests are preferable to germinal tests, despite the fact that it is germinal mutations which are feared.

Tiselius demonstrated that the immunologically active components of immune sera migrated electrophoretically in the gamma globulin region. His findings illuminated the classic observations of Jenner regarding development of resistance to infection, and those of von Pirquet, Pasteur, and Arthus regarding the transfer and specificity of resistance. Conceptual integration of these observations provided the impetus for the present modern era of immunology. Subsequent to Tiselius's work, multiple, rapid advances have occurred in the study of congenital and acquired immune deficiency states in mice, chickens, and humans. These studies have readily demonstrated that the immunologic ability of an organ ism to protect itself from environmental influences is a prerequisite for survival. Indeed, this necessity for protection from microenvironmental influences has promoted the evolu tionary development of immunologic diversification, namely, host dependence upon a sophisticated, multifaceted network of cells and effector mechanisms responsible for the clearance and neutralization of toxins and potentially harmful pathogens. The obligate dependence of animals upon the functional integrity of their immunologic systems is illus trated by the ready invasion of ubiquitous organisms when the host is in a state of immune defense derangement. Nevertheless, derangements in immune function can range from par tial to complete and can be compatible with survival. The consequences of such derange ments run the gamut from subclinical disease to inevitable mortality."

This book has its origin in my experience as a teacher of pharmacokinetics in many universities in four different continents. It was not my intention to write a popular book; what distinguishes this one from many others on the same subject is its large use of algebra and calculus. For this I make no apologies; in fact a serious study of pharmacokinetics without the help of mathematics is, in my opinion, impossible. The exact definition of many pharmacokinetic quantities, even the most common, and the correct use of many equations, even the most simple, requires the constant use of mathematical language. On the other hand I have made a considerable effort to use only elementary algebra and elementary calculus, as commonly taught in most introductory university courses. For the few exceptions, when less common mathematical concepts were needed, I have supplied the necessary explanations in four appendices. The first three chapters are a general introduction to the scientific method. Chapters 4 to 12 show different specific methods to deal with pharmacokinetic pr- lems. There is considerable overlap among those chapters; this is intentional and its p- pose is to convince the reader that every problem can be solved in more than one way, including ways that were not mentioned in this book and that intelligent readers can find for their own pleasure. Chapters 13 to 17 show how different parameters of importance in pharmacokinetics can be exactly defined and measured.

From Ayurvedic texts to botanical medicines to genomics, ideas and expertise about veterinary healing have circulated between cultures through travel, trade, and conflict. In this broad-ranging and accessible study spanning 400 years of history, Susan D. Jones and Peter A. Koolmees present the first global history of veterinary medicine and animal healing. Drawing on inter-disciplinary and multi-disciplinary perspectives, this book addresses how attitudes toward animals, disease causation theories, wars, problems of food insecurity and the professionalization and spread of European veterinary education have shaped new domains for animal healing, such as preventive medicine in intensive animal agriculture and the need for veterinarians specializing in zoo animals, wildlife, and pets. It concludes by considering the politicization of animal protection, changes in the global veterinary workforce, and concerns about disease and climate change. As mediators between humans and animals, veterinarians and other animal healers have both shaped, and been shaped by, the social, cultural, and economic roles of animals over time.

Die 7. Auflage von Schalm's Veterinary Hematology bietet eine einzigartige Fulle an Themen zu Bluterkrankungen bei Tieren. Die uberarbeitete umfassende Auflage deckt nicht nur eine Vielzahl von Tierarten ab, sondern bietet als das Standardwerk durchgangig neue Themen und Informationen aus dem Fachgebiet. Ein neues Kapitel zu hamolymphatischem Gewebe erlautert die wissenschaftlichen Grundlagen. Die Kapitel zu den Tierarten wurden erweitert und um neue Spezies erganzt. Das zugangliche Referenzwerk, geschrieben von einer internationalen Expertengruppe, uberzeugt durch seine zusammenhangende Darstellung des Fachgebiets und detaillierten Informationen zur Hamatologie bei Tieren. Schalm's Veterinary Hematology ist unverzichtbar fur klinische Pathologen in der Veterinarmedizin, Personal in Veterinarlabors, Internisten und Fachveterinare unterschiedlichster Disziplinen. - Vollstandige UEberarbeitung dieses umfassenden und ausfuhrlichen Referenzwerks zur Hamatologie bei Tieren. - Neues Kapitel zu hamolymphatischen Gewebe und den wissenschaftlichen Grundlagen. - Beschreibt noch mehr Tierarten. - Mit vielen neuen Themen. - Neues, ubersichtlicheres Inhaltsverzeichnis.

This volume is an important advancement in the application ofpharmacokinetic (PK) and pharmacodynamic (PO) principles to . drug development. The series of topics presented deal with the application of these tools to everyday decisions that a pharmaceutical scientist encounters. The ability to integrate these topics using PK and PO methods has optimized drug development pathways in the clinic. New technologies in the areas of in vitro assays that are more predictive of human absorption and metabolism and advancement in bioanalytical assays are leading the way to minimize drug failures in later, more expensive clinical development programs. of Pharmacokinetics and pharmacodynamics have become an important component understanding the drug action on the body and is becoming increasingly important in drug labeling due to it's potential for predicting drug behavior in populations that may be difficult to study in adequate numbers during drug development. The ability to correlate drug exposure to effect and model it during the drug development value chain provides valuable insight into optimizing the next steps to derive maximum information from each study. These principles and modeling techniques have resulted in an expanded and integrated view of PK and PO and have led to the expectations that we may be able to optimally design clinical trials and eventually lead us to identifying the optimal therapy for the patient, while minimizing cost and speeding up drug development. There is wide utility for the book both as a text and as a reference.

Animal welfare is attracting increasing interest worldwide, especially in developed countries where the knowledge and resources are available to (at least potentially) provide better management systems for farm animals, as well as companion, zoo and laboratory animals. The key requirements for adequate food, water, a suitable environment, appropriate companionship and good health are important for animals kept for all of these purposes. There has been increased attention given to farm animal welfare in many co- tries in recent years. This derives largely from the fact that the relentless pursuit of nancial reward and ef ciency, to satisfy market demands, has led to the devel- ment of intensive animal production systems that challenge the conscience of many consumers in those countries. In developing countries, human survival is still a daily uncertainty, so that p- vision for animal welfare has to be balanced against human needs. Animal welfare is usually a priority only if it supports the output of the animal, be it food, work, clothing, sport or companionship. In principle the welfare needs of both humans and animals can be provided for, in both developing and developed countries, if resources are properly husbanded. In reality, however, the inequitable division of the world's riches creates physical and psychological poverty for humans and a- mals alike in many parts of the world.

The Conference on the Ecotoxicity of Heavy Metals and Organohalogen Com pounds was held under the auspices of the NATO Science Committee as part of its continuing effort to promote the useful progress of science through international cooperation. Science Committee Conferences are deliberately designed to focus atten tion on unsolved problems, with invited participants providing a variety of complementary expertise. Through intensive group discussion they seek to reach a consensus on assessments and recommendations for future research emphases, which it is hoped will be of value to the larger scientific commu nity. The subjects treated in previous Conferences have been as varied as science itself-e.g., computer software, chemical catalysis, oceanography, and materials and energy research. This volume presents an account of a meeting which evolved from studies within the Science Committee's advisory panel on Eco-Sciences. Environmental monitoring of toxic substances from industrial and agricultural sources is pro ducing a growing volume of data on the quantities of such substances in terres trial and aquatic milieus. Before this information can be used to assess biological effects, knowledge is required of the chemical form of the pollutants, the mecha nisms by which they enter and move through organisms, their concomitant transformations, the nature of the toxic reactions within tissues, and the way in which the physiology and behavior of individuals is affected.

This is the first comprehensive work to review blood platelet biochemistry, physiology, pharmacology, and function. It provides up-to-date information on how platelets function, the biochemical mechanisms that modulate their physiology and function, as well as the pharmacology of platelet inhibitory drugs.

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.

There has been a significant surge of interest in the study of the physiology and biochemistry of plant host-parasite interactions in recent years, as evidenced by the number of research papers currently being published on the subject. The in creased interest is probably based on the evidence that effective management of many plant diseases is, for the most part, contingent upon a clear understanding of the nature of host-parasite interactions. This intensified research effort calls for a greater number of books, such as this one, designed to compile, synthesize, and evaluate widely scattered pieces of information on this subject. The study of host-parasite interactions concerns the struggle between plants and pathogens, which has been incessant throughout their coevolution. Such in teractions are often highly complex. Pathogens have developed sophisticated of fensive systems to parasitize plants, while plants have evolved diversified defen sive strategies to ward off potential pathogens. In certain cases, the outcome of a specific host-parasite interaction seems to depend upon the presence or efficacy of the plant's defense system. A plant may become diseased when a parasite manages to invade it, unhindered by preexisting defense systems and/or without eliciting the plant's induced resistance response(s). Absence of disease may re flect the inability of the invading pathogen to overcome the plant's defense sys tem(s).

The Permanent Commission and International Association on Occupational Health (PCIAOH) established in 1969 a Subcommittee on the Toxicology of Metals under the chairmanship of Lars Friberg. This committee, which later was named the Scientific Committee on the Toxicology of Metals, has organized a number of previous meetings that have led to publications in three major areas of metal toxicology: a preliminary meeting in Slanchev Bryag, Bulgaria in- 1971, followed by a meeting in 1972 in Buenos Aires, Argentina which produced two reports (Dukes and Friberg, 1971; Task Group on Metal Accumulation, 1973), that discussed the metabolism of metals with special reference to absorption, excretion and biological half-times. The effects and dose-response relationships of toxic metals, including a discussion of general principles, was the second major topic addressed by the Scientific Committee at a meeting in Tokyo in 1974 (Nordberg, 1976). The philosophy of this conference, as well as the previous one in Buenos Aires, was based on the concept of a "threshold dose" for the occurrence of adverse effects. In a conference held in Atlanta, USA in 1980, the scope of discussion on metal effects was broadened to include the role of metals in carcinogenesis. Thus, for the first time, the Scientific Committee took under consideration the possibility of non-threshold relationships (Belman and Nordberg, 1981). In addition, the Scientific Committee on the Toxicology of Metals organized a workshop on metal interactions in Stockholm 1977 (Nordberg et al.

The development of the modern organic insecticides has contri- buted a major chapter to the history of neurotoxicants. From their roots in the organochlorines and organophosphates discovered prior to and during the Second World War, to the carbamates developed in the 1950's, and most recently to the extremely potent and promising synthetic pyrethroids, the most important organic insecticides have been those whose wite of action lies within the nervous system. In this regard, man is only mimicking nature in attacking the nervous system with lethal intent since potent neurotoxins are cornmon compo- nents of the venoms with which animals of all types defend themselves and subdue their prey. This central role of the nervous sytem as a broad target for pesticides may also be projected into the future - a prediction to which this volume is devoted. The nervous system in its diversity is likely to be of central concern to those charged with discovering novel pesticides whether they be modifications of familiar chemical groups or structurally novel neurotoxicants such as the nitromethyl- ene insecticides described here. On a second front, the ability to influence insect behavior through the nervous system will become increasingly important in pest management. Pheromones represent one obvious example of this; recent work described in this volume indi- cates that the forrnamidine pesticides may represent another.

The ready acceptance and wide demand for copies of the first two volumes of Chemical Mutagens: Principles and Methods Jar Their Detection have demon strated the need for wider dissemination of information on this timely and urgent subject. Therefore, it was imperative that a third volume be prepared to include more detailed discussions on techniques of some of the methods that were presented from a theoretical point of view in the first two volumes, and to update this rapidly expanding field with current findings and the new developments that have taken place in the past three years. Also included is a special chapter by Dr. Charlotte Auerbach giving the historical background of the discovery of chemical mutagenesis. Methods for recognizing mutagenic compounds in vitro are a necessary preliminary step toward arriving at satisfactory solutions for recognizing significant mutation rates in man, which must be done before our test tube methods of detection can be considered reliable. Two chapters in this volume make important contributions to this problem. Due to the increasing activity in efforts to perfect techniques for detecting chemical mutagens and their effects on man, it is planned to continue this series of volumes as necessary to keep abreast of current findings.

The articles published in this volume are based on the papers del ivered at a conference on the Role of Metal Ions in Biological Systems held November 20 and 21, 1972, at Argonne National Laboratory. The purpose of the conference was to present to an interdiscipl inary audience of physical scientists some recent developments illustrating the chemical and environ mental participation of the heavy metal ions in the biological system. The invited speakers at the conference are special ists in the fields they describe, and the articles presented here are at a level of interest to readers with backgrounds in physical sciences who are not necessari Iy doing research in the areas described. The articles are referenced through 1972, and in some cases early 1973, and thus should also be of value to research workers. It is hoped that the book wi II be of particular interest to chemists, biologists, workers in the fields of en vironmental science and publ ic health, as wei I as graduate and senior undergraduate students in these discipl ines. The conference was sponsored by the Central States Universities, Inc., a consortium of sixteen midwestern univer sities, the Center for Educational Affairs, Argonne National Laboratory, and the United States Atomic Energy Commission. It is my pleasure to thank the members of the conference committee for their ideas and active help in organizing the conference."

Tiselius demonstrated that the immunologically active components of immune sera migrated electrophoretically in the gamma globulin region. His findings illuminated the classic observations of Jenner regarding development of resistance to infection, and those of von Pirquet, Pasteur, and Arthus regarding the transfer and specificity of resistance. Conceptual integration of these observations provided the impetus for the present modern era of immunology. Subsequent to Tiselius's work, multiple, rapid advances have occurred in the study of congenital and acquired immune deficiency states in mice, chickens, and humans. These studies have readily demonstrated that the immunologic ability of an organ ism to protect itself from environmental influences is a prerequisite for survival. Indeed, this necessity for protection from microenvironmental influences has promoted the evolu tionary development of immunologic diversification, namely, host dependence upon a sophisticated, multifaceted network of cells and effector mechanisms responsible for the clearance and neutralization of toxins and potentially harmful pathogens. The obligate dependence of animals upon the functional integrity of their immunologic systems is illus trated by the ready invasion of ubiquitous organisms when the host is in a state of immune defense derangement. Nevertheless, derangements in immune function can range from par tial to complete and can be compatible with survival. The consequences of such derange ments run the gamut from subclinical disease to inevitable mortality."

As editor I want especially to thank Dr. Ernst Freese for helpful co operation in preparing these volumes, and to express my appreclatlOn to Drs. Kurt Hirschhorn and Marvin Legator, the other members of the editorial board. Alexander Hollaender January 1971 Preface The purpose of these volumes is to encourage the development and ap plication of testing and monitoring procedures to avert significant human exposure to mutagenic agents. The need for protection against exposure to possibly mutagenic chemicals is only now coming to be generally realized. The recently issued Report of the Secretary's Commission on Pesticides and Their Possible Effects on Health (the Mrak Report-U.S. Department of Health, Education and Welfare, December 1969) has made an important start. Its Panel on Mutagenicity recommends that all currently used pesticides be tested for mutagenicity in several recently developed and relatively simple systems. Whether recommendations such as these are actually put into effect will depend on convincing government, industry, and the public that the problem is important, that the proposed tests would be effective, and that they can be conducted at a cost that is not prohibitive. Why is it important to screen environmental agents for mutagenic activity? To those who will read this book, the answer is self-evident. The sine qua non of all that we value and all that we are is our genetic heritage.

This volume on enzootic bovine leukosis (EBL) and bovine leukemia virus (BLV) is the second in our series "Developments in Veterinary Virology". Each book in this series is devoted to a major virus disease of agricultural significance. The chapters in each volume are planned to supply information on a range of subjects from pathogenesis of the causative virus to vaccination, eradication, and rules regarding disease control. The present volume on enzootic bovine leukosis and bovine leukemia virus updates the reader on the disease and its causative agent and includes the nucleotide sequence of the BLV genome as well as data on its integration into the DNA of the tumor cell. Insights into diagnosis, veterinary legislation, and the economic aspects of EBL are also provided. Intense research conducted on EBL and BLV during the course of a decade is presented in a most concise and in-depth manner, so as to provide the reader with a comprehensive overview of this economically important disease of cattle. I wish to thank the editors, A. Burny and M. Mammerickx, as well as all the authors, for making this excellent book available at a stage when the knowledge on bovine leukemia virus will also contribute to our understanding of the virus causing human AIDS.

Health Effects of Ambient Air Pollution provides the reader with an overview of the health effects of air pollution in human subjects. The majority of the book is devoted to the discussion of the health effects of common widespread air pollutants regulated by the U.S. Environmental Protection Agency through national ambient air quality standards. The book reviews the sources and fate of common air pollutants in ambient air and researches the adverse effects of these outdoor and indoor air pollutants in 'in vivo' cell systems, animals, and humans. Research for the book was conducted in controlled laboratory studies and epidemiologic studies. Special emphasis throughout Health Effects of Ambient Air Pollution is placed on the effects of air pollution in subjects with asthma.

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

Pulmonary Immunotoxicology is a comprehensive exploration of the effects of various inhaled materials upon the immune system of the respiratory tract. It will be useful to investigators in the field of pulmonary toxicology and immunotoxicology, and to those involved in administration and regulation of matters related to inhaled materials. It can also serve as a textbook for a course in pulmonary immunotoxicology at graduate or advanced undergraduate level. Pulmonary Immunotoxicology comprises four sections. The first provides basic background concepts essential for understanding pulmonary immunotoxicology, including discussions of the normal structure and function of the respiratory system, its basic immunology, and the manner by which inhaled particles and gases are removed from the air and deposited upon respiratory tract surfaces. The second section provides an overview of the major types of pathological consequences which can arise from immunomodulation within the respiratory tract, including hypersensitivity and asthma, inflammation and fibrosis, as well as immunosuppression and autoimmunity. The third section, which comprises the largest portion of the book, deals specifically with major classes of airborne agents that are known to alter the immune function of the respiratory tract. These are arranged into major classes: organic agents, metals, gases, particles, biologics, and complex mixtures. The fourth and final section of the book explores the area of risk assessment, including discussions of the basic concepts of risk assessment as they apply specifically to immunotoxicologic effects upon the lungs, and the use of biomarkers as indices of potential pulmonary immunotoxic responses to inhaled materials.

Humans are exposed daily to low concentrations of metals that are released into the environment by both natural and industrial processes. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity examines concerns about the acute and/or chronic exposure of humans to concentrations of these metals that are below the threshold levels established by various federal regulatory agencies. Some of these metals are accumulated in various tissues and over time this may result in the accumulation of a significant body burden. This could increase the risk of developing a variety of diseases later in life, at a time when thresholds for such effects may already be reduced by the processes of aging. Such possibilities could only further compromise the quality of life in the elderly population and could contribute to the rising cost of health care in this country. Studies that have been conducted to determine the possible risks associated with exposure to relatively non-toxic concentrations of environmental metals have been hampered by a lack of appropriate models and a lack of funding. It has also been difficult for researchers to demonstrate a correlation between the exposure of humans or animals to low concentrations of environmental pollutants and disease. This book examines recent technological advances in the areas of molecular biology, biochemistry, and computer-enhanced image analyses that provide researchers with the tools to begin elucidating the genotoxic effects of environmental metal pollutants and the mechanisms by which these metals cause DNA damage. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity presents data that demonstrate that certain environmental metal pollutants are genotoxic. The authors describe the role of reactive oxygen intermediates in causing the DNA damage induced by environmental metal pollutants and discuss their possible role in human disease.