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."

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.

Since its launch in 1998 the European Society for Intravenous Anaesthesia (EuroSIVA) has come a long way in providing educational material and supporting the research and clinical application of intravenous anaesthesia. After the first two annual meetings held in Barcelona and Amsterdam in 1998 and 1999, three other successful meetings took place in Vienna, Gothenburg and Nice in 2000, 2001 and 2002. Next to these main meetings, starting in the year 2000, a smaller winter meeting has been organised every last week of January in Crans Montana, Switzerland. Both the main summer and the winter meetings breathe the same atmosphere of sharing the latest on intravenous anaesthesia research in the presence of a friendly environment and good company. Since the first meetings the educational tools of EuroSIVA have increased in quantity and technical quality allowing digital slide and video presentation along with the use of the computer simulation program TIVAtrainer during the speaker sessions and the workshops. Furthermore, EuroSIVA now exploits a website www. eurosiva. org that allows for continuous exchange of information on intravenous anaesthesia, the TIVAtrainer, the EuroSIVA meetings and online registration for these meetings. The EuroSIVA is currently engaged in friendly contacts with the Asian Oceanic Society for Intravenous Anaesthesia (AOSIVA), the United Kingdom Society for Intravenous Anaesthesia (UKSIVA), the Korean Society for Intravenous Anaesthesia (KSIVA), the European Society of Anaesthesiology (ESA) and the International Society for Applied Pharmacology (ISAP).

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."

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.

Within the last few years, iron research has yielded exciting new insights into the under standing of normal iron homeostasis. However, normal iron physiology offers little protec tion from the toxic effects of pathological iron accumulation, because nature did not equip us with effective mechanisms of iron excretion. Excess iron may be effectively removed by phlebotomy in hereditary hemochromatosis, but this method cannot be applied to chronic anemias associated with iron overload. In these diseases, iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Iron chelating therapy has changed the quality of life and life expectancy of thalassemic patients. However, the high cost and rigorous requirements of deferoxamine therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Such development, and the evolution of improved strategies of iron chelating therapy require better understanding of the pathophysiology of iron toxicity and the mechanism of action of iron chelating drugs. The timeliness of the present volume is underlined by several significant develop ments in recent years. New insights have been gained into the molecular basis of aberrant iron handling in hereditary disorders and the pathophysiology of iron overload (Chapters 1-5)."

This book contains the proceedings of the first meeting on invertebrate immunity ever sponsored as a summer research conference by the Federation of American Societies for Experimental Biology (FASEB). The conference was held in Copper Mountain, CO from July 11-16, 1999. It was a an extension of a New York Academy of Sciences meeting entitled "Primordial Immunity: Foundations for the Vertebrate Immune System" held on May 2-5,1993 at the Marine Biological Laboratories in Woods Hole, MA. The proceedings of that meeting were published in The Annals of the New York Academy of Sciences (volume 712). At that meeting all the attendes agreed that this type of conference (a relatively small focused gathering) allowed for participation by investigators at all levels of their careers. We further agreed that we should search for a forum that would allow this meeting to continue. The FASEB Summer Research Conference was an excellent vehicle for this type of meeting. Furthermore, this year's participants decided to continue this meeting as a regularly scheduled FASEB sponsored event. This was a unique conference in the sense that it focused upon mechanisms of development and defense in protostome and deuterostome invertebrates and lower vertebrates. There was a strong emphasis on evolutionary cell biology, phylogenetic inferences and the evolution of recognition and regulatory systems.

The localized attachment of circulating leukocytes to endothelium has been recognized as the cellular hallmark of the inflammatory response. This adhesive interaction, a necessary antecedent to the emigration of leukocytes from the blood into the tissues, is mediated by vascular adhesion molecules. Leukocyte Recruitment, Endothelial Cell Adhesion Molecules and Transcriptional Control: Insights for Drug Discovery outlines some of the cellular and molecular mechanisms of inflammation with contributions from top researchers. This volume provides an overview of three of these endothelial adhesion molecules, as examples of key mediators of leukocyte recruitment. It reviews the structure and regulation of these cell surface proteins and focus on the rapidly expanding field of transcriptional regulation of these inducible proteins, and closes with a discussion of drug discovery possibilities that target the regulation of leukocyte recruitment. This book will be of interest for any researchers, in academia or industry, looking for an overview of leukocyte recruitment or novel approaches to drug discovery.

A variety of metabolic processes are known to be intimately involved in the maintenance of cellular structure and function. It has also become clear that metabolic events involved in the synthesis and hydrolysis of ATP as well as for the synthesis of proteins and phospholipids are essential for cellular health. The regulation of cell function is generally achieved through participation of a wide variety of hormones and different signal transduction mechanisms for the activation/deactivation of some specific metabolic processes. In this regard cyclic AMP and calcium seem to play a crucial role. Various hormones are also known to affect the genetic machinery of all the cell; however, the exact signals for genetic control of cellular function are not well defined. In particular, the sequence of events concerned with remodelling of different types of cells under various pathological situations is poorly understood. In this book we have therefore dealt with some of these issues from biochemical, molecular biological, physiological, and pharmacological viewpoints. Special emphasis has been laid on understanding heart function and metabolism in health and disease in general, and cardiac hypertrophy, heart failure, and ischemic heart disease in particular. It is hoped that this multidisciplinary information will be of value to basic scientists and clinical investigators.

The 23rd annual meeting of the International Society on Oxygen Transport to Tissue took place from August 23-27, 1995, at the Station Square Sheraton along the shores of the Monongahela River where it meets with the Allegheny and Ohio Rivers to form the "Point" of the city of Pittsburgh. Pittsburgh was a convenient location for the meeting be ing between both the East and West coasts of the United States and between the Asian and European continents. It is easily accessible by air via its large international airport. In ad dition, Pittsburgh has just recently undergone a transition from the steel mills and indus tries of old to an age of computers and biotechnology as evidenced by the new Biotechnology Center of the University of Pittsburgh where a lunch and tour were pro vided for interested participants. On the tour, the participants got to see the mix of projects ranging from molecular biology to clinical projects studying membrane oxygenators, ven tricular assist devices, oxygen carriers, and more, representing the forefront of research on oxygen delivery systems to tissue.

It is a great pleasure for me to introduce this great deal of information from various insti- manual for the diagnosis of parasites of domes- tutes and universities. tic animals. It is a unique publication in many The result is an impressively comprehen- respects. Books concerning parasitic anima I sive, beautifully illustrated and, above all high- diseases - comprehensive textbooks, but also ly serviceable manual. It is easy to consult. Its field manuals - abound. These generally deal systematic and colour-coded layout allows the with aetiology, c1inical signs and pathology, as user to steer swiftly and surely through a vast weil as control and treatment. However, while amount of information. Clinical pictures and methods for diagnosis are often mentioned, figures show the parasite stage of diagnostic these are rarely sufficiently practical and spe- interest, facilitating a rapid and accurate diag- cific to allow the person ne I in field laborato- nosis. The book has been designed to be used ries to reach a concise, rapid dia gnosis of the by veterinarians and technicians, by teachers parasite species involved in any particular case. and students - in fact, by anyone dealing with Parasitic Infections of Domestic Animals suc- the diagnosis of diseases in domestic animals. ceeds in redressing these shortcomings.

Peste de Petits Ruminants (PPR) is a highly contagious viral disease of domestic and wild small ruminants that can significantly affect economies. The authors are experts in the field and provide an up-to-date and comprehensive review covering all aspects of the disease. The book is divided into seven chapters highlighting genome organization, virus replication and the determinants of virulence, pathophysiology and clinical disease, immunology and immunopathogenesis, epidemiology, diagnostic assays and vaccines, and the challenges concerning global eradication. It is an invaluable reference work, presenting the latest information for virologists, microbiologists, immunologists, veterinarians, and scientists working in PPR research.

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.

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.

There has been a great upsurge in interest in light microscopy in recent years due to the advent of a number of significant advances in microscopy, one of the most important of which is confocal microscopy. Confocal microscopy has now become an important research tool, with a large number of new fluorescent dyes becoming available in the past few years, for probing your pet structure or molecule within fixed or living cell or tissue sampies. Many of the people interested in using confocal microscopy to further their research do not have a background in microscopy or even cell biology and so not only do they find considerable difficulty in obtaining satisfactory results with a confocal microscope, but they may be mislead by how data is being presented. This book is intended to teach you the basic concepts ofmicroscopy, fluorescence, digital imaging and the principles of confocal microscopy so that you may take full advantage ofthe excellent confocal microscopes now available. This book is also an excellent reference source for information related to confocal microscopy for both beginners and the more advanced users. For example, do you need to know the optimal pinhole size for a 63x 1. 4 NA lens? Do you need to know the fluorescence emission spectrum of Alexa 568? Access to the wealth of practical information in this book is made easier by using both the detailed index and the extensive glossary.

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.

Voltage-gated calcium channels are critical regulators of cytoplasmic levels of calcium, the universal signaling ion. As such, calcium channels trigger a wide range of cellular functions, from muscle contraction to neurotransmitter secretion, and are important players in human disease. Prominent in the nervous, cardiovascular, and endocrine systems, members of the calcium channel family are targets for existing antihypertensive and anticonvulsant drugs. In addition, they are emerging targets for drugs to treat an extraordinarily diverse group of disorders, including pain, cerebral ischemia, cardiac arrhythmia, and migraine. This book reviews the compounds that target individual calcium channel subtypes and the cellular and behavioral functions governed by each different channel. It contains information for basic scientists using calcium channel antagonists as experimental tools, for behavioralists studying animal models of human disease, and for pharmaceutical scientists interested in creating the next generation of calcium channel-targeted drugs. Several factors make an entire book on calcium channel pharmacology timely.

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."

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.

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.