B. Raymond Fink Sheldon Roth and Keith Miller have asked me to record that the Third Conference on Molecular and Cellular Mechanisms of Anesthesia was held in Calgary last May "in my honor. " Such was my dear friends' gracious way of continuing a series that began at the University of Washington, where I hosted two, four, or five previous ones, 1,3-6 depending 2 on how far back one wishes to count. At that, Seattle took up where Paris left off in 1951. These occasions create their own unforgettable memories. This book captures the fine, invigorating ambience of the University of Calgary and the exciting explorations and com panionship of a gathering in a frontier territory of neuroscience. So, floreant symposia. They have progressively refined the quarry, from pathway to synapse to lipoprotein membrane to receptor and single channel, in heuristic convergences of neuronal physiology, biochemistry, and pharmacology. Nevertheless, the anesthesiologist in me senses a certain disquiet, a certain claustrophobia provoked by the narrow confines of micropipettes. How much more tubular must tunnel vision become before the desired broad view emerges? At present, the advances in molecular neurobiology seem continually to increase the apparent complexity of the total problem and the conceptual distance between the reductionists in the laboratories and the holists in the operating rooms. Happily, what is also growing is the excitement in trying to bridge the gap. Perhaps it would be timely to regard general anesthesia not as a state but as a syndrome."

This book draws together the most relevant and recent advances in the area of ionic transport in animals. In particular, it describes the role of modern cell and molecular biology research techniques in this rapidly advancing field. These techniques have led to important advances in our knowledge of cellular mechanisms of ion transporting epithelia, the role and expression of osmoregulatory hormones and a new understanding of whole body salt and water balance.

Wide and fascinating is the field of research on tryptophan, a most versatile amino acid, transformed, as it is, in our organism into many biologically active substances. This volume contains the proceedings of the Eighth International Meeting on Tryptophan Research, held at the University of Padova, Padova, Italy, from June 25 to 29 1995, under the auspices of the University of Padova, National Research Council, Italian Chemical Society-Division of Pharmaceutical Sciences, Region ofthe Veneto and City of Padova. The meeting was held in Padova to commemorate Prof. Luigi Musajo twenty years after his death and the editors dedicate this book to him in recognition of his pioneering work in tryptophan metabolism. Prof. Osamu Hayaishi delivered the Musajo Memorial Award Lecture: Tryptophan oxygenase. and sleep. Figure I shows the ISTRY President Prof. Simon N. Young presenting the Musajo Memorial Medal to Prof. Hayaishi during the Opening Ceremony. Two hundred scientists from twenty two countries participated in the meeting. These proceedings contain 121 papers encompassing a variety of topics and disciplines.

The frontispiece, Leonardo da Vinci's drawing of the embryo in the womb, was chosen as a starting point for this book. It was Leonardo who in his notebooks and drawings combined artistic composition and accurate recording of the anatomy of the human body. Leonardo studied human anatomy in order to execute artistic drawings. His aim was to clarify form and function of human organs including reproductive organs. He followed up his extensive research with graphic representa tion and thereby initiated record keeping as a basis of scientific investigation. His records, accurate three-dimensional drawings, allowed others to reproduce his find ings and to test for correctness. Results could be updated and refined. Only after these steps can abnormalities be ascertained and defined as pathology. Though Leonardo was both artist and scientist, it is assumed that his anatomic drawings were used to improve his art, and thus scientific endeavor was at the service of his art. Anatomy, the offspring of science and art, is an integration of the two and became an accepted branch of the natural sciences. Although art and science continued to interact throughout the Renaissance, art was often placed in the service of science. In the course of history that followed, art and science in creasingly followed separate ways."

This book has a dual purpose, to review in depth the control of fuel homeostasis in the brain and the role of the nervous system in the control of fuel deposition in the body. From the methodological point of view the emphasis is on the application of advanced technologies to assess fuel transport and brain metabolism, the role of peptides in the neuroendocrine system and the response of the brain to hypoglycemia. These technologies include positron emmission tomography, nuclear magnetic resonance, immunocytochemistry, molecular biology, autoradiography. To study fuel homeostasis in the body advanced tracer methods that include modelling are set out. From the pathophysiological point of view the emphasis is on abnormalities in stress, brain metabolism in diabetes, eating and degenerative disorders. This book contains contributions from endocrinologists, physiologists, neurologists, psychoneuroendocrinOlogists, biophysicists, biochemists and experts in nutrition. This authorship represents a unique diversity of researchers who, for the first time, cover comprehensively the interaction between the nervous system and fuel homeostasis, both in health and disease. We hope this book will be an important source of information for both researchers and practicing clinicians. Mladen Vranic Suad Efendic Charles Hollenberg v ACKNOWLEDGEMENTS The Symposium from which this volume arose (University of Toronto, June 27-28, 1990) was the first Toronto-Stockholm symposium on Perspectives in Diabetes Research. These Symposia are organized triennially by the Banting and Best Diabetes Centre, University of Toronto and the Department of Endocrinology, Karolinska Institute, Stockholm.

This is the proceedings of the fourth in a series of inter national gatherings on kindling held on the University of British Columbia campus, June 15-17, 1989. Since the last gath ering in 1985, kindling continues to attract an ever-increasing number of investigators as reflected by the phenomenal increase in the number of kindling-related research reports. No other acute or chronic model has been exploited so extensively using electrophysiological, pharmacological, biochemical and behav ioural approaches involving a variety of brain sites and ani mal species. The continuing search, during the past few years, for the mechanism underlying the enduring change induced by kindling is beginning to shed some light on aspects of its molecular basis and to suggest the future direction of research. The late Graham Goddard, the original kindler, would have been delighted with this development. We were all shocked and saddened by his tragic death, but his spirit is very much alive among all of us who gathered together to share new information and collectively reassess the present state of knowledge at this symposium. I must say that we miss him very, very much. We know he is happy in his heaven knowing that he accomplished more in a short lifetime than most and that his love for mankind, and life's challenges, remain as a legacy, and goal, for us all.

Over the past decade, the study of microglial cells has gained increasing importance, in particular for those working in the fields of degeneration and regeneration. Microglia in the Regenerating and Degenerating CNS supports the assertion that understanding microglial biology could perhaps be pivotal for unraveling the pathogenetic mechanisms that underlie Alzheimer's disease, currently the most widely studied disorder of the central nervous system. In addition, microglia are also critical for understanding the sequelae of traumatic brain and spinal cord injury, and for the vitally important post-traumatic repair processes. This book gives an up to date account of the role of microglia in degeneration and regeneration of the nervous system and also reviews microglial cell function and physiology. Cellular neurobiologists will find that this is a valuable guide to the importance and role of microglia in the CNS.

Invertebrate animals represent a diversity of solutions to life's challenges. Success in a wide range of environments has been achieved by an almost bewildering range of invertebrate body forms. These body forms are reflected in the wonderful diversity of their nervous systems. Despite this apparent diversity, studies of the development of invertebrates and vertebrates are yielding common themes at the molecular level. Likewise, the phenome non of neural regeneration is based upon properties intrinsic to neurons and responses to a remarkably conserved chemical lan guage. This monograph focuses on the diversity and commonal ity of responses to neural injury. The rough and tumble of life may frequently damage some part of the body, particularly the appendages or sensory sys tems. The nervous system is usually involved in repair of other body systems and often may itself require repair. Some animals are particularly successful in regenerating the nervous system or body parts. We particularly marvel at these feats of regeneration because we human beings are not particularly successful, despite our relatively long life and the advantages that would seem to accrue from such repair. It is no wonder that we would hope to learn the secrets of the more successful animals and strive to emulate them Mechanisms of neural regeneration are often more acces sible in invertebrates than in vertebrates because questions of specificity are more easily addressed using the identifiable neu rons of the relatively simpler nervous systems of some inverte brates."

This volume addresses a fundamental puzzle in biology and medicine, namely, how does tissue develop, repair and replace itself. The answer appears to lie in growth factors and their regulation. To thrive and survive we need growth factors and this book concentrates on two factors that are related to growth hormone. Growth hormone does not act directly on all tissues, but mediates many of its actions through the release of insulin-like growth factors from the liver. The growth factors were originally called somatomedins by McConaghey and Sledge (1), who discovered that they mediated growth-like effects of growth hormone. However, the factors were purified on the basis of their insulinomimetic actions on fat and muscle and it is their relationship to the insulin family of pep tides that now gives them their name (2,3) of insulin-like growth factors (IGFs). They mediate the actions of. growth hormone on the proteoglycan synthesis of cartilage and produce mitogenic effects in fibroblast cultures.

Hyperthermia as a safe and effective cancer treatment modality is rapidly evolving propelled by widespread research and clinical efforts worldwide. Presentations on Hyperthermia experience are now commonplace at Oncology meetings, as are congresses dedicated entirely to the intertwined interactions between basic sciences and patient treatment that together are forming the structure of a new medical specialty. Such was the XII International Symposium on Clinical Hyperthermia held in Rome, Italy, April 27 - 29, 1989. Papers presented therein constitute the backbone of this book. Biology research has provided data describing mechanisms of action for the cancer cell killing and physiological effects of Hyperthermia. Physics research has led to the development of equipment enabling treatment of many areas of the human body, as well as explained the limitations that still constrain our ability to treat, especially in the areas of deep seated tumor heating and non-invasive thermometry. The main question that will decide the future of this modality is that of its clinical use. To put it succinctly, what do we do with this potentially useful tool in an everyday clinical oncological practice . ** ? This is the main question addressed in this book as "Consensus on Hyperthermia for the 1990s. " The book in cludes 28 presented papers and 25 invited chapters from some of the leading experts in the field. Their basic mechanisms of action were physics principles, treatment quality assurance and especially, clinical indications.

It has been acknowledged that the physiological effects of dietary fiber are an exceedingly complex matter which requires a multidisciplinary research effort. The increased scientific involvement of the medical community, nutritionists, chemists and physicists is not only warranted but it has become mandatory. This is because we are entering a more advanced research phase in which the observed . in vivo effects should not be only recorded, but they should be systematically correlated with the physicochemical and analytical properties of the individual dietary fibers. The Division of Agricultural and Food Chemistry of the American Chemical Society has recognized this for some time, and has asked us to organize another International Symposium, similar to one in 1982, which would address the latest developments in this field. We decided to ask a cross section of leading experts from industrial and academic research institutions to assess the state of the art in dietary fiber, namely in the areas of the physiological effects, physicochemical attributes, and in existing and proposed analytical methods. We also felt that chemistry and physical chemistry should playa greater role in fiber research to complement and better explain the existing . in vivo data. There is a large volume of animal and human physiological and nutritional data available. Unfortunately, the generated information is frequently confusing. One reason is that this research is not conducted with well characterized compounds, but rather with loosely defined complex mixtures or entities.

This extensively revised and expanded new edition offers concepts, principles and applied information that relates to the wellbeing of reptiles. As a manual on health and welfare in a similar vein to volumes addressing the sciences of anatomy, behaviour or psychology, this book thoroughly examines the biology of reptile welfare and is about meeting biological needs. The editors, acknowledged experts in their own right, have once again drawn together an extremely impressive international group of contributors. Positive and negative implications of general husbandry and research programs are discussed. In addition to greatly revised original content are nine new chapters offering readers novel insight into: * sensory systems * social behaviour * brain and cognition * controlled deprivation and enrichment * effects of captivity-imposed noise and light disturbance on welfare * spatial and thermal factors* evidential thresholds for species suitability in captivity * record keeping as an aid to captive care * arbitrary husbandry practices and misconceptions The authors have adopted a user-friendly writing style to accommodate a broad readership. Although primarily aimed at academic professionals, this comprehensive volume is fundamentally a biology book that will also inform all involved in captive reptile husbandry. Among others, zoo personnel, herpetologists, veterinarians, lab animal scientists, and expert readers in animal welfare and behavioural studies will benefit from this updated work.

Ivermectin and abamectin, members of the avermectin family of compounds, were introduced to the market in the 1980's as a veterinary antiparasitic drug and agricultural pesticide, respectively. Their acceptance and commercial success have been remarkable; both are highly effective and in worldwide use. The efficacy of ivermectin in river blindness has expanded the interest in its use in human medicine. In response to the intense scientific and industrial interest in ivermectin and abamectin and the likelihood that they will be forerunners of an expanding family of drugs, this comprehensive monograph satisfies the need for a review and synthesis of current knowledge about the use of these substances in crop protection as well as in cattle, sheep, swine, horses, dogs, cats, birds, fish, reptiles, and in man. This overview presents chemical, biochemical, and microbiological data, as well as pharmacological, safety, and environmental aspects and covers practical use of the compounds as antiparasitic and pesticide agents, as well as the available safety data that have emerged from the clinical experience with human applications.

an attempt to rationalize these terminological and conceptual difficulties we have considered the origins of mammalian heat production from two different points of view. The scheme depicted in Fig. 1. 1 illustrates the fate of energy in the body as seen by the nutritionist. After allowing for losses of energy in faeces and urine, the metabolizable energy obtained from food is utilized for main taining and increasing body energy content (maintenance, external work, growth and production). The transformation of metabolizable energy into these forms of net energy also involves inevitable energy losses in the form of heat - thermic energy. Similarly, maintaining homeothermy in cold en vironments involves shivering and non-shivering thermogenesis (NST) and the energy costs of assimilating nutrients and retaining net energy results in obligatory heat losses due to diet-induced thermogenesis (DIT). This obligatory DIT is mainly due to the energy cost of protein and fat synthesis but, in addition to this, there is an adaptive component of DIT that helps maintain body energy content (i. e. body weight) by dissipating the metabolizable energy consumed in excess of the requirements for maintenance, growth and production. In Fig. 1. 2, we have converted this nutritionist's scheme (A) into one that A B r-------. . ., I I Production, Growth I I External work I I I I Essential energy expenditure NET BASAL Obligatory 1 I ENERGY Maintenance HEAT heat I FASTING at (BMR) productlpn for t ROC thermoneutrallty homeothermia r."

The last decades have brought a significant increase in research on acoustic communi cation in animals. Publication of scientific papers on both empirical and theoretical aspects of this topic has greatly increased, and a new journal, Bioacoustics, is entirely devoted to such articles. Coupled with this proliferation of work is a recognition that many of the current issues are best approached with an interdisciplinary perspective, requiring technical and theoretical contributions from a number of areas of inquiry that have traditionally been separated. With the notable exception of a collection edited by Lewis (1983), there have been fewvolumes predominatelyfocused on technical issues in comparative bioacoustics to follow up the earlyworks edited by Lanyon and Tavolga (1960) and Busnel (1963). It was the tremendous growth of expertise c: ()ncerning this topic in particular that provided the initial impetus to organize this volume, which attempts to present fundamental information from both theoretical and applied aspects of current bioacoustics research. While a completely comprehensive review would be impractical, this volume offers a basic treatment of a wide variety of topics aimed at providing a conceptual framework within which researchers can address their own questions. Each presentation is designed to be useful to the broadest possible spectrum of researchers, including both those currently working in any of the many and diverse disciplines of bioacoustics, and others that may be new to such studies."

Biological effects of magnetic fields have been studied in many animals and plants. The magnetic fields were of a wide intensity range and, as alternating fields, of a wide frequency range and of a variety of impulse shapes. Effects on the cellular level, on bio chemical processes, growth and development, interactions with physiology, sensory input, reflexes and rhythm control, to name just a few, have been reported. Numerous magnetically induced changes in behavior have also been described. Recently, the amount of literature covering biological effects of magnetic fields has been rapidly increasing. By now it has grown to such an extent that it can no longer be covered in one volume. Most reviews specialize and focus on particular aspects and/or types of fields or effects. For example, the book edited by MARET et al. (1986) gives an overview on biological effects of steady magnetic fields, MISAKIAN et al. (1993) reviewed those of extremely low frequency magnetic fields, focusing on in vitro effects. BERN HARD (1992) reported on 'electromagnetic smog' in view of pos sible effects on human health and well-being, and a series of papers edited by AMEMIYA (1994) summarizes Japanese research on effects of electromagnetic fields ranging from extern ely low to ultra-high frequencies. TENFORDE (1979) and ADEY (1981) sum marized and discussed tissue interactions, REITER (1993a) neu roendocrine and neurochemical changes associated with various kinds of electromagnetic fields. The book edited by KIRSCHVINK et al."

Harderian glands, first described by Jacob Harder in two species of deer in 1694, are large, intraorbital glands which, with but few exceptions, are found in all land vertebrates. Certainly, their relatively large size, their phylogenetic age, and persistent conservation in all groups as they emerged from an aqueous to an air/land environment lend strong support to the logical deduction that they probably play an important role in the physiological adaptation to terrestrial life. Yet, few biologists know even what or where these glands are. For a variety of reasons, the Harderian glands have not received the attention they deserve and, as a result, the published works available have been scarce and scattered throughout the world literature. The current situation is remarkably similar to that which existed in regard to the pineal gland prior to the mid-1960s, i. e. , scattered literature, unknown function, few investigators, and little interest. Yet, following a few key papers, interest in the pineal gland expanded and soon an explosive increase in the knowledge and understanding of the pineal gland took place and continues today. Will history repeat itself? Originally, a few of us discussed the desirability of an informal Symposium on the Harderian glands.

6 Ions can pass through a single membrane channel at a rate of 10 ions/second. Over the last decade the ability to measure ion flux so precisely and to document the opening and closing of individual ion channels has provided a powerful tool to those working on smooth muscle physiology and vascular reactivity. The use of potassium channel blockers by Tom Lloyd in the 1960s and calcium channel blockers by Ivan McMurtry in the 1970s indicated the importance of ion flux in regulating pulmonary vascular tone. Recent advances in technology. principally the patch-clamp technique and fluorescent ion-sensitive dyes. now permit a more detailed description of physiologic mechanisms. This volume arises from the Sixth Grover Conference on the Pulmonary Circulation. a NATO Advanced Research Workshop. held in Colorado in October 1992. A group of international sCientists who are leaders in the field of ion flux focused their attention on the problems of the pulmonary vasculature. The chapters in this book describe the present state of knowledge of the movement and storage of ions in vascular endothelial and smooth muscle cells. Those who are not familiar with the techniques of patch clamping and calcium imaging will find an introduction to these methods in the chapters by Leblanc and Wan and Archer et al. The role of potassium channels in oxygen sensing illustrates the rapid progress which the study of ion currents has made possible.

It is two years since a general meeting of the Gesellschaft fur Biologische Chemie first requested us to organize the 21 st Mosbach Colloquium on mammalian reproduction, and one year since we received final authorization to do so. The present volume contains the papers read at the Colloquium, but the discussions have been omitted because writing and proof reading them would have delayed the appearance of this volume for an unjustifiable long time. Besides, in most cases the discussion was of a relatively specific nature and we did not consider it essential, bearing in mind that the purpose of the Mosbach Col loquia is to provide advanced further education for the non specialist. One of us has referred to this and to the topical structure of the 21 st Colloquium in the introductory and final remarks. Helpful suggestions for organizing the program were made by some of the invited speakers, but the first important impulses VON BERSWORDT-WALLRABE, Dr. ELGER, Dr. came from Dr. GERHARDS, Dr. NEUMANN, and Dr. UFER to whom we here wish express our thanks. Thanks are also due to those whose donations, some of which were very generous, made it financially possible to organize the Colloquium. HEINZ GIBIAN July 1970 ERNST JURGEN PLOTZ Contents Introduction. H. GIBIAN (Berlin) 1 General Outline about Reproductive Physiology and its Developmental Background. A. JOST (Paris) .. 4 The Significance of Hormones in Mammalian Sex Differentia tion as Evidenced by Experiments with Synthetic Andro gens and Antiandrogens. W. ELGER, F. NEUMANN, H.

Advances in Compararative and Environmental Physiology helps biologists, physiologists, and biochemists keep track of the extensive literature in the field. Providing comprehensive, integrated reviews and sound, critical, and provocative summaries, this series is a "must" for all active researchers in environmental and comparative physiology. Cellular volume and osmolality in animals is a well studied topic and this specific volume in the series provides the reader with a thorough grounding in this area of physiology. Consisting of two parts, the text discusses osmolality and volume control in terms of both inorganic and organic ions which as a result gives an excellent overview to those working and interested in this field.

Various endogenous and environmental challenges of homoiostasis have resulted in the evolution of apparently quite different mechanisms for the same or similar functions in individual representatives of the animal kingdom. One of the prominent achievements of comparative physiology over the last few decades has been the description of regula- tory features common to many studied species beyond the extreme diversity of their morphological forms. Delineation of functional princi- ples universally applicable to the physiology and biochemistry of living systems became often possible through technical advances in the devel- opment of numerous new techniques, in many cases modified and adopted from other fields of science, but also by approaching certain problems using multifactorial analysis. The advance in technology has facilitated studies of minute functional details of mechanisms, which finally lead to better understanding of generally similar functions, covered by the multiple developments of Nature as a response to an extreme variety of different conditions. Improved understanding of specific mechanisms, however, has presented new problems at the level of system integration. The importance of the integrative aspect became particularly apparent during an international symposium on 'Mecha- nisms of Systemic Regulation in Lower Vertebrates: Respiration, Circu- lation, Ion Transfer and Metabolism' (organized in 1990 by Norbert Heisler and Johannes Piiper at the Max-Planck-Institut flir experimen- telle Medizin at Gottingen/Germany).

Comparative endocrinology helps to find the roots of homeostatic regulation in organisms. In this context, many years ago a series of experiments were done, which demonstrated the hormonal regula tion also on the invertebrate level. The mechanisms are partly similar, partly different, from those found in vertebrates. The new receptor era of mammalian endocrinology stimulated research on invertebrate hormone receptors, and sophisticated methods are applied also to determine hormones. The experiments demonstrated the existence and even similar function of these structures and signaling molecules. However, data on hormones and receptors at the lowest level of metazoan life and the highest level of protozoan life were not at our disposal. About two decades ago, first observations on the presence of hormone receptors reacting to vertebrate hormones in protozoa were made. Since the early 1980s we know that hormone-like molecules similar to those of higher vertebrates are present also in unicellular organisms. The presence of some second messengers in Tetrahymena was recognized. Since then, the research has been extended and many structures - previously believed to be solely vertebrate characteristics, such as opiate receptors, similar to mammalian ones - were found in unicellular organisms. These observations justified the assumption of a complete endocrine system at protozoan level, where - considering the unicellularit- this seemed to be not required. However, it became clear that the roots of endocrine communication date back at least 2 billion years."

Presenting an analysis of the water relationships of the major groups of organisms: fungi, plants and animals, the text examines water stress at all levels of biological organization. Topics covered include: 1) organic osmotic agents: their distributions, modes of action, and mechanisms of regulation; 2) desiccation stress; mechanisms for preserving cellu lar integrity under conditions of low cellular water activity; 3) water stress and water compartmentation in plants; and 4) freezing stress: the prevention and regulation of ice formation in biological fluids, and mechanisms for overcoming the damaging effects of low temperatures on cellular integrity. Common adaptive strategies in diverse organisms are emphasized, as well as the fundamental physical-chemical properties of aqueous solutions that establish the nature of the interactions among water, low molecular weight solutes and macromolecules.

In recent years many of the conventional methods of insect control by broad spectrum synthetic chemicals have come under scrutiny because of their unde sirable effects on human health and the environment. In addition, some classes of pesticide chemistry, which generated resistance problems and severely affected the environment, are no longer used. It is against this background that the authors of this book present up-to-date findings-relating to biochemical sites that can serve as targets for developing insecticides with selective prop erties, and as the basis for the elucidation of resistance mechanisms and countermeasures. The book consists of eight chapters relating to biochemical targets for insec ticide action and seven chapters relating to biochemical modes of resistance and countermeasures. The authors of the chapters are world leaders in pesti cide chemistry, biochemical modes of action and mechanisms of resistance. Biochemical sites such as chitin formation, juvenile hormone and ecdysone receptors, acetylcholine and GABA receptors, ion channels, and neuropeptides are potential targets for insecticide action. The progress made in recent years in molecular biology (presented in depth in this volume) has led to the iden tification of genes that confer mechanisms of resistance, such as increased detoxification, decreased penetration and insensitive target sites. A combina tion of factors can lead to potentiation of the resistance level. Classifications of these mechanisms are termed gene amplification, changes in structural genes, and modification of gene expression.

A comparison of the adaptations made by invertebrates in polar deserts with those of temperate and subtropical deserts. These regions represent some of the most hostile environments on earth, demanding an array of strategies for survival. Polar species are well adapted to the cold and have to cope with arid conditions due to low precipitation and lack of liquid water during the winter. Similarly, temperate desert invertebrates have adapted to dry conditions and are also exposed to low winter temperatures. Terrestrial arthropods maintain their water-balance through behavioural and physiological adaptations. Tardigrades and nematodes are remarkable in their ability to shed all their water before entering a state of anhydrobiosis only to be revived when moisture once again becomes available.