The research field of somatosensory processing in mammals has experienced revolutionary changes in recent years. Accumulation of basic and clinical data has greatly accelerated, and new phenomena have emerged. With the aid of new, refined methods, molecular and cellular changes have been described, underlying the signal transduction-transmission between the internal/external environment and the central nervous system have been described. The discovery of the interaction between the nervous and the immune system has, for example changed our view on the development of inflammatory diseases, while the cloning of genes encoding different trophic factors has boosted studies revealing profound changes in the regeneration of neurons, and induction of changes in phenotype. The study of the pre-and postsynaptic modulation of transmitter release, and the examination of the combined effects of amino acid and peptide transmitters has become recently possible by using cultured cell lines and in vitro techniques. Although it is in embryonic state, computational properties of single DRG cells under normal and pathological conditions are being investigated. Results soon or later will have a great impact on pain research and consequently ultimately in clinical pain management. This brief introduction indicates how our knowledge of the somatosensory system has increased dramatically recently. However, many investigators cultivate only a very specific field in the growing area of somatosensory research and find it difficult to integrate a more universal knowledge of their work.

Space missions subject human beings or any other target of a spacecraft to a radiation environment of an intensity and composition not available on earth. Whereas for missions in low earth orbit (LEO), such as those using the Space Shuttle or Space Station scenario, radiation exposure guidelines have been developed and have been adopted by spacefaring agencies, for exploratory class missions that will take the space travellers outside the protective confines of the geomagnetic field sufficient guidelines for radiation protection are still outstanding. For a piloted Mars mission, the whole concept of radiation protection needs to be reconsidered. Since there is an increasing interest ci many nations and space agencies in establishing a lunar base and lor exploring Mars by manned missions, it is both, timely and important to develop appropriate risk estimates and radiation protection guidelines which will have an influence on the design and structure of space vehicles and habitation areas of the extraterrestrial settlements. This book is the result of a multidisciplinary effort to assess the state of art in our knowledge on the radiation situation during deep space missions and on the impact of this complex radiation environment on the space traveller. ]t comprises the lectures by the faculty members as well as short contributions by the students given at the NATO Advanced Study Institute "Biological Effects and Physics of Solar and Galactic Cosmic Radiation" held in Armacao de Pera, Portugal, 12-23 October, 1991.

A number of remarkable recent breakthroughs have made the study of nitric oxide one of the most exciting fields in physiology and pathophysiology. This authoritative edited volume reviews the progress to date and opens perspectives to novel diagnostic and therapeutic strategies. The contributors are leading authorites, in most cases the investigators who have pioneered the ideas explored in the book.

The past two decades have witnessed an unprecedented growth in the field ofneuroendocrinology. The conjoint research contributions by clinicians and basic scientists have promulgated revolutionary concepts at a breakneck speed. This first volume in Clinical Surveys in Endocrinology, The Pituitary Gland, has been written with but one purpose in mind: to integrate the current knowledge in this dynamic field with the existing body of information already available to the clinician. The chapters in this book attempt to portray current research information seen through the eyes of a clinician. The contributions of pioneers in each field have been placed in a perspective relevant to the practicing endocrinologist. The selection of the almost 1500 references from a bewil of literature has been inftuenced by the degree to which these dering body articles-original as weil as review papers-contributed to the growth of pi tuitary endocrinology. Despite the most scrutinizing attempts, it is inevitable and regrettable that works of importance must be excluded due to the practical limitations of any comprehensive work. Nevertheless, to the researcher these references are complete enough to serve as a significant resource. To the reader who wishes to gain an indepth clinical perspective of pituitary disor ders, this work is written precisely from that vantage point. The single authorship of this work notwithstanding, several friends have been instrumental in the completion of this work. I deeply appreciate the incessant zeal and excellent assistance of Ms."

I had the good fortune to first meet Gerald Kuchling in 1985 when attending a conference held at the CNRS research centre, the Centre d'Etudes Biologiques des Animaux Sauvages (CEBAS), which is a wonderful scientific field station tucked away in the Foret de Chize, not far from the southwest town of Niort in France. The topic of the meeting, which included many invited overseas scientists, was "Physiological Regulations as Adaptive Mechanisms", and it was superbly organised by Ivan Assenmacher and Jean Boissin who together edited the impor- tant volume of papers published from the meeting. My stay in Chize was, unfor- tunately, cut short as the wife of a very close colleague died on the night of the first day of the meeting and I had to return to Paris to assist with the funeral -but not before I had the chance to meet and talk with Gerald. He was presenting some of his work on a terrestrial tortoise (or turtle depending upon one's origins) - Testudo hermanni - a species that is now extremely rare in France but still relatively abundant in the then Yugoslavia. Gerald had been working in Yugoslavia, collecting blood samples from both males and females in an attempt to decipher details of its reproductive biology.

This book is a compendium of proceedings from the Symposium on Growth Hormone II: Basic and Clinical Aspects. The intent of the sym posium was to review current aspects of the rapidly expanding science of growth hormone (GH) neuroendocrinology, especially those develop ments that occurred since our last meeting in 1985. The meeting was timely since there have been many new and exciting developments in basic research on the GH axis, and several new clinical applications for GH other than growth have been identified. For example, significant strides have been made into use of the bioengineered hormone as an anabolic in debilitated states and as an immunorestorative agent. Both these areas have received most attention as they relate to geriatric popu lations. Furthermore, recent focus on a novel family of GH secretagogues that complement the action of GHRH has shown that in animal models, these compounds have the potential to restore GH secretion in deficient or insufficient states, including growth retardation, obesity, and aging. Accordingly, these xenobiotics may have significant potential as drug products to stimulate physiological GH secretion and, thus, resist or reverse some of the maladaptive changes in form and function resulting from GH insufficiency. The importance of these agents as drug candidates is underscored by the diversity of molecules that have been studied by various pharmaceutical companies and the recent discovery that non peptide analogs with high oral bioavailability can be synthesized."

The auditory system has a remarkable ability to adjust to an ever-changing environment. The six review chapters that comprise Plasticity of the Central Auditory System cover a spectrum of issues concerning this ability to adapt, defined by the widely applicable term "plasticity." With chapters focusing on the development of the cochlear nucleus, the mammalian superior olivary complex, plasticity in binaural hearing, plasticity in the auditory cortex, neural plasticity in bird songs, and plasticity in the insect auditory system, this volume represents much of the most current research in this field. The volume is thorough enough to stand alone, but is closely related a previous SHAR volume, Development of the Auditory System (Volume 9) by Rubel, Popper, and Fay. The book fully addresses the difficulties, challenges, and complexities of this topic as it applies to the auditory development of a wide variety of species.

This volume, The Adrenal Gland, is the second in the Clinical Surveys in Endo crinology series. Like its predecessor on the pituitary gland, this work is written with one purpose in mind-to view the vast, relevant adrenal literature through a clinician's eyes. The intricate, and often complex, interrelationship between the clinical and research perspectives of "adrenology" poses a challenge. This is, in part, due to the commonly held belief that the milieux of steroid hormone research and clinical medicine are parallel phenomena, not destined to meet. But the twain do meet, and often with relative ease, when viewed as twin facets of the same gem. The view presented in this work is from the vantage point of the clinical endocrinologist who applies the research literature to understand adre nal diseases more clearly. Adrenal pathology is arguably the most fascinating of all endocrinopathies. The images of patients suffering from adrenal diseases are of kaleidoscopic quality: the newborn child with ambiguous genitalia, in whom the very first ritual of assigning sex becomes shrouded with uncertainty; the revitalized pa tient with hitherto undiagnosed Addison's disease, who but for the cognitive powers of the endocrinologist would have ultimately succumbed, undiagnosed; the virilized female with adrenal tumor and its attendant onslaught on the body and mind; the febrile patient with pheochromocytoma masquerading as fever of undetermined origin for months."

In some countries, especially on the European continent, there still exists a remarkable veal market. This type of meat production seems, irrespective of any economic forecasts, to remain unchallenged so long as consumers expect that restaurants should offer courses like "r6ti de veaux," "vitello a la casa" or "Kalbsschnitzel." Producers, at least since about the past 1-/2 decades, have been aware of the beneficial effect of anabolic agents in veal production. This is possible due to the lack of endogenous sexual hormones during the juvenile or prepuberal status of these animals. A discussion about the benefit / risk - evaluation in connection with the use of anabolic agents in general was promoted in recent years by the public. This concern occurred concomitantly with the detection of illegally treated veal calves and the occurrence of diethylstilbestrol (DES) residues in canned food containing veal. The aim of this paper is to summarize the present status of residue data in edible tissues and excreta in order to allow the evaluation of the risk (given in the paper of Hoffmann within this program) and to consider reasonable monitoring measures. We have to face the fact that without an efficient control system the illegal treatment of calves can not be excluded. Therefore, this paper will not only consider different compounds and formulations, but will also deal with practised routes of administration.

While there have been many recent books on the cell surface and a few on the topic of cilia and flagella, this is the fIrst volume that attempts to bring together the available informa- tion on ciliary and flagellar membranes. This reflects a slow awakening by cell biologists and other scientists to the signifIcance of ciliary and flagellar surfaces. When Michael Sleigh edited an excellent book entitled Cilia and Flagella in 1974, not one of the sixteen chapters was devoted to ciliary or flagellar surfaces. When W. B. Amos and J. G. Duckett edited the very fIne 25th Symposium of the Society for Experimental Biology on Prokaryotic and Eukaryotic Flagella in 1982, only two of the twenty chapters on eu- karyotic cilia and flagella were devoted to ciliary and flagellar surfaces. Only in 1989 has the timing become right to produce a volume entirely devoted to the nonaxonemal struc- tures and functions of eukaryotic cilia and flagella. The fIfteen chapters in this volume cover a wide spectrum of organisms (from protozoa and algae to birds and mammals) and an equally wide spectrum of topics (from sexual interactions in the algae to the binding of pathogens in the lung).

Legumes are an important source of protein for humans and animals. They provide nutritionally rich crop residues for animal feed, and playa key role in maintaining the productivity of soils particularly through biological nitro gen fixation. They are, therefore, of immense value in rainfed farming systems. The International Center for Agricultural Research in the Dry Areas (ICARDA) has a responsibility for research on food, pasture, and forage legumes. The Center also has the broad objective of improving livestock production in rainfed farming systems. Although food legumes have be n known and grown by farmers in the WANA region for a long time, their productivity has remained low and variable. Forage legumes, on the other hand, are not so well known by farmers of the region, and their role in the farming systems is not so well understood. Thus, we need to develop the concept of using forage legumes as crops and to fit them into cropping systems. In its efforts to increase the productivity of food legumes and develop the legume-based crop/livestock systems, ICARDA has established a network of scientists in the different National Agricultural Research Systems in the region. To further strengthen this network, ICARDA convened a workshop on 'The Role of Legumes in the Farming Systems of Mediterranean Areas' in Tunis, Tunisia, 20-24 June 1988. This workshop was co-sponsored by UNDP, who also contributed funds for this publication."

Even though transmitter release and re-uptake are very complementary and physically in close proximity, researchers usually focus on only one of these two aspects. This volume, however, covers both processes and brings together two major presynaptic events in transcellular communication. It comprises 24 chapters and is divided into two parts: Part I, Neurotransmitter Release, and Part II, Neurotransmitter Uptake. The included topics range from ultrastructure and molecular control mechanisms to pathophysiology of some diseased states. Neuronal as well as non-neuronal mechanisms are treated. The concluding chapter emphasizes the importance of interdisciplinary collaboration and provides a link between the events in the presynaptic terminal and behavior.

70 years after the discovery of secretory neurons, internationally leading experts gathered to discuss the latest developments in neuropeptide research and endocrinology, concentrating on the molecular, cellular, supracellular and systemic aspects. A variety of neuropeptidergic systems are considered under comparative and evolutionary aspects.

The XIIth North American Testis Workshop was held in Tampa, Florida, April 13 to 16, 1993. The program consisted of 23 invited lectures and 120 poster presentations. In keeping with the tradition of the Testis Workshop, every attempt was made to emphasize recent develop- ments in the study of endocrine and gametogenic functions of the male gonad. Although the main emphasis, reflected in the title of the pro- ceedings, was on the function and control of somatic cells in the testis, one session was devoted to germ cells and one to the studies of male reproductive development and function. The last session of the workshop was included in the program of the Postgraduate Course of the American Society of Andrology, which held its annual meeting in Tampa imme- diately following the workshop. This volume consists of 21 chapters prepared by the speakers and 8 chapters contributed by presenters of the posters. The Program Committee consisted of Drs. Nancy Alexander, C. Wayne Bardin, Andrzej Bartke (Chairman), Kevin J. Catt, Claude Desjardins, Maria Dufau, Michael Griswold, Norman Hecht, Aaron Hsueh, Dolores J. Patanelli, Bernard Robaire, and Richard Sherins. The workshop was generously funded by Serono Symposia, USA, which also agreed to handle registration, local arrangements, and publication of this volume. On behalf of the Program Committee and all participants, I would like to thank Dr. Bruce Burnett of Serono Symposia, USA and his staff for their efforts and support in every aspect of the organization of the workshop.

The fourth Oxford Conference entitled "Control of Breathing: A Model ing Perspective" was held in September of 1988 at Grand Lake, Colorado. Grand Lake, also called Spirit Lake, was chosen for the fourth meet i ng so as to continue the meditative atmosphere of the previ ous meetings and to put the conference on a new higher plane (8,500 feet). The weather, as promised, exhibited its random-like rain showers. The snow report became essential for traveling the 12,000 foot passes to and from Grand Lake. Even the servi ces such as telephone and elect ri city proved to be uncertain. In all, the overall atmosphere of Spirit Lake contributed to an uninhibited free-style of presentation and interaction. All of us who attend the Oxford Conferences share a common interest in exploring respiratory control and the regulation of breathing. Modeling has become an adjunct to our exploration process. For us, models are tools that extend our ability to conceptualize just as instruments are tools that extend our ability to measure. And so these meetings attract physicians, physiologists, mathematicians and engineers who are modelers and modelers who are engineers, mathematicians, physiologists and physicians. Four of these physician-modelers have now passed away. They have been very important mentors for many of us. J. W. Bellville was my Ph.D. dissertation advisor at Stanford who introduced me to the intrigue of respiratory control. G. F. Filley was my colleague at the University of Colorado who enhanced my thinking about respiratory control. E. S.

Deserts, whether hot or cold, are considered to be one of the most difficult environments for living systems, lacking the essential free water which ac counts for approximately 60-70% of their body mass and more than 98% of their constituent atoms {Macfarlane 1978}. Amongst vertebrates, reptiles are usually thought of as the animals most adapted or suited to such environments because of their diurnal habit, based on a need for external heat, and their ability to survive far from obvious sources of water. This impression is rein forced when one examines the composition of vertebrate faunae characteristic of deserts and arid zones: reptiles predominate and they are often the only vertebrates to be found in hyper-arid areas, such as some parts of the Sahara {Monod 1973}. I recently had occasion to examine this assumption carefully, however, and was led inexorably to the conclusion that reptiles represent a particularly successful desert group, not because of their evolution of superior adaptations, but because of their possession of a basic suite of behavioural and physiologi cal characteristics that suit them uniquely to this very resource-limited environment {Bradshaw 1986a}. These fundamental reptilian characteristics are: 1. their low rates of metabolism, compared with birds and mammals, which result in extremely low rates of resource utilisation and lead to considerable economy in the handling of water 2."

An excellent survey of the most recent advances in the area of cellular and molecular biology of glial cells and their involvement in remyelination and functional repair in the CNS. A major part of this book deals with signaling paths within and among neural cells. Glial cells (astrocytes, oligodentrocytes, microglial cells) themselves release substantial amounts of cytokines, growth factors and other signaling molecules, which play an important role during injury and regeneration. Another signaling route between neurons and glial cells follows ion channels and neurotransmitter receptors. In addition to animal models, human oligodentrocytes in cell culture and in the human MS brain are characterized with respect to their immunocytochemistry and function.

The second edition of the book on language comprehension in honor of Pim Levelt's sixtieth birthday has been released before he turns sixty-one. Some things move faster than the years of age. This seems to be especially true for advances in science. Therefore, the present edition entails changes in some of the chapters and incorporates an update of the current literature. I would like to thank all contributors for their cooperation in making a second edition possible such a short time after the completion of the first one. Angela D. Friederici Leipzig, November 23, 1998. Preface to the first edition Language comprehension and production is a uniquely human capability. We know little about the evolution of language as a human trait, possibly because our direct ancestors lived several million years ago. This fact certainly impedes the desirable advances in the biological basis of any theory of language evolution. Our knowledge about language as an existing species-specific biological sys tem, however, has advanced dramatically over the last two decades. New experi mental techniques have allowed the investigation of language and language use within the methodological framework of the natural sciences. The present book provides an overview of the experimental research in the area of language com prehension in particular."

The auditory system presents many features of a complex computational environment, as well as providing numerous opportunities for computational analysis. This volume represents an overview of computational approaches to understanding auditory system function. The chapters share the common perspective that complex information processing must be understood at multiple levels; that disciplines such as neurobiology, psychophysics, and computer science make vital contributions; and that the end product of computational analysis should be the development of formal models.

This monograph contains the contributions to the NATO Advanced Studies Institute on "Vascular Endothelium: Responses to Injury", which took place in Crete, Greece from June 18 to 27, 1994. This was the fourth in the series of NATO-supported ASIs in selected specific areas of endothelial cell biology, which began in 1988. Each time, it has combined clinical with basic scientists and renowned experts with novices in the field, in an attractive setting conducive to dissemination of knowledge, high quality discussions and exchange of ideas. This, as well as previous ASIs, reflects the hard work of numerous people. As Co- Directors, we have been particularly fortunate to benefit from the expert advice of the Organizing Committee, which included Elizabetta Dejana, Alberto Mantovani and Magdi Yacoub. Their insightful suggestions helped formulate the scientific program of the ASI. We are also grateful for the work and dedication of the local organizing committee of Thomie Douraki, Stylianos Orfanos, Panayotis Behrakis, Michael Maragoudakis and Lydia Argyropoulos who tirelessly looked after the main details necessary to ensure that all of us enjoyed the meeting. Similarly, we wish to thank Jim Parkerson, Connie Snead, Andreas Papapetropoulos and Nandor Marczin for their assistance in various aspects of the many preparations for the conference. A very special thanks goes to Annie Cruz, the ASI Co- ordinator, for her efficient, solicitous and pleasant demeanor during the months prior to the ASI and especially during the ten days of the conference.

nd The 22 meeting of the International Society on Oxygen Transport to Tissue (LS. O. T. T. ) of which this volume is the scientific proceedings, was held in Istanbul, Turkey on August 22-26, 1994. It was a historical occasion in that it was almost 200 years to the day that one of the founding fathers of oxygen research, Antoine Lavoisier, on May 8, 1794 found his early demise at the hands of the guillotine. This spirit of history set the tone of the conference and in the opening lecture the contribution that this part of the world has given to the understanding of oxygen transport to tissue was highlighted. In particular, the contribution of Galen of Pergamon (129-200) was discussed who for the first time demon strated that blood flowed through the arteries and whose view on the physiology of the circulation dominated the ancient world for well over a millennium. A forgotten chapter in the history of the circulation of the blood is the contribution made by Ibn al Nafis of Damascus (1210-1280) who for the first time described the importance of the pulmonary circulation by stating that all venous blood entering the right ventricle ofthe heart passes to the left ventricle, not through pores in the septum of the heart as had been postulated by Galen, but through the circulation of the lungs."

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."

The Springer Handbook oj Auditory Research presents a series of com prehensive and synthetic reviews of the fundamental topics in modern auditory research. It is aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes will introduce new investigators to important aspects of hearing science and will help established investigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume is intended to present a particular topic comprehensively, and each chapter will serve as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The series focuses on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature. Each volume in the series consists of five to eight substantial chapters on a particular topic. In some cases, the topics will be ones of traditional interest for which there is a solid body of data and theory, such as auditory neuroanatomy (Vol. 1) and neurophysiology (Vol. 2). Other volumes in the series will deal with topics which have begun to mature more recently, such as development, plasticity, and computational models of neural processing."

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, De- cember 2nd_4th, 1996. Liver cirrhosis is one of the main causes of death in occidental countries. There are other hepatic dysfunctions such as fulminant hepatic failure, Reye's syndrome, or congenital deficiencies of urea cycle enzymes which can also lead to hepatic encephalopathy, coma and death. However, the molecular bases ofthe pathogenesis of hepatic encephalopathy remain unclear. One ofthe consequences of hepatic failure is the reduced ability to detoxify ammonia by incorporating it into urea. This leads to increased blood ammonia levels. Hyperam- monemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy and classical clinical treatments are directed towards reducing blood ammo- nia levels. Altered neurotransmission is an essential step in the pathogenesis of hepatic encephalopathy. The first part of the book is devoted to the discussion of the recent advances in the understanding of the alterations of different neurotransmitter systems in hepatic encephalopathy. The alterations of tryptophan metabolism and neurotransmission in hepatic encephalopathy and the implications for the clinical use of neuropsychoactive drugs are reviewed. The alterations in glutamate transport and neurotransmission in hepatic encephal- opathy due to acute liver failure are also reviewed. The role of NMDA receptors in the molecular mechanism of acute ammonia toxicity is discussed as well as its modulation by metabotropic glutamate receptors and muscarinic receptors.

The Third International Symposium on Excitation-Contraction Coupling in Skeletal, Cardiac, and Smooth Muscle, organized by George Frank, C. Paul Bianchi, and Henk E. DJ. ter Keurs, was held in Banff Centre, Banff, Alberta, Canada during June 26 to June 30, 1991. The theme of these symposia has been to recognize the similarities and dissimilarities of excitation-contraction coupling in skeletal, cardiac, and smooth muscle. Cross fertilization of concepts of excitation-contraction coupling in these three types of muscle has occurred since the early studies in the late fifties and early sixties on skeletal muscle. Investigators in each field meet only at specialized symposia which exclude investigators in the other fields. The purpose of the symposia has been to bring together international investigators studying excitation-contraction coupling in skeletal, cardiac, and smooth muscle so that we may learn from each other and hence provide a more global concept of excitation-contraction. The Third International Symposia has accomplished its objective as we recognize that calcium channels of the sarcolemma and the sarcoplasmic reticulum play key essential roles in excitation-contraction coupling in all three types of muscles. In skeletal muscle the recognition that E-C coupling consists of two parallel mechanisms, one dependent upon a dihydropyridine voltage-sensitive sensors coupled to calcium release from the terminal cisternae via the ryanodine sensitive channel in the foot structure of the triad.