Since 1959, the International Society of Arterial Chemoreception (ISAC) has organized in a variety of countries fifteen scientific meetings devoted to the mechanisms of peripheral arterial chemoreception and chemoreceptor reflexes. After the meeting held in Philadelphia with Sukhamay Lahiri as president, ISAC membership elected Lyon (CNRS, University Claude Bernard, France) as the site of the xv" ISAC Symposium. The Symposium was effectively held in Lyon from the 18th to the 22nd of November 2002 and Jean-Marc Pequignot was its president. The organizers were Jean-Marc Pequignot and Yvette Dalmaz Lyon (CNRS, University Claude Bernard, France) and the Scientific Committee was formed by John Carroll (University of Arkansas for Medical Sciences, USA), Constancio Gonzalez (University of Valladolid, Spain), Prem Kumar (University of Birmingham, U. K. ), Sukhamay Lahiri (University of Pennsylvania, Philadelphia, USA), Colin Nurse (McMaster University, Hamilton, Ontario, Canada), and Nanduri Prabhakar (Case Western University, Cleveland, Ohio, USA). The Symposium in Lyon intended to follow the path opened in Philadelphia gathering people working at the interface of cellular and molecular biology with researchers in the more classical topics of chemoreception pathways and reflexes. The aim was to join experts with different perspectives. Along these lines, some participants are engaged in the exploration of the intimate mechanisms of oxygen sensing and cellular responses, with their work centered in a great number of preparations covering a broad spectrum from bacteria, to chemoreceptor cells or to central nervous systems neurons.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here

Knowledge about the structure and function of the inner ear is vital to an understanding of vertebrate hearing. This volume presents a detailed overview of the mammalian cochlea from its anatomy and physiology to its biophysics and biochemistry. The nine review chapters, written by internationally distinguished auditory researchers, provide a detailed and unified introduction to sound processing in the cochlea and the steps by which the ensuing signals are prepared for the central nervous system.

Parameters such as membrane transport, metabolism and protein incorporation govern the fate of amino acids in living tissue. Is it possible to use positron tomography to measure some of them, and what is their meaning in normal and pathological situations? These questions have been addressed for a long time and no satisfactory answer has yet been given. This book, which derives from an EEC workshop organized in the frame of the Concerted Action on PET Investigation of Cellular Regeneration and Degeneration', held in Lyon in February 1992, gives the present state of knowledge in this field based on the most recent studies. Contributions from 24 leading European and American scientists are presented and discussed in the following four parts: biochemistry and animal studies; amino acids labelling with positron emittors, quality control and metabolites measurement; kinetic modelling of amino acids transport, metabolism, and protein incorporation; clinical use of amino acids. This book will aid and interest biochemists, radiochemists, pharmacologists, neurologists, oncologists and medical imaging scientists.

In March 1996 the Society of Experimental Biology (UK) together with two other international scientific societies, the Australian and New Zealand Society for Comparative Physiology and Biochemistry and the Society for Integrative and Comparative Biology (formally the American Society for Zoology) joined forces with Springer-Verlag, Heidelberg to produce one of the first fully electronic online, peer-reviewed biological journals, Experimental Biology Online. The present product represents the fruits of this joint venture and encapsulates Volumes 1 and 2 of the journal. This will be an ongoing series such that an archival version of the journal will be available to all libraries as well as the on-line version. At the outset this was "new land" for all concerned but the launching of a journal which would cover experimental biology in terms of Animal, Cell and Plant topics was daunting but we all felt that the use of electronic media and the internet would be ideally suited to this purpose.

Diabetes is an autoimmune, inflammatory disease affecting many different organ systems and exhibiting both primary and secondary defects. Because diabetes affects a wide range of cellular systems, a multidisciplinary effort has been mounted over the past several decades using a wide range of investigative techniques and methodologies in order to identify molecular mechanisms responsible for cellular dysfunction. Because primary defects at various levels of sub-cellular signaling, intracellular calcium handling, protein expression and energy regulation are often a primary consequence of diabetes. This volume is a compilation of new multidisciplinary research that will broaden our current understanding of diabetes and cardiovascular disease as well as provide the basis for the development of novel therapeutic interventions.

Gasps, sighs, and yawns are recognized by even a casual observer as involuntary expressions of emotion through the "medium" of respiration. In recent years, scientific observation has focused on sensation and behavior as researchers investigate the relation of emotion and stress in disorders such as asthma, hyperventilation, and panic disorder. Until now, however, the interplay of psychological factors and physiological responses has not been approached from the interdisciplinary perspective reported in this book. Brought together here is the work of physiologists, psychologists, and researchers in behavioral medicine, together with - for the first time - specialists and practitioners of traditional Japanese arts and culture. Knowledge of the art and control of breathing, which are essential features of such disciplines as Zen and Noh, opens a new and until now unexplored path for scientists seeking to understand the relation between respiration and emotion.

This, the 148th volume of the Handbook of Experimental Pharmacology series, focuses on the very core of pharmacology, namely receptor theory. It is fitting that the originator of receptor pharmacology, A. J. CLARK, authored the fourth volume of this series 63 years ago. In that volume CLARK further developed his version of receptor theory first described four years earlier in his classic book The Mode of Action of Drugs. An examination of the topics covered in volume 4 reveals a striking similarity to the topics covered in this present volume; pharmacologists today are still as interested in unlocking the secrets of dose-response relationships to reveal the biological and che mical basis of drug action as they were over half a century ago. Sections in that 1937 volume such as "Curves relating exposure to drugs with biological effects" and "Implications of monomolecular theory" show Clark's keen insight into the essential questions that required answers to move pharma cology forward. With the advent of molecular biological cloning of human receptors has come a transformation of receptor pharmacology. Thus the expression of human receptors into surrogate host cells helped unlock secrets of receptor mechanisms and stimulus-transduction pathways. To a large extent, this elim inates the leap of faith required to apply receptor activity of drugs tested on animal receptor systems to the human therapeutic arena. However, a new leap of faith concerning the veracity of the effects found in recombinant systems with respect to natural ones is now required.

This volume, originally published in 1981, provides a comprehensive account of the structure, development, evolution, functional adaptations and growth of the skull of the placental mammals. A special feature, and indeed principal purpose of the approach, is the integration of the purely anatomical aspects of structure and development of the skull largely worked out in the later years of the nineteenth and early years of the twentieth century with the findings of modern investigations of the evolution, function and postnatal growth of the skull. The significance of further advances becomes more readily understandable when seen against the background of comparative anatomy and embryology. Professor Moore's fresh approach to his subject will be welcomed by anatomists, embryologists, palaeontologists, comparative zoologists and physical anthropologists.

The peoples of the high-altitude regions of the world have long fascinated both scientists and laymen from the lowlands. This book, while it draws heavily on the research conducted in the International Biological Programme, is a comprehensive review of our knowledge about the biology of the high-altitude peoples of the world. While several other accounts have considered the general problems of human populations living and working under the reduced oxygen pressure found at high altitude, this volume is the first attempt to analyse the total human biology of the peoples of the world living in extremely high mountain areas. The contributors are experts in a variety of topics within human biology. In addition, each has conducted personal research in the high-altitude areas such as the Andes, Ethiopian highlands, Himalayas or Tien Shan mountains. While the book is not designed for the layman, technical language has been reduced in an effort to make the various topics covered comprehensible to professionals working in any branch of the sciences concerned with man.

Animal Cell Culture nimal cell culture began in 1912 when Alexis Carrel grew bits of chick heart A in vitro by placing them into a drop of horse plasma. When the plasma clotted, it formed a solid surface into which the heart cells explanted. Left unattended, these cells died within several days. By regularly feeding the grow ing cells with aqueous extracts of whole chick embryos and periodically sub dividing them, Carrel was able to maintain the cells for extended periods. From these initial experiments, cell culture has expanded into an important component of biological research and commercial production. Animal cell culture is an important tool for the study of complex biologi cal systems. In vivo it is often impossible to target a treatment to one specific cell type or to adequately control the environment. For example, it is impos sible to selectively depolarize endothelial cells in vivo to determine the role of transmembrane potential in the transduction of fluid mechanical forces generated by blood flow to a biochemical response. Depolarizing all of the cells within the vascular system by injecting potassium chloride into the animal's bloodstream clearly is not an option, as it will lead to cardiac arrest."

The first edition of this book was well received by updated. The two of us have made further collab orative efforts to present a better understanding of medical students, graduate students, and clinicians interested in furthering their understanding of basic the function of the kidney in conjunction with the principles of renal physiology. Most of the reviews most recent anatomical findings. of the first edition and comments from the various The second edition consists of 13 Chapters and 3 instructors who used the book were very positive Appendices. As in the first edition, the anatomical and complimentary with regard to the presentation description of the kidney is incorporated into the of the physiological information and the use of the various chapters dealing with kidney functions. Most system analysis approach to describe renal function. of the anatomical information was written by Wil These positive and encouraging comments over the helm Kriz. The physiological information was writ past nine years, since the publication of the first ten by Esmail Koushanpour, except for Chapter 12 edition, gave us the impetus to consider the prepa which was jointly written. Chapters 1 through 3 were ration of a second edition."

The study of plant development using molecular and genetic techniques is rapidly becoming one of the most active areas of research on flowering plants. Developmental Biology of Flowering Plants relates classical developmental work with the outstanding problems of the future in the study of plant development. An important feature of this book is the integration of results from molecular and genetic studies on various aspects of plant development in a cellular and physiological context.

This monograph covers the entire field of blood group serology, with its main emphasis on the chemical and biochemical basis of blood group specificity. Full consideration is given to molecular biology investigations, in particular to studies on the structure of blood group genes and the molecular biological basis of alleles and rare blood group variants, whereby relevant literature up to the year 2000 is covered. The text is supplemented by numerous illustrations and tables, and detailed reference lists.

th This volume contains selected lectures presented at the 12 International Conference on Advances in Prostaglandin, Leukotriene and Other Bioactive Lipid Research: Basic Science and Clinical Applications which was held in Istanbul, Turkey, on August 25-29, 2002. This meeting brought together basic and clinical scientists for the purpose of discussing advances in bioactive lipid research with.special attention to cancer, cardiovascular diseases, gastrointestinal diseases and respiratory diseases. Topics covered included: the role of leukotrienes and lipoxins in of inflammation, the cytochrome P450 pathway, the genetics and genomics bioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes, receptors and inhibitors, cyclooxygenase and lipoxygenase pathways and inhibitors, prostaglandin synthases and receptor signaling, phospholipases and inhibitors. Sessions included plenary lectures with expertise in particular areas, oral presentation on selected topics and general poster sessions. J.M. Drazen (Boston, USA) discussed anti-leukotriene treatment in asthma patients while C. Brink (paris, France) presented the recent advances in leukotriene receptors. The recent advances in cytochrome p450 pathway described in the session organized by J.C. McGiff (Valhalla, NY, USA). T. Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an update on phospholipases and arachidonic acid peroxydation. The editors are greatful to the Organizing, Programme and Advisory Committees for their valuable contributions. We greatfully acknowledge the generous financial support provided by PharmaciaIPfizer, Fako Pharmaceuticals Inc. and Novartis Pharmaceuticals Inc. ofthe contributors to this volume, in particular We are also greatful to all to those who delivered their manuscripts by or before the requested deadline.

First printed in 1983, this book concerns the comparative physiological adaptations of vertebrate animals, especially mammals, to cessation of breathing. These adaptations were originally identified in species living in aquatic habitats. The argument is presented that the natural divers display a well-developed and conveniently studied example of a more general defence against asphyxia. The topics considered include the diving response, metabolic and cardiovascular adaptations, variations in resistance to asphyxia, neural control mechanisms, which govern the respiratory and circulatory responses, perinatal asphyxia, applications to the human species and medical implications. The book's purpose is to acquaint its readers with some advances resulting from research in this field.

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process."

Highlighting the current developments and future directions in GABA and glycine research, this volume covers the major inhibitory neurotransmitters from the molecular mechanisms of signal transduction to their role in health and disease. It is of topical importance because these neurotransmitters are essential for brain function and therapy of diseases such as anxiety disorders, insomnias, epilepsy, depression, spasticity, and memory deficits. Distinguished scientists at the forefront of research contributed reviews on the role of these transmitters in governing neuronal networks, their signalling pathways, their receptors, the pharmacology of GABA A- and GABA B- and GABA C-receptors as well as of GABA- and glycine-transporters, and their role in disease. The volume serves as reference for pharmacologists/toxicologists, neuroscientists, neurologists and psychiatrists.

A review of the current state of the clinical and basic science of the pharmacology of sleep. The information provided ranges from a historical perspective to current concepts of sleep mechanisms, including the interaction between pharmacology and sleep-wake regulation and between chronopahrmacology and sleep-wake rhythms. For the first time in one single volume, both the basic mechanisms of sleep, and the basic and clinical aspects of the pharmacology of sleep are dealt with in a thorough, comprehensive and authoritative manner. The chapters, written by the foremost scientific authorities in this field, integrate the latest information on the basic mechanisms of drugs as they relate to their effects on sleep.

The NATO Advanced Study Institute on "Cerebral Blood Flow: Mathematical Models, Instrumentation, and Imaging Techniques" was held in L'Aquila, Italy, June 2-13, 1986. Contributions to this program were received from the University of L'Aquila, Consiglio Nazionale delle Ricerche, Siemens Elettra S.p.A., and Bracco S.p.A. Recent studies of the cerebral blood circulation have lagged behind analysis of other parameters such as glucose utilization, transmitter distribution, and precursors. This Advanced Study Institute tried to fill this gap by analyzing in detail different physical techniques such as Autoradiography (including Double-Tracer Auto radiography and highly specific tracers as Iodoantipyrine, Micro spheres), Single Photon Emission Computed Tomography, Nuclear Magnetic Resonance. Each method was analyzed in regards to its precision, resolution, response time. A considerable part of this Institute was devoted to the mathematics of CBF measurement, in its two aspects, i.e. the modeling of the underlying kinetic system and the statistical analysis of the data. The modeling methods proposed included the development of a differential algebra whereby the differential and integral equations involved could be solved by simple algebraic methods, including graph theoretical ones; the statistical methods proposed included the illustration of different parametrizations of possible use in the interpretation of experimental results.

Adopting an interdisciplinary approach to the chemistry and physics of materials, their biocompatibility, and the consequences of implantation of such devices into the human body, this text introduces readers to the principles of polymer science and the study of metals, ceramics and composites, and also to the basic biology required to understand the nature of the host-transplant interface. Topics covered include the macromolecular components of cells and tissues, self-assembly processes, biological cascade systems, microscopic structure of cells and tissues, immunology, transplantation biology, and the pathobiology of wound healing. The materials science section includes the structures and properties of polymers, metals, ceramics and composites, and the processes for forming materials as well as the pathobiology of devices. The final two chapters deal with tissue engineering and the relations between the biology of cells and tissue transplantation, and the engineering of tissue replacements using passaged cells.

Experimental approaches to auditory research make use of validated animal models to determine what can be generalized from one species to another. This volume brings together our current understanding of the auditory systems of fish and amphibians. To address broader comparative issues, this book treats both fish and amphibians together, to overcome the differing theoretical and experimental paradigms that underlie most work on these groups.

Hypoxia, defined as reduced oxygen tension, is a common physiological phenomenon in both normal embryonic development and malignancy progression. Although severe hypoxia is generally toxic for both normal tissue and tumors, neoplastic cells gradually adapt to prolonged hypoxia though additional genetic and genomic changes with a net result that hypoxia promotes tumor progression and therapeutic resistance. Hypoxia promotes cancer progression by regulating various aspects of cancer biology, including radiotherapy resistance, metabolism, angiogenesis and invasion/migration.

A presentation of the most elementary form of pulsatile flow as an important prerequisite for the study of other flow applications in biological systems. The book provides in a single source a complete treatment of the fluid dynamics of flow with the required mathematics and emphasis on the basis mechanics. The style and level of this book make it accessible to students and researchers in biophysics, biology, medicine, bioengineering and applied mathematics working in theoretical and clinical work on the cardiovascular system, as well as in the design of new instrumentation, medical imaging systems, and artificial organs. With problems and exercises.