Gamma-Glutamyl Transpeptidases ( -GTs) are members of the N-terminal nucleophile hydrolase superfamily, enzymes that cleave the -glutamyl amide bond of glutathione to liberate cysteinylglycine. The released -glutamyl group can be transferred to water (hydrolysis) or to amino acids or short peptides (transpeptidation). -GT plays a key role in the gamma glutamyl cycle by regulating the cellular levels of the antioxidant glutathione, hence it is a critical enzyme in maintaining cellular redox homeostasis. -GT is upregulated during inflammation and in several human tumors, and it is involved in many physiological disorders related to oxidative stress, such as Parkinson's disease and diabetes. Furthermore, this enzyme is used as a marker of liver disease and cancer. This book covers current knowledge about the structure-function relationship of -GTs and gives information about applications of -GTs in different fields ranging from clinical biochemistry to biotechnology and biomedicine.

Mathematical modelling of physiological systems promises to advance our understanding of complex biological phenomena and pathophysiology of diseases. In this book, the authors adopt a mathematical approach to characterize and explain the functioning of the gastrointestinal system. Using the mathematical foundations of thin shell theory, the authors patiently and comprehensively guide the reader through the fundamental theoretical concepts, via step-by-step derivations and mathematical exercises, from basic theory to complex physiological models. Applications to nonlinear problems related to the biomechanics of abdominal viscera and the theoretical limitations are discussed. Special attention is given to questions of complex geometry of organs, effects of boundary conditions on pellet propulsion, as well as to clinical conditions, e.g. functional dyspepsia, intestinal dysrhythmias and the effect of drugs to treat motility disorders. With end of chapter problems, this book is ideal for bioengineers and applied mathematicians.

This book dealing with stance and motion was planned in June 1986 at a meeting held in Moscow and Leningrad between a group of Soviet and French scientists interested in motor control. This meeting took place in the framework of an exchange program between the USSR Academy of Seiences and the French Centre National de la Recherche Scientifique. It was very successful event and was greatly appreciated by all those who attended it. Several participants put forward the proposal that the possibility of publishing a book was worth exploring. What were the reasons for publishing a book on stance and motion ? The interest aroused in the participants by each others contributions was not a sufficiently decisive argument. It was feit, however, that a large proportion of the orginal material presented at the meeting, especially in the field of posture and locomotion but also on other aspects covered by the book could be presented in a summarized form which should appeal to a larger audience because the facts and hypotheses they contained especially those from the Soviet participants, were not very familiar among international circles, and that many scientists would appreciate having a single volume containing a survey ofthe current state of research in this field. This was also the opinion of Plenum Press, who agreed to publish the book. Each participant at the meeting submitted a paper which was examined by two referees before being accepted.

The aim of this book is to focus on the important relationships between the heart and the brain in health and disease. The brain and nervous system may cause or influence heart disease, e. g. , by causing arrhythmias or modi- fying the response to ischemia. Disorders of the heart and circulation may cause brain damage, e. g. , by releasing emboli resulting in cerebral infarc- tion. Furthermore, both the brain and the heart are frequently targets of the same disease process. The heart and brain have electrophysiologically active cells, which may respond in similar ways to diseases and various interventions. Finally, many drugs affect both the brain and the heart, and drugs used for heart diseases usually have side effects on the brain and vice versa. With today's increasing subspecialization in medicine, we feel the time has come to present a book that integrates basic and clinical aspects of cardiology, neurology, cardiovascular surgery, and neurosurgery. We hope this cross fertilization will broaden horizons and advance both understand- ing and practice. This book is based on a symposium held at the University of TromS!/l, Norway, 24-27 June 1987, organized by Ilmar A. Sulg, Knut Rasmussen, Svein Ivar Mellgren, Dag S!/lrlie, and Helge Refsum of the Departments of Clinical Neurophysiology, Medicine, Neurology, Surgery, and Physiology, respectively. Weare grateful to the distinguished group of contributors for not only outlining their pioneering studies, but also describing their recent work and indicating important possibilities for the future.

It has been over 50 years since Hans Selye formulated his concept of stress. This came after the isolation of epinephrine and norepinephrine and after the sympathetic system was associated with Walter Cannon's "fight or flight" response. The intervening years have witnessed a number of dis coveries that have furthered our understanding of the mechanisms of the stress response. The isolation, identification and manufacture of gluco corticoids, the identification and synthesis of ACTH and vasopressin, and the demonstration of hypothalamic regulation of ACTH secretion were pivotal discoveries. The recent identification and synthesis of CRR by Willie Vale and his colleagues gave new impetus to stress research. Several new concepts of stress have developed as a result of advances in bench research. These include the concept of an integrated "stress sys tem," the realization that there are bi-directional effects between stress and the immune system, the suggestion that a number of common psychiatric disorders represent dysregulation of systems responding to stress, and the epidemiologic association of stress with the major scourges of humanity."

to the Endothelin System David M. Pollock ascular endothelial cells form a monolayer lining in all of the blood vessels of V the circulation. Initially, they were thought to function as a crude filter allow- ing nutrients from the blood stream to diffuse through to the underlying tissues without letting proteins or blood cells escape. We now know that endothelial cells are important regulators of circulatory function, due in large measure to their rec- ognized ability to synthesize and release many factors that regulate vascular smooth muscle tone. Endothelial-derived factors, including relaxing and contracting sub- stances such as prostacyclin, nitric oxide (NO), and endothelin (ET), have been identified as important contributors in the regulation of vascular tone. Endothe- lial cells have a highly active metabolic function and are involved in clearing a number of agents from circulating blood. In addition, they have the enzyme that inactivates bradykinin and converts angiotensin I into the very potent pressor agent, angiotensin II (Ang II). Endothelial cells also generate various proteins like von Willebrand's factor, tissue plasminogen activator, growth promoting factors and lipids such as platelet activating factor. It is now clear that in addition to the regu- lation of vascular tone and hemodynamics, endothelial cells playa critical role in regulating growth and proliferative processes, inflammation and hemostasis.

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the "Biology of Extracellular Matrix" series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

Taurine, or 2-aminoethane sulfonic acid, has long been known to be the major organic product formed from the breakdown of the sulfur-containing amino acids, methionine and cysteine. It is excreted as such in the urine or as bile acid conjugates in the bile. Research over the last 25 years, however, has uncovered an amazing variety of phenomena involving taurine. Despite the fact that the mechanism of action of taurine in some of these phenomena remains to be elucidated, it is clear that taurine is of far more physiological relevance than being the mere metabolic debris of sulfur amino acid catabolism. It also has numerous pharmacological actions that are beginning to be developed, as exemplified by some of the studies reported in this volume. This volume reports the proceedings of the latest of a series of international symposia, continuing on from the initial meeting held in Tucson, Arizona, in 1975. The latest symposium was the first to be held in Germany, in Cologne from August 29 through September 1, 1993. It continued the multidisciplinary approach that has been the norm for taurine symposia. We hope the publication of the proceedings will stimulate further investigations on this simple but fascinating compound.

Complete reference on hypoxic pulmonary vasoconstriction and hypoxia-mediated pulmonary hypertension. Can be utilized by the physician-scientist and researcher in the laboratory as both a technical manual and reference. Designed for clinicians to guide and improve clinical treatment and diagnosis of patients with hypoxia mediated pulmonary vascular disease and right heart failure.

Most of the following chapters were presented as plenary lectures or symposium talks at the 1986 XXXth Congress of the International Union of Physiological Sciences in Vancouver, B.C. A distinguished international group of endocrinologists and physiologists have contributed up-to-date reviews of their particular fields. The early chapters are largely concerned with the brain and neuroendocrine mechanisms controlling the secretion of gonadotropin releasing hormone (GnRH) and its action on the anterior pitui- tary gland. Later chapters focus on the gonads themselves and the systemic and intrinsic hormones influencing the functional cytology of ovarian and testicular cells. Such comprehensive subjects as sex differentiation, puberty, placentation and parturition are also discussed authoritatively. According to Pfaff and Cohen and Arai et al., gonadal steroids, especially estrogen, exert multiple effects on certain hypothalamic and preoptic neurons, including growth, protein synthesis and electrical changes, which promote plasticity and facilitate synaptogenesis. The electrophysio- logy of the hypothalamic GnRH pulse generator in the rhesus monkey is reviewed more specifically by Knobil. In ovariectomized ewes, Clarke finds both positive and negative effects of estrogen on hypothalamic release of GnRH as well as on pituitary responsiveness to the peptide. Flerk6 et al.

The function of the vascular system is to transport oxygen and nutrients to the cells and to remove carbon dioxide and metabolites. It also transports hormones and locally produced neurohumoral substances which, in part, regulate its own function. These interrelationships are essential to homeostasis. The vascular system is not an assembly of simple (elastic) tubes but a dynamic system with many external and intrinsic regulatory mechanisms. The endothelium plays a major role in the intrinsic regulation of the system. The system is also often subject to disease processes of which atherosclerosis is the most important. As a result of atherosclerosis, and other disease processes, replacement of vessels with prosthetic devices may be required to reestablish adequate tissue blood flow. It is therefore imperative to gain insight into the details of vascular function, especially the dynamics, and the endothelium, the processes of atherosclerosis development, the vascular prosthetic possibilities and, last but not least, the interrelationships between these sub-specialties.

This volume is the third in a series entitled" Advanced Methods of Physiological System Modeling" and the fifth in a series of research volumes published by Plenum under the sponsorship of the Biomedical Simulations Resource (BMSR) at the Uni versity of Southern California in the context of dissemination activities supported by the Biomedical Research Technology Program of the National Center for Research Resources at the National Institutes of Health under Grant No. P41 RR-OI861. These volumes are edited by BMSR principal scientists and report on recent research de velopments in the area of physiological systems modeling, as well as on advanced methods for analysis of physiological signals and data. As in the previous two volumes of this series, the work reported herein is con cerned with the development of advanced modeling methodologies and their novel application to problems of biomedical interest, with emphasis on nonlinear aspects of physiological function. The term "advanced methodologies" is used to indicate that the scope of this work extends beyond the ordinary type of analysis, which is confined traditionally to the linear domain. As the importance of nonlinearities in understanding the complex mechanisms of physiological function is increasingly recognized, the need for effective and practical modeling methodologies that address the issue of nonlinear dynamics in life sciences becomes more and more pressing.

"The Path from Biomarker Discovery to Regulatory Qualification "is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science.

For complimentary access to chapter 13, "'""Classic' Biomarkers of Liver Injury, " by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site: http: //tinyurl.com/ClassicBiomarkers
Contains a collection of experiences of different groups taking different types of biomarkers to different levels of qualification and provides insightful case studies of an important area of regulatory science

Focuses on practical advice, concepts, strategies and overall outcomes to support those working toward biomarker qualification for clinical use

Offers a valuable resource for members of the regulatory, pharmaceutical and biomarker development communities. "

This volume was originally published in 1982. Ergonomics is the study of people, primarily in relation to their work, but also with reference to transport, sport and leisure activities. The general purposes of this book were to apply to ergonomics the established principles of anatomy, physiology and psychology and to provide a comprehensive textbook and source of information in this area.

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

Herbert Henri Jasper is a scientist whose research activities have initiated and encompassed many of the major themes of neuroscience. He has pioneered in single unit recording, chronic neuronal studies, neurochemistry, electroencephalography, and many other disciplines. His students now hold important positions in universities and hospitals around the world. From July 21 to 23, 1986, a symposium entitled Neurotransmitters and Cortical Function: From Molecules to Mind was held in Montreal to honor Professor Jasper and to continue his pioneering efforts. The following chapters originated in that meeting. They summarize the current v vi PREFACE status of our knowledge in some of the fields influenced by Professor Jasper. They share a focus on neurotransmitters in cortical function, where we presume higher mental events originate. Professor Jasper has made contributions to the understanding of three different classes of neuro transmitters: GABA, acetylcholine, and catecholamines. It is an interest in trying to link neu rochemical events to some aspects of complex brain function and behavior that has characterized his work, and it is this philosophy that led to the present symposium to honor him. We dedicate this volume to Professor Jasper and the integrative approach that he has fostered. The Editors Montreal Contents 1. H. H. Jasper, Neuroscientist of Our Century .......................... ."

Biology of the Arterial Wall is intended as a general reference text concerned with the biology of the vascular cells and the blood vessel wall under physiological and pathological conditions. One of the major functions of the arteries is to maintain a continuous blood flow to the organs whatever the pressure conditions, thanks to the vasomotor tone of the smooth muscle cells. Great advances have been made over the last decade in the understanding of the endothelial cells as integrators and transducers of signals originating from the blood stream. The pluripotent control functions of the endothelial cells in the vessel wall are now well recognized. A review of endothelial functions and dysfunctions is presented. Cell biology and molecular genetic studies have now identified an array of molecules elaborated by endothelial cells and vascular smooth muscle cells and by the blood-borne elements which interact with artery cells, defending the artery against injury and modulating evolving abnormal processes. Molecules which induce or inhibit endothelial and/or smooth muscle cells are currently under great scrutiny. Angiogenesis, which plays a major role in tumor growth, but may also be beneficial as a healing process in muscle ischemia, is discussed. Apoptosis, or programmed cell death, has only recently been recognized as an essential process in blood vessel modeling and remodeling. An overview of apoptosis in the vascular system is presented. It is increasingly evident that the adjustments of the blood vessel wall are made in the presence of deforming disease processes such as hypertension and atherosclerosis. The second part of the book is concerned with the blood vessel wall in disease conditions. Several chapters review the role of the vessel and vascular cells in inflammation, and vascular remodeling during arterial hypertension and aging. One chapter is devoted to atherogenesis, atheroma and plaque instability, followed by the pathophysiology of post-angioplasty restenosis, which is a crucial issue in modern interventional cardiology.

Pulmonary Biology in Health and Disease was conceived as a companion to a handful of expensive, multivolume textbooks. This is part of the promising trend to publish shorter textbooks on the subjects of lung biology and remodeling. Whoever is familiar with human biology and the far-reaching consequences of the genome and postgenome revolutions is apt to concede that the centerpiece in remodeling lies in the ?eld of m- ecular cardiobiology. The ?eld of molecular cardiobiology includes the syndrome of chronic heart failure as well as ischemic cardioprotection. By analogy, the centerpiece in pulmonobiology is chronic asthma. Key topics in the present volume include s- naling mechanisms regulating the endothelium and smooth muscle cells,in?ammatory cells, mediators, airway surface liquid, and pharmacological therapy that focuses on how in?amed airways are altered. Written primarily for predoctoral and postdoctoral graduates in the basic medical sciences, the medical student and postdoctoral physician, graduates in the allied s- ences, nurses, pulmonologists, and physicians in critical care medicine, this book p- vides many of the fundamentals of contemporary pulmonology. It is divided into several parts devoted to the control of respiration, arterial chemoreceptors,muscles of ventilation, pulmonary physiology, and gas exchange in health, exercise, and disease. Special emphasis is placed on emphysema and its pathobiology, acute lung injury, asthma and inhaled toxicants. Because the ?eld is always evolving, each chapter includes recommended readings that lead the reader to sources of additional information, such as the review on remodeling of the blood gas barrier by West and Mathieu-Costello.

The chapters of this book report cutting-edge research on molecular events in adiposity and type 2 diabetes, thus opening the way for innovative drug-based therapeutic strategies. It addresses all those who wish to keep in touch with recent developments in the field.

On December 6, 1961, a contract was signed by which the research institute of the Wander AG in Freiburg became the Max-Planck-Institut fUr Immunbiologie. The transfer of ownership took place during a happy expansion phase of the Max-Planck Society in which a growing economy in Germany allowed the foundation of many new research institutes by the Max-Planck-Society and other organizations. Nevertheless, it was a remarkable event. The acquisition by an academic organization of an institute formerly operated by an industrial company was rather unusual, not to speak ofthe fact that not only the facilities but also the entire scientific personnel were taken over. Retrospectively, the 40 years of the institute in the Max-Planck Society can be divided into 2 very different phases of 20 years each. The first 20 years were characterized by a continuation of the research that had begun in the Wander institute and centered on the structure and function of the bacterial compound endotoxin. During the second 20 years, the institute more than doubled in size and developed into an interdisciplinary research center that focuses on the development and organization of multicellular systems by combining studies in two fields of research: immunology and developmental biology. th The 40 anniversary of the foundation of the Max-Planck-Institute was celebrated by a ceremony including a scientific symposium. The first part of this volume presents the lectures given at the symposium by six leading biologists."

In this new volume, Dr. Gregory Fanelli, of the Geisinger Medical Center and a reknowned expert on knee injuries, provides orthopaedic surgeons with an unprecedented review of the most recent and advanced knowledge needed to successfully diagnosis and treat PCL injuries. This comprehensive and practical volume covers everything from biomechanics and anatomy, evaluation and non-operative treatment to the latest surgical treatments of PCL injuries using arthroscopy, grafts and synthetic ligament substitutes. In addition, contributions from such well-known specialists as Drs. M. Malek, Roger Larson and Fred Flandery make this an essential text for every orthopaedic surgeon.

Part of Springer's "The Receptors," series, this text is the first ever overview on the research of 5-HT2c receptors. 5-HT2c receptor research has been productive for twenty-five years, but recent years have seen an extraordinary increase in both amount produced and insight gained. 5-HT2c is a prominent central serotonin receptor subtype widely expressed within the central and the peripheral nervous system and is thought to play a key role in the regulation of numerous behaviors. This text covers the molecular, cellular, anatomical, biochemical and behavioral aspects of this receptor, highlighting its distinctive regulatory properties and the emerging functional significance of constitutive activity and RNA-editing in vivo. It also investigates the receptors' therapeutic potential in many diseases, treated individually in separate chapters, including depression, drug abuse, schizophrenia, eating disorders, Parkinson's disease, Prader-Willi Syndrome, Alzheimer's disease and epilepsy.

Humans engage in a seemingly endless variety of different behaviors, of which some are found across species, while others are conceived of as typically human. Most generally, behavior comes about through the interplay of various constraints - informational, mechanical, neural, metabolic, and so on - operating at multiple scales in space and time. Over the years, consensus has grown in the research community that, rather than investigating behavior only from bottom up, it may be also well understood in terms of concepts and laws on the phenomenological level. Such top down approach is rooted in theories of synergetics and self-organization using tools from nonlinear dynamics. The present compendium brings together scientists from all over the world that have contributed to the development of their respective fields departing from this background. It provides an introduction to deterministic as well as stochastic dynamical systems and contains applications to motor control and coordination, visual perception and illusion, as well as auditory perception in the context of speech and music.

Offering a systematic comparative approach to Western and Eastern medicine, this unique textbook enables students and practitioners of Chinese medicine to develop a core understanding of conventional medical language and treatments. Acupuncture practitioners increasingly find themselves working alongside Western healthcare professionals. Now in its second edition, this book is a guide to conventional medical diagnoses, symptoms and treatments, and using examples drawn from the author's experience and knowledge of TCM it encourages reflection on how these diagnoses may be interpreted from a more holistic medical perspective. It includes introductory sections on physiology, pathology and pharmacology, chapters devoted to the physiological systems of the body and the conventional approach to the treatment of diseases that can affect them, and information on dealing with patients in practice. Accompanying online material, including self-testing questions and answers and checklists for revision, is available for those wishing to use the text for systematic study.