Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

Scientific advances over the past two decades have afforded unprecedented oppor tunities to understand the structure and function of receptors, receptor-ligand interactions, and receptor signaling. The extent ofprogress in this area is underscored by the recent Nobel Prize for Medicine and Physiology to Alfred Gilman and Martin Rodbell, both of whose work in understanding receptorlG-protein interactions has redefined the way in which we think of how hormones and neurochemicals exert their activity on cellular function. This book is replete with examples of current research approaches to help us better understand the cellular roles in which the renin-angiotensin system and the angiotensin receptors participate. Clearly, defining the structure of angiotensin receptor subtypes is an important first step in cJarifying the mechanisms by which these receptors take part in cellular function. However, the chapters within this book range far beyond structural studies and encompass research on tissue specific expression of the angiotensin receptor subtypes, the genetic regulation ofthese receptors, and the unique function ofvarious angiotensin subtypes in different organ systems, such as the brain, the reproductive system, adipose tissue, the heart, and the kidneys."

'Further establishes the reputation of the series...an invaluable resource.' -Trends in Pharmacological Sciences, from a review of Volume 3 Volume 4 explores such emergent topics as: three-dimensional conceptions of ion channel proteins based on the available structural and functional data; the structure, pharmacology, and regulation of the GABAA receptors; and the Ca2+-dependent K+ channels in adrenal chromatic cell membranes.

The following are the proceedings of the Third International Workshop on Perception held in Pavia, Italy, on September 27-30, 1993, under the auspices of four institutions: the Group of Cybernetic and Biophysics (GNCB)s of the National Research Council (CNR), the Italian Association for Artificial Intelligence (AI * IA), the Italian Association of Psychology (AlP), and the Italian Chapter of the International Association for Pattern Recognition (IAPR). The theme of this third workshop was: "Human and Machine Vision: Analogies and Divergencies." A wide spectrum of topics was covered, ranging from neurophysiology, to computer architecture, to psychology, to image understanding, etc. For this reason the structure of this workshop was quite different from those of the first two held in Parma (1991), and Trieste (1992). This time the workshop was composed of just eight modules, each one consisting of two invited lectures (dealing with vision in nature and machines, respectively) and a common panel discussion (including the two lecturers and three invited panellists).

Here is the first effort in a single volume to cover all of the integrative functions of calcium signalling - how changes in intracellular calcium coordinate a variety of coherent cellular responses. Written by a team of internationally established researchers, Integrative Aspects of Calcium Signalling provides the latest experimental data and concepts, bringing together a detailed analysis of the events, processes, and functions regulated by calcium signalling. A unique resource for professionals and students of physiology, biophysics, neurobiology, biochemistry, and all related fields.

Although there is general agreement that exogenous electric and electromagnetic fields influence and modulate the properties of biological systems. there is no concensus regarding the mechanisms by which such fields operate. It is the purpose of this volume to bring together and examine critically the mechanistic models and concepts that have been proposed. We have chosen to arrange the papers in terms of the level of biological organization emphasized by the contributors. Some papers overlap categories. but the progression from ions and membrane surfaces. through macromolecules and the membrane matrix to integrated systems. establishes a mechanistic chain of causality that links the basic interactions in the relatively well understood simple systems to the complex living systems. where all effects occur simultaneously. The backgrounds of the invited contributors include biochemistry. biophysics. cell biology. electrical engineering. electrochemistry. electrophysiology. medicine and physical chemistry. As a result of this diversity. the mechanistic models reflect the differing approaches used by these disciplines to explain the same phenomena. Areas of agreement define the common ground. while the areas of divergence provide opportunities for refining our ideas through further experimentation. To facilitate the interaction between the different points of view, the authors have clearly indicated those published observations that they are trying to explain. i.e. the experiments that have been critical in their thinking. This should establish a concensus regarding important observations. In the discussion of theories.

This conference and monograph were the result of many collective efforts. The whole concept was formulated one early Wednesday morning at our weekly research meeting at Children's Hospital in our division of urology. We have been most fortunate to have a close collaboration with Bob Levin, Ed Macarak, and Pam Howard who have helped steer the course of our division's growing interest in basic science. At our weekly meetings our laboratory fellow will summarize their current work. Other ongoing areas of investigation in our labs and elsewhere are discussed. We have always made an effort to try and understand what other groups are doing who are working in the area of bladder smooth muscle research. It occurred to us that the best way to really know what everyone working in this field was doing would be to sponsor a 2-day meeting where we could all gather to discuss our ongoing work. A major limitation of the annual meeting of the American Urologic Association or the urology section of the American Academy of Pediatrics is that the scientfic sessions are limited as these are meant to be primarily clinical meetings (as they should be). For this reason the idea of a meeting devoted solely to research about the urinary bladder had great appeal. In addition to allowing for longer presentations than the standard 5 to 7 minutes, every effort would be made to encourage a dialogue amongst the presenters and the audience.

Since programmed cell death was first described in insects in 1964 and apoptosis was described in 1972, rapid progress has been made in understanding the basic mechanisms and genes regulating programmed cell death and apoptosis. In addition, defects in various genes regulating programmed cell death have been delineated in several experimental models of human diseases. This volume surveys various aspects of these rapidly developing areas of research in programmed cell death/apoptosis. This volume should be of interest to basic immunologists and molecular biologists. The volume begins with a historical perspective of cell death. The remainder of the volume is divided into four different parts. Part I deals with the signaling pathways in apoptosis, including cell cycle control of apoptosis, role of ceramide in apoptosis, role of antibody signaling, and biochemical regulation of apoptosis. The mechanisms for recognition of apoptotic lymphocytes by macrophages are also reviewed. Part II examines the role of various genes that regulate apoptosis, including the role ofFas, FasL, and other TNF family members in apoptosis and homeostatic regulation of immune response. Recently described splice variants and their influence on apoptosis are also reviewed, and the role of the members of the Bcl-2 family in apoptosis is discussed in detail. Part III reviews various aspects of apoptosis in B lymphocytes, including mechanisms that regulate apoptosis/survival of B lymphocytes and the regulation of Fas-mediated apoptosis in B lymphocytes.

Proteins are still gaining importance in the pharmaceutical world, where they are used to improve our arsenal of therapeutic drugs and vaccines and as diagnostic tools. Proteins are different from "traditional" low-molecular-weight drugs. As a group, they exhibit a number of biopharmaceutical and formulation problems. These problems have drawn considerable interest from both industrial and aca demic environments, forcing pharmaceutical scientists to explore a domain previ ously examined only by peptide and protein chemists. Biopharmaceutical aspects of proteins, e.g., low oral bioavailability, have been extensively investigated. Although all possible conventional routes of ad ministration have been examined for proteins, no real, generally applicable alter native to parenteral administration in order to achieve systemic effects has yet been discovered. Several of these biopharmaceutical options have been discussed in Volume 4 of this series, Biological Barriers to Protein Delivery. Proteins are composed of many amino acids, several of which are notorious for their chemical instability. Rational design of formulations that optimize the native structure and/or bioactivity of a protein is therefore of great importance when long shelf life is required, as it is for pharmaceutical products. This issue has also been examined in two prior volumes of this series: Volume 2: Stability of Protein Pharmaceuticals (Part A) and Volume 5: Stability and Characterization of Protein and Peptide Drugs.

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.

As we approach the twenty-first century the problems of industrialization are evident: we find there is a greenhouse effect, the ozone layer is being depleted, the rain is acidified, and there is a terrible problem of increasing C0 concentrations in the atmo 2 sphere. The carbonic anhydrases are a unique family of enzymes that solve these problems in the human body: they are responsible for converting C0 (a gas) to 2 HC0-, which is the biggest intracellular buffer, with a concomitant decrease in a 3 hydroxyl ion. Globally, the functions of the carbonic anhydrases in photosynthesis in rain forests and in the algae and plankton that cover our oceans indicate that they are also of utmost importance in the maintenance of the acid-base balance on our planet. Although the whole field of C0 metabolism is enormous and still rapidly 2 expanding, because of the research interests of the editors this book is mainly concerned with mammalian carbonic anhydrases. However, if the interested reader intends to purify carbonic anhydrases from nonmammalian sources, Dr. Cheg widden has provided the necessary information in Chapter 7. The carbonic anhydrases were first discovered in 1933; until1976 there were thought to be only two isozymes. Since then CA ill, IY, V, VI, and Vll have been discovered and well characterized. There is, of course, no reason to believe that we have found them all."

The predecessor to this book was A Guide to the Laboratory Use of the Squid Loligo pealei published by the Marine Biological Laboratory, Woods Hole, Massachusetts in 1974. The revision of this long out of date guide, with the approval of the Marine Biological Laboratory, is an attempt to introduce students and researchers to the cephalopods and particularly the squid as an object of biological research. Therefore, we have decided to expand on its original theme, which was to present important practical aspects for using the squid as experimental animals. There are twenty two chapters instead of the original eight. The material in the original eight chapters has been completely revised. Since more than one method can be used for accomplishing a given task, some duplication of methods was considered desirable in the various chapters. Thus, the methodology can be chosen which is best suited for each reader's requirements. Each subject also contains a mini-review which can serve as an introduction to the various topics. Thus, the volume is not just a laboratory manual, but can also be used as an introduction to squid biology. The book is intended for laboratory technicians, advanced undergraduate students, graduate students, researchers, and all others who want to learn the purpose, methods, and techniques of using squid as experimental animals. This is the reason why the name has been changed to its present title. Preceding the chapters is a list of many of the abbreviations, prefixes, and suffixes used in this volume.

This volume describes the current state of our knowledge on the neurobiology of muscle fatigue, with consideration also given to selected integrative cardiorespiratory mechanisms. Our charge to the authors of the various chapters was twofold: to provide a systematic review of the topic that could serve as a balanced reference text for practicing health-care professionals, teaching faculty, and pre-and postdoctoral trainees in the biomedi cal sciences; and to stimulate further experimental and theoretical work on neurobiology. Key issues are addressed in nine interrelated areas: fatigue of single muscle fibers, fatigue at the neuromuscular junction, fatigue of single motor units, metabolic fatigue studied with nuclear magnetic resonance, fatigue of the segmental motor system, fatigue involving suprasegmental mechanisms, the task dependency of fatigue mechanisms, integrative (largely cardiorespiratory) systems issues, and fatigue of adapted systems (due to aging, under-and overuse, and pathophysiology). The product is a volume that provides compre of processes that operate from the forebrain to the contractile proteins.

The study of primate locomotion is a unique discipline that by its nature is interdis ciplinary, drawing on and integrating research from ethology, ecology, comparative anat omy, physiology, biomechanics, paleontology, etc. When combined and focused on particular problems this diversity of approaches permits unparalleled insight into critical aspects of our evolutionary past and into a major component of the behavioral repertoire of all animals. Unfortunately, because of the structure of academia, integration of these different approaches is a rare phenomenon. For instance, papers on primate behavior tend to be published in separate specialist journals and read by subgroups of anthropologists and zoologists, thus precluding critical syntheses. In the spring of 1995 we overcame this compartmentalization by organizing a con ference that brought together experts with many different perspectives on primate locomo tion to address the current state of the field and to consider where we go from here. The conference, Primate Locomotion-1995, took place thirty years after the pioneering confer ence on the same topic that was convened by the late Warren G. Kinzey at Davis in 1965."

This book is the compilation of papers presented at the International Symposium on In Vivo Body Composition Studies, held in Houston, Texas, November 10-12, 1992. The purpose of this conference was to report on the state-of-the-art techniques for in vivo body composition measurements and to present the most recent human data on normal body composition and changes during disease. This conference was the third in a series of meetings on body composition studies held in North America, and follows the successful meetings at Brookhaven National Laboratory in 1986, and the one in Toronto in 1989. A large number of excellent research papers were offered for consideration at this Conference which demonstrates the rapid growth of the field in the last three years. However, we had to limit the presentations to approximately 90 papers which provided a broad spectrum of the applications and recent interest in the subject. The proceedings of the Brookhaven meeting "In Vivo Body Composition Studies," is published by The Institute of Physical Sciences in Medicine, London. The proceedings of the Toronto meeting "In Vivo Body Composition Studies" was published by Plenum Press in its basic life science series. Both these meetings placed more emphasis on technical aspects while the current Houston meeting tried to emphasize more the emerging clinical applications of these techniques. The general sessions used at the Conference for presentations forms the basis of the order of appearance of the papers in this book.

This book contains aseries of review papers related to the lectures given at the Third Course on Bioelectrochemistry held at Erice in November 1988, in the framework of the International School of Biophysics. The topics covered by this course, "Charge Separation Across Biomembranes, " deal with the electrochemical aspects of some basic phenomena in biological systems, such as transport of ions, ATP synthesis, formation and maintenance of ionic and protonic gradients. In the first part of the course some preliminary lectures introduce the students to the most basic phenomena and technical aspects of membrane bioelectrochemistry. The remaining part of the course is devoted to the description of a selected group of membrane-enzyme systems, capable of promoting, or exploiting, the processes of separation of electrically charged entities (electrons or ions) across the membrane barrier. These systems are systematically discussed both from a structural and functional point of view. The effort of the many distinguished lecturers who contributed to the course is aimed at offering a unifying treatement of the electrogenic systems operating in biological membranes, underlying the fundamental differences in the molecular mechanisms of charge translocation.

In this introductory text, Dr. Birdi demonstrates experimental methods and analyses of fractal dimensions in natural processes. In addition to a general overview, he discusses in detail problems in the fields of chemistry, geochemistry, and biophysics. Both students and professionals with a minimum of mathematics or physical science training will learn to find and model shapes and patterns from their own everyday observations.

In the last decade, research on platelet-activating factor (PAF) has expanded exponentially. Previous conferences on PAF in Paris, 1983, and the subsequent conferences in Gatlinburg, Ten nessee, Tokyo, Snowbird, Utah, and Berlin, at three-yearly intervals, have chronicled the devel opments in the field ofPAF. This volume records the proceedings of the Fifth International Con gress on PAF and Related Lipid Mediators, held at the Free University Medical Hospital Ben jamin Franklin in Berlin, from September 12-16, 1995. We are very much indebted to Free Uni versity Berlin for providing tremendous facilities and financial support. It was a great pleasure to have positive and generous input from the German Science Council (DFG), Bonn, Germany, and British.Biotech, Oxford, United Kingdom. Their support was crucial in making the congress a scientific success. Twenty other organizations provided additional financial support, for which we extend our deepest appreciation. The editors would like to thank all of those who participated in this congress and the authors for their contributions. The organization and planning of the Berlin Congress were carried out by an organizing committee. We gratefully acknowledge the support and assistance of the organizing commit tee members, especially Renate Nigam and Renate Roux for their untiring efforts to make the congress successful. Many colleagues also supported the congress with dedication, hard work, and expert input. We are grateful to them. We also wish to acknowledge the support of G. Sravan Kumar and Louis Kock for their efforts in producing this volume."

A number of factors have come together in the last couple of decades to define the emerging interdisciplinary field of structural molecular biology. First, there has been the considerable growth in our ability to obtain atomic-resolution structural data for biological molecules in general, and proteins in particular. This is a result of advances in technique, both in x-ray crystallography, driven by the development of electronic detectors and of synchrotron radiation x-ray sources, and by the development ofNMR techniques which allow for inference of a three-dimensional structure of a protein in solution. Second, there has been the enormous development of techniques in DNA engineering which makes it possible to isolate and clone specific molecules of interest in sufficient quantities to enable structural measurements. In addition, the ability to mutate a given amino acid sequence at will has led to a new branch of biochemistry in which quantitative measurements can be made assessing the influence of a given amino acid on the function of a biological molecule. A third factor, resulting from the exponential increase in computing power available to researchers, has been the emergence of a growing body of people who can take the structural data and use it to build atomic-scale models of biomolecules in order to try and simulate their motions in an aqueous environment, thus helping to provide answers to one of the most basic questions of molecular biology: the relation of structure to function.

In the past few years, the scientific community has witnessed significant progress in the study of ion channels. Technological advancement in biophysics, molecular biology, and immunology has been greatly ac celerated, making it possible to conduct experiments which were deemed very difficult if not impossible in the past. For example, patch-clamp techniques can now be used to measure ionic currents generated by almost every type of cell, thereby allowing us to analyze whole-cell and single channel events. It is now possible to incorporate purified ion channel components into lipid bilayers to reconstitute an "excitable membrane." Gene cloning and monoclonal antibody techniques provide us with new approaches to the study of the molecular structure of ion channels. A variety of chemicals have now been found to interact with ion channels. One of the classical examples is represented by tetrodotoxin, a puffer fish poison, which was shown in the early 1960s to block the voltage-activated sodium channel in a highly specific and potent manner.

This book was originated from a series of lectures given in a course on the physical properties of biological membranes and their functional implica tions. The course was intended to allow students to get acquainted with the physical techniques used to study biological membranes. The experience was valuable and we feel that a detailed description of the procedures used and of various examples of the results obtained allowed many students to become familiar with a theme that is not often part of regular courses on membrane physiology or biophysics. This book is designed as a tutorial guide for graduate students interested in understanding how physical methods can be utilized to study the proper ties of biological membranes. It includes first a detailed description of applications of physical techniques-such as X-ray fiber diffraction methods (Chapter 1), 2H and 13C NMR spectroscopy (Chapter 2), and calorimetry (Chapter 3)-in the study of the properties of lipid model membranes. A description of how to measure molecular mobility in membranes (Chapter 4) follows, and the book concludes with three chapters in which biological membranes are the subject of study. Chapter 5 deals with the acetylcholine receptor and its membrane environment; Chapter 6 discusses how fluorescence techniques can be applied in the study of the calcium ATPase of sarcoplasmic reticulum; and Chapter 7 explains how protein lipid interactions modulate the function of the sodium and proton pumps."

This book is dedicated to the memory of two colleagues and friends, Amico Big- nami and Hendrick Vander Los. They were both pioneers in their fields: Bignami on on- togenesis and function of neuroglia, and Van der Los on brain plasticity and neuronal circuitry. Their ideas are further pursued by the authors in this book. Some of the chapters are products of a conference dedicated to these two scientists entitled "Recent Advances in Neurobiology: Plasticity and Regeneration." The conference was organized by the Insti- tute of Developmental Neuroscience and Aging and sponsored by the Region della Valle d' Aosta. Also, several chapters are written by colleagues who knew well either Amico or Hendrick and were invited to contribute to this dedication. The book is divided in four sections. The first part covers neurons, neuroglia includ- ing microglia, their plasticity and phenotypic expression, and specific functions and inter- actions. It is now established that neuroglia are an intimate component of the neuronal environment and thought to regulate several neuronal functions. More recently microglia have become prominent as the immune cells in the CNS. This part contributes new infor- mation for these cellular interactions. The second part deals with neuronal and glial cell plasticity as it relates to regeneration and neurodegeneration, more or less an extension of Part I. In recent years the role of transplantation in regeneration has become promising.

In recent years experimental and numerical studies have shown that chaos is a widespread phenomenon throughout the biological hierarchy ranging from simple enzyme reactions to ecosystems. Although a coherent picture of the fundamental mechanisms responsible for chaotic dynamics has started to appear it is not yet clear what the implications of such dynamics are for biological systems in general. In some systems it appears that chaotic dynamics are associated with a pathological condi tion. In other systems the pathological condition has regular periodic dynamics whilst the normal non-pathological condition has chaotic dyna mics. Since chaotic behaviour is so ubiquitous in nature and since the phenomenon raises some fundamental questions about its implications for biology it seemed timely to organize an interdisciplinary meeting at which leading scientists could meet to exchange ideas, to evaluate the current state of the field and to stipulate the guidelines along which future research should be directed. The present volume contains the contributions to the NATO Advanced Research Workshop on "Chaos in Biological Systems" held at Dyffryn House, St. Nicholas, Cardiff, U. K., December 8-12, 1986. At this meeting 38 researchers with highly different backgrounds met to present their latest results through lectures and posters and to discuss the applica tions of non-linear techniques to problems of common interest. . In spite of their involvement in the study of chaotic dynamics for several years many of the participants met here for the first time."

I have been asked to write a brief foreword to this volume honoring Hisako Ikeda, providing a review of the accomplishments in our field over the past four decades, when Hisako was an active participant. This I am delighted to do. It has been a most exciting time in vision research and Hisako has been right in the middle of much of the excitement, publishing on a wide variety of topics and providing much new data and many new insights. Hisako's research career can be divided by decades into four quite distinct areas of inquiry. In the 1950s, as a student in Japan, her research interests were psychophysical in nature, and she was concerned with visual illusions, figural aftereffects, and motion detec tion. In the 1960s, after her move to London, she began electrophysiological studies. Much of her work in the 1960s was concerned with the electroretinogram (ERG), its components, and the use of this electrical response for evaluating spectral sensitivities of the eye and retinal degenerations. This work represented the beginning of her electrodiagnostic clinical work, which continued until her retirement."

William P. Cooney III, R. A. Berger, and K. N. An Orthopedic Biomechanics Laboratory Department of Orthopedic Surgery Mayo Clinic and Mayo Foundation Rochester, MN 55905, U. S. A. As surgeons struggle to find new insights into the complex diseases and deformities that involve the wrist and hand, new insights are being provided by applied anatomy, physiology and biomechanics to these important areas. Indeed, a fresh new interaction of disciplines has immersed in which anatomists, bioengineers and surgeons examine together basic functions and principles that can provide a strong foundation for future growth. Clinical interest in the hand and wrist are now at a peak on an international level. Economic implications of disability affecting the hand and wrist are recognized that have international scope crossing oceans, cultures, languages and political philosophies. As with any struggle, a common ground for understanding is essential. NATO conferences such as this symposium on Biomechanics of the Hand and Wrist provides such a basis upon which to build discernment of fundamental postulates. As a start, basic research directed at studies of anatomy, pathology and pathophysiology and mechanical modeling is essential. To take these important steps further forward, funding from government and industry are needed to consider fundamental principles within the material sciences, biomechanical disciplines, applied anatomy and physiology and concepts of engineering modeling that have been applied to other areas of the musculoskeletal system.