"Provides analytical chemists and biomedical scientists with an excellent summary of progress...This is a book that can be recommended to all analytical scientists interested in fluorimetry." (Analytical Chimica Acta) "This is a useful overview and gives the nonspecialist a feeling for the advantages and limitations of the methods. Overall this book is a worthwhile read and a good source of references." (TRAC)
The book is divided into chapters on new methods, new appli- cations, fluorescence immunoassays, fluorometric analysis and fluorescence spectroscopy in biomedical sciences. Specific topics are fluorescence spectroscopy using synchrotron radiation, picosecond fluorescence spectroscopy, fluorescence microscopy, fluorescence scattering by synthetic polymers, fluorescence immunoassays, fluorescence for environmental monitoring, fluorescence in flow injection analysis, hydro-geological studies, fluorescence of proteins, lipids and membranes, cell fluorescence, calcium transients.

Though it is a pleasure to write a short foreword to this collection of excellent scientific papers covering a range of biological topics, the rather depressing feature is the small number of papers. All-electronic publishing is developing and your Editors do have great faith in it. One problem for potential authors has been the reluctance of the abstracting journals to pay any attention to electronic journals - perhaps Springer should make a rapid move in this area and start the first all-electronic journal abstracting this type of literature. However, even the paper citation journals are starting to pay attention to the medium. The particular advantages of all-electronic publishing are beginning to emerge more clearly and it is clear that publishing video material is a unique advantage of our format. Several papers took advantage of this - for example those by Riehle and others on cell behaviour in tunnels, by Bereiter-Hahn and Voss on zonation in the plasmalemma and by Pavlikova, Zicha, Chaloupkova and Vesely on cell motility of tumour cells. These papers made essential and extensive use of video material, publishing some material of great originality. The work on cell pola rity and calcium ions in Fucus embryos by Brownlee, Manison and Anning used animation to present their results in an especially clear way. The facility of use of animation is another special advantage of our type of publication that should be more widely used."

This section will consider the structure and function of muscle receptors, as well as the central nervous system mechanisms with which they are concerned. In volume I of this Handbook, receptor mechanisms are discussed in detail. Also, the crustacean stretch receptor and the frog muscle spindle have been considered. The present section will be concerned with vertebrate muscle receptors with an emphasis on mammals. Muscle receptors provide interesting examples of specialized mechanorecep tors. The muscle spindle is a striking case of a receptor which is regulated in its function by the central nervous system in efferent neurons. Muscle receptors have long been known to playa crucial role in the reflex regulation of movement. In recent years it has become apparent that these receptors are also important in sensory phenomena such as the perception of position and movement. St. Louis, July 1974 c.c. HUNT Contents Chapter I The Morphology of Muscle Receptors. By D. BARKER. With 99 Figures . . . . . . . . . . . . . . . .. 1 Chapter II The Physiology of Muscle Receptors. By C.C. HUNT. With 21 Figures . . . . . . . . . . . . . . . . . 191 Chapter III Central Actions of Impulses in Muscle Afferent Fibres. By A. K. McINTYRE. With 8 Figures 235 Author Index 289 Subject Index 299 List of Contributors BARKER, David Department of Zoology, University of Durham, Science Laboratories, South Road, Durham DH1 3LE, Great Britain HUNT, Carlton C. Department of Physiology and Biophysics, Washington University, School of Medicine, 660 South Euclid Avenue, St. Louis, Mo. 63110, USA McINTYRE, A. K."

In 1976, when Springer-Verlag commissioned Professors Giebisch, Tosteson, and Ussing to edit what was destined to become a monumental five-volume Handbuch (" Membrane Transport in Biology", 1978 [Vols I, II, III] and 1979 [Vols IV A, B]), the subject of transepithelial secretion was still in its infancy. Not surprisingly, therefore, their Handbuch concentrated mainly on trans- epithelial absorption, although substantial chapters dealing with some secre- viz. "Ion Transport Across the Choroid Plexus" tory organs were included, (by E. M. Wright), "Sweat Glands" (by J. H. Thaysen), "Lacrimal Gland" (by J. H. Thaysen) and "Transport Across Insect Excretory Epithelia" (by J. P. H. Maddrell) in Volume III and "Transport in Salivary and Salt Glands" (by J. A. Young and E. W. Van Lennep), "Gastric Secretion" (by T. E. Machen and J. G. Forte), "Transport Processes in the Exocrine Pan- creas" (by I. Schulz and K. J. Ullrich), and "Transport of Ions in Liver Cells" (by M. Claret) in Volume IVB. The publication in 1977 of the seminal paper of Silva and his colleagues on the mechanism of secretion of salt and water in the salt excreting gland of the dogfish (American Journal of Physiology 233, F298-F306, 1977) provided physiologists with their first real insight into the mechanisms underlying transepithelial fluid secretion, however, and, in the ensuing years, interest in the topic has exploded as is evidenced by the numerous international symposia on exocrine secretion held since that date.

Since the endothelium plays such an important role in the pathophysiology of the circulatory system, the readers attention is directed here towards the possible involvement of these polypeptides in the aetiology of ischaemic heart disease, cerebrovascular accidents, hypertension, atherosclerosis and renal failure.

Skeletal muscle consumes significant amounts of oxygen, and its oxygen flux increases significantly under conditions of exercise and muscle contraction. This makes the muscle vulnerable to oxidative stress since concomitantly with the increase of oxygen flow there is an increase of free oxygen radicals which are a byproduct of muscle respiration. A number of studies in the last decade have documented the involvement of free oxygen radicals in exercising muscles. The consequences of muscle oxidative stress have resulted mainly in increased muscle protein oxidation, elevation of lipid peroxidation, and depletion of muscle antioxidants. The mechanisms of this oxidative stress are under extensive investigation in laboratories around the world and are topics of the chapters in this volume. This book is intended for professionals who are interested in muscle function, physiology, pathophysiology and well-being, such as therapists, trainers and medical professionals as well as for researchers in the field of muscle physiology.

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.

A new presentation of physiological regulatory mechanisms and therapeutic applications is given in this book. It represents a collection of the most up-to-date information in cholecystokinin (CCK) research, especially focusing on the development and characterization of CCK antagonists. The book contains chapters on the synthesis, biochemical and pharmacological characterization of potent and selective CCK antagonists as well as physiological applications of these compounds. The last section of the book is devoted to the involvement of CCK in pathological states and potential clinical applications of CCK antagonists.

One of the prerequisites for survival is the ability of cells to maintain their volume. Thus, during the course of evolution cells have "learned" a variety of strategies to achieve volume homeostasis. This volume regulatory machinery involves regulation of both, cellular metabolism and cellular transport and is exploited by hormones and transmitters to regulate cellularfunction. This book to illustrates the complex interplay of cell volume regulatory mechanisms and cellular function in a variety of tissues. However, our knowledge is still far from being conclusive, and the present collection of reviews is thought to foster further experimental efforts to unravel the role of cell volume in the integrated function of cells.

The authors, all accomplished and world-renowned experts in their topic areas, have provided controversial and up-to-date accounts of the current status of research in calcium and bone metabolism by reviewing major areas of basic science which have an impact on the understanding of bone diseases and related disorders.

Idiopathic cardiomyopathy has been categorized for over 10 years by the World Health Organization as dilated, hypertrophic, or restrictive. These categories have somewhat vague boundaries; however, idiopathic dilated cardiomyopathy (IDC) finds its general definition from unexplained four-chamber dilatation, prominent systolic dysfunction with depressed ejection fraction, a marked increase in total myocardial mass without wall thickening, myocyte hypertrophy and nuclear polyploidy, rarity of frank myocardial scars, but increased interstitial connective tissue and myocyte atrophy, all in the setting of anatomically normal heart valves and coronary arteries. Mural thrombi within cardiac chambers and atrioventricular valve regurgitation are common secondary con- comitants. Myocardial inflammation is rare, but immunological abnormalities have been suggested. Ultrastructural features in- clude increased mitochondrial numbers, lipid deposits, and myo- fibrillar loss. Progressive pump failure with or without rhythm disturbances typically leads to ever-intensified medical therapies, and ultimately to transplantation or early death. The need for better understanding of IDC is represented by incidence rates varying from 5 to 8/100000 population across several populations, 10 000-20000 IDC deaths annually in the United States, and the generally increasing prevalence of the disease. More than 50% of heart transplant recipients have IDC as their primary myocardial disease. The half-life of patient sur- vival without transplantation is generally less than 5 years. Treat- ment with antiarrhythmics, calcium channel blockers, ~-adrenergic blockers, and angiotensin-converting enzyme inhibitors is being evaluated in clinical trials, but the role of such treatments in the pathobiology of progressive disease is unclear.

Sympathetic afferent fibers originate from a visceral organ, course in the thoracolumbar rami communicantes, have cell bodies located in dorsal root ganglia, and terminate in the gray matter of the spinal cord. Sympathetic afferent fibers from the heart transmit information about noxious stimuli associated with myocardial ischemia, i. e. angina pectoris. Previous reviews have described the characteristics of cardiovascular sympathetic afferent fibers (Bishop et al. 1983; Malliani 1982). This review summarizes that work and focuses on the neural mechanisms underlying the complexities of angina pectoris. In order to understand anginal pain, cells forming the classical pain pathway, the spinothalamic tract (STn, were chosen for study. These cells were chosen to address questions about anginal pain because they transmit nociceptive informa of pain. Antidromic tion to brain regions that are involved in the perception activation of STT cells provided a means of identifying cells involved with trans mission of nociceptive information in anesthetized animals. Other ascending pathways may also transmit nociceptive information, but many studies show that the STT plays an important role. Visceral pain is commonly referred to overlying somatic structures. The pain of angina pectoris can be sensed over a wide area of the thorax: in the retrosternal, precordial anterior thoracic, and anterior cervical regions of the chest; in the left or sometimes even the right shoulder, arm, wrist, or hand; or in the jaw and teeth (Harrison and Reeves 1968)."

Modern Methods of Plant Analysis When the handbook Modern Methods of Plant Analysis was first introduced in 1954 the considerations were: 1. the dependence of scientific progress in biology on the improvement of existing and the introduction of new methods; 2. the difficulty in finding many new analytical methods in specialized journals which are normally not accessible to experimental plant biologists; 3. the fact that in the methods sections of papers the description of methods is frequently so compact, or even sometimes so incomplete that it is difficult to reproduce experiments. These considerations still stand today. The series was highly successful, seven volumes appearing between 1956 and 1964. Since there is still today a demand for the old series, the publisher has decided to resume publication of Modern Methods of Plant Analysis. It is hoped that the New Series will be just as acceptable to those working in plant sciences and related fields as the early volumes undoubtedly were. It is difficult to single out the major reasons for success of any publication, but we believe that the methods published in the first series were up-to-date at the time and presented in a way that made description, as applied to plant material, complete in itself with little need to consult other publications. Contributing authors have attempted to follow these guidelines in this New Series of volumes.

The most comprehensive and conceptual one-volume treatment of this field available and the first to emphasize the cellular and molecular aspects of gut peptide biology. Authored by an array of internationally distinguished scientists, it deals with issues of peptide localization and biosynthesis in gastrointestinal cells, mechanisms of peptide release and inactivation and the nature of peptide receptors. The breadth and readability make it an invaluable reference source for scientists in all disciplines interested in any aspect of brain-gut peptides.

Contents Introduction .......................................... . 1 The Primate Eye ...................................... . 2 Embryology of Retina and Choroid ....................... . 4 Microscopic Anatomy .................................. . 4 Retina ............................................ . 4 Choroid ........................................... . 8 Material and Methods .................................. . 10 Fine Structure of the Retina 14 RetinaI Pigment Epithelium ............................. . 16 Photoreceptor Cells ................................... . 30 Outer Plexiform Layer and Horizontal Cells .................. . 64 Bipolar, Radial Clial, and Amacrine Cells .................... . 76 Canglion Cells and InternaI Limiting Membrane ............... . 98 Spatial Density of RetinaI Cells .......................... . 112 Fine Structure of the Choroid ........................... . 116 Choroidocapillaris and Its Fiber System ..................... . 118 Arteries, Veins, and Lymphatic Spaces ...................... . 134 Choroidal Nerves .................................... . 142 Cells of Choroidal Connective Tissue ....................... . 148 References ........................................... . 153 Index ................................................ . 157 vii This volume describes the morphology of the primate re tina as seen with the electron microscope. As it is an atlas, the electron micrographs are its most In trad lietian important part. The text accompanies the figures, highlighting selected topics either to explain structures or to point out structure-function relation ships. A scholarly review of the whole spectrum of research on the re tina and choroid is not feasible in a single volume. Thus, whenever available, review artides or monographs, rather than original work, are cited for reference."

The details of the receptor mechanism are not yet fully understood for any sensory system. However, sufficient data are available (for the vestibular system and for other systems) to permit meaningful tracking of the sensory messages through the nervous system and via conscious experience. The reception, process ing, storage and output of information in man and other animals, as done by means of receptors, neurons, secretory cells and muscle fibers, are collectively referred to as mind. Sensory physiologists tend to disbelieve in extrasensory perception. Sensory physiology in general is an area upon which different sciences and methods converge. Anatomists, physiologists, psychologists, physicists, chemists, and engineers have made important contributions to sensory physiology. What is special about vestibular physiology is the fact that many research workers are clinicians, living under the constant pressure of their patient's demands. This is a disadvantage when it comes to writing handbooks, but an advantage for the pa tient, since research is guided by clinical practice and can be quickly applied. Modern methods, such as recording from single nerve units and the correlation of electrophysiological and psychophysical data, have greatly contributed to our knowledge, yet the study of lesions is still important, especially in the vestibular field."

After the pioneering studies by Ussing and co-workers, studies of epithelial Nael transport have come a long way. The first phase of the phenomenological description of the cell as a black box has been follow ed by studies of cellular mechanisms, the interplay of the different trans port components, and the mechanisms of regulation. A broad spectrum of methods has been applied to many epithelia in a variety of species. For the individual epithelia transport schemes have been proposed, and, at this point I think it is appropriate to take a pause and search for elements common to several epithelia. This aspect triggered the publica tion of this book, and in fact the various chapters emphasize that the funetional eomponents, expressed in the various epithelia, are not in finite in number, but they occur in epithelia which are separated in evolu tion by several hundred million years. The authors come both from the field of veterinary and human physiology as weIl as from biology. In my opinion, the close contacts and eollaborations between physiologists and biologists have been essential for the progress in this field. I wish to thank all authors for their con tributions, and I hope that the reader will appreciate this collection of up to date reviews on epithelia in nonvertebrates and vertebrates."

Coronary heart disease is one of the major health problems in indus trialized nations because of its high incidence and severity. Recent innovations in medical and surgical treatment of coronary heart dis ease have increased the importance of accurate diagnostic methods for determining the severity of coronary disease, identifying potential treatment alternatives, and evaluating the results of treatment. Great advances have also been made in basic research on coronary circula tion and its interaction with myocardial contraction and relaxation and neural and humoral control. With respect to these developments, the papers included in the present monograph deal with important topics concerned with the basic mechanism of coronary circulation as well as ones of clinical relevance. It is directed toward physicians (cardiologists, cardiac surgeons, cardiac radiologists, anestheologists, and others) and basic scientists (e.g., physiologists, bioengineers). We would like to em phasize the importance of a multidisciplinary approach in which basic scientists and clinicians work closely together. This volume consists of nine chapters. Chapter 1 contains macro scopic and microscopic descriptions of coronary vascular anatomy, which is closely related to the functions of coronary circulation. In Chap. 2 two methods in current use to evaluate phasic coronary blood velocity waveforms are presented, i.e., the laser Doppler and ultrasound Doppler methods. Chapter 3 describes the mechanical properties of coronary circulation, a knowledge of which is indispens able for an understanding of coronary arterial and venous blood flow velocity waveforms in relation to cardiac contraction and relaxation."

The Editorial Board and the Publishers of the Handbook of Experimental Pharmacology wish to express their profound grief at the untimely death of Professor Peter Baker. Aware of his international recognition as an expert on the ubiquitous role of calcium in physiological processes and their pharma cological control, the Board was gratified when Professor Baker accepted its invitation to edit a new Handbook volume on "Calcium in Drug Actions". He went about this task with his usual energy and effectiveness so that, in the few months before his unexpected death, Professor Baker had mustered his distinguished contributors, got them to provide their manuscripts, and seen almost the entire material into the press. This achievement is all the more remarkable when one bears in mind the extraordinary number of his other commitments during the same time; they are mentioned in Sir Alan Hodgkin's preface to this volume. With so many other professional and personal responsibilities upon him, the Board of the Handbook wishes to record its grateful appreciation for the admirable way in which Professor Baker took on and carried out the additional work of bringing this fine book into existence; and the Board wishes it to be dedicated to the memory of Professor Peter Frederick Baker. The Editorial Board: G. V. R. BORN, P. CUATRECASAS, H. HERKEN, A.

Endocrinologic investigations during pregnancy have focused in the last decades on placental hormones, the maternal endocrine system and maternal fetal interactions. Less is known about the fetus itself and the interaction of fetal hormonal response and physiological parameters. In this book physiologists, pediatricians and obstetricians active in experimental studies in both physiology and endocrinology combine both aspects of investigations. Historical remarks on the endocrine development of the fetus are followed by observations of the hormonal control of the cardiovascular system. Basic mechanisms of fetal endocrine control such as brain development, fetal growth, fetal behaviour, and thermoregulation are given particular consideration. Finally, carbohydrate metabolism and the mechanism of parturition are outlined.

This book attempts to present new aspects on electrophysiologi- cal mechanisms and catecholaminergic contributions in the set- ting of acute and chronic myocardial ischemia. Special emphasis is placed on the full scope from basic molecular and cellular mechanisms to experimental models of close clinical proximity. A number of internationally distinguished scientists present their latest findings in this significant research area within the peri- meter of cardiovascular disease which continues to lead mortality statistics in most industrialized countries. Contents of this book cover in addition to other subjects re- lease and uptake of catecholamines in ischemia, regulation of re- ceptors, adrenergic contribution to ventricular arrhythmias and mechanisms of ischemic malignant arrhythmias as well as un- derlying changes in membrane currents and the electrophysiolog- ical response to beta-adrenergic blocking drugs. In addition to original contributions, a number of editorial chapters are in- cluded for conclusions and future development in these areas. The main purpose of this book is to provide further inside in two traditionally separated research topics that are gravitating to more collaborative work and inspire more joint research ventures in the future. It provides a comprehensive view on clinically sig- nificant problems where basic research may stimulate further studies in man. Therefore this book may prove to be valuable to both cardiologists and interested clinicians as well as basic scien- tists.

This volume contains the lectures presented at the NATO Advanced Study Institute (ASI) on "Trafficking of Intracellular Membranes: From Molecular Sorting to Membrane Fusion", held in Espinho, Portugal, from June 19 to June 30,1994. The objective of this Institute was to survey recent developments and to discuss future directions in the rapidly advancing field of membrane cell biology, with particular emphasis on the dynamical properties and intracellular flow of membranes. A wide range of interrelated topics around the central theme of intracellular trafficking of membranes was covered, including lipid flow, membrane fusion, dynamics of membrane components, protein folding and assembly, vesicular transport in membrane biogenesis, exocytosis and endocytosis. A large variety of experimental techniques and systems, including the application of viruses and model systems, to study these processes was also considered. Membrane cell biology is a broad discipline which encompasses many scientific areas including cell biology, biochemistry, biophysics, virology, immunonology and genetics. Indeed, recent advances in the cell biology of membranes could not have been made without this multidisciplinary approach. Significant progress achieved during the last few years in understanding how newly synthesized lipids and proteins find their way to the cell organelles, how molecular sorting and the continuous flow of membranes allow each cellular membrane to maintain its own distinct molecular composition, and, thereby, the individuality of the various intracellular compartments, was discussed in considerable detail in this Institute.

A qualitative leap in the understanding of cardiovascular and n- ral regulation by the renin-angiotensin system, and of the role of this s- tem in tissue damage, has occurred as a result of the many recent advances in molecular genetic techniques. The cloning of the genes for the components of the renin-angiotensin system, the design of specific angiotensin receptor ligands, and the use of embryonic gene targeting te- niques for the creation of mutant strains have established that the renin- angiotensin system is important in blood pressure regulation, ion and fluid homeostasis, and tissue growth and remodeling Further investigation of the mechanisms by which this system p- ticipates in cardiovascular regulation may shed some light on the pat- genesis of several cardiovascular diseases, e. g. , hypertension, congestive heart failure, and chronic renal failure. Despite the promise of this system as a target for therapeutic interventions for these diseases, there are great challenges in the integration of the attempts to close the gap between the traditional literature of medicine and the explosion of information from the new technologies. This book's title, Angiotensin Protocols, reflects the authors' strong efforts to translate expert knowledge into easy-to-follow practice. The book opens with introductory chapters, and each specialty section provides detailed methods covering a wide variety of techniques, ranging from genetic manipulation of targeted genes to functional studies of the renin- angiotensin system.

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.