This volume explores all aspects of vascular biochemistry and includes chapters that provide an understanding of vascular function with descriptions of tissue components present in the vascular wall as well as an exploration of the hemodynamic and metabolic activities associated with this function. In addition, some chapters explore the vasculature under conditions which mimic various disease states. The information provided in this volume will provide new insights into the mechanisms that control vascular function as well as therapies designed to treat vascular disease.

The duplicity theory of vision concerns the comparisons (both differences and similarities) and interaction between the cone and rod systems in the visual pathways, with the assumption that the cone system is active during daylight vision and the rod system functions in low light (night time). Research on this aspect of vision dates back to the 17th century and the work of Newton, and is still ongoing today. This book describes the origin and development of this fundamental theory within vision research - whilst also examining the Young-Helmholtz trichromatic colour theory, and the opponent colour theory of Hering - and presents evidence and ideas in light of modern conceptions of the theory. Written for academic researchers and graduate students, the book brings back knowledge of the tradition of duplicity theory, inspiring questions related to anatomy, comparative biology, molecular biology, photochemistry, physiology, genetics, phylogenetics and psychophysics.

"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.

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.

It is a great honor and pleasure for me to introduce this book; an honor, because of the scientific renown and authority of the investigators who have edited the volume and contributed the chapters; a pleasure, because my own long-lasting interest in the baroreflexes has always gone in the same directions as those along which the authors of this book have conceived and organized their work. It is particularly meaningful, in my opinion, that the very title of this volume underlines the integrative functions and the clinical aspects of baroreceptor reflexes. Under the aspect of integration, it is more and more apparent that baroreceptor reflexes, though preponderantly influencing cardiovascular functions, are not limited to cardiovascular control. Their influence on respiration has been well known since the earliest studies on baroreflexes, and wider influences have more recently been shown, e. g. , on hormone release, on sleep and vigilance, and on emotional behavior. Even within the scope of cardiovascular regulation, the integrated action of baroreflexes is not only directly exerted on the heart and blood vessels, but is also exerted through more devious but no less important routes, such as renin release from juxtaglomerular cells and sodium and water reabsorption by the renal tubules.

In the cardiovascular sciences, an increasing demand for the use of modern methods of cell biology has developed. The use of specific cell culture models of the various tissues involved is essential for most of these novel approaches. This book meets the demand for acomprehensive and easy accessible source for cell cul- ture methods in cardiovascular research as it was not previously available. The basic methods for cultures of cardiomyocytes (embryonic and adult), endothelial cells (micro- and macrovascular), smooth muscle cells and pericytes are described in detail by an international selection of experts. Special chapters discuss the use of growth factors and attachment substrates, techniques for co-cultures, cultures on permeable filter membranes and microcarrier cultures. The methodological descriptions are sufficiently detailed for an immediate application in the laboratory. All chapters also contain a critical evaluation of alternative approaches.

Proceedings of an International Workshop held in Sheffield, UK, September 1-4, 1997

MOTOOMI NAKAMURA As we approach the 21st century, ischemic heart disease is the major cause of death in most of the developed nations of the world. Since the 1970s, much effort and expense have led to designs of coronary thrombolytic therapy, percutaneous coronary angioplasty (PTCA), coronary artery bypass grafting, heart transplantation, automatic defibrillators, as well as to the formation of beta blockers and com pounds which block the calcium channel. Socio-educational programs directed at exercise, diet, instruction in the risk factors of smoking, hyperlipidemia and hypertension have contributed to the decrease in the rate of morbidity and mortality of patients with ischemic heart disease. However, the first clinical event of ischemic heart disease, the so-called "heart attack" and sudden cardiac death continues to present problems, as the mechanisms involved in these events are poorly understood. It has long been thought that ischemic heart disease is the sequence of an organic fixed atherosclerotic obstruction of the epicardial coronary arteries and the role of coronary vasomotion has been given much less attention. Recent clinical and laboratory animal studies revealed that increased tonus and spasm of the large epicardial coronary arteries are the cause of various stages of ischemic heart disease. The role of coronary vasospasm in the development of un stable angina, sudden cardiac death and acute myocardial infarction remains open to debate. Pharmacophysiological studies showed that the epicardial large coronary artery contributes only 5% to regulation of normal coronary flow."

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.

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.

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."

Stability of the internal environment in which neuronal elements are situated is unquestionably an important prerequisite for the effective transmission of information in the nervous system. During the past decade our knowledge on the microenvironment of nerve cells has expanded. The conception that the microenvironment of neurones comprises a fluid with a relatively simple and stable composition is no longer accepted; the microenvironment is now envisaged as a dynamic structure whose composition, shape, and volume changes, thereby significantly influencing neuronal function and the trans mission of information in the nervous system. The modern conception of the neuronal microenvironment is based on the results of research over the last 20 years. The extracellular space (ECS) is comprehended not only as a relatively stable microenvironment containing neurones and glial cells (Bernard 1878), but also as a channel for communica tion between them. The close proximity of the neuronal elements in the CNS and the narrowness of the intercellular spaces provides a basis not only for interaction between the elements themselves, but also between the elements and their microenvironment. Substances which can cross the cell membranes can easily find their way through the microenvironment to adjacent cellular elements. In this way the microenvironment can assure non-synaptic com munication between the relevant neurones. Signalization can be coded by modulation of the chemical composition of the ECS in the vicinity of the cell membrane and does not require classic connection by axones, dendrites, and synapses.

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)."

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."

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.

Advances in Compararative and Environmental Physiology helps biologists, physiologists, and biochemists keep track of the extensive literature in the field. Providing comprehensive, integrated reviews and sound, critical, and provocative summaries, this series is a "must" for all active researchers in environmental and comparative physiology. Cellular volume and osmolality in animals is a well studied topic and this specific volume in the series provides the reader with a thorough grounding in this area of physiology. Consisting of two parts, the text discusses osmolality and volume control in terms of both inorganic and organic ions which as a result gives an excellent overview to those working and interested in this 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 development of a new antiarrhythmic drug involves many people with disparate skills. The organic chemist who makes it is guided not only by the structure-action relations of previous compounds, but by anticipation of a requirement for a particular type of action. In fact several of the best-known antiarrhythmics, including lidocaine, mexiletine, amiodarone and verapamil, were originally synthesized for other purposes. Physicians have to determine whether the new drug works, and pharma cologists how it works. For some years I have believed that there was room for a work which could be understood by all these groups and which could enlighten each about the point of view of the others. Thus when I was invited by Springer-Verlag to prepare a volume in their series Handbook of Experimental Pharmacology, I already had a firm conception of what its form should be. In any multi-author work there are two objectives which cannot always readily be reconciled. The first is to select topics which would relate to each other in a coherent manner. to give a logical and orderly shape to the volume as a whole. The second is to offer authors the greatest possible freedom to express themselves as they wish. When the general design was complete, prospective contributors were invited to write specific chapters, being provided with a complete list of their coauthors and chosen topics, so that they could avoid overlap."

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.

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.