This volume is based on a series of lectures delivered at a one-day teach ing symposium on functional and metabolic aspects of NMR measure ments held at the Middlesex Hospital Medical School on 1st September 1985 as a part of the European Nuclear Medicine Society Congress. Currently the major emphasis in medical NMR in vivo is on its poten tial to image and display abnormalities in conventional radiological im ages, providing increased contrast between normal and abnormal tissue, improved definition of vasculature, and possibly an increased potential for differential diagnosis. Although these areas are undeniably of major importance, it is probable that NMR will continue to complement con ventional measurement methods. The major potential benefits to be de rived from in vivo NMR measurements are likely to arise from its use as an instrument for functional and metabolic studies in both clinical re search and in the everyday management of patients. It is to this area that this volume is directed."

ARCHIVE COpy DO NOT REMOVE The public in industrialized countries shows a mounting concern about biological effects of electrical and magnetic fields. As a result, experimental studies on this subject are being published in increasing numbers throughout the world. Prof. H. L. Konig, of the Technical University of Munich, West Germany, a leading expert and pioneer in this field, has written an authoritative text in a lucid style which makes the material also accessible to lay readers. The book describes the effects of natural as well as artificial electromagnetic energies covering the en tire measurable frequency range from the highest frequencies, x-rays, through microwaves, radio waves, and finally extremely low frequency (ELF) waves. Cit ing the evidence from scientific studies in various countries, Konig also appraises the biologic effects of microwaves and high tension power lines, which have become controversial issues in recent years. Other contributions to the book have been made by Prof. Albert P. Krueger, University of California, Berkeley, on air ionization effects and by the mete orologist Walter Sonning on biometeorology, documenting the influence of atmo spheric electrical currents on health and disease. Moreover, the late Dr. Siegnot Lang, a former coworker of Dr. Konig, has contributed to this book."

Cardiovascular dynamics is a field in which modelling and systems analysis have formed an extremely important discipline. For example, understanding of even such a fundamental function of the circulation as the relationship between central venous pressure apd cardiac output has required evolution of a pertinent model based on years of exhaustive ex perimental investigations by Starling, Starr, and Guyton. Hemodynamic analyses of pulsatile pressures and flows in the arteries and veins have been a continuing challenge taken up by champions of fluid dynamics such as Frank, Wetterer, Taylor, and Wormersley, just to mention a few names, and some kind of model was always proposed as a conceptual framework. An even greater challenge to cardiovascular dynamicists was how to analyze the intermittent coupling of the ventricle and the arterial or venous vasculature through the valve. The availability of numerical solutions by computer and the recently evolved ventricular model with a time-varying elastance and a pressure-dependent internal resistance opened the way to analysis of this coupling. The ever increasing speed of computers has also facilitated trips between the fre quency and the time domain, even on-line for some experimental studies. This book contains many analyses dedicated to the interactions between the heart and the vasculature, providing the reader with findings at the cutting edge of current research in this field."

The recent surge of interest in designing, validating, and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation be tween the carcinogenicity and mutagenicity of chemicals and physical agents and by the assumption that DNA alteration, mutations, and chromosome aberrations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from the environment and would lead the public to avoid them. The actual response, however, is quite different. Governmental departments shy away from making any decisions on the basis of in vitro test systems. The public at large is becoming irritated by daily an nouncements that many of their cherished habits could adversely affect their health. Industry appears to feel threatened and may reduce its search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to uncertainty about the in volvement of mutations in neoplastic transformation, partly due to the present difficulty of extrapolating results from various endpoints obtained on numerous organisms to man, and partly due to a multitude of complex events that lead in vivo to the evolvement of benign or malignant tumors."

The objective of this book is to provide information that will be useful to people in a variety of disciplines who wish to learn more about normal aging processes in the human body. Although gerontologists in the biological sciences are making great strides in research on human aging and documenting this work in mono graphs, texts, and review chapters, this information is generally not easily acces sible nor is it comprehensible to nonprofessionals in these fields. This book is intended to provide a summary of this work, along with its implications for psy chological functioning of the aging individual. The majority of the book is devoted to describing the results of research on the physiological changes in the human body with aging and to seeking explana tions for these age effects. This description has been approached in such a way as to make it readable for the nonspecialist, but also to focus on research issues that will be useful reading for those who are currently working in these parti cular areas. In addition, throughout the book, I have tried to develop some themes regarding physiological and psychological adaptation during adulthood."

High altitude physiology and medicine has again become important. The excep tional achievements of mountaineers who have climbed nearly all peaks over 8,000 m without breathing equipment raise the question of maximal adaptation ca pacity of man to low oxygen pressures. More importantly, the increase in tourism in the Andes and the Himalayas brings over 10,000 people to sites at altitudes above 4,000 and 5,000 m each year. At such heights several kinds of high alti tude diseases are likely to occur, and these complications require detailed medical investigations. Medical authorities need to inform both mountaineers and tourists as to how great a physical burden can be taken in the mountain environment without risk to health. Physicians need to know what kind of prophylaxis is to be employed at high altitudes to prevent the development of diseases and what therapeutic measures should be used once high altitude diseases have occurred. Moreover, the physical condition of the indigenous population living at higher altitudes such as the Andes and the Himalayas, who are exposed continuously to the stress of high altitude, requires our attention. We have become familiar with symptoms characteristic of chronic high-altitude disease: under special conditions this popu lation has a tendency to develop pulmonary hypertension, which is associated with pulmonary edema, pulmonary congestion, and right heart failure."

Platelets playa fundamental, life-saving role in hemostasis and blood clotting at sites of vascular injury. Unwanted platelet activation and arterial thombus formation are, however, implicated in the onset of myocardial infarction, stroke, and other cardiovascular diseases. Acceptance that platelets play a major role in the pathogenesis of atherosclerosis including coronary heart disease has revolutionized the pharmacological treatment of cardiovascular diseases, and aspirin is now an essential antiplatelet drug and the golden standard for future developments. Yet the search for better and perhaps safer antiplatelet drugs is one of the most active areas of investigation in both basic and clinical research. Platelets, especially human platelets, have also emerged as one of the major models for the study of inter- and intracellular signal transduction pathways. Many biochemists, cell biologists, pharmacologists, pathologists, hematologists, and cardiologists find platelets useful for studying processes such as adhesion, inside-out and outside-in signalling through the plasma membrane, channels, calcium homeostasis, protein kinases, the network of intracellular signal transduction cascades, and the release of vasoactive substances. The aim of the editors has been to compile chapters summarizing the current state-of-the-art information on the biochemistry, cell biology, pharmacology, and physiologic and pathophysiologic roles of human platelets. We hope that this volume represents the major aspects of current platelet research although it is perhaps inevitable that certain areas are covered less thoroughly than others. We would like to acknowledge the excellent help and support of the Springer-Verlag staff, in particular that of Ms. Doris Walker.

In planning The Handbook volumes on Audition, we, the editors, made the decision that there should be many authors, each writing about the work in the field that he knew best through his own research, rather than a few authors who would review areas of research with which they lacked first hand familiarity. For the purposes of the chapters on Audition, sensory physiology has been defined very broadly to include studies from the many disciplines that contribute to our understanding of the structures concerned with hearing and the processes that take place in these structures in man and in lower animals. A number of chapters on special topics have been included in order to present information that might not be covered by the usual chapters dealing with anatomical, physi ological and behavioral aspects of hearing. We wish to thank all authors of the volumes on Audition for the contributions that they have made. We feel confident that their efforts will also be appreciated by the many scientists and clinicians who will make use of the Handbook for many years to come. WOLF D. KEIDEL WILLIAM D. NEFF Erlangen Bloomington August 1974 Contents Introduction. By G. v. BEKESY t. With 3 Figures. . . . . . . . 1 Chapter 1 Consideration of the Acoustic Stimulus. By R. R. PFEIFFER. With Chapter 2 19 Figures. . . . . . . . . . . . . . . . . . . . . . . . . 9 Comparative Anatomy of the Middle Ear. By O. W. HENSON Jr. With Chapter 3 23 Figures. . . . . . . . . . . . . . . . . . . . . . . 39 . . . . ."

In this book we attempt a synthesis of knowledge from two investigative extremes. On the one hand, neurophysiology and neuropharmacology are progressing via the single neuron to a subcellular level; on the other, clinicians are studying the function ofthe human urinary system in vivo as a whole. A special effort must be made over the next decade to bridge this gap. We hope that the information summarized here will catalyse the process. In 1968, de Groat and Ryall published a group of papers in the Journal of Physiology in which modern quantitative electrophysiological techniques were applied to the study ofthe reflexes that regulate bladder Junction. These papers represent alandmark in the history of bladder neurophysiology, forming a dividing li ne between old and new. The earlier techniques of lesioning and stimulation of nervous structures yielded mainly qualitative information which was open to criticism because of lack of precise control over what was actually being destroyed or stimulated. Much of this earlier work was reviewed in an authoritative volume by Bors and Comarr in 1971, entitled Neurolqgical Urology. The 16 years have seen great advances in our understanding ofthe control oflower subsequent urinary tract function.

The XIIth North American Testis Workshop was held in Tampa, Florida, April 13 to 16, 1993. The program consisted of 23 invited lectures and 120 poster presentations. In keeping with the tradition of the Testis Workshop, every attempt was made to emphasize recent develop- ments in the study of endocrine and gametogenic functions of the male gonad. Although the main emphasis, reflected in the title of the pro- ceedings, was on the function and control of somatic cells in the testis, one session was devoted to germ cells and one to the studies of male reproductive development and function. The last session of the workshop was included in the program of the Postgraduate Course of the American Society of Andrology, which held its annual meeting in Tampa imme- diately following the workshop. This volume consists of 21 chapters prepared by the speakers and 8 chapters contributed by presenters of the posters. The Program Committee consisted of Drs. Nancy Alexander, C. Wayne Bardin, Andrzej Bartke (Chairman), Kevin J. Catt, Claude Desjardins, Maria Dufau, Michael Griswold, Norman Hecht, Aaron Hsueh, Dolores J. Patanelli, Bernard Robaire, and Richard Sherins. The workshop was generously funded by Serono Symposia, USA, which also agreed to handle registration, local arrangements, and publication of this volume. On behalf of the Program Committee and all participants, I would like to thank Dr. Bruce Burnett of Serono Symposia, USA and his staff for their efforts and support in every aspect of the organization of the workshop.

Of all the areas of biological science, there is, perhaps, none that has experienced in recent decades so great an increase in findings as neurobiology, the discipline that concerns memory in all of its myriad aspects. The notion of exploring memory, that capacity to store and recall individual experience, has received attention increasingly in our society. Of course, animals can exhibit astounding powers of memory, but memory is of paramount importance to human beings due to the significant role it plays in the transmission of our cultural traditions. It is tradition, after all, that ensures the passing on of qualities established by lineage, a continuous link from generation to generation, between past and present. And it is tradition that inspires bodies of thought (knowledge and customs, for example) to be handed down by a multiplicity of information bearing devices (i. e. , word, writing, picture, electronic data carriers). The objective of this book is to inform the reader in one clear volume of the groundwork which has been established in memory research from the diverse disciplines of neurobiology. It is intended, primarily, for students of medicine, zoology, biology, psychology and psychiatry, but will certainly prove to be a valuable resource to others with a healthy interest in the area.

Since the awarding of the Nobel Prize to Drs. Guillemin and Schally iJ) 1971 for isolation and chemical characterization of gonadotropin releasing hormone, we have experienced a remarkable period of growth of interest in this hormone. The last 20 years have been characterized by a swift translation of basic science discovery into clinical utility. Approval of GnRH and its analogs for treatment of prostate cancer, endometriosis, of ovulation indicate the range and precocious puberty and for induction of these agents. of usefulness In order to bring together the leaders in the basic and clinical science of GnRH, a conference was organized on "Modes of Action of GnRH and GnRH Analogs" and held in Scottsdale, Arizona, February 26 to March 2, 1991. The presentations, given as chapters in this volume, show both the advances in the body of information in this discipline and the efforts underway to reduce basic science to clinical practice. The audience was a combination of representatives from universities, government, industry, and physicians in practice. The lively discussions and insightful questions indicated the interest in the topics discussed and frequently served to catalyze planned interactions of the meeting participants. The organizers are grateful to the speakers and poster presenters for their contributions and for the timely preparations of the manuscripts included in the present volume. We are also thankful to the staff of Serono Symposia, USA, for the organizational skills and support that allowed the meeting organizers to focus on the science and medicine presented.

Lithium and Cell Physiology explores the role of lithium in a wide range of physiologic contexts. The contributions reflect the most recent advances in our understanding of the biochemical, pharmacological, and clinical applications of this metal ion. The book discusses how lithium modulates cells of the immune system, stimulates granulopoiesis, and influences the course of viral infections. The effect of lithium on the skin, as well as on inositol phosphate metabolism, cell growth, magnesium-dependent enzymes, and essential fatty acids and prostaglandins is discussed.

First published in 1986, Professor Tonomura's book explains at the molecular level how cells use energy harnessed as adenosine triphosphate to perform the fundamental physiological functions such as muscle contraction and the active transport of cations. In all cases, ATPases enzymes are involved and the detailed reaction mechanisms are carefully described. Young collaborators helped Professor Tonomura to put together the first draft of the book, for he was particularly anxious that the text should be accessible to students who were less familiar with the intricacies of the field than he himself, and should reflect their needs. After his sudden, untimely death, Professor Ebashi and his colleagues at the National Institute of Physiological Sciences, Okazaki, updated and completed the text. The result is a well-written, interesting account of the field and this volume forms a worthy memorial to one of the foremost workers in this area of biochemical research.

This volume is an overview of research examining the relationship between hormones and aggressive behavior. The last 15 years have witnessed a tremen dous growth of knowledge in this area, yet reviews written by specialists are virtually nonexistent. This work is an attempt to provide a comprehensive and cohesive synthesis of this literature. Chapters 1-7 provide an analysis of hor monal influences on the major forms of aggressive behavior, including intermale, interfemale, shock-induced, maternal, territorial, and predatory aggression. The focus of Chapters 8-12 is an examination of the mechanisms through which hormones might act to produce changes in agonistic responding. Genetic, de velopmental, neural, and biochemical influences are considered. It is well known that environment, social context, and experience modulate the effects of hor mones on behavior. Thus, Chapters 13-15 are designed to review the literature concerning hormone-pheromone interactions, hormonal responses to compe tition, and the influence of social context on the endocrine system and aggressive behavior. Frequently, the principles advanced by behavioral endocrinologists are based on research in one species, the rodent. To provide a more comparative perspective and to examine specifically the generality of those principles gen erated for rodents, Chapters 16-22 examine hormone-aggression relationships in a variety of species, including fish, birds, amphibians, reptiles, infrahuman primates, humans, ungulates, and insects. This volume should be useful to both beginning and advanced researchers in animal behavior, behavioral endocri nology, physiological psychology, neuroendocrinology, zoology, physiology, and psychiatry."

Three years ago, most authors contributing to this book gathered at the Heinrich Fabri Institute of the University of Tubingen at Blaubeuren near Ulm in Germany for the third conference on "Pineal Gland and Cancer." In 1987, the late Derek Gupta organized the second meeting and published the first book on the topic, 10 years after Vera Lapin, as part of the 25th anniversary celebrations of the Vienna Cancer Research Institute, had held the first meeting. It was in Vienna during the 1930s and 1940s that W. Bergmann and P. Engel demonstrated that pineal extracts possess growth inhibitory properties on experimental rodent tumors and R. Hofstatter reported favorable results when these extracts were given to cancer patients. In the 1970s, Vera Lapin and others reported that surgical removal of the pineal gland (pinealectomy) stimulates experimental tumor growth rendering fundamental support for an involvement of the pineal gland in malignancy. A focal question of past and present research in this field is whether the pineal gland exerts its tumor inhibitory activity primarily or exclusively via melatonin. Currently, it appears that the action of melatonin on experimental tumor growth criti cally depends on the circadian timing of its administration as weH as on the type and stage of cancer, and that primarily highly differentiated tumor ceHs are controHed. Initial clinical applications of the pineal hormone for incurable cancers raise hopes for a promising future use, particularly when combined with other therapies (e. g."

This is the first comprehensive work to review blood platelet biochemistry, physiology, pharmacology, and function. It provides up-to-date information on how platelets function, the biochemical mechanisms that modulate their physiology and function, as well as the pharmacology of platelet inhibitory drugs.

In this unique book, Sir Donald Harrison draws on his wide-ranging experience as a surgeon and comparative anatomist to produce an authoritative and detailed account of the anatomy and physiology of the mammalian larynx. His investigation of the larynx has involved the study of over 1400 specimens of mammalian larynges from around the world, as well as using data from his own clinical experiences. The comparative morphology of the larynx is discussed from a developmental and functional perspective and the involvement of the larynx in respiration, locomotion and vocalisation is highlighted. Throughout the book the relationship of structure to function is drawn out and the clinical relevance of features of the human larynx is emphasised. This book will be an invaluable reference for all researchers and clinicians involved in laryngology as well as for anatomists, zoologists and anaesthesiologists.

Omnis cellula e cellula, "every cell from a cell," was dogma to the 19th century cellular physiologist and the cornerstone of Virchow's Cellular pathologie. "Spread out a cell into a layer and you will find that, in ceasing to be a cell, it has ceased to act as such," wrote the British 1 physiologist G . R. Lewes more than a century age. "The cell remains vital as long as its wall remains intact . . . " keeping its content "pure and clear" and thus preserving the "vital principle" within, echoed Claude 2 Bernard a few years later. The notion of the cell membrane as a pro tecting envelope held sway until it became clear that it could not account for the "coalescence" of poorly differentiated embryonic "vesicles" and for their transformation into "cell-like structures" capable of auto regulation and yet subject to what the grandfather of one of us defined as the "federal obligations imposed by the whole organism., 3 A new concept was needed, and soon the membrane was described as a structure capable of uniting as well as separating adjacent cells. Morphologic evidence for this dual function was obtained several years later when the electron microscope revealed the existence of tight and gap junc tions which, acting as intercellular bonds and channels, allowed the cells to communicate with one another and thus coordinate their biologic activities."

Calcium plays an enormous and varied role in living systems now widely appreciated by clinicians.
Calcium in Internal Medicine demonstrates the physiological significance of calcium in clinical medicine and discusses the abnormal calcium metabolism in disorders such as renal failure, hypertension, atherosclerosis and osteoporosis.
Hirotoshi Morii (Editor) linked the clinical use of vitamin D analogues in bone diseases, Yoshiki Nishizawa (Editor) researched the connection between calcium metabolism and atherosclerosis and Shaul G. Massry (Editor) was the first to systematize the importance of excess PTH in chronic renal failure. In addition to these areas, Calcium in Internal Medicine covers basic physiology, pathophysiology, nutritional requirements and the role of calcium in the development and treatment of other various diseases. The importance of calcium and its regulatory systems is brought together in one publication providing a useful reference tool for internists, rheumatologists and endocrinologists.

Advances in cellular physiology and molecular biology have now disclosed the metabolic changes and adaptational responses of the heart to various kinds of stresses. Topics covered in this volume include the regulation of myocardial proteins in mechanical overload, the alteration of adrenoceptors in the stressed heart, metabolic adaptation in cardiac hypertrophy, intracellular calcium metabolism in the ischemia-reperfused myocardium, calcium overload as a cause of myocardial stunning, acquisition of ischemic tolerance by ischemic preconditioning, factors that accelerate myocardial injury, and ventricular remodeling in the ischemic heart. As an update of the latest findings in basic cardiology, this book will benefit both researchers and clinical practitioners.

Advances in the field of glycoprotein hormones necessitated a second international symposium on this topic, held March 11 to 14, 1993, in Santa Barbara, California, and again sponsored by Serono Symposia, USA. The meeting was twofold in its concept: (1) the dissemination of the current research in the field and (2) honoring three scientists who have greatly contributed to this field, Drs. Harold Papkoff, Robert Ryan, and Darrell Ward, upon their retirements. We were honored to have Dr. John Pierre present as a participant at the meeting and also serving as master of ceremonies at the banquet. Certainly one of the highlights at the first meeting, held in 1989, was the cloning of the CG/LH receptor. This second meeting was also filled with insightful and innovative scientific presentations. Significant advances in the regulation of gene transcription of the gonadotropins were presented by Pamela Mellon, James Hoeffler, John Nilson, Bruce Weintraub, and Joel Habener. These presentations reflected major advances from the in the understanding concepts offered at the last meeting. Other advances of hormone structure/function included the continuing work by Joyce Lustbader on the determination of the three-dimensional structure of hCG, including a new approach using nonisotopic labels for 3-D and 4-D NMR imaging. New insights into biosynthesis of hCG were proposed by Irving Boime. Studies directed at identifying receptor contact regions were presented by Henry Keutmann and David Puett.

The field of oxygen study is immense. No single work on the subject can be comprehensive, and this volume makes no such claim. Indeed, coverage here is selective and the selection is somewhat personal. However, the choice of topics is vast There are chapters on the history of oxygen, oxygen in the universe, the biochemistry of oxygen, and clinical uses of oxygen. An alternate title could have been, "Some things you always wanted to know about oxygen, but didn't know where to find them easily." Some information in this wide-ranging work can not be found elsewhere. This book is intended not only for specialists, but also for nonspecialists engaged in or curious about any field of oxygen study, particularly if they wish to know more about other fields of oxygen. Thus, those who are interested in oxygen and are historians, astronomers, chemists, geochemists, evolutionists, biochemists, physiolo gists, pathologists, or clinicians will find here much of extreme value. It is intended to be read and understood at the graduate or advanced undergraduate level. This volume is divided into four parts. The first constitutes the background for Parts II and III, and the last integrates the preceding material with an overall perspective on oxygen in living organisms."

In his review of the Proceedings of the First International Workshop on Respiratory Muscles in Chronic Obstructive Pulmonary Disease, organized in Montescano in 1986, Thomas K. Aldrich stated that "there is little information on nutrition". We felt that the need to supplement the evaluation of respiratory muscles by studying nutritional problems was an important enough matter to justify producing a specific study on the subject. This book is the result of the efforts made in this direction. Since 1986, many of the problems associated with nutrition and ventilatory function have been elucidated, and we hope that the contents of this book may contribute towards spreading interest and knowledge in this sector, particularly among those working in the field of respiratory rehabilitation. The physiological and clinical aspects of nutritional problems and the therapeutic approaches adopted in different disease conditions are dealt with in these pages by some of the best-known researchers in the field, providing abundant evidence, if any should be needed, that rehabilitation is not merely exercise. The picture strongly emerging over these last few years is that rehabilitation is not merely a matter of knowledge of lung or respiratory muscles, but also of heart-lung interaction, metabolic equilibrium and nutrition. So much for recent developments, but what does the future hold in store? May 1992 RENATO CORSICO Preface Nutrition and ventilation are inextricably related.