This volume contains refereed manuscripts prepared from presentations made at the 2ih annual meeting of the International Society on Oxygen Transport to Tissue (ISOTT). The meeting was held in Hanover, NH, USA, at Dartmouth Medical School, the 3rd oldest medical school in the USA. ISOTT attempts to produce high quality pUblications on cutting edge topics relating to oxygen in living systerns. The goal is to allow contributors to contribute original data, as with a main-stream journal article, but also to voice individual opinions and ideas in a more relaxed scientific forum. The meeting brought together an international group of scientists who share a common interest in the measurement and role of oxygen in living systems. The organizers of ISOTT99 made a special effort to bring together people from industry, medicine, and basic sciences in order to improve the links in the chain of discovery through to application. As a result, this volume contains publications on a range of subjects. There are contributions from companies on modifiers of oxygen carrying capacity (allosteric modifiers of hemoglobin and infusible oxygen carriers or blood substitutes); technical reports on oxygen measurement devices including advances in near-infrared spectroscopy and imaging, oxygen electrodes, magnetic resonance spectroscopy and imaging, and fluorescence based measurements. There are medically related sections on modifying and measuring tumor oxygenation in order to improve therapy, assessment and interpretation of oxygenation in the central nervous system, and general issues relating oxygen to pathological conditions.

Filling a gap in the anatomical and ENT literature, the authors show the various approaches to the middle ear which allow safe surgical manipulations, such as through the tympanic membrane or the Eustachian tube.

This volume contains papers presented at the Fourth International Altschul Sympo- sium, held June 27-29, 1996, at the University of Saskatchewan in Saskatoon, Saskatche- wan, Canada. The Altschul Symposia Series are held in memory of Rudolf Altschul, a graduate of the University of Prague and a pioneer in the fields of vascular and nervous system biology. Dr. Altschul was head of the Department of Anatomy at the University of Saskatchewan from 1955 to 1963. The Altschul Symposia are made possible by an endow- ment left by Anni Altschul, Dr. Altschul's wife, and by other contributions given by the sponsors listed at the end of this Preface. The objective of the Fourth Altschul Symposium, entitled Cell Biologv and Pathol- ogv of Myelin: Evolving Biological Concepts and Therapeutic Approaches, was to facili- tate the transfer of ideas on the biology and pathology of myelin from the research laboratory to the clinic by providing a forum for discussing the evolving biological con- cepts regarding myelin function in health and disease.

This volume represents the proceedings of the 9th International Proton Transport Conference, "Mechanisms and Consequences of Proton Transport" held in Leura, Australia, August 19 -21, 200 I. This conference has been held since 1971 every 3 to 4 years with few exceptions in association with the Congress of the International Union of Physiological Sciences. The first meeting was held in Frankfurt, Germany, at the Max-Planck'Institute. Countries hosting the conference have been Germany (twice), Sweden (twice), India, Canada, USA, Great Britain, and now Australia. Over the past 30 years participants at these Proton Transport Conferences have been principal contributors to the major discoveries in the physiology, biochemistry and pharmacology of gastric acid secretion. These include development of the H2-receptor blockers, defining the signaling pathways for the regulation of acid secretion, identifying the gastric proton pump, discovery and development of proton pump inhibitory drugs, and elucidating the physiology and biochemistry of Helicobacter pylori.

One of the main attractions of research into hypersensitivity disorders is that it brings together scientists from a very broad range of disciplines. As the most common hu man immunologic disorder, it excites the interest and concern of clinicians, geneticists, basic and clinical immunologists, molecular biologists, biochemists, and physiologists. General agreement has been forged on the the pathophysiology of the disease and the mechanisms responsible for its maintenance, but many areas remain as black boxes for which we have only hypotheses. In 1992 Vienna hosted an international symposium to consider the explosion of in formation being generated by the identification, cloning, and expression of common envi ronmental allergens: The present second international conference on the MOLECULAR BIOLOGY OF ALLERGENS AND THE ATOPIC IMMUNE RESPONSE, again jointly organized and co-chaired by Professors Alec Sehon (Winnipeg) and Dietrich Kraft (Vi enna), provided an exciting opportunity for many leaders in this field to share data, argue hypotheses and seek future opportunities to enlarge our understanding of these very com plex diseases. This symposium was co-sponsored by the International Union of Immu nological Societies (I. U. I. S. ) and the International Association of Allergology and Clinical Immunology. It was held in the hospitable and comfortably elegant surroundings of Que bec City.

During the last decade, rapid progress has been made in the area of microbial immu- nity. New conceptual frameworks have emerged with regard to the processing and presen- tation of peptides and nonpeptide antigens from microbes, especially bacteria, to T cells in the context of classical MHC class I and nonconventional MHC I molecules. Experimen- tal models have been instrumental in defining some of these pathways for generating pro- tective immune responses against microbes, which form the basis for the design of new vaccines. New evidence has stressed the importance of innate immunity in microbial in- fections. The concept of dichotomy within T helper cells has revealed the role of these cell types in resistance and susceptibility to microbial-mediated pathology. These latest devel- opments in microbial immunity are discussed in this volume. Natural killer cell development is known to be regulated by the presence of MHC class I antigens. Receptors for MHC class I molecules on NK cells have been discovered. Interaction of these receptors with their specific ligands leads to inhibition of cytotoxicity. Vinay Kumar and colleagues review NK cell differentiation and ontogeny, and functions of NK cells in experimental animals. Lewis Lanier discusses the role of a newly discov- ered molecule, DAP 12, in KIR and other receptor-mediated signal transduction in NK cells. Eric Long describes the regulation of immune response by inhibitory receptors.

Recent advances in our understanding of the fundamental role of bioactive lipids in normal and abnormal physiology was the theme of the XVlth International Spring Sympo- 6-9, 1996 at the George Washington University School sium on Health Sciences held on May of Medicine in Washington, D.C. Over 250 participants shared their latest findings on fundamental mechanisms in lipid metabolism, transport, and signal transduction. Most of the papers presented at the plenary sessions have been collected in this volume, which is divided into seven parts. The focus of Part I is on the new roles that fatty acids and esters play in cellular function. These activities include regulation of gene expression, control of eicosanoid-me- diated responses, and intracellular calcium sequestration. Most biological effects of fatty acids, esters, and phospholipids are transmitted via the interaction of these lipid molecules with specific lipid binding proteins. The chapters in Part II detail the involvement of these in the transport of fatty acids, fatty acyl CoA esters, and phospholipids, and in the proteins modulation of the fatty acid-induced activation of the peroxisome proliferator-activated receptors. The study of arachidonic acid metabolism continues to be the subject of intense interest and research. A number of studies in Part III deal with the substantial differences between the constitutive prostaglandin H synthase isozyme (PGHS-l or COX-I) and the inducible form PGHS-2 (COX-2) regarding compartmentation, control, and expression.

The aim of this Atlas is to present the three-dimensional arrangement of the liver structures, which should be familiar to those who diagnose and treat diseases of the liver, particularly in an era when the methods of diagnostic imaging and surgical treatment are becoming increasingly sophisticated. For this purpose a series of corrosive preparations of the blood vessels and bile ducts of the liver was made and photographed. In addition to the normal situations, many frequent and rare variations are shown. The Atlas also shows some blood vessels that have not been adequately described or are not well-known in the reference literature, but are nevertheless of great importance in performing segmental liver resections.This Atlas takes a fresh approach to the subject. The method used allows the size, three-dimensional arrangement and structure of the blood vessels and bile ducts of the liver to be preserved. The majority of photographs were taken from the direction from which surgeons see the liver during an operation. This, together with the schematic presentations complementing most of the photographs, gives a further instructional value to the work. With colour photographs and explanatory text, the Atlas forms a basic guide to orientation inside the liver parenchyma, to understanding and diagnosing certain pathological processes and to planning surgcial procedures.

This translation from Russian into English of the monograph Hematopoi- etic and Lymphoid Tissue in Culture by E. A. Luriya provides us for the first time with a comprehensive review of the massive amount of work carried out in the USSR in this important area of biological research. Historically, the pioneering tissue culture studies of Maksimov, Popov, Chasovnikov, and their colleagues working in Russia in the early part of this century provided much of the impetus for subsequent studies on lymphopoiesis and hematopoiesis in vitro and much of the basic information used subsequently to achieve immune responses in vitro and to develop the methodology for cloning hematopoietic stem cells. Particularly welcome in this translation is the addition of the Appendix, in which Drs. Luriya and Fridenshtein describe in some detail the methodology that has been developed in their laboratories for the study of a variety of cell types in cell and tissue culture. For many of us, this description provides information that had previously not been accessible to us: porosity of millipore fIlters in relation to growth properties; colony-forming cell adhesiveness; pro- liferation kinetics of stromal cells; differential effectiveness of various media used for culture of liver cells; details of washing procedures for fIlter substrates used in culture.

This book is the first modern history of medieval European anatomical images. Richly illustrated, it explores the many ways in which medieval surgeons, doctors, monks and artists understood and depicted human anatomy. Taylor McCall refutes the common misconception that Renaissance artists and anatomists such as Leonardo da Vinci and Andreas Vesalius were the ‘fathers’ of anatomy, and the first to perform scientific human dissection; on the contrary, she proves these Renaissance figures drew upon centuries of visual and written tradition in their works. This interdisciplinary book will appeal to general audiences interested in the history of the body and medical professionals curious about the history of their discipline, as well as historians of art, medicine and medieval culture.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This becomes increasingly important as full-length recep- tors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other de- tails can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmitters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others including receptors involved in bacterial motion. The text of this information is substantial so as to require its publica- tion in two volumes. Consequently, a division was made by grouping receptors depending upon the nature of their ligands. Thus, in volume 1 there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone re- ceptor, human chorionic gonadotropin receptor, follicle stimulat- ing hormone receptor, thyrotropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor receptor, insulinlike growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.

The ISOTT 2001 local organizing committee was pleased to welcome over 140 delegates from around the world to the 29th annual general meeting of the International Society for Oxygen Transport to Tissue. The meeting was held in historic Philadelphia, USA, on the campus of the University of Pennsylvania from August 11 to 15, 2001. In the tradition of ISOTT, the conference was a total immersion experience. Attendees were encouraged to eat together and spend their evenings relaxing together in a style that maximized exchange of ideas and interactions of younger scientists with their more senior colleagues. Delegates participated in a total of 122 presentations including poster displays, selected oral presentations, seminars by invited speakers and a round table discussion. In choosing invited speakers and oral presenters, special emphasis was placed on methods for oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. All of the manuscripts contained in this volume underwent both an editorial and scientific review, and only those meeting both criteria have been published. However, while all efforts have been made to eliminate editorial errors, some have undoubtedly been overlooked, for which the editors apologize.

The papers in this book, illustating the present status of knowledge related to the vacuolar compartment of fungi and plants, were presented at an Advanced Research Workshop entitled "Plant Vacuoles. Their Importance in Plant Cell Compartmentation and their Applications in Biotechnology" held in Sophia-Antipolis, France, on July 6-11, 1986. The organizers were fortunate in being able to assemble representative leaders of all the above fields of research concerning this compartment. These scientists from all over the world were invited to present their latest results and to exchange views and plans for continued research in this highly exciting field, which is very important for the improving the industrial aspect of plant biotechnology related to the production of molecules with a high added value. To ensure maximal flexibility and opportunity for dicussion, the chairmen of the various sessions were asked to introduce their respective topics, after which they were given the freedom of organizing their sessions in a more or less improvised fashion, with brief presentations of relevant new information by participants following a schedule fixed relatively shortly before the workshop. This procedure proved to be highly successful, giving rise to most productive and stimulating discussions among the representatives of the various fields.

This volume of Cerebral Cortex is dedicated to Sir John Eccles, who was an active member of the advisory board for the series until his death in May 1997. His input as to what topics should be covered in future volumes of this series will be sorely missed. The present volume is concerned with neurodegenerative disorders and age related changes in the structure and function of the cerebral cortex, a topic that has attracted increasing interest as longevity and the number of aged individuals in the population increase. Although much of the research on the neurodegenerative effects of aging has been centered on Alzheimer's disease, most of the aging popu lation will not be afflicted by this disease. They will, however, be affected by the consequences of normal aging, so the first few chapters of this volume are con cerned with that topic. Chapter 1, by Marilyn S. Albert and Mark B. Moss, gives an account of the cognitive changes that accompany normal human aging. Chapter 2, by Mark B."

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process."

Although cell fusion is an omnipresent process in life, to date considerably less is still known about the mechanisms and the molecules being involved in this biological phenomenon in higher organisms. In Cell Fusion in Health and Disease Vol 1 & Vol 2 leading experts will present up-to-date overviews about cell fusion in physiological and patho-physiological processes, which further covers the current knowledge about cell fusion-mediating molecules. Volume 1 deals with Cell Fusion in Health and will cover aspects of cell fusion in fertilization, placentation, in C. elegans, in skeletal muscle development and tissue repair, and the use of cell fusion for cellular reprogramming and cancer vaccine development. Volume 2 focuses on Cell Fusion in Disease with a particular emphasis on the role of cell fusion in cancer development and progression. Thus, Cell Fusion in Health and Disease Vol 1 & Vol 2 represents a state-of-the-art work for researchers, physicians or professionals being interested in the biological phenomenon of cell fusion and beyond.

Numerous studies have proven the biological basis of memory formation and have begun to identify the biochemical traces and cellular circuits that are formed by experience, and which participate int the storage of information in the brain, its retention for long durations, and its retrieval upon demand. Cells in the nervous system have the capability of undergoing extremely long-lasting alterations in response to hormonal, pharmacological, and environmental stimulations. The mechanisms underlying this neuronal plasticity are activated by experiential inputs and operate in the process of learning and the formation of memories in the brain. This volume presents research areas which have not been highlighted in the past. In addition to studies on the involement of functional proteins in neuronal adaptation, this volume presents recent developments on the critical roles of bioactive lipids and nucleotides in these processes. In addition to the widely studied role of second messengers, a review of studies on extracellular phosphorylation systems operating on the surface of brain neurons is presented.The first section of the volume presents studies of basic mechanisms operating in a wide range of adaptive processes. The second section presents recent advances in investigations that have demonstrated the clinical implications of this research. These include: state of the art use of transgenic models in studies of molecular and cellular mechanisms implicated in familial Alzheimer's disease and Amyotrophic Lateral Sclerosis; studies of specific proteins implicated in Alzheimer's disease, including an adapter that binds to the beta-amyloid precurser protein (beta-APP) and the microtubular protein Tau and its membrane-bound counterpart. The advantages of using cell culture models for elucidating the causes of neuronal degeneration and for identifying mechanisms of neuroprotection are also presented among the chapters in the section on clinical implications.

Hypoxia is a constant threat throughout life. International experts from many different fields, including clinicians, clinical researchers, and basic scientists, have contributed to this volume, presenting state-of-the-art information regarding normal and abnormal (pathophysiological) responses to hypoxia. The topics covered include visitors to high altitude, the latest developments on high-altitude cerebral and pulmonary edema, the brain in hypoxia, high-altitude headache, and similarities between ischemic and hypoxic injury to the brain. In addition topics are covered such as blood-brain barrier in hypoxia, hypoxia interactions with vascular growth, and how humans adjust to extreme hypoxia.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" published in Organogenesis (Holt Rinehart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular morpho genesis, despite the enormous growth of interest that occurred nationally and inter nationally. Most writings on the subject have been scholarly compilations of the proceedings of major national or international symposia or multi authored volumes, without a specific theme. What is missing are the unifying concepts that can often make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardiovascular mor not only as an important archival and didactic reference phogenesis that will serve source for those who have recently come into the field but also as a guide to the evo lution of a field that is clearly coming of age.

Recently, attention has been called to the role that microvascular organization plays in the functional morphology of all organs and tissues, both in normal and pathological conditions. Since its development by Murakami, the corrosion cast method for scanning electron microscopy has come to be considered one of the most efficient means in clarifying the three-dimensional features of the microcirculation of organs and tissues. Scanning Electron Microscopy of Vascular Casts: Methods and Applications was planned to supply fundamental and new information regarding microcirculation studies to general biologists, anatomists, pathologists and clinicians. The contributions to this volume, contain original findings and excellent electron micrographs obtained by using recently improved corrosion cast methods. The rich variety of papers in this book will be useful to many, and will provide both the basic and clinically oriented readers with good ideas, suggestions, and original and worthwhile information.

If one were to design the ideal nuisance for cell cultures, the resultant might well be similar to mycoplasmas. These micro organisms are very prevalent in nature, being found in the oral cavity, blood, the mucous membranes of the respiratory and uro genital tract and other tissues of both man and animals. They are relatively difficult to detect microbiologically and chemically. Lacking cell walls, they do not routinely produce turbidity in cell cultures and are resistant to antibiotics that act on cell walls. Mycoplasmas grow to high titers in cell cultures. Concen 7 8 trations of 10-10 colony forming units per ml of supernatant medium are representative. Additionally, more numbers are attached to cell membranes. Further, mycoplasmas have been shown to mimic in vitro effects of viruses and toxic chemicals. In various cell culture systems, mycoplasmas have been known to cause cell death, decrease or increase cell growth, affect virus tite s, induce interferon, cause chromosome damage, induce transformation, cyto pathic effects, alter phenotypic expression, and significantly alter metabolic pathways and products of cells. The presence of such high concentrations of mycoplasmas in cell cultures constitutes a true in vitro infection. Such infected cell cultures, with a 8 9 total of 10 _10 or more actively metabolizing mycoplasmas, have no place in controlled, standardized cell culture procedures. Numerous reports have been published on mycoplasma assay pro cedures, effects of infection, and preventive and elimination measures."

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

We have considered it to be a demanding assignment to provide a complete exposition dealing with the nature of radiation, its effects, and protection against it to workers in health-related activities. "Radiation" (and more precisely "ionizing radiation") is emitted by X-ray machines, nuclear reactors, and nuclear weapons, but also comes from natural sources to which we are all exposed. It would have been easier to deal with this subject area with the terminology and mathematics employed by specialists. However, although most of the potential readers probably have obtained further pertinent knowledge, we assume no more than a high school education in science and mathematics and the challenge was to provide maximum information within this constraint. This book contains five sections: (A) Radiation Physics, (B) Radiological Physics, (C) Radiation Biology, (D) Radiation Effects on Human Populations, and (E) Radiation Protection. Each section is preceded by a synopsis covering its essential features. It provides sufficient information to enable readers to obtain a general under standing of the subject of the section and an adequate background for comprehension of other sections. The more detailed presentation in the bulk of each section is followed by appendixes that generally contain more advanced topics. This scheme necessarily involves some repetition but permits a more flexible approach for readers who are especially interested in the contents of particular sections.