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 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.

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.

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."

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."

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.

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.

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."

Over the last twenty-five years, there has been an extensive effort, still growing for that matter, to explore and understand the organization of extrastriate cor tex in primates. We now recognize that most of caudal neocortex is visual in some sense and that this large visual region includes many distinct areas. Some of these areas have been well defined, and connections, neural properties, and the functional consequences of deactivations have been studied. More recently, non invasive imaging of cortical activity patterns during visual tasks has led to an expanding stream of papers on extrastriate visual cortex of humans, and results have been related to theories of visual cortex organization that have emerged from research on monkeys. Against this backdrop, the time seems ripe for a review of progress and a glance at the future. One caveat important to emphasize at the very onset is that the reader may be puzzled or confused by the use of different terminologies. Individual investi gators commonly tend to favor different terminologies, but in general some prove more advantageous than others. As discussed by Rowe and Stone (1977) as well as by others, there is an unfortunate tendency for role-indicating names to lead to fixed ideas about function, in contrast to those that are more neutral and adaptable to new findings.

The NATO Advanced Study Institute on "Cellular and Molecular Control of Direct Cell Interactions in Developing System" has been attended by 15 invited main lecturers and 60 participants. According to its purpose senior scientists, postdoctoral trainees and graduate students working in areas like biology, biochemistry, electrophysiology, medicine etc . . . could discuss their common interest in the various structural, ultrastructural, molecular and functional aspects of cell interactions in developing in vivo and in vitro systems. Whereas the topics of the first week have been mostly concerned with the general aspects of cell interactions in embryogenesis (section I and II of this book), the second week has been mainly devoted to the structures and functions of the direct cell contact sites at the membrane level as gap junctions, including electrophysiological aspects, dye coupling and selective cell-cooperation in some model systems as the neuro-muscular junctions (section III-V of this book). A multidisciplinary and stepwise approach, from initial cell contacts in early embryogenesis up to well defined selective cell cooperation, appeared to be an efficient means to provide answers to the question of how cells control, in a dynamic system as given in a differentiating embryo, their multiple temporary and permanent interactions so necessary for ordered cell positioning, cell linking and well established cell-to-cell communication.

During October 18-31, 1980, the first course of the Inter- national School of Pure and Applied Biostructure, a NATO Advanced Study Institute was held at the "Et tore Majorana Center for Scien- tific Culture" in Erice, Sicily, co-sponsored by national and international agencies. The subject of the course was "Cell Growth", with participants (from 16 different countries) selected worldwide. The study of cell growth has been one of humanity's most challenging problems and it has been approached from many differ- ent points of view, such as biochemistry, genetic engineering, cell biology, zoology, oncology, immunology, biophysics and a few other fields. It has been very difficult to keep such varied points of view all in one room and in one audience, because of the heterogeneity of background and inherent difficulty of communica- tion, with occasional nominalistic rather than factual debates. This Institute aimed to bypass those limitations by approaching in a structured and tutorial fashion the problem of cell growth in three dimensions: (1) in terms of the various disciplines involv- ed, from molecular to cellular biology, from genetic engineering to clinical oncology, from biophysics to immunology; (2) in terms of the system studied, from prokaryotes to eukaryotes and cancer cells; (3) in terms of the various levels of macromolecular orga- nization, from membrane to cytoskeleton and chromatin.

Advances in Cell Biology has been initiated as a continuing, multi-volume series to report on the progress of a wide spectrum of problems of cell structure and cell func tion. In arranging these volumes individual contributors are asked not only to review the major new information, but especially to present the state of a given problem or area by discussing the current central issues, speculations, concepts, hypotheses, and technical problems. We intend, in addition, that these volumes will not be concerned with comprehensive reviews of the recent literature but will consist rather of presenta tions of an interpretative and integrative nature, based on selection of major research advances. It is our aim that these volumes should provide the means whereby cell biologists may keep themselves reasonably well informed about the current progress in research areas in cell biology in which they are not immediately or directly involved themselves. The articles, nevertheless, are expected to bring into focus the experimental objectives of the specialists in a given research area. D.M.P. L. G. E. M. vii Contents v Contributors Preface vii Bacterial Chromosome Replication 3 I. Peter L. Kuempel 57 2. Structure and Replication of Eukaryotic Chromosomes David M. Prescott Ultrastructure and Interaction of the Kinetochore and Centriole 3.

This volume documents the proceedings of a symposium on "Lung in its Environment" held at the Ettore Majorana 'Center for Scientific Culture, in Erice, Sicily, between 16th June and 21st June 1980. This was attended by about 200 participants drawn from Europe as a whole, but the majority were from Southern Europe. The discussion was recorded either in English or Italian and the tapes were reduced to a verbatim typescript by the Ente Nazionale Interpreti Congresso. The verbatim typescript has been edited using a few guiding principles as follows: - 1. Titles and honorifics have been eliminated unless the statement is addressed to a specific person. 2. The style of the speakers in the discussion has been preserved as far as possible and not reduced to a strictly grammatical format. 3. Where references to illustrations (e.g., on the blackboard) are made, the comments have been left unaltered and many are understandable. Removing them detracted from the sense. 4. The air of informality in the proceedings has been preserved so far as possible. 5. The responsibility for the discussion rests solely with the editors, and no contributor has had the opportunity of correcting what he said. 6. No manuscript was received from two participants, but the discussion of their presentations has been included since it contains some points of substance. 7.

Many factors may influence the release of neurotransmitters from airway nerves 1]. This is likely to be important in physiological control of airway functions and may be particularly relevant in airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Neural elements in airways interact in a complex manner and the activation of certain neural pathways may profoundly influence the release of transmitters from other neural pathways. Similarly inflamma tory mediators released from inflammatory cells in the airways may also modulate neurotransmitter release. There are marked differences be tween species in airway innervation and in neuromodulatory effects and, wherever possible, studies in human airways have been emphasised, although information on neuromodulation in human airways is some what limited at present. Release of neurotransmitters from nerve terminals occurs via a Ca2+ dependent secretion evoked by a nerve action potential, but may also be evoked experimentally by a high extracellular K + concentration which directly depolarises the nerve terminal membrane. Modulation refers to the alteration of neurotransmitter release, which may either be increased (facilitation) or reduced (inhibition) by the action of a particular agent, thus changing the magnitude of the neurally-mediated response. Such agents would normally act on receptors on the nerve terminal which are referred to as pre-junctional (or presynaptic) receptors, in contrast to post-junctional (or post-synaptic) receptors located on the target cells which are influenced by that particular transmitter."

The brine shrimp Artemia has become an important experimental system for studies of the developmental process. In recent years the shrimp has yielded considerable information on the pattern of development, bio chemistry, and gene structure and expression of crustaceans. This book is a compilation of research activity from twenty five of the most active re search laboratories working with brine shrimp in the above areas. It also represents the proceedings of a NATO Advanced Research Workshop held in Montreal, Canada, August 11-13, 1988. The book contains twenty nine full papers covering the major areas discussed at the workshop. In addition, one page abstracts representing seventeen poster presentations which were given at the workshop, and which were deemed to be most relevant to the theme of the book, are included. These are designated with an al in the Table of Contents following the title of each paper. A considerable amount of discussion which took place during the workshop has not been included in the book because of space limitations. However, the editors will endeavour to make some of this in formation available at a later date through the Artemia Newsletter. In addition to the high percentage of invited speakers who attended and contributed to the workshop, the organizers would like to thank a number of participants who made valuable contributions to the major dis cussion sessions. These include: John Freeman, Michael Horst, Herman Slegers, Jack Vaughn, Frank Conte, Sandy McLennan, Clive Trotman and Patrick Sorgeloos."

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume."

* The definitive reference work on arterial hemodynamics. * Fully updated and revised to cover all recent advancements in the field.

vi The word ppotein, coined one and a half century ago from the 1TpOTE:toa ("proteios" = of primary importance), underlines the "primary importance" ascribed to proteins from the time they were described as biochemical entities. But the unmatched compl~xity of the process involved in their biosynthesis was (understandably) overlooked. Indeed, protein biosynthesis was supposed to be nothing more than the reverse of protein degradation, and the same enzymes known to split a protein into its constituent amino acids were thought to be able, under adequate conditions, to reconstitute the peptide bond. This oversimplified view persisted for more than 50 years: It was just in 1940 that Borsook and Dubnoff examined the thermodynamical aspects of the process, and concluded that protein synthesis could not be the reverse of protein degradation, such an "uphill task being thermody- namically impossible *** * " The next quarter of a century witnessed the unravelling of the basic mechanisms of protein biosynthesis, a predictable aftermath of the Copernican revolution in biology which followed such dramatic de- velopments as the discovery of the nature of the genetic material, the double helical structure* of DNA, and the determination of the ge- netic code. Our present understanding of the sophisticated mechan- isms of regulation and control is a relatively novel acquisition, and recent studies have shed some light into the structure and organi- zation of the eukaryotic gene.

The fetal period of human growth and development has become an area of intense study in recent years, due in large part to the development of diagnostic ultrasound. More than 2,000 articles have been published in the last five years describing anatomy and pathology in utero, as reflected in sonographic images. Yet, no stan dard reference exists to correlate these images with fetal gross anatomy and at tempts to draw parallels from adult structure have often led to false assumptions. The dictum "the newborn is not a miniature adult" is all the more valid for the fetus. This text aims to provide a comprehensive reference for normal sectional anat omy correlated with in utero ultrasound images. In addition, magnetic resonance images of therapeutically aborted or stillborn fetuses are paired with similar gross sections to serve as a foundation upon which current in vivo studies may build. Lastly, a miscellaneous section illustrates several anatomic points useful in the understanding of fetal anatomy. These points include the changing anatomy of the fetal brain during gestation and the anatomy of the meninges, the fetal heart, and ductus venosus. It is our hope that this atlas will provide a clear picture of fetal anatomy, rectify some of the confusion which exists in antenatal diagnosis, and stimulate further interest in fetal development."

The roots of this book and its sister volume, Mammal Phylogeny: Placenta/so go back to discussions and plans, shelved for a while, between F. S. Szalay and W. P. Luckett during the international and multidisciplinary symposium on rodent evolution sponsored by NATO, July 2-6, 1984, in Paris. That conference, orga nized by W. P. Luckett and J. -L. Hartenberger, the proceedings of which were published in 1985, proved an inspiring experience to all of the participants, as this was repeatedly expressed both during and after the meetings. In addition to issues relating to rodents, general theoretical topics pertaining to the evolutionary biol ogy and systematics of other groups of mammals regularly surfaced during the presentations and discussions. M. J. Novacek, who was also a participant in the rodent symposium, shared with Luckett and Szalay the enthusiasm acquired there, and he also expressed strong interest for a meeting on mammal evolution with a general focus similar to that of the rodent gathering. In 1988, Szalay and Luckett, after having planned in detail a program, direc tion, and core list of participants, were awarded a $30,000 grant by the Alfred P. Sloan Foundation through the Research Foundation of the City University of New York. The grant was contingent upon obtaining additional funds sufficient to assure that the symposium would be held. Raising the remaining funds proved to be a problem.