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 function. Jn 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 presentations of an interpretive 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 Contributors v Preface vii 1 1. The Regulation of DNA Synthesis in Eukaryotes James Douglas Watson 2. D.RNA Containing Ribonucleoprotein Particles and Messenger RNA Transport 47 G. P. Georgiev and 0. P. Samarina Recent Developments in the Synchronization of 3. Tetrahymena Cell Cycle 111 Eric Zeuthen 153 4. Repetitious DNA Christopher Bostock 5. Mitosis 225 R. Bruce Nicklas Specific Enzyme Production in Eukaryotic Cells 299 6."

Unique features of the present work include: Only authorized English translation of the original Spanish text, adhering as much as possible to the letter, with correction of the obvious errors already predicted by Cajal in his Preface. Added facts appearing in the French version, with correction of old as well as new errors, the latter probably due to inaccuracies in translating into French some nuances of the Spanish language. Uniform of nomenclature according to contemporary scientific English. Annotations on Cajal s changing concepts over time, the elucidation of certain structures that do not have present day equivalents, and explanations of the many symbols appearing in illustrations but not mentioned in the corresponding original legends. Most illustrations are reproductions of Cajal s original art work, still extant at the Cajal Museum in Madrid, with cross references to figure numbers of the Spanish and French versions. Citations are given by author and year in the text, with an alphabetical list at the end of the volume, completed and corrected for accuracy against original publications. Taxonomy glossary of species appearing in the text, with present scientific names, and their colloquial English counterparts."

The discovery of the human T cell leukemia virus type I in the late 1970s heralded a new era in retrovirology. For the first time, it was demonstrated that a retrovirus could play a role in the development of a human disease, in this case adult T cell leukemia (ATL). Several years later, the acquired immunodeficiency syndrome (AIDS) epidemic began, and it was dem- strated that a retrovirus, originally designated the human T cell lymp- tropic virus type 3, was the causal agent of this syndrome. This virus, later named the human immunodeficiency virus type 1 (HIV-1), has since been extensively studied in terms of its pathogenesis as well as its ability to elicit immune responses. In that time, a tremendous amount of information has been obtained about the virus. Although recent drug regimens have been useful in significantly lowering viral loads and perhaps maintaining an asymptomatic state among individuals infected with HIV-1, an established "cure" for AIDS eludes us. In addition, the effective drug therapies are very expensive, and are not available to infected people in the third world, where greater than 90% of new infections occur. Furthermore, the development of viral resistance against the drug therapies is an additional concern. Despite extensive study, no effective vaccine has been developed. One of the problems in developing an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelop glycoprotein, to undergo amino acid hypervariability.

The day it rained in Wepion ..... . The NATO Course on Regulation of Function and Growth of Eukaryo tic Cells by Intracellular Cyclic Nucleotides was organized in Wepion (Belgium) from September 23 to October 1, 1974, by L. Birn baumer (Chicago), B.L. Brown (London), R.W. Butcher (Worcester), J.E. Dumont (Brussels), M. Paiva (Brussels) and G. Van den Berghe (Louvain), under the benevolent and most efficient aegis of Dr. T. Kester (NATO, Brussels). The formula of the Course was inspired by the Gordon Con ference with its combination of a pleasant, friendly and easygoing atmosphere together with a solid and critical scientific diet offered in the morning and evening, the afternoon being free. For these reasons, the meeting was located in a pleasant motel in beautiful surroundings by the side of the Meuse river, in the country, but close to the town of Narnur. Everything, absolutely everything, from swimming to tennis, to horse riding, was available to make the afternoons agreeable and to facilitate social contacts."

Anatomy, to be sure, is the essential foundation of clinical practice, but it is much more than that. First and foremost, anatomy is a biological science. There is order and logic to the organization of the human body and the arrangement of its parts. And, as all sciences, anatomy offers challenge and discovery. Concepts in Anatomy is not a textbook, but more of a brief handbook that is selective rather than encyclopedic in scope, conception rather than particular in its approach. It stresses general principles, so as to minimize rote learning, and it provides order and direction to the study of gross anatomy. Anatomy is inherently complicated and confusing; this volume helps you make sense of it in a way that also aims to inspire its study. Richly illustrated with original drawings, Concepts in Anatomy is a valuable resource for anyone currently studying or teaching the subject, or as a reference for advanced researchers.

This monograph, Senescence; Dominant or Recessive In Somatic Cell Crosses? represents the second annual workshop to promote theory and concept development in aging research. These workshops are part of a resource to bank cultured cells of special interest to aging research that was established at the Institute for Medical Research in Camden. New Jersey. by the National Institute on Aging in 1974. The underlying theme of the workshops is the use of cultured cells in a variety of somatic cell genetic systems designed to define mechanisms of in vitra cellular scen escence and the possible insights that this may provide to the problems of in viva aging. The concept also includes bringing together workers from a variety of disciplines to stimulate new and innovative thoughts and work in the area. The current work shop focuses on the relative role of nucleus and cytoplasm on determining the in vitra lifespan of human diploid cells as well as the relative influence of old and young cells when combined within a single cell structure. The techniques and procedures discussed should make significant contributions to understanding in vitra senescence and may lead to the mapping of an area or areas of the genome linked to senescence as is being accomplished with viral transformation of normal cells. Warren W. Nichols Donald G. Murphy ~i Contents Theoretic Mechanisms of in vitpo Senescence 1 F. MaPott Sinex . . . . . . . . . . . . Senescence in Ce1l Cu1ture: An Accumu1ation of Errors or Terminal Differentiation? 13 Vincent J. GPistofaZo . . . . . . . . . . . . . .

Crash Course - your effective every-day study companion PLUS the perfect antidote for exam stress! Save time and be assured you have the essential information you need in one place to excel on your course and achieve exam success. A winning formula now for over 20 years, each series volume has been fine-tuned and fully updated - with an improved full-colour layout tailored to make your life easier. Especially written by senior students or junior doctors - those who understand what is essential for exam success - with all information thoroughly checked and quality assured by expert Faculty Advisers, the result are books which exactly meet your needs and you know you can trust. Each chapter guides you succinctly through the full range of curriculum topics, integrating clinical considerations with the relevant basic science and avoiding unnecessary or confusing detail. A range of text boxes help you get to the hints, tips and key points you need fast! A fully revised self-assessment section matching the latest exam formats is included to check your understanding and aid exam preparation. The accompanying enhanced, downloadable eBook completes this invaluable learning package. Series volumes have been honed to meet the requirements of today's medical students, although the range of other health students and professionals who need rapid access to the essentials of anatomy and physiology will also love the unique approach of Crash Course. Whether you need to get out of a fix or aim for a distinction Crash Course is for you! Provides the exam syllabus in one place - saves valuable revision time Written by senior students and recent graduates - those closest to what is essential for exam success Quality assured by leading Faculty Advisors - ensures complete accuracy of information Features the ever popular 'Hints and Tips' boxes and other useful aide-memoires - distilled wisdom from those in the know Updated self-assessment section matching the latest exam formats - confirm your understanding and improve exam technique fast

This monograph analyses all aspects related to the etiopathogenesis, pathomorphology, diagnosis and treatment of lumbar disc herniation. It includes 24 chapters, over 500 illustrations, partly in colour, and 2800 bibliographic entries, going from the historical to the most recent ones. Five chapters are dedicated to biological and pathomorphologic aspects both of lumbar disc herniation and the conditions most often associated with herniation. The etiopathogenesis is analysed in the light of the most significant and recent studies. Five chapters deal with the clinical presentation and diagnostic tests in an extremely wide and detailed way. Large space is reserved to conservative management. The chapters on invasive treatments and on the results and complications of surgery define the advantages and limitations of the old and new percutaneous or surgical treatments. Two chapters are dedicated to surgical management of patients with spinal conditions associated with herniation, and two other deal with the surgical failure. This monograph is aimed at satisfying the requirements of both experts and young doctors. Some chapters are of particular interest to the spine specialist, whilst others are useful to the novice to acquire a general knowledge of the subject.

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.

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.

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.

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 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.