Rubin and Damjanov's latest volume of Pathology Reviews highlights the latest progress in the interface of biology and disease. Forefront techniques and experimental models that were once considered exotic or esoteric, are explored here in the context of understanding more fully the processes involved in human disease. Topics include: regulation of liver growth * contractile cells in lungs * mineral formation in bone * folate metabolism * the "riddle of the mast cell" * HLA antigens * interleukin 6 * IgA nephropathy * Goodpasture syndrome * anti-basement membrane glomerulonephropathy * molecular mechanisms of oncogenesis * molecular diagnosis of cancer * inhibition of intercellular communication in carcinogenesis * DNA repair and its pathogenetic implications * human and rat mammary tumorigenesis. Pathology Reviews * 1990 is essential reading for everyone concerned with the mechanisms of disease.

Specialists from diverse disciplines discuss the important topics of Tissue Repair and Fibrosis. The Role of Myofibroblast. The Myofibroblast is implicated in many processes, such as tissue repair, fibrosis, and stromal reaction to tumors. This book seeks to provide an overview of the knowledge accumulated since this cell was first describes 25 years ago. Discussions focusses on three main topics: - Cellular and molecular biology of fibroblast and myofibroblasts - Wound healing: experimental models, and - Human fibrocontracted diseases

This comprehensive book, lavishly illustrated with over 700 colour pictures, addresses the subject of bone in internal medicine. It is based on biopsies of bone and first describes the normal range of physiological findings in iliac crest biopsies in young, middle-aged and elderly individuals. The book then deals systematically with the osseous disorders most frequently encountered in internal medicine, and some that would be considered in the differential diagnosis. Numerous up-to-date references are included. The clinical applications of biopsies of bone are emphasized as well as their clinical interpretation; sections on histomorphometry and functional aspects of bone cells are also included. The book will be of particular interest to specialists in internal medicine, endocrinology, nephrology, haematology and oncology, as well as being a bench manual for the practising pathologist.

Needle biopsy of the liver is now an accepted procedure in most large hospitals, and surgeons and laparoscopists are more likely to biopsy the liver under direct vision than in the past. Consequently, increasing demands are being made on pathologists for rapid diagnosis. This full colour atlas provides a practical guide to the histopathological diagnosis of liver disorders, with particular emphasis on clinicopathological correlation and the need for the pathologist to be in full possession of all the available clinical information. Although containing over 350 colour illustrations, the book is more than just an atlas and each section includes a brief description of the main clinical and pathological features of the subject under discussion. For this second edition, many chapters have been rewritten - e.g. on viral hepatitis - and many new illustrations added. The book is intended for the practising and trainee pathologist and the clinician who performs liver biopsies, but will also be of value to postgraduates, residents and students in other branches of medicine.

The 1997 European Conference on Spectroscopy of Biological Molecules (ECSBM) is the seventh in a biennial series of conferences devoted to the applications of molecular spectroscopy to biological molecules and related systems. The interest of these conferences rests mainly on the relationship between the structure and physiological activity of biological molecules and related systems of which these molecular species form part. This volume ofECSBM contains articles prepared by the invited lecturers and those making poster presentations at the seventh ECSBM. The reader will find mainly applications of vibrational spectroscopy to protein structure and dynamics, biomembranes, molecular recognition, nucleic acids and other biomolecules and biological systems containing specific chromophors. Biomedical applications of vibrational spectroscopy are expanding rapidly. On the other hand, a significant number of the papers describe applications of other methods, such as NMR, circular dichroism, optical absorption and fluorescence, X-ray absorption and diffraction and other theoretical methods. One aim has been to achieve a well balanced, critically comparative review of recent progress in the field of biomolecular structure, bonding and dynamics based on applications of the above spectroscopic methods. A great part of the contributions included in this volume are devoted to biomedical and biotechnological applications and provide a broadly based account of recent applicationS in this field. The content of this book has been organized in sections corresponding mainly to the different types of biological molecules investigated. This book includes also another section related to theoretical methods where MO calculations of vibrational frequencies dominate clearly the topic.

Principles of Insect Pathology, a text written from a pathological viewpoint, is intended for graduate-level students and researchers with a limited background in microbiology and in insect diseases. The book explains the importance of insect diseases and illuminates the complexity and diversity of insect-microbe relationships. Separate sections are devoted to * the major insect pathogens, their characteristics, and their life cycles * the homology that exists among invertebrate, vertebrate, and plant pathogens * the humoral and cellular defense systems of the host insect as well as the evasive and suppressive activities of insect disease agents * the structure and function of passive barriers * the heterogeneity in host susceptibility to insect diseases and associated toxins * the mechanisms regulating the spread and persistence of diseases in insects. Principles of Insect Pathology combines the disciplines of microbiology (virology, bacteriology, mycology, protozoology), pathology, and immunology within the context of the insect host, providing a format which is understandable to entomologists, microbiologists, and comparative pathologists.

As an industry, biotechnology may be likened to the Hymn Book, being both ancient and modern. Whereas activities such as baking, brewing, the fermenting of foods date from our earliest attempts to control and utilise the environment, the application of recombinant DNA technology is recognised as being at the forefront of novel industrial development. Perhaps because of its association with processing foodstuffs together with the benefits derived from applications in the early organic chemistry and pharmaceutical industries, biotechnology has been regarded as being inherently safe. Yet unlike other modern industries, such as chemical and nuclear, where regulation has followed from incidents or accidents, modern biotechnology has been subject to close scrutiny and regulation almost from its inception. The process of regulation itself is somewhat unusual in that it was initially self-imposed by the very scientists who developed the fundamental techniques of recombinant DNA technology. They recognised the signific ance of their development but were concerned of the effects on humans and the environment of uncontrolled application of the new, powerful technology. Concern about the possible consequences of genetic manipula tion has undoubtedly been the driving force behind the regulations that are now in place in many parts of the world and which are the subject of this book. Safety issues in the biotechnology industry can be categorised under three headings: worker, environmental and consumer (product) safety."

The localized attachment of circulating leukocytes to endothelium has been recognized as the cellular hallmark of the inflammatory response. This adhesive interaction, a necessary antecedent to the emigration of leukocytes from the blood into the tissues, is mediated by vascular adhesion molecules. Leukocyte Recruitment, Endothelial Cell Adhesion Molecules and Transcriptional Control: Insights for Drug Discovery outlines some of the cellular and molecular mechanisms of inflammation with contributions from top researchers. This volume provides an overview of three of these endothelial adhesion molecules, as examples of key mediators of leukocyte recruitment. It reviews the structure and regulation of these cell surface proteins and focus on the rapidly expanding field of transcriptional regulation of these inducible proteins, and closes with a discussion of drug discovery possibilities that target the regulation of leukocyte recruitment. This book will be of interest for any researchers, in academia or industry, looking for an overview of leukocyte recruitment or novel approaches to drug discovery.

Historically we have separated the disciplines of Chemistry and Biochemistry by recognizing that the distinguishing characteristic of Biochemistry is the catalysis of reactions by enzymes. Enzymes permit metabolic reactions which would otherwise require extremes of temperature, pressure or pH, often associated with Chemistry, to proceed under ambient conditions of the body. Under some conditions chemical reactions occur in vivo in which products of enzymatic reactions proceed to undergo further reactions non- enzymatically with cellular macromolecules. The results can often be seen as toxic or carcinogenic responses. The chemicals that initiate these reactions are termed "biological reactive intermediates. " The International Symposia on Biological Reactive Intermediates (BRI) began in 1975 at the University of Turku, Finland and have since convened at the University of Surrey, Guildford, The United Kingdom (1980), the University of Maryland, College Park, Maryland (1985), the University of Arizona, Tucson, Arizona (1990), the GSF Forschungszentrum and Technical University of Munich (1995) and, most recently, at the Universite Rene Descartes, Paris, France (2000). The Symposium was organized by an International Planning Committee co-chaired by P. Dansette (Paris, France) and TJ. Monks (Austin, Texas). The committee included: P. H. Beaune (Paris, France), M. De\aforge (Saclay, France), G. P. Gervasi (Pisa, Italy), G. G. Gibson (Guildford, UK), H. Greim (Munich, Germany), DJ. Jollow (Charleston, South Carolina), P. Moldeus (Sodertalje, Sweden), I. G. Sipes (Tucson, Arizona), R. Snyder PJ. van Bladderen (Zeist, The Netherlands). They were (Piscataway, New Jersey), and assisted by an International Scientific Program Advisory Committee which included: TJ.

It is well known that estrogen is "somehow a protective hormone for various age-related disorders. This book provides a solid knowledge of estrogen s neuroprotective activities in the brain with a special emphasis on neurodegenerative disorders such as Alzheimer s Disease. The focus is (1) to describe the biochemical, molecular, and cellular basis of the protective activity of estrogen and (2) to transfer this knowledge into the hospitals by discussing preventive and therapeutic approaches such as estrogen replacement therapy for post-menopausal women. Besides up-to-date information on estrogen and the brain, this book explains in a highly understandable manner molecular and cellular techniques by which basic data have been collected. The reader, which may include the professional specialist as well as the interested non-specialist, will also gain insight into the scientific transfer process of knowledge from basic science to the clinical situation and therefore "from bench to bed ."

The role of carcinogenic agents in the deveolopment of human cancers is now being defined using a variety of human cells as experi mental model systems. A workshop on "neoplastic transformation in human cell systems in vitro: mechanisms of carcinogenesis" was held at the Georgetown University Medical Center, Washington, DC, on April 25-26, 1991. The aims of the workshop were to present the state-of-the art in the transformation of human cells in culture, as well as to provide insight into the molecular and cellular changes involved in the conver sion of normal cells to a neoplastic state of growth. The following topics were closely related to the theme of the workshops: 1. Derivation of in vitro model systems (epithelial, fibroblastic, and hematopoietic). 2. Factors modulating cellular transformation. 3. Usefulness of defined in vitro model systems for viral, chemical, and radiation carcinogenesis. 4. Multistep nature of human cell carcinogenesis. 5. Role of activated and suppressor oncogenes in neoplastic trans formation. The workshop was organized by J. S. Rhim and A. Dritschilo (cochairmen), G. Jay, J. little, M. McCormick, R Tennant, and R R Weischelbaum. There were 32 speakers, 30 poster presentations, and about 190 participants."

Chronic obstructive pulmonary disease (COPD) ranges amongst the commonest diseases in the world. The relentless progression of the disease causes a pressing need for a better understanding of and therapies for COPD. This volume provides state-of-the-art information on the pathophysiology of COPD including an outlook on new therapies. It is of interest to researchers and clinicians in academia as well as in the pharmaceutical industry.

This year marks the tenth anniversary of the International Symposium on Medical Virology. In the Foreword to the book of the 1980 Symposium, we stated, "However, the challenges still lying ahead are more numerous than our past accomplishments". Little did we know at the time, that within a few years the spread of human immunodeficiency virus type I was going to occur. This worldwide epidemic has, like no other disease in recent history, awakened the scientific community and the public at large. It is a reminder to all of us that regardless of our vast technical advances, Nature provides such great opportunity for biological diversity, that it will always be one step ahead of our scientific knowledge. Although our understanding of virology, molecular biology and immunology have increased by leaps and bounds over the last decade, we are still at the point of being unable to effectively control the spread of this viral infection. We hope that our Symposium this year has helped researchers to come together and exchange' ideas, so that our growing knowledge of viral infections will help produce better approaches to control them. Luis M. de la Maza Irvine, California Ellena M. Peterson March, 1991 v ACKNO~EDGEMENTS It would be impossible to single out all those individuals who helped us make this Symposium a reality, however, we would like to take this oppor tunity to express our appreciation for their efforts.

The study of atherosclerosis centered since the first decade of the present century on etiology and pathogenesis. In fact, the studies of the military academy of medicine in St. Petersburg have opened the way of inducing atherosclerosis in animals. Pathogenesis of atheroma has been studied since then in humans and animals naturally prone to the development of the disease and by a variety of dietary and other procedures. The various experimental studies allowed science to evaluate the relative importance of different factors (genetic, dietary, hormonal, pharmacological. mechanical, circulatory, etc.) in atherogenesis. Epidemiological studies as well as biochemical plasma lipid and lipoprotein estimations coupled with light microscopic, histo chemical and electron microscopic investigations decreased the gap between observations on the human and experimental animal research. The enormous literature covering this field allows the intelligent reader to formulate a comprehensive concept regarding etiological factors and pathogenesis of atherosclerosis. Its impact on pre ventive and curative medicine was however limited in scope."

For more than 35 years the Swiss Society of Neuropathology has organiseditstraditionalInternationalWinterMeeting.Themainaimofthis venue is to bring together neuropathologists and clinicians as well as neuroscientistsinterestedindiseasemechanisms.TheXVIIIthInternational WinterMeeting washeld inMarch 2000 in St. Moritz, Switzerland. The topicofthe2000Meetingwas"NeuropathologyandGeneticsofDementia." Aprogrammeofinvitedplenarylecturesofhigheducationalvalueaswellas platform andposterpresentations given by manyparticipantscoveredthe broadspectrumofdementingdisorders.Encouragedbythehighstandardof the meeting, and probably also influenced by the advent of a new Millenniumwedecided, togetherwithKluwerAcademiclPlenumPublishers, topublishtheProceedingsofthe2000Meetinginthepresentbook. The increaseofthe agedpopulation challenges social and health care systemsinindustrializedsocieties.Maintenanceofhealthandautonomyinto oldage isakeyfactor, andtheautonomyandindependenceofoldpersons crucially depend on mental health. However, neurodegenerative disorders accompanied bydementiaaffect 5-10%ofindividualsoverthe ageof65, and for the age group between 65 and 95 the prevalence of cognitive dysfunction doubles every 5 years. With this challenge in mind, Rossor discusses the clinical syndrome of dementia which encompasses an enormousvarietyofunderlyingdisorders. Over the last few years it has become apparent that many neurodegenerative disorders are characterised by protein misfolding and aberrant polymerization and may therefore be viewed as "aggregation proteopathies." Among them a substantial subsetofdementing disorders, either with or without motor dysfunction, are characterised by abundant v VI Preface neuronaland/orglialaccumulationofhyperphosphorylatedtauprotein.The molecular parametersofthese "tauopathies" are reviewed by Delacourte. Therecentdiscoverythatmutationsofthetaugenearecausativeforfamilial formsoffrontotemporaldementiaandParkinsonism(FTDP-17)broughtthe "taupathway"and the"tauopathies"tothecentrestage.Thisextraordinary breakthroughwillbecoveredbySpillantiniandGoedert.Thereisincreasing evidence that argyrophilic grain disease is much more frequent in older patients than previously thought. Tolnay et al. are reviewing recent contributionstothepathologyofthislate-onsetdementingdisorderinwhich ofamyloidbetadeposits, isalmost taupathology, inthealmosttotalabsence exclusivelyrestricted to the limbic lobe and the amygdala. Schultzet al. report an intriguing age-related progression of neuronal and glial tau pathologyinbaboonsthusrenderingthe baboonapotentialprimatemodel forage-relatedhuman"tauopathies." Gotzetal. introducetransgenicmice expressingmutated human tau as valuable animal models for reproducing formationofneuro-andglialfibrillarylesions.

This volume represents a series of papers presented at the Second International Workshop on HPV Immunology held at the University of Cambridge July 5-7 1993. This Workshop and its predecessor held in Amsterdam in May 1992 were two of the major activities of the European Concerted Action "Immunology of Human Papillomavirus and Vaccine Development." The Concerted Action (CA) was supported by grants from the Commission of the European Communities (EC), the French Association for Cancer Research (ARC) and the European Association for Medical Research (EAMR). Twenty two laboratories throughout Europe and Scandinavia were members of the CA, the objectives of which were to develop collaborations, implement scientific exchanges and co-operate in a collective effort to develop vaccination strategies for HPV. HPV's are ubiquitous pathogens and evidence which has been accumulated over the past decade leaves little doubt that infection with certain HPV types (the so called "oncogenic HPV's" 16, 18 and their relatives) is the major risk factor in the development of cancer of the uterine cervix in women. Since an infectious agent, a virus, is implicated as the main aetiologic factor in this disease, the possibility is raised that if one could prevent HPV infection or treat established infections this would be an effective anti-cancer strategy against what is the commonest cancer in women worldwide."

The title of this monograph, Brain Tumor Research and Therapy, is the name of the Conference itself, which had its inaugural meeting in the United States in 1975 andhas since progressed to the international scale. In Japan, the first conference ofits kind was organized by Dr. Takao Hoshino and me and was held at Nikko in 1980, hence its name, the Nikko Conference on Brain Tumor Research and Therapy. Though it started as a small, closed meeting, the conference has grown considerably, and in 1992 it was reorganized as the Japanese Conference on Brain Tumor Research and Therapy and was opened to all neurosurgeons and neuropathologists interested in the study of brain tumor problems and who are participating in this field. The main purpose of the Conference on Brain Tumor Research and Therapy is the candid and informed discussion of the most up-to-date developments in basic re search and clinical treatment of brain tumors. The 3rd Japanese Conference on Brain Tumor Research and Therapy was held at Nasu (Tochigi Prefecture), Japan, in No vember 1994. It was a great honor to welcome many distinguished guests from over seas who kindly attended each session and made valuable contributions.

The past 20 years have seen a surge of research into colorectal cancer, which is a reflection of the need to improve our methods of treating patients suffering from this increasingly common form of cancer. Greater knowledge of the basic mechanisms involved in colorectal carcinogenesis is an essential prerequisite to improvements in cancer prevention. In this volume the editors have brought together an impressive list of experts to cover the epidemiology, pathophysiology, morphology and basis for new diagnostic and therapeutic approaches to early detection and prevention. This broad scientific approach provides the reader with up-to-date review of our current state of knowl edge of colorectal carcinogenesis and indicates how this information can be used to generate more research and create new opportunities for diagnosis and treatment. This is a book of knowledge and ideas, some of them still at the stage of theoretical interest, but others with practical potential for the care of patients. I recommend it to those who have a research interest in colorectal carcinogenesis, as well as to readers who wish to know just how far medical scientists have progressed in their efforts to achieve the ideal of cancer prevention."

Autopsy derives from the greek word autopsia, which means act of seeing with one's own eyes. It remains the most objective and accurate method to understand human. disease. Unfortunately, the volume of autopsies in teaching hospitals has decreased dramatically over the past years. The crucial factors that account for this are the recent progress and development of new technologies, especially in diagnostic imaging, immunology, cell biology and genetics. Additionally, the perpetual fear of legal liability by physicians accounts for its further decline. Consequently, physicians and medical students are engaged in fewer autopsies and are not reaping the rich educational rewards that accompany these examinations. The purpose of the autopsy is not only to establish the cause of death, but also to determine the nature and course of the disease process. Our goal with this book is to emphasize the importance of the post-mortem exam and the correlation between pathologic material and clinical data by analyzing actual cases with problem-based methodology. The focus of this handbook is on cardiovascular disease, and when appropriate, other disease categories are included if they have an impact on cardiovascular function. The approach is more than the usual clinico-pathological correlation. Rather, we attempt to present the material from the perspective of the autopsy table. We use the clinical data as the initial framework and the autopsy findings to develop a true understanding of the disease and the associated pathophysiology of the condition.

This two-volume work contains the full text of the oral and poster presentations and the general discussion at the round table discussion of the Second International Conference on Alzheimer's and Parkinson's Diseases: Basic and Therapeutic Strategies, held at the Kyoto Park Hotel in Kyoto, Japan, on November 6-10, 1989. The First Conference was held at the Aviya Sonesta Hotel in Eilat, Israel, on March 24-27, 1985. , The record of this First Conference was published by Plenum Press in 1986 as Volume 29 in Advances in Behavioral Biology, under the title "Alzheimer's and Parkinson's Diseases: Strategies for Research and Development." We are happy that the comprehensive texts of the oral and poster presentations of the Second Conference could again be published within the framework of this series. Since the First Conference in 1985, rapid progress has been made in both basic and therapeutic aspects of these diseases. About 700 scientists from allover the world participated in the Second Conference, and 300 papers were presented in oral and poster sessions. Many people and organizations have helped to organize this multi disciplinary international conference and hence have contributed to the scientific quality of these two volumes. We thank the members of the organizing committee, the organizations that provided financial support, and the contributing scientists for their enthusiastic participation.

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Ataxia-telangiectasia or A-T is a fatal progressive neurological disease of children. The symptoms indicate disruptions in the development of such diverse body parts as cerebellum, thymus and chromosomes. The patients are unduly sensitive to ionizing radiation, immunodeficient, and a third of them develops cancer. All of this stems from defects of a single gene. Provided here is an up-to-date review of all important work in thefield. A wide spectrum of topics is covered, namely genetics, chromosome 11 mapping, radiobiology, complementation, heterozygote identification, clinical variants, biochemistry, and treatment of A-T.

Atlas of Selective Lymphadenectomy for Melanoma, Breast Cancer and Colon Cancer emphasizes a multidisciplinary approach combining the experiences of a nuclear medicine physician, surgeon, and pathologist. This is an important reference also for researchers and clinicians who want to become familiar with sentinel lymph node mapping. The underlying thesis in solid tumor biology is that metastasis in general starts in an orderly progression with lymphatic spread first to the sentinel lymph node (SLN) in the nearest lymph node basin. Therefore, the logical approach is to harvest that specific SLN for thorough analysis.

As an addition to the European postgraduate training system for young neurosurgeons, we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbuhl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have been associated throughout with this senes. The fact that the English language is now the international medium for communication at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contri butions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publication of any volume for scrutiny and suggestions for revision. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

This volume provides a history of Eosinophilic Esophagitis (EoE), a basic understanding of the physiology of the eosinophil, and a current understanding of the pathophysiology and genetics of EoE. The emphasis is on clinical applications including presenting symptoms, diagnosis and treatment options for patients with EoE. Written by both pediatric and adult experts in the fields of gastroenterology, allergy and pathology, this volume includes the most up to date information. Providing practical information useful in the treatment of patients, this book will be of great value to gastroenterologists, allergists, pathologists, medical residents, fellows, internists, and general practitioners who treat patients with eosinophilic esophagitis.