Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

The tendency of fungi pathogenic for humans to have shapes in tissue distinct from their usual saprophytic morphologies has fascinated the pathologist and medical mycologist for almost a century. A primary rea son for this fascination is the possibility that fungal duality of form, or dimorphism, may be an important virulence factor that allows the zoo pathogenic fungus to survive host defenses. A second reason relates to the desire to gain basic insights into the regulation of cellular develop ment and morphogenesis among the etiological agents of human mycoses. Many excellent treatises have appeared within the recent past dealing with fungal dimorphism. However, it is becoming increasingly clear that it may be beyond the capability of one or a few authors to review this subject adequately. Instead, the ever-increasing volume ofliterature asso ciated with fungal dimorphism and the diversity offungi now recognized to exhibit a type of dimorphism suggest that a volume comprised of con tributions by numerous researchers may be more appropriate. This per ception provided me with the motivation to compile a multiauthor volume."

The NATO Advanced Research Workshop entitled "The Photosynthetic Bacterial Reaction Center: Structure, Spectroscopy, and Dynamics" was held May 10-15, 1992, in the Maison d'H6tes of the Centre d'Etudes Nuc1eaires de Cadarache near Aix-en-Provence in the south of France. This workshop is the most recent of a string of meetings which started in Feldafing (Germany) in March 1985, soon after the three-dimensional structure of the bacterial reaction center had been elucidated by X-ray crystallography. This was followed, in September 1987, by a workshop in Cadarache and, in March 1990, by a second meeting in Feldafing. Although one of the most important processes on Earth, photosynthesis is still poorly understood. Stimulated by the breakthrough of solving the bacterial reaction center structure at atomic resolution, the field of relating this structure to the function of the reaction center, i. e. the remarkably efficient conversion and storage of solar energy, has been developing vigorously. Once the general organization of the cofactors and some details of the protein-cofactor interactions were known, it became possible to combine a variety of spectroscopic techniques with the powerful tool of site-directed mutagenesis in order to address increasingly incisive questions about the specific role of some amino acid residues in the electron transfer process. Still another promising tool is being developed, namely the exchange of a number of the native bacteriochlorophyll and bacteriopheophytin cofactors by chemically modified pigments.

The publication of this volume of The Viruses entitled The Togaviridae and Flaviviridae comes at an appropriate time. The structure and rep lication strategies of these viruses are now known to be sufficiently di verse to warrant the removal of flaviviruses from the Togaviridae family and establish them as an independent family. Flaviviridae have a special place in the history of virology. The prototype virus-yellow fever virus was the first virus to be identified as the cause of a human disease. Some of the history of this discovery is described in Chapter 1 of this volume; in Chapter 10 the complete sequence of the RNA genome of the virus is presented. This sequence not only defines the primary structure of the viral proteins, it also clarifies the mechanism of translation of the fla vivirus genome. Knowledge of the sequence of the structural proteins of these viruses represents an important step in the potential goal of using purified flavivirus glycoproteins as vaccines. Many of the chapters in this volume focus on the structure and replication of the Togaviridae. These viruses have provided valuable models for studies in cell biology, partic ularly with regard to the cotranslational and posttranslational steps re quired for the synthesis and localization of membrane glycoproteins. Fur thermore, Togaviridae have been pivotal in our growing understanding of how enveloped viruses enter and exit from cells. The broad outlines of the structure and gene expression of Togavir idae and Flaviviridae are known, but important questions remain."

These Proceedings of the Fourth International Congress on the Cornea continue a tradition of summarizing the state-of-the art basic and clinical research in cornea and ex- ternal diseases since the first Congress was held in 1964. Reflecting the emerging impor- tance of refractive surgery, two of the twelve sessions of the Congress were devoted to refractive surgery; this is reflected in an emphasis in these Proceedings. In addition, an en- tire session was devoted to the molecular and cellular biology of the cornea with impor- tant new information on the role of growth factors and cytokine modulation of corneal wound healing. Within these Proceedings an international group of expert researchers and practitioners provide the latest insights into the tear film and ocular surface, corneal trans- plantation and eyebanking, the corneal stroma and endothelium, contact lenses, microbial and nonmicrobial keratitis, keratoconus, and world corneal health. Notable subjects covered include the latest understanding of the barrier function of the ocular surface epithelium, corneal hydration control, the molecular mechanisms con- trolling gene expression in corneal wound healing, stromal~pithelial interactions in the cornea, the immunology of blepharitis, the effect of contact lenses on the conjunctiva, morphologic and functional evaluation of the human corneal endothelium, long-term fol- low-up of penetrating keratoplasty in keratoconus, the Tampa trephine penetrating kerato- plasty, and the refractive results of the Nidek EC-5000 excimer laser.

Blastomycosis remains the most enigmatic of human mycotic infections. The enigmas encompass the natural habitat of the etiologic agent, extent of exposure and subclinical infections in endemic areas, distribution of en demic foci throughout the world, inconsistency of serologic evaluation of infected patients, and varying response of such patients to standard treat ment regimens. In spite of diligent investigations by many competent investigators, we still do not know the ecological niche inhabited by the etiologic agent. We have many tantalizing clues but no definite answers. Nor do we know the extent of the endemic areas in the world for this disease. Skin testing, so useful in defining the distribution of histoplasmosis and coccidioidomycosis, has been of no value in mapping endemic areas for blastomycosis. Even the serologic evaluation of known cases of the disease has been too erratic in results to be useful as a diagnostic or prognostic procedure. The enigmas of blastomycosis go straight to the disease itself. There is an extensive literature on the debate concerning the presence and extent of subclinical infections. Case report series demonstrate that such transient infections do occur but, unlike other mycoses, the extent to which this phe nomenon is common in the general population still cannot be assessed. Even the diagnosis of established disease is a major clinical problem.

Fluorescence is a very powerful tool for work at the frontier of cell biology, photobiology and bioinstrumentation. The stated aim of the workshop was to highlight the significance of fluorescence work for the understanding of cell and tissue physiology, physiopathology and pharmacology, particulary in terms of the analytical use of fluorescent probes in oncology. In the organization of the workshop a multidisciplinary approach was selected. The purpose of the Advanced Research Workshop (ARW) was to bring together researchers in the various disciplines of tissue optics, imaging, microspectrofluorometry and state of the art probes, in order to explore the full benefits that can be derived in biomedicine through the convergence of these approaches. When applied to in vivo and in situ studies, fluorescence and related optical methods enable us to explore within tissues, cells and organelles photon effects previously understood only in solution photochemistry. Processes which can be studied at the molecular level by photophysics, photochemistry and physical chemistry can be evaluated in living tissue by fluorescence spectroscopy and imaging at the intracellular level in terms of structure and function. Thus, fluorescence adds a new dimension to cell biology and physiology. This approach is now supported by a full and versatile, rapidly growing armamentarium of new selective probes for organelles, enzymes, cations, cytoskeleton and metabolic control.

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

It is necessary to realize that the term "photosynthetic prokaryotes" encom- passes the widest and most diverse grouping of bacteria, but in itself has no taxonomic or phylogenetic significance. It means those organisms, other than eukaryotes, which require, obligately or facultatively, light for growth. The re cent application 16S rRNA sequencing to microbial phylogeny, asso- ciated mainly with the work of Woese, emphasizes the evolutionarily dis- persed nature of purpIe and green photosynthetic bacteria as weIl as the rather coherent phylogenetic connections of the cyanobacteria. It is not surprising, therefore, that a volume such as this which seeks to give an introduction to this collection of organisms must be highly selective; ac- cordingly, several important features are discussed only superficiaIly, e. g. , differentiation, life cycles, and biochemical aspects of nutrition. Rather, we have attempted to provide adescription of the essential features which are common and those which are characteristic, e. g. , the physiology of photo- synthesis and ecological distribution. Bearing in mind the aim of the series, we have asked our authors to emphasize aspects of the importance of these organisms in nature and their industrial applications. As will be seen from the text, these organisms have an ancient history in "biotechnology," having been used as foodstuffs by several cultures, but their exploitation has been limited to their natural patterns and products of growth.

This concise yet comprehensive text surveys the field of bacterial metabolism in terms useful to students and researchers. Emphasis is on those metabolic reactions occurring only in bacteria. Thus, the book describes in detail the energy metabolism of the various groups of bacteria. In addition it examines pathways used by bacteria for the degradation of organic compounds, the synthesis of cellular consituents, the regulation of bacterial metabolism and the fixation of molecular nitrogen. The general arrangement of the first edition has been retained. However, it has been thoroughly revised and updated in recognition of the rapid progress of research in this field. Readers will also appreciate the increased emphasis on membrane-associated processes. From the review of the second edition: If there is a better textbook in its fields, I'm not aware of it, and I feel the book deserves a place on the shelf of any serious student of microbiology. -ASM News

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

This book details recent findings in the field of cave microbiology and builds on fast-paced efforts to exploit an unconventional and underexplored environment for new microorganisms which may provide an untapped source of drugs: microorganisms from caves.

Hantaviruses are found world-wide and are associated with two severe disease syndromes, hemorrhagic fever and hantavirus pulmonary syndrome. The recent studies in this volume provide a basis for understanding the high human pathogenicity of theses viruses and their continued maintenance and transmission within rodent populations.

For years, toxoplasmosis has been known as disease mostly affecting newborns. Since immunocompromised patients (AIDS) present a high risk of reactivation of chronic toxoplasmosis this parasitic disease has gained increasing interest. Besides presenting clinical and therapeutical concepts, this volume provides current knowledge about genetics and immunology of T. gondii and the interaction with its 'host'. Since in vivo and in vitro models of toxoplasmosis exist, and genetic manipulation has become possible, this protozoan parasite has recently been accepted as a model for understanding the pathogenesis and persistance of other intracellular parasites. The articles of the book compromise both reviewing current concepts and reporting on yet unpublished results of leading scientists in this field.

Dr. Hilary Koprowski is the pioneer of live polio vaccine, the first researcher to advance the diagnostic and therapeutic use of monoclonal antibodies, and the developer of the "gold standard" rabies vaccine. A world-reknowned maverick in biomedical research, Koprowski's research methods were often considered controversial and even radical. Nonetheless, he acquired key positions in many research organizations, such as the Rockefeller Foundation, Lederle Labs, and Wistar Institute, initiating landmark studies from cancer research to multiple sclerosis. One of his crowning achievements, the successful crusade for monoclonal antibodies, resulted in his founding of Centocor, a forerunner in the corporate world of biomedicine. This account of Koprowski's life history is a mixture of personal interviews, anecdotes, and legends of the art and science behind the man.

In this book, outstanding researchers from the US and Japan review recent progress in Epstein-Barr virus research. Most people carry EBV in memory B-cells in a latent stage. Many malignancies such as T/NK cell lymphoma, AIDS-associated B-cell lymphoma, gastric carcinoma and Hodgkin's disease have been causally linked to EBV. The development of molecular biology technique has allowed us to study the roles of individual EBV genes that act in the maintenance and disruption of EBV latency.

The means by which non-enveloped viruses penetrate cellular membranes during cell entry remain poorly defined. Recent findings indicate several members of this group share a common mechanism of membrane penetration in which the virus particle undergoes programmed conformational changes, leading to capsid disassembly and release of small membrane-interacting peptides. A complete understanding of host cell entry by this minimal system will help elucidate the mechanisms of non-enveloped virus membrane penetration in general

Part I The Nano-Scale Biological Systems in Nature; Molecular bio-motors in living cells - by T. Nishizaka; The form designed by viral genome - by K. Onodera; Part II Detection and Characterization Technology; Atomic force microscopy applied to nano-mechanics of the cell - by A. Ikai; Design, synthesis and biological application of fluorescent sensor molecules for cellular imaging - by K. Kikuchi; Dynamic visualization of cellular signaling - by Q. Ni and J. Zhang; Part III Fabrication Technology; Surface acoustic wave atomizer and electrostatic deposition - by Y. Yamagata; Electrospray deposition of biomolecules by V.N. Morozov; Part IV Processing Technology; Droplet handling - by T.Torii; Integrated microfluidic systems - by S. Kaneda and T. Fujii; Part V Applications; A novel non-viral gene delivery system: Multifunctional envelope-type nano device - by H. Hatakeyama, H. Akita, K. Kogure, and H. Harashima; Biosensors - by M. Saito, H.M. Hiep, N. Nagatani, and E.Tamiya; Micro bioreactors - by Sato and T. Kitamori

The National Institute of Dental Research sponsored a workshop on "Genetically Engineered Vaccines: Prospects for Oral Disease Prevention," held at the National Institutes of Health (NIH) on November 6-8, 1991. The purpose of the workshop was to convene molecular biologists and immunologists to address the state of the science in vaccine development and to explore the potential of developing vaccines for prevention of oral diseases. The goal was to elicit new research initiatives and recommendations for vaccine development with emphasis on the prevention of oral diseases and diseases affecting the orofacial tissues. The workshop was attended by more than 100 persons who heard 30 presentations, and the speakers provided the papers for this volume. The workshop focused on the following topics: oral diseases and host immune responses, update on vaccines and vaccine development, vaccines and the mucosal immune system, optimizing mucosal and systemic immune responses, delivery systems and immune analysis, target antigen selection and vaccine development, immunological correlates of protection and future direc tions/recommendations. Three key areas were identified: Optimizing the Mucosal Immune Response, Antigen Delivery Systems, and Target Antigens and Immunological Correlates of Protection. The summary and recommendations from these deliberations is included at the end of this volume."

In the last few decades there has been an ever-increasing component in most BSc Zoology degree courses of cell biology, physiology and genetics, for spectacular developments have taken place in these fields. Some aspects of biotechnology are now also being included. In order to accommodate the new material, the old zoology courses were altered and the traditional two-year basis of systematics of the animal kingdom, comparative anatomy (and physiology) and evolution, was either severely trimmed or reduced and presented in an abridged form under another title. Soon after these course alterations came the swing to modular teaching in the form of a series of shorter, separate courses, some of which were optional. The entire BSc degree course took on a different appearance and several different basic themes became possible. One major result was that in the great majority of cases taxonomy and systematics were no longer taught and biology students graduated without this basic training. We field biologists did appreciate the rising interest in ecology and environ mental studies, but at the same time lamented the shortage of taxonomic skills, so that often field work was based on incorrect identifications. For years many of us with taxonomic inclinations have been bedevilled by the problem of teaching systematics to undergraduates. At a guess, maybe only 5% of students find systematics interesting. It is, however, the very basis of all studies in biology - the correct identification of the organism concerned and its relationships to others in the community."

Chronic viral hepatitis has emerged as one of the most common causes of disease and death worldwide. Because of their unique modes of replication and intimate association with the host immune system, hepatitis B virus (HBV) and hepatitis C virus (HCV) pose challenging problems to scientists in basic and applied research as well as to clinicians engaged in disease management. Although approved antiviral therapy is available for chronic HBV, the emergence of viral resistance provides a rationale for the development of novel chemotherapeutic agents. The lack of a robust cell culture system for HCV replication and a readily accessible small-animal model of HCV infection have hampered the development of antiviral agents for HCV. Neverthe-less, new antiviral agents targeting HCV are now in preclinical and clinical development.

This monograph, providing an up-to-date overview of the field of Hepatitis Prevention and Treatment, includes contributions from internationally recognized experts in the field of viral hepatitis, and covers the current state of knowledge and practice regarding the molecular biology, immunology, biochemistry, pharmacology and clinical aspects of chronic HBV and HCV infection. The volume includes salient topics such as: the history and epidemiology of HBV and HCV; recent insights into the molecular mechanisms of viral replication; the host immune response to infection and a discussion of the use (HBV) or potential development (HCV) of vaccines; the current standard of care for chronically-infected patients; and emerging therapies and issues associated with current antiviral treatments. The latest information to researchers and clinicians actively engaged in viral hepatitis research is provided, but also sufficient background and discussion of the literature to benefit the newcomer to the field.

-Integration of Systems Biology with Bioprocess Engineering: L-Threonine Production by Systems Metabolic Engineering of Escherichia Coli, By Sang Yup Lee and Jin Hwan Park; -Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum, By Christoph Wittmann; -Systems Biology of Industrial Microorganisms, Marta Papini, Margarita Salazar, and Jens Nielsen; -De Novo Metabolic Engineering and the Promise of Synthetic DNA, By Daniel Klein-Marcuschamer, Vikramaditya G. Yadav, Adel Ghaderi, and Gregory N. Stephanopoulos; -Systems Biology of Recombinant Protein Production in Bacillus megaterium, Rebekka Biedendieck, Boyke Bunk, Tobias Furich, Ezequiel Franco-Lara, Martina Jahn, and Dieter Jahn; -Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering; By Jurgen Seibel, Hans-Joachim Joerdening, and Klaus Buchholz; -Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds; By Andrea Weckbecker, Harald Groeger, and Werner Hummel;

The complement system is a group of proteins which plays a major role in the processing and removal of microorganisms and tissue breakdown products from the circulation and extracellular spaces. The system is activated by a wide range of targets, and activation leads to the production of opsonins, chemotaxis of granulocytes, cell lysis and other biological activities. Inappropriate overactivation of the system contributes to inflammatory tissue damage in the host, while inadequate activation leads to accumulation of immune complexes and other debris in the circulation, and susceptibility to infection. The biology and biochemistry of the system is now adequately understood, and attempts can be made to manipulate the activation and activities of the system for potential therapeutic purposes. The reviews in this volume summarise what is known of the ways in which the complement system can be activated, by interaction with antibodies, microorganisms, cell debris, and complex carbohydrates and how the activities and activation of the system have been modified, accidentally or by design, in vitro or in vivo by drugs, venoms, particulate carbohydrates, specific antibodies, synthetic peptides and other reagents.

IS CROHN'S DISEASE A MYCOBACTERIAL DISEASE'! The fact that the differential diagnosis of inflammatory bowel disease includes intestinal infections has been a source of much interest and clinical concern for many years. Since the recognition of ulcerative colitis and Crohn's disease as clinical entities, numerous attempts have been made to identify a specific organism resulting in the clinical and pathologic picture of Inflammatory Bowel Disease. The first suggestion about a connection between Johne's disease, a chronic mycobacterial enteritis in cattle, and Crohn' s disease occurred in 1913, when Dalziel described enteritis in humans which, although resembling intestinal tuberculosis, he believed to be a new disorder. Since the work of Crohn in the thirties a few investigators attempted to look for mycobacteria in Crohn's disease. Until now the work of Van Patter, Burnham and others did not receive widespread recognition. In 1984 the isolation of M. paratuberculosis was reported by Chiodini et al. This report initiated the current interest and controversy about a mycobacterial etiology in Crohn's disease. The hypothesis "Crohn's disease is Johne's disease" did not receive widespread recognition, but has lead to the first muIticentered efforts to determine whether or not mycobacteria are associated with Crohn's disease.

The explosion of new information on Helicobacter pylori-related disease, both in the basic sciences and in clinical medicine, has continued to progress at an unprecedented pace. In many instances H. pylori infection, both in man and in the laboratory animal, has become a model to investigate fundamental biological issues such as micro-organism host interactions, intracellular signaling, development of mucosal atrophy, mechanism of microbial resistance, disease modifying factors etc. In view of this bewildering flood of new information, another meeting on H. pylori in the successful series Basic mechanisms to clinical cure' was organized in January 1998 in San Diego, California, to define the state-of-affairs' in H. pylori research at this time. The main objective was to integrate this new information in a series of top-quality presentations and discussions between investigators and clinicians addressing all aspects of H. pylori research and to review the current position and future research directions. The format included state-of-the-art presentations by world experts heavily involved in H. pylori research followed by in-depth discussion on intriguing or controversial issues. The presentations were grouped according to the leading theme: characteristics of the organism, mode of transmission, mechanisms of H. pylori-induced inflammation, causation of disturbances of gastric secretory and motor function, aspects of clinical presentation and management, problems related to H. pylori-associated gastric adenocarcinoma and MALT-lymphoma, novel aspects of antimicrobial therapy and vaccination. The meeting concluded with a synoptic agenda of suggested future studies for the microbiologist, the histopathologist and the clinician. The chapters published in these proceedings accurately reflect the content of the superb presentations. The reader will readily appreciate the excellent level of the cutting-edge' research which was described and discussed. These proceedings are another testimony to the enormous impact on basic science and clinical medicine of the H. pylori discovery. Although much was achieved, it is also readily apparent that many questions remain to be answered and many problems remain to be solved.