The international symposium "New Trends in Allergy," held in Munich from July 13 to 15, 1990, brought together for the third time since 1980 some of the most experienced researchers working in the field of allergy. This volume comprises the papers presented at this meeting. All over the world, and not merely in the industrialized countries, allergy is becoming a cause of evermore serious diseases. In recent years, research in the field of allergy has provided numerous impor tant and fascinating results extending our knowledge considerably. Despite the new insights into basic mechanisms of allergic reactions, improved diagnostic methods, and new therapeutic approaches, how ever, many questions remain to be answered, including: Are allergies really increasing in frequency? If so, what are the reasons? Especially, does environmental pollution playa role? Which factors influence IgE synthesis? Can the IgE immune response be switched off? Does the nervous system interact with allergic reactions? If so, what are the mechanisms? Are new approaches in allergy prophylaxis and allergy therapy effi cient? What measures have proven useful and deserve to be employed in daily practice? In this volume, these questions and other current topics are dealt with. As each issue is covered by authors competent in the respective fields, the result is an extensive and critical review of the state of the art. Going through these papers, one comes to the conviction that allergy research is a multifacetted, explosively expanding, most stimulating field of work."

Alzheimer's disease is one of the major scientific, medical and social challenges of our time. This book, the first in the new series "Research and Perspectives in Alzheimer's " "Disease," presents a particularly up-to-date approach of immunological and biochemical aspects. It is written by the most outstanding scientists and contains recent data. The following are among the most interesting ideas contained in this book: - Alzheimer's disease is a cerebral form of amyloidosis. - some data are in accordance with an immunological hypothesis of this disease. - degeneration of microvessels - including amyloid angiopathy - could be very important in the changes in the brain with Alzheimer's disease. - the molecular study of A4 protein and its precursor is important for the understanding of the disease. This synthesis by prominent scientists provides a stimulating hypothesis about the determinism of the disease.

All but one* of the following articles represent comprehensive reports on a workshop held between 7 and 9 May 1981 at the Institute of Virology and Immunobiology, University of Wfuzburg, Federal Republic of Germany. The title of the workshop was "The Involvement of Endogenous Retroviruses inN ormalFunction and Pathological Growth of Lymphocytes." Rather than collecting and printing manuscripts of the individual communications, the organizers asked selected parti cipants to write, after the workshop, concise articles each compris ing several contributions and discussions on major topics. In so doing, we hope to present to a larger audience a synopsis of the various information and views exchanged at the meeting. Such a procedure seemed the more appropriate as the workshop was intended to bring together specialists from two rather diverse fields: RNA-tumor virology and immunobiology. While this created some initial problems of terminology, it was quite effective in making representatives of one field more aware of the significance and the contributions ofthe other. It also great ly contributed to realization of the complexity of the problems involved in virus-induced leukemogenesis."

The development of new techniques such as immuno phenotyping, cytogenetic investigations and, more recently, molecular studies has considerably increased our diagnostic repertoire and broadened our ideas about the biology of acute leukemias. While immunophenotyping with mono clonal antibodies has yielded increased diagnostic precision and made it possible to develop a highly reproducible classification of acute leukemias based on cell-biological features, further insights have been gained into the patho genetic mechanisms involved in leukemogenesis by means of cytogenetic detection of acquired structural chromosomal abnormalities. Analysis of the leukemia-associated chromo somal breakpoints using molecular techniques can now pinpoint many genomic sites essential for normal develop ment and maturation of hematopoietic cells but functionally disrupted in leukemic cells. The main goal of the international workshop that we held in Berlin with a select group of scientists and clinicians involved in leukemia research was to describe the state of the art and new developments in the immunologic, cytogenetic, and molecular characterization of acute leukemias and to discuss the clinical importance of cell biological features. After introductory survey lectures dealing with the immunological and molecular-biological characteristics of normal vs. malignant lymphatic and myeloid progenitor cells, the workshop centered on con tributions characterizing the immunophenotype and both numerical and structural chromosomal abnormalities in acute leukemias."

The eighth workshop in this series on Mechanisms in B-Cell Neoplasia 1990 was held in Wilson Hall at the National Institutes of Health, Bethesda, Maryland on March 28-30. Five major topics formed the basis for the discussions: 1) progress in experimental models of B-cell tumorigenesis, 2) the role of IL-6 in plasma cell tumor formation with particular emphasis on human myeloma, 3) immortaliza tion and regulation of mitosis in B-cells, 4) the mYQ gene in B-cell neoplasia, and 5) the role of EBV and other oncogenes in transforma tion of human B-Iymphocytes. A meeting on the Epidemiology of Myeloma was held at the N. I. H. on the preceding day, and many of those interested in the clinical aspects of myeloma were also participants at the workshop. Experimental Models of B-Cell Tumor Development We have seen in the last eight years the steady growth of model experimental systems, many of which have been designed to be counter parts of the major forms of human B cell tumors, e. g., follicular lymphomas, Burkitt's lymphomas, acute B-cell leukemia and multiple myeloma. A variety of novel ways of inducing these tumors has been described. Advantage has been taken of the "experiments in nature" to identify critical genes that playa role in tumor pathogenesis. These genes have been identified by being near to viral insertion and chromosomal translocation sites, or by having been incorporated or transduced into a defective transforming retrovirus."

After the discovery of the function of MHC molecules, namely to provide the context for T cell recognition of foreign antigens, in 1974 Zinkernagel and Doherty made the first drawing of MHC+X (Fig. 1 from Zinkernagel and Doherty, Nature, 251: 547, 1974). Over the next 18 years a very large number of similar drawings ensued, some of real artistic beauty. One side of the problem, the nature of the T cell receptor, was unraveled; however, we still do not know exactly what kind of a structure the T cell receptor recognizes, al though in 1987 we learned so much about the structure of MHC molecules and antigen presentation. In schematic presentations no one is now placing the foreign antigen beside the MHC molecule, but rather on top of it, as pointed out by J. L. Strominger at the MHC + X meeting in Paris. The complex of MHC and antigen is named MHC + X, but the precise meaning of this formula remains a "problem perplex," as illustrated in these proceedings by Peter Par ham. When planning the Ommen/Amsterdam meeting at the begin ning of 1987, its major aim was seen as to discuss the question of whether MHC + X can induce antibodies and, consequently, their specificity. In other terms, whether - in analogy to antigen specific MHC restricted T cells - MHC restricted antibodies also exist."

In the field of Hodgkin's lymphoma, many new data have been collected during the last decade both on the cell of origin of this disease and on more effective therapies to cure the majority of pa tients even in the advanced stages. Therefore, it seems to be justi fied to compile these new data in a special volume of Recent Re sults in Cancer Research. This volume summarizes the contribu tions presented at the First International Symposium on Hodgkin's Disease that took place in Cologne (FRG) on October 2-3, 1988. There is little doubt that the Hodgkin and Reed-Sternberg (H and RS) cells and their variants represent the malignant population in Hodgkin's lymphoma; however, there is still a fierce debate as to the possible cell of origin of Hand RS cells. Many of the problems confounding earlier research into this question were related to the difficulty or virtual impossibility, of obtaining purified populations of Hand RS cells. Most of the recent progress stems from the establishment of permanent cell lines of Hand RS cells in culture.

Urticaria is one of the most common dermatological and allergological cutaneous reactions and, compared to other diseases, it is easily recognized by patients and physicians alike. Nevertheless, the disease is highly complex regarding its eliciting causes, its clinical manifestations and its therapy. Thus, a famous New York dermatologist once mentioned that he would rather have a lion than a patient with chronic urticaria walk into his office. This may seem surprising since, to the uninitiated, different types of urticaria look alike, and the pathomechanisms are rather well understood, with mast cells being almost invariably the main effector cells. In 1986, a monograph of the first editor (Prof. Czarnetzki, now with the married name Henz) appeared, giving a detailed and thorough review of the then current state of knowledge regarding all aspects of the disease. Since then, two updates of this book have appeared in the German language, with coworkers of the clinic of Prof. Henz helping in the revision of the various chapters of the old monograph, and with particular emphasis on practical aspects of the disease. The present book is mainly a translation of the second German edition, with only minor updates and with more citations from the literature since the 1986 monograph is no longer available for purchase.

In June 1986 a symposium was held in Giessen on Modern Trends in Virology. It was initiated by the Deutsche Forschungsgemeinschaft, which had supported virus research for the past 18 years in the Sonderforschungsbereich 47 at the University of Giessen. The purpose of the meeting was to serve as a forum for the members of the Sonderforschungsbereich to discuss scientific topics of mutual interest with about 200 virologists that had come from various parts of Europe, the United States, and Japan. It was not by chance that the symposium took place shortly after the 60th birthday of Rudolf Rott, who had founded the Sonderforschungsbereich in 1968 and has been its speaker ever since. Without his vision and his never resting energy Giessen would not have gained the position in the field of virology that it has today. This Festschrift, which contains the contributions presented at the plenary sessions of the symposium, is therefore dedicated to Rudolf Rott. HEINZ BAuER HANS-DIETER KLENK CHRISTOPH SCHOLTISSEK Table of Contents A Genetic Approach to Determining Glycoprotein Topology: The Influenza B Virus NB Glycoprotein has an Extracellular NHz-Terminal Domain Containing two N-linked Carbohydrate Chains R. A. LAMB and M. A. WILLIAMS . . . . . . . . . . . . . . . . . . . . . . . . . 1 Paramyxovirus Metabolisms Associated with the Cytoskeletal Framework Y. NAGAI, T. ToYODA, and M. HAMAGUCHI . . . . . . . . . . . . . . . . . . . 15 Correlation of High Evolutionary Rate of Influenza A Viruses in Man with High Mutation Rate Measured in Tissue Culture: A Hypothesis P. PALESE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Natural resistance is now coming to be recognized as a potentially important phenomenon in host defense against infection and ma lignancy. Genetically controlled resistance mechanisms are usUally effective early in infection and before conventional immune responses are generated. Comparisons of experimental systems where natural resistance plays a prominent role demon strate the complexities of the host defense mechanisms involved, as evidenced in the present volume. Nevertheless, some com mon components of genetic resistance are discernible and largely comprise natural killer cells, macrophages, and interferon These and additional factors would seem to constitute a first line of de fense in host resistance against both viruses and tumors. It is evi dent that considerable variation in the relative importance of di stinct mechanisms may be found among various resistance sy stems and that, most likely, additional effector functions will be discovered. Resistance to tumors and most viruses is under polygenic control, has a complex mode of inheritance, and depends on appro priately complex effector mechanisms. Instances, however, whe re a single gene locus determines resistance or susceptibility to a virus, as in the case of resistance to flaviviruses or influenza viru ses, would seem to offer good prospects for elucidating the basic factors involved. Resistance to influenza virus would indeed seem to represent a comparatively simple situation: resistance is expressed at the host cell level, and interferon is its main media tor. The present volume provides insight into current concepts of such resistance mechanisms."

The breadth of research efforts represented by the many excellent papers in these proceedings is an eloquent testimonial to the idea of one man Dr. Josiah Brown-to whose memory this volume is dedicated. His tragic and unexpected loss in a swimming accident in August 1985 brought to an abrupt close a long and distinguished career as a physician and scientist. The possibility of using fetal pancreas tissue for transplantation into insulin-deficient diabetic recipients had intrigued Dr. Brown for several years prior to 1972, when he began in earnest to assemble a research team to explore this idea in detail. He felt that improvements in the formulation and administration of insulin (even the later recombinant human insulin) had taken us about as far as we could go in treating diabetes, and that methods for achieving complete cures must be explored. Numerous advantages of the fetal pancreas quickly became apparent, and were explored scientifically by Dr. Brown and his group. Transplanted pancreas tissue from a fetal donor of the appropriate developmental stage engrafts quickly, and can reverse diabetes very efficiently (1-3). By shunting the venous'drainage of the graft into the hepatic portal vein, a single pancreatic rudiment can, in time, provide enough insulin to restore normoglycemia and urine volume in a diabetic adult recipient (4). As with fetal pancreas rudiments in culture, transplanted fetal pancreas tissue loses its exocrine character, while continuing to develop and maintain endocrine function.

The period that followed World War II has witnessed a dramatic change in neurology. From being a discipline in which its partici- pants were castigated for being interested solely in diagnosis, usually of disorders of unknown causation without effective therapy, neurology has evolved into a highly active treatment- orientated subject. This transition is clearly reflected in the ap- proach to diseases of the peripheral nervous system, and to the Guillain-Barre syndrome (GBS) in particular. In a state-of-the- art review made in 1952, Elkington (1952) observed that no less than 56% of neuropathies remained undiagnosed, and amongst those of unknown causation he listed GBS. With intensive in- vestigation and follow-up, the proportion of neuropathies seen at tertiary referral centres which elude diagnosis is now as little as 13% (McLeod et al. 1984). Overall, of course, the proportion is even less. This change is partly because of the introduction of new diagnostic techniques and partly because of the application of the great expansion in knowledge evident throughout medicine. In this book, Professor Richard Hughes has assembled current information on GBS and related disorders, including chronic in- flammatory demyelinating polyneuropathy (CIDP), the existence of which was not appreciated until Austin's perspicacious study published in 1958. In the Introduction, Professor Hughes gives an account of the way in which recognition of the GBS emerged and matured, and shows that it followed, pari passu, with the realisation that paral- ysis and sensory loss may result from peripheral nerve disorders.

During the past 50 years, systemic lupus erythematosus (SLE) has been the main subject in the field of immunopathology. Each individual discovery was followed by the discovery of a multitude of related immune phenomena. This book reflects the present status of our understanding of this protean disease. Various animal models clearly show that different gene combinations can lead to the final clinical expression of SLE, with HLA class II genes probably responsible for the targeting of the autoimmune response. Similarly, research on cytokines in SLE patients has shown that SLE is a syndrome depending on different pathways. Finally, the question of prognosis is discussed. Fortunately, with every passing decade, the prognosis for patients with SLE gets better and better.

Autoimmune diseases are common and often associated with considerable morbidity or - in diseases such as IDDM, myasthenia gravis and multiple sclerosis - mortality. In this volume, experts of international stature in basic science and clinical medicine with a common interest in understanding the normal and aberrant immune response present their experiences. It was their intention to fur- ther the understanding of potential clinical application of scientific observations and to help to comprehend the huge amount of results in autoimmunity research.

Although immunologists know rather a lot about the manif estation of immunological memory, an understanding of the mechanism of memory at cellular and biochemical levels eludes us. Indeed, as we shall see, it is not even clear which of the several models used to explain the working of memory approximates to the truth. It is in order to report on approaches to this problem and on recent experimental advances in the field of memory cells that this volume has been put together. In the past 4-5 years cell surface molecules that may enable us to define memory Band T cells have been identified. It may now be possible to ask how memory cells are generated and to define what signals are required during or after antigenic encounter for a cell to enter the memory cell pool rather than to terminally differentiate into an effector cell. The transition from virgin cell to memory cell is clearly accompanied by several biochemical changes. For B cells, isotype switching and somatic mutations (leading to affinity maturation) are well-defined phenomena, although the molecular mechanisms remain mys terious. Both have received attention in many excellent reviews of late and so are not considered in detail in this book. Neither switching nor somatic mutation is a feature of peripheral T-cell maturation; biochemical differences between virgin and mem ory T cells may only relate to differing activation requirements and possibly changes in the expression of accessory molecules.

The twentieth century will close with 5 billion people added to the current global population. Between 1980 and the year 2000, the total world population will increase from 4 billion 10 a liUle over 6 billion. There will be half as many morc people on earth during these 20 years than the number accumulated since the origin of man to 1980. Overpopulation is particularly acute in economically developing countries, where contraception has become a social necessity. Comraceplion Researcll for Today and Ihe Nineties carries the proceedings of an international symposium convened in New Delhi in October, 1986, to review the status of current research in contraception. Major organizations supporting basic and applied research in contraception-The Population Council, World Health Organization (WHO), The Rockefeller Foundation, United States Agency for International Development (USAID), International Development Research Center of Canada (IDRC), National Institutes of Health (NIH), and the Indian Council of Medical Research (ICMR)- were represented by the heads of divi sions who projected respective programs and strategies. Principal scientists responsible for many of the new leads participated."

The purpose of this volume is to highlight some current areas of poxvirus research which are likely to be particularly fruitful in the upcoming few years. The first chapter, by Drs. Condit and Niles, discusses poxvirus genetics. Work in this area has provided mutants, produced practical procedures to simplify the manipulation of viral genes, and generated information about the molecular architecture and organization of genes characteristic of pox viruses. One of the most intensively studied regions of the viral genome is the HindIII D region of vaccinia, in which a combination of classical and molecular genetic analysis of the region has been particularly revealing. Within this region are open reading frames, some of which are expressed early and others late, organized in a fashion which is now known to be typical of these viruses. Other studies, related to temperature sensitive, drug resistant, and drug dependent mutants, are also discussed. Each of the other reviews included in this volume summarizes areas of research which have depended heavily on the genetics of the system. The intracellular site of a poxvirus infection is mostly, if not exclusively, limited to the cytoplasm which dictates several interesting biological ramifications. For example, poxvirus transcription must occur in the cytoplasm, rather than in the nucleus. The virus copes with this situation by incorporating into the virion the enzymatic machinery necessary to initiate transcription from input virus.

Several discoveries are noteworthy for allowing us to probe the recesses of the virus infected cell and to search for cryptic viral genomes which might provide clues in our studies of cancer etiology or developmental biology. One of the most notable was the dis covery of reverse transcriptase. This marked a momentous occasion in the history of molecular biology. Not only did it provide insight into the mechanism of persistence of retroviruses but it also provided us with an enzyme that could synthesize a DNA copy of any RNA. This DNA copy could then be used as a hybridization reagent to search for both complementary DNA and viral-specific RNA. Thus one could follow the course of any viral infection or probe in tumor cells for hidden viral genomes. Second, a great deal of credit must be given to the geneticists who isolated the various deletion mutants in the 'avian retrovirus system and thus provided us with the frrst means of isolating gene-spe cific probes. Finally, the laboratories which have mapped the genome have provided us with the framework in which to ask very specific questions with our gene-specific probes. Recently, numerous excellent reviews concerning various aspects of the retroviruses have appeared. In this review I shall not even attempt to present a comprehensive review of retroviruses."

Main topics covered: B-Cell Development; Immunoglobulin Gene Rearrangement; Multiple Myeloma, Plasmactomas; Lymphomas: B-CLL, Folli- cular Lymphomas BCL-2, BCL-1; Lymphomas: EBV, AIDS Associa- ted Lymphomas; Oncogenes and Transcriptional Factors (text to follow)

This second volume reports on the reaction patterns of lymph nodes in neoplastic and immunodeficient diseases. Based on the contents of volume 1, it presents a detailed survey of lymph node structures and their cellular components under these conditions. The patterns of nodal reactions to the development and spread of cancer have recently been investigated and discussed by several authors. Here, the immediate interactions between tumor tissue and the regional nodes have been assessed in experimental models and in human material. Using modern morphological methods such as im munohistochemistry on the light and electron microscopic level, new insights have been gained into the stepwise process of lymphogenous metastasis. Macrophages/reticulum cells were found to playa signifi cant role in this process, which is duly emphasized. Based on appro priate animal models, one chapter focuses on various subtypes of these cellular elements and their role in the two separate phases of tumor spread and the development of true metastases. The induction of fibronectin in lymph nodes is effected by tumor cells forming a special part of the extracellular matrix. The multifunctional fibronec tin molecule serves as a mediator between tumor cells and fibroblasts, furthering the formation of tumor stroma. This volume also contains a comprehensive survey of primary im munodeficiency syndromes and their nodal manifestations, reference being made to the most recent immunological knowledge."

At this writing the decade of the 1980s is rapidly coming to a close, and it is an appropriate time to review the picornavirus field. During the past decade there has been a remarkable reemergence of interest in picornaviruses and a virtual explo- sion of experimentation. The renaissance of picorna viruses can be attributed to several developments near the beginning of the 1980s. In 1981 the nucleotide sequence of the first picornavirus genome, that of poliovirus, was determined, providing a genetic map that would be the basis for a number of experimental questions regarding gene function and expression (Kitamura et ai. , Nature 291: 547; Racaniello and Baltimore, Proc Natl Acad Sci USA 78: 4887). In the same year it was reported that a cloned eDNA copy of the poliovirus genome is infectious when transfected into cultured mammalian cells (Racaniello and Baltimore, Science 214: 916, 1981). This discovery, which enables construction of poliovirus mutants and recombinants, has since been used for the study of many picornaviruses. Furthermore, the availability of cloned copies of viral genomes permits manipulation of gene products apart from infected cells. Third, the use of hybridoma technology to generate anti- picornavirus neutralizing monoclonal antibodies permitted mapping of antigenic sites (for example, Evans et ai. , Nature 304: 459, 1983). Finally, at mid-decade the three-dimensional structures of poliovirus (Hogle et ai. , Science 229: 1358, 1985) and rhinovirus (Rossmann et ai. , Nature 317: 145, 1985) were solved.

Research in diabetes has accelerated in two areas, both of which are being reviewed in CTMI. The first is the use of a variety of animal models; the second is basic research in human investigation, islet cell antigens, and mapping of genes as sociated with susceptibility to disease. Dr. Thomas Dyrberg accepted editorial responsibility for this volume, which covers the first area. A second book, to be published later in the year, is edited by Drs. Brekkeskov and Hansen (CTMI 164, see page VI for contents). Although the contributors to both volumes represent the international scientific community, the editors are from the Hagedorn Research Laboratory in Denmark. Work at this institute and the Steno Memorial Hospital has been dedicated to research in diabetes for decades, and the insti tutions were appointed WHO Collaborating Centres for Re search and Training on the Pathogenesis of Diabetes Mellitus in 1983. It is worth noting that while addressing the hypothesis of the role of class II major histocompatibility glycoproteins in autoimmune diabetes (insulin-dependent diabetes, IDDM) a number of investigators established animal models in which class II molecules were expressed under the control of the rat insulin promoter. While generating interesting information on 100M, the finding of immunologic tolerance in such transgenic mice has attracted the attention of several basic immunologic laboratories for quite different reasons. Thus, we are reminded again of the Pasteur dictum that "chance favors the prepared mind. " Michael B. A. Oldstone, M. D."

Malignant melanoma is the focus of investigations which range from basic re search to clinical trials with conventional therapy and with biological response modifiers. The involvement of investigators with different backgrounds in combi nation with recent progress in biotechnology has facilitated the characterization of the antigenic profile of melanoma cells, the analysis of the structural and function al properties of melanoma-associated antigens, and the application of immuno diagnostic and immunotherapeutic approaches to melanoma. As a result, a large body of information about various aspects of melanoma has been rapidly accumu lated during the past few years. In organizing this book I aimed at providing a readily available source of infor mation on the current research in melanoma. To this end I invited investigators with active research programs to contribute chapters describing and discussing the significance of their most recent results. To facilitate the preparation of the manu scripts and to avoid duplicating other recently published books on melanoma, I discouraged the contributors from providing extensive reviews of the literature on the various topics. Although I made every effort to be as complete as possible in the selection of the contributors, while writing this preface I realized that I had overlooked at least three investigators whose work should have been included.

The Second International Symposium on Narcolepsy was held at Fairchild Auditorium, Stanford University, on 6-7 July 1985 under the presidency of Drs. William C. Dement and Christian Guillemi nault. It succeeded the First International Symposium on Narco lepsy held in La Grande Motte, France, organized by Pierre Pas souant in July 1975 in commemoration of the 100th anniversary of the publication of Jean B. E. Gelineau's paper which proposed the naming of narcolepsy. At the second narcolepsy symposium, many important research reports on both basic and clinical aspects of narcolepsy were given by investigators from many countries of the world. Audience inter est was particularly attracted by the section on the relationship be tween HLA and narcolepsy, in which recent evidence that almost all narcoleptic patients are HLA-DR2 positive was reported by in vestigators from Japan, England, France, Canada, and the United States. The close relationship between the HLA antigens, hitherto considered as immune-related genetic markers encoded by genes on human chromosome 6, and narcolepsy appeared to open a new approach not only for the research of narcolepsy but also for the mechanism of sleep in general. Publication of all these new findings on the association of HLA and narcolepsy was considered; an outline was worked out and all the groups agreed to prepare a contribution covering the various aspects of this topic."