The development of innovative molecular techniques such as pulse-field gel electro phoresis, cDNA subtraction libraries and chromosome hopping libraries coupled with the increasing popularity in the prospect of sequencing mammalian genomes, has triggered a resurgence of interest in finding and characterizing genes that playa role in modifying immune processes and diseases. Genetically defined strains of mice (e. g., inbred strains and recently derived stocks of wild mice) provide ideal models for examining the genetic control of diseases as a result of their syntenic relationship with man in genetic composition as well as linkage conserva tion. Due to the relative ease of producing a specific genotype via appropriate breeding schedules, murine models may provide the only hope for unravelling those complex disease processes under mUltigenic control. This issue of CTMI is a collection of papers on the characterization and mapping of genes involved in mutations and dysregulated immune responses which produce disease phenotypes. These papers were presented at a workshop which was devoted to examining reverse genetic approaches at localizing, cloning and characterizing genes involved in a variety of developmental, autoimmune, neoplastic and infectious disease processes. In the first of three sections, a series of papers outline the most currently used methods of mapping and isolating genes whose products are unknown. The papers, following, are devoted to specific gene systems whose dysregulation is likely to produce mutant or disease phenotypes."

I have been a student of Sjogren's syndrome for virtually all of my professional life. My education in this disease began in 1962 when I arrived at the National Institutes of Health to begin a Clinical Asso- ciateship with Dr. Joseph J. Bunim. Bunim introduced me to a pat- ient with Sjogren's syndrome of 8 years duration who had devel- oped malignant lymphoma 6 months previously. He told me that there were other such patients. I obtained serum samples from these patients and studied them by the then new technique of immuno- electrophoresis. We observed that an initial hypergammaglobulin- emia could progressively decline to hypogammaglobulinemia with loss of autoantibodies. One patient in this initial series had macrog- lobulinemia. We published this report and suggested that the auto- immunity predisposed to the malignant transformation. Thus began my love affair with this disease. In those days many rheumatologists considered Sjogren's syn- drome simply a variant of rheumatoid arthritis. It's curious that two decades ago there was little confusion between Sjogren's syndrome and systemic lupus erythematosus, whereas today there is great con- fusion. There is still a great need for internationally agreed upon di- agnostic criteria, which merely illustrates once again the difficulty of accurate diagnosis in our profession. The multidisciplinary aspects of Sjogren's syndrome require au- thorities in several areas of medicine. The various chapter contribu- tors are experts in their field and have often put aside other respon- sibilities to complete their contributions and not delay publication.

This volume of Current Topics in Microbiology and Immunology is concerned with a class of molecules that are the most potent polyclonal stimulators of T lymphocytes of several species. These molecules have been named "superantigens" because they use a mechanism of T cell stimulation closely mimicking MHC-restricted recognition of specific antigen: they act on variable parts of T cell antigen receptors and are presented by MHC class II molecules. Prototypes of these molecules are the pyrogenic exotoxins produced by S. aureus and S. pyogenes, of which the staphylococcal enterotoxins and the toxic shock syndrome toxin are the best known. Superantigens also occur endogen ously in mice, most notably the enigmatic Mis determinants, that have withstood characterization for nearly 20 years. Only very recently was it found that Mis is probably encoded by endogenous retroviruses. The list of candidates that are implicated as being superantigens is growing. In many cases, however, the proof that a given molecule indeed falls into this category is still missing.

It has long been known that every individual has a large number of antibodies of different specificities. Antibodies are gammaglobulins, and protein structure in cells is genetically determined. The extreme multiplicity of structure of the combining sites of antibodies relative to the degree of multiplicity generated by ordinary genetic mechanisms is a fascinating problem of bio-medical importance. The functional heterogeneity of reactions mediated by immunoglobulins-is remarkable, ranging from protection against life-threatening toxins and microbes to the production of laryngeal edema leading to suffocation and death from anaphylaxis. An approach to the understanding of immunoglobulin polymorphism based upon "a knowledge of genetic markers of immunoglobulin structure is not biased by the question of whether or not this polymorphism is related to combining site diversity. Though several recent reviews of the multifacetted problems related to immuno globulins are available, it was decided to publish this survey in the belief that know ledge of the genetic markers of immunoglobulins prqvides such information about immunoglobulin differentiation and its control as cannot be obtained from other sources. Several of the human genetic im unoglobulin markers are well understood at the molecular level. The Gm system may serv as a model for other immuno genetic systems. The published data on the human immunoglobulin factors are widely scattered in journals of different perspectives. There is a need for a systematic presentation of these data and for their critical evaluation."

Why another series on infectious disease? The question is a fair one in view of the proliferation of monographs, texts, and periodicals on the vast subject of infectious disease. The goal of this series is to provide an additional service to the clinician in the form of clinical information not usually assembled in one convenient volume. One type of monograph presented in this series will cover a specific infection, detailing microbiologic, research and clinical aspects. It is hoped that such a compilation will be helpful in both its thoroughness and breadth to the clinician interested in this particular problem. The other type of monograph that this series will provide will discuss a clinical presentation that comprises many possible specific etiologies. Volumes in the series will be multiauthored, giving us the opportunity to invite authorities in each specific area to contribute their expertise and experience. Regular revisions are planned so that each volume will remain as current as it is thorough. We hope that our goals are met and that the present series of mono graphs establishes its own identifiable and valuable niche in the growing compendium of resource material available to the clinician. Preface to the Second Edition Since the first edition of Infectious Mononucleosis was published, we have seen exciting advances in our understanding of this disease."

Readers will be aware that asthma is one of the commonest chronic diseases of industrialised societies, with an increase in morbidity and mortality, despite the availability of a range of different drugs. In an effort to improve the treatment of asthmatic patients, international guidelines have recently recognised asthma as an inflammatory disease, and there has been a change in emphasis from bronchodilator drugs towards earlier use of anti-inflammatory treatments. This volume brings together the latest developments in our understanding of the mechanisms of asthma, considers the safety ofbeta-adrenoceptor agonists, and explores latest developments in the use of phosphodiesterase (PDE) inhibitors in asthma therapy. The second international conference on "New Drugs in Allergy and Asthma" was held in Davos on 8-10 July 1992. There were six sessions with specialist chairmen: PDE isoenzymes (c. D. Nicholson), atopy and the environment (8. Villiger), adhesion molecules (R. H. Gundel), cytokines (M. Baggiolini), airway hyperreactivity (S. Makino) and neurotransmitters (J. G. Widdicombe). The success of the meeting was ensured by a high standard of presentation, with extensive reference to recent experimental data. The chairmen were instrumental in fostering stimulating discussion periods, that considerably enlivened the meeting. Particular thanks are due to the Swiss Institute for Asthma and Allergy Research (SIAF) and also to the e1inicians of Davos for their assistance and hospitality. In addition, a number of pharmaceutical companies were kind enough to support this meeting that was devoted to academic aspects of drug discovery. John Morley FRCPath.

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."

The data summarized in this chapter show that morphological transformation and oncogenesis by adenoviruses are brought about by the coordinated activity of regions E1A and E1B. Gene products of each of these subregions appear to fulfill distinct roles in oncogenic transformation, with the possible exception of the product(s) encoded by the O. 9-kb E1A mRNA. Also unclear is the func- tion of the 20-kd E1B protein, which has a small role, if any, in morphological transformation, but appears to be essential for the development of the oncogenic phenotype, as defined by the ability of transformed cells to grow in immuno- deficient nude mice. The differences in biological properties of oncogenic and nononcogenic adenoviruses must be attributed to differences in the primary structure of the respective E1A and E1B gene products, in particular of the product(s) of the 1. 0-kb E1A mRNA and of the 55-kd protein encoded by the 2. 2-kb EiB mRNA. The availability of cold-sensitive adenovirus mutants has enabled us to conclude that the transformed phenotype is maintained as a result of continuous expression of at least region E1A gene products, and is therefore not the result of a hit-and-run mechanism. Despite the progress in our understanding of adenovirus transformation and oncogenesis, virtually nothing is known about the precise mechanism by which the viral gene products bring about the neoplastic changes in cells. The only exception is the demonstration that Ad12 region E1A (1.

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."

This book is a collection of critical reviews about a diverse group of virus families with two features in common: the stable repository of genetic information in each virus is RNA, and each virus modifies and appropriates a particular patch of the eukaryotic cell membrane system to complete its structure. The reviews take the reader from the level of virus genome structure and expression through the quaternary interactions between virus-specified elements and cellular components that cooperate to produce virus particles. There are spectacular illustrations in this volume, but it is much more than a picture gallery. Reading widely in this book can be an effective antidote to overspecialization: in these pages, you are likely to learn much about viruses and about cells that you didn't know before; you'll discover illuminating parallels between diverse virus families; you'll come away with a sharpened awareness of important things that are still to be learned. Memphis, Tenn. , Summer 1984 David W. Kingsbury Preface This book was written at the suggestion of Dr. David W. Kingsbury made at a work shop on viruses organized by the Multiple Sclerosis Society in Aspen, Colorado, U. S. A. , three years ago. Originally, we had thought to focus on the morphological aspects of viral assembly. Later, during our discussions on the process of budding of enveloped RNA viruses, it became evident that we should include biochemical data in our review and correlate them with the structural aspects of virus maturation.

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.

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."

AIDS continually presents new questions for the obstetrician and gynecologist. The effect on pregnancy, the possibility of perinatal transmission, HIV positive tests, and risk to staff are just a few of the issues confronting clinicians and practitioners today. These and other questions were addressed by the 19th Study Group of the Royal College of Obstetricians and Gynaecologists, whose findings are reported here.

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.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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.

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.

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.

Postreplicative methylation of bacterial DNA has long been known to be the molecular basis of" modification," which protects DNA against destruction by restriction endonucleases. More recently, another function of DNA methylation was found in Escherichia coli, where methy- lation is involved during DNA replication in the recogni- tion of old and newly synthesized strands. The intensive search for new restriction enzymes during the 1970s yielded an enormous arsenal of such enzymes and re- vealed the ubiquitous distribution of restriction/modifi- cation systems in the bacterial kingdom without provid- ing much information on the corresponding modifica- tion methyltransferases. However, it is obvious that DNA methyltransferases represent an ideal class of en- zymes to those interested in protein/DNA interactions; these enzymes are at least as interesting as the restriction enzymes, with which they share the capacity to recognize and interact with specific sequences of DNA. In recent years the interest in DNA methylation has been greatly stimulated by two discoveries: the correla- tion between gene expression and hypomethylation in eukaryotes and the convertability of DNA into its Z form through cytosine methylation. In fact, studies on DNA methylation are now being intensively performed in many laboratories. A description of the state of the art of DNA methylation has been the topic of two con- gresses: The Cologne Spring Meeting in 1981 organized by WALTER DOERFLER and an EMBO Workshop at Nethybridge in 1982 organized by ROGER ADAMS.