Recent experimental and clinical progress in the evaluation of cytokines in treatment concepts for cancer patients is the central theme of this book in the ESO Monographs series. The discussion revolves on the experimental basis as well as current clinical experience with the use of human recombinant cytokines. It gives the state of the art and, as such, puts into perspective potential areas of growth and future research.

Radiation induces a variety of chemical processes in biological tissues. This volume is a synthesis of up-to-the-minute reviews on such photochemical and photobiological sensitized reactions with particular relevance to photomedicine. The first part gives a description of experimental techniques for the study of the primary processes after radiation absorption by biological systems. It is followed by chapters on singlet oxygen and photomedicine, considering both phototherapy and photochemotherapy. These sections also discuss the next generation of potential photosensitizing drugs.

The idea for this volume was conceived during a discussion in the hallway at a conference in early 1990. "What is the best way to detect and define pluripotent hematopoietic stem cells?" was the question posed by Dr. Fritz Melchers. After discussing the pros and cons of the available assays for quite some time, it became apparent that this topic required a wider expertise and merited a larger forum. Thus, we decided to extend the discussion and to compile the results in this volume. Much to our delight. many of the pioneers of recent experimental and theoretical developments in stem cell research agreed to contribute their expertise to answer the question. These authors review both past findings and present insights, thus providing an overview of the evolution that has been and is occurring in the field of stem cell research. In the light of recent trailblazing developments in both experimental models and in clinical application it is indeed time to reevaluate our knowledge about stem cells. Trans plantation of hematopoietic stem cells has become more and more prevalent as a curative therapy in a variety of acquired and genetic diseases, including cancer, radiation accident, as an agent for gene therapy, and perhaps even as treatment for autoimmune diseases. Stem cells are now derived not only from bone marrow but also from peripheral blood, cord blood, and fetal liver, greatly increasing their availability for human transplantation and in some cases (fetal tissues) obliterating the need to match donors and hosts."

The amazing world of the mononuclear phagocytes keeps expanding at a truly awesome pace. As a result, maintaining currency with the latest developments and controversies that pertain to this cell type is increasingly difficult. The aspects covered in this volume have been selected to provide an overview of subject areas that either have recently become much better understood or hold the promise of new levels of understanding as they are developed in the future. The scope of topics ranges from how these cells develop, through the means that are used to regulate them, to the roles that they have in different tissues and in a variety of infectious diseases.

Rapid progress continues to be made in understanding the molecular and cellular events that comprise B-Iymphocyte differentiation. This is due in part to the high level of inter est shown by many investigators from diverse disciplines, who find this subject suitable for addressing some of the fundamental issues of immunobiology. B-cell developmen tal models are being extensively used to investigate cell-cell interactions, molecular mediators of differentiation and proliferation, differential onset of gene programs, and gene rearrangement and expression, as well as the generation of the immune response itself. Not surprisingly, increased understanding of B-cell differentiation sometimes results from the application of new techniques that permit greater insight into the cells comprising the system and the genetic mechanisms by which these cells express their differentiative potential. However, experimental strategies based upon the novel application of established technologies have also led to the clarification of many issues, as well as to the discov ery of previously unrecognized problems. One problem, well recognized by those active in the field, is how to keep up with significant developments as they appear. The purpose of this book, part of a series devoted to analysing current issues in biology, is to help overcome this problem. No attempt at comprehensive cov erage of all of the issues has been made. Rather, a more thorough analysis of a few topics is presented."

The third component of complement, C3, is one of the most versatile proteins and an important participant in immune surveillance and immune response pathways. Its multifunctio nality is based on its ability to interact specifically with multiple serum complement proteins, cell surface receptors, and mem brant;-associated regulatory proteins. One of its most intriguing strategies of interaction with cell surfaces is the covalent binding of activated C3 through the internal thioester. The field has expanded over the past 10 years and a wealth of information has accumulated. C3 from various species and many of the human C3 binding proteins have been cloned and expressed. Numerous cellular responses mediated by the diffe rent fragments of C3 have been described. The findings that C3 interacts in a ligand-receptor-like fashion with proteins of nonself origin such as the gC of herpes simplex virus, a 70-kDa protein from Candida albicans, proteins from Epstein-Barr virus, etc. has opened a new field of investigation. The papers assembled in this volume summarize the wealth of data on the various aspects of the C3 interactions; together they bring to the reader new information on the chemistry, molecular gene tics, biology, and pathophysiology of C3 and C3-binding proteins. Emphasis is given to structural features as they relate to functions. Spring 1989 JOHN D. LAMBRIS, HANS J. MULLER-EBERHARD Table of Contents J. E. VOLANAKIS: Participation of C3 and Its Ligands in Complement Activation . . . . . . . . . . . 1 S. R. BARNUM, G. FEY, and B. F. TACK: Biosynthesis and Genetics of C3 . . . . . . . . . . . . .

Through numerous discussions with colleagues it became apparent that the time was right to begin a series of workshop-like meetings on myeloid tumorigenesis. Myeloid tumors are the nonlymphocytic tumors of the hematopoietic system which include tumors of the neutrophilic, monocytic, erythrocytic, basophilic (mast cell) and megakaryocytic lineages. Pioneering studies in myeloid tumorigenesis were initially made in chickens with the discovery of retroviruses that induce various kinds of myeloid tumors acutely (myelocytomatosis, myeloblastosis, and erythroblastosis). These avian retroviruses were subsequently shown to contain the oncogenes v-myb, v-~, v-~, v-erbA, or v-erbB. There have been dramatic advances in studying the pathogenesis of hematopoietic tumors in genetically defined mammalian systems. Many of the well developed model systems in inbred mice, have focused on T- and B-1ymphoma development. Although myeloid tumors have been found in mice, they have not been studied as intensively as lymphoid tumors. Possibly this is because myeloid tumors are less common than lymphoid tumors. Recently, there has been renewed interest in murine myeloid tumor systems. This focus has resulted from 1) the discovery of inbred strains of mice (e. g. BXH-2, AKXD- 23, SJL/J) that are highly susceptible to spontaneous or induced myeloid tumorigenesis; 2) establishment of transplantable murine myeloid tumors (e.

The Brescia division of the Italian Association of Blood donors (AVIS Brescia) celebrated its 50th anniversary in 1985. The idea of organizing a Postgraduate Course on Viral Hepatitis on this occasion developed for ob vious reasons. Viral hepatitis is a major concern in blood transfusion and Brescia is located in the region of Lombardy characterized by a high HBsAg carrier rate in its population. Thus it seemed timely to convene a scientific forum in which the present state of knowledge on viral hepatitis would be summarized. This would allow us to review the tremendous progress achieved over the last 15 years, and also to focus on latest developments which pave the way for future investigation. The publication of the proceedings of this meeting was considered use ful, since it provides a tangible reminder of a comprehensive overview of the broad topic of viral hepatitis, its complications, and its connections with the practice of blood transfusion. The organizers were fortunate in obtaining the active participation of recognized experts in a variety of hepatological diSCiplines. Their contri butions summarized the more mature areas of knowledge in the field, in cluding clinical aspects, epidemiology and morphology, as well as newer developments in the forefront of hepatitis research, like new diagnostic techniques, oncogenesis, treatment, and vaccination."

From the preface: "The importance of the lymphatic system has been known for a long time. It was therefore surprising to learn that the status of dermal lymphatics, under both normal and pathological conditions of man, had been largely neglected to date, particularly with respect to their ultrastructure. Moreover, the existing information is incomplete, relating only to narrow segments of the skin, and it is controversial. This monograph represents an effort to overcome some of the existing deficiencies in the area of the structure (with emphasis on ultrastructure) of lymphatic capillaries. It is an account of our experience in the evaluation of dermal lymphatics in normal, edematous, and some other pathological conditions in man and in experimental animals. It is hoped that this information will prove useful for other investigators as a basis for evaluation of the structural and functional status of dermal lymphatics under a wide variety of pathological conditions."

In 1976 the International Committee on Taxonomy of Vi ruses (ICTV) created the family Iridoviridae to encompass several different vertebrate and invertebrate viruses that did not fit into any of the other established groups. The unifying features of this new family were (1) polyhedral symmetry; (2) large (approximately 170 kilobase pairs), lin ear, double-stranded DNA genomes; and (37) a cytoplas mic site of replication. The name "iridovirus" was derived from the observa tion that larvae infected with many of the insect viruses, as well as purified pellets of these viruses, glowed with a blue or green iridescence - presumably due to the Bragg effect of the viral crystals. However, none of the vertebrate "iridoviruses" displayed this particular characteristic. An attempt was made to substitute the more descriptive name of "icosahedral cytoplasmic deoxyribovirus," but not only was this term too unwieldy, it also did not conform to the latinized nomenclature the ICTV wished to adopt. So, for both historical and esthetic reasons, "Iridoviridae" was adopted as a family name, with Iridovirus as the genus represented by the type 1 iridescent insect virus, Tipula iri descent virus. At the 1982 ICTV Meeting, enough biochem ical data had accumulated to permit the establishment of the following five genera in the family Iridoviridae: English vernacular International Type species name name 1. Small iridescent Iridovirus Tipula iridescent virus insect virus (Type 1) 2. Large iridescent Chloriridovirus Mosquito iridescent insect virus virus (Type 2) 3."

M. B. A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i. e. , workers in molecular biology, cancer research, virology, immunobiology, etc. , because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OWSTONE and PETERS 1978). For example, HINMAN et al.

Current Topics in Medical Mycology, is intended to summarize current research areas in medical mycology for medical my- cologists and other scientists who are working in microbiology and immunology. Topics to be included in each volume will serve as contemporary reviews, summaries of current advance- ments and future directions, and mechanisms to enhance the interdisciplinary use of medically important fungi in under- standing pathogenesis, epidemiology, mycotoxins, taxonomy, and other areas where basic, applied, and clinical sciences are used. Michael R. McGinnis v Contents Series Preface v Contributors ix Ultrastructural Correlates of Antimycotic Treatment MARCEL BORGERS 2 Soluble Polysaccharides of Cryptococcus neoformans ROBERT CHERNIAK 40 3 Tinea Imbricata RODERICK J. HAY 55 4 Adhesion and Association Mechanisms of Candida albicans MICHAEL J. KENNEDY 73 5 Peptide Transport in Candida albicans: Implications for the Development of Antifungal Agents FRED NAIDER and JEFFREY M. BECKER 170 6 Epidemiology of Coccidioidomycosis DEMOSTHENES PAPPAGIANIS 199 7 Immune Response to Paracoccidioides brasiliensis in Human and Animal Hosts ANGELA RESTREPO M. 239 vii Vlll Contents 8 Morphogenetic Transformation of Fungi MAXWELL G. SHEPHERD 278 9 Epidemiology of Nosocomial Fungal Infections DAVID J. WEBER and WILLIAM A. RUTALA 305 Melanins and Their Importance in 10 Pathogenic Fungi MICHAEL H. WHEELER and ALOIS A. BELL 338 11 Cytochrome P-450 of Fungi: Primary Target for Azole Antifungal Agents Yuzo YOSHIDA 388 Index 419 Contributors JEFFREY M. BECKER, Ph.D.

During the past few decades we have witnessed an era of remarkable growth in the field of molecular biology. In 1950 very little was known of the chemical constitution of biological systems, the manner in which information was transmitted from one organism to another, or the extent to which the chemical basis of life is unified. The picture today is dramatically different. We have an almost bewildering variety of information detailing many different aspects oflife at the molecular level. These great advances have brought with them some breath-taking insights into the molecular mechanisms used by nature for replicating, distributing and modifying biological information. We have learned a great deal about the chemical and physical nature of the macro molecular nucleic acids and proteins, and the manner in which carbohydrates, lipids and smaller molecules work together to provide the molecular setting of living systems. It might be said that these few decades have replaced a near vacuum of informa tion with a very large surplus. It is in the context of this flood of information that this series of monographs on molecular biology has been organized. The idea is to bring together in one place, between the covers of one book, a concise assessment of the state of the subject in a well-defined field. This will enable the reader to get a sense of historical perspective what is known about the field today - and a description of the frontiers of research where our knowledge is increasing steadily."

This volume deals with the structure and function of molecules that have, during the last decade, turned out to have a central role in immune responses. Trans plantation antigens were discovered and characterized by Gorer about 50 years ago, and the biological basis for the unequalled complexity of their variability between individuals within a species, in spite of extreme conservation between species, was the subject of intense research and discussion for many years. During the days of belief in "immune surveillance" against spontaneously developing tumors, it was suggested that histoincompatibility between members of one species would prevent cancer from being a contagious disease and thus a threat to the species. Immunologists involved in human transplantation had to learn and care about the complexity, especially after 1967, when it was found that HLA antigens were the products of the human MHC. Rejection of HLA-identical sib kidney grafts was so rare, even in those days, that cases of rejection were described in scientific papers."

Anergic reactions and anergic diseases are found in many fields of medicine. As wen as affecting the skin, allergic diseases occur in internal organs such as the lungs and the kidneys and in the vascular and nervous systems. Interdisciplinary understanding and cooperation thus seem necessary to get a better insight into allergic reactions in the different fields of medicine in order that we may give our patients the best diagnostic and therapeutic care. Allergic diseases are on the increase. Studies from Sweden show that 15% of the population there are atopic, and some people speculate that in Germany about 10%-15% of all adults suffer from one of the many different allergic conditions. We in our clinic also have the impression that the incidence of atopic reactions has increased in recent years. The figure of 15% would mean something like 200 000 people in Munich alone We all know that a wide variety of environmental factors can induce allergic reactions in the skin, the respiratory system, or internal organs. The most important anergens in our environment are pollen, molds, animal dander, housedust mite, food or food additives, various insects, industrial compounds and drugs. The direct costs of hospital and community medical care, other services, and drugs to help patients with asthma, hay fever, and skin allergies have in creased considerably in the last 10 years. The figures should make it clear to everybody that we are dealing with a health and environmental problem of great practical importance."

F. B. Michel Asthmology is the neologism I suggested for ideas which were acceptable at the begin the title of a book published in 1981 on ning of the 20th century, and in particular bronchial asthma [4,5]. to Pasteur's concept of "one cause, one ill ness", many syndromes like high blood Among a certain number of scientific pressure or asthma are the result of the publications on this subject, it is one of the overlapping of hereditary factors and ac few suggestions that I have the weakness to quired factors. This is one reason why asth feel somewhat proud of. In fact, this word has had the career I hoped it would and, ma is not really an illness in the real sense judging by the frequency with which it is of the word but, a clinical and functional respiratory syndrome [1]. used in both written and spoken language, it did answer a need. I had no intention of The innate, the "terrain", transmitted by suggesting one more neologism but it heredity, can possibly concern two factors: seemed to me that the word asthmology The bronchial hyperreactivity factor (BHR), had an element of novelty and, above all, is often present in early childhood and its produced the necessary awareness of the reality is a result of the studies of large need to bring together, within a kind of groups of homo- and heterozygotic twins.

The fourth workshop on Mechanisms in B-Ce11 Neoplasia was held in Bethesda. Maryland. at the National Institutes of Health on March 24. 25 and 26. 1986. The meeting was attended by approximately 150 participants and 58 presentations were given. The purpose of these workshops and the yearly publications has been to provide a means for exchanging the rapidly developing information in this field and to bring maJor problems into focus. Edited trans- cripts of the 1983 and 1985 workshops were published by Editiones Roche Bas1e, Switzerland. Papers brought to the 1984 workshop were published in Current Topics in Microbiology and Immunology, Vol. 113. Numerous retrovira1 recombinant viral constructs are now in general use in a variety of test systems, both in vivo and in vitro. These are proving to have interesting bio10gica1-prQperties. ------- Kecent1y developed systems for inducing B cell tumors are described: 1) The development of spontaneous ~-ce11 tumors in transgenic mice carrying deregulated mlGBP genes and the Ig heavy chain promoter; 2) a method for inducing *p1asmacytomas in BAL~/c mice with short latent periods of ca 70 days by infecting pristane treated mice with retroviruses carrying various types of deregulated mlGBP genes; 3) induction of pre-B cell tumors with erbB containing recombinant retroviruses; 4) induction of B-ce11 and other tumors by infection of neonates with recombinant retroviruses. Several retrovira1 constructs containing mlGBP sequences do not induce B-ce11 tumors in pristane conditioned mice *.

When I entered the field of allergy in the early 1970s, the standard textbook was a few hundred pages, and the specialty was so compact that texts were often authored entirely by a single individual and were never larger than one volume. Compare this with Allergy Frontiers: Epigenetics, Allergens, and Risk Factors, the present s- volume text with well over 150 contributors from throughout the world. This book captures the explosive growth of our specialty since the single-author textbooks referred to above. The unprecedented format of this work lies in its meticulous attention to detail yet comprehensive scope. For example, great detail is seen in manuscripts dealing with topics such as "Exosomes, naturally occurring minimal antigen presenting units" and "Neuropeptide S receptor 1 (NPSR1), an asthma susceptibility gene." The scope is exemplified by the unique approach to disease entities normally dealt with in a single chapter in most texts. For example, anaphylaxis, a topic usually confined to one chapter in most textbooks, is given five chapters in Allergy Frontiers. This approach allows the text to employ multiple contributors for a single topic, giving the reader the advantage of being introduced to more than one vi- point regarding a single disease.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

Any professional concerned with immunology will be interested in this book dedicated to the memory of Milan Hasek, former director of the Prague Institute of Experimental Biology and Genetics. Prof. Hasek was a congenial scientist and most amiable person - a personal friend of almost all leading immunologists around the world. He was displaced from his post of director in 1970, yet had a lasting impact upon his students and the group known as the Prague School of Immunogenetics. The topics covered in the contributions range from tolerance, immune network, and immunogenetics to the immunology of bacterial and viral infections. They are written by 27 of Prof. Hasek's former co-workers who emigrated to western countries around or after 1968 and became well-known and distinguished scientists in the field. The papers include their personal reflections of the Prague Institute, their impressions upon arriving abroad and their interesting experimental work since then. The book also provides a complete bibliography of their publications after leaving Czechoslovakia.

Sepsis and infection are the major enemies of the intensive care patient in whom immunological defenses are severely impaired. This major problem is thefocus of attention in this book, based on the presentation of the First International Congress on the Immune Consequences of Trauma, Shock, and Sepsis, which is one of the first attempts to exchange ideas on the state-of-the-art in this area of immunology. Both basic and clinical research, including new centres of attention, are described. The growing role of immunology in medicine opens new avenues to the under- standing of trauma and sepsis and will allow the design of novel therapeutic approaches.

This volume contains the contributions to the workshop "The Semiotics of Cellular Communication in The Immune System" which took place at "11 Ciocco" in the hills north of Lucca, Italy, September ~-12, 1986. The workshop was the first meeting of what we hope will be a broad consideration of communication among lymphocytes, and focused on the new interdisciplinary branch of biological sciences, immunosemiotics. It is in the realm of the possible, if not the probable, that in the future a number of scientists larger than the thirty present at 11 Ciocco will find immunosemiotics to fill a need in scientific thinking and a gap between biology and the humanities. This might lead to growth and flourishing of the branch, and in this case the first conference and this first book could be blessed by the impalpable qual ity of becoming "historical", if in an admittedly 1 imited sense. Just in case this should happen the organizers/editors think it wise to set the record straight at this particular time, about the sequen~e of events and circumstances that crystallized the archeology of the "11 Liocco" gathering. They feel a sort of obligation to this endeavor: it has happened all too often that innocent historians have been left in utter confusion by the careless founders of new religions, schisms, revolutions, et cetera, who simply forget to jot down the facts before the whirlwind of time engulfs them in its fog.