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.

The 8th volume in the Proteases in Biology and Disease series focuses on the role of proteases in virus function and their potential as anti-viral targets. Viral infections are still difficult to threat and some remained life-threatening diseases in spite of antiviral drug research over decades. Proteases are still regarded as an Achilles heel of the pathogens and, thus, protease inhibitors may help to handle the known and the emerging viral threads. The book discusses viral proteases of the most important pathogenic viruses, responsible for severe diseases: AIDS, SARS, Hepatitis, Cytomegalovirus, T-cell lymphotropic virus, Picornavirus. This book focuses specifically on the viral proteases, crucial prerequisites for viral entry into cells and viral replication. Viral proteases represent an important pharmaceutical target. The current stage of protease inhibitor development and therapy are summarised and discussed by experts in the field. This volume represents a timely and valuable continuation of the Proteases in Biology and Disease series. The reader will learn the potential for proteases as targets for effective anti-virals. This book will be a valuable source of information on viral proteases and provoke further research in this important field."

The 12th Workshop on ""Mechanisms in B-Cell Neoplasia"" continues this series of meetings on intriguing new developments in human and experimental B-cell tumors. The integration of knowledge from basic B-cell biology to the clinical problems of multiple myelomas, follicular lymphoma, mantle cell lymphoma and B-CLL present the challenges that were discussed in the meeting.
The discussion focusses on:
- Cellular components of the "myeloma clone"
- Genomic instability in B-cells and B-cell tumors
- The CD5 antigen and B1 cells
- Regulation of cell cycle and apoptosis
- Role of IL-6, BCL-2, BCL-1, myc in B-cell development

ADP-ribosylating toxins have been the focus of intensive research for more than 30 years. Researchers from diverse fields of science have taken an interest in these bacterial toxins; they are studied, for example, by microbiologists, biochemists, cell biologists, and pharmacologists. There are two principal reasons for the broad and still growing interest in ADP ribosylating toxins. First, insights into the structure and functions of the toxins might be the key to prevention and treatment of diseases caused by the toxin-producing infectious micro organisms. Second, the ADP-ribosylating toxins provide potent and often unique pharmacological tools for the study of the physiological functions of their target proteins. The latter is especially the case with cholera and pertussis toxins, which both modify the IX-subunits of heterotrimeric G-proteins involved in signal transduction pathways. These toxins have proved invaluable in extending our basic understanding of the regulation of hormone-controlled signal transduction. This volume provides a review and an update of recent studies on the basic properties of bacterial ADP-ribosylating tbxins and/or exoenzymes. Our current knowledge of the cel lular entry mechanisms of ADP-ribosylating toxins is reviewed by MADSHUS and STENMARK. WILSON and COLLIER then deal with recent insights into the enzyme mechanism and active site structure of diphtheria toxin and Pseudomonas aeruginosa exotoxin A, which modify elongation factor 2. Toxins which ADP-ribosylate heterotrimeric G-proteins involved in trans membrane signal transduction are the subject of the next two chapters."

Peritrophic membranes are secretion products of the midgut. For long they have been related only to insects, but they occur widely in the animal kingdom. They effect a part of the gut lumen and function not only as a mechanical protection barrier, but also as an ultrafilter, a barrier to parasites, and as envelopes for fecal pellets. Such peritrophic envelopes are of great ecological importance in marine environments. The book is divided into the following themes: - Occurrence - Formation and Structure - Degradation - Chemical Composition - Functions. It is the first comprehensive compilation of all data concerning peritrophic membranes and will provide a basis for future researches in this up to now often neglected field.

Parasitic Disease in Clinical Practice is the sixth monograph to appear in the now established and flourishing Bloomsbury Series in Clinical Science. Written by a distinguished authority in the field, the book gives a comprehensive and detailed description of parasitic infections and their clinical consequences. Such infections are no longer confined to tropical parts of the world and now have a widespread distribution. Rapid advances are being made in understanding their epidemiology and in diagnosing and treating particular infections. Current literature is largely directed to the parasites, their characteristics and their isolation; a clinical review is clearly needed. This has now been provided, for the author's stated objective is to "inculcate a greater awareness, understanding and appreciation of human parastic disease in the minds of all clinicians". London, March 1990 Jack Tinker Preface Homo sapiens has always existed in a finely balanced equilibrium with a great diversity of infective agents, almost all of them of great antiquity. Many must have exerted a profound effect on the evolution of the human genome. While the average physician is usually aware of potentially pathogenic viruses, bacteria (and rickettsia), and to a lesser extent fungi, hislher knowledge of protozoan and helminthic infections is frequently imperfect and often rudimentary.

Since the discovery of Australia antigen and its association with type B hepatitis, molecular characterization of the components making up hepatitis B virus (RBV) have been pursued with worldwide interest. Over the past two decades, such characterization has led to the development of sensitive assays to screen and exclude contaminated units from blood banks and has recently resulted in the licensing of several RBV vaccines. That more than 200 million people worldwide are chronically infected with RBV, and that they are at a high risk for the development of chronic hepatitis and hepatocellular carcinoma, still represent formidable problems in our understanding of host-virus relationships on the molecular level. In the absence of a suitable tissue culture system, and with a very limited host range of infection, characterization of RBV on the molecular level has made remarkable progress recently with the advent of genome cloning, sequencing and expression of individual virus genes by recombinant DNA technology. The presence of hepatitis B-like viruses in an expanding number of animal hosts, and the possibility of virus replication in cells other than hepatocytes, provide great promise that future work will elucidate the molecular mechanisms operative in the various outcomes of RBV infection.

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."

Profound progress has been made in the fields of chronobiology and psychobiology within the past decade, in theory, experiment and clinical application. This volume integrates these new developments on all levels from the molecular, genetic and cellular to the psycho social processes of everyday life. We present a balanced variety of research from workers around the globe, who discuss the funda mental significance of their approach for a new understanding of the central role of ultradian rhythms in the self-organizing and adaptive dynamics of all life processes. The years since the publication of Ultra dian rhythms in physiology and behavior by Schultz and Lavie in 1985 have seen a burgeoning realization of the ubiquity and importance of ultradian rhythms within and between every level of the psychobiological hierarchy. The experimental evidence lies scattered through a disparate litera ture, and this volume attempts, albeit in a highly selective manner, to bring together some of the different strands. The editors are very conscious of the omission of many important current aspects; e.g. we have not included any of the fascinating and indeed long and well-established experiments with plants (Bunning 1971, 1977; Guillaume and Koukkari 1987; Millet et al. 1988; 10hnsson et al. 1990) that are widely regarded as having initiated the whole field of chronobiology (De Mairan 1729). Neither have we reviewed recent developments on glycolytic oscillations, since a great deal of the seminal work was already completed by 1973 (Chance et al. 1973).

The intention of the series Developments in Veterinary Virology is to provide monographs dealing with the major animal viral diseases. Each volume will include the latest achievements in fundamental research and practical applications and should be readable for people from various disciplines and different backgrounds. The multi-author approach provides the best opportunity to keep each chapter at the highest level and makes the composition of the volumes manageable to the editors. This monograph on Avian Leukosis presents comprehensive reviews on the recent history of avian retrovirus research, on epizootiological, virological, pathological aspects, on tumor induction, the immune response to avian retro viruses, virus-cell interactions and on techniques for diagnosis. The volume deals mainly with exogenous avian leukosis virus (ALV) infections, but one chapter is entirely devoted to endogenous avian leukemia virus. Molecular biology aspects are confined to various oncogenes and to lymphoma induction since retroviruses, including those specific for avian species, have recently been described in detail in the Cold Spring Harbor Laboratory series "Molecular Biology of Tumor Viruses." Two chapters are devoted to the practical application of insights obtained from avian leukosis research: influences of AL V infection on production performance and eradication procedures."

Although long known as a parasite of medical and veterinary importance, interest in Toxoplasma gondii has increased with its emergence as a major cause of death in immunosuppressed individuals, and with recognition of its suitability as a model system for molecular and cellular investigations of apicomplexan parasites. The NATO workshop brought together 32 scientists working in different areas of toxoplasmosis research to gain an overview of progress in the field. Molecular studies have been carried out on genomic and extrachromosomal DNA. They reveal that Toxoplasma is very highly conserved, genetic mapping is underway and preliminary linkage analysis suggests recombination is rare; moreover all virulent strains share the same isoenzyme markers and are seen to be essentially clonal by RFLP analysis [Boothroyd, Darde, Wilson]. Despite considerable structural homology between Toxoplasma and related apicomplexan parasites there is little direct overlap in gene sequence data. Good progress has been made in cloning functional genes and in elucidation of PI anchors [Cesbron-Delauw, Johnson, Mercereau-Puijalon, Striepen]. The structure of molecules on the surface and within dense granules, rhoptries and micronemes has in some cases been determined and provides clues as to the targetting and function of these proteins.

Retroviruses arguably belong to the most fascinating of all viruses because of their unusual and highly efficient mode of replication involving reverse transcription and integration of the viral genome and a complex system of transcriptional and post transcriptional regulatory mechanisms. The importance of ret roviruses as human and animal pathogens has also enhanced scientific and medical interest in this diverse group of viruses and has spurred an intensive search for novel and improved antiviral agents. More recently, analysis of retroviral replication and in particular understanding the formation and composition of the virus particle has received additional attention because of the promise of retroviral vectors as vehicles for human somatic gene therapy. Many recent advances have been made in our understanding of the molecular mechanisms governing as sembly and release of infectious retrovirus particles. This book attempts to summarize these recent developments and to provide an overview of our current knowledge on retrovirus particle formation. The individual chapters of the book deal with specific steps in the pathway of retroviral morphogenesis and maturation, starting at the time when the components of the virus have been synthesized within the infected cell and ending once the infectious virion has been released from the cell. An introductory chapter provides a comparative description of the structure and morphology of various retroviruses."

On the occasion of a research visit to Thailand in my capacity as a member of the governing board of the South Asia Institute of the University of Heidelberg, I saw for the first time the severe clinical picture of dengue with haemorrhagic symptoms among Thai children. This visit had been made possible by Profes sor Dr. med. Dr. rer. nat. Ouay Ketusinh of Bangkok, to whom I wish to express my sincere thanks in this place. In 1972 the German medical literature - the periodical Medizinische Klinik, vol. 87, pp. 152-56, to be precise - had drawn attention to this new phenomenon in the disease panorama of South East Asia, indicating a change in dengue fever from being a relatively benign tropical dis ease to a form having serious clinical and epidemiological ramifications. During the ten years following my first publication the new clinical picture, described as "dengue haemorrhagic fever," has become a standard component in the Thailand's system of notifiable diseases. So too, the World Health Orga nization publishes regular reports in its Weekly Records. On March 30/31, 1981, its Regional Office for South East Asia convened a special conference in New Delhi, thus emphasizing the significance of the diffusion of this new clini cal picture in the states of South East Asia."

This book brings together various contributions aimed at the elucida tion of the structural and functional organization of the bacterial nucleoid. Most of these papers, spanning the fields of physical chemistry through biochemistry to genetics, were presented at the session on bac terial chromatin during the Symposium "Selected topics on chromatin structure and function" held at the University of Camerino, Italy, at the end of May 1985. Times when the bacterial DNA was regarded as "naked" or, at most, complexed with polyamines, and when the absence of histones and organized chromatin was considered to be a distinct feature of the pro karyotic cell, now appear remote. Our concepts of how DNA is packaged in bacteria are changing rapidly. Studies on the structure of the bacterial nucleoid are not new. Recently, however, investigations in this field have flourished again, leading to some important contributions such as the elucidation of the three-dimensional structure of what appears to be the major protein constituent of the bacterial nucleoid or the development of methods to titrate the extent of DNA supercoiling within the bacterial cell."

Elucidating Mechanisms of Eukaryotic Genetic Expression by Studying Animal Viruses AARON 1. SHATIGN* Eukaryotic genetic expression is carefully regulated. Normal cell growth and division, tis sue differentiation, and organism development all depend on a strictly ordered progres sion of specific events. Perturbation of the control of these processes, for example by ex posure to harmful chemicals or infection with viruses leads to aberrant forms of meta bolism, often resulting in malignancies and cell death. One of the most challenging problems in biology is to derme at the molecular level the mechanisms that govern gene function in higher organisms, including ultimately man. This goal serves to unify the diverse efforts of many investigators, whether studying the precise patterns of embryo genesis, the loss of control that occurs during neoplastic growth or the redirection of biosynthetic pathways in virus-infected cells. Recently there has been remarkable and exciting progress toward understanding the molecular biology of eukaryotic expression. Much of this rapidly increasing new infor mation has come from studies of animal virus systems. Just as investigations of the relatively simple, rapidly assayed, and easily manipulated bacteriophages lead to basic discoveries about prokaryotic cells, analyses of animal viruses and their interactions with host cells have provided fundamental information about how eukaryotic nucleic acids are organized for regulated replication, transcription, and translation. For example, the small genome of SV, like cellular DNA in chromatin, is associated with histones to 40 form nucleosomal arrays (Griffin 1975)."

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 technique of microinjection along with viral genetics and molecular biology has proven useful in the correlation of retroviral polynucleotide structure with function. The advantage of this technique is the involvement of living cells where rare activities may be observed and where properties of living cells can be assayed. Future studies involving recombinant DNA molecules and the asso- ciation of proteins with nucleic acids promise to yield additional insight into the nucleotide sequences involved in the expression of viral activities. References Anderson SM, Chen JH (1981) In vitro translation of avian myeloblastosis virus RNA. J Virol 40: 107-117 Berget SM, Moore C, Sharp PA (1977) Spliced segments of the 5' terminus of adenovirus 2 late mRNA. Proc Nat! Acad Sci USA 74:3171-3175 Bishop JM (1978) Retroviruses. Annu Rev Biochem 47:35-88 Capecchi MR (1980) High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22:479-488 Chien, Y-H, Junghans RP, Davidson W (1980) Electron microscopic analysis of the structure of RNA tumor virus nucleic acids. In: Stephenson JR (ed) Molecular biology of RNA tumor viruses.

In this book the current knowledge on human cytomegalovirus (HCMV) as a human pathogen is lucidly summarized, bringing the reader fully up to date with current knowledge concerning HCMV and all the known clincial and medical aspects of diseases caused by, and associated with, HCMV. The book is divided into four parts: (I) Human cytomegalovirus and human diseases; (II) human cytomegalovirus infections and the immunocompromised host; (III) diagnosis, treatment, and prevention of human cytomegalovirus and human diseases; and (IV) molecular aspects of human cytomegalovirus. Each part is put together from chapters written by experts in the respective fields, providing basic medical and molecular knowledge in addition to more specific understanding of HCMV infections.

Interest in the lentivirus subfamily of retroviruses has greatly intensified due to the realization that HIV-1 and HIV-2 are members of this previously obscure group. Related lentiviruses have now been isolated from sheep, goats, horses, cattle, cats, monkeys, and humans. This issue of CTMI is devoted to the lentiviruses of nonhuman primates, referred to as simian immunodeficiency viruses (SIVs). The SIVs provide valuable tools for our quest to understand and control the HIVs, which are obviously important new human pathogens. Included in this volume are discussions of the distribution and molecular phylogeny of the SIVs and their use as animal models for the study of AIDS pathogenesis, and the chapters clearly illustrate how SIV models are contributing to our understanding of the ability of host immune responses to control infection at least temporarily and the ability of virus to evade these host immune defenses.

To the entomologist all insects have six legs; the layman tends to use the term "insect" to include the eight-legged spiders and mites. All these creatures are correctly classified as arthropods. Many thousands of the hundreds of thousands of recognised species of arthropods are found in the human environment-domestic, occupational and rec reational. Those species which are obligate parasites of man, the human scabies mite and the head and body lice, produce familiar clinical syndromes. They remain important in medical practice and have been the subject of a great deal of recent research. This is beginning to throw much light on the immunological mechanisms which largely determine the reactions of the host. Dr. Alexander has provided a detailed survey of this work. The wasps, bees, ants and other Hymenoptera which may sting man in self-defence can cause painful, even fatal reactions. The recent work on this important subject has also been thoroughly reviewed. Every dermatologist of experience will admit that he sees many patients in whom he makes a diagnosis of "insect bites," if he has the confidence to do so, or of "papular urticaria" or "prurigo" when he lacks such confidence, mainly because he is at a loss to know which arthropod is likely to be implicated. In his survey of the enormous literature in the entomological, public health and dermatology journals Dr. Alexander has provided an invaluable guide in which the solutions to these clinical mysteries can be sought."

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."

The last decade has witnessed rapid progress in our under standing of the mechanisms of protein export and secretion in both prokaryotic and eukaryotic cells. Studies of protein secretion across the membranes of the rough endoplasmic reticulum have led to the formulation of the now-classic signal hypothesis, which has stimulated many discussions and new ideas, and the identification of the signal recogni tion particle as an organelle in the initiation of the export process. However, more recent work pertaining to intrage nic information related to targeting specific proteins for either secretion or membrane localization, the energetics of protein secretion, the timing of synthesis versus the initia tion of export, structural requirements for the processing of precursor proteins, and the identification of the proces sing enzymes (signal peptidases), has been the result of a combined biochemical and genetic approach to the study of protein localization in bacteria. While reviews on the biochemistry and genetics of pro tein secretion have appeared frequently in recent years, this book attempts to summarize the current status and the future perspectives of this rapidly moving field in a single volume. Topics covered in this book include the genetics of protein secretion in E. coli, biochemical analysis of pro tein export in vitro, signal peptidases, excretion of colicins and hemolysin in E. coli, protein secretion in Bacillus, and protein secretion cloning vectors."