It goes almost without saying that there has been a marked increase in the incidence of sexually transmitted diseases throughout the world in the past two to three decades. Indeed, despite the progress that has been made in methods of diagnosis and treatment, the sexually transmitted diseases as a whole are the most common communicable diseases and as such constitute an important health problem. The increase in incidence may be accounted for by changes in sexual behaviour, the introduction of contraceptives and the increasing mobility of the population. In addition, during the same time period, the number of infectious agents recognized as being sexually transmitted has increased considerably. These include Chlamydia trachomatis, herpes simplex virus, cytomegalovirus and hepatitis B virus. Indeed, some are as dependent on sexual transmission as the agents which cause the traditional venereal diseases and collectively they cause morbidity which has out-stripped that caused by gonorrhoea and syphilis. It could almost be said that to know the sexually transmitted diseases is to know micro biology. However, the approach taken in this book has not been to consider individual infectious agents and evaluate what they do and do not cause but to consider clinical conditions and what might be responsible for them. To cover the complete spectrum of the sexually transmitted diseases in a comprehensive way now takes a text book of massive proportion."

The SecretoryPathway The transport ofproteins and lipids from their site ofsynthesis at the endoplasmic reticu- lum (ER) to the cellsurface ismediated by the secretory pathway and isan essential process in eukaryotic organisms. A great variety ofmolecules are extruded from cellsby the action ofthe secretory pathway, including extracellular matrix components that provide the foundation for constructing tissuesand organs. Moreover, this pathway playsa major role in the biogenesisof the plasma membraneand itsexpansion before celldivision. Therefore, withoutsecretion there would be no cells,tissuesor organs, and so it issafeto saythat we oweourvery existence to the secretory pathway. To understand the process ofsecretion we must learn about the organelles that compose the secretory pathway; the ER and Golgi apparatus, and the transport vesicles these or- ganelles produce. The membrane ofthese organelles is primarily synthesized and assembled at the ER but with contributions from mitochondria (phosphatidylethanolamine) and the Golgi apparatus (sphingolipids). Newly synthesized proteins destined for secretion gain en- try into the secretory pathway by translocation across the ER membrane. This translocation apparatus also integrates proteins into the membrane and establishes their topology with respect to the lipid bilayer (seeChapter 7). Many secretory proteins are covalently modified with oligosaccharides to produce glycoproteins, a biosynthetic process initiated in the ER and continued in the Golgi apparatus. Once proteins are properly folded and modified in the ER, they are allowed to leave and are ushered into COPlI-coated carrier vesiclesforming at specific exit sites (see Chapters 1 and 8).

The substantial and impressive changes in microbial ecology can scarcely be chronicled in a meaningful fashion, and a review series such as Advances in Microbial Ecology can thus not do justice to the numerous studies that have been published in recent years. On the other hand, the mere existence of this series bears testimony to the many and diverse activities. The growing concern with microbial communities and processes in natural ecosystems is not restricted to scientists in one region and is not limited to particular groups of organisms or to individual theoretical or applied problems. The recent and successful international symposium on microbial ecology held in New Zealand-sponsored in part by the International Commission on Microbial Ecology, as is the Advances-and the general microbiology and ecology conferences and congresses have included reports from investigators from all corners of the globe and have explored both new and traditional areas, agricultural and public health problems, individual species and complex communities, and heterotrophs and autotrophs as well as ecosystem models relying on mathematical concepts and environmental processes needing sophisticated chemistry for their definition. The reviews in the present volume thus can offer only a minute sampling of the multitude of topics being actively explored at the present time. Two of the reviews focus attention on biogeochemical cycles regulated by microorganisms, in particular the way these organisms contribute to or control the levels and identities of chemical substances in the atmosphere. The chapter by Y. Dommergues, L. W. Belser, and E. L.

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.

The larvae of Anisakis, whose adult form lives on sea mammals such as whales, seals, and dolphins, are parasitic upon many species of salt-water fish. When the final host animals eat paratenic hosts, the larvae grow to adulthood in the hosts' stomach. However, when hu mans eat these infested fish, the larvae die instead, causing a disease called anisakiasis. In 1960, in the Netherlands, van Thiel et al. found a worm in the intestinal wall of a patient who had eaten raw herring and had suffered symptoms of acute abdomen. The impact of this report was tremendous among Japanese parasitologists because of the Japanese habit of eating raw fish. In 1964, the Special Research Group from the Ministry of Education was established to investigate the disease, stimulating progress in the study of anisakiasis. Three types of worm, Anisakis simplex larva (previously known as Anisakis larva type I), Anisakis physeteris larva (Anisakis larva type II), and Pseudoterranova decipiens larva type A, are believed to cause anisakiasis. As many as 165 kinds of fish and squid in the seas near Japan are hosts to Anisakis simplex, and 9 species are hosts to Pseudoterranova decipiens larvae. Contra caecum has experimentally been observed to invade the gastrointestinal tract, but no infection by this larva has been reported in humans. A case of infection by Pseudoterranova decipiens type B has been described. In Japan, the name Terranova decipiens (Shiraki 1974) has been adopted instead of Phocanema decipiens (Mozgovoi 1953)."

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."

Tropical diseases such as leishmaniasis, malaria. trypanosomiasis, toxoplasmosis and amebiasis continue to plague the world, resulting in considerable morbidity and mortality, especially in the third world countries. These diseases are caused by a group of protozoa which have, over the years, undergone evolutionary adaptation to live often intracellularly in a parasitic way of life. So well-adapted have they become that they recognize the right hosts or cells to parasitize, yet at the same time they escape recognition and destruction by the host immune system. The mechanisms of such recognition and the escape of recognition are governed largely by host-parasite surface membrane interactions at the cellular and molecular level. Unique molecules produced by unusual pathways of these parasites have also been discovered and found to play important roles in their survival in the host. Understanding these mechanisms and pathways is essential not only to formulate a rational strategy for chemo- and immuno-prophylaxis and -therapy but also to unravel the mystery of biological evolution in symbiosis and parasitism. In the advent of our knowledge on the molecular biology and biochemistry of parasite membrane and other molecules, it is opportune to examine and discuss their possible roles in host-parasite recognition and interaction in a comparative approach. To highlight the recent advances of this area in various host-parasite systems, a NATO advanced Research Workshop was held from September 27 to October 1, 1986 at Hotel Villa del Mare, Acquafredda di Maratea, Italy.

Genital Papillomavirus Infections provides a state of the art survey on the clinical aspects, diagnosis, treatment, and prevention of genital papillomavirus infections, written by experts in the respective fields. Two introductory sections on epidemiology and molecular biology are followed by chapters on new techniques for the detection of genital papillomaviruses and their presence in genital carcinomas. Contributions on the clinical aspects cover infections of the cervix, male and female external genitalia, urethra, and oral cavity. A discussion of the immunobiology of papillomaviruses ends in an evaluation of the prospects for vaccination, and the application of podophyllotoxin, cryosurgery, laser therapy, and interferon treatment are described in detail. This book is unique in placing a strong emphasis on clinical aspects of genital papillomavirus infections. Mainly addressed to clinicians, it provides practical guidelines on methods for their diagnosis and treatment.

In the rapidly evolving field of Helicobacter infection new data on pathogenetic and pathophysiological mechanism have appeared. New methods which will be more sensitive and specific in the diagnosis of the infection are being developed and in this proceedings the first attempt using PCR technology is published. From the clinical point of view, a challenging aspect that needs clarification, is the observation which suggests an appearance of a correlation between the presence of the bacteria and abdominal pain and other symptoms in children whereas in old age no such correlation is evident. The relationship of H. pylori and gastric cancer is studied with histopathological data and epidemiological approaches. On the treatment side schemes using short courses and new antibiotic combinations are being investigated and preliminary data are reported.

Stress, high blood pressure, smoking, pollution, fast foods, overweight, excessive travelling, surgery, less movement are common features in our modern life. These features are risky for blood clotting disorders. According to WHO, over 29% of the total mortalities worldwide are due to thrombosis. By the year, 2020 cardiovascular diseases (CVDs) may cause an estimated 25 million deaths per year, thus antithrombotic therapy is of great interest.

The available thrombolytic agents such as urokinase are highly expensive, antigenic, quite unspecific, pyretogenic and hemorrhagenic. Therefore, the production of fibrinolysing enzymes, which rapidly dissolute thrombi within the vascular tree, without the detriments by microorganisms, as described in this book, is the desirable aim of today s research. "

Attention to viral infections and pathology previously focussed on diseases of economically important fish. In recent years, however, much new information on molecular virology and oncogenicity derives from viruses occurring in amphibians. New insights into the field of zoonosis were gained by studies of lower vertebrates serving as intermediate hosts in multiple human infections. Certain viruses, e.g. the influenza virus or calicivirus, seem capable of bridging species lines and even the land - sea interface. Global developments in aquaculture are indicated in influenza pandemics. These proceedings present research findings on viruses of fish, amphibians and reptiles, including defence mechanisms, zoonoses, evolutionary considerations and diagnostic approaches.

Parasitic Disease, second edition remains unique in its emphasis on depictions of complete life cycles and its skillful knitting of basic and clinical information. Superbly illustrated with black and white and color photomicrographs and halftone drawings, it is an ideal text for medical, graduate, and advanced undergraduate students of parasitology and an excellent reference for physicians and researchers.

With the advent of genetic engineering methods and improved biochemical tech niques, much has been learned about the replication of influenza viruses, their structure and their epidemiology. It appears that the time is ripe to review these efforts and to provide a molecular perspective of influenza virology. It is hoped that this book will stimulate our thinking, help us in designing new experiments, and possibly show avenues leading to the control of the diseases associated with influenza viruses. Peter Palese, New York, N. Y. August 1983 David W. Kingsbury, Memphis, Tenn. Contents List of Contributors. . . . . . . . . . . . . . . . . XV 1. The Evolution of Influenza Viral Genetics - A Perspective. By E. D. Kilbourne. . . . . . . . . . . . . . . . 1 I. Introduction. . . . . . . . . . . . . . . . . 1 II. The Development of Modern Influenza Viral Genetics 2 A. Early Evidence of Genetic Variation in the Laboratory 2 B. Application of Formal Genetic Techniques to Studies of Influenza Virus . . . . . . . 3 C. Genetic Markers. . . . . . . . . 3 D. Development of Plaquing Systems. . . 4 E. The Use of Conditional Lethal Mutants 5 F. New Approaches in Influenza Virus Genetics. 6 1. The Biochemical Identification of Viral Gene Products in the Unambiguous Definition of Viral Inheritance . . . 6 2. Mapping of the Influenza Virus Genome by Correlative Physico-Chemical and Biological Techniques. . . . . . 7 3. The Application of Molecular Biological Techniques to the Study of Viral Genetic Variation. . . . . . . . . 8 4. Oligonucleotide Mapping of Viral RNA's . . . . . . . 8 5. Contribution of Protein and RNA Sequencing to Influenza Viral Genetics-Intragenic Mapping . . . . . . . 8 III. Viral Genetics and the Understanding of Viral Virulence and Pathogenicity . . . . . . . . . . . . . . . . . . ."

During the late 1970's the application of hybridoma technology led to an explosion in the discovery and characterization of proteins expressed at the surface of hematopoietic cells. The understanding of T lymphocyte biology benefited enormously from this advance and from newly developed techniques for obtaining clonal T cells. Application of these methodologies resulted in the identification of the clonally restricted T cell antigen receptors (TCRs) and of a number of other molecules expressed more broadly on T cells. Among these, the CD4 and CD8 glycoproteins stood out because they were differentially expressed on distinct functional subsets of T lymphocytes. Moreover, blocking studies with monoclonal antibodies sug gested a functional role for CD4 and CD8 in T cell responses to antigen. Shortly thereafter, it was shown that T helper cells were the primary targets for the human immunodeficiency virus (HIV) and that CD4 serves as the viral receptor on these cells. These findings fueled an intense interest in CD4 during the last decade, in the hope that understanding the molecular nature of the HIV-CD4 interaction could hold the key to controlling AIDS.

This volume on enzootic bovine leukosis (EBL) and bovine leukemia virus (BLV) is the second in our series "Developments in Veterinary Virology". Each book in this series is devoted to a major virus disease of agricultural significance. The chapters in each volume are planned to supply information on a range of subjects from pathogenesis of the causative virus to vaccination, eradication, and rules regarding disease control. The present volume on enzootic bovine leukosis and bovine leukemia virus updates the reader on the disease and its causative agent and includes the nucleotide sequence of the BLV genome as well as data on its integration into the DNA of the tumor cell. Insights into diagnosis, veterinary legislation, and the economic aspects of EBL are also provided. Intense research conducted on EBL and BLV during the course of a decade is presented in a most concise and in-depth manner, so as to provide the reader with a comprehensive overview of this economically important disease of cattle. I wish to thank the editors, A. Burny and M. Mammerickx, as well as all the authors, for making this excellent book available at a stage when the knowledge on bovine leukemia virus will also contribute to our understanding of the virus causing human AIDS.

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.

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.

(Director: Pierre J. COURTOY) Two years after its first gathering in Oeiras, Portugal, the European Endocytosis Group convened for a second workshop at the Pasteur Institute, Paris, on October 1-5, 1990. The meeting is reported in detail in this volume; a preliminary coverage, based on the overviews of each session, has appeared in the New Biologist (1991, 3:243-252). The three main objectives, to broaden the audience, to present a more comprehensive view of the multiple aspects of endocytosis, from basic biology to health, disease and therapy, as well as to clarify controversial issues, have been largely fulfilled. The Second European Workshop on Endocytosis was attended by more than tOO participants, originating from 18 countries. 59 lectures and 35 posters were presented. In addition, vivi~ roundtables allowed to thoroughly discuss the dynamics and the regulation of the endocytic apparatus, as well as the role of endocytosis in antigen presentation. Endocytosis is a general and distinctive property of all eukaryotic cells, including protists, plants and fungi.

Human gene therapy holds great promise for the cure of many genetic diseases. In order to achieve such a cure there are two requirements. First, the affected gene must be cloned, its se quence determined and its regulation adequately characterized. Second, a suitable vector for the delivery of a good copy of the affected gene must be available. For a vector to be of use several attributes are highly desirable: these include ability to carry the intact gene (although this may be either the genomic or the cDNA form) in a stable form, ability to introduce the gene into the desired cell type, ability to express the introduced gene in an appropriately regulated manner for an extended period of time, and a lack of toxicity for the recipient. Also of concern is the frequency of cell transformation and, in some cases, the ability to introduce the gene into nondividing stem cells. Sev eral animal viruses have been tested as potential vectors, but none has proven to have all the desired properties described above. For example, retroviruses are difficult to propagate in sufficient titers, do not integrate into nondividing cells, and are of concern because of their oncogenic properties in some hosts and because they integrate at many sites in the genome and, thus, are potentially insertional mutagens. Additionally, genes introduced by retroviral vectors are frequently expressed for relatively short periods of time. A second virus used as a vector in model systems has been adenovirus (Ad)."

Helieobaeter pylori has recently been recognized as a new genus according to specific taxonomic criteria; the "popular" name Campylobaeter pylori has been corrected by scientific progress. Following the discovery of the spiral microorgan ism in gastric mucosa by Marshall and Warren in 1982, it took only a few years for H. pylori to become established as a factor in the pathogenesis of gastritis and peptic ulcer disease. Interest in different aspects of H. pylori has grown continuously and has attracted scientists from various medical and biological disciplines such as gastroenterology, microbiology, pathology, immunology, and pharmacology. Indeed H. pylori provides an excellent model for interdisciplinary interaction and cooperation. To promote this concept of interdisciplinary research and exchange of knowledge, a European Campylobacter (Helicobacter) Pylori Study Group was founded in 1987 in Copenhagen. The second meeting of this expanding group was held from October 12-14,1989 in Ulm, FRG. The fact that more than 500 participants attended the conference and that 187 original contributions from all five continents were presented clearly confirmed that H. pylori has "scientifically infected" the whole world. Our understanding of the microbiological and pathogenetic aspects of H. pylori is continuously being challenged as new results follow swifthy from different research areas. This book includes an update and progress report on the various aspects of H. pylori presented and discussed in special workshops held during the meeting in Ulm.

The International Congress on Rapid Methods and Automation in Microbiology and Immunology, held in 1990 (RAMI-90) in Helsinki Espoo, Finland, attracted considerable interest from the international scientific community. This reflects both the rapid progress and numerous new challenges in the field covered by RAMI-90. New biotechnical approaches, such as the polymerase chain reaction, recombinant gene products and synthetic peptides are gaining wide acceptance. New important pathogens have emerged, such as hepatitis C, Helicobacter pylori, Borrelia burgdorferi, herpes virus 6 and Chlamydia pneumoniae. "Super streptococci" are recognized again as well as the agent responsible for bovine spongiform enceph alopathy. The current diagnostic methods are clearly unsatisfactory for many of these and other microbes. Moreover, there is an increas ing need for more accurate microbial control of our environment, and of the food and water we consume. What is needed are rapid, sensitive and reliable procedures which, on the one hand, should be suitable for automation and, on the other hand, presented in a cost-effective version suitable for field use. We view these needs as a clear and loud challenge for future RAMI congresses. This volume provides an up-to-date presentation of the highlights of RAMI-90 and prospects for the future. For the preparation of this volume we wish to thank Dr. Maija Leinonen for her invaluable con sultation and Ms. Virpi Tiilikainen for secretarial assistance. ANTTI V AHERI RICHARD C. TILTON ALBERT BALOWS Contents Nucleic Acid Detection Controlled Synthetic Oligonucleotide Networks for the Detection of Pathogenic Organisms M. S. Urdea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

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)

Oral immunization has a fascinating and frequently successful history, yet it has been largely overshadowed by other immunization methods. Various vaccines that lead to the induction of antibodies in respiratory, gastrointestinal, and genitourinary tracts are currently under development, and others are in use for the immunization of animals as well as humans. This volume gives oral immunization the attention it deserves in light of recent methodological and technical advances in antigen delivery systems.

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."

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.