I have cured the Empress of Boolampoo of a Cramp she got in her tongue by eating Pork and buttered parsnips .... The Earl of Rochester-17th Century As the modern outpouring of biological information continues at ever increasing pace, two kinds of reviews are needed to keep the torrent in manageable form. The one assumes a working knowledge of the field in question and tries to bring the reader up to date by reporting and assessing the recent developments. The other attempts to assimilate the recent developments into a coherent restatement of the whole subject. This book falls in the latter category. Trichinella spiralis infection has been in the medical and biological limelight for more than a century, and interest in it continues una bated-as evidenced by what Norman Stoll called the "perennially exuberant" research on trichinosis. The infection seems to offer some thing for almost everyone. For the physician, it offers a patient with painful and sometimes fatal disease; for the public-health official, a threat to the commonweal; for the experimental biologist, a life cycle that is unique yet easily and rapidly maintained in the laboratory; for the field ecologist, a symbiont with an affinity for an extraordinary range of wildlife species; for the pork producer, a poorer profit; for the cook, a culinary constraint; and for the diner, a dietary danger. Yet, despite this breadth of interest, and the cascade of new data, the only comprehensive books on the subject in English are those of S.E."

The all new Concepts in Viral Pathogenesis III contains the widely praised format of presenting up-to-date information in pithy, easily read "mini-review" style and complements previous editions with contributions by leading international authorities on structure-function relationships, gene regulation, cell biology of viral infections, transgenic mice, expression of viral genes, retroviruses, and evolving concepts in viral diseases. Taken together, Volume I, II and III of Concepts in Viral Pathogenesis contain 145 unique chapters each representing the latest thinking in important areas of virology by the foremost investigators in the field. Clinicians, laboratory scientists, students, and others seeking authoritative overviews of current knowledge on the mechanism of viral diseases will welcome this valuable resource.

In metastasis, tumor cells disseminate from the primary lesion and home to secondary organs where they may remain dormant for a long time. Metastasis formation is still the most feared manifestation for tumor patients and clinicians. Although improvements have been made concerning earlier detection and specific therapy, most of the cancer patients still die of distant metastases. The purpose of these three volumes is to review the recent progress in molecular metas tasis research and to attempt to further understand the biol ogy of this multifocal process. With respect to present day molecular biology, the pioneers of metastasis research established the basic concepts of metasta sis formation in the 1970s and 1980s, namely, clonal selection of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the importance of angio genesis (Fidler, Kripke, Nicolson, Folkman and others). In the 1980s and 1990s, several of the molecules involved were identified and their network interactions elucidated. These three volumes of Current Topics in Microbiology and Immuno logy compile the most recent developments on these meta stasis-related molecules; their interactions, regulation, and ways to interfere with their action. It became evident that metastasis-related molecules are confined to distinct cellular compartments, such as the extracellular space, the cell membrane, the cytoplasmic signalling network, and the nuclear regulatory system. For the complex metastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes."

Nitric Oxide (NO) an endogenous free radical, has been shown recently to mediate several important biological effects. It plays a neuro-transmitter like role in vascular endothelium, a scond-messenger role in N-methyl-D-aspartate (NMDA) responsive neurons in the central nervous system (CNS), a neurotoxic role after its release from these neurons, and a cytotoxic role after its release by macrophages.
This volume reviews among other topics the basic chemistry and physical properties of S-nitrosothiols (RS-NO) and their biochemical mechanisms of action, NO synthase isozymes, NO synthase structure, mechanisms of NO synthesis, regulation of NOS expression and posttranslational modification, and mechanisms involving NO of CNS's damage in virus infections.

This volume focuses on the evidence for or against molecular mimicry as a cause of autoimmunity. Contributions from recognized experts present their original findings, and the final chapter reviews the overall perspective of molecular mimicry, how to use its principles in clinical investigation and list the conceptual traits by which autoimmune disaese can occur.

Marburg and Ebola virus, the two species within the family Filoviridae, are among the most pathogenic agents causing fulminant hemorrhagic fever in humans and nonhuman primates. The chronology of filovirus epidemics and epizootics proves that these viruses are prototypes of emerging/re-emerging pathogens. Since the discovery of Marburg virus in 1967 until the recent Ebola virus outbreaks in Central and West Africa filoviruses have not only raised the interest of scientists, but have also been a matter of high public concern. With the advent of recombinant DNA technology our knowledge on the genome structure and the replication strategies of these agents has significantly increased. This volumes gives an overview on many aspects of filovirus research and summarizes recent advances in the field. The topics addressed include the molecular biology of filoviruses, pathogenesis, epidemiology, immune response, as well as clinical aspects and diagnostic measures.

CURRENT TOPICS IN MEDICAL MYCOLOGY, VOLUME 4, like the pre- ceding three volumes in the series, is intended to summarize current research advances inmedical mycology. Topics ex- plored in this volume include skin kinetics of azole anti- fungal drugs; killer system interactions; fusarium-caused hyalohyphamycosis; molecular technique for epidemiologic ty- ping of Candida species; and the need for a mycoses-repor- ting system.

The Second International Symposium on "The Influence of Antibiotics on the Host Parasite Relationship" was held in Munich, F. R. G. , from March 28 to 30,1985. The topics of the meeting dealt with the aspects of changes in bacterial metabolism and structure which occur under the influence of antibiotics, and with the effects of such changes on the antibacterial host resistance. The influence on pathogenicity factors, changes in the outer membrane of bacteria, as well as the influence on the individual components of the defence system were analysed in detail. In addition, these studies showed that antibiotics proved to be an excellent tool for the examination of bacterial physiology, so that, 50 years after the introduction of antibiotics, additional important knowledge can be gained about the effect of these substances on bacteria. Considering the observations reported, it appears justifiable to postulate that new antibiotics should be routinely tested with respect to their possible effects on antiinfectious resistance. Of course, a consensus will have to be found on which to base methods and criteria employEUROd. The symposium documented an increasing interest of microbiologists and clini cians for this field of research. It would not have been possible to organize it without the substantial support of the Paul Ehrlich Society as well as of Squibb-Von Heyden Pharma, Inc. Particular help concerning the organization has been given by Werner Kremer of Squibb-Von Heyden Pharma.

Fungal diseases have been with us from antiquity; interest in the chemo therapy of fungal disease has exploded in the past decade. To plan and pro duce a book on the topic of antifungal chemotherapy has come as a personal challenge - and something of an eye-opener - towards the end of my re search career. A landmark publication which still merits reading is Antifungal Chemotherapy (John Wiley & Sons, Chichester, UK), edited by David Speller, which appeared in 1980. However, the fact that ketoconazole, the first of the modern, orally active, wide-spectrum antifungals, attracted no more than two sentences in it indicates just how far we have come in the 1980s. A steady stream of original papers and a number of conference proceedings have chronicled this progress in drug research; outstanding among the latter are the proceedings of an international telesymposium, entitled Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents, edited by Robert Fromtling (J.R. Prous, Barcelona, 1987) and volume 544 of the Annals of the New York Academy of Sciences, entitled Antifungal Drugs, edited by Vassil St. Georgiev, and containing papers and posters presented at a most enjoyable 3-day conference held at Garden City, New York, in the autumn of 1987."

Whether or not an mRNA is translated is often thought to be a simple function of its steady-state concentration and the ab- sence of inhibitory proteins or RNA structures in the 5' and 3' noncoding regions. The articles presented in this volume show an unexpected flexibility of the eukaryotic translational appara- tus in the mechanism of translational initiation and provide new opportunities for regulation. Most or all mRNA molecules synthesized by RNA poly- 7 merase II in eukaryotic cells contain a 5' terminal mGpppG dinucleotide, also known as the "cap structure. " RNAs carrying a cap structure have been shown to be more resistant to attack by exoribonucleases than their uncapped counterparts. Further- more, the cap facilitates transport of the RNAs from the nucleus to the cytoplasm. In the cytoplasm, the cap functions as a binding site for the cap binding protein complex eIF-4, which enhances the translation of the RNAs by the eukaryotic trans- lational apparatus. Specifically, it has been postulated that bind- ing of e1F-4 to the 5' terminal cap facilitates the recruitment of ribosomal subunits onto the mRNAs via their free 5' ends (cap- dependent translation). Accordingly, uncapped RNAs are generally translated more poorly than capped RNAs. However, during the past 6 years both viral and cellular mRNAs have been discovered that can be translated cap-independently.

By their powers of reason scientists will be able to extract from nature the answers to their questions. From: Critique of Pure Reason, 1781 Immanuel Kant (1724-1804), German Philosopher History is a composite of stories. The history of the biological disciplines has been written by all those who opened the gates of new knowledge by generating ideas and the experiments to support them. Previous authors have attempted various approaches to the history of virology, as is reflected in the numerous books and book-series issuing from the publishing houses. This volume is an attempt at a compre hensive yet compact survey of virology, which has meant penetrating the rigid limits of the separate disciplines of biology in which virologists have worked. Writing this history of experimental virology was really a search for the origins and for vital signposts to portray the wide scope of the knowledge attained thus far. This was done in com plete awareness of the fact that every presentation depends heavily upon the perspective of the observer, and of necessity communi cates only a part of the whole. The present scientific story hopes to recount the most important knowledge achieved during this past century - the first century of the exciting developments in virology."

The growing concern about where energy rich chemicals for the future will come from has stimulated a resurgence of interest in the potentialities of microbial fermentations to assist in meeting anti cipated demands for fuels and chemicals. While much attention has been given recently to the early deployment of alcohol production plants and similar currently available technologies, the potential future developments have received much less attention. One of the intentions of the present symposium was to look ahead and try to perceive some of the prospects for future fermentation technology. In order to accomplish this, a symposium program of sizable diversity was developed with workers giving a representative cross section of their particular specialty as an indicator of the status of basic information in their area. In addition, an attempt was made to elicit from the various participants the types of fundamental infor mation which should be generated in the coming years to enable new fermentation technology to proceed expeditiously. In organizing the symposium particular effort was made to involve workers from the academic, industrial and governmental scientific communities."

This book resulted from presentations at an international conference on bacterial p1asmids held January 5-9, 1981 in Santo Domingo, Dominican Republic. This was the first meeting of its kind in the Southern Hemisphere. The meeting place was selected for its relaxed and comfortable climate, conducive to interactions among participants. More importantly the locale facilitated the participation of nearby Latin American clinical and research scientists who deal directly with the health manifestations of pathogenic p1asmids. Diseases and socio-economic practices of developing countries exist in the Dominican Republic whose scientific community could directly benefit from having the meeting there. The book includes the talks as well as extended abstracts of poster presentations from the meeting. This combination, which provides readers with reviews as well as recent findings, captures the full scientific exchange which took place during the 5-day meeting. As one indication of pathogenicity related to p1asmids, the conferees were surveyed for gastro-intestina1 problems during and after their stay in the Dominican Republic. The results are summarized at the end of this book.

What do the following have in common: the promise of Botox as the key to everlasting youthful looks; E. coli O157 hamburger disease; a mysterious illness which killed 35 heroin users in 2000; and the assassination by poisoned umbrella-tip of a Bulgarian dissident in the 1970s? The answer is that all of these are caused by toxins, the powerful biological poisons released by bacteria and some plants.
In Toxin, Alistair Lax reveals the panoply of ways in which bacterial toxins overcome the defenses of our cells. He explains how they work, how they are so successful in causing major diseases, the terrible human impact they have had, and how apparently "new" diseases arise from them. He also discusses how we can combat toxins, and how we can harness their actions for beneficial purposes. Enlivened by the very human story of the persistence, rivalries, and insights from which modern microbiology grew, Toxin is the first widely accessible account of this exciting and important topic.

This volume is not intended as review of the large literature on tumor antigenicity and efforts at tumor immunotherapy. Its pur pose, rather, is to present discursively an outline of the likely approaches to immunological intervention in neoplastic diseases which present themselves today, in light ofthe probable antigenic properties of cancer cells. References are cited only selectively, in illustration of some of the major considerations to which allusion is made and of some of the supportive evidence. No attempt is made at inclusiveness in the citation of concepts and fmdings. If undue emphasis appears to be given to some aspects of the litera ture and only sparse documentation to others, the grounds do not lie necessarily with a critical estimation of the extent or quality of reported work, but rather with the bias of the writer who consi ders stress on some facets of the field more appropriate than on others for elaboration of his arguments. The references brought in support of a given point are often intentionally varied, including both reports of original work and reviews, very recent observa tions and contributions that gave initial impetus to investigations, in an attempt to exemplify the pertinent literature; and reference is made both to data presented and to concepts advanced."

Since the first observations of viral interference with antigen presentation in the MHC class-I pathway, the field has advanced to a detailed analysis. We know numerous genes and for some of them we have profound information on their mechanistic function. The antigen presentation pathway is affected at all stages starting from proteasomal degradation of an antigenic viral protein, as shown for EBV, transfer of the proteasomal cleavage products as peptides in the ER by specific transporters, the loading of the nascent MHC class-I molecule, and finally the transport of the complex to the surface and presentation in a normal or deranged form. All these different steps of the MHC class-I antigen presentation pathway are targets for viral proteins. Not only MHC class-I but also MHC class-II proteins are a target of viral influence either by direct downregulation and degradation of proteins or by interference of signal transduction pathways.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

Venezuelan equine encephalitis (VEE) virus was first isolated in 1938 by Kubes and Rios (1) from the brain of a horse which died during an epizootic of a previously unrecognized disease in Venezuela. VEE-related viruses were subsequently isolated during t~e period of 1943-1963 in Venezuela, Colombia, Peru, Trinidad, Brazil, Surinam, Argentina, Panama, Mexico, and the United States (2) * Shope et ~. (3) fi rst defi ned the vi ru ses in the VEE comp 1 ex t-y showing serological relationships between classical VEE, ~lucambo, and Pixuna viruses. Young and Johnson (2) serologically characterized a variety of VEE isolates and proposed that the complex t>e divided into four subtypes (I, II, III, and IV). Viruses in subtype I were divided into five variants designated IA through IE. During 1069-1~71 a VEE epizootic-epidemic occurred in South America, Central America, and the United States involving a subtype lAB virus which caused high mortality among equines and human d i sea se (4). Venezuelan equine encephalitis viruses are alpha-togaviruses w~ic~ contain a positive strand rit>onucleic acid genome enclosed in an icosa~edral nucleocapsid. The virion has an envelope which contains blO glycoproteins: E2 of 5F,000 daltons (gp56) and E1 of ~O,OOO daltons (gp50) (5,6). Viral neutralization (N) and hemagglutiration (HA) sites have been placed on E2 by the use of monospecific rabtdt antisera and monoclonal antibodies specific for purified viral structural proteins (7-10). Only anti-E2 antisera neutralized virus infectivity or blocked virus hemagglutination.

Research on antiviral drugs and their mode of action in infected cells. in animals and in man. has led to a better understanding of the molecular pro cesses involved in virus replication. Screeninq of large numbers of natural and semisynthetic compounds resulted in the characterization of certain sub stances that had a limited efficiency as antiviral druqs. A few chemically synthesized compounds were also found to be effective as antiviral agents in the chemotherapy of human virus diseases. A major difficulty in the develop ment of effective antiviral agents has been the lack of selectivity. and toxicity for uninfected cells. of drugs that effectively inhibited virus replication in vitro. Further understanding of the molecular processes of virus replication in infected cells has resulted in the development of new antivirals directed at virus-coded enzymes or proteins. Recent studies on antivirals that are activated by the herpes simplex virus type l-coded thy midine kinase from a prod rug to an antiviral drug have opened new directions in the development of effective antiviral drugs. The present book deals with a number of antiviral drugs effective against herpes simplex viruses and provides some insight into the molecular aspects of virus replication. It also throws light on the new approaches to the development of antiviral drugs. The molecular basis of the antiviral activity of new and known drugs and their possible use in chemotherapy of viral disease are presented in this book."

Recent reviews of respiratory-tract affections caused by M. pneumoniae under- score the benign and often subclinical course of the infection. Severe pneumonia with a reticular or acinar pattern is certainly unusual and a fatal outcome is rare, but the incidence of both is underestimated. Erythromycin and tetracyclines are the first-choice antibiotics. There is evidence indicating the importance of im- munopathogenic mechanism in provoking pneumonia and even respiratory failure. REFERENCES 1. Krech U, Price PC, Jung M: The laboratory diagnosis and epidemiology of mycoplasma pneumoniae in Switzerland. Infection 4:33, 1976. 2. Fischman RA, Marschall KE, Kislak JW: Adult respiratory distress syndrome caused by mycoplasma pneumoniae. Chest 74:471, 1978. 3. Reigner Ph, Domenighetti G, Feihl F, Bonjour JPh, Perret CI: Syndrome de detresse respiratoire aigu sur infection a mycoplasme. Sch Med W 110:220, 1980. 4. Kaufman JM, Cuvelier CA, Van der Straeten M: Mycoplasma pneumonia with fulminant evolution into diffuse interstitial fibrosis. Thorax 35:140, 1980. 5. Murray HW, Masur H, Senterfit L, Roberts R: The protean manifestations of mycoplasma pneumoniae infection in adults. Am J Med 58:229, 1975. 6. Levine DP, Lerner AM: The clinical spectrum of Mycoplasma pneumoniae infections. Med Clin N Am 62:961,1978. 7. Twomey JA, Espir ML: Neurological manifestations and Mycoplasma pneumoniae infection. BMJ 2:832, 1979. 8. Kingston JR, Chankock RM, Mufson MA, Hellman LP, James WD, Fox HH, Mankoma C, Boyers J: Eaton agent pneumonia. JAMA 176:118, 1961.

Influenza virus is an important human pathogen, frequently causing widespread disease and a significant loss of life. Much has been learned about the structure of the virus, its genetic variation, its mode of gene expression and replication, and its interaction with the host immu nologic system. This knowledge has the potential of leading to ap proaches for the control of influenza virus. In addition, research on influ enza virus has led to important advances in eukaryotic molecular and cellular biology and in immunology. A major focus of this book is the molecular biology of influenza virus. The first chapter, which serves as an introduction, describes the structure of each of the genomic RNA segments and their encoded pro teins. The second chapter discusses the molecular mechanisms involved in the expression and replication of the viral genome. In addition to other subjects, this chapter deals with one of the most distinctive features of influenza virus, namely the unique mechanism whereby viral messenger RNA synthesis is initiated by primers deaved from newly synthesized host-cell RNAs in the nudeus. Among the most significant accomplish ments in influenza virus research has been the delineation of the three dimensional structure of the two surface glycoproteins of the virus, the hemagglutinin and neuraminidase. This has provided a structural basis for mapping both the antigenic sites and the regions involved in the major biological functions of these two molecules."

S. TRACY Late in the 1940s, a virus was isolated from a young patient with a flaccid par alysis in the sleepy Hudson River town of Coxsackie in the state of New York. Within the next few years, it was apparent that this and other similar viruses were not polioviruses but were indeed a new group of viruses, viruses that by the mid- 1950s had been found to be commonly associated with pediatric inflammatory heart disease. Two groups of coxsackieviruses (A and B) were differentiated on the basis of the type of paralysis induced in suckling mice by these viruses. Group B coxsackieviruses, because of their primacy as etiologic agents of human acute viral myocarditis and its relatively common sequela, dilated cardiomyopathy, are the focus of this volume. of the century approaches, the massive international effort to eradi As the end cate polioviruses through vaccination as causes of human disease has been success ful in the Western Hemisphere and in many parts of Europe, and it is expected that worldwide eradication may be achieved within the near future. While this is wonderful news, there are sadly no similar efforts being planned to combat the numerous other human enteroviruses that daily incur widespread morbidity and mortality throughout the world. While this is due in part to the lack of specific know ledge about the other human enteroviruses, it is also due to the perceptions of industry that there is insufficient profit to be made by developing these vaccines.

The pathology caused by baculoviruses in insect popula- tions was described centuries ago, notably in the larvae of insects such as the silkworm (Bombyx mori) which has been appreciated for the quality and beauty of its products. In the 1940s baculoviruses and their structure and physiolo- gy were intensively investigated, particularly by Bergold's group in Tiibingen. The following decades saw excellent progress, laying a solid virological base for later investiga- tions on the system. Further studies mushroomed in the 1970s with the advent of tissue culture systems for insect cells which eventually facilitated the molecular biological approach that came to the fore in the 1980 s. One of the reasons for pursuing research on the baculo- virus system was the prospect of eventually using these vi- ruses as insect pest control agents. While this practical as- pect may appeal to many, molecular biologists had addi- tional reasons to be interested in baculoviruses. Here was a large DNA viral genome, probably fraught with problems of replication and regulation that hopefully would open inroads into the molecular biology of interesting insect cell systems. In the days when genetechnology promises laurels, and after several virus systems had been skilfully exploited as highly efficient eukaryotic expression vectors, it came as no surprise that baculoviruses were also investigated in that respect. Indeed, the Autographa californica nuclear po- lyhedrosis virus became a good vector. Insect cells also seem to collaborate in modifying and processing the gene- technologically synthesized polypeptides.

For medical scientists, biologists and geographers interest- ed in geomedical problems the helminthiases can be a fas- cinating object of research. Their distribution is due to the in part very complicated parasite life cycles which fre- quently depend on the presence of intermediate hosts. The search for the causes of the distribution of helminthiases requires to take into account not only such geofactors as affect the parasite developmental stages outside man but go beyond this and include the entire web of factors which contribute to the conditions for the distribution of their in- termediate hosts. Last, but by no means least, it is, however, man who through his customs and habits, his settlements and dwellings, his population density and, above all, his interference in the environment, determines the distri- bution of helminthiases. The frequency, persistence and areal expansions are a consequence of the interplay and in- teraction of all the geofactors. The aim of every geomedi- cal analysis must be to prove the causes of their distri- bution through a chain of causation which has no gaps. A classic example of such a chain had already been set out in the 1920s when Ernst Rodenwaldt investigated the occur- rence of brugiasis in the Serajoe Delta on Java, and it is Rodenwaldt's analysis which has served as a model for this work. The idea of producing the monograph presented here arose from the Geomedical Monograph Series edited by Helmut 1. Jusatz.

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."