Hantaviruses are found world-wide and are associated with two severe disease syndromes, hemorrhagic fever and hantavirus pulmonary syndrome. The recent studies in this volume provide a basis for understanding the high human pathogenicity of theses viruses and their continued maintenance and transmission within rodent populations.

The Liver in Biology and Disease was conceived as a sequel in the series "Principles of Medical Biology," whose general aim continues to be the integration of human biology and molecular cell biology into modern molecular medicine. It is a volume molded by the Information Revolution which few will deny has forced the teaching faculties in our medical schools to curtail and prune the teaching load and focus on fundamentals and principles. With this intention in mind, a volume of this nature takes into account the close dependence of progress in the medical sciences on bioinformatics (gene and protein analysis) or more precisely, computational biology and of course, the Internet. In general, it follows the pattern of its predecessors.
*Chapters are illustrated with numerous figures and references are current
*Clear, concise and accurate text about a large number of liver diseases
*Describes the liver's histology, biochemistry, and pathology in molecular terms

Virus Variability and Impact on Epidemiology and Control of Diseases E. Kurstak and A. Hossain I. INTRODUCTION An important number of virus infections and their epidemic developments demonstrate that ineffec tiveness of prevention measures is often due to the mutation rate and variability of viruses (Kurstak et al., 1984, 1987). The new human immunodeficiency retroviruses and old influenza viruses are only one among several examples of virus variation that prevent, or make very difficult. the production of reliable vaccines. It could be stated that the most important factor limiting the effectiveness of vaccines against virus infections is apparently virus variation. Not much is, how ever, known about the factors influencing and responsible for the dramatically diverse patterns of virus variability. II. MUTATION RATE AND VARIABILITY OF HUMAN AND ANIMAL VIRUSES Mutation is undoubtedly the primary source of variation, and several reports in the literature suggest that extreme variability of some viruses may be a consequence of an unusually high mutation rate (Holland et al., 1982; Domingo et al., 1985; Smith and Inglis, 1987). The mutation rate of a virus is defined as the probability that during a single replication of the virus genome a particular nucleotide position is altered through substitution, deletion, insertion. or recombination. Different techniques have been utilized to measure virus mutation rates, and these have been noted in the extent of application to different viruses."

The oral cavity supports a rich and diverse microbial population. Oral health is dependent on the maintenance of stable microbial communities; disease occurs when this balance is disturbed and more pathogenic species outgrow the commensals. Health and disease in the mouth are active processes in which the ecology of communities, not of single organisms, is paramount. In this book, expert contributors from around the world provide an update on recent developments in the burgeoning field of oral microbial ecology. The chapters are arranged into five sections: microbial populations in oral biofilms, the structure of oral biofilms, communication and sensing within biofilms, health to disease, and new approaches for oral biofilm control.

-Integration of Systems Biology with Bioprocess Engineering: L-Threonine Production by Systems Metabolic Engineering of Escherichia Coli, By Sang Yup Lee and Jin Hwan Park; -Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum, By Christoph Wittmann; -Systems Biology of Industrial Microorganisms, Marta Papini, Margarita Salazar, and Jens Nielsen; -De Novo Metabolic Engineering and the Promise of Synthetic DNA, By Daniel Klein-Marcuschamer, Vikramaditya G. Yadav, Adel Ghaderi, and Gregory N. Stephanopoulos; -Systems Biology of Recombinant Protein Production in Bacillus megaterium, Rebekka Biedendieck, Boyke Bunk, Tobias Furich, Ezequiel Franco-Lara, Martina Jahn, and Dieter Jahn; -Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering; By Jurgen Seibel, Hans-Joachim Jordening, and Klaus Buchholz; -Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds; By Andrea Weckbecker, Harald Groger, and Werner Hummel;

This book tackles the difficult challenge of uncovering the pathogenic cause, epidemiological mechanics and broader historical impacts of an extremely deadly third-century ancient Roman pandemic. The core of this research is embodied in a novel systems synthesis methodology that allows for ground-breaking historical-scientific problem-solving. Through precise historical and scientific problem-solving, analysis and modelling, the authors piece together a holistic puzzle portrait of an ancient plague that is fully consistent, in turn, with both the surviving ancient evidence and the latest in cutting edge twenty-first-century modern medical and molecular phylogenetic science. Demonstrating the broader relevance of the crisis-beset world of the third-century Roman Empire in providing guiding and cautionary historical lessons for the present, this innovative book provides fascinating insights for students and scholars across a range of disciplines.

Biologically active compounds isolated from microorganisms continue to be vital to the development of new drugs and agricultural chemicals. This book was prepared by current and past members of the laboratory of Dr. Satoshi Omura of the Kitasato Institute in Japan. Dr. Omura and his colleagues have discovered and studied a number of important antibiotics, and in their work they have pioneered new methods for screening microbes for interesting and important compounds. This book presents strategies and methods for identifying novel molecules with several types of biological activity. In addition, the book discusses the identification of microbial compounds of agrochemical importance, presents information on chemical screening methods, and concludes with chapters on microbial strain selection, fermentation technology, and genetic engineering of antibiotic-producing microorganisms. This book will be of great interest to scientists working in the very active and competitive fields of antibiotic and agrochemical discovery.

Authoritative investigators active in the discovery, development, and application of biological anti-infective agents concisely review their use and potential in preventing and treating human disease. Focusing on biotherapeutic entities that have been tested in controlled studies, the prominent experts illuminate the scientific underpinnings of their therapeutic power, assess their possible risks in the treatment of infectious diseases, and outline the research needed to better define their effectiveness. In addition, they also consider how biotherapeutic agents may be genetically engineered for maximum intestinal and vaginal production of bioactive substances in vivo. Biotherapeutic Agents and Infectious Diseases brings together all the evidence needed to understand and capitalize on the considerable promise of this significant new class of biotherapeutic entities.

In this new volume of the globally recognized Forensic Pathology Reviews, Dr. Michael Tsokos has gathered chapters from the top experts in the field to reveal both the applied and scientific areas of expertise along the broad spectrum of forensics studies. Volume 5 piques the mind as leading forensic pathologists from the United States and around the world offer advanced insight into death caused environmental conditions, trauma, neuropathology, natural causes, and ballistics. The authors of this volume further their exploration as they impart research related to identification, serial murder, histopathology, and age estimation. While unveiling unsurpassed and cutting-edge knowledge, Forensic Pathology Reviews, Volume 5 will also inspire emerging forensic scientists to immerse themselves in innovative research. Written for: Forensic pathologists and scientists

Years ago when we were asked to write a book on the present-day knowledge of the molecular biology of poliovirus, we did not expect that such an apparently simple task could involve so much time and effort. Our writing was hampered by the fact that both of us are full time "workers," so that this monograph is mainly a spare time expedience. The main attention of this book focuses on a detailed review of the molecular biology of poliovirus and especially on the advances of the last decade; medical and environmental aspects are only briefly mentioned. Observations from older studies are considered in view of more recent information. Some of the older ob servations provided fundamental insights and paved the way for present day research; too often such data has been neglected or independently rediscovered. Today, poliovirus research has again attracted considerable interest. High points gained within the last few years were the elucidation of the complete nucleotide sequences of the RNAs of the three poliovinls serotypes and the corresponding vaccine strains, the demonstration of genome evolution during transmission of poliovirus in an epidemic, further characterization of the antigenic sites on the virus particle and of the antigenic drift, characterization of alternate conforma tional states of the virion capsid, the development of monoclonal antibodies against some of the virus proteins, observations on the role of the plasma membrane, cytoskeleton, and cytoplasmic membranes as mediators in the virus induced redirection of the synthetic machinery of the host cell, and characteriza"

The ability to remember an antigenic encounter for several decades, even for a life time, is one of the fundamental properties of the immune system. This phenomenon known as "immunological memory," is the foundation upon which the concept if vaccination rests. Therefore, understanding the mechanisms by which immunological memory is regulated is of paramount importance. Recent advances in immunology, particularly in the field of innate immunity, suggest that the innate immune system plays fundamental roles in influencing immunological memory. Indeed, emerging evidence suggests that events that occur early, within hours if not minutes of pathogen or vaccine entry profoundly shape the quantity, quality and duration of immunological memory. The present volume assembles a collection of essays from leading experts that span the entire spectrum research from understanding the molecular mechanisms of innate immune recognition, to dendritic cell function, to the generation and maintenance of antigen-specific B and T-cell responses.

There is a high demand for antimicrobials for the treatment of new and emerging microbial diseases. In particular, microbes developing multidrug resistance have created a pressing need to search for a new generation of antimicrobial agents, which are effective, safe and can be used for the cure of multidrug-resistant microbial infections. Nano-antimicrobials offer effective solutions for these challenges; the details of these new technologies are presented here.

The book includes chapters by an international team of experts. Chemical, physical, electrochemical, photochemical and mechanical methods of synthesis are covered. Moreover, biological synthesis using microbes, an option that is both eco-friendly and economically viable, is presented. The antimicrobial potential of different nanoparticles is also covered, bioactivity mechanisms are elaborated on, and several applications are reviewed in separate sections. Lastly, the toxicology of nano-antimicrobials is briefly assessed."

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

The result of modern pathological research, this book offers quickly accessible and clearly arranged information on the 29 most important diseases that belong to the complex of rheumatic diseases: It includes clinical features, helpful marginal notes, an extensive subject index, a comprehensive bibliography, and approximately 300 illustrations, most of which are light, electron, or scanning electron micrographs. The reader is presented with a useful basis for diagnostic considerations and therapeutic decisions. By intensively analysing disease processes and their stuctures and by integrating modern immunological and molecular biological knowledge, the author has succeeded in providing the different pathological entities with a more distinct profile. New results have been achieved, particularly in the fields of Rheumatoid Arthritis, Seronegative Spondarthritides, and Osteoarthritis.

Over the past ten years, many powerful new techniques have been developed that have dramatically changed malaria research. The second edition of" Malaria: Methods and Protocols" expands upon the previous edition with current, detailed techniques for laboratory research. With new chapters on parasite culture techniques, genome manipulation methods, 'omic' approaches, and techniques for studying the biology of the red blood cell and pre-erythrocytic stages of" Plasmodium." Written in the highly successful" Methods in Molecular Biology " series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, "Malaria: Methods and Protocols, Second Edition," offers a comprehensive set of standard techniques for laboratory researchers."

This book provides a detailed overview of the current state of knowledge regarding the pathophysiology of both primary headaches - migraine, tension-type headache (TTH), and cluster headache - and the very important and frequent type of secondary headache, medication overuse headache (MOH). After an introductory chapter describing relevant neuroanatomy and vascular anatomy, the evidence gained from animal models regarding the pathophysiology of migraine and the other primary headaches is reviewed. Knowledge of the genetic component in the different types of headache is then examined with reference to recent evidence, for example regarding the implication of the trigeminovascular system and cortical spreading depression in migraine. Detailed information is provided on insights into primary headaches from imaging studies, including functional magnetic resonance imaging and positron emission tomography and on their neurophysiology and biochemistry. A further series of important chapters describe present knowledge of the pathophysiology of each specific type of headache and consider future directions. Written by acknowledged experts in their fields from Europe and the United States, clinicians and students will find Pathophysiology of Headaches to be an excellent source of up-to-date information on why patients experience headaches. In addition, it will be of value for pain researchers investigating the underlying mechanisms of headache.

The International Symposium on Frontiers in Microbiology has been de dicated to Prof. P. De Somer, whom I succeeded shortly after his death on 17 June 1985 as Rector of this now more than 560-year old University. When Prof. De Somer became the head of the University he started to remodel it, giving our old Alma Mater a more transparent administrative structure, strengthening its scientific and cultural autonomy, and establishing close links with the most prestigious national and foreign institutions. This made De Somer to one of the greatest, if not the greatest, of rectors in the history of Belgian Universities. He was a great leader, a perfect organizer, a clever negotiator, and a brilliant orator. In his speeches one immediately sensed his intuitive cognition and witty evaluation of the values of life. He knew perfectly well how to persuade the unwilling and to disenchant the illusionist. Sometimes a visionary himself, he would not pursue his ideas unless there was a chance of success. As innovative Prof. P. De Somer was in providing to this University a new face, or should I say facelifting, as international is his reputation as the founder, and, since its inception, only director, of the Rega Institute. Built now more than 30 years ago, the Rega Institute has re mained one of the world's leading centers in microbiological research."

"Corynebacterium diphtheriae" is the classical etiological agent of diphtheria and the type strain of the genus "Corynebacterium." While diphtheria of the respiratory tract became rare with the introduction of vaccination programs in industrialized countries, even today several thousand cases per year are reported to the World Health Organization. This shows that diphtheria is not completely eradicated and that reservoirs exist. The book summarizes the latest advances made in understanding "C. diphtheriae" and the closely related species "Corynebacterium ulcerans" and" Corynebacterium pseudotuberculosis." Topics addressed are genomics of toxigenic corynebacteria, host-pathogen-interaction, detection, surveillance and treatment as well as application aspects.

Antimicrobial Peptides: Challenges and Future Perspectives covers the latest developments about antimicrobial peptides in the scenario of drug resistance. The book is divided into 16 chapters arranged in sequence and preceded by chapters on historical developments and their role as regulatory molecules in innate defense mechanism. Emphasis is given to purification techniques and characterization suitable for interdisciplinary research. Chapters provide an inventory of various antimicrobial peptides, from a diverse array of organisms such as bacteria, fungi, insects, amphibians, plants and mammals. A section on marine ecosystem broadens readers understanding on marine based antimicrobial peptides. Additional sections provide an informative overview on peptides with antiviral properties and those targeting multi-drug resistant bacteria. Recent reports and mechanism on resistance against antimicrobial peptides are also provided, along with key insights into the challenges and future perspectives of peptide drug development.

This book intensively examines the efficacy of plant-derived products that have been used for over a thousand years by practitioners of so-called Traditional Chinese Medicine in the light of recent chemotherapeuticals. The chapters were written by renowned Chinese medical researchers and are supplemented by results obtained in German antiparasitic research projects. Parasites and emerging diseases are a major threat of our time, which is characterized by an enormous increase in the size of the human population and by an unbelievably rapid globalization that has led to the daily transport of millions of humans and containers with goods from one end of the earth to the other. Furthermore the slow but constant global warming offers new opportunities for many agents of diseases to become established in new areas. Therefore it is essential that we develop precautions in order to avoid epidemics or even pandemics in overcrowded megacities or at the large-scale farm animal confinements that are needed to secure a steady flow of food in the crowded regions of the world. Of course intensive research in the field of chemotherapy since 1900 has produced unbelievable breakthroughs in therapies for formerly untreatable and thus deadly diseases. However, a large number of untreatable diseases remain, as well as a constantly growing number of agents of disease that have developed resistances to standard chemical compounds. As such, it is not only worthwhile but also vital to consider the enormous amounts of information that have been obtained by human "high cultures" in the past. Examples from the past (like quinine) or present (like artemisinin, a modern antimalarial drug) show that plant extracts may hold tremendous potential in the fight against parasites and/or against vector-transmitted agents of diseases.

Antiviral chemotherapy has come of age, and, after an initial slow pro gress, the development of new antiviral agents has proceeded at a more rapid pace and the perspectives for their clinical use have increased considerably. Now, 25 years after the first antiviral assay (idoxuridine) was introduced in the clinic, it is fitting to commemorate the beginning of the antivirals' era. In its introductory chapter B.E. Juel-Jensen touches on what may be con sidered as five of the most fundamental requirements of an antiviral drug: efficacy, relative non-toxicity, easy solubility, ready availability and rea sonable cost. Surely, the antiviral drugs that have so far been used in the clinic could still be improved upon as one or more of these five essential demands are concerned. How is all began is narrated by W.H. Prusoff. The first antiviral drugs to be used in humans were methisazone and idoxuridine, the former, which is now of archival interest, in the prevention of smallpox, the latter, which was approved for clinical use in the United States in 1962, for the topical treatment of herpetic keratitis. In terms of potency, also because of solubility reasons, idoxuridine has been superseded by trifluridine in the topical treatment of herpes simplex epithelial keratitis. H.E. Kaufman did not find trifluridine or acyclovir ef fective in the treatment of deep stromal keratitis or iritis and he reckons that other antiviral drugs (i.e. bromovinyldeoxyuridine) would not be effec tive either."

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.