Alessandro Condivilla of Bologna first attempted a resection of the head of the pan creas in 1898, but several decades of further trial-and-error attempts ensued before the prototype procedure of pancreatoduodenectomy (PD) was established by Whipple in 1935. In the half-century following that landmark, refinements of surgical technique, including pancreatico-and bilio-entero anastomosis as well as develop ment of new technology to support perioperative management and patient care have contributed to the decrease in mortality and morbidity rates for obstructive jaundice and pancreatic fistula. The improvement in mortality and morbidity rates associated with PD has led to an increase in the number of patients undergoing the procedure and in the number of institutions performing it. Indications for PD have also been expanded. In the early years after PD was established as a viable procedure, periampullary carcinoma was the most common indication; now PD is indicated for a number of benign and malignant diseases. Some surgeons believe that PD is the procedure of choice for certain types of chronic pancreatitis, pancreatico-biliary maljunction, and pancreatic and duodenal trauma. Other surgeons have reported the necessity of PD for lymph node dissection of gallbladder carcinoma. Consequently, the basic procedure has been greatly modi fied to accommodate the specific conditions of each disease. For patients with malig nancy, extended procedures have been developed to improve the curative resection rate and ensure complete lymph node dissection.

This book will assemble the views of many of the world's experts in the field of viruses and diabetes. It will look critically at some unanswered questions, in the field. Among these, How do viruses destroy or modify the pancreatic islet? Which viruses are involved? What is the role of virus-induced cytokines> Could vaccines prevent virus-induced diabetes? Until recent technological advances, progress in the understanding of the relationship between viruses and diabetes has been hampered. New technologies are helping shed new light on these mysteries. This will be the first comprehensive volume on this topic.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

This collection of translations of some of Koch's important essays represents an important first. It includes three of his essays on anthrax, three on tuberculosis, two on cholera, one on wound infections, and a relective essay entitled "On Bacteriological Research." These papers clearly reflect the coherence and inter-connectedness of Koch's thought. They include the initial presentation of his ideas and also provide examples of his tenacious and devasting responses to his critics. While they only represent some of the many areas of Koch's interests, they serve as excellent samples of his finest contributions. The volume also includes a long introduction which establishes the historical context of Koch's work and of the particular essays translated here.

Learn the what, how, and why of pathophysiology! With easy-to-read, in-depth descriptions of disease, disease etiology, and disease processes, McCance and Huether's Pathophysiology: The Biologic Basis for Disease in Adults and Children, 9th Edition helps you understand the most important and most complex pathophysiology concepts. This updated text includes more than 1,300 full-color illustrations and photographs to make it easier to identify normal anatomy and physiology, as well as alterations of function. It's the most comprehensive and authoritative pathophysiology text available! Unparalleled coverage of pathophysiology content makes this the most comprehensive and authoritative pathophysiology text on the market. Consistent presentation of diseases includes pathophysiology, clinical manifestations, and evaluation and treatment. Over 1,300 full-color illustrations and photographs depict the clinical manifestations of disease and disease processes ? more than in any other pathophysiology text. Algorithms and flowcharts of diseases and disorders make it easy for you to follow the sequential progression of disease processes. Lifespan content includes ten separate pediatric chapters and special sections with aging and pediatrics content. Coverage of rare diseases and epigenetics further explores genetic disease traits. Obesity and Nutritional Disorders chapter thoroughly covers these growing global concerns. Chapter summary reviews provide concise synopses of the main points of each chapter. More than 30 3D animations on the companion Evolve website bring difficult concepts to life for a new perspective on disease processes. NEW! More than 50 new or revised illustrations visually reinforce pathophysiology concepts. NEW! Emerging Science boxes highlight the most current research and clinical developments.

One Health is an emerging concept that aims to bring together human, animal, and environmental health. Achieving harmonized approaches for disease detection and prevention is difficult because traditional boundaries of medical and veterinary practice must be crossed. In the 19th and early 20th centuries this was not the case then researchers like Louis Pasteur and Robert Koch and physicians like William Osler and Rudolph Virchow crossed the boundaries between animal and human health. More recently Calvin Schwabe revised the concept of One Medicine. This was critical for the advancement of the field of epidemiology, especially as applied to zoonotic diseases. The future of One Health is at a crossroads with a need to more clearly define its boundaries and demonstrate its benefits. Interestingly the greatest acceptance of One Health is seen in the developing world where it is having significant impacts on control of infectious diseases. "

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs). This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade. The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer's diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis and neuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

Scientists often look askance at their colleagues whose research appears too strongly focused on a single gene or gene product. We are supposed to be interested in the "big picture" and excessive zeal in pursuit of a single pixel might seem to border on an obsession that is likely to yield only details. However as this volume of Current Topics in Microbiology and Immunology demonstrates, this is certainly not the case for myc. Intense study of this en- matic proto-oncogene over the last twenty years has only broadened our view of its functions and led to insights into mechanisms relating to transcriptional regulation as well as to cell growth, proliferation, differentiation, apoptosis and organismal development. The myc gene originally came to light as a retroviral oncogene (v-myc) associated with a wide range of acute neoplasms. It was later shown to be a virally transduced cellular gene (c-myc) which is a member of family of on- genes (c-myc,N-myc,L-myc). These family members are themselves subject to a bewildering assortment of genetic rearrangements associated with many different types of tumors derived from many different types of cells. These rearrangements (including chromosomal translocation, viral integration, and gene ampli?cation) act to uncouple expression of the myc family genes from their normal physiological regulators. The chapter by LIU and LEVENS - scribes the key pathways leading to regulation of myc expression, showing that such regulation occurs at several different levels and through multiple mechanisms.

In recent years, the development of new molecular biology tools and the elucidation of whole genome sequences have revolutionized research on pathogenic fungi. Such advances have led to the development of faster, more reliable, diagnostic techniques for medically important pathogens such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. In addition, they have led to a major breakthrough in the approach for the generation of novel anti-fungal agents. Now it is possible to search for agents that target essential genes. Research in this area has never been more exciting. In this book, a panel of expert international mycologists critically review the most important cutting-edge topics. Chapters are written from a molecular and genomic perspective, and through the provision of extensive reference sections positively encourage readers to pursue the subject in greater detail. Topics include: gene expression and regulation, heterozygosity in Candida, molecular diagnosis

Many new antileukotriene drugs are now marketed as antiasthma drugs and represent the first new drugs in this field since the 1970s. This book covers the steps that have led to the discovery and development of these new drugs and offers detailed descriptions of their clinical applications. The review chapters on the main aspects of basic and applied leukotriene research are written by leading specialists in the field, and the volume takes a new approach in presenting information of particular interest to both scientists and clinicians in the fields of asthma, inflammation and allergic diseases.

A practical hands-on bench book covering difficult areas of autopsy for the modern pathologist. Rutty's book is unique - chapters deal with issues never previously discussed and have been specifically selected to fill a gap in the market, not just re-hash old ideas.

Designed for consultants and trainees alike, not only pathologists of all types but also non-medics involved with the dead in any way - lawyers, police, bereavement officers, undertakers. The first volume has become a reference aid to autopsy issues for all grades of lawyers. Thus the audience that the book reaches is greater than a pure autopsy or forensic pathology textbook.

The era of molecular pathology has arrived. From its promising beg- nings in research laboratories, the field has grown, and continues to grow, to become a vital part of the care of an ever-increasing number of patients. Because of its recent emergence from the research taboratory, many molecuIar pathology protocols we still to be found in the primary litcramre, and have not appeared in a text. MO~PCU~Q~ Padhoiogy Protocob contains la- ratory protocoIs that have been developed by many of the authors for use in clinical molecular pathology laboratories and describe in detail Row to perform these assays. This book is therefore intended for clinical laboratory use by medical technologists and pathologists. It will dso be of interest to research workers who are performing these assays. In its broadest meaning, pathology is the study of disease, and therefore it follows that any disease for which the molecular basis is understood would be suitable as a topic for inclusion in this work. When seiecting protocols, it was necessary to place limits on the number of chapters that could be feasibly presented in a single work. Those protoculs that were selected are performed more frequently, or have achieved recognition as having important diagnostic utility in contemporary practice. A decision was made to exclude inherited genetic diseases with certain exceptions, such as those diseases that are associated with thrombotic states and are part of the traditional dumain of pathology.

The discovery of wide-spread RNA-based regulation in bacteria has led to new evaluations of the importance of bacterial regulatory RNA in every aspect of bacterial physiology. In Bacteria Regulatory RNA: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study bacterial regulatory RNA. These include methods and techniques to identify regulatory RNAs, characterizing the function and expression of regulatory RNAs in bacterial cells, RNA structure prediction, and interactions between regulatory RNAs and proteins. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Bacteria Regulatory RNA: Methods and Protocols seeks to aid scientists in the further study of bacterial regulatory RNA.

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

In eukaryotic cells, the nuclear genome and its transcriptional apparatus is separated from the site of protein synthesis by the nuclear envelope. Thus, a constant flow of proteins and nucleic acids has to cross the nuclear envelope in both directions. This transport in and out of the nucleus is mediated by nuclear pore complexes (NPCs) and occurs in an energy and signal-dependent manner. Thus, nucleocytoplasmic translocation of macro molecules across the nuclear envelope appears to be a highly specific and regulated process. Viruses that replicate their genome in the cell nucleus are therefore forced to develop efficient ways to deal with the intracellulZlr host cell transport machinery. Historically, investigation of Polyomavirus replication allowed identification ofsequences that mediate nuclear import, which led subsequently to our detailed understanding of the cellular factors that are involved in nuclear import. Transport ofmacromolecules in the opposite direction, however, is less well understood. The investigation of retroviral gene expression in recent years pro vided the first insights into the cellular mechanisms that regulate nuclear export. In particular, the detailed dissection of the function of the human immunodeficiency virus type I (HIV-I) Rev trans-activator protein identified CRMI, as a hona fide nuclear export receptor. CRM I appears to be involved in the nucleocytoplasmic translocation of the vast majority of viral and cellular proteins that have subsequently been found to contain a Rev-type leucine-rich nuclear export signal (NES)."

This volume provides an overview of the latency strategies developed during the estimated 200 Myears long coevolution of Alpha-, Beta- and Gammaherpesvirinae and their host species. The main emphasis is on herpesviruses infecting humans. However, relevant cases if herpesviruses infecting animals are covered as well. Special emphasis is drawn on results on molecular mechanisms regulating latent promoters of herpesvirus genomes and signals and molecular pathways resulting in reactivation of latent viral genomes. To balance the volume, epigenetic mechanisms (DNA methylation, histone modification, chromatin structure) involved in cell type specific expression of growth-transformation-associated Gammaherpesvirus genes will also be discussed at length)

Post-mortems may have become a staple of our TV viewing, but the long history of this practice is still little known. This book provides a fresh account of the dissections that took place across early modern Europe on those who had died of a disease or in unclear circumstances. Drawing on different approaches and on sources as varied as notes taken at the dissection table, legal records and learned publications, the chapters explore how autopsies informed the understanding of pathology of all those involved. With a broad geography, including Rome, Amsterdam and Geneva, the book recaptures the lost worlds of physicians, surgeons, patients, families and civic authorities as they used corpses to understand diseases and make sense of suffering. The evidence from post-mortems was not straightforward, but between 1500 and 1750 medical practitioners rose to the challenge, proposing various solutions to the difficulties they encountered and creating a remarkable body of knowledge. The book shows the scope and diversity of this tradition and how laypeople contributed their knowledge and expectations to the wide-ranging exchanges stimulated by the opening of bodies.

Molecular diagnostic procedures have been described in a number of recent books and articles. However, these publications have not focused on virus detection, nor have they provided practical protocols for the newer molecular methods.
Written by the inventors or principal developers of these technologies, Molecular Methods for Virus Detection provides both reviews of individual methods and instructions for detecting virus nucleic acid sequences in clinical specimens. Each procedure includes quality assurance protocols that are often ignored by other methodology books. Molecular Methods for Virus Detection provides clinically relevant procedures for many of the newer diagnostic methodologies.
Key Features
* Provides state-of-the-art PCR methods for amplification, quantitation, " in situ" hybridization, and multiplex reactions
* Goes beyond PCR with protocols for 3SR, NASBA, LCR, SDA, and LAT
* Covers important virus detection methods such as "in situ" hybridization; Southern, dot, and slot blots; branched chain signal amplification; and chemiluminescence
* Includes quality control information crucial in research and clinical laboratories
* Most chapters are written by the inventors and principal developers of the methodologies
* Includes color plates, 77 figures, and 18 tables

Since penicillin and salvarsan were discovered, a number of new drugs to combat infectious diseases have been developed, but at the same time, the number of multi-resistant microorganism strains is increasing. Thus, the design of new and effective antibacterial, antiviral and antifungal agents will be a major challenge in the next years. This book reviews the current state-of-the-art in antimicrobial research and discusses new strategies for the design and discovery of novel therapies. Topics covered include the use of genetic engineering, genome mining, manipulation of gene clusters, X-ray and neutron scattering as well as the antimicrobial effects of essential oils, antimicrobial agents of plant origin, beta-lactam antibiotics, antimicrobial peptides, and cell-wall-affecting antifungal antibiotics.

The OHOLO conferences are sponsored by the Israel Institute for Biological Research and take their name from the site of the ?rst meeting on the shores of Lake Kinnereth. The purpose of these meetings is, as it was at their inception over 50 years ago, "to foster interdisciplinary communication between scientists in Israel, and to provide added stimulus by the participation of invited scientists from abroad". The core of the organizers of the OHOLO conferences are scientists from the Israel Institute for Biological Research. From time to time a particular OHOLO conference cooperates with an international scienti?c organization. The present 46th OHOLO Conference marks the resumption of the OHOLO tradition after 8 years of interruption caused by events beyond our control. It is my belief that our uncomp- mising commitment to excellence in research and development in the various areas of science in Israel is essential to our survival in this troubled region. The OHOLO conference tradition is a re?ection of this conviction. The present 46th OHOLO Conference entitled: The Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures intends to address the unique virulence features and ho- pathogen interactions of microorganisms constituting emerging biothreat with emphasis on Y. pestis, B. anthracis, F. tularensis and Orthopox viruses. Accordingly we selected classical microbiological as well as genomic, proteomic & transcr- tomic approaches towards developments of novel prophylactic and post-exposure treatment, as well as updated strategies of diagnostics and bioforensics.

The books in this acclaimed series are the most detailed, up-to-date accounts of the field available. Volume 3 explores the oncogenic potential shared by retroviruses of different species, the widespread presence of retrovirues in nature, and the role of retroviruses in normal development and pathogenesis.