Medical Intelligence Unit – serie

The increase in drug resistance among many bacterial species has increased the need for new bacterial vaccines. This book serves as a comprehensive reference on the major aspects of developing new bacterial vaccines. The distinctive feature of this book is that it focuses upon new vaccines now under development by reviewing key issues for each vaccine target and new technologies being applied to developing new vaccines. This book should prove useful for students in the life sciences, scientists, developers of vaccines and biotechnology products, clinicians, regulators, and health-care practitioners.

NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo­ Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me­ thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat­ terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac­ tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.

Chagas' disease, which results from infection with the single cell parasite Trypanosoma cruzi, is a debilitating condition that is a major problem in many parts of Latin America. Rapid technical progress is now facilitating dissection of the molecular mechanisms of disease pathogenesis, a process that will ultimately provide new strategies to alleviate the enormous public health burden associated with the infection. In this book, international experts review the buoyant status of Chagas' disease research as we enter the "post-genome" era and speculate on how the new findings will impact on drug and vaccine development. The chapters outline how progress is being made on several fronts ranging from parasite population genetics to human immunology. Researchers, physicians and students with an interest in any aspect of molecular parasitology should find this book to be a valuable reference

Fibrogenesis: Cellular and Molecular Basis is the first volume to provide a synopsis of the rapid progress that has been documented in fibrogenesis over last couple of years, which significantly enhanced our understanding of the pathomechanisms of fibrotic diseases. Knowledge on molecular and celluar basis of fibrotic diseases has provided opportunities to develop selective and effective gene-based therapeutic options.The chapters in this book have been selected to provide comprehensive information on fibrogenesis, which is not limited to any specific organ. Individual chapters present mechanisms of fibrotic diseases involving lung, liver, kidney, heart, blood vessels, and more. The relevance and significance of inflammatory cytokines, chemokines, transcriptional factors, fibrogenic molecules, signaling cascade, and matrix remodeling in fibrogenesis are explained in depth, providing the reader with current and updated information.

Hematopoietic Stem Cells brings together articles covering the biology of hematopoietic stem cells during embryonic development, reporting particular aspects of fly, fish, avian and mammalian models. Thus, this book allows a comparative overview of hematopoietic stem cell generation in the different classes, emphasizing the conserved trends in development. This book culminates with state-of –the art knowledge on hematopoietic development in human species and discussions of the most recent breakthroughs with relevance to both researchers and clinicians.

MALT Lymphomas is a multidisciplinary book that covers all the aspects of MALT lymphomas, from the molecular biology, the aetiology and the pathology, to all the possible therapeutic approaches. Extranodal marginal zone B cell lymphoma of MALT type (MALT lymphoma) is one of the lymphoma subtypes that has allowed us some of the most interesting steps forward in the understanding and treatment of human cancers. The eight contributions have been written by a team of international experts and represent an essential reading for oncologists, haematologists, gastroenterologists, pathologists and all the other physicians and researchers involved in cancer. The book is also supported by a series of figures illustrating the histology and the clinical features and the treatment.

"VEGF and Cancer" is a comprehensive and up to date review of current knowledge on the role of vascular endothelial growth factor (VEGF) in cancer. Key features include: discussion of VEGF as potent angiogenic factor and its role in tumor angiogenesis; review of the biology, molecular properties and regulation of VEGF; discussion of the role of VEGF in a range of different tumor types, both solid tumors and haematological cancers; review of the therapeutic potential of different approaches to block VEGF; review of recent evidence that in addition to its role as an endothelial cell mitogen; VEGF may also be an autocrine growth factor for tumor cells; and regulating survival and invasion. This book is aimed at scientists new to angiogenesis and VEGF biology and provides new information for established researchers and scientists. It will also be a useful text for clinicians interested in anti-angiogenic therapy for treatment of human cancers.

Oral tolerance is a major immunological property of the gastrointestinal mucosa. It plays a critical role in immune defence by preventing inflammatory and allergic responses to dietary and non pathogenic microbial antigens. The interest in oral tolerance has been renewed in the recent years, due to novel insights on its cellular mechanisms and potential clinical applications in the treatment of autoimmune diseases. Oral Tolerance: Cellular and Molecular Basis, Clinical Aspects, and Therapeutic Potential, has been designed as a concise yet comprehensive overview of the newest fundamental and clinical advances in the field. Based on the outstanding contribution of world experts, this book will be helpful to students, clinicians, and researchers working in mucosal immunology and gastroenterology. The first part of this volume describes the structure and functions of the gastrointestinal mucosa and the fundamental features and mechanisms of oral tolerance, including the role of T cells, cytokines, IgA antibodies, and bacterial antigens. The second part explores the clinical implications of the disruption of oral tolerance in Inflammatory Bowel Diseases, food and milk allergies, and coeliac disease in particular. The final chapter focuses on the clinical potential of oral tolerance as a promising therapeutic tool.

Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs.Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.

This volume is unique to the existing literature in the Peptide Nucleic Acid field, in that it focuses on comparing and contrasting PNA with other available oligonucleotide homologues and considers areas in which these biomolecules could be profitably applied to clinical and diagnostic applications. Part I of the book addresses comparative strengths and weaknesses of various nucleoside homologues. Part II of the book addresses specific translational or clinical applications for PNA and related antisense biomolecules. The editors have succeeded in presenting a balanced yet broad view of the methods available for gene targeting and modification.

Mitochondrial diseases are often hard to diagnose. From the time they were first researched without animal models, patients of mitochondrial diseases were of equal interest to both clinical and basic scientists. With the new research done, this book includes updates on the normal structure, function, and molecular biology of the mitochondrial respiratory chain, information on traditional diagnostical methodologies, and an overview of the diagnostic promise of new technologies. The hypermetabolism of Luft disease, although only seen twice, is also studied. There are critical reviews of symptoms and signs associated with syndromes, as well as updates on the genetic defects of either the mitochondrial or the nuclear genome responsible for many disorders.

In the past five years, a large number of new chemokines and chemokine receptors have been identified. Alarming progress in the areas of bioinformatics and expressed sequence tag (EST) databases attributed to this development. Recent discoveries provide compelling evidences supporting the roles of these messengers and their receptors in the control of viral infection as well as in aiding virus survival. Chemokines in Viral Infections is the first to provide a comprehensive write up on the various evidences available to date on the interactions between host chemokine system and viral chemokines. This book intends to unravel the chemokine constellation in the context of viral infections, a versatility that was not fully understood five years ago. This book is excellent reading material and will be of interest to research scientist, clinicians and postgraduate students.

Historical Introduction The Marfan Syndrome: From Clinical Delineation to Mutational Characterization, a Semiautobiographic Account VictorA. McKusick l n 1876, E. Williams, an ophthalmologistin Cincinnati, Ohio, described ectopia lentis in a brother and sister who were exceptionally tall and had been loosejointed from birth. I Although there is a Williams syndrome that has aortic manifestations (supravalvar aortic stenosis), the name Williams was never associated with the disorder we now call Marfan syndrome. The reason is clear: Williamswas geographically removed from the leading medical centers and published in the Transactions of the American Ophthalmological Society; surely his report attracted little attention and the non-ocular features were not emphasized. 2 The case report that brought the disorder to attention was provided by a prominent Pari- sian professor of pediatrics, Antoine Bernard-Jean Marfan (1858-1942), who did much to establish pediatrics as a specialty in France and elsewhere. He was the author of widely read textbooks and monographson pediatrictopics and waseditor of Le Nourrisson for a great many years.In addition to the syndromeunder discussion here, his name is often attached to "Marfan's law" (that immunity to pulmonary phthisis is conferred by the healing of a local tuberculous 3 lesion) and Marfan's subxiphoid approach for aspiratingfluid from the pericardial sac. (Please pardon my use of the possessive form of the eponym in these two instances!) Pictures of Marfan (Fig.

Although, Phagocytosis was first described nearly 120 year ago, we are just recently beginning to understand the molecules that phagocytic cells use to bring about this complex cell function. Molecular Mechanisms of Phagocytosis was prepared as a series of up-to-date essays (chapters) that describe the present knowledge on the various steps of the phagocytic process from initial cell contact, through internalization of the foreign particle, to the final phagosome formation where the phagocytosed particle is destroyed.

Lysosomes are membrane-surrounded organelles which are present in all animal cells. The importance of this organelle is underlined by an increasing number of human diseases, which are associated with an impaired function of the lysosomal compartment.This book summarizes the current state-of-the art knowledge about this unique organelle. It addresses the biogenesis of this compartment, the transport of lysosomal proteins, the role of the lysosomal membrane in lysosomal stability and transport, the function of lysosomal proteases and hydrolases, lysosomal storage disorders, and new concepts on how to treat these diseases. In addition to these classical topics, new insights into lysosomal functions are covered by chapters dealing with specialized lysosomes involved in bone resorption and plasma membrane repair, the lysosomal transciptome, and proteome and the emerging role of lysosomes in special forms of autophagy.This book will provide readers with a comprehensive overview into how this fascinating organelle works and how research in the field is developing.

apid progress in the understanding of carcinogenesis and pathology of epitheUal skin cancer has led to new strategies for the prevention Rand treatment of these malignancies. The goal of this volume is to comprehensively cover in a highly readable overview our present knowledge of pathogenetic mechanisms and molecular biology of Basal Cell and Squamous Cell Carcinomas. Topics that are discussed in-depth by leading researchers and clinicians range from the newest findings in epidemiology, histology, photobiology, immunology, cytogenetics, and molecular pathol­ ogy to new concepts for prophylaxis and treatment. Experts in the field as well as health care professionals not intimately involved in these specialized areas are provided with the most significant and timely information related to these topics. It is the aim of this book to summarize essential up-to-date information for clinicians and scientists interested in the biology of Basal Cell and Squamous Cell Carcinomas. The chapters are written by authors who are experts in their respective research areas, and I am gratefixl for their willingness to contribute to this book. I would also like to express my thanks to Ron Landes, Cynthia Conomos, Sara Lord and all the other members of the Landes Bioscience staff for their expertise, diligence and patience in helping me complete this work. Jorg Reichrathy Prof, Dn med. CHAPTER 1 The Epidemiology of Basal Cell and Squamous Cell Carcinoma Hao Wang and Thomas L.

We are excited to bring together recent research on the molecular biology of Axenfeld-Rieger syndrome (ARS) disorders. In the following chapters we will review and provide direct evidence for the molecular basis of this group of heterogeneous disorders, which include Rieger syndrome and Rieger anomaly. While ARS patients were initially diagnosed in the early 1930s the genetic basis for ARS was unknown until the recent identification of chromo- somal loci associated with this genetic disorder. In the mid-1990s Drs. Jeffrey C. Murray and Elena V. Semina identified PITX2 through positional cloning tech- niques as a gene associated with ARS. These researchers were able to iden- tify point mutations in PITX2 that were linked with ARS patients. ARS patients presented clinically with several developmental anomalies that fur- ther provided clues about the function of the PITX2 homeobox tran- scription factor. The phenotypic variability of ARS patients indicates that PITX2 can participate with many other faaors to control normal development processes. The hallmarks of ARS developmental anomalies are eye, tooth and umbilical defects.However, abnormal pituitary, heart, and craniofacial development are also detected. Thus, ARS patients provided the first link of PITX2 involvement in the development of these organs and structures. Some of these anomalies are recapitulated in epigenetic and genetic mouse, chick, zebrafish and frog studies which will be reviewed in the following chapters.

Reproductive Immunology is a growing area in both immunology and reproductive sciences and is helping us to better understand several complications of pregnancy. Immunology of Pregnancy is the first book to give a complete and up to date review of our knowledge related to the role of the immune system during pregnancy and the interactions between the placenta and the maternal immune system.This new title covers in detail all the different hypotheses and studies related to the immunology of implantation and provide a practical approach for the application of basic reproductive immunology research to pregnancy complications such as preeclampsia, pre-term labor and IUGR.

Molecular Mechanisms of Fanconi Anemia will give research students a platform for further investigation, and act as a source of information regarding experimental design. Clinicians will find this title useful for its comprehensive description of Fanconi Anemia and information on the latest molecular theories underlying its causes.

Fas Signaling is focused on the signaling mechanisms and biology of the prototypic death receptor Fas, also called CD95 or APO-1. The chapters of this book cover, besides the well recognized apoptosis-related functions of Fas, its emerging role as a proinflammatory cytokine and as an inducer of alternative forms of cell death. Fas Signaling aims to provide the reader with an up-to-date survey of the various aspects of Fas biology and the open questions of the field are addressed. This title is intended for Ph.D and post-doctoral students starting to work in the field, but is also useful for everyone with an interest in the biology of this exciting molecule.

Rb and Tumorigenesis examines how recent advances have demonstrated the interaction of Rb with chromatin remodeling enzymes. This new title explores the potential roles of these interactions in Rb functions and provides some evidence that distinct Rb co-repressor may target different genes in different phases of the cell cycle.

Hepatitis Delta Virus is an up-to-date guide to hepatitis D virus (HDV), a human virus with a number of distinctive features. Each chapter of this book describes one of the broad aspects of HDV from virology to molecular biology, and from diagnosis to therapy.

Following an introductory overview, Hyperthermia In Cancer Treatment: A Primer comprehensively describes the biological reasons for associating hyperthermia with radiation and chemotherapy and the biological and clinical effects of hyperthermia on cancerous and normal tissues. The volume’s 20 chapters are arranged in three principal parts: physical and methodological studies, biologic principles, and clinical studies.

DNA Repair and Human Disease highlights the molecular complexities of a few well-known human hereditary disorders that arise due to perturbations in the fidelity of diverse DNA repair machineries.

utoimmunity is the downstream outcome of a rather extensive and coordinated series of events that include loss of self-tolerance, peripheral lymphocyte Aactivation, disruption of the blood-systems barriers, cellular infiltration into the target organs and local inflammation. Cytokines, adhesion molecules, growth factors, antibodies, and other molecules induce and regulate critical cell functions that perpetuate inflammation, leading to tissue injury and clinical phenotype. The nature and intensity of this response as well as the physiological ability to restore homeostasis are to a large extent conditioned by the unique amino acid sequences that define allelic variants on each of the numerous participating mol­ ecules. Therefore, the coding genes in their germline configuration play a primary role in determining who is at risk for developing such disorders, how the disease progresses, and how someone responds to therapy. Although genetic components in these diseases are clearly present, the lack of obvious and homogeneous modes of transmission has slowed progress by prevent­ ing the full exploitation of classical genetic epidemiologic techniques. Furthermore, autoimmune diseases are characterized by modest disease risk heritability and m- tifaceted interactions with environmental influences. Yet, several recent discoveries have dramatically changed our ability to examine genetic variation as it relates to human disease. In addition to the development of large-scale laboratory methods and tools to efficiently recognize and catalog DNA diversity, over the past few years there has been real progress in the application of new analytical and data-manage­ ment approaches.

More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. In addition, between 17 and 40 million people have insulin resistance, impaired glucose tolerance, or the cluster of abnormalities referred to variably as the metabolic syndrome, the dysmetabolic syndrome, syndrome X, or the insulin resistance syndrome. In all of these disorders, a central component of the pathophysiology is insulin resistance, i.e., reduced responsiveness to insulin in tissues such as muscle, fat and liver. Insulin resistance is also closely linked to other common health problems, including obesity, polycystic ovarian disease, hyperlipidemia, hypertension, and atherosclerosis. In this book, we will attempt to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. We explore insulin action at the most basic levels, through complex systems. The book will be appealing to basic and clinical scientists.

Human immunosenescence contributes to morbidity and mortality in later life. The age-associated increasing incidence of cancer and cardiovascular disease plateaus at around 80 years of age in industrialised countries, but death due to infectious disease continues to increase up to 100 years of age and beyond. Understanding the reasons for age-associated alterations to protective immunity in the elderly would facilitate the development of interventions to reconstitute appropriate immune function, increase responsiveness to vaccination and extend healthspan. The majority of the papers collected in this volume therefore address not only the mechanisms responsible for immune ageing in humans but consider what might be accomplished to redress the erosion of immune competence with age.

More than 18 million people in the United States have diabetes mellitus, and about 90% of these have the type 2 form of the disease. In addition, between 17 and 40 million people have insulin resistance, impaired glucose tolerance, or the cluster of abnormalities referred to variably as the metabolic syndrome, the dysmetabolic syndrome, syndrome X, or the insulin resistance syndrome. In all of these disorders, a central component of the pathophysiology is insulin resistance, i.e., reduced responsiveness to insulin in tissues such as muscle, fat and liver. Insulin resistance is also closely linked to other common health problems, including obesity, polycystic ovarian disease, hyperlipidemia, hypertension, and atherosclerosis. In this book, we will attempt to dissect the complexity of the molecular mechanisms of insulin action with a special emphasis on those features of the system that are subject to alteration in type 2 diabetes and other insulin resistant states. We explore insulin action at the most basic levels, through complex systems. The book will be appealing to basic and clinical scientists.

Human immunosenescence contributes to morbidity and mortality in later life. The age-associated increasing incidence of cancer and cardiovascular disease plateaus at around 80 years of age in industrialised countries, but death due to infectious disease continues to increase up to 100 years of age and beyond. Understanding the reasons for age-associated alterations to protective immunity in the elderly would facilitate the development of interventions to reconstitute appropriate immune function, increase responsiveness to vaccination and extend healthspan. The majority of the papers collected in this volume therefore address not only the mechanisms responsible for immune ageing in humans but consider what might be accomplished to redress the erosion of immune competence with age.