Humana Press Inc.

Superantigen Protocols assembles experimental protocols that have proved useful for the study of superantigens. These techniques will allow researchers from various areas of cell biology, microbiology, immunology, biochemistry, and molecular biology to assess the physical characteristics and biological effects of well-known superantigens as well as of putative substances that might have superantigenic activities, and to explore therapies for superantig- induced effects. Microbial exotoxins have been studied for decades as virulence factors because of their pathogenic effects. The term "superantigen" was coined by Marrack and Kappler a decade ago for some of these molecules because of their potent T-cell stimulatory activities. In recent years, advances in mole- lar biology provide recombinant as well as natural superantigens in highly purified form for physical characterization. Superantigens are now used extensively as tools to study interactions between receptors on cells of the immune system as they bind to major histocompatibility complex class II m- ecules on antigen-presenting cells and V regions of T-cell receptors. The b- ? logical effects that result from these interactions are studied both in vitro and in vivo. The intent of this book is, therefore, to bring together up-to-date te- niques developed by experts in the field of biochemistry, immunology, and molecular biology for the study of superantigens. Superantigen Protocols begins with an overview of the field to provide background information on the various classes of superantigens and their str- ture.

The revelation that aspirin and aspirin-like compounds have notableantineo- plastic properties has revolutionized cancer research. COX-2 Blockade in Cancer Prevention and Therapy chronicles the evidence and presents exciting new op- portunities for the use of cyclooxygenase-2 (COX-2) blockade in the prevention and treatment of cancer. The text is divided broadly into five areas. First, an historical overview documents the scientific discovery ofCOX-2 and the pharma- ceutical development of nonsteroidal anti-inflammatory drugs (NSAIDs) designed for selective COX-2 inhibition. The process by which essential poly- unsaturated fatty acids (PUF As) stimulate prostaglandin biosynthesis and cancer development, and its interruption by COX-2 inhibition, is elucidated. This is followed by a section on the epidemiology of NSAIDs and cancers of the colon and breast, and other anatomic sites. These chapters reflect significant cancer protection owing to the regular use of common NSAIDs such as aspirin and ibuprofen. A section on animal models of carcinogenesis presents comprehensive evidence that general NSAIDs inhibit a variety of malignant neoplasms in vivo, and highlights recent findings which show that COX-2 blocking agents produce striking chemopreventive effects against colon cancer and breast cancer as well as other malignancies. Genetic models are presented confirming the critical role of COX-2 in carcinogenesis. Section IV then discusses the molecular biology of COX -2 vis-a-vis the role of COX -2 and, to a lesser extent, COX -1, in modulating a number of important processes in molecular carcinogenesis such as mutagen- esis, cell division, angiogenesis, cell differentiation, and apoptosis.

The aim of MHC Protocols is to document protocols that can be used for the analysis of genetic variation within the human major histocompatibility complex (MHC; HLA region). The human MHC encompasses approximately 4 million base pairs on the short arm of chromosome 6 at cytogenetic location 6p21. 3. The region is divided into three subregions. The telomeric class I region contains the genes that encode the HLA class I molecules HLA-A, -B, and -C. The centromeric class II region contains the genes encoding the HLA class II molecules HLA-DR, -DQ, and -DP. In between is the class III region, originally identified because it contains genes encoding components of the complement pathway. The entire human MHC has recently been sequenced (1) and each subregion is now known to contain many other genes, a number of which have immunological functions. The study of polymorphism within the MHC is well established, because the region contains the highly polymorphic HLA genes. HLA polymorphism has been used extensively in solid organ and bone marrow transplantation to match donors and recipients. As a result, large numbers of HLA alleles have been identified, a process that has been further driven by recent interest in HLA gene diversity in ethnic populations. The extreme genetic variation in HLA genes is believed to have been driven by the evolutionary response to infectious agents, but relatively few studies have analyzed associations between HLA genetic variation and infectious disease, which has been difficult to demonstrate.

In "Cancer Neurology in Clinical Practice", leading neuro-oncologists from around the world comprehensively review the neurologic symptoms that cancer patients experience, and show how they should be interpreted and evaluated. Organized by both symptom and organ, the book carefully describes each diagnostic neurologic entity - from symptomatology to diagnostic studies to management and prognosis - and presents each major type of cancer in terms of it neurologic problems and how they should be handled. The role of surgery, radiation, chemotherapy, and other palliative measures are considered for each type of problem. Multidisciplinary and up-to-date, "Cancer Neurology in Clinical Practice" explains to the busy physicians treating cancer patients the latest findings in neuro-oncology that will help them to focus their differential diagnosis, diagnostic strategy, and treatment plan for the cancer patient with neurologic symptoms and findings.

Leading investigators critically evaluate the latest information on how anesthetics work at the molecular, cellular, organ, and whole animal level. These distinguished experts review anesthetic effects on memory, consciousness, and movement and spell out in detail both the anatomic structures and physiological processes that are their likely targets, as well as the cellular and molecular mechanisms by which they operate. Comprehensive and authoritative, "Neural Mechanisms of Anesthesia" draws together and critically reviews all the recent research on anesthetic mechanisms, highlighting the precise routes along which these substances operate, and how this deeper understanding will lead to the design of effective drugs free of undesirable side effects.

In Tumor Targeting in Cancer Therapy, Dr. Michel Page and a panel of authoritative experts from the drug industry, clinics, and academia introduce the principles and techniques of tumor targeting and critically survey their applications from laboratory to bedside. By concisely synthesizing the many technical details, the authors illuminate this innovative technique, ranging from the fundamentals of drug targeting and in vivo and in vitro experimentation, to such emerging therapeutic uses as radioimmunotherapy, radioimmunodetection, therapy with cytotoxic antibodies, immunotoxins, enzyme prodrug immunotherapy, and immunotherapeutics with fusion proteins. There are also reviews of targeting tumors with radioimmunoconjugates, photodynamic therapy, and magnetic drugs, as well as discussions of the internalization of antibodies, bioconjugation and biodistribution, the use of cytotoxic drugs, and the pros and cons of targeting by antibody or ligand.

Since the cloning of the cystic fibrosis transmembrane conductance re- lator (CFTR) nearly a decade ago, cystic fibrosis (CF) research has witnessed a dramatic expansion into new scientific areas. Basic researchers, clinicians, and patients increasingly rely on fundamental techniques of genetics, molecular biology, electrophysiology, biochemistry, cell biology, microbiology, and immunology to understand the molecular basis of this complex disease. Research into the pathophysiology of CF has established numerous paradigms of ion channel dysfunction that extend from inflammation and infection in the airways of patients to basic mechanisms of protein processing and regulation in intracellular components. With these rapid advances has come an increasing need for research scientists to understand and utilize a growing array of basic laboratory tools. This volume of Methods in Molecular Medicine, Cystic Fibrosis Methods and Protocols satisfies that need by providing detailed protocols for the laboratory techniques used throughout CF research. From electrophysiology and cell biology, to animal models and gene therapy, the comprehensive set of methods covered here provide step-by-step instructions needed for investigators to incorporate new approaches into their research programs. Contributions have been chosen to reflect the rich diversity of techniques and to provide a cohesive framework for understanding challenges that are currently at the forefront of CF research. It is hoped that this volume will serve as a valuable reference that will not only foster interdisciplinary investigations into current problems encountered in CF, but also facilitate the translation of new scientific discoveries into clinical solutions.