This book discusses specific immune cell regulatory pathway(s), immune cell types, or other mechanisms involved in host responses to tuberculosis that can be potentially targeted for host-directed therapy (HDT). The pathways/mechanisms investigated are either protective - thus calling for pathway/factor enhancing drugs - or maladaptive - thus calling for pathway/factor inhibitory drugs. Discovery and development (pre-clinical and clinical) of candidate HDT agents will also be elucidated, as well as approaches for HDT of other diseases. The benefit to the reader will derive from learning about the biology of multiple host pathways involved in health and disease, how these pathways are disrupted or dysregulated during tuberculosis, and which druggable targets exist in these pathways. This book provides the reader with a roadmap of current and future directions of HDT against tuberculosis. Since the host pathways/factors involved in protective or maladaptive responses to tuberculosis are not disease-specific, information learned from the context of tuberculosis likely will be relevant to other infectious and non-infectious diseases.

Standardizing Pharmacology: Assays and Hormones, Volume Two in the Discoveries in Pharmacology series, presents selected articles from historic discoveries that are enhanced with commentary from contemporary scholars who present discussions on the importance of each chapter, along with an updated bibliography on the subject and contributions from a Nobel Prize winner and other pioneers in pharmacology. Academic and industry researchers in pharmacology and medicine, as well as advanced students will find this series a useful teaching tool and launch to new discoveries. Sections cover key discoveries in receptor theory, pharmacological methods and the development of hormone therapy, including J. Parascandola on the development of receptor theory, R.S. Yalow on radioimmunoassay, M. van Rossum and J.T L.A. Hurkmans on bioassays, M. Tausk on androgen therapy and C. Djerassi on oral contraceptives, with commentaries from experts such as T. Hoekfelt and V.C. Jordan.

Phagocytosis is the engulfment of particulate matter by cells. It is a fundamental (and probably "primitive") cell biological process which is important in single celled organisms such as amoeba; multicellular animals including coelenterates; and in higher animals. In humans and other mammals, specialised immune cells (phagocytes) utilise phagocytosis in their crucial role of engulfing and destroying infecting microbes. Yet, surprisingly, the biophysics and biochemistry underlying the process has only become clear recently with the advent of genetic manipulation and advances in single cell imaging. In this volume, the aim is to bring together recent fundamental advances that give a clear picture of the underlying mechanism involved in phagocytosis. Not only is this an important topic in its own right, but a full understanding of the process will have a potential impact on human medicine, since as antibiotics become less effective in fight infection, researchers are looking at alternative approaches, including enhancing the "natural" immunity brought about by immune phagocytes. The aim is to provide a comprehensive volume on the topic, with separate chapters on identified recent advances, each written by the major contributors in each area. In addition, the volume will attempt to give a wider overview than is often the case in single author reviews, with an emphasis here on the cell biological understanding of phagocytosis using biophysical approaches alongside the biochemical and imaging approaches.

This timely book discusses antimicrobial drug resistance, specifically, the resistance against the beta-lactam class of antibiotics by Gram-Negative bacteria. The book is broadly divided into five sections. The first section describes the underlying mechanisms of antimicrobial resistance in Gram-negative bacteria. It gives an insight into the beta-lactamases, their types, classification, inhibitors, etc. The second section delves deep into the genetic basis of resistance. It talks about transposons, integrons, insertion sequences associated with antibiotic-resistant genes. The next section describes phenotypic and molecular methods to detect beta-lactam resistance. The fourth section talks about the epidemiology and prevalence of beta-lactamases in the environment. The last section of the book describes the various therapeutic options to combat this growing public threat of antimicrobial resistance. It talks about the current reserve drugs, as well as the newer antibiotic agents that are in the pipeline. This book is essential for clinical practitioners, students, and researchers in basic and medical microbiology.

This detailed volume collects updates on the technical advances in hematopoietic stem cell research and incorporates new techniques focused on the molecular/genetic, cellular, and whole organism levels. Exploring methods that apply stress to hematopoiesis, the book also contains chapters focused on better understanding the role of hematopoietic niches and their cellular components, as well as in vivo models that test and quantitate stem cell function and are key to further development of therapeutic applications. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Hematopoietic Stem Cells: Methods and Protocols serves as a valued addition to laboratories focused on understanding hematopoietic stem cell biology and the therapeutic advances that can be derived from it.

The collection of chapters in this proceeding volume reflects the latest research presented at the Aegean meeting on Tumor Microenvironment and Cellular Stress held in Crete in Fall of 2012. The book provides critical insight to how the tumor microenvironment affects tumor metabolism, cell stemness, cell viability, genomic instability and more. Additional topics include identifying common pathways that are potential candidates for therapeutic intervention, which will stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery.

The book presents current affairs of Sporotrichosis as emergent disease with emphasis on the potential factors associated with genetic polymorphisms in Sporothrix complex. Constitutive and inducible factors play an essential role in the response of the fungal cell to the environment as determinant in the immunopathogenicity, highlighting clinical forms of Sporotrichosis and host immunocompetence. Also, a current issue interest in zoonotic transmission showing that a cat is the animal species most affected by Sporothrix species and their importance in the involvement in the human transmission. Readers can associate parameters of experimental immune response to disease development as well as the diagnostic, prophylaxis, and therapies that can be applied in the near future.

Session I.- Breast Mucin and Associated Antigens in Diagnosis and Therapy.- Peptide Epitopes in Breast Cancer Mucins.- Does a Novel Form of the Breast Cancer Marker Protein, MUC1, Act as a Receptor Molecule that Modulates Signal Transduction?.- Cancer Metastasis Determined by Carbohydrate-Mediated Cell Adhesion.- Experimental Immunotherapy of Breast Cancer Using Alpha Interferon Conjugated to Monoclonal Antibody Mc5.- Circulating and Tissue Markers in the Longitudinal Management of Breast Cancer Patients.- Session II.- Engineering of Antibodies for Breast Cancer Therapy: Construction of Chimeric and Humanized Versions of the Murine Monoclonal Antibody BrE-3.- Humanization of an Anti-Mucin Antibody for Breast and Ovarian Cancer Therapy.- Towards an Immunotherapy for p185HER2 Overexpressing Tumors.- Session III.- Branching N-Linked Oligosaccharides in Breast Cancer.- Specificity of the IgG Response in Mice and Human Breast Cancer Patients Following Immunization Against Synthetic Sialyl-Tn, an Epitope with Possible Functional Significance in Metastasis.- Vaccination Against Breast Cancer - Studies in an Animal Model.- Anti-Idiotype Antibodies as Potential Therapeutic Agents for Human Breast Cancer.- The Simultaneous Expression of c-erbB-2 Oncoprotein and Laminin Receptor on Primary Breast Tumors has a Predicting Potential Analogous to that of the Lymph Node Status.- Multivariate Prognostic Model for Infiltrating Ductal Carcinoma of the Breast in the Axillary Node-Free Patient.- The Use of Monoclonal Antibody Immunoconjugates in Cancer Therapy.- Radioimmunolocalization of Breast Cancer Using BrE-3 Monoclonal Antibody.- Suppression of Human Anti-Mouse Antibody Response to Murine Monoclonal Antibody L6 by Deoxyspergualin: A Phase I Study.- Overview of Radioimmunotherapy in Advanced Breast Cancer Using 1-131 Chimeric L6.- Contributors.

Wolf's discovery demonstrating that a reporter gene is expressed in myocytes subsequent to injection of naked DNA, was exploited by immunologists and vaccinologists to develop a new generation of vaccines. This observation galvanized the research and in a short lapse of time, an oceanic volume of knowledge has been accumulated. The research carried out in a variety of animal models showed the efficacy of genetic immunization against viruses, bacteria, and some parasites by the ability to induce a strong priming effect resulting from long-lasting persistence of plasmid as episomes. Furthermore, it was demonstrated that newborn or infant immune unresponsiveness to classical vaccines can be corrected by genetic immunization. The applications of genetic immunization for prophylaxis of infections was extended to immunotherapy, namely, cancerous, auto immune, and allergic diseases. Immunologists have provided pertinent information on the cellular basis of the immune responses elicited by genetic immunization, and molecular biologists have established the molecular basis of intrinsic adjuvant properties of plasmids."

Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, functional diversity and plasticity are hallmarks of these cells.

Macrophages may also play a detrimental role. An overwhelming body of literature has indicated their crucial role in pathogenesis. The list includes sepsis, cancer, metabolic syndrome, immunodeficiency, auto-immune disease-virtually impacting every major pathology that we know. These observations have suggested macrophages and their related molecules as potential targets in therapeutic applications. Available evidence proclaims macrophages as a key player in homeostasis, host defense and disease. Crucial developments in the past few years call for a re-evaluation and update of our understanding of macrophages. The present book is an endeavour that attempts provide state-of-the art knowledge of these cells in health and disease.

The lung forms an integral part of the body's immune system and is subject to a range of diseases which are either autoimmune in nature or have clear-cut immunological abnormalities. "Autoimmune Aspects of Lung Disease" provides a concise review of the lung's role in the immune system and a detailed account of both primary and secondary lung diseases which are characterised by immunological perturbation or frank autoimmunity. The volume presents a detailed, up-to-date account of disorders ranging from infection to neoplasia and is written in both an informative and stimulating style by a prestigious group of authors. The chapters are extensively referenced and provide numerous insights into the aetiopathogenesis and clinical features and treatment of immunologically-linked pulmonary disease. The book is intended as both an overview for physicians and scientists with an established interest in diseases of the lung, immunologists seeking to learn more about relevant disorders in the lung and general physicians, whether specialists or in training, seeking to enrich their knowledge of the links between the pulmonary and immune systems.

Recent outbreaks of swine influenza and avian influenza, along with the remaining and in some cases expanding threats from HIV, dengue virus, and the viruses causing hepatitis, have reinforced the need for rapid, accurate and cost-effective diagnosis of viral disease. Diagnostic Virology Protocols, Second Edition brings the field fully up-to-date with a focus on protocols involving nucleic acid detection, most often through some form of the polymerase chain reaction (PCR). The expert contributors also delve into the key technology of robotics as well as future prospects, such as further refined point-of-care testing and the increasing importance of mathematical modelling. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief 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 cutting-edge, Diagnostic Virology Protocols, Second Edition captures the dramatic changes in the virus diagnostic laboratory in order to better prepare scientists to combat the inevitable threats to public health from future and present infectious diseases.

Morphology.- The Pineal Gland of Mammals: Some Open Morphological Questions.- Demonstration of Nerve Fibers Immunoreactive to met-Enkephalin, leu-Enkephalin, and ss-Endorphin in the Bovine Pineal Gland.- Comparative Studies of VIP-, PHI-, and NPY-Immunoreactive Nerve Fibers in the Pineal Gland of the Sheep.- Biochemistry.- Pharmacological Regulation of Receptor-Mediated Indoleamine Metabolism in the Mammalian Pineal Gland.- Regulation of Melatonin Synthesis and Release: Paracrine Relationships in Mammalian Pineal Gland.- New Aspects Concerning the Regulation of Pineal Indoleamine Metabolism: Implications for Neuroimmunology.- The Use of Perifusion Technique in the Research of Pineal Neuroendocrinology. The Role of Different Neurotransmitters in the Regulation of Pineal Melatonin Secretion.- Interferon-? Modulates Indoleamine Metabolism in Rat Pineal Gland in Organ Culture.- Melatonin Receptors.- High-affinity Melatonin Receptors in Mammals: Localization, G-Protein Coupling and Signal Transduction.- Melatonin Receptors in Discrete Areas of Rat and Hamster Brain: Modulation by Melatonin, Testosterone and the Photoperiod.- Melatonin Binding Sites in the Nervous and Immune Systems.- 2-?125I? Iodomelatonin Binding in Normal and Neoplastic Tissues.- Melatonin in the gastrointestinal tract.- Biochemical Characteristics of Melatonin Receptors in Different Organs and Translation of Hormonal Signal in the Nucleus.- Physiology.- Annual Changes in the Daily Pattern of Melatonin Synthesis and Release.- Integration of Environmental Signals by the Pineal Gland and its Significance for Seasonality in Small Mammals.- Opioid Involvement in Melatonin Action.- Effect of Melatonin on NADH-Oxidoreductase Activity and Cyclic Nucleotide Levels in Rat Adrenals.- Temporal Profile of Superoxide Dismutase Activity in the Pineal Gland and the Liver of Rats.- Pineal-Harderian Gland Interactions: Morphological and Physiological Evidences for an Endocrine Function of the Syrian Hamster Harderian Gland.- Melatonin Enhances GABA-Mediated Effects when Administered by Micropressure Ejection in Single Unit Neuronal Recordings.- Immunology.- Action of Melatonin on Immune System.- Opioids in Immune Cells.- Spleen Morphology and Lymphoproliferative Activity in Short Photoperiod Exposed Hamsters.- Melatonin Reconstitutes the Decreased CFU-S Content in the Bone Marrow of Hypothalamus - Lesioned Mice.- Oncology.- Melatonin Action on Oncogenesis.- The Effects of Melatonin and Melatonin Analogues on the P388, DLD-1 and MCF-7 Tumor Cell Lines.- Is there a Role for the Pineal Gland in Neoplastic Growth?.- Clinical Studies.- Melatonin, Immunity and Cancer in Humans.- Evidence for a Sex-Specific Facilitatory Effect of Melatonin on Prolactin Secretion. Is Pineal-Prolactin Interaction Relevant to the Clinical Course of Breast Cancer?.- Pineal-Interleukin 2 Interactions and their Possible Importance in the Pathogenesis of Immune Dysfunctions in Cancer.- Significance of Melatonin to Chronobiology: Immunological Correlations.- Circadian Profile of Serum Melatonin in Cushing's Syndrome and Acromegaly.- Urinary 6-Sulfatoxymelatonin Excretion in Breast Cancer Patients and Control Subjects.- Interindividuel Differences in the Responses of Serum and Salivary Melatonin to Light.- Contributors.

This volume focuses on the laboratory and clinical experience with targeting viral onco-antigens, while also reviewing the approaches to targeting self-cancer antigens in cancers of non-viral origin, where self-tolerance has been a challenge. It emphasizes the importance of selecting the right vaccine platform to induce a successful immune response against cancer antigens. In addition, the volume discusses the advances made with genetic vaccines, including recent advances with DNA vaccines and the rapid transition of mRNA vaccines from the laboratory to bedside. The new avenues opening up for cancer immunotherapy underline the importance of combinational approaches using cancer vaccines with costimulatory antibodies, which may dramatically improve cancer treatment. This book is intended for all translational researchers and clinicians who aspire to develop novel vaccination approaches for cancer patients with unmet clinical needs.

This detailed volume covers diverse aspects of P2X7 receptor analysis, ranging from its molecular structure to related pharmacological and immunological tools, via its analysis in heterologous expression systems as well as assays using primary cells and whole animal models. After three introductory chapters that focus on its structure, ligands, and physiological functions, the book details the generation of antibody and nanobody tools for P2X7 receptors, provides protocols for the analysis of expressed P2X7 receptors with a focus on their electrophysiological analysis, as well as protocols for the investigation of P2X7 down-stream signaling in immune cells by flow cytometry. Mouse models and procedures suited to investigate P2X7-mediated effects in other primary cells and in vivo are also explained. Written for the highly successful Methods in Molecular Biology series, 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, The P2X7 Receptor: Methods and Protocols is a valuable reference not only for the growing community fascinated by this unusual ion channel but also for a broad readership interested in ion channels or purinergic receptors.

This textbook discusses the systemic consequences of cancer, covering a range of topics from tumor-promoting systemic effects to the development of cachexia, as summarized in the introductory chapter 1. Part I of this textbook focuses on tumor-promoting systemic effects and begins with a chapter on how tumor-derived extracellular vesicles and particles lay the foundation for future metastases (Chapter 2). Chapter 3 discusses how metastatic cells that have colonized the bone impact the local bone microenvironment, neighboring muscles, and host physiology. Chapter 4 summarizes the available strategies for targeting metastatic cancer and emphasizes the need to incorporate a systemic view of the disease. Following this overview of the systemic effects of cancer progression, Part II of the textbook discusses cancer-induced cachexia, a debilitating systemic effect of advanced cancer. Chapters 5-7 examine the key signaling pathways (interleukin-6/GP130, NF-kB, and muscle proteolysis) that drive the development of cancer cachexia. Chapters 8 and 9 in Part III of this textbook explore how toxicities from anti-cancer therapy are associated with the onset of cachexia in cancer patients, and provide insight into potential approaches to simultaneously target both cancer and cachexia. Chapters 10 and 11 (Part IV) conclude this textbook by outlining promising approaches for the diagnosis and treatment of cachexia as well as strategies to prevent the development of cachexia through exercise. An understanding of the systemic effects of cancer is essential for the design of effective anti-cancer and anti-cachexia treatment strategies. As such, this textbook provides key information for both students and scientists engaged in cancer research and oncology.

Describes the immunological aspects of blood transfusion medicine, examining the immuno-chemistry of blood group antigens, the immune destruction of cells, correlations between blood groups and disease, and the effect transfusion-induced retroviral infection has on immune response.

T-Helper Cells: Methods and Protocols presents a broad selection of cutting edge protocols that will enable the reader to capture the unique features of TH cells with tools developed for the isolation of TH cells from various tissues and subsequent analysis of their functional properties in vitro, ex vivo and in vivo. Chapters cover methods of isolating T cells from various tissues in mice, protocols for the analysis of T cell function and phenotype using various cutting edge technologies, methods allowing for the manipulation of T cell function in vitro and in vivo, and in vivo models of diseases in which T cells play a central role in the pathogenesis. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, T-Helper Cells: Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies in an effort to further the study of this amazingly versatile and potent cell type.

In autumn 2002, the Ernst Schering Research Foundation Workshop sponsored the 45th in its series of conferences devoted to emerging areas in basic and applied biomedical research. These conferences bring together a critical mass of top scientists working in an impor- tant area in an intimate setting that fosters the free exchange of knowledge and ideas. In this spirit, Workshop 45 assembled leaders in the field of chemokines - hemotactic cytokines that coordinate leukocyte trafficking - amid the scenic vineyards and wineries of Napa Valley, to discuss the latest concepts of how these molecules regulate the immune response and disease. Chemokines were se- lected as a conference topic because they have revitalized the study of leukocyte trafficking and are widely considered to be potential new targets for drug development, in diseases ranging from acute in- flammation and autoimmunity to HIV and cancer. Discovered in the 1980s, the chemokine superfamily currently has 43 human members, making it the largest subset of cytokines. Mem- bers are defined by conserved sequences and a common three-di- mensional fold, and can be divided into two major functional groups - homeostatic and inflammatory - depending on whether they are produced constitutively, and thereby control basal lymphocyte traf- ficking, or whether they must be induced, for example by pathogens or injury, and thereby control deployment of effector leukocytes in emergencies.

The Role of Nutrition in Wound Healing (S.J. Dudrick). Chronic Wounds: Growth Factors and Comprehensive Surgical Care (D.R. Knighton). Wound Healing and Infection (D.E. Fry). The Plug Repair for Recurrent Inguinal Hernias (A.G. Shulman). Open Tensionfree Repair of Primary Inguinal Hernias in Adult Males (A.G. Shulman). Sepsis and Its Related Disorders: Definitions, Epidemiology, Pathogenesis and Pathophysiology (B.M. Friedman). The Septic Patient: Future Directions (T.J. Gallagher). Prophilaxis and Therapeutic Clinical Trials in Severe Sepsis and Septic Shock (G.J. Slotman). Pharmacologic Management of Postoperative Infections (J.D. Sutton). The Resuscitation Game (M.C. McCarthy). Transfusion Guidelines for Elective Surgery: The Transfusion Trigger (R.K. Spence). Physiologic Predictors of Transfusion Need in the Intensive Care Unit (L.D. Nelson). Preoperative Autologous Blood Donation (L.T. Goodnough). Component Therapy (K.F. O'Malley). The Anesthesiologist's Viewpoint: Transfusion, Hemodilution, and Cooperation (L. Stehling). Physicians' Assistants: An Overview (J.F. Byrnes, Jr.). Physicians Assistants: A Costefficient Solution for the Surgical Practice (L.A. Garry, D.L. Priore). Future 2000 for Nurses (Z.R. Wolf). Index.

Pocket Guide to Gene Level Diagnostics in Clinical Practice is an abbreviated, pocket-size, quick-reference guide that provides a point-by-point synopsis of the vast wealth of information contained in CRC Handbook of Gene Level Diagnostics in Clinical Practice. All sections and subsections in the Pocket Guide are cross-referenced to corresponding pages in the Handbook. The book works well on its own as a quick reference, but also can be used in conjunction with the larger Handbook for detailed coverage and references to specific information. Pocket Guide to Gene Level Diagnostics in Clinical Practice also includes extensive supplements featuring material not included in the Handbook. These are intended to provide an up-dated, practical source of information useful to anyone involved in molecular diagnostic research and/or service. Supplements are cross-referenced to the main text of the Pocket Guide, that complement and enhance the material covered. Pocket Guide to Gene Level Diagnostics in Clinical Practice will be a handy reference for professionals and students in pathology, biotechnology, biology, and medicine.

Allergic and Immunologic Diseases: A Practical Guide to the Evaluation, Diagnosis and Management of Allergic and Immunologic Diseases is a valuable resource for researchers and others involved in the day-to-day practice of allergy and immunology, with specific information, protocols and algorithms to guide their thinking. The book provides practical information and an explanation of why and how we do things, while also addressing the limitations of testing and treatment. Other sections focus on scientific based practices and the known pathophysiology of allergic and immunologic diseases, along with mechanisms of action in various treatment modalities. This book is unique in that it explains the rationale behind everything we do in allergy and immunology, hence it offers readers specific information on procedures and how to order tests and treat allergic and immunologic diseases.