Chronic Inflammation In Conditions Associated With A Deficient Clearance Of Dying And Dead Cells Their Remnants And Intracellular Constituents

In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue remodelling. The proper and swift clearance of apoptotic cells is essential to prevent cellular leakage of damage associated molecular patterns (DAMPs) which would lead to the stimulation of inflammatory cytokine responses. In addition to the clearance of apoptotic cells (efferocytosis), backup mechanisms are required to cope with DAMPs (HMGB-1, DNA, RNA, S100 molecules, ATP and adenosine) and other intracellular material (uric acid, intracellular proteins and their aggregates) released from cells, that were not properly cleared and have entered the stage of secondary necrosis. Furthermore, under certain pathologic conditions (e.g. gout, cancer, diabetes) non-apoptotic cell death may transiently occur (NETosis, necroptosis, pyroptosis) which generates material that also has to be cleared to avoid overloading tissues with non-functional cellular waste. Efficient efferocytosis is therefore indispensable for normal tissue turnover and homeostasis. The characterization of various signalling pathways that regulate this complex and evolutionary conserved process has shed light on new pathogenetic mechanisms of many diseases. Impaired clearance promotes initiation of autoimmunity as well as the perpetuation of chronic inflammation, but may also foster anti-tumor immunity under certain microenvironmental conditions. Immunological tolerance is continuously being challenged by the presence of post-apoptotic remnants in peripheral lymphoid tissues. Besides the autoimmune phenotype of chronic inflammatory rheumatoid disorders a plethora of pathologies have been associated with defects in genes involved in clearance, e.g. atherosclerosis, cancer, gout, diabetes, some forms of blindness, neuropathy, schizophrenia and Alzheimer’s disease. The main goal of this research topic is to collect contributions from various disciplines committed to studying pathogenetic mechanisms of the aforementioned disorders and dealing with alterations in the clearance of dying and dead cells, their remnants, and their constituents that leak out after membrane rupture. Integrating the combined collection of knowledge on efferocytosis and clearance of dead cells and their derived waste from different fields of research in physiology and pathophysiology could improve the molecular understanding of these increasingly prevalent diseases and may ultimately result in new therapeutic strategies.

Animal Lectins: Form, Function and Clinical Applications presents up-to-date knowledge of animal lectins. Detailed descriptions on biological activities, tissue and/or subcellular distribution, molecular structure, gene organization, possible functions, clinical applications, lectin-ligand interactions and their intervention for therapeutic purposes are provided. The recently discovered C-type lectins as well as further novel super-families of this group of molecules are described in detail. Furthermore, the clinical significance of animal lectins in inflammatory diseases, defects of immune defense and autoimmunity are described and their application as drugs and therapeutic targets is discussed. With the increasing interest in lectins in biomedical research and their therapeutic applications, this book on animal lectins and associated proteins is a must have for researchers in the area.

Systemic Lupus Erythematosus combines basic science with clinical science to provide a translational treatment of the disease and is a useful reference for specialists in the diagnosis and management of patients with SLE, a tool for measurement of clinical activity for pharmaceutical development and basic research of the disease and a reference work for hospital libraries. Provides the very latest overview of the pathogenesis of SLE Distills current understanding of the cellular, molecular, genetic and environmental factors that instigate and drive the disease Includes comprehensive coverage of clinical features, including fatigue, organ system manifestations, overlap syndromes, infections, and more Conveys the very latest understanding of mechanisms of tissue damage, including immune complexes, antibodies, and other mechanisms that lead to organ damage Discusses the latest treatment options on disease modifying or disease controlling agents Provides 'one stop' coverage of all the latest scientific and clinical developments in SLE

The 4th edition of this textbook, now in full color, presents both general pathology and special pathology in one comprehensive resource. Coverage includes a brief review of basic principles related to anatomy, structure and function, followed by congenital and functional abnormalities and discussions of viral, bacterial, and parasitic infections and neoplasia. Logically organized chapters discuss normal functions of the body system, followed by pathologic conditions found in domestic and companion animals. While focusing primarily on diseases in North America, the text also includes pathologic conditions found in other parts of the world, as well as those being brought into this country, such as West Nile virus, through the importation of cattle, sheep, and other animals. Contributors are recognized in their area of expertise and are well known in research and education. Now in full color throughout with vivid new illustrations that clarify difficult concepts. Includes six new chapters covering general pathology that discuss topics such as cellular and tissue responses to injury, vascular disorders, inflammation, and tumor biology. All chapters emphasize mechanisms of disease (organ, tissue, cell, and molecular injury). Features sequential presentations of disease processes (portal of entry * target cells * cellular injury * visual appearance of injury * resolution of injury * clinical outcomes). Emphasizes portals of entry for microbes and injurious agents. Focuses on defense mechanisms against microbes and injurious agents.

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

A single tick bite can have debilitating consequences. Lyme disease is the most common disease carried by ticks in the United States, and the number of those afflicted is growing steadily. If left untreated, the diseases carried by ticks-known as tick-borne diseases-can cause severe pain, fatigue, neurological problems, and other serious health problems. The Institute of Medicine held a workshop October 11-12, 2010, to examine the state of the science in Lyme disease and other tick-borne diseases.