Download or read book Integrin Activation on Circulating Inflammatory Monocytes written by Greg Allen Foster and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Coronary artery disease (CAD) results in the narrowing of the small blood vessels that supply oxygen to the heart and is the major cause of morbidity and mortality in the U.S. Since CAD is largely asymptomatic, clinicians rely on biomarkers in the blood (e.g., low- and high-density lipoprotein cholesterol, C-reactive protein, and triglyceride levels) to determine cardiovascular risk and to guide therapy for an individual patient. However, these conventional biomarkers lack in specificity to inform on vascular health, as they fail to identify >20% of subjects at risk for future complications resulting from coronary blockage. Atherosclerosis underlying CAD is dependent on the recruitment of circulating monocytes to inflamed endothelium expressing vascular cell adhesion molecule-1 (VCAM-1). Therefore, the objectives of this work were: 1) develop unique assays to assess the functional phenotype of circulating monocytes during inflammation associated with atherogenesis, 2) characterize the relationship between activated monocytes and cardiovascular risk, and 3) elucidate the mechanism through which activated blood monocytes recruit to inflamed endothelium. To address the objectives of this dissertation, we fabricated a microfluidic based lab-on-a-chip to quantify the adhesion efficiency of monocytes sheared in whole blood on VCAM-1. The lab-chip device, combined with fluorescent antibody labeling against CD14 and CD16, allowed us to characterize the recruitment efficiency of monocyte subsets, in particular the inflammatory CD14++CD16+ (Mon2). We found that Mon2 adhered with 7-fold higher efficiency than other subsets and capture was dependent on integrins CD11c/CD18 and very late antigen-4 (VLA-4). To characterize the relationship between capture of inflammatory Mon2 and cardiovascular risk, we studied a range of subjects that included otherwise healthy individuals with elevated serum triglyceride levels to patients presenting with acute myocardial infarction resulting from coronary disease. We found that Mon2 from hypertriglyceridemic subjects exhibited increased CD11c expression and capture on VCAM-1 compared to subjects with normal serum triglyceride levels. CD11c expression and capture efficiency was further elevated in patients with known CAD suggesting a hierarchal relationship between activation of Mon2 and cardiovascular disease risk. Upregulation of CD11c in blood was attributable to Mon2 uptake of triglyceride rich lipoproteins and subsequent signaling via a phospholipase C (PLC)-dependent mechanism to increase CD11c expression, VLA-4 function, and integrin co-clustering within focal adhesive sites on VCAM-1. Using a unique antibody that allosterically binds CD11c and induces a high affinity conformation, we found that outside-in activation of CD11c on the membrane directly activated VLA-4 adhesion via phospho-spleen tyrosine kinase (pSyk) and paxillin within focal adhesion complexes. In summary, this work reveals that CD11c is an inducible integrin on inflammatory Mon2, whose expression correlates with monocyte inflammatory state in subjects at risk for atherogenesis and in patients with CAD. Therefore CD11c on Mon2 is a biomarker of cardiovascular risk and a potential target for drug therapy to ameliorate the recruitment of inflammatory monocytes during atherogenesis.
Download or read book Inflammation and the Microcirculation written by D. Neil Granger and published by Morgan & Claypool Publishers. This book was released on 2010 with total page 99 pages. Available in PDF, EPUB and Kindle. Book excerpt: The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References
Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Download or read book Adhesion Molecules Function and Inhibition written by Klaus Ley and published by Springer Science & Business Media. This book was released on 2007-10-27 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume gives a comprehensive overview on the most relevant leukocyte and endothelial adhesion molecules. The chapters are written by leaders in the field and focus on the biology, structure, function, and regulation of adhesion molecules. Currently approved adhesion molecule-based therapies are reviewed and an outlook for future approaches is also provided. The book is of interest to clinicians and scientists from immunology, physiology, cancer research, rheumatology, allergology, infectious diseases, gastroenterology, pulmonology and cardiology.
Download or read book Leucocyte Trafficking written by A. Hamann and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: An essential component of inflammation is the migration of circulating leukocytes from blood into tissues. This process is characterized by a multistep paradigm of sequential cell adhesion and activation events that lead to the extravasation of specific leukocyte subsets to different tissues in health and disease. The first step of leukocyte extravasation, the rolling of leukocytes, is primarily mediated by the interactions of selectins and their ligands. It has recently become evident that fucosyltransferases are crucial for selectin ligand synthesis, inflammation, and skin homing. This book provides an in-depth overview of the mechanisms of leukocyte trafficking and of the molecular mechanisms of selectin/selectin ligand interactions and discusses options for pharmacological intervention to treat inflammatory diseases.
Download or read book The Impact of Food Bioactives on Health written by Kitty Verhoeckx and published by Springer. This book was released on 2015-04-29 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
Download or read book Mechanisms of Vascular Disease written by Robert Fitridge and published by University of Adelaide Press. This book was released on 2011 with total page 589 pages. Available in PDF, EPUB and Kindle. Book excerpt: New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.
Download or read book Arrest chemokines written by Klaus Ley and published by Frontiers Media SA. This book was released on 2015-05-20 with total page 109 pages. Available in PDF, EPUB and Kindle. Book excerpt: Arrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Whether soluble chemokines can promote integrin activation and arrest is controversial (Alon-Gerszten). Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. We welcome reports that help clarifying this crucial first step in the process of leukocyte transendothelial migration.
Download or read book Blood Purification in Intensive Care written by Claudio Ronco and published by Karger Medical and Scientific Publishers. This book was released on 2001-01-01 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the last twenty years, critical care medicine has been established as a specialty with its own therapies and procedures, with significant implications for clinical nephrology regarding severe acute renal failure. This typically multi-factorial condition is today predominantly seen in intensive care units. The complex knowledge and skills necessary to handle it have resulted in a field called Critical Care Nephrology, where nephrologist and intensivist either work side by side or have formally acquired expertise and training in both specialties. Extracorporeal renal replacement therapies, although originally used to treat end-stage renal disease patients, rapidly gained importance for acute patients. This has had far-reaching implications for the initiation and possible role of blood purification in the management of critically ill patients, widening the scope of interaction between the nephrologist and the intensivist.Experts in the field have contributed to the present book, providing a comprehensive review of the different blood purification techniques relevant in the intensive care unit in the case of multiple organ failure. The resulting mix of established knowledge and recent results from both clinical trials and basic research constitutes a valuable tool for all professionals involved in the care of the critically ill patient.
Download or read book M1 M2 Macrophages The Arginine Fork in the Road to Health and Disease written by Charles Dudley Mills and published by Frontiers Media SA. This book was released on 2015-03-23 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either “Kill” or “Repair”. Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to “activate” or “alternatively activate” macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health.
Download or read book Molecular Basis of Health and Disease written by Undurti N. Das and published by Springer Science & Business Media. This book was released on 2011-04-02 with total page 591 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book describes how the balance between pro- and anti-inflammatory molecules is related to health and disease. It is suggested that many diseases are initiated and their progress is influenced by inflammatory molecules and a decrease in the production and/or action of anti-inflammatory molecules and this imbalance between pro- and anti-inflammatory molecules seems to have been initiated in the perinatal period. This implies that strategies to prevent and manage various adult diseases should start in the perinatal period. An alteration in the metaolism of essential fatty acids and their anti-inflammatory molecules such as lipoxins, resolvins, protecitns, maresins and nitrolipids seems to play a major role in the pathobiology of several adult diseases. Based on these concepts, novel therapeutic approaches in the management of insulin resistance, obesity, type 2 diabetes mellitus, metabolic syndrome, cancer, lupus, rheumatoid arthritis and other auto-immune diseases are presented. Based on all these evidences, a unified concept that several adult diseases are due to an alteration in the balance between pro- and anti-inflammatory molecules is discussed and novel methods of their management are presented.
Download or read book The Endothelium Part I written by Michel Félétou and published by Biota Publishing. This book was released on 2011-05-01 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Download or read book Encyclopedia of Medical Immunology written by Ian R. Mackay and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Offering a broad appeal to microbiologists, immunologists, and infectious disease specialists, this four volume encyclopedia covers all autoimmune, tropical, and infectious diseases. Emphasis will also be placed on genetics, physiology, metabolism, pathogenesis and applied microbiology. Under the leadership of some of the most world renowned names in the field, the encyclopedia will bring together an outstanding collection of contributions by top scientists in a variety of fields. Volumes 1-3: Diseases will be divided by the 11 main sections of the body, namely Integumentary, Skeletal, Respiratory, Digestive, Urinary, and Reproductive. For some of the autoimmune disease, more then one system will be involved but the delineation serves to broadly break down the diseases into systems. Volume 4 will cover the vaccines for said diseases and future prospects will be offered by leaders in industry and academia. Volume 4 will also be broken down into all the body systems, as in the other two volumes. For each vaccine, for each disease, and in each system the following will be included: • A list of the vaccines currently available along with a list of the companies that manufacture them • Molecular Immunology of the Vaccine • Type of Immunity involved in protection • Mode of Vaccination for each vaccine; repeated boosters and length of immunological memory • Commercial production of vaccines • Storage of vaccines • Standardization and Control of Vaccines • WHO programs and World-Wide Disease Eradication Programs based upon Vaccines.
Download or read book The Non Thrombotic Role of Platelets in Health and Disease written by Steve W. Kerrigan and published by BoD – Books on Demand. This book was released on 2015-11-18 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: Platelets play a key role in thrombosis and haemostasis. However recent evidence clearly demonstrates that the functional role of platelets extends to many other processes in the body. With an internationally recognised list of contributing authors, The Non-Thrombotic Role of Platelets in Health and Disease, is a unique and definitive source of state-of-the-art knowledge about the additional role of platelets outside thrombosis and haemostasis. The intended audience for The Non-Thrombotic Role of Platelets in Health and Disease includes platelet biologists, microbiologists, immunologists, haematologists, oncologists, respiratory physicians, cardiologists, neurobiologists, tissue engineers, as well as students and fellows in these areas.
Download or read book Inflammation in Heart Failure written by Matthijs Blankesteijn and published by Academic Press. This book was released on 2014-12-05 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammation in Heart Failure, edited by W. Matthijs Blankesteijn and Raffaele Altara, is the first book in a decade to provide an in-depth assessment on the causes, symptoms, progression and treatments of cardiac inflammation and related conditions. This reference uses two decades of research to introduce new methods for identifying inflammatory benchmarks from early onset to chronic heart failure and specifically emphasizes the importance of classifying at-risk subgroups within large populations while determining the patterns of cytokines in such classifications. Further, the book details clinical applications of the pathophysiological mechanisms of heart failure, diagnosis and therapeutic strategies. Inflammation in Heart Failure's breadth of subject matter, easy-to-follow structure, portability, and high-quality illustrations create an accessible benefit for researchers, clinicians and students. - Presents updated information and research on the relevant inflammatory mediators of heart failure to aid in targeting future translational research as well as the improvement of early diagnosis and treatment - Provides research into better understanding the different inflammatory mediators that signal the underlying diseases that potentially lead to heart failure - Contains 20 years of research, offering a brief overview of the topic leading to current opinions on, and treatment of, heart failure - Provides a structured, systematic and balanced overview of the role of inflammation in heart failure making it a useful resource for researchers and clinicians, as well as those studying cardiovascular diseases
Download or read book Mast Cells and Basophils written by Gianni Marone and published by Academic Press. This book was released on 2000-05-25 with total page 738 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mast Cells and Basophils will be essential reading for immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.
Download or read book Hematology written by Ronald Hoffman and published by Elsevier Health Sciences. This book was released on 2013-01-01 with total page 2789 pages. Available in PDF, EPUB and Kindle. Book excerpt: This leading text reflects both the new direction and explosive growth of the field of hematology. Edited and written by practitioners who are the leaders in the field, the book covers basic scientific foundations of hematology while focusing on its clinical aspects. This edition has been thoroughly updated and includes ten new chapters on cellular biology, haploidentical transplantation, hematologic manifestations of parasitic diseases, and more. The table of contents itself has been thoroughly revised to reflect the rapidly changing nature of the molecular and cellular areas of the specialty. Over 1,000 vivid images, now all presented in full color for the first time, include a collection of detailed photomicrographs in every chapter, selected by a hematopathology image consultant. What's more, this Expert Consult Premium Edition includes access to the complete contents of the book online, fully searchable and updated quarterly by Dr. Hoffman himself. - Publisher.
