Activators And Inhibitors Of Complement

Author : Robert B. Sim
Publisher : Springer Science & Business Media
Page : 243 pages
File Size : 45,9 Mb
Release : 2012-12-06
Category : Medical
ISBN : 9789401127578

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Activators and Inhibitors of Complement by Robert B. Sim Pdf

The complement system is a group of proteins which plays a major role in the processing and removal of microorganisms and tissue breakdown products from the circulation and extracellular spaces. The system is activated by a wide range of targets, and activation leads to the production of opsonins, chemotaxis of granulocytes, cell lysis and other biological activities. Inappropriate overactivation of the system contributes to inflammatory tissue damage in the host, while inadequate activation leads to accumulation of immune complexes and other debris in the circulation, and susceptibility to infection. The biology and biochemistry of the system is now adequately understood, and attempts can be made to manipulate the activation and activities of the system for potential therapeutic purposes. The reviews in this volume summarise what is known of the ways in which the complement system can be activated, by interaction with antibodies, microorganisms, cell debris, and complex carbohydrates and how the activities and activation of the system have been modified, accidentally or by design, in vitro or in vivo by drugs, venoms, particulate carbohydrates, specific antibodies, synthetic peptides and other reagents.

Author : John D. Lambris,Dimitrios C. Mastellos,Edimara S. Reis
Publisher : Frontiers Media SA
Page : 185 pages
File Size : 40,9 Mb
Release : 2020-02-14
Category : Electronic
ISBN : 9782889634705

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Therapeutic Modulation of the Complement System: Clinical Indications and Emerging Drug Leads by John D. Lambris,Dimitrios C. Mastellos,Edimara S. Reis Pdf

The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune activation and irreversible tissueinjury that collectively exacerbate both acute and chronic pathologies. Indeed,complement dysregulation or excessive activation have been widely recognized askey pathogenic drivers in a wide spectrum of inflammatory or immune-mediateddiseases. Targeted modulation of the complement system at various points ofthe cascade has revealed promising therapeutic targets for ameliorating diseasescores in a number of conditions ranging from ocular, neurodegenerative andthromboinflammatory disorders, to cancer, periodontal diseases, chronic hemolyticanemias, ischemia-reperfusion organ injury, antibody-mediated transplant rejectionand hemodialysis-triggered inflammation. Elegant pre-clinical studies employing a diversified toolbox of highly specificcomplement inhibitors in rodent or primate models of disease have opened newavenues of therapeutic exploration by providing proof of concept for the therapeuticefficacy of complement modulation. At the same time, the clinical experience gainedduring this last decade with the sole complement-specific drug currently in the clinic,eculizumab, has rekindled the interest of biopharmaceutical companies in developingnew and potent complement therapeutics for complement-driven diseases. In this respect, the complement field is witnessing a new surge of clinical trialsthat are evaluating the safety, PK/PD profile and clinical efficacy of promising drugcandidates in a number of clinical conditions driven by complement imbalance orover-activation.

Author : Janos Szebeni
Publisher : Springer Science & Business Media
Page : 566 pages
File Size : 40,5 Mb
Release : 2007-05-08
Category : Medical
ISBN : 9781402080562

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The Complement System by Janos Szebeni Pdf

As a phylogenetically old system complement is now regarded as a part of innate immunity. But it is much more than that. It bridges innate and adapted immunity, participates not only in host defense but also in many essential physiological processes, old and new diseases and adverse conditions. Indeed, complement became a term that almost defies categorization. What was for a long time a subject for a limited number of specialists has now moved into the mainstream of experimental and clinical immunology. In 1973 I visited the Basel Institute of Immunology and met its director, the eminent scientist and Nobel laureate Nils Jerne. When I entered his office he greeted me with the following words: “Complement, does that really exist?” I was never certain whether he wanted only to tease me or whether he sincerely believed that the complement system was an unimportant biological curiosity, a misstep of evolution. But, of course, missteps do not survive the evolutionary process. Little did I foresee the dramatic developments of recent years when Hans J. Müller-Eberhard and I started to unravel the specifics of the action of the cobra venom factor on the complement system in 1968 and defined a new pathway to its activation. An elucidation of the role of the system in diseases and its control for therapeutic reasons is now getting closer to actual realization in the clinic although many problems, in particular those of highly specificinhibition free of side effects, have still to be resolved.

Author : John D. Lambris
Publisher : Springer Science & Business Media
Page : 333 pages
File Size : 48,6 Mb
Release : 2012-02-04
Category : Medical
ISBN : 9780387789521

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Current Topics in Complement II by John D. Lambris Pdf

Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory functions in the context of inflammation and also serving as a vital link between the innate and adaptive immune response. In the post-genomic era, our knowledge of the innate immune system is enriched by findings that point to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or Inflammation. Several studies indicate that complement proteins exert functions that are either more complex than previously thought, or go well beyond the innate immune character of the system. The advent of high-throughput platforms for genome and proteome-wide profiling, together with the enormous amount of raw genetic information that has accumulated in the databases, have stirred new expectations in biomedical research. They have led complementologists to revisit established biological systems, such as the complement system, from a global and integrative perspective. Complement research is now faced with the challenge of trying to integrate isolated biochemical pathways into complex gene and protein regulatory circuits. In this respect, scientists from around the world convened at the Fourth Aegean Conferences Workshop on Complement Associated Diseases, Animal Models, and Therapeutics (June 10-15, 2007), to discuss recent advances in this fast evolving field. This volume represents a collection of topics on the “novel” functions of complement, patho-physiology, protein structures, design of complement inhibitors, and complement assays discussed during the conference.

Author : John D. Lambris,V. Michael Holers,Daniel Ricklin
Publisher : Springer Science & Business Media
Page : 323 pages
File Size : 48,5 Mb
Release : 2012-09-19
Category : Medical
ISBN : 9781461441175

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Complement Therapeutics by John D. Lambris,V. Michael Holers,Daniel Ricklin Pdf

This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.

Author : John D. Lambris,V. Michael Holers
Publisher : Springer Science & Business Media
Page : 280 pages
File Size : 40,9 Mb
Release : 2000-04-15
Category : Medical
ISBN : UOM:39015049491346

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Therapeutic Interventions in the Complement System by John D. Lambris,V. Michael Holers Pdf

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Author : H.J. Müller-Eberhard,P.A. Miescher
Publisher : Springer Science & Business Media
Page : 469 pages
File Size : 43,5 Mb
Release : 2012-12-06
Category : Medical
ISBN : 9783642824166

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Complement by H.J. Müller-Eberhard,P.A. Miescher Pdf

Activation of the complement system gives rise to a number of molecular species which can interact with host-derived cells and regulate their function. This interaction is mediated through distinct cell surface complement receptors, and receptor engagement produces biologic responses which can either modulate host defense reactions or enhance inflammation. Although the first complement receptor was recognized more than 30 years ago [80J, detailed biochemical information concerning the receptors has only recently become available. Currently, eight distinct complement receptors are recognized. Five receptors (CRl, CR2, CR3, C3a receptor, and C3e receptor) react with various regions on C3 while the other receptors display specificity for Clq, C5a, or Factor H. This chapter focusses on the chemistry of the various ligands and receptors and discusses the biologic activities which arise as a result of receptor-ligand interaction. II. CIQ Receptor A. The Ligand Clq is the recognition molecule of the classical complement pathway [reviewed in 20, 130]. In serum, it is part of a calcium-dependent penta molecular complex containing one molecule ofClq and two molecules each of the pro enzymes Clr and CIs. During classical pathway activation, the macromolecular complex becomes associated with the activator through the Clq subcomponent. Bound Clq undergoes a conformational change and induces the proteolytic autoactivation of Clr which in turn effects the proteolytic activation of CIs. This process is controlled by the Cl inhibitor (ClINH) which binds irreversibly to activated Clr and CIs, and inhibits their enzymatic activities.

Author : Holger Heine
Publisher : Springer Science & Business Media
Page : 248 pages
File Size : 51,5 Mb
Release : 2007-12-07
Category : Science
ISBN : 9783540739302

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Innate Immunity of Plants, Animals and Humans by Holger Heine Pdf

This book has been cunningly designed to provide an overview of our current knowledge about the innate immune systems of these three types of organisms. It not only covers the innate immune mechanisms and responses of such diverse organisms as plants, Cnidaria, Drosophila, urochordates and zebrafish, but also the major receptor systems in mammalians and humans. It delves too into the central defense mechanisms, antimicrobial peptides and the complement system.

Author : B. Paul Morgan,Andrew L. Harris
Publisher : Academic Press
Page : 382 pages
File Size : 46,5 Mb
Release : 1999-02-18
Category : Medical
ISBN : 0080529569

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Complement Regulatory Proteins by B. Paul Morgan,Andrew L. Harris Pdf

From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators in vivo are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate! Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious. Complement regulators--structure, functional roles and mode of action Comprehensive reviews of each of the individual regulators Roles of Complement regulators in vivo,in health and disease: Consequences of deficiency Roles in the reproductive system Interactions with pathogens Exploitation for therapy Complement regulators in other species

Author : William Clarke,Mark Marzinke
Publisher : Academic Press
Page : 1070 pages
File Size : 44,9 Mb
Release : 2020-06-11
Category : Science
ISBN : 9780128158333

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Contemporary Practice in Clinical Chemistry by William Clarke,Mark Marzinke Pdf

Contemporary Practice in Clinical Chemistry, Fourth Edition, provides a clear and concise overview of important topics in the field. This new edition is useful for students, residents and fellows in clinical chemistry and pathology, presenting an introduction and overview of the field to assist readers as they in review and prepare for board certification examinations. For new medical technologists, the book provides context for understanding the clinical utility of tests that they perform or use in other areas in the clinical laboratory. For experienced laboratorians, this revision continues to provide an opportunity for exposure to more recent trends and developments in clinical chemistry. Includes enhanced illustration and new and revised color figures Provides improved self-assessment questions and end-of-chapter assessment questions

Author : Maciej Cedzyński,Nicole M. Thielens,Tom Eirik Mollnes,Thomas Vorup-Jensen
Publisher : Frontiers Media SA
Page : 631 pages
File Size : 44,9 Mb
Release : 2019-11-18
Category : Electronic
ISBN : 9782889631599

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The Role of Complement in Health and Disease by Maciej Cedzyński,Nicole M. Thielens,Tom Eirik Mollnes,Thomas Vorup-Jensen Pdf

Author : Craig Halberstadt,Dwaine F. Emerich
Publisher : Elsevier
Page : 696 pages
File Size : 40,9 Mb
Release : 2011-10-10
Category : Science
ISBN : 9780080469041

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Cellular Transplantation by Craig Halberstadt,Dwaine F. Emerich Pdf

There have been tremendous strides in cellular transplantation in recent years, leading to accepted practice for the treatment of certain diseases, and use for many others in trial phases. The long history of cellular transplantation, or the transfer of cells from one organism or region of the body to another, has been revolutionized by advances in stem cell research, as well as developments in gene therapy. Cellular Transplants: From Lab to Clinic provides a thorough foundation of the basic science underpinning this exciting field, expert overviews of the state-of-the-art, and detailed description of clinical success stories to date, as well as insights into the road ahead. As highlighted by this timely and authoritative survey, scale-up technologies and whole organ transplantation are among the hurdles representing the next frontier. The contents are organized into four main sections, with the first covering basic biology, including transplant immunology, the use of immunosuppressive drugs, stem cell biology, and the development of donor animals for transplantation. The next part looks at peripheral and reconstructive applications, followed by a section devoted to transplantation for diseases of the central nervous system. The last part presents efforts to address the key challenges ahead, such as identifying novel transplantable cells and integrating biomaterials and nanotechnology with cell matrices. Provides detailed description of clinical trials in cell transplantation Review of current therapeutic approaches Coverage of the broad range of diseases addressed by cell therapeutics Discussion of stem cell biology and its role in transplantation

Author : Paul L. Wood
Publisher : Springer Science & Business Media
Page : 411 pages
File Size : 46,8 Mb
Release : 2002-12-18
Category : Medical
ISBN : 9781592592975

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Neuroinflammation by Paul L. Wood Pdf

In this thoroughly updated and revised edition of his much praised book, Paul L. Wood and a panel of leading researchers capture these new developments in a masterful synthesis of what is known today about the inflammatory mediators and cells involved in neurodegenerative diseases. This second edition contains extensive updates on the mediators produced by microglia and their role in neuroinflammatory-induced neuronal lysis. There is also increased coverage of the animal models used in the study of neuroinflammatory mechanisms, of the new imaging methods that allow the noninvasive evaluation of microglial activation in human neurodegernerative disorders, and of the role of neuroinflammation in amyloid-dependent neuronal lysis.

Author : Hans-Werner Vohr
Publisher : Springer
Page : 0 pages
File Size : 45,5 Mb
Release : 2005-06-01
Category : Medical
ISBN : 3540441727

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Encyclopedic Reference of Immunotoxicology by Hans-Werner Vohr Pdf

This work provides rapid access to focused information on topics of Immunotoxicology not only for scientists and those dealing with laboratory aspects but also for lecturers and advanced students. Over 200 contributing authors – including many of the world’s top specialists – have contributed full essays on all relevant topics, supplemented by keyword definitions of related terms. Full essays are structured uniformly to provide reader-friendly information on all aspects of Immunotoxicology, including methods of testing and analysis, characteristics of substances, the regulatory environment and the relevance of these to humans. The single A–Z format of both types of entry makes this reference book very easy to use. The Encyclopedic Reference of Immunotoxicology is intended to be a comprehensive work of reference which will provide easy access to relevant information in the fast-growing field of Immunotoxicology.

Author : Tom S. Neuman,Stephen R. Thom
Publisher : Elsevier Health Sciences
Page : 637 pages
File Size : 51,6 Mb
Release : 2008-06-05
Category : Medical
ISBN : 9781416034063

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Physiology and Medicine of Hyperbaric Oxygen Therapy by Tom S. Neuman,Stephen R. Thom Pdf

Written by internationally recognized leaders in hyperbaric oxygen therapy (HBOT) research and practice, this exciting new book provides evidence-based, practical, useful information for anyone involved in HBOT. It outlines the physiologic principles that constitute the basis for understanding the clinical implications for treatment and describes recent advances and current research, along with new approaches to therapy. This book is an essential tool for anyone who cares for patients with difficult-to-heal wounds, wounds from radiation therapy, carbon monoxide poisoning, and more. Provides comprehensive coverage of pathophysiology and clinically relevant information so you can master the specialty. Covers the relevance of HBOT in caring for diverse populations including critical care patients, infants and pediatric patients, and divers. Features a section on the technical aspects of HBOT to provide insight into the technology and physics regarding HBO chambers. Presents evidence to support the effectiveness of HBOT as well as the possible side effects. Describes situations where HBOT would be effective through indication-specific chapters on chronic wounds, radiation and crush injuries, decompression sickness, and more.