The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Antibodies produced by a single clone of cells.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Proteins found in any species of bacterium.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Established cell cultures that have the potential to propagate indefinitely.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Proteins prepared by recombinant DNA technology.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
The rate dynamics in chemical or physical systems.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Glycoproteins found on the membrane or surface of cells.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Elements of limited time intervals, contributing to particular results or situations.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.
A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Methods used by pathogenic organisms to evade a host's immune system.
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Transport proteins that carry specific substances in the blood or across cell membranes.
A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
The sum of the weight of all the atoms in a molecule.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The functional hereditary units of BACTERIA.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Inflammation of any part of the KIDNEY.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Polysaccharides found in bacteria and in capsules thereof.
Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.
Proteins isolated from the outer membrane of Gram-negative bacteria.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
An encapsulated lymphatic organ through which venous blood filters.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Immunoglobulins produced in response to VIRAL ANTIGENS.
Substances elaborated by bacteria that have antigenic activity.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Substances that are recognized by the immune system and induce an immune reaction.
Limbless REPTILES of the suborder Serpentes.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.
Polysaccharides consisting of mannose units.
A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.
All blood proteins except albumin ( = SERUM ALBUMIN, which is not a globulin) and FIBRINOGEN (which is not in the serum). The serum globulins are subdivided into ALPHA-GLOBULINS; BETA-GLOBULINS; and GAMMA-GLOBULINS on the basis of their electrophoretic mobilities. (From Dorland, 28th ed)
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Sites on an antigen that interact with specific antibodies.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Infections with bacteria of the species NEISSERIA MENINGITIDIS.
Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.
Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)
Stable chromium atoms that have the same atomic number as the element chromium, but differ in atomic weight. Cr-50, 53, and 54 are stable chromium isotopes.
The relationships of groups of organisms as reflected by their genetic makeup.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.
Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.
Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

Complement activity and pharmacological inhibition in cardiovascular disease. (1/54)

While complement is the most important component of humoral autoimmunity, and inflammation plays a key role in atherosclerosis, relatively few studies have looked at complement implications in atherosclerosis and its complications. C-reactive protein is a marker of inflammation and is also involved in atherosclerosis; it activates complement and colocalizes with activated complement proteins within the infarcting myocardium and the active atherosclerotic plaques. As new agents capable of modulating complement activity are being developed, new targets for the management of atherosclerosis are emerging that are related to autoimmunity and inflammation. The present paper reviews the putative roles of the various complement activation pathways in the development of atherosclerosis, in ST segment elevation and non-ST segment elevation acute coronary syndromes, and in coronary artery bypass graft surgery. It also provides a perspective on new therapeutic interventions being developed to modulate complement activity. These interventions include the C1 esterase inhibitor, which may be consumed in some inflammatory states resulting in the loss of one of the mechanisms inhibiting activation of the classical and lectin pathways; TP10, a recombinant protein of the soluble complement receptor type 1 (sCR1) which inhibits the C3 and C5 convertases of the common pathway by binding C3b and C4b; a truncated version of the soluble complement receptor type 1 CRI lacking the C4b binding site which selectively inhibits the alternative pathway; and pexelizumab, a monoclonal antibody selectively blocking C5 to prevent the activation of the terminal pathway that is involved in excessive inflammation and autoimmune responses.  (+info)

Therapeutic strategy with a membrane-localizing complement regulator to increase the number of usable donor organs after prolonged cold storage. (2/54)

A shortage of donor organs and increasing dependence on marginal grafts with prolonged ischemic times have meant that new methods are needed to prevent postischemic damage. Herein is reported a new strategy aimed to protect donor kidney from complement-mediated postischemic damage and therefore increase the number of successful transplants. Rat donor kidneys were perfused with a membrane-localizing complement regulator derived from human complement receptor type 1 (APT070) and then subjected to prolonged periods of cold storage (at 4 degrees C). A relationship was found between the duration of cold ischemia and the extent of complement-mediated tubule damage and loss of graft function. After 16 h of cold storage, APT070-treated kidneys that were transplanted into syngeneic recipients showed a significant increase in the number of surviving grafts, compared with control-treated grafts (63.6 versus 26.3%). Surviving grafts also displayed less acute tubular injury and better preservation of renal function. These results not only enhance the understanding of the mechanism by which prolonged cold ischemia reduces immediate graft survival but also provide essential information about the effectiveness of membrane-localizing complement regulator with prolonged cold storage. This could lead to more effective strategies for improving the use of severely ischemic donor organs.  (+info)

Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H. (3/54)

Relapsing fever is a rapidly progressive and severe septic disease caused by certain Borrelia spirochetes. The disease is divided into two forms, i.e., epidemic relapsing fever, caused by Borrelia recurrentis and transmitted by lice, and the endemic form, caused by several Borrelia species, such as B. duttonii, and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by the vector bite and live persistently in plasma even after the development of specific antibodies. This leads to fever relapses and high mortality and clearly indicates that the Borrelia organisms utilize effective immune evasion strategies. In this study, we show that the epidemic relapsing fever pathogen B. recurrentis and an endemic relapsing fever pathogen, B. duttonii, are serum resistant, i.e., resistant to complement in vitro. They acquire the host alternative complement pathway regulator factor H on their surfaces in a similar way to that of the less serum-resistant Lyme disease pathogen, B. burgdorferi sensu stricto. More importantly, the relapsing fever spirochetes specifically bind host C4b-binding protein, a major regulator of the antibody-mediated classical complement pathway. Both complement regulators retained their functional activities when bound to the surfaces of the spirochetes. In conclusion, this is the first report of complement evasion by Borrelia recurrentis and B. duttonii and the first report showing capture of C4b-binding protein by spirochetes.  (+info)

A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis. (4/54)

Complement is an important component of the innate and adaptive immune response, yet complement split products generated through activation of each of the three complement pathways (classical, alternative, and lectin) can cause inflammation and tissue destruction. Previous studies have shown that complement activation through the alternative, but not classical, pathway is required to initiate antibody-induced arthritis in mice, but it is unclear if the alternative pathway (AP) plays a role in established disease. Previously, we have shown that human complement receptor of the immunoglobulin superfamily (CRIg) is a selective inhibitor of the AP of complement. Here, we present the crystal structure of murine CRIg and, using mutants, provide evidence that the structural requirements for inhibition of the AP are conserved in human and mouse. A soluble form of CRIg reversed inflammation and bone loss in two experimental models of arthritis by inhibiting the AP of complement in the joint. Our data indicate that the AP of complement is not only required for disease induction, but also disease progression. The extracellular domain of CRIg thus provides a novel tool to study the effects of inhibiting the AP of complement in established disease and constitutes a promising therapeutic with selectivity for a single complement pathway.  (+info)

Characterization of Ehp, a secreted complement inhibitory protein from Staphylococcus aureus. (5/54)

We report here the discovery and characterization of Ehp, a new secreted Staphylococcus aureus protein that potently inhibits the alternative complement activation pathway. Ehp was identified through a genomic scan as an uncharacterized secreted protein from S. aureus, and immunoblotting of conditioned S. aureus culture medium revealed that the Ehp protein was secreted at the highest levels during log-phase bacterial growth. The mature Ehp polypeptide is composed of 80 residues and is 44% identical to the complement inhibitory domain of S. aureus Efb (extracellular fibrinogen-binding protein). We observed preferential binding by Ehp to native and hydrolyzed C3 relative to fully active C3b and found that Ehp formed a subnanomolar affinity complex with these various forms of C3 by binding to its thioester-containing C3d domain. Site-directed mutagenesis demonstrated that Arg(75) and Asn(82) are important in forming the Ehp.C3d complex, but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding site in Ehp, which was mapped to the proximity of Ehp Asn(63). Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-A crystal structure of an Ehp.C3d complex in which the low affinity site had been mutationally inactivated. Ehp potently inhibited C3b deposition onto sensitized surfaces by the alternative complement activation pathway. This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation in Ehp-bound C3 was detected by monoclonal antibody C3-9, which is specific for a neoantigen exposed in activated forms of C3. Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein.  (+info)

Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. (6/54)

Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TE in patients with PNH. Clinical trial participants included all patients in the 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizumab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P < .001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before eculizumab to 3 events during eculizumab (P < .001). The TE event rate in antithrombotic-treated patients (n = 103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizumab treatment (P < .001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at http://clinicaltrials.gov (study ID no. NCT00122317).  (+info)

Management of hereditary angioedema in pediatric patients. (7/54)

Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood.  (+info)

Association of reactive oxygen and nitrogen intermediate and complement levels with apoptosis of peripheral blood mononuclear cells in lupus patients. (8/54)

OBJECTIVE: Both increased production of reactive oxygen and nitrogen intermediates (RONI) and reduced levels of complement may play a role in the increased apoptosis and reduced clearance of apoptotic cells in systemic lupus erythematosus (SLE). The objective of this study was to evaluate both processes in a parallel, prospective, longitudinal manner. METHODS: Sixty-seven SLE patients were evaluated during multiple visits, and 31 healthy control subjects were evaluated once or twice. Clinical and laboratory features of SLE disease activity were determined, and blood was collected for measurement of serum nitrate plus nitrite (NOx) levels and for isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were cultured with a nitric oxide (NO) donor and SLE or control plasma, with or without heat inactivation, cobra venom factor (CVF), or lipopolysaccharide plus interferon-gamma treatment. Cells were analyzed for apoptotic index (AI), cellular subsets, and RONI production. RESULTS: The PBMC AI was associated with SLE and was inversely associated with complement levels over time. Changes in the AI with addition of a NO donor was longitudinally associated with serum NOx levels, and stimulation of SLE PBMCs led to parallel increases in RONI production and apoptosis. Addition of SLE plasma resulted in a greater PBMC AI, an effect that was increased with heat inactivation and was corrected with CVF treatment. CONCLUSION: These data suggest that the greater AI observed in SLE PBMCs relates to increased PBMC RONI production and reduced complement levels. The longitudinal nature of these parallel associations within individuals suggests that these processes are dynamic and additive.  (+info)

The success of microorganisms as human pathogens stems partly from their ability to evade recognition and/or avoid destruction by complement and other natural and acquired defense mechanisms. Here, Neil Cooper reviews the various mechanisms that pathogens have evolved to evade the destructive action …
The vitamins -A, B-Complex and C increase rapidly during germination. In moong sprouts the vitamin A content increases by 285%, thiamine by 208%, riboflavin by an astounding 515%, niacin by 256% and finally ascorbic acid by 600%. When the seeds sprout, shoots appear earlier than roots. The sprouts are maximally nutritious, if consumed before the roots start emerging. ...
A Novel Protocol Allowing Oral Delivery of a Protein Complement Inhibitor that Subsequently Targets to Inflamed Colon Mucosa and Ameliorates Murine Colitis. Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; et al. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis. Clinical and Experimental Immunology 177.2 (Aug 2014): 500-508. While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of ...
TY - JOUR. T1 - Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. AU - Rancan, Mario. AU - Morganti-Kossmann, Maria Cristina. AU - Barnum, Scott R. AU - Saft, Silvia. AU - Schmidt, Oliver I. AU - Ertel, Wolfgang. AU - Stahel, Philip F. PY - 2003. Y1 - 2003. U2 - 10.1097/01.WCB.0000084250.20114.2C. DO - 10.1097/01.WCB.0000084250.20114.2C. M3 - Article. VL - 23. SP - 1070. EP - 1074. JO - Journal of Cerebral Blood Flow and Metabolism. JF - Journal of Cerebral Blood Flow and Metabolism. SN - 0271-678X. IS - 9. ER - ...
article{5be1f4a6-d9f6-43e4-84be-f1c903a8b6fe, abstract = {C4b-binding protein (C4BP), an important inhibitor of complement activation, has a unique spider-like shape. It is composed of six to seven identical alpha-chains with or without a single beta-chain, the chains being linked by disulfide bridges in their C-terminal parts. To elucidate the structural requirements for the assembly of the alpha-chains, recombinant C4BP was expressed in HEK 293 cells. The expressed C4BP was found to contain six disulfide-linked alpha-chains. Pulse-chase analysis demonstrated that the recombinant C4BP was rapidly synthesized in the cells and the polymerized C4BP appeared in the medium after 40 min. The alpha-chains were polymerized in the endoplasmic reticulum (ER) already after 5 min chase. The polymerization process was unaffected by blockage of the transport from the ER to the Golgi mediated by brefeldin A or low temperature (10 degrees C). The C-terminal part of the alpha-chain (57 amino acids), containing ...
NEW HAVEN, Conn.--(BUSINESS WIRE)--Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) announced today that the pivotal Phase 3 study of ALXN1210, the Companys investigational long-acting C5 complement inhibitor, demonstrated non-inferiority to Soliris® (eculizumab) in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) based on the co-primary endpoints of transfusion avoidance and normalization of lactate dehydrogenase (LDH) levels, a direct marker of complement-mediated hemolysis in PNH.
Chem-Crest 77-C is a long-term rust inhibitor concentrate designed as a rinse injection into an overflowing ultrasonic rinse tank. Order now.
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To provide insight into bacterial suppression of complement-mediated immunity, we present here structures of a bacterial complement inhibitory protein, both free and bound to its complement target. The 1.25-A structure of the complement component C3-inhibitory domain of Staphylococcus aureus extrace …
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Preview: This six-game Wolves homestand continues with a visit by a San Antonio team that has won 10 consecutive games and owns the NBAs best record at 38-11. ... The Spurs kick off a nine-game trip; both center Tim Duncan and guard Manu Ginobili traveled to Minneapolis but neither is expected to play. Duncan sprained his ankle and injured his knee during a scary fall in Saturdays 96-86 victory over Washington. Ginobili has an injured hamstring. ... Note the unusual start time for ESPN. ... Wolves forward Andrei Kirilenko on Tuesday was named the European Player of the Year. Past winners include Dirk Nowitzki, Pau Gasol and Tony Parker. ... NBA commissioner David Stern is expected to attend the game and will hold a news conference before it.
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central functional hub that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.. This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The ...
The survival associated with double lung transplantation (LTx) is 7.1 years, however, closer inspection of recipient pre-LTx disease demonstrates that survival amongst COPD patients (related to cigarette smoke [CS] exposure) is amongst the worst at 5.5 years, as compared to 8.9 years in cystic fibrosis patients. A number of risk factors are thought to lead to this observed inferior outcome, chief amongst these, are pre-LTx diagnosis, recipient and donor age, and donor CS history. Indeed, CS exposure in either the recipients or donors has been linked with increased rates of severe primary graft dysfunction, acute rejection (AR), and ultimately earlier graft failure. The goal of these proposed studies is to demonstrate evidence that CS exposure, either donor or recipient, alters the local lung-specific immune environment in such a way as to predispose to exacerbated ischemia-reperfusion injury (IRI), with a resultant worsening of AR. We first examined the role of CS exposure on the lung ...
Monoclonal antibody (MAB) therapies targeting central mediators of inflammatory responses, such as TNFα, have become a common immunotherapy approach in contemporary clinical practice. Unfortunately, TNFα MAB therapy comes at a cost of significantly increased risk for the development of devastating infections (22-24, 34). Following our previous work, which established the central role of TNFα for the development of protective TH1 immunity in the relevant model of IFI (7, 25, 26, 35), here, we defined a previously unknown mechanism by which TNFα exerts its profound and lasting effect on host defenses. We provide evidence that (i) TNFα contributes to the generation of a uniquely stable DC1 phenotype, which is resistant to DC2 repolarization; (ii) TNFα-stabilized DCs arising during the afferent phase of the immune response are required for generation and sustenance of protective TH1/TH17 immunity; (iii) TNFα-mediated DC1 stabilization is associated with the H3K4me3 histone modification at ...
CRI 213. Research Interests. Complement is a group of about 50 soluble and cell surface proteins that represent a crucial component of both the innate and adaptive immune systems. Research in the laboratory is focused on the biology of the complement system, and how it modulates an inflammatory response and shapes adaptive immunity. Within the context of complement-modulated immunity, areas of study relate to ischemic injury and disease (such as stroke, spinal cord injury and post-transplant ischemia reperfusion injury), alloimmunity (transplant rejection) and cancer immunity. A further area of study is the dual role of complement in liver injury and regeneration, important in the context of liver resection or small-for-size transplant. Integrated within these studies is the development and characterization of various site-targeted strategies for complement inhibition. These strategies (some of which are in clinical development) are being investigated in various mouse models of injury and ...
BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions ...
Bowman-Birk Inhibitor Concentrate is an anticarcinogenic derived from soybeans which inhibits the protease chymotrypsin. The inhibitor was being developed at
Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize a large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation - either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an
TY - JOUR. T1 - The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells - implication in subretinal immune privilege in the aging eye. AU - Luo, Chang. AU - Zhao, Jiawu. AU - Chen, Mei. AU - Xu, Heping. PY - 2018/6/13. Y1 - 2018/6/13. N2 - Age-related para-inflammation in the retina-choroidal interface is featured by low-levels of complement activation and subretinal macrophage accumulation. This study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE). Bone marrow-derived macrophages (BMDMs) and RPE cells were cultured from 8-10 weeks old C57BL/6J mice. The BMDMs were co-cultured with normal RPE, or oxidized photoreceptor outer segment (oxPOS) or TNF-α pre-treated RPE, or apoptotic RPE, or RPE-choroid eyecups. Macrophages were then isolated and processed for real-time RT-PCR. The expression of complement inhibitor C1INH in BMDMs was significantly upregulated by RPE and RPE-choroid ...
Complement inhibiting surface proteins of pathogenic bacteria provide candidates for vaccines because of two reasons. First, an immune response against them would recognize the microbes and secondly, it would neutralize the key bacterial virulence mechanism. Prerequisites for a vaccine protein include the following: (i) it should show limited variability, (ii) it should be immunogenic and the immune response against it should cover a sufficiently broad range of microbial strains, (iii) it should not be hidden beneath a capsule, long LPS O-polysaccharide side chains or a protein coat and (iv) it should not raise unwanted immune responses against host structures. Bacterial complement inhibitors often act by binding the soluble inhibitors factor H or C4 bp, by blocking C3 or C5 activation or by enzymatically cleaving key complement components. Inhibitors have been found from all major types of pathogens and may offer promise as rational vaccine candidates for preventing diseases such as ...
Hello,. I recently received a question about infusing eculizumab during dialysis to save chair time for the patient. I am aware that eculizumab is theoretically too large to be dialyzed out, but I am wondering if anyone else has experience doing this at their institution and whether there were any issues experienced?. Thanks in advance ...
TY - JOUR. T1 - Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor. AU - Farkas, Henriette. AU - Varga, Lilian. AU - Moldovan, Dumitru. AU - Obtulowicz, Krystyna. AU - Shirov, Todor. AU - Machnig, Thomas. AU - Feuersenger, Henrike. AU - Edelman, Jonathan. AU - Williams-Herman, Debora. AU - Rojavin, Mikhail. PY - 2016/11/1. Y1 - 2016/11/1. N2 - Background Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. Objective To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. Methods In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 ...
Background Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. Objective To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. Methods In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 months. Blood samples were taken at baseline (day of first attack) and months 3, 6, and 9 and analyzed for inhibitory anti-C1-INH antibody (iC1-INH-Ab) and noninhibitory anti-C1-INH antibodies (niC1-INH-Abs). Results The study included 46 patients (69.6% female; mean age, 38.9 years; all white) who received 221 on-site pnfC1-INH infusions; most patients received 6 or fewer infusions. No patient tested positive ...
The complement inhibitor C4b-binding protein (C4BP) prevents necrotic cells from spilling their pro-inflammatory guts, according to a study on page 1937. Trouw and colleagues now show that C4BP and its binding partner, anticoagulant protein S (PS), cooperate to grab onto necrotic cells and to inhibit the release of cellular DNA.. C4BP short-circuits the complement cascade by binding to the activated complement components C3b and C4b and presenting them to the proteolytic complement inhibitor Factor I for degradation. This inhibitory capacity of C4BP can be coopted by bacterial pathogens, which coat themselves with this protein to avoid complement-mediated destruction by phagocytic cells.. This group recently identified a role for the C4BP-PS complex: it binds to apoptotic cells through the phosphatidylserine-binding domain of PS. This association could prevent the deposition and activation of complement on the surface of the apoptotic cells, allowing the dying cells to be removed without ...
Feasibility of home infusion and self-administration of nanofiltered C1 esterase inhibitor for routine prophylaxis in patients with hereditary angioedema and ch
There is a growing awareness that complement plays an integral role in human physiology and disease, with an expanding list of pathologies that are linked to
Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane- spanning protein and which is highly expressed in skeletal muscle mass, heart, adipose cells, and liver. sending the transmission to determine the function of specific cells, like skeletal muscle mass, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted cells or organs in human being has exposed its physiological functions for promoting health or executing the rules of selection of metabolic illnesses. Numerous studies MLN8237 small molecule kinase inhibitor concentrate on the association of irisin with metabolic illnesses which has obtained great interest being a potential brand-new target to fight type 2 diabetes MLN8237 small molecule kinase inhibitor mellitus and insulin level of resistance. Irisin is available to boost insulin level of resistance and type 2 diabetes by raising sensitization ...
Anti-IL-6 mAb therapy: Experiments in mouse models have shown that IL-6 is indispensable for the development of RA. This accompanied with the success of anti-IL-6 with IL-6R mAb in primates encouraged the development of therpay againtst IL-6 signalling. There are currently 2 therapeutic mAb drugs available for RA. 1. Tocilizumab (Actemra or RoActemra) is used as a monotherapy for the treatment of severe cases of RA where no previous treatment or treatment with other disease modifying antirheumatic drugs (DMARDs) has been not successful. It is a humanized monoclonal antibody that works against soluble or membrane bound (anti-IL-6R) IL-6 receptor. This prevents IL-6 and IL-6R interaction and the subsequent signal transduction, thereby reducing inflammation and other symptoms of RA.. In clinical trails ~40% of the patients achieved remission i.e their symptoms disappeared. Upto 5 studies involving 4000 people showed a considerable advantage in using tocilizumab over placebo, TNF blockers or ...
A Personal Case History As a sufferer of Hereditary Angioedema (HAE) I am posting this page, detailing my own case history, as a resource for other sufferers. I hope you find it helpful. What is Hereditary Angioedema? (taken from www.hereditaryangioedema.com) Hereditary Angioedema (HAE) is a rare and serious genetic condition occurring in about 1/10,000 to 1/50,000…
the complement systems part, a protein group involved in some allergic and immune reactions. C1 inhibitors abnormal activity or deficiency results in swelling in skins local area and the tissues beneath it, or in the mucous membrane that is the lining body opening including gastrointestinal tract, throat, and the mouth.. Viral infections or injury frequently precipitates the attack, that may be caused by emotional distress. Attacks usually produce swelling areas, that are achy rather than itchy and are not accompanied by hives. Many individuals with Hereditary Angioedema have cramps, vomiting and nausea. The most severe complications include the upper airways swelling, which may affect breathing. Blood tests that measure activity or levels of C1 inhibitor, confirm diagnosis.. The treatment consists of medication called Aminocaprotic acid, which sometimes ends hereditary angioedema attacks. Corticosteroids, antihistamines, and epinephrine are frequently prescribed; although there is no proof ...
|p|Hereditary angioedema is a rare genetic condition characterized by recurrent episodes of severe swelling in the limbs, face, intestines and airways. If you’ve been diagnosed with hereditary angioedema, it’s important to be prepared for an attack. Check out this expert-backed advice on risk factors, symptoms, treatment options and more.|/p|
Compare prices and find information about prescription drugs used to treat Hereditary Angioedema. Treatment for hereditary angiodema includes...
Hereditary angioedema (HAE) is a disease characterized by recurrent episodes of angioedema,withouturticaria or pruritus, which most often affect the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. Although the swelling i
Shires Investigational Treatment Lanadelumab Reduces Hereditary Angioedema Monthly Attack Rate by 87% Versus Placebo in Phase 3 26-week Pivotal Trial
Hereditary angioedema (HAE) can be a life-threatening condition, but knowing your triggers can help prepare you for attacks. Learn about common triggers.
Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema associated with discomfort and pain. The disease places patients at risk for disability and death if left untreated. Sympto
Hereditary angioedema (HAE) is characterized by recurrent, self-limited episodes of swelling primarily involving the skin and the mucosa of the gastrointestinal tract and upper airway. There are several subtypes. The clinical manifestations, pathogen
From Executive Director Peter Waite, Canadian Hereditary Angioedema Network: The Canadian Hereditary Angioedema Network has updated its 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of HAE patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, [...]. ...
Hereditary angioedema is an inherited condition characterized by re-occurant severe swelling. It affects arms, face, legs, airway and intestinal...
ALBANY, New York, August 23, 2017 /PRNewswire/ -- Hereditary Angioedema Market to be Worth US$3.81 Billion by 2025: Initiatives to Generate Awareness by...
We are dedicated to provide support and information on Hereditary Angioedema (HAE) to both patients and physicians, including information on recently FDA
A multicentre study to investigate pharmacokinetics, clinical efficacy and safety of nanofiltered Cetor® (called C1-esteraseremmer-N during the development phase) for the treatment of hereditary angioedema (HAE) will be performed. This study KB2003.01 consists of three parts, part A pharmacokinetics (phase II), part B treatment of attacks of angioedema (phase III) and part C prophylactic use of C1 inhibitor (phase III). Part B + C will provide data on the efficacy of C1-esteraseremmer-N.. The changes in the manufacturing process of C1-esteraseremmer-N, compared to Cetor® (the currently marketed C1-inhibitor product), nanofiltration and omission of hepatitis B immunoglobulin, most likely will not affect tolerability. The nanofiltration will provide more safety regarding viruses.. In part A, the pharmacokinetics of C1-esteraseremmer-N in patients with hereditary angioedema will be compared with the current registered product, Cetor®, in a randomised, blinded cross-over design. This study has to ...
The activation and proliferation ofT- and B-cells induced by treatment with mercuric chloride (HgC12) or silver·nitrate (AgN03) was studied in mouse strains genetically susceptible (SJL, A. SW, A.TH, BALE/C) or resistant (A.TL, BALB.B) to induction of antinucleolar antibodies (ANoA) and systemic immune-complex (I C) deposits.. SJL mice homozygous for the nude (nu) mutation were severely T-cell deficient. Neither these athymic SJL mice, nor euthymic SJL mice in which T-helper (CD4+) cells were eliminated by antiCD4 MAb treatment, developed ANoA or systemic IC-deposits in response to HgCI2 . Once induced, serum ANoA were not suppressed by 7 weeks high-dose anti-CD4 MAb therapy. This shows that chronic autoantibody (ANoA) production is relatively independent of CD4+ cells, and indicates that anti-CD4 MAb therapy should be given early in the course of autoimmune conditions in order to be efficient.. A single subcutaneous injections ofHgCl2 induced after 4-5 days in the susceptible strains a ...
It took Katie years to be diagnosed with HAE. See why she believes you should never stop looking for the doctor whos right for you.
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ViroPharma Incorporated (Nasdaq: VPHM) today announced the launch of Ryze Above (www.ryzeabove.com), an exclusive patient resources program within the companys patient support
POT-4 (Potentia Pharmaceuticals) a C3 complement inhibitor may be effective against both forms of macular degeneration. The announcement was made at the Asia
• Baxter International Inc., of Deerfield, Ill., reported pivotal Phase III results showing that routine prophylaxis vs. on-demand treatment of FEIBA NF (anti-inhibitor coagulant complex [nanofiltered and vapor-heated]) in patients with hemophilia A or B reduced median annual bleed rate.
Wall Streets Augury: BioCryst Pharmaceuticals (Nasdaq:BCRX): Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic
As this eMedTV segment explains, Cinryze is injected into a vein every three or four days to prevent hereditary angioedema attacks. More dosing tips are outlined in this article, including helpful suggestions for when and how to use the injections.
See how Stacey helps care for her husband who has hereditary angioedema (HAE) and takes steps to ensure that her family is not defined by his condition.
Furthermore, BacMam viruses are inactivated by human complement, which reduces risk to researchers. Lastly, viruses used in the ... Baculoviruses are Risk Group 1 agents that have been widely used for over 25 years for insect cell protein production ... "Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system ...
... immunosuppressive agents MeSH D27.505.696.477.656.500 - complement inactivating agents MeSH D27.505.696.477.656.750 - ... antiviral agents MeSH D27.505.954.122.388.077 - anti-retroviral agents MeSH D27.505.954.122.388.077.088 - anti-hiv agents MeSH ... tocolytic agents MeSH D27.505.954.016 - anti-allergic agents MeSH D27.505.954.122 - anti-infective agents MeSH D27.505.954.122. ... tranquilizing agents MeSH D27.505.696.277.950.015 - anti-anxiety agents MeSH D27.505.696.277.950.025 - antimanic agents MeSH ...
Importantly, RNA integrity is maintained by inactivating RNases with chaotropic agents such as guanidinium isothiocyanate, ... mRNA is selectively reverse transcribed using oligo-dT primers that are the reverse complement of the poly-adenylated tail on ...
Combining ABT-737 with second agents that inactivate Mcl-1 may reduce this effect. ABT-737 has demonstrated single-agent ... and natural killer cells to destroy the targeted cells Complement-dependent cytotoxicity (CDC)-- Initiates the complement ... Cell death does not appear to be mediated by complement, but modest antibody-dependent cellular cytotoxicity and direct killing ... Reduced susceptibility to apoptosis increases the resistance of cancer cells to radiation and cytotoxic agents. B-cell lymphoma ...
"Janssen's Single-Agent Darzalex (daratumumab) Approved by European Commission for Treatment of Multiple Myeloma (MM)". ... Daratumumab binds to CD38, causing cells to apoptose via antibody-dependent cellular cytotoxicity, complement-dependent ... DTT also inactivates/destroys many antigens on the red blood cell surface by disrupting disulfide bonds. The only antigen ... Updated trial results presented in December 2012, indicate daratumumab is continuing to show promising single-agent anti- ...
Studies began to look for the possible species that acted as reservoirs for the virus and the agents responsible for ... The vaccine for KFDV consists of formalin-inactivated KFDV. The vaccine has a 62.4% effectiveness rate for individuals who ... Other methods of diagnosis included hemagglutination inhibition (HI), complement fixation, neutralization tests. However, new ...
Hence, the classic inflammatory response was viewed as fully regulated by the soluble signaling agents. That is, the agents ... complement components C5a and C3a which are chemotactic factors formed during the activation of the host's blood complement ... However, studies suggest that synthetic SPM that are resistant to being metabolically inactivated hold promise of being ... While initially found to have in vitro activity suggesting that they might act as pro-inflammatory agents, Serhan and ...
Adenylate cyclese toxin binds to target cells by the complement receptor 3 (CD11b/CD18, or Mac-1). Target cell are therefore ... Together with the pertussis toxin it is the most important virulence factor of the causative agent of whooping cough, ... Besides attachment to bacterial proteins, aggregation also inactivates the toxin. This quick inactivation highlights the ...
Tissue plasminogen activator (t-PA) and urokinase are the agents that convert plasminogen to the active plasmin, thus allowing ... Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products ... Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin-activatable ... Thrombolysis refers to the dissolution of the thrombus due to various agents while fibrinolysis refers specifically to the ...
... s have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs (see drug metabolism), ... in which calcium is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a solution ... complement, and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes. Synthesis of ... "Wheat extracts as an efficient cryoprotective agent for primary cultures of rat hepatocytes". Biotechnology and Bioengineering ...
becoming the first approved oncolytic agent in the western world. It is based on herpes simplex virus (HSV-1). It has also been ... Although it poses a hurdle by inactivating viruses, the patient's immune system can also act as an ally against tumors; ... Magge D, Guo ZS, O'Malley ME, Francis L, Ravindranathan R, Bartlett DL (June 2013). "Inhibitors of C5 complement enhance ... Directed evolution was applied on human adenovirus, one of many viruses that are being developed as oncolytic agents, to create ...
Its causative agent is lymphocytic choriomeningitis mammarenavirus (LCMV), a member of the family Arenaviridae. The name was ... However, some authors note that such complement-fixation tests are insensitive and should not be used for diagnosis. Dr. Clare ... In addition, LCMV can also be inactivated by heat, ultraviolet light or gamma irradiation. Studies have indicated that human ... Such agents had been developed in the animal care facility, which periodically screened sentinel animals for extraneous ...
The human genome already contains remnants of retroviral genomes that have been inactivated and harnessed for self-gain. Indeed ... This prevents infection by effectively destroying the foreign DNA introduced by an infectious agent (such as a bacteriophage). ... and excision repair cross complementing 1(ERCC) appear to mimic the action of RM-systems in bacteria, and the non-homologous ... gene transfer agents or generalized transduction in order to move between genomes. Methylation Restriction enzyme Luria SE, ...
... as the electrophilic properties of glutathione allow it to react with cytotoxic agents, inactivating them. In some cases, ... The cisplatin-resistant cells upregulate expression of the excision repair cross-complementing (ERCC1) gene and protein. Some ... In colorectal cancer cells, inhibition of NF-κB or MDR1 caused increased apoptosis in response to a chemotherapeutic agent. ... 2004-07-15). "Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents". Cancer ...
The squadrons flew agents and supplies into southern France with B-24 Liberators that had all armament removed except in the ... When assigned to Harrington, the 801st Bombardment Group (Provisional) was inactivated in a name-only manner. Headquarters and ... HHS 39th Service Group 18th Weather Squadron 35th Station Complement Squadron Regular Army Station Units included: Headquarters ... However, the Japanese surrender canceled those plans and the Group was inactivated in October. After the war, Harrington ...
... A71 (EV-A71) is notable as one of the major causative agents for hand, foot and mouth disease (HFMD), and is ... There are two types of vaccines available to prevent polio: inactivated poliovirus vaccine given as an injection in the leg ( ... complement proteins, and proapoptotis proteins have been implicated. There are three serotypes of poliovirus, PV-1, PV-2, and ...
... signals that inactivate the phosphatases that restrict a given MAP kinase. Such signals include oxidant stress. Tyrosine- ... "The protein kinase complement of the human genome". Science. 298 (5600): 1912-1934. doi:10.1126/science.1075762. PMID 12471243 ... either natural ligands or crosslinking agents) and proteins associated with them (mutations that simulate active state) b) ...
A causative agent may not be isolated in about half of cases despite careful testing. In an active population-based ... In the lower airways, reflexes of the glottis, actions of complement proteins and immunoglobulins are important for protection ... attempt to inactivate the bacteria. The neutrophils also release cytokines, causing a general activation of the immune system. ... The causative agent is determined in only 15% of cases with routine microbiological tests. Pneumonitis refers to lung ...
These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins; kinins (especially bradykinin) are ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ... The version related to histamine is due to an allergic reaction to agents such as insect bites, foods, or medications. The ...
The M-protein aids in immune evasion by inhibiting phagocytosis and inactivating the complement system. Furthermore, ... Second-line agents include macrolides and clindamycin, although increasing resistance, due to both efflux and target ... Antimicrobial Agents and Chemotherapy. 19 (5): 716-725. doi:10.1128/aac.19.5.716. ISSN 0066-4804. PMC 181512. PMID 7027921. ...
... groups on each monomeric enzyme molecule that react equally fast with the modifying agent, and n e s s e n t i a l {\ ... but it complements Tsou's approach in useful ways. Suppose that an enzyme has two groups G 1 {\displaystyle \mathrm {G_{1}} } ... is inactivated in a first-order reaction with a different rate constant k 2 {\displaystyle k_{2}} , then the remaining activity ... for which modification of just one essential group by diethyl pyrocarbonate was sufficient to inactivate the enzyme. A little ...
Inactivated. Main article: Inactivated vaccine. Some vaccines contain inactivated, but previously virulent, micro-organisms ... The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and ... Meri S, Jördens M, Jarva H (December 2008). "Microbial complement inhibitors as vaccines". Vaccine. 26 Suppl 8: I113-7. doi: ... Formaldehyde is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted ...
These neurons become highly sensitized to convulsant agents. It has been shown that seizures early in life can predispose one ... The increased calcium concentration (and subsequent depolarization of the membrane) inactivates sodium channels and targets ... Intrinsic plasticity contributes to encoding memory and complements other forms of activity-dependent plasticity including ...
Later that year, it moved to Fort McPherson, where it remained until it inactivated Oct. 1, 1973. In December 1982, Third Army ... This means First Army is the regional DoD planning agent for military support to civil authorities during a response to natural ... filling a vital defense need and complementing USARCENT's rich heritage and proud traditions. Under the leadership of Gen. ...
Specifically, it is used to target specific sites of the brain and directly introduce pharmacological agents to the brain which ... Paddick, Ian (2006). "A simple dose gradient measurement tool to complement the conformity index". Journal of Neurosurgery. 105 ... Stereotactic radiosurgery utilizes externally generated ionizing radiation to inactivate or eradicate defined targets in the ... generated by using medical images acquired with contrast agents. The work of Spiegel and Wycis sparked enormous interest and ...
Medications commonly associated with rebound hypertension include centrally-acting antihypertensive agents, such as clonidine ... Licht C, Fremeaux-Bacchi V (February 2009). "Hereditary and acquired complement dysregulation in membranoproliferative ... an enzyme that normally inactivates circulating cortisol to the less-active metabolite cortisone. At high concentrations ...
In 1997, it was approved by the FDA as an antimicrobial agent for use on food. In 2002, the FDA approved ozone for use on food ... The WHO states bringing water to rolling boil then naturally cooling is sufficient to inactivate pathogenic bacteria, viruses ... but rather as secondary means to complement another purification technique. It is most commonly implemented for pre- or post- ... Untreated water may contain potentially pathogenic agents, including protozoa, bacteria, viruses, and some larvae of higher- ...
Reducing agents are not used with steel casting, because they can carburize the metal during casting. Up to 3% of "cushioning ... At the temperatures that copper and iron are poured, the clay is inactivated by the heat, in that the montmorillonite is ... Besides replacing older methods, additive can also complement them in hybrid models, such as making a variety of AM-printed ... In addition to the sand, a suitable bonding agent (usually clay) is mixed or occurs with the sand. The mixture is moistened, ...
These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins;[22] kinins (especially bradykinin) are ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ... In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement system due to a deficiency ...
Embryonic stem cells have constitutive cyclin E-CDK2 activity, which hyperphosphorylates and inactivates Rb. This leads to a ... Biochemical cascades include: The Complement system The Insulin Signaling Pathway The Sonic hedgehog Signaling Pathway The Wnt ... cascades in lymphocytes is the secretion of molecules that can suppress altered cells or eliminate pathogenic agents, through ... complement, coagulation and fibrinolytic systems and iron homeostasis Regulate iron homeostasis (acute phase independent) Via ...
Alphonse Laveran got the 1907 Nobel Prize for his research on the role of protozoans as disease agents (notably, his discovery ... 112 They concluded that a series of three or four early injections of such heat-inactivated bacteria can effectively inoculate ... especially the implication of antibodies and the mechanisms of action of the complement; ... between Pasteur and Berthelot after the publication of Claude Bernard's posthumous essay regarding the nature of the agents ...
... a is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of ... These agents known as vitamin K antagonists (VKA), inhibit the vitamin K-dependent carboxylation of Factors II (prothrombin), ... These agents have several theoretical advantages over current therapy. They may be given orally. They have rapid onset of ... LMWH shows increased inactivation of Factor Xa compared to unfractionated heparin, and fondaparinux, an agent based on the ...
Clonal Anergy theory, proposed by Nossal, in which self-reactive T- or B-cells become inactivated in the normal individual and ... Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate ... These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... Specific immunomodulatory therapies, such as the TNFα antagonists (e.g. etanercept), the B cell depleting agent rituximab, the ...
First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the ... a direct effect upon a pathogen, such as antibody-initiated complement-dependent bacteriolysis, opsonoization, phagocytosis and ... This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquired immunity against ... The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease ...
... is a disease-modifying antirheumatic drug and monoclonal antibody that works by inactivating tumor necrosis factor- ... Similar agents[edit]. *Certolizumab pegol. *Etanercept. *Golimumab. *Infliximab. References[edit]. *^ a b c .mw-parser-output ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Baboons and pigs carry myriad transmittable agents that are harmless in their natural host, but extremely toxic and deadly in ... Pig cells have been engineered to inactivate all 62 PERVs in the genome using CRISPR Cas9 genome editing technology,[42] and ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ...
Saiz, JC; Martín-Acebes, MA «Zika virus: a race in search for antivirals» (en anglès). Antimicrob Agents Chemother., 2017; Mar ... Zika Virus Purified Inactivated Vaccine (ZPIV) Accelerated Vaccination Schedule Study (Z001)» (en anglès), ClinicalTrials.gov/U ... fet que podria desencadenar una resposta defensiva del cos contra el virus i també contra el seu propi sistema del complement, ... Rossignol, JF «Nitazoxanide: A first-in-class broad-spectrum antiviral agent» (en anglès). Antiviral Res, 2014 Oct; 110, pp: 94 ...
"Evid Based Complement Alternat Med. 2 (3): 285-99. doi:10.1093/ecam/neh107. PMC 1193547 . PMID 16136207. Archived from the ... For H5N1, Aventis-Pasteur and Chiron are both producing investigational lots of inactivated H5N1 vaccine preparations[when?]; ... Agents Chemother. 50 (11): 3724-33. doi:10.1128/AAC.00644-06. PMC 1635187 . PMID 16966399.. ... "To address the H9N2 threat, NIAID contracted with Chiron Corporation to produce investigational batches of an inactivated ...
Complement-component studies". The New England Journal of Medicine. 285 (4): 185-9. doi:10.1056/NEJM197107222850401. PMID ... It stimulates genes that promote cell growth and inactivates growth regulating molecules.[44] ... In 2015 the World Health Organization recommended tenofovir or entecavir as first-line agents.[82] Those with current cirrhosis ...
Efforts to develop an inactivated whole-cell vaccine began soon after B. pertussis was cultured that year. In the 1920s, Louis ... complement fixation test).[35] The bacteria can be recovered from the person only during the first three weeks of illness, ... may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.[6] ...
MAC (not to be confused with the Membrane Attack Complex formed by complement activation, also commonly denoted as MAC), also ... are mutated or inactivated in diseased cells, and further genes (such as bcl-2) also modify their expression in tumors. Some ... The addition of agents such as Herceptin, Iressa, or Gleevec works to stop cells from cycling and causes apoptosis activation ... "Human Papillomavirus Type 16 E6 and HPV-16 E6/E7 Sensitize Human Keratinocytes to Apoptosis Induced by Chemotherapeutic Agents ...
Shiga-toxin directly activates the alternative complement pathway and also interferes with complement regulation by binding to ... A variety of viruses have also been implicated as a causative agent. It is now the most common cause of acquired acute renal ... the binding action of Shiga-toxin inactivates a metalloproteinase called ADAMTS13, the deficiency of which causes the closely ... complement factor H, an inhibitor of the complement cascade. Shiga-toxin causes complement-mediated platelet, leukocyte, and ...
Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent ... Meri S, Jördens M, Jarva H (December 2008). "Microbial complement inhibitors as vaccines". Vaccine. 26 Suppl 8: I113-7. doi: ... Inactivated. Main article: Inactivated vaccine. Some vaccines contain inactivated, but previously virulent, micro-organisms ... The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and ...
If the mismatch is not repaired and the cell enters the cell cycle the strand carrying the T will be complemented by an A in ... This may serve as a novel therapeutic agent to treat atherosclerosis, although no human studies have been conducted thus far.[ ... state that definitely inactivates transcription. In particular, DNA methylation appears critical for the maintenance of mono- ... An ex vivo experiment using the demethylating agent Decitabine (5-aza-2 -deoxycytidine) was shown to induce MCT3 expression in ...
They named the virus CCA (Chimpanzee Coryza Agent),[45] although it was later realized that the chimpanzees caught the ... Attempts to develop an RSV vaccine began in the 1960s with a formalin-inactivated vaccine that was developed for use in infants ... During replication of the negative-sense viral genome, RNA-dependent RNA polymerase synthesizes a positive-sense complement ... Blount RE, Morris JA, Savage RE (July 1956). "Recovery of cytopathogenic agent from chimpanzees with coryza". Proceedings of ...
Samuels TL, Johnston N (Nov 2009). "Pepsin as a causal agent of inflammation during nonacidic reflux". Otolaryngology-Head and ... 2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu(II).[31] ... because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow ... however pepsin is not fully denatured or irreversibly inactivated until pH 8.0.[13] Therefore, pepsin in solution of up to pH ...
Infectious agents, which increase the pathogenicity of reovirus in the joints of chicken, include Mycoplasma synoviae, ... Vaccines are available (ATCvet codes: QI01AA04 (WHO) for the inactivated vaccine, QI01AD10 (WHO) for the live vaccine, plus ... They can be confirmed using virus isolation, complement fixation, ELISA, immunodiffusion or histopathology (following ... Van der Heide, L.; Lutticken, D.; Horzinek, M. (1981). "Isolation of avian reovirus as a possible etiologic agent of ...
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (Dec 2002). "The protein kinase complement of the human genome". ... some tyrosine phosphatases are also involved in inactivating MAP kinases (e.g. the phosphatases HePTP, STEP and PTPRR in ... it is natural that ERK1/2 inhibitors would represent a desirable class of antineoplastic agents. Indeed, many of the proto- ... are successful antineoplastic agents against various types of cancer.[39][40] ...
... and as a result are able to increase their resistance to complement-mediated killing [33] or even down-regulate complement ... Being of crucial importance to Gram-negative bacteria, these molecules make candidate targets for new antimicrobial agents. ... Neutrophils, macrophages and dendritic cells produce this lipase, acyloxyacyl hydrolase (AOAH), which inactivates LPS by ... Pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood.[43] High ...
However, whole virus inactivated bivalent vaccines against Hantaan virus and Seoul virus are available in China and South Korea ... Integrins are considered to be the main receptors for hantaviruses in vitro but complement decay-accelerating factor (DAF) and ... Agents of HPS found in South America include the Andes virus (also called Oran, Castelo de Sonhos - Portuguese for "Castle of ... globular heads of complement C1q receptor (gC1qR) have mediated attachment in cultured cells too. Entry may proceed through a ...
The solution was incubated at 60 °C for 10 hours to inactivate the agent of serum hepatitis. The result was a 45 g/l human ... After reimplantation, complement fixation and tissue damage occurred in a similar pattern. There was some correlation between ... Murray R, Diefenbach WCL (1953). "Effect of heat on the agent of homologous serum hepatitis". Proc Soc Exp Biol Med. 84 (1): ... The magnesium was also provided as a metabolic inhibitor following Kamiyama's demonstration that it was an effective agent in ...
Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... The complement cascade in kidney disease: from sideline to center stage. Am J Kidney Dis. 2013 Sep;62(3):604-14. doi: 10.1053/j ... Complement fragments C3a and C5a: the salt and pepper of the immune response. Eur J Immunol. 2010 Mar;40(3):668-70. doi: ... Gasque P. Complement: a unique innate immune sensor for danger signals. Mol Immunol. 2004 Nov;41(11):1089-98. Review. ...
Complement C3. Complement Inactivating Agents. Immunologic Factors. Physiological Effects of Drugs. Immunosuppressive Agents. ... Complement protein C3 plasma levels [ Time Frame: Up to 14 days after treatment. ]. *Complement protein C4 plasma levels [ Time ... complement inhibition. C3 complement inhibitor. AMY-101. Compstatin Cp40. Paroxysmal Nocturnal Hemoglobinuria (PNH). C3 ... AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the ...
Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. To Top ... Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic ... Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic ... ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement ...
Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological Effects of Drugs. To Top ... The complement system in COVID-19: friend and foe? JCI Insight. 2020 Aug 6;5(15). pii: 140711. doi: 10.1172/jci.insight.140711 ... Current treatment with a complement inhibitor or. *Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on ...
Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. ... Complement Activation* / drug effects * Complement Inactivating Agents / therapeutic use * Complement System Proteins / ... Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun;20(6):343-344. doi: 10.1038/s41577-020-0320-7. Epub 2020 Apr 23. ... Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. ...
... is widely regarded as an archetypal complement-mediated disorder that has propelled complement drug discovery in recent decades ... Its pathology is driven by chronic complement dysregulation resulting from the lack of the glycosyl phosphatidyl inositol- ... Complement Inactivating Agents / therapeutic use* * Complement System Proteins / physiology* * Hemoglobinuria, Paroxysmal / ... This complement imbalance fuels persistent C3 activation on affected erythrocytes, which culminates in chronic complement- ...
Furthermore, BacMam viruses are inactivated by human complement, which reduces risk to researchers. Lastly, viruses used in the ... Baculoviruses are Risk Group 1 agents that have been widely used for over 25 years for insect cell protein production ... "Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system ...
Vaccines, Inactivated, Bacterial. Class Summary. These agents may be used to prevent and control outbreaks of serogroup C ... Jarva H, Ram S, Vogel U, Blom AM, Meri S. Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. J ... Diuretics, Osmotic Agents. Class Summary. These agents are used to control ICP during elective intubation. Osmotic diuretics ... Inotropic Agents. Class Summary. These agents are used to support circulation in patients with shock. ...
Complement component 3 (C3) is a key component responsible for inactivating many antigens, particularly infectious agents [15 ... IgM antibodies and the C3b inactivator cleaved third component of complement in macrophage phagocytosis," Agents and Actions, ... Complement component 3 (C3) plays a central role in the activation of complement system [15]. People with C3 deficiency are ... Agents inhibiting these responses may prove to be therapeutic for radiation combined injury and improve chances for survival. ...
... immunosuppressive agents MeSH D27.505.696.477.656.500 - complement inactivating agents MeSH D27.505.696.477.656.750 - ... antiviral agents MeSH D27.505.954.122.388.077 - anti-retroviral agents MeSH D27.505.954.122.388.077.088 - anti-hiv agents MeSH ... tocolytic agents MeSH D27.505.954.016 - anti-allergic agents MeSH D27.505.954.122 - anti-infective agents MeSH D27.505.954.122. ... tranquilizing agents MeSH D27.505.696.277.950.015 - anti-anxiety agents MeSH D27.505.696.277.950.025 - antimanic agents MeSH ...
The product is treated with solvents and detergents to inactivate any blood-borne virus. IVIG may work via several mechanisms, ... An open label clinical trial of complement inhibition in multifocal motor neuropathy. J Peripher Nerv Syst. 2011 Jun. 16(2):84- ... Immunomodulatory Agents. These medications are used to improve the clinical and immunologic aspects of GBS. They may decrease ... Which medications in the drug class Immunomodulatory Agents are used in the treatment of Guillain-Barre Syndrome?. Updated: Jun ...
Inactivate.. To make biologically inactive, as viruses or bacteria, toxins, or serum complement, by any of various means, such ... 1. The agent must be shown to be present in every case of the disease by isolation in pure culture. ... Inactivated polio vaccine (IPV).. A sterile suspension of three types of inactivated polioviruses. The viruses are grown ... The infectious agent may circulate in the blood for long periods of time (months or years) and is characteristically ...
Atopy and smoking are not risk factors for OA caused by LMW agents as they are for OA caused by HMW agents. Some of the better- ... They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in ... Isocyanates can block beta 2-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Moreover, ... Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from ...
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. ... C4bp complement protein. physiological aspects. agonists. Carrier Proteins. chemical synthesis. Complement Inactivating Agents ... C4bp complement protein. Known as: C4bC3bINA Cofactor, Complement C3b C4b Inactivator Cofactor, Protein, Complement C4b-Binding ...
... complement-inactivated rabbit plasma. The in vitro bactericidal killing rates were determined by the macrodilution method in ... Antimicrobial Agents and Chemotherapy Feb 1998, 42 (2) 468-470; DOI: 10.1128/AAC.42.2.468 ... Antimicrobial Agents and Chemotherapy Feb 1998, 42 (2) 468-470; DOI: 10.1128/AAC.42.2.468 ... B4 Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. 1996 22 American Society ...
... followed by assay of components of the complement complex thereby formed; whereby the extent and nature of complement ... Also described is a method for assaying an antibody against a specific antigen or hapten for its effectiveness in complement ... immobilized antigen or hapten to form an immobilized antibody/antigen or hapten complex which is then contacted with complement ... using an inactivated sample of the serum used as source of the antibody and/or complement. Non-specific binding can be reduced ...
These phenotypes were complemented by supplying a functional copy of priA elsewhere in the chromosome. The N. gonorrhoeae priA ... The priA mutant was also more sensitive to the oxidative damaging agents H2O2 and cumene hydroperoxide compared to the parental ... Insertionally inactivated and inducible recA alleles for use in Neisseria. Gene188:215-220. ... 4A). This repair defect was fully restored in the priA complement strain. We also tested whether priA is involved in the repair ...
"Vaccination" means that an organism is challenged with an infectious agent, e.g., an attenuated or inactivated form of the ... comprising small peptides and complement factors. ... The organism, thus, is immunized against the agent/protein ... Preferably, the virus is inactivated by β-propriolacton. According to this embodiment of the invention, the inactivated virus ... Thus, a second infection with the same or a very similar infectious agent causes much milder symptoms or no symptoms at all, ...
... considered as a model for the vCJD and CJD agents.18 To complement the existing virus elimination / inactivation mechanism in ... PRV and the two model viruses for HCV, BVDV and SFV, were inactivated within 1/10, and HIV within 1/2 of the incubation time ( ... agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior ... Because Carimune® NF is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the ...
... including contacting the composition with an organic solvent and an ethyleneimine oligomer inactivating agent, are disclosed. ... Methods and compositions for selectively inactivating viruses in biological compositions, ... The solvent-detergent mixture and the selective inactivating agents complement each other and can be used simultaneously. The ... b) contacting the composition with an inactivating agent under viral inactivating conditions, wherein said inactivating agent ...
Use of the terminal complement inhibitor eculizumab in paediatric heart transplant recipients. Law, Y. M., Nandi, D., Molina, K ...
The preferred organic agent is diethyl ether which is used in an amount and over a period of time sufficient to kill the ... The uninfected components are returned to the patient and the infected components are treated with organic agents. ... complement, clotting factors, enzymes, and blood factors; said organic agents being otherwise proportionately too harmful to be ... To inactivate the virus a dose higher than 2.5 105 rad would be needed. It was also found that LAV reverse transcriptase ...
... high levels of cell killing largely required active complement, since CDC was almost absent in heat-inactivated NHS, NHS ... whereas the single agents induced only 5% and 10% lysis respectively. Despite high single agent activity of Hx-CD37 and Hx-CD20 ... Complement in therapy and disease: Regulating the complement system with antibody-based therapeutics. Mol Immunol. 2015;67(2, ... Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement- ...
However, the parasite was not lysed if the plasma was heat-inactivate ... However, the parasite was not lysed if the plasma was heat-inactivated at 37°C for 2 h or after the addition of ... The alternative pathway of complement activation is the mechanism of innate immunity against C. salmositica. The present study ... Treatment of Cryptobia-resistant plasma with either ethylenebis(oxyethylenenitrilo)tetraacetic acid, a Ca2+-chelating agent, or ...
Complement C1 Inhibitor Protein. Phase 1. 42. Complement C1s. Phase 1. 43. Complement Inactivating Agents. Phase 1. ...
introduced a point mutation into the XPG gene which inactivates the nuclease (zeige DCLRE1C Antikörper) catalytic site but ... XPG mRNA expression was not predictive of trabectedin efficacy as single agent in hormone-positive, HER-2 (zeige ERBB2 ... Weitere Produktkategorien zu DNA Repair Protein Complementing XP-G Cells Antikörper * 91 anti-DNA Repair Protein Complementing ... anti-DNA Repair Protein Complementing XP-G Cells (ERCC5) Antikörper. Bezeichnung:. anti-DNA Repair Protein Complementing XP-G ...
soluble complement inhibitor 1 Medicine & Life Sciences * Complement Inactivating Agents Medicine & Life Sciences ... The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by ... The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by ... The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by ...
The ability of the furDn gene to complement a furEc mutant suggested that the Fur protein was likely to be functional in D. ... We have identified a fur homologue in Dichelobacter nodosus, the causative agent of ovine footrot, and shown that it ... nodosus VCS1703A by double-crossover events that insertionally inactivated the fur gene (data not shown). All further studies ... The D. nodosus fur gene complements an E. coli fur mutant.The ability of H1780(pJIR2300) to form pink colonies on iron-replete ...
2. The patients serum is heated in the complement fixation test in order to A) activate antibodies. C) inactivate complement. ... Immunogen: any agent capable of inducing an immune response. Antigen: any agent capable of binding specifically to components ... a. Antibodies allow scientists to target and identify specific disease agents because they bind to antigens to counteract them ... Activity 1.1.5 ELISA 1. Explain why the antibodies allow scientists to target and identify specific disease agents. The ...
Patients with complement deficiencies can receive any live or inactivated vaccine. Factors to consider in assessing the general ... Numerous agents are often given in combination with other agents (especially chemotherapy) and are immunosuppressive when given ... People with terminal complement deficiencies, including anyone receiving the complement component inhibitor eculizumab, have ... In particular, lymphocyte-depleting agents (thymoglobulin or alemtuzumab) and B cell-depleting agents (rituximab) are more ...
  • Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing. (semanticscholar.org)
  • Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated. (elsevier.com)
  • This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. (cdc.gov)
  • This assumption has been supported with EAMG resistance of complement factor C3 knockout (KO), C4 KO and C5 deficient mice and amelioration of EAMG symptoms following treatment with complement inhibitors such as cobra venom factor, soluble complement receptor 1, anti-C1q, anti-C5 and anti-C6 Abs. (utmb.edu)
  • 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. (missouri.edu)
  • Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. (edu.au)
  • ACE inhibitors of the urine using agents that metabolizes intracellular and aP-1 Platelets adhere to reduce mortality. (imagenenaccion.org)
  • ACE inhibitors of the urine using agents that metabolizes intracellular and aP-1. (imagenenaccion.org)
  • We reviewed previously reported cases and discussed diagnosis and treatment strategies, including novel complement inhibitors, as potential future therapy. (elsevier.com)
  • In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. (elsevier.com)
  • Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented. (bvsalud.org)
  • The plasma protein inhibitors are factor H and C4-binding protein, and the regulatory membrane proteins located on cell surfaces are complement receptors 1 (CR1), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). (justia.com)
  • To date, there are no inhibitors of complement activation used in the clinic, though certain candidates for clinical use exist, specifically, a recombinant form of complement receptor 1 known as soluble complement receptor 1 (sCR1) and a humanized monoclonal anti-05 antibody (5G1.1-scFv). (justia.com)
  • Thus, up to 7 % of lung adenocarcinomas that have acquired somatic mutations that inactivate ATM may respond extremely well to radiotherapy, while lung cancers that express functional ATM are anticipated to be radiosensitized by ATM kinase inhibitors. (biomedcentral.com)
  • ATR kinase inhibitors also kill cell lines with mutations in either ATM or TP53 with greater efficacy than complemented control cell lines. (biomedcentral.com)
  • Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. (clinicaltrials.gov)
  • The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor. (clinicaltrials.gov)
  • Moreover, the complement inhibitor decay accelerating factor (DAF) KO mice exhibit increased susceptibility to EAMG. (utmb.edu)
  • As other immunosuppressive agents were considered dangerous because of the risk of infections in the face of severe hypogammaglobulinemia, we administered eculizumab, an inhibitor of the terminal complement pathway, which led to a persistent control of her disease. (elsevier.com)
  • Complement deposition assays revealed that gigastasin is an effective inhibitor of complement activation in vivo, especially for activation via the lectin pathway. (edu.au)
  • Within this phage, we discovered a novel variant of staphylococcal complement inhibitor (SCIN), a secreted protein that interferes with activation of the human complement system, an important line of host defense. (wur.nl)
  • These data suggest that modification of this phageencoded complement inhibitor plays a role in the host adaptation of S. aureus and are important to understand how this pathogen transfers between different hosts. (wur.nl)
  • 12 A complement deficiency that is a functional deficiency in the complement component C1 inhibitor leading to hereditary angioedema (HAE) involving swelling due to leakage of fluid from blood vessels into connective tissue. (malacards.org)
  • An important gene associated with C1 Inhibitor Deficiency is SERPING1 (Serpin Family G Member 1), and among its related pathways/superpathways are Formation of Fibrin Clot (Clotting Cascade) and Immune response Lectin induced complement pathway . (malacards.org)
  • Thus, up to 14 % of NSCLCs may respond to single agent therapy with an ATM kinase inhibitor. (biomedcentral.com)
  • Thus, up to 7 % of lung adenocarcinomas that have acquired somatic mutations that inactivate ATM may respond to single agent therapy with an ATR kinase inhibitor. (biomedcentral.com)
  • Herein, the IL-6-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), immunoglobulin M (IgM), and prostaglandin E 2 (PGE 2 ) were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. (hindawi.com)
  • Agents associated with an immunologic cause can be further divided into HMW agents, usually allergens such as proteins from laboratory animals, flour, or plants, or LMW agents, usually chemicals such as isocyanates, biocides, or drugs. (clevelandclinicmeded.com)
  • There are currently known 4 counter-regulatory proteins (Factor H, Factor I, MCP, thrombomodulin) in which inactivating mutations lead to excessive complement activity. (omicsonline.org)
  • There are 2 proteins (Factor B, C3) that are integral complement component in which gain of function mutations lead to excessive complement activity. (omicsonline.org)
  • Mutations in genes encoding complement regulatory proteins have been reported both in familial and in nonfamilial cases, mainly in idiopathic forms ( 5 , 6 ) but also in cases of pregnancy-associated ( 5 ) and postpartum HUS ( 8 , 9 ), ticlopidine-induced HUS ( 5 ), and postinfectious HUS ( Neisseria meningitidis ) ( 10 ). (asnjournals.org)
  • By use of purified proteins and cell-expression system, they explored thrombomodulin's role in regulation of the complement system and characterized the mechanisms. (medpagetoday.com)
  • In vivo, regulation of complement at the C3 and C5 activation steps is provided by both plasma and membrane proteins. (justia.com)
  • These proteins inhibit the C3 and C5 convertases (multi-subunit proteases), by promoting dissociation of the multisubunit complexes and/or by inactivating the complexes through proteolysis (catalyzed by factor I). Several pharmacological agents that regulate or modulate complement activity have been identified by in vitro assay, but most have been shown in vivo to be of low activity or toxic. (justia.com)
  • Immunologic characteristics include high ANA and anti-dsDNA, presence of anti-Smith (anti-Sm) proteins, antiphospholipid antibodies (APAs), low complement, and direct Coombs test. (uspharmacist.com)
  • The immune system identifies invading "foreign" compositions and agents primarily by identifying proteins and other large molecules which are not normally present in the individual. (justia.com)
  • There are several vaccine strategies for presenting pathogen proteins which include presenting the protein as part of a non-infective or less infective agent or as a discreet protein composition. (justia.com)
  • One strategy for immunizing against infection uses killed or inactivated vaccines to present pathogen proteins to an individual's immune system. (justia.com)
  • Ribosome-inactivating proteins (RIPs) such as Shiga-like Toxin 1 (SLT-1) represent powerful scaffolds for developing selective anticancer agents. (biomedcentral.com)
  • Currently, targeted agents such as monoclonal antibodies and recombinant proteins account for more than a quarter of all cancer therapeutics that have been newly approved or are presently in clinical trials [ 3 , 4 ]. (biomedcentral.com)
  • The present thesis is concentrated on discussing two properties of M. catarrhalis, - binding and inactivation of alpha1-anticnymotrypsin (ACT) and complement component 3 (C3) for which M. catarrhalis outer membrane proteins "ubiquitous surface proteins" (Usp) A1/A2 are responsible. (avhandlingar.se)
  • We established that M. catarrhalis is able to bind and inactivate ACT through the two active domains on both UspA1 and A2 proteins. (avhandlingar.se)
  • IVIG may work via several mechanisms, including the blockage of macrophage receptors, the inhibition of antibody production, the inhibition of complement binding, and the neutralization of pathologic antibodies. (medscape.com)
  • It was postulated that inhibition or depletion of complement attenuates aspiration-induced lung injury. (elsevier.com)
  • The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by cobra venom factor (n = 7) on lung injury was evaluated. (elsevier.com)
  • The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. (cdc.gov)
  • These findings have brought forward improvisation of novel therapy methods based on inhibition of classical and common complement pathways in MG treatment. (utmb.edu)
  • The patient developed a subsequent flare of her systemic lupus erythematosus, potentially indicating that complement inhibition by eculizumab is not effective in preventing lupus flares. (elsevier.com)
  • Taken together, we describe a unique case of life-threatening and difficult-to-treat CAPS with a good clinical response after terminal complement complex inhibition with eculizumab. (elsevier.com)
  • Mechanistic studies indicate that eqSCIN blocks equine complement activation by specific inhibition of the C3 convertase enzyme (C3bBb). (wur.nl)
  • Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. (bvsalud.org)
  • We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. (aacrjournals.org)
  • The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera. (aacrjournals.org)
  • ATR kinase inhibition sensitizes cells to agents that induce replication stress and selectively kills cells with ATM and TP53 mutations. (biomedcentral.com)
  • Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness through inhibition of YAP activation and increases susceptibility to chemotherapeutic agents. (abcam.com)
  • Structural basis for therapeutic inhibition of complement C5. (ox.ac.uk)
  • At the same time, complement inactivated plasma from scrub typhus donors was assessed for in vitro inhibition of HIV using cryopreserved peripheral blood mononuclear cells infected with a non-laboratory-adapted Thai strain of clade E virus (NP1668). (i-base.info)
  • This leaves the proximal complement pathway intact while inactivating the terminal part of the pathway, thereby eliminating the production of the membrane attack complex. (omicsonline.org)
  • The most characteristic finding of muscle pathology in both MG and EAMG is the abundance of IgG and complement deposits at the nerve-muscle junction (NMJ), suggesting that AChR-Ab induces muscle weakness by complement pathway activation and consequent membrane attack complex (MAC) formation. (utmb.edu)
  • Activation of C3 by complement pathway C3 convertases and its subsequent attachment to target surface leads to assembly of the membrane attack complex and ultimately to damage or lysis of the target cells. (justia.com)
  • Complement-mediated tissue injuries are directly mediated by the membrane attack complex, and indirectly by the generation of C3a and C5a. (justia.com)
  • Activation of the classical complement pathway [ Time Frame: Up to 14 days after treatment. (clinicaltrials.gov)
  • Here, we review the current state of complement therapeutics with a focus on the clinical development of C3-targeted and alternative pathway-directed drug candidates for the treatment of PNH. (nih.gov)
  • The alternative pathway of complement activation is the mechanism of innate immunity against C. salmositica . (springer.com)
  • The present study also shows that there is functional heterogeneity amongst the complement components activated via the alternative pathway within a species (brook charr) and between species (brook charr and goldfish) of fishes. (springer.com)
  • Infection, surgery, autoimmune disease and pregnancy are the major activators of the complement pathway. (omicsonline.org)
  • The first identified genetic cause was deficiency in complement factor H (CFH) ( 8 , 11 - 14 ), a plasma glycoprotein that plays an important role in the regulation of the alternative pathway of complement ( 15 ) by controlling both spontaneous fluid phase C3 activation and its deposition on host cells. (asnjournals.org)
  • These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. (aacrjournals.org)
  • Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. (aacrjournals.org)
  • Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival. (hindawi.com)
  • The recent development of therapeutic anti-complement antibody preparations has enabled the clinician to capitalize on these scientific advances by treating these disorders in a targeted fashion. (omicsonline.org)
  • 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. (missouri.edu)
  • Since thrombomudulin simultaneously suppresses the complement and coagulation systems, its administration may have therapeutic value for some patients with the atypical hemolytic-uremic syndrome. (medpagetoday.com)
  • Novel melanoma-targeted therapeutic agents are needed to improve prognosis, since traditional treatments such as dacarbazine (DTIC) and IL-2 only yield a 5% survival advantage of more than five years for patients with advanced melanoma [ 2 ]. (biomedcentral.com)
  • Antibodies specific for CD37, a target that is abundantly expressed on healthy and malignant B cells, are generally poor inducers of complement-dependent cytotoxicity. (haematologica.org)
  • Here we demonstrate that introduction of the hexamerization-enhancing mutation E430G in CD37-specific antibodies facilitates highly potent complement-dependent cytotoxicity in chronic lymphocytic leukemia cells ex vivo . (haematologica.org)
  • Strikingly, we observed that combinations of hexamerization-enhanced CD20 and CD37 antibodies cooperated in C1q binding and induced superior and synergistic complement-dependent cytotoxicity in patient-derived cancer cells compared to the single agents. (haematologica.org)
  • Conclusion Explain why antibodies allow scientists to target and identify specific disease agents. (studymode.com)
  • Antibodies allow scientists to target and identify specific disease agents because they bind to antigens to counteract them. (studymode.com)
  • Acquired auto-antibodies resulting in excessive activity include: Inactivating Factor H antibodies, C3 nephritic factor stabilizing C3 convertase, and C4 nephritic factor stabilizing C4 convertase. (omicsonline.org)
  • correlation with serum-neutralizing and complement-fixing antibodies. (mdedge.com)
  • However, the parasite was not lysed if the plasma was heat-inactivated at 37°C for 2 h or after the addition of ethylenediaminetetraacetic acid (EDTA) to chelate the free Mg 2+ ions. (springer.com)
  • Heat-inactivation (56 °C, 1 hr) destroyed the killing effect of immune serum but the borreliacidal activity of heat-inactivated immune serum could be restored by the addition of pre-immune serum. (uri.edu)
  • Complement is activated by three pathways: classical, lectin, and alternative. (edu.au)
  • Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. (aacrjournals.org)
  • Complement component C3 plays a central role in activation of all three pathways. (justia.com)
  • Experiments by non-influenza scientists have defined common cell signaling pathways for acute lung injury caused by different agents, including inactivated H5N1 influenza virus. (wiley.com)
  • These pathways include several molecular targets that are up-regulated in acute lung injury and down-regulated by anti-inflammatory and immunomodulatory agents, including statins, fibrates, and glitazones. (wiley.com)
  • The UspA2 has been demonstrated to inhibit both the classical and the alternative pathways of the complement. (avhandlingar.se)
  • It is produced by the liver and binds to phosphocholine on microbes assisting in complement binding to foreign and damaged cells and enhancing phagocytosis by macrophages expressing CRP receptors. (hindawi.com)
  • They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. (nih.gov)
  • These possess receptors, combined oral agents in patients are added to disease. (musicaenlamochila.net)
  • Eculizumab is a humanized anti-complement monoclonal antibody that has been utilized in the treatment of complements mediated diseases, including: Paroxysmal Nocturnal Hemoglobinuria (PNH), aHUS, C3G, and catastrophic anti-phospholipid syndrome. (omicsonline.org)
  • Interestingly, eculizumab therapy was associatedwith a further decline of complement C3 and C4 serumlevels. (elsevier.com)
  • In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukosequestration. (elsevier.com)
  • Methods and compositions for selectively inactivating viruses in biological compositions, including contacting the composition with an organic solvent and an ethyleneimine oligomer inactivating agent, are disclosed. (google.com)
  • Here we report the discovery and properties of a single chain ribosome-inactivating protein (scRIP) derived from the cytotoxic A subunit of SLT-1 (SLT-1A), harboring the 7-amino acid peptide insertion IYSNKLM (termed SLT-1A IYSNKLM ) allowing the toxin variant to selectively target and kill human melanoma cells. (biomedcentral.com)
  • In an attempt to elucidate the role of PBP2 in the expression of methicillin resistance, we selectively inactivated each of the two domains of this protein by point mutations in key amino acids and determined the impact on antibiotic resistance in the background of the highly and homogeneously resistant MRSA strain COL. (pnas.org)
  • Intensive research into the molecular causes of cancer has led to the development of a range of innovative and targeted therapies which are used to selectively inactivate the molecular mechanisms responsible for tumour progression and the growth of cancer cells. (fh-krems.ac.at)
  • Paroxysmal nocturnal hemoglobinuria (PNH) is widely regarded as an archetypal complement-mediated disorder that has propelled complement drug discovery in recent decades. (nih.gov)
  • Two types of OA are distinguished by whether or not they appear after a latency period: (1) immunologic, characterized by a latency period, encompassing (a) that caused by high- (HMW) and low-molecular-weight (LMW) agents for which an immunologic (IgE) mechanism has been proven, and (b) that caused by agents (e.g., western red cedar) for which a specific immune mechanism has not been identified. (clevelandclinicmeded.com)
  • In a next step, the researchers inactivated the Cxcr4 gene function, leaving intact the molecular switch that helps them detect the immigrated immune cells. (uni-bonn.de)
  • To complement molecular detection systems for potential bioterror agents, as required by international biodefense regulations, sets of mAbs were generated by B cell hybridoma technology and used to develop immunological assays. (biomedcentral.com)
  • To investigate the role of PriA in recombination and repair in Neisseria gonorrhoeae , we identified, cloned, and insertionally inactivated the gonococcal priA homologue. (asm.org)
  • As Southern hybridization analysis of different clinical isolates of D. nodosus indicated that the fur gene was present in all of these strains, the fur gene was insertionally inactivated to determine its functional role. (asm.org)
  • About half of patients with atypical presentation have mutations in genes involved in the regulation of the complement system, the authors said. (medpagetoday.com)
  • By 1998, Milstein, Cristina Rada, and Neuberger noticed that certain genetic models could separate intronic mutations into discrete phases: an agent that caused G:C mutations and one that caused A:T mutations. (jci.org)
  • Yersinia enterocolitica YadA mediates complement evasion by recruitment and inactivation of C3 products. (semanticscholar.org)
  • 18 To complement the existing virus elimination / inactivation mechanism in the Carimune ® NF manufacturing process, nanofiltration (removing viruses via size-exclusion) was introduced as an additional virus removal step into the manufacturing process. (nih.gov)
  • In vitro thrombomodulin binds to complement factor C3b (a promoter of complement activation and opsonization) and negatively regulates complement by accelerating factor I-mediated inactivation of C3b, the authors said. (medpagetoday.com)
  • Cultured cells expressing thrombomodulin variants had a diminished capacity to inactivate C3b and to promote inactivation of the anaphylatoxins, thereby diminishing protection against activated complement. (medpagetoday.com)
  • Both of these substances have been shown to suppress complement activation in in vivo animal models (Kalli et al. (justia.com)
  • Since vector competence appeared to be related to the activity of host antibody and complement in the tick midgut, I determined whether substances existed in I. scapularis that might inhibit or inactivate antibody or complement. (uri.edu)
  • The complement system is profoundly involved in the pathogenesis of acetylcholine receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). (utmb.edu)
  • Objectives: To examine the role of complement in the development of acid aspiration-induced lung injury in the rat. (elsevier.com)
  • T he role of complement activation as a primary etiology and a secondary exacerbater of kidney disease have long been known. (omicsonline.org)
  • Recent advances in complement physiology have elucidated the central role of complement dysregulation as the root cause of hematologic, glomerular and systemic diseases. (omicsonline.org)
  • Treatment with pepsin at pH 4 rapidly inactivates enveloped viruses. (nih.gov)
  • This invention relates to methods and compositions for inactivating viruses in biological compositions. (google.com)
  • Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. (asm.org)
  • In the search for safe and effective vaccines for immunizing individuals against infective pathogenic agents such as viruses, bacteria, and infective eukaryotic organisms, several strategies have been employed thus far. (justia.com)
  • Whereas SCIN-A from human S. aureus isolates exclusively inhibits human complement, eqSCIN represents the first animal-adapted SCIN variant that functions in a broader range of hosts (horses, humans, and pigs). (wur.nl)
  • describes the use of a phage-displayed combinatorial random peptide library to identify a 27-residue peptide that binds to C3 and inhibits complement activation. (justia.com)
  • This bacterium inhibits the chemotaxis of neutrophils, suppresses the opsonins (both complement and immunoglobulin) and phagocytes, could rapidly react to abrupt changes in ROS (Lavoie et al. (thefreedictionary.com)
  • 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. (missouri.edu)
  • HMW agents can induce an immunoglobulin E (IgE) response in susceptible individuals and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. (clevelandclinicmeded.com)
  • Immunofluorescence studies show no immunoglobulin or complement deposits. (slideplayer.com)
  • In addition, aggregation of CBP + /PA − strains was drastically reduced when serum complement was inactivated. (asm.org)
  • three foot-and-mouth disease virus type a isolates recovered from field outbreaks in the department of san martin, peru, during the period 1975 to 1981 were compared with each other, and the south american vaccine strains a24 and a27, by complement fixation (cf), virus neutralization (vn) and polyacrylamide gel electrophoresis (page). (liverpool.ac.uk)
  • complement fixation and vn tests gave comparable results distinguishing the field isolates from each other and from the vaccine strains. (liverpool.ac.uk)
  • O-antigen-negative strains were found to be sensitive to complement and cationic peptides, but they displayed significant resistance to bile salts and short-chain organic acids. (asm.org)
  • The mecA gene encodes for a 78-kDa penicillin-binding protein (PBP) 2A, which has unusually low affinity for all β-lactam antibiotics-a property that translates to the virtually complete resistance of MRSA strains to the entire β-lactam family of antimicrobial agents. (pnas.org)
  • In our current model of methicillin resistance, the low-affinity PBP2A is assumed to take over the cell wall biosynthetic functions of normal PBPs in the presence of β-lactam antibiotics, which rapidly acylate (and inactivate) each of the four native staphylococcal PBPs at concentrations that are far below the minimum needed to inhibit the growth of most MRSA strains ( 6 , 7 ). (pnas.org)
  • The complement regulatory protein decay-accelerating factor (DAF or CD55) was induced following PGE 2 treatment of LS174T colon cancer cells. (elsevier.com)
  • whereby the extent and nature of complement activation by the antibody in the sample may be determined. (google.es)
  • We previously demonstrated that the natural process of antibody hexamer formation on targeted cells allows for optimal induction of complement-dependent cytotoxicity. (haematologica.org)
  • In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. (cdc.gov)
  • Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. (bmj.com)
  • In such vaccines, the pathogen is either killed or otherwise inactivated using means such as, for example, heat or chemicals. (justia.com)
  • Killed or inactivated pathogen vaccines provide protection by directly generating T-helper and humoral immune responses against the pathogenic immunogens. (justia.com)
  • Attenuated vaccines are often produced by passaging several generations of the pathogen through a permissive host until the progeny agents are no longer virulent. (justia.com)
  • Abstract Despite the best efforts of influenza scientists, companies and health officials to prepare for the next pandemic, most of the world's people will not have access to affordable supplies of vaccines and antiviral agents. (wiley.com)
  • 2-7 Vaccine companies have worked hard to develop more efficient H5N1 vaccines, 8 and the promise of using antigen sparing, adjuvanted inactivated vaccines that are cross-protective is now well established. (wiley.com)
  • 10 Nonetheless, if a pandemic virus should emerge within the next few years, the world would have to depend on a limited supply of egg-based inactivated vaccines. (wiley.com)
  • The preferred organic agent is diethyl ether which is used in an amount and over a period of time sufficient to kill the infected cells and the cell-free virus. (google.ca)
  • Auf www.antikoerper-online.de finden Sie aktuell 91 DNA Repair Protein Complementing XP-G Cells (ERCC5) Antikörper von 19 unterschiedlichen Herstellern. (antikoerper-online.de)
  • Zusätzlich bieten wir Ihnen DNA Repair Protein Complementing XP-G Cells Kits (12) und DNA Repair Protein Complementing XP-G Cells Proteine (5) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Insgesamt sind aktuell 115 DNA Repair Protein Complementing XP-G Cells Produkte verfügbar. (antikoerper-online.de)
  • Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. (cdc.gov)
  • Co- trimoxazole reduces the longest-acting agent that enter cells. (imagenenaccion.org)
  • If this switch is activated with a special agent, stem cells in the bone marrow, from which all blood-circulating immune cells originate, produce a colored fluorescent protein. (uni-bonn.de)
  • PU.1/microRNA-142-3p targets ATG5/ATG16L1 to inactivate autophagy and sensitize hepatocellular carcinoma cells to sorafenib. (abcam.com)
  • DNA sequences both natural and synthetic encoding for the expression of immunogenic agents which are capable of causing an immune response in animals when fed in edible plants, plant tissues, or derived plant materials are constructed, and plants transformed for stable or transient expression in plant cells. (freepatentsonline.com)
  • The cells may be contacted cells with a cell stimulating agent. (justia.com)
  • were generated by immunising mice with inactivated B. melitensis or B. abortus cells. (biomedcentral.com)
  • Specifically, the SLT-1 A subunit encodes all functions necessary to route itself out of cellular organelles in order to reach and inactivate ribosomes present in the cytoplasm of eukaryotic cells. (biomedcentral.com)
  • Additionally, the Luminex assay works in a multiplex format, simultaneously detecting four category A and B bacterial bioterrorism agents and is suitable for detecting Brucella in complex samples. (biomedcentral.com)
  • The approach makes use of the cytotoxic A subunit of a bacterial ribosome-inactivating protein (RIP), namely Shiga-like Toxin 1 (SLT-1), as a protein scaffold to design anticancer agents. (biomedcentral.com)
  • Complement is implicated in several disease states, including various autoimmune diseases, and has been found to contribute to other clinical conditions such as adult respiratory syndrome, heart attack, rejection following xenotransplantation and burn injuries. (justia.com)
  • Typically, this dope can be gained in Incline is a general fee in clinical pilot patients with diseases potentially receptive to design, regardless of the genus of litigation being con- these agents. (chesapeakehumane.org)
  • Vitronectin binds to the head region of Moraxella catarrhalis ubiquitous surface protein A2 and confers complement-inhibitory activity. (semanticscholar.org)
  • complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). (cdc.gov)
  • These emerging clinical needs have sparked a true resurgence of complement therapeutics that offer the promise of even more effective, disease-tailored therapies for PNH. (nih.gov)
  • The item Complement therapeutics, John D. Lambris, V. Michael Holers, Daniel Ricklin, editors represents a specific, individual, material embodiment of a distinct intellectual or artistic creation found in University of Missouri Libraries . (missouri.edu)
  • Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. (bvsalud.org)
  • Complement component 3 (C3) is a key component responsible for inactivating many antigens, particularly infectious agents [ 15 ]. (hindawi.com)
  • Like complement, fibrin and a polypeptide that is released by lymphocytes upon contact with certain antigens act as nonspecific opsonins. (thefreedictionary.com)
  • Its pathology is driven by chronic complement dysregulation resulting from the lack of the glycosyl phosphatidyl inositol-linked regulators DAF and CD59 on susceptible erythrocytes. (nih.gov)
  • Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. (edu.au)
  • Here, we urge immunologists and clinicians to consider the potential of targeting the complement system in these patients. (nih.gov)
  • The complement system comprises the frontline of the innate immune system. (cdc.gov)
  • The complement system in COVID-19: friend and foe? (wustl.edu)
  • Complement System Activation in Cardiac and Skeletal Muscle Pathology: Friend or Foe? (missouri.edu)
  • During the sepsis the coagulation cascade, the complement system and the activation system are activated, in different moments, and this contributes to the development of multiple organ failure. (unipa.it)
  • We here show that this equine variant of SCIN, eqSCIN, is a potent blocker of equine complement system activation and subsequent phagocytosis of bacteria by phagocytes. (wur.nl)
  • The complement system is the first line of immunological defense against foreign pathogens. (justia.com)
  • Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. (justia.com)
  • The administration of killed or inactivated pathogen into an individual presents the pathogen to the individual's immune system in a noninfective form and the individual can thereby mount an immune response against it. (justia.com)
  • By investigating several parameters in vitro, we could show that galU and R-LPS mutants were more sensitive to short-chain organic acids, cationic antimicrobial peptides, the complement system, and bile salts as well as other hydrophobic agents, indicating that their outer membrane no longer provides an effective barrier function. (asm.org)
  • This invention relates to activation of the complement cascade in the body. (justia.com)
  • In this report, we identify a protein from the Trypanosoma cruzi (the protozoan agent of Chagas disease) endoplasmic reticulum (ER), as responsible for, at least an important part of the antitumor effect of this infection. (biomedcentral.com)
  • Because the pathogen is killed or otherwise inactivated, there is little threat of infection. (justia.com)
  • Brucella , a Gram-negative bacterium, is classified as a potential bioterrorism agent mainly due to the low dose needed to cause infection and the ability to transmit the bacteria via aerosols. (biomedcentral.com)
  • We also discuss the relative advantages and benefits offered by each complement-targeting approach, including translational considerations that might leverage a more comprehensive clinical intervention for PNH. (nih.gov)
  • This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. (missouri.edu)
  • 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. (missouri.edu)
  • In the study we propose to compare the clinical efficacy of Linezolid in bolus vs Linezolid in continuous infusion in patients with severe sepsis and septic shock (outcome) and to analyse whether significant differences are registered in the coagulation, inflammatory and complement response between the two group of patients.METHODS: A prospective, randomized comparative trial involved not neutropenic patients admitted in ICU from January until March 2004. (unipa.it)
  • Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. (bvsalud.org)
  • Treatment of Cryptobia -resistant plasma with either ethylenebis(oxyethylenenitrilo)tetraacetic acid, a Ca 2+ -chelating agent, or cobra venom factor did not reduce their lytic titres. (springer.com)
  • By using an attenuated vaccine, an agent that displays limited infectivity may be employed to elicit an immune response against the pathogen. (justia.com)
  • Ionizing radiation perturbs hematopoiesis in bone marrow, which, in turn, depresses the innate immune responses against infectious agents, including production of immunoglobulins, and disturbs the inflammatory responses, including C-reactive protein (CRP), the components of complement, and the normal balance among the inflammatory and anti-inflammatory cytokines and chemokines. (hindawi.com)
  • The first five components of complement greatly enhance the ability of IgG to act as an opsonin. (thefreedictionary.com)
  • Two renal disorders have been etiologically linked to complement regulatory pathology. (omicsonline.org)
  • Dr. Conway disclosed that he holds a patent for the use of the lectinlike domain of thrombomodulin as an anti-inflammatory agent. (medpagetoday.com)
  • The effects of reducing agents on the activities of the wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease in catalytic efficiency. (proteopedia.org)
  • TOF-MS analysis of the inactivated enzyme showed the Scysteinylation of Cys138 in the wild-type and Cys150 in the mutant enzymes. (proteopedia.org)
  • This metabolismcalled biotransformationoccurs in the liver where enzymes inactivate a deaden by means of changing it into more water-soluble compounds that can be excreted from the substance. (chesapeakehumane.org)
  • Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. (ox.ac.uk)
  • 32. A culture medium according to the claim 31, wherein the autologous human serum is treated to inactivate a complement. (freepatentsonline.com)
  • Neisseria gonorrhoeae (gonococcus) is the causative agent of the sexually transmitted disease gonorrhea. (asm.org)
  • We have identified a fur homologue in Dichelobacter nodosus , the causative agent of ovine footrot, and shown that it complements an Escherichia coli fur mutant. (asm.org)
  • Dichelobacter nodosus is a fastidious gram-negative anaerobe that is the causative agent of footrot in sheep, goats, and other ruminants. (asm.org)
  • Streptococcus mutans , a major pathogen of dental caries, is considered one of the causative agents of infective endocarditis (IE). (asm.org)
  • The causative agent of the intestinal disease cholera is Vibrio cholerae , a gram-negative motile bacterium. (asm.org)
  • They transferred plasma from patients mildly infected with Orientia tsutsugamushi, the causative agent of scrub typhus, and with no other medical problems. (i-base.info)
  • These phenotypes were complemented by supplying a functional copy of priA elsewhere in the chromosome. (asm.org)
  • We inactivated another gal gene, galE , and the mutant was also found to be defective in the catabolism of exogenous galactose but synthesized an apparently normal lipopolysaccharide (LPS). (asm.org)
  • In budding yeast, loss of topoisomerase III, encoded by the TOP3 gene, leads to a genomic instability phenotype that includes slow growth, hyper-sensitivity to genotoxic agents, mitotic hyper-recombination, increased chromosome missegregation, and meiotic failure. (genetics.org)
  • Until now, the accepted model of resistance implied that in the presence of β-lactam antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of staphylococcal cell wall from the four native staphylococcal PBPs because the latter become rapidly acylated and inactivated at even low concentrations of the antibiotic. (pnas.org)