Complement Factor H: 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).Complement Factor B: 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.Complement C3b Inactivator Proteins: 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.Macular Degeneration: 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.Complement Factor I: 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.Complement C3b: 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.Complement C3: 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.Complement Activation: 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.Complement Factor D: 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.Complement System Proteins: 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).Hemolytic-Uremic Syndrome: A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.Complement Pathway, Alternative: 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.Complement C2: 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).Complement C3d: 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).Complement C4: 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.Glomerulonephritis, Membranoproliferative: 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.Optic Disk Drusen: Optic disk bodies composed primarily of acid mucopolysaccharides that may produce pseudopapilledema (elevation of the optic disk without associated INTRACRANIAL HYPERTENSION) and visual field deficits. Drusen may also occur in the retina (see RETINAL DRUSEN). (Miller et al., Clinical Neuro-Ophthalmology, 4th ed, p355)Complement C5: 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.Complement C5a: 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.Complement C3-C5 Convertases: 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.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Complement C1q: 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 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.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Complement Pathway, Classical: 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.Retinal Drusen: Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium.Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the RETINA and SCLERA.Complement Inactivator Proteins: 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.Antigens, CD46: 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.Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Choroidal Neovascularization: A pathological process consisting of the formation of new blood vessels in the CHOROID.Complement C9: 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 C3a: 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.Retinal Pigment Epithelium: The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment.Complement Hemolytic Activity Assay: 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.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Geographic Atrophy: A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.Complement Activating Enzymes: 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.Complement C4b: 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).Receptors, Complement 3b: 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.Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses.Protein Binding: 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.Homozygote: An individual in which both alleles at a given locus are identical.Chromosomes, Human, Pair 1: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Complement C4b-Binding Protein: 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).Complement C3 Convertase, Alternative Pathway: 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.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Antigens, CD55: 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.Molecular Sequence Data: 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.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Amino Acid Sequence: 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.Complement C6: 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.Complement C1: 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.Surface Plasmon Resonance: 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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Properdin: 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.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Complement C3c: 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.Chromosomes, Human, Pair 10: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Pigment Epithelium of Eye: The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye.Complement Pathway, Mannose-Binding Lectin: 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.Complement C1 Inhibitor Protein: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Mutation: 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.Histidine: An essential amino acid that is required for the production of HISTAMINE.Complement Fixation Tests: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Blood Bactericidal Activity: 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.Protein Structure, Tertiary: 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.Bacterial Proteins: Proteins found in any species of bacterium.Enzyme-Linked Immunosorbent Assay: 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.Complement C7: 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.Receptors, Complement 3d: 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.Cobra Venoms: 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.Complement C8: 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.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Anaphylatoxins: 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.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.C-Reactive Protein: A plasma protein that circulates in increased amounts during inflammation and after tissue damage.Genetic Variation: Genotypic differences observed among individuals in a population.Recombinant Proteins: Proteins prepared by recombinant DNA technology.

Protein H, an antiphagocytic surface protein in Streptococcus pyogenes. (1/741)

Surface-associated M protein is a major virulence factor in Streptococcus pyogenes which confers bacterial resistance to phagocytosis. However, many S. pyogenes strains also express additional structurally related so-called M-like proteins. The strain studied here is of the clinically important M1 serotype and expresses two structurally related surface proteins, the M1 protein and protein H. Mutants were generated that expressed only one or none of these proteins at the bacterial surface. For survival in human blood either protein H or M1 protein was sufficient, whereas the double mutant was rapidly killed. The protein-binding properties of protein H, M1 protein, and the mutants suggest that bacterial binding of immunoglobulin G and factor H or factor H-like protein 1, which are regulatory proteins in the complement system, contribute to the antiphagocytic property.  (+info)

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer. (2/741)

BACKGROUND: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results. METHODS: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.2 years) presenting with signs, symptoms, or preliminary diagnostic results suggestive of this disease. Cystoscopy was the standard of detection. RESULTS: In the 100 patients found to have bladder cancer, the overall sensitivities of the BTA TRAK assay (at a previously determined decision threshold of 14 kilounits/L) and cytology were 66% (66 of 100) and 33% (33 of 100), respectively (P <0.001). The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grades I and II and for stage Ta and T1 tumors. In contrast, the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69% (83 of 120) and that of cytology was 99% (119 of 120; P <0.001). The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer (76%; n = 89) than in patients with these conditions. When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone, increases in overall sensitivity and equivalent specificity were observed. CONCLUSION: Because of its relatively high sensitivity, the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer.  (+info)

In vitro analysis of complement-dependent HIV-1 cell infection using a model system. (3/741)

Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors.  (+info)

Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. (4/741)

Factor H, a secretory glycoprotein composed of 20 short consensus repeat modules, is an inhibitor of the complement system. Previous studies of inherited factor H deficiency revealed single amino acid substitutions at conserved cysteine residues, on one allele arginine for cysteine 518 (C518R) and on the other tyrosine for cysteine 941 (C941Y) (Ault, B. H., Schmidt, B. Z., Fowler, N. L., Kashtan, C. E., Ahmed, A. E., Vogt, B. A., and Colten, H. R. (1997) J. Biol. Chem. 272, 25168-25175). To ascertain if the phenotype, impaired secretion of factor H, is due to the C518R substitution or the C941Y substitution and to ascertain the mechanism by which secretion is impaired, we studied COS-1 and HepG2 cells transfected with wild type and several mutant factor H molecules. The results showed markedly impaired secretion of both C518R and C941Y factor H as well as that of factor H molecules bearing alanine or arginine substitutions at the Cys518-Cys546 disulfide bond (C518A, C546A, C546R, C518A-C546A). In each case, mutant factor H was retained in the endoplasmic reticulum and degraded relatively slowly as compared with most other mutant secretory and membrane proteins that are retained in the endoplasmic reticulum. These data indicate that impaired secretion of the naturally occurring C518R and C941Y mutant factor H proteins is due to disruption of framework-specific disulfide bonds in factor H short consensus repeat modules.  (+info)

Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. (5/741)

Familial hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) carry a very poor outcome and have been reported in association with decreased serum levels of the third complement component (C3). Uncontrolled consumption in the microcirculation, possibly related to genetically determined deficiency in factor H--a modulator of the alternative pathway of complement activation--may account for decreased C3 serum levels even during disease remission and may predispose to intravascular thrombosis. In a case-control study by multivariate analysis, we correlated putative predisposing conditions, including low C3 serum levels, with history of disease in 15 cases reporting one or more episodes of familial HUS and TTP, in 25 age- and gender-matched healthy controls and in 63 case-relatives and 56 control-relatives, respectively. The relationship between history of disease, low C3, and factor H abnormalities was investigated in all affected families and in 17 controls. Seventy-three percent of cases compared with 16% of controls (P < 0.001), and 24% of case-relatives compared with 5% of control-relatives (P = 0.005) had decreased C3 serum levels. At multivariate analysis, C3 serum level was the only parameter associated with the disease within affected families (P = 0.02) and in the overall study population (P = 0.01). Thus, subjects with decreased C3 serum levels had a relative risk of HUS or TTP of 16.56 (95% confidence interval [CI], 1.66 to 162.39) within families and of 27.77 (95% CI, 2.44 to 314.19) in the overall population, compared to subjects with normal serum levels. Factor H abnormalities were found in four of the cases, compared with three of the healthy family members (P = 0.02) and none of the controls (P = 0.04) and, within families, factor H abnormalities were correlated with C3 reduction (P < 0.05). Reduced C3 clusters in familial HUS and TTP is likely related to a genetically determined deficiency in factor H and may predispose to the disease. Its demonstration may help identify subjects at risk in affected families.  (+info)

Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. (6/741)

BACKGROUND: In a recent study of three families we have found that inherited haemolytic uraemic syndrome (HUS) maps to a region of chromosome 1q containing the gene for complement factor H. In one of these families and also in a case of sporadic D-HUS, we have identified mutations in the factor H gene. A further family with inherited HUS has therefore been investigated. METHODS: DNA extracted from the family members and DNA extracted from archival post-mortem material from a deceased family member, was studied. Review of renal biopsies and study of complement components was also undertaken. RESULTS: This family demonstrates an inherited deficiency of complement factor H. Non-diarrhoeal HUS has affected at least two family members with half normal levels of factor H. CONCLUSION: These findings represent further evidence of the association between factor H dysfunction and HUS.  (+info)

Identification of human complement Factor H as a ligand for L-selectin. (7/741)

The selectin family of adhesion molecules (E-, P- and L-selectins) is involved in leukocyte recruitment to sites of inflammation and tissue damage. Recently it has been shown that L-selectin is involved not only in leukocyte tethering and rolling, but also plays an important role in leukocyte activation. For example, glycosylation-dependent cell-adhesion molecule 1 (GlyCAM-1), a known ligand for L-selectin, has been shown to enhance beta2-integrin function. GlyCAM-1 is a secreted protein and is present in mouse serum at a concentration of approx. 1.5 microg/ml. There is no obvious GlyCAM-1 homologue in man and, to date, L-selectin ligand(s) from human serum have not been characterized. Therefore we have used L-selectin affinity chromatography, followed by ion-exchange chromatography, to isolate specific ligand(s) for L-selectin. Using this procedure, we have isolated three major glycoproteins of apparent molecular masses 170 kDa, 70kDa and 50 kDa. The 170 kDa protein band was digested with trypsin and peptides were analysed by delayed extraction matrix-assisted laser desorption ionization MS and protein database searching. The 170 kDa protein was identified as the human complement protein Factor H. Human Factor H, isolated by a different method, was shown to bind specifically to L-selectin in the presence of CaCl2, and binding was inhibited by anti-L-selectin antibodies, fucoidan and lipopolysaccharide. Only a part of the purified Factor H preparation bound to immobilized L-selectin. The interaction of Factor H with leukocyte L-selectin was shown to induce the secretion of tumour necrosis factor-alpha (TNF-alpha). Pretreatment of Factor H with sialidase reduced both the binding of L-selectin to Factor H and the Factor H-induced L-selectin-mediated TNF-alpha secretion by leukocytes. Taken together, these results demonstrate that a post-translationally modified form of human plasma Factor H is a potential physiological ligand for L-selectin.  (+info)

Resistance to both complement activation and phagocytosis in type 3 pneumococci is mediated by the binding of complement regulatory protein factor H. (8/741)

To study the role of surface-associated proteins in the virulence of Streptococcus pneumoniae, we used two serotype 3 strains, ATCC 6303 and WU2, and two PspA-negative mutants of WU2, an encapsulated one, JY1123 (Caps(+)/PspA(-)), and an unencapsulated one, DW3.8 (Caps(-)/PspA(-)). ATCC 6303 and WU2 were highly virulent in mice, while the virulence of JY1123 was slightly decreased (50% lethal doses [LD(50)s], 24, 6, and 147 CFU/mouse, respectively); DW3.8 was avirulent (LD(50), 2 x 10(8) CFU). In vitro, ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) strongly resisted complement activation and complement-dependent opsonophagocytosis, whereas DW3.8 (Caps(-)/PspA(-)) was easily phagocytized in fresh serum. Trypsin treatment of ATCC 6303, WU2, and JY1123 (Caps(+)/PspA(-)) resulted in enhanced complement activation and complement-dependent opsonophagocytosis. Trypsin had no deleterious effect on the polysaccharide capsule. In addition, trypsin pretreatment of ATCC 6303 strongly reduced virulence upon intraperitoneal challenge in mice. This indicated that surface proteins play a role in the resistance to complement activation and opsonophagocytosis and contribute to the virulence of type 3 pneumococci. In subsequent experiments, we could show that the modulation of complement activation was associated with surface components that bind complement regulator factor H; binding is trypsin sensitive and independent of prior complement activation. Immunoblotting of cell wall proteins of the virulent strain ATCC 6303 with anti-human factor H antibody revealed three factor H-binding proteins of 88, 150, and 196 kDa. Immunogold electron microscopy showed a close association of factor H-binding components with the outer surface of the cell wall. The role of these factor H-binding surface proteins in the virulence of pneumococci is interesting and warrants further investigation.  (+info)

Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice.
4AYI: Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria meningitidis FHbp Variant 3 Wild type
Purpose: Several key components of the complement cascade are associated with the pathogenesis of age-related macular degeneration (AMD), including the Y402H variation in the gene encoding complement factor H (CFH), which confers a several-fold increased risk for developing AMD. Earlier studies, including ours, demonstrated an association between drusen, a hallmark of early AMD, and increased inflammatory cytokines in retina of postmortem eye tissues. In this study, we address the correlation between plasma cytokines and drusen load, choroidal thickness and the Y402H polymorphism in CFH gene in patients with dry AMD.. Methods: Forty-four patients with dry AMD were recruited. Drusen area and volume were determined using the spectral-domain optical coherence tomography (SD-OCT) software, and choroidal thickness was measured using enhanced depth imaging (EDI). The subjects blood samples were analyzed for multiple cytokines using Bio-Plex suspension assays and genotyped for the CFH Y402H ...
Purpose: : Previous studies have demonstrated that the Y402H polymorphism in the complement factor H (CFH) gene is associated with an approximately 3-fold increased risk for age-related macular degeneration (AMD) in Caucasians of predominantly European descent. The prevalence of AMD varies widely among persons of different ethnicities. In this study we sought to determine the frequency of this polymorphism in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Moreover, we investigated whether specific AMD phenotypes are associated with this polymorphism. Methods: : Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=100), and Japanese (n=82). Individuals were genotyped using NIaIII restriction digestion. The frequency of the histidine (His) allele at position 402 of the CFH gene was determined. A bioinformatic approach was used to identify single nucleotide polymorphisms in ...
TY - JOUR. T1 - Synthesis of complement factor H by retinal pigment epithelial cells is down-regulated by oxidized photoreceptor outer segments. AU - Chen, Mei. AU - Forrester, John Vincent. AU - Xu, Heping. PY - 2007/4. Y1 - 2007/4. N2 - Complement activation is thought to be involved in the pathogenesis of age-related macular degeneration (AMD), in part because certain gene polymorphisms in complement factor H (CFH), an important regulator of the alternative complement activation pathway, are high risk factors for AMD. How CFH is regulated locally at the retina/choroid interface and how this contributes to AMD development remain unknown. In the present study, we have confirmed that CFH was detectable by immunohistochemistry in the choroid, and at low levels in the RPE cell and interphotoreceptor matrix, but appeared to be concentrated in dense patches in Bruchs membrane. In vitro, cultured human and mouse RPE cells expressed high levels of CFH as evidenced by immunohistochemistry and western ...
SR GROUP - Exporter, Importer, Manufacturer, Distributor, Supplier, Trading Company of Rat CFH(Complement Factor H) ELISA Kit based in Delhi, India
Nontypeable Haemophilus influenzae (NTHi) cause a range of illnesses including otitis media, sinusitis, and exacerbation of chronic obstructive pulmonary disease, infections that contribute to the problem of antibiotic resistance and are themselves often intractable to standard antibiotic treatment regimens. We investigated a strategy to exploit binding of the complement inhibitor Factor H (FH) to NTHi as a functional target for an immunotherapeutic containing the NTHi binding domain of FH fused to the Fc domain of IgG1. Chimeric proteins containing the regions that most FH-binding bacteria use to engage human FH, domains 6 and 7 (FH6,7/Fc) and/or 18 through 20 (FH18-20/Fc), were evaluated for binding to NTHi. FH6,7/Fc bound strongly to each of seven NTHi clinical isolates tested and efficiently promoted complement-mediated killing by normal human serum. FH18-20/Fc bound weakly to three of the strains but did not promote complement dependent killing. Outer-membrane protein P5 has been implicated in FH
Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Recent studies have identified a factor H-associated form of HUS, caused by gene mutations that cluster in the C-terminal region of the complement regulator factor H. Here we report how three mutations (E1172Stop, R1210C, and R1215G; each of the latter two identified in three independent cases from different, unrelated families) affect protein function. All three mutations cause reduced binding to the central complement component C3b/C3d to heparin, as well as to endothelial cells. These defective features of the mutant factor H proteins explain progression of endothelial cell and microvascular damage in factor H-associated genetic HUS and indicate a protective role of factor H for tissue integrity during thrombus formation.. ...
Hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Recent studies have identified a factor H-associated form of HUS, caused by gene mutations that cluster in the C-terminal region of the complement regulator factor H. Here we report how three mutations (E1172Stop, R1210C, and R1215G; each of the latter two identified in three independent cases from different, unrelated families) affect protein function. All three mutations cause reduced binding to the central complement component C3b/C3d to heparin, as well as to endothelial cells. These defective features of the mutant factor H proteins explain progression of endothelial cell and microvascular damage in factor H-associated genetic HUS and indicate a protective role of factor H for tissue integrity during thrombus formation.. ...
The complement control protein (CCP) modules (also known as short consensus repeats) are defined by a consensus sequence within a stretch of about 60 amino acid residues. These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. In all, 548 structurally important nuclear Overhauser enhancement cross-peaks were quantified as distance restraints and, together with 41 experimentally measured angle restraints, were incorporated into a simulated annealing protocol to determine a family of closely related structures that satisfied the experimental observations. The CCP structure is shown to be based on a beta-sandwich arrangement; one face made up of three beta-strands hydrogen-bonded to form a triple-stranded region at its centre ...
The complement control protein (CCP) modules (also known as short consensus repeats) are defined by a consensus sequence within a stretch of about 60 amino acid residues. These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. In all, 548 structurally important nuclear Overhauser enhancement cross-peaks were quantified as distance restraints and, together with 41 experimentally measured angle restraints, were incorporated into a simulated annealing protocol to determine a family of closely related structures that satisfied the experimental observations. The CCP structure is shown to be based on a beta-sandwich arrangement; one face made up of three beta-strands hydrogen-bonded to form a triple-stranded region at its centre ...
SEA635Mu, CF-H; FH; FHL1; ARMD4; ARMS1; CFHL3; HF1; HF2; HUS; H Factor 2; Age-Related Maculopathy Susceptibility 1; Adrenomedullin binding protein | Products for research use only!
Nita Amornsiripanitch1, Shaolin Hong1, Michael J. Campa1, Michael M. Frank2, Elizabeth B. Gottlin1, and Edward F. Patz Jr.1,3 Author Affiliations. Corresponding Author: Edward F. Patz, Jr., Duke University Medical Center, Department of Radiology, Box 3808, Durham, NC 27710. Phone: 919-684-7311; Fax: 919-681-7165; E-mail: [email protected] ...
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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
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Progress in Understanding AMD Genetics. While a number of environmental and dietary risk factors have been linked with AMD, progress in identifying genetic components associated with the disease has been somewhat slower. However significant progress has been made over the last few years: up to six regions of the genome have been identified as potentially harboring AMD genes.. One region repeatedly linked to AMD in family based studies is located on chromosome 1. This year, several independent research teams reported a strong association of AMD with a chromosomal 1 gene that encodes the protein, complement factor H (CFH). A single base change in the CFH gene introduces a single amino acid change into the sequence of the variant CFH protein it produces, replacing the amino acid tyrosine with histidine. Understanding this simple genetic alteration - a change in a single unit of DNA out of the 3 billion or so units that make up our genetic blueprint - could hold future promise for those at risk for ...
1: AMD and complement factor H (CFH). Common sequence variants of CFH have major roles in determining susceptibility to age-related macular degeneration (AMD)....
Complement, C3 Convertase, Regulation, Cells, Disease, Complement Factor H, Inhibition, Therapeutic, Transplant, Allograft, Donor, Donors, and Graft
Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. ...
In the case of AMD, Erica Fletcher et al. have interestingly reviewed the new means of detecting the signs of early-stage disease.[46] , [47] AMD has genetic and environmental risk factors. Genetic testing is now readily available using a combination of 16 genes to help predict the risk profile of an individual. Among the genes associated with an increased risk of developing AMD is complement factor H (CFH), the mutations of which contribute to explain immune dysregulation in AMD. Considering retinal imaging, Hogg et al. have recently highlighted that a particular form of drusens called reticular pseudo-drusen, at a subretinal level, is a risk-factor for progression to late-stage disease. [48] A research team in the Netherlands has developed a software to analyze color fundus photographs so as to quantify and characterize drusens and determine a risk assessment. Using fundus autofluorescence (FAF), the RPE cell dysfunction can be detected through the accumulation of lipofuscin. Some scientists ...
T Cells, Mice, Phenotype, Regulatory T Cells, Cell, Cells, Muscle, Myopathies, Myopathy, Patients, Complement Factor H, Animals, Memory, Administration, Blood, Bone, Bone Marrow, Bone Marrow Transplantation, Cell Numbers, Cell Transplantation
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
This study explores the relationship between defined antigens of the C3 molecule and those surface structures that are involved in interaction with factors I and H. Methylamine treatment at pH 11 followed by neutralization converts C3 into a modified state in which the molecule is optimally susceptible to cleavage by factor I in the presence of factor H. The modified C3 is characterized by an antigenic profile with expression of antigens of the C3(N), C3(S), and C3(D) subsets. These antigenic properties closely mirror those of physiologically bound C3b, suggesting that modification of antigenic expression upon denaturation of C3 reflects a regulatory mechanism for I and H function. Immunochemical studies of the alkaline-denatured C3 suggested that factor H interacts with surfaces of C3 that are situated within the C3c fragment and that are defined by C3(SN) antigens, while factor I predominantly interacts with C3(SN) antigens associated with the C3d fragment and with C3(D) antigens hidden in ...
The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity ...
References for Abcams Recombinant Human FH protein (ab116496). Please let us know if you have used this product in your publication
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This gene is a member of a small complement factor H (CFH) gene cluster on chromosome 1. Each member of this gene family contains multiple short consensus repeats (SCRs) typical of regulators of complement activation. The protein encoded by this gene has nine SCRs with the first two repeats having heparin binding properties, a region within repeats 5-7 having heparin binding and C reactive protein binding properties, and the C-terminal repeats being similar to a complement component 3 b (C3b) binding domain. This protein co-localizes with C3, binds C3b in a dose-dependent manner, and is recruited to tissues damaged by C-reactive protein. Allelic variations in this gene have been associated, but not causally linked, with two different forms of kidney disease: membranoproliferative glomerulonephritis type II (MPGNII) and hemolytic uraemic syndrome (HUS). [provided by RefSeq, Jan 2010 ...
Membranoproliferative Glomerulonephritis type II {1:Abrera-Abeleda et al. (2006)} summarized features of MPGN relevant to the complement cascade. MPGN type II, also known as dense deposit disease, causes chronic renal dysfunction that progresses to end-stage renal disease in about half of patients within 10 years of diagnosis. MPGN types I and III are variants of immune complex-mediated disease; MPGN II, in contrast, has no known association with immune complexes ({2:Appel et al., 2005}). MPGN II accounts for less than 20% of cases of MPGN in children and only a fractional percentage of cases in adults. Both sexes are affected equally, with the diagnosis usually made in children between the ages of 5 and 15 years who present with nonspecific findings such as hematuria, proteinuria, acute nephritic syndrome, or nephrotic syndrome. More than 80% of patients with MPGN II are positive for serum C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the convertase of the alternative ...
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it is caused by chronic, uncontrolled activation of the complement system, a branch of the bodys immune system that destroys and removes foreign particles. The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death. The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane cofactor protein), or is occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components, for example anti-factor H antibodies. Despite the use of supportive care, historically an estimated 33-40% of patients died or developed end-stage renal disease (ESRD) with the first ...
Atypical hemolytic uremic syndrome (aHUS) is frequently associated in humans with loss-of-function mutations in complement-regulating proteins or gain-of-function mutations in complement-activating proteins. Thus, aHUS provides an archetypal complement-mediated disease with which to model new therapeutic strategies and treatments. Herein, we show that, when transferred to mice, an aHUS-associated gain-of-function change (D1115N) to the complement-activation protein C3 results in aHUS. Homozygous C3 p.D1115N (C3KI) mice developed spontaneous chronic thrombotic microangiopathy together with hematuria, thrombocytopenia, elevated creatinine, and evidence of hemolysis. Mice with active disease had reduced plasma C3 with C3 fragment and C9 deposition within the kidney. Therapeutic blockade or genetic deletion of C5, a protein downstream of C3 in the complement cascade, protected homozygous C3KI mice from thrombotic microangiopathy and aHUS. Thus, our data provide in vivo modeling evidence that ...
This is a Phase 3, multicenter study of OMS721 in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The uncontrolled, open-label study will evaluate the effect of OMS721 in subjects with plasma therapy-resistant aHUS and plasma therapy-responsive aHUS. This study has four periods: Screening, Treatment Induction, Treatment Maintenance, and Follow-up. Approximate enrollment is 80 subjects. An interim analysis will be performed after 40 subjects have completed 26 weeks of treatment for potential registration ...
Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors. ...
Zuber J, Le Quintrec M, Krid S, Bertoye C, Gueutin V, Lahoche A et al (2012) Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 12(12):3337-3354. doi:10.1111/j.1600-6143.2012.04252.x CrossRefPubMedGoogle Scholar ...
Sphingolipids are bioactive molecules associated with oxidative stress, inflammation, and neurodegenerative diseases, but poorly studied in the context of age-related macular degeneration (AMD), a prevalent sight-threatening disease of the ageing retina. Here, we found higher serum levels of hexosylceramide (HexCer) d18:1/16:0 in patients with choroidal neovascularization (CNV) and geographic atrophy (GA), two manifestations of late stage AMD, and higher ceramide (Cer) d18:1/16:0 levels in GA patients. A sensitivity analysis of genetic variants known to be associated with late stage AMD showed that rs1061170 (p.Y402H) in the complement factor H (CFH) gene influences the association of Cer d18:1/16:0 with GA. To understand the possible influence of this genetic variant on ceramide levels, we established a cell-based assay to test the modulation of genes in the ceramide metabolism by factor H-like protein 1 (FHL-1), an alternative splicing variant of CFH that also harbors the 402 residue. We first ...
Dense deposit disease (DDD) is a condition that primarily affects kidney function. Signs and symptoms usually start between the ages of 5 and 15 but may also begin in adulthood. The major features of DDD are due to kidney malfunction, and often include proteinuria; hematuria; reduced amounts of urine; low levels of protein in the blood; and swelling in many areas of the body. About half of affected people develop end-stage renal disease (ESRD) within 10 years after symptoms start. DDD can have genetic or non-genetic causes. It can be caused by mutations in the C3 and CFH genes; it may develop as a result of both genetic risk factors and environmental triggers; or it can result from the presence of autoantibodies that block the activity of proteins needed for the bodys immune response. Most cases are sporadic (occurring by chance in people with no history of the disorder in their family ...
There is increasing evidence that human complement factor H-related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin-resistant LADC cell line CDDP-R (derived from H460) was also ...
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 ...
Nineteen years after Gasser et al. [1] reported HUS, an interesting report was published in the Lancet [10]. This report indicated that although C3-predominant activity is initiated in the blood vessels in TMA patients, this is not observed in typical cases of HUS, suggesting that complement activation is involved in aHUS onset [12]. Subsequently, numerous researchers have elucidated further information on the pathology of aHUS. At present, the reported causes of aHUS include, complement regulation abnormalities, cobalamin metabolism disorder, infection with Streptococcus pneumoniae and other microorganisms, drugs, pregnancy, and autoimmune diseases.. The complement system plays an important role as part of the immune systems of living organisms. It is activated via 3 pathways, the classical, alternative, and lectin pathways. As a result of the activation of the hosts alternative and classical pathways, C5b-9, a membrane attack complex, is generated and destroys cells by forming transmembrane ...
Background: Cytologic examination of specimens obtained from the respiratory tract is a lung cancer diagnostic procedure with high specificity, but moderate sensitivity. The use of molecular biomarkers may enhance the sensitivity of cytologic examination in the detection of lung cancer. Methods: Complement factor H, a protein secreted by lung cancer cells, was quantified in a series of bronchoalveolar lavage supernatants from lung cancer patients and patients with non-malignant respiratory diseases. Albumin, total protein content, and hemoglobin were also analyzed. Results were validated in independent sets of bronchoalveolar lavage and sputum supernatants. Results: There was a significantly higher concentration of factor H in bronchoalveolar lavage samples from lung cancer patients. The sensitivity and specificity of the factor H test was 82% and 77%, respectively. These results were validated in an independent set of patients with nearly identical results. Furthermore, 70% and 45% of ...
An international team of scientists has identified a protein that is strongly linked to the commonest cause of blindness in developed countries when its levels are raised in the blood. The discovery is a major step forward in the understanding of age-related macular degeneration (AMD), which affects 1.5 million people in the UK alone. The study, carried out by a team from the Universities of Manchester, Cardiff, London, and Nijmegen, and Manchester Foundation NHS Trust was published online on February 7, 2020 in Nature Communications. The open-access article is titled ""Increased Circulating Levels of Factor H Related Protein 4 Are Strongly Associated with Age-Related Macular Degeneration." The protein, Factor H-Related Protein 4 (FHR4), was found by the team to be present at higher levels in the blood of patients with AMD compared to individuals of a similar age without the disease. The findings were confirmed in 484 patient and 522 control samples from two independent collections across ...
Envisioning A Cure For AMD (by Rick Trevino, OD). I would like to quote from an article by Dr. Rick Travino, who is active in our online community and who hosts one of the most informative web sites about vision research and developments. In his commentary, "Envisioning A Cure For AMD," he wrote:. "One of the most exciting developments in the field of AMD research has been the discovery of a relatively small number of genes that seems to control a large amount of the risk of developing the disease.. "Most of the genes that are known to influence the risk of developing AMD involve various components of the complement cascade. Most prominent among these is complement factor H (CFH); however, variants in genes coding for other components of the complement system have also been discovered and shown to be associated with AMD risk and protection. The complement system is very important in regulating the bodys immune system and directing inflammatory processes. Several lines of evidence suggest that ...
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In a significant development the FDA in the USA approved Soliris (Eculizumab) for use in atypical Hemolytic Uremic Syndrome. To those saying,
The Center for Life at Newcastle upon Tyne, UK, is organizing a conference for patients and their family on atypical Hemolytic Uremic Syndrome on Sat...
This is an interesting follow-up study from Lukiws group on the possible role of microRNAs in AD. Here, the authors identify a novel regulatory pathway (NFκB , miR-146a , complement factor H) potentially involved in the inflammation response in AD brain. Hence, apart from modulating directly BACE1 and Aβ levels (as shown by us and Peter Nelsons group), the microRNA network is emerging as a potential important contributor to AD pathology.. The findings presented in this paper originate from the observation that miR-146a levels are elevated in AD brain. Whether these changes in miR-146a are confirmed in an independent set of patient samples remains to be seen. Indeed, current studies in humans suggest no or minimal overlap in changes in microRNA expression profiles in AD brain. While this does not exclude a role for microRNAs in neurodegeneration-which is clearly supported by studies in animals-it is important to take into consideration the experimental variables which may explain these ...
Information for healthcare professionals for diagnosing and treating Atypical Hemolytic Uremic Syndrome. Soliris is the only therapy approved for the treatment of aHUS.
aHUS patients raised the question " are the predisposing genetic factors of aHUS fully catalogued?" as a topic of research which matters to them in their Global Research Agenda.. Those affected by aHUS know well that it is imperfections in components of the Complement System that made them susceptible to the disease when one of many "triggering hits" over their lives caused a catastrophic onset of aHUS.. They know that there are different imperfections in different aHUS patients, some not yet found. But how many and who is keeping a record of what to look for as an aHUS "susceptibility imperfection" , or "mutation" or "significant variant".. At University College London, the Department of Structural and Molecular Biology has been collating variants in the Complement System for 15 years and creating a database of information about them. It is known as the Database of Complement Gene Variants and can seen online , click here.. Designed for use by scientist and clinicians the information held is ...
Read about a case report study describing the clinical case of a patient with atypical hemolytic uremic syndrome (aHUS) associated with heart disease.
Theresa Kwon, Marie-Agnes Dragon-Durey, Marie-Alice Macher, Veronique Baudouin, Anne Maisin, Michel Peuchmaur, Veronique Fremeaux-Bacchi and Chantal Loirat. in Nephrology Dialysis Transplantation Published on behalf of European Renal Association - European Dialysis and Transplant Assoc ...
CONTROL AND ANALYSIS OF PARTICULATE MATTER BY MEMBRANE FILTRATION. This system has exhibited tadalafil stability in the sense of, bar a number of notable exceptions, surface temperature remaining within the bounds required for liquid water and so a significant biosphere. Based on whether the PCT level was monitored or not, we divided patients into regular group and PCT group. C4NeFs were not detected in tadalafil 20 mg 150 patients with another complement-mediated kidney disease, atypical hemolytic uremic syndrome. The absorption of hydrophobic drugs and nutrients from the intestine is principally determined by the tadalafil 20 mg canadian drug stores amount that can be dissolved by the endogenous fluids present in the gut. The MLE algorithm searches for the image that has the maximum probability to generate the projection data.. Processing of pain- and body-related verbal material in chronic pain patients: central and peripheral correlates. However, genotyping of the flanking sequences on 22q ...
The alternative pathway is continuously activated at a low level, analogous to a car engine at idle, as a result of spontaneous C3 hydrolysis due to the breakdown of the internal thioester bond (C3 is mildly unstable in aqueous environment). The alternative pathway does not rely on pathogen-binding antibodies like the other pathways.[2] C3b that is generated from C3 by a C3 convertase enzyme complex in the fluid phase is rapidly inactivated by factor H and factor I, as is the C3b-like C3 that is the product of spontaneous cleavage of the internal thioester. In contrast, when the internal thioester of C3 reacts with a hydroxyl or amino group of a molecule on the surface of a cell or pathogen, the C3b that is now covalently bound to the surface is protected from factor H-mediated inactivation. The surface-bound C3b may now bind factor B to form C3bB. This complex in the presence of factor D will be cleaved into Ba and Bb. Bb will remain associated with C3b to form C3bBb, which is the alternative ...
N.C. Communicable Disease Branch page for hemolytic uremic syndrome (HUS). Includes a definition of the illness, prevention information, and links to relevant CDC resources.
Postpartum Hemolytic Uremic Syndrome (PHUS) is a rare disease characterized by spontaneous renal failure occurring immediately after delivery to 10 we..
OBJECTIVES: I. Determine the effect of SYNSORB Pk therapy on mortality and frequency of severe extrarenal complications observed in children with acute stage E. coli-associated hemolytic uremic syndrome.. II. Determine the effect of SYNSORB Pk therapy on the need for the duration of dialysis in these patients.. III. Determine the effect of SYNSORB Pk therapy on the recovery of renal function and resolution of urinary abnormalities in these patients. ...
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Atypical HUS, is a rare disease among children causing kidney failure and high blood pressure. Offering support and information including, treatment, symptoms, case studies and research. ...
Factor B antibody, Internal (complement factor B) for FACS, IHC-P, WB. Anti-Factor B pAb (GTX80605) is tested in Human samples. 100% Ab-Assurance.
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Vi fikk nøyaktig 20 mm, og jeg er glad for hver dråpe. Det kan hende vi får mer i kveld, og da melder de om torden igjen. Det fikk vi ikke i går, og det er nesten så jeg ønsker at det skulle komme, for det går nesten ikke an å puste her. Høy luftfuktighet, og tett skydekke er årsaken til det. Men jeg skal ikke klage ...
Factor H binding protein (fHbp) is one of the main antigens of the 4-component meningococcus B (4CMenB) multicomponent vaccine against disease caused by serogroup B Neisseria meningitidis (MenB). fHbp binds the complement down-regulating protein human factor H (hfH), thus resulting in immune evasion. fHbp exists in 3 variant groups with limited cross-protective responses. Previous studies have described the generation of monoclonal antibodies (mAbs) targeting variant-specific regions of fHbp. Here we report for the first time the functional characterization of two mAbs that recognize a wide panel of fHbp variants and subvariants on the MenB surface and that are able to inhibit fHbp binding to hfH. The antigenic regions targeted by the two mAbs were accurately mapped by hydrogen-deuterium exchange mass spectrometry (HDX-MS), revealing partially overlapping epitopes on the N terminus of fHbp. Furthermore, while none of the mAbs had bactericidal activity on its own, a synergistic effect was observed for
TABLE-US-00001 TABLE Y Comp. No. R1 R2 R3 R4 R8a R8b R8c Y.001 H H H H 4-Cl H H Y.002 CH3 H H H 4-Cl H H Y.003 CH2CH3 H H H 4-Cl H H Y.004 (CH2)2CH3 H H H 4-Cl H H Y.005 CH(CH3)2 H H H 4-Cl H H Y.006 F H H H 4-Cl H H Y.007 H H CH3 H 4-Cl H H Y.008 H H CH2CH3 H 4-Cl H H Y.009 H H (CH2)2CH3 H 4-Cl H H Y.010 H H CH(CH3)2 H 4-Cl H H Y.011 H H F H 4-Cl H H Y.012 CH3 CH3 H H 4-Cl H H Y.013 CH2CH3 CH3 H H 4-Cl H H Y.014 (CH2)2CH3 CH3 H H 4-Cl H H Y.015 CH(CH3)2 CH3 H H 4-Cl H H Y.016 F CH3 H H 4-Cl H H Y.017 CH3 H CH3 H 4-Cl H H Y.018 CH2CH3 H CH3 H 4-Cl H H Y.019 (CH2)2CH3 H CH3 H 4-Cl H H Y.020 CH(CH3)2 H CH3 H 4-Cl H H Y.021 CH3 H F H 4-Cl H H Y.022 CH2CH3 H F H 4-Cl H H Y.023 H H CH3 CH3 4-Cl H H Y.024 H H CH2CH3 CH3 4-Cl H H Y.025 H H CH(CH3)2 CH3 4-Cl H H Y.026 H H CH3 F 4-Cl H H Y.027 H H CH2CH3 F 4-Cl H H Y.028 H H (CH2)2CH3 F 4-Cl H H Y.029 H H CH(CH3)2 F 4-Cl H H Y.030 H H F F 4-Cl H H Y.031 CH3 H CH3 F 4-Cl H H Y.032 CH3 H CH2CH3 F 4-Cl H H Y.033 CH3 H (CH2)2CH3 F 4-Cl H H Y.034 CH3 H ...
From NCBI Gene:. This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]. From UniProt: ...
YB1, 0.1 mg. CRASP-1, or Complement Regulator-Acquiring Surface Protein 1, is a multifunctional protein of Lyme disease-causing B.
Periodontitis is a chronic inflammatory disease that affects over 116 million adults in the United States. A shift in the normal microflora occurs as periodontal disease develops resulting in a larger number of Gram-negative anaerobes and spirochetes. An increase in the oral spirochete, Treponema denticola, is highly correlated with periodontal disease progression and severity. The ability of this periopathogen to thrive in the subgingival crevice is dependent on complement evasion mechanisms. Earlier analyses demonstrated that the primary mechanism of T. denticola serum resistance is binding of the human complement regulatory protein, Factor H (FH), to the factor H-binding protein (FhbB). FH serves as cofactor in the Factor-I mediated cleavage of C3b and accelerates the decay of the C3 convertase complex, leading to downregulation of C3b production. Several pathogens bind FH, and a number of these bacterial binding proteins have been shown to bind plasminogen. Plasminogen is a plasma
The kidney is particularly susceptible to complement-mediated injury in a number of clinical settings, and congenital deficiency or defects in the complement-regulatory proteins MCP and factor H are strongly associated with the development of renal disease. In the current study, we demonstrated that Crry (the murine homolog of MCP in the kidney) is the only membrane-bound regulator of complement expressed by murine TECs. Crry is expressed on the cell membrane, and its expression is concentrated in the basolateral portion of the cell. Polarized TECs regulate complement more efficiently on the basolateral surface of the cells than on the apical surface, in part because of Crry expression at this site. As with renal ischemia/reperfusion (I/R) (21), chemical hypoxia of the TECs causes a reduction in surface Crry levels, and the distribution within the cell is also altered.. Spontaneous complement activation on the surface of TECs is also controlled by endogenous factor H. When rH 19-20 was added to ...
A diagnosis of thrombotic microangiopathy on kidney biopsy in a patient presenting with hypertensive emergency has historically elicited the diagnosis of malignant hypertension-associated thrombotic microangiopathy. Recent studies, however, have raised awareness that a number of these patients may actually represent atypical hemolytic uremic syndrome. To further investigate this premise, we performed next-generation sequencing to interrogate the coding regions of 29 complement and coagulation cascade genes associated with atypical hemolytic uremic syndrome in 100 non-elderly patients presenting with severe hypertension, renal failure and a kidney biopsy showing microangiopathic changes limited to the classic accelerated hypertension-associated lesion of arterial intimal edema (mucoid intimal hyperplasia) in isolation and without accompanying glomerular microthrombi ...
Alexions product Soliris® (eculizumab), is a therapy indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).
PURPOSE. We explored associations between age-related macular degeneration (AMD) and genetic variants of 10 genes in a nationwide Chinese population.. METHODS. In this multicenter case-control study, 535 AMD patients and 469 controls were recruited from 16 centers that spread from the north to the south of China. All participants underwent comprehensive eye examinations, and 40 single nucleotide polymorphisms (SNPs) of 10 genes were selected. DNA samples were genotyped with the MassArray system. The effect of the genotypes and haplotypes on AMD was assessed with logistic regression analysis, adjusted for age, sex, long-term residence, and family origin.. RESULTS. In our study, 11 SNPs in complement H (CFH), 2 in age-related maculopathy susceptibility 2 (ARMS2), and 2 in high-temperature requirement factor A1 (HTRA1) were associated significantly with AMD. They were rs551397, rs800292, rs1329424, rs1061170, rs10801555, rs12124794, rs10733086, rs10737680, rs2274700, rs1410996, and rs380390 in CFH; ...
TY - JOUR. T1 - Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium. AU - Tripodo, Claudio. AU - Agostinis, Chiara. AU - Rizzi, Lucia. AU - Tedesco, Francesco. AU - Radillo, Oriano. AU - De Seta, Francesco. AU - Ghebrehiwet, Berhane. AU - Bossi, Fleur. AU - Bulla, Roberta. AU - Debeus, Alessandra. PY - 2008. Y1 - 2008. N2 - This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free ...
Recurrence of hemolytic uremic syndrome after renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study. Quan A, Sullivan EK, Alexander SR. Transplantation 2001;72(4):742-745.. ABSTRACT:. Hemolytic uremic syndrome (HUS) is a leading cause of renal failure in children. Although 90% of children with typical or classic HUS (associated with E. coli O157:H7) fully regain normal renal function, 5% die and 5% develop end-stage renal disease (ESRD) and require subsequent dialysis and renal transplantation. Among HUS renal transplant recipients, the incidence of recurrence of HUS in renal allografts has varied from 0% to 50%. Atypical HUS, use of cyclosporine, and early transplantation after HUS are possible risk factors. This report reviews the data from 61 (54%) of 114 HUS patients within the North American Pediatric Renal Transplant Cooperative Study registry who have had a transplant. Of these 61 patients, 5 patients (with 6 renal transplants) ...
PMID 20132989] Phenotype and Genotype Characteristics of Age-related Macular Degeneration in a Japanese Population [PMID 20678803] Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular Degeneration [PMID 21174599] Pigment Epithelium-Derived Factor Gene Polymorphisms in Exudative Age-Related Degeneration in a Chinese Cohort ...
The IUPHAR/BPS Guide to Pharmacology. complement factor B - S1: Chymotrypsin. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Renal transplantation in patients with hemolytic uremic syndrome: high rate of recurrence and increased incidence of acute rejections. Artz MA, Steenbergen EJ, Hoitsma AJ, Monnens LAH, Wetzels JFM. Transplantation 2003;76(5):821-826. ABSTRACT:. Approximately 5% to 15% of patients with hemolytic uremic syndrome (HUS) develop end-stage renal disease (ESRD). Renal transplantation is the preferred treatment for patients with ESRD although the reported outcome of transplantation in patients with HUS has varied greatly. This Dutch study of 35 patients with HUS-associated ESRD assessed the recurrence of HUS after first renal transplantation and the incidence of acute rejection. Among the 18 children studied, 28% had diarrhea-associated HUS, 33% were not associated with diarrhea, and another 39% had unknown causes although the authors thought it most likely that in these patients HUS was also diarrhea-associated. In these 18 patients, no definite recurrence of HUS developed after renal transplantation, ...
Objective: Activation of the alternative pathway of the complement system, in which factor H (fH; CFH) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. To study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance.. Research Design and Methods: Circulating fH and fB were determined by ELISA in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes and stromo-vascular cells (SVC) (n=13). The effects of weight loss and rosiglitazone were investigated in independent cohorts.. Results: Both circulating fH and fB were positively associated with BMI, waist diameter, triglycerides and inflammatory parameters; and negatively with insulin sensitivity and HDL-cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with ...
This collaborative 3-year research grant was awarded to young investigators Dr. Yongzhi Qiu and Dr. Satheesh Chonat under the mentorship of Dr. Wilbur Lam. Using a novel `microvasculature-on-a-chip technology, these Aflac researchers, along with Dr. Larry Greenbaum (Emory University), Dr. Traci Leong (Emory University) and Dr. Richard Smith (University of Iowa), will examine small blood clots are formed as a result of damage to the endothelium. The knowledge gained will advance understanding of atypical hemolytic uremic syndrome (aHUS), a rare genetic disorder that causes anemia, low platelet count and kidney damage ...
German researchers identified a novel genetic variant of the CFH gene that was associated with the development of atypical HUS, a case report shows.
The hemolytic uremic syndrome is a medical condition marked by acute renal failure, thrombocytopenia, hemolytic anemia, and platelet deficiency. It usually occurs in children with sudden gastrointestinal bleeding. Treatment: dyalisis, transfusion, steroids. Although most children recover, fatal cases occurs as a result of Rh incompatibility with mothers blood. ...
In April, I spoke at a Carter Bloodcare event in Mesquite, TX at he Resistol Arena. This was by far the biggest crowd I have ever spoken in front of. It was very emotional for me. I was able to share my story with aHUS and thank the many donors that possibly helped to save my life. This event was for the top donors in 2015. ...
Dr Simon Clark, a Medical Research Council Career Development Fellow, led the research: "FHL-1 is a smaller version of FH, in fact it is about a third of the size. However, it has all the necessary components to regulate the immune system and is still subject to the genetic alterations that affect AMD risk. Our research has shown that the FHL-1, because it is smaller than FH, can get into structures of the back of the eye which cannot be reached by the larger FH.". He continues: "Therefore, this research suggests that it is FHL-1 rather than FH which protects the back of the eye from immune attack and that insufficient FHL-1 in the back of the eye may result in inflammation that eventually results in vision loss from AMD. FHL-1, although very similar to FH in many ways, does have a totally unique tail structure at its end. This tail seems to mediate how FHL-1 binds tissue. As such, this work has identified a new target for therapeutics aimed at readdressing immune imbalance in the eye, thereby ...
The consumption of fruit is particularly effective in reducing risk for age-related macular degeneration (AMD), but new research shows, for the first time, that caffeine might also be protective.
Nye funksjonelle materialer er essensielle komponenter i fremtidens energiteknologi. Gruppe for faststoff elektrokjemi ved Kjemisk Institutt, Universitetet i Oslo, har i en årrekke ledet an i forskning på keramiske materialer som selektivt leder protoner, dvs. hydrogen uten sitt ene elektron. I en brenselcelle, hvor elektrisk energi dannes fra hydrogen-rikt brensel og luft, med vann som produkt, kan disse materialene bli sentrale. Disse keramiske materialene er bygd opp av små tettpakkede korn. I doktorgradsarbeidet "Thermodynamics and transport of protons in functional oxides" har protonenes transport over korngrensene vært en sentral del. Her ble det funnet ut at en opphopning av positive ladninger inne i korngrensen danner en barriere for protonledningsevnen. En god keramisk protonleder beholder en høy konsentrasjon av protoner opp til en relativt høy temperatur. Den termodynamiske parameteren som reflekterer dette kalles hydratiseringsentalpien. De eksperimentelle metodene for å finne ...
NORM-atlas gir tilgang til databasen i NORM for utvalgte bakteriearter og antibiotika over tid og fordelt på regioner. Verktøyet fremstiller norske resistensdata for ulike kliniske prøvematerialer, enten som andel resistente mikrober (R) eller samlet andel mikrober med resistens og intermediær følsomhet (R + I). Resistente mikrober (R) kan ikke behandles med det aktuelle antibiotikum. Mikrober som er intermediært følsomme (I) er forandret i forhold til villtypen, men kan fortsatt behandles dersom man bruker en høyere dose eller det aktuelle antibiotikum har en høy konsentrasjon på infeksjonsstedet. Andel med resistens og intermediær følsomhet (R + I) uttrykker samlet resistensutvikling ...
Looking for online definition of Complement factor b in the Medical Dictionary? Complement factor b explanation free. What is Complement factor b? Meaning of Complement factor b medical term. What does Complement factor b mean?
TY - JOUR. T1 - No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2. T2 - Age-Related Eye Disease Study 2 Report No. 18. AU - van Asten, Freekje. AU - Chiu, Chi Yang. AU - Agrón, Elvira. AU - Clemons, Traci E.. AU - Ratnapriya, Rinki. AU - Swaroop, Anand. AU - Klein, Michael. AU - Fan, Ruzong. AU - Chew, Emily Y.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned ...
14:52 - The punchline: aHUS and TTP diagnosis algorithm. Publications. Stromsness B. et al. Physician Interpretation of Equivocal Results for aHUS Genetic Testing Varies Greatly and is Frequently at Odds with Laboratory Views. J Clin Apheresis. 2019; (abstract P-82).. Ero, MP, Kain, JS, inventors; Machaon Diagnostics, Inc., assignee. 2018 Dec 18. Method of diagnosis of complement-mediated thrombotic microangiopathies. United States patent US 10,155,983.. Tao J. et al. A rare case of Alport syndrome, atypical hemolytic uremic syndrome and Pauci-immune crescentic glomerulonephritis. BMC Nephrology. 2018;19:355.. Kain J. et al. Additional Genes Associated with Atypical Hemolytic Uremic Syndrome. ASN 2018 Abstract TH-PO713. 2018; (abstract).. Switala L. et al. Complement factor abnormalities detected in patients with suspected Heparin-induced Thrombocytopenia (HIT) but not in Thrombotic Thrombocytopenia Purpura (TTP). ISLH 2017 Abstract Proceedings. 2017; (abstract).. Ipe T. et al. An extremely rare ...
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF ...
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF ...
Eculizumab is a monoclonal antibody that prevents complement activation. It has been found to be an effective treatment for atypical hemolytic-uremic syndrome (aHUS). This retrospective study is the largest collection of previously published and unpublished cases to date. Eculizumab was effective at both preventing and treating recurrence of aHUS.. ...
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adult patients with plasma therapy-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).
Mesangiocapillary glomerulonephritis type 1 information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
When mixed with normal human serum, wild-type pathogenic Yersinia enterocolitica, previously incubated at 37 degrees C, fixed less C3b than its variant cured of the virulence plasmid pYV. Mutants unable to secrete the Yop proteins were still protected against C3b deposition. By contrast, mutants deficient in the production of outer membrane protein YadA fixed more C3b than their YadA+ parent. Gene yadA, cloned as a minimal polymerase chain reaction fragment and introduced in trans, complemented the mutations. Production of YadA by recombinant Escherichia coli LK111 also resulted in a reduction of the amount of C3b deposited on the bacterial surface. The reduction of C3b at the surface of Y. enterocolitica YadA+ compared with YadA- cells correlated with an increase of the amount of factor H fixed at the bacterial surface. The YadA monomer separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane was able to bind factor H. We conclude that ...
1. HainesJL, HauserMA, SchmidtS, ScottWK, OlsonLM, et al. (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308: 419-421.. 2. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661-678.. 3. RipkeS, ODushlaineC, ChambertK, MoranJL, KählerAK, et al. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 45: 1150-1159.. 4. CARDIoGRAMplusC4D Consortium, DeloukasP, KanoniS, WillenborgC, FarrallM, et al. (2013) Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 45: 25-33.. 5. MorrisAP, VoightBF, TeslovichTM, FerreiraT, SegrèAV, et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44: 981-990.. 6. WrayGA (2007) The evolutionary significance of cis-regulatory mutations. ...
This case report represents how eculizumab reversed neurologic impairment and improved GW786034 renal damage in severe atypical hemolytic uremic syndrome. hemolytic uremic syndrome eculizumab safely reverses neurologic impairment and eliminates the need for dialysis. The optimal duration of treatment with eculizumab remains to be determined. also causes a severe form of hemolytic uremic syndrome unrelated to Shiga or Shiga-like toxin-producing organisms.8 9 A minority of hemolytic uremic syndrome cases generally unrelated to Shiga/Shiga-like toxin or mutations with cardiac complications in 20% of cases are associated with a worse long-term survival. mutations are associated with a 10-year survival rate of only 40%-50% compared with cases of anti-CFH antibodies mutations and mutations which have a 10-year survival rate of around 80%-90%. Furthermore hereditary testing supplies the clinician with prognostic and predictive information regarding the disease GW786034 program treatment response and ...
CRP seems to be not only a biomarker for atherosclerosis but also a mediator of plaque formation.3 By binding to enzymatically degraded low-density lipoprotein, CRP is able to activate the classical pathway of complement,13 serving as a potential link between complement activation and atherosclerosis.9,10 To protect against complement-mediated cell lysis, nucleated cells express complement inhibitor proteins on their surface. By upregulating the expression of these proteins in endothelial cells, CRP may serve to protect ECs from complement-mediated injury.. The ability of CRP to bind to nucleated cells and cause complement activation without cytolysis14 has been largely attributed to its ability to recruit the inhibitory plasma protein factor H.15 However, our results indicate that CRP may play a more active, protective role by stimulating the expression of DAF, CD46, and CD59 in endothelial cells. The kinetics of DAF expression were analyzed in greater detail because DAF seems to be the most ...
Activation of the complement cascade is clearly implicated in the pathology of multiple sclerosis (MS). However, the extent and nature of its involvement in specific athological processes remains uncertain. We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive MS, examining 35 different plaques, and 16 control donors, including 9 with CNS disease. Plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, TCC) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite no other evidence of on-going inflammation. Complement immunolabelling was most apparent in plaque and peri-plaque areas but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. Cellular ...
Factor H Binding protein (fHbp) is an important meningococcal virulence factor, enabling the meningococcus to evade the complement system, and a main target for vaccination. Recently, the structure of fHBP complexed with factor H (fH) was published. Two fHbp glutamic acids, E(283) and E(304), form salt bridges with fH, influencing interaction between fHbp and fH. Fifteen amino acids were identified forming hydrogen bonds with fH. We sequenced fHbp of 254 meningococcal isolates from adults with meningococcal meningitis included in a prospective clinical cohort to study the effect of fHbp variants on meningococcal disease severity and outcome. All fHbp of subfamily A had E304 substituted with T304. Of the 15 amino acids in fHbp making hydrogen bonds to fH, 3 were conserved, 11 show a similar distribution between the two fHbp subfamilies as the polymorphism at position 304. The proportion of patients infected with meningococci with fHbp of subfamily A with unfavorable outcome was 2.5-fold lower than that
en] OBJECTIVE: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. METHODS: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. RESULTS: We report an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 x 10(-11); odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations ...
AMD is strongly associated with the over-activation of complement pathways [16]. Supporting evidence comes from the detection of various complement proteins in the drusen of patients with AMD [9] and the close association between AMD and the alternative pathway. Furthermore, the association of genetic variants in complement genes, including the human factor B gene, is a risk factor for all forms of AMD [5,9,22,24]. In addition, it has been shown that polymorphisms of genes encoding the alternative pathway proteins CFH, factor B, and C3, as well as the classical pathway protein C2, are also associated with AMD [23,46]. Studies in animal models of choroidal neovascularization (CNV), a major pathologic association with wet AMD, also supports a role for complements in AMD. Furthermore, a targeted inhibitor specific for the AP of complement significantly reduces CNV and the physiologic consequences of CNV on retinal function [11,47]. Additional evidence for a role of the AP pathway in AMD exists. For ...
For thrombotic microangiopathies (TMAs), the diagnosis of atypical hemolytic uremic syndrome (aHUS) is made by ruling out Shiga toxin-producing Escherichia coli (STEC)-associated HUS and ADAMTS13 activity-deficient thrombotic thrombocytopenic purpura (TTP), often using the exclusion criteria for secondary TMAs. Nowadays, assays for ADAMTS13 activity and evaluation for STEC infection can be performed within a few hours. However, a confident diagnosis of aHUS often requires comprehensive gene analysis of the alternative complement activation pathway, which usually takes at least several weeks. However, predisposing genetic abnormalities are only identified in approximately 70% of aHUS. To facilitate the diagnosis of complement-mediated aHUS, we describe a quantitative hemolytic assay using sheep red blood cells (RBCs) and human citrated plasma, spiked with or without a novel inhibitory anti-complement factor H (CFH) monoclonal antibody. Among 45 aHUS patients in Japan, 24% (11/45) had moderate-to-severe (
This page provides relevant content and local businesses that can help with your search for information on Age-Related Macular Degeneration Treatment. You will find informative articles about Age-Related Macular Degeneration Treatment, including Age-related Macular Degeneration (AMD), the Silent Disease that Causes Loss of Sight. Below you will also find local businesses that may provide the products or services you are looking for. Please scroll down to find the local resources in Milledgeville, GA that can help answer your questions about Age-Related Macular Degeneration Treatment.
Eculizumab, a humanized anti-complement C5 monoclonal antibody for treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, blocks the terminal complement pathway required for serum bactericidal activity (SBA). Because treated patients are at ,1000-fold increased risk of meningococcal disease, vaccination is recommended, but whether vaccination can protect by opsonophagocytic activity in the absence of SBA is not known. Meningococci were added to anticoagulated blood from 12 healthy adults vaccinated with meningococcal serogroup B and serogroup A,C,W,Y vaccines. Bacterial survival was measured after 3 hours incubation in the presence of eculizumab or, a control complement factor D inhibitor, ACH-4471, that blocks the alternative complement pathway (AP) and is in phase 2 development for treatment of PNH. In the absence of inhibitors, CFU/ml in blood from all 12 immunized subjects decreased from ~4000 at time 0 to sterile cultures at 3 hours. In the presence ...
PSAP Complement component 4, partial deficiency of; 120790; C1NH Complement factor H deficiency; 609814; HF1 Complement factor ... GLA Factor V and factor VIII, combined deficiency of; 227300; MCFD2 Factor V deficiency; 227400; F5 Factor XI deficiency, ... F11 Factor XII deficiency; 234000; F12 Factor XIIIA deficiency; 613225; F13A1 Factor XIIIB deficiency; 613235; F13B Failure of ... LCAT Fletcher factor deficiency; 612423; KLKB1 Focal cortical dysplasia, Taylor balloon cell type; 607341; TSC1 Focal dermal ...
It binds to complement factor D (CFD). Enrollment in Phase 3 clinical trials was initiated in 2014. Phase 3 trials are usually ... These two failures have called into question whether complement inhibition is a sound strategy for geographic atrophy. World ...
Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... "Entrez Gene: CFHR5 complement factor H-related 5". McRae JL, Duthy TG, Griggs KM, et al. (2005). "Human factor H-related ... 2006). "Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with ... Complement factor H-related protein 5 is a protein that in humans is encoded by the CFHR5 gene. CFHR5 is structurally related ...
Díaz-Guillén MA, Rodríguez de Córdoba S, Heine-Suñer D (1999). "A radiation hybrid map of complement factor H and factor H- ... Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an expanding family of complement-regulatory proteins ... "Two additional human serum proteins structurally related to complement factor H. Evidence for a family of factor H-related ... Complement factor H-related protein 2 is a protein that in humans is encoded by the CFHR2 gene. GRCh38: Ensembl release 89: ...
"Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement". The Journal of Biological ... Nucleolin is also able to act as a transcriptional coactivator with Chicken Ovalbumin Upstream Promoter Transcription Factor II ...
These SNPs were located in the gene encoding complement factor H, which was an unexpected finding in the research of ARMD. The ... "Complement factor H variant increases the risk of age-related macular degeneration". Science. 308 (5720): 419-21. doi:10.1126/ ... "Complement factor H polymorphism in age-related macular degeneration". Science. 308 (5720): 385-9. doi:10.1126/science.1109557 ... In addition to the conceptual framework several additional factors enabled the GWA studies. One was the advent of biobanks, ...
The genes for the complement system proteins factor H (CFH), factor B (CFB) and factor 3 (C3) are strongly associated with a ... Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP (2006). "Complement factor H polymorphism, complement ... on chromosome 10 at location 10q26 Complement Factor B/Complement Component 2 (CFB/CC2) on chromosome 6 at 6p21.3 Polymorphisms ... Absence of the complement factor H-related genes R3 and R1 protects against AMD. Two independent studies in 2007 showed a ...
Malhotra R, Ward M, Sim RB, Bird MI (1999). "Identification of human complement Factor H as a ligand for L-selectin". Biochem. ... The molecule is composed of multiple domains: one homologous to lectins, one to epidermal growth factor, and two to the ... The embryo secretes human chorionic gonadotropin (hCG), which downregulates anti-adhesion factor, MUC-1, located on the uterine ...
"Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration". Science. 308 (5720): 419-21. doi:10.1126/ ... Some of the factors that should be considered are the level of efficacy of various genetic tests in the general population, ... "individual risk factors". Perhaps the most critical issue with the commercialization of personalised medicine is the protection ... there are a number of factors that must be considered. The detailed account of genetic information from the individual will ...
... factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and thrombomodulin). This results in ... The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane ... of complement can result from production of anti-factor H autoantibodies or from genetic mutations in any of several complement ... "Platelet-associated complement factor H in healthy persons and patients with atypical HUS". Blood. 114 (20): 4538-4545. doi: ...
Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... CFHR4 complement factor H-related 4". Hageman GS, Hancox LS, Taiber AJ, et al. (2007). "Extended Haplotypes in the Complement ... Complement factor H-related protein 4 is a protein that in humans is encoded by the CFHR4 gene. GRCh38: Ensembl release 89: ... 2000). "Functional properties of complement factor H-related proteins FHR-3 and FHR-4: binding to the C3d region of C3b and ...
1989). "20 KDa homologous restriction factor of complement resembles T cell activating protein". Biochem. Biophys. Res. Commun ... When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the ... Ninomiya H, Sims PJ (1992). "The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain ... 1992). "Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 ...
"Entrez Gene: CFHR3 complement factor H-related 3". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Diaz-Guillen MA, Rodriguez de Cordoba S, Heine-Suner D (Jul 1999). "A radiation hybrid map of complement factor H and factor H- ... Complement factor H-related protein 3 is a protein that in humans is encoded by the CFHR3 gene. GRCh38: Ensembl release 89: ... 2000). "Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes ...
Complement factor H-related protein 5 (CFHR5) nephropathy (also known as Troodos nephropathy) is a form of inherited kidney ... 26 August 2010). "Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with ... "Recurrence of Complement Factor H-Related Protein 5 Nephropathy in a Renal Transplant". American Journal of Transplantation. 11 ... A kidney biopsy in patients with CFHR5 nephropathy classically shows deposition of complement C3 in the kidney, without any ...
Complement factors are decreased in rheumatoid arthritis and lupus arthritis. Microscopic analysis of synovial fluid is ... Jay, GD; Britt, DE; Cha, CJ (March 2000). "Lubricin is a product of megakaryocyte stimulating factor gene expression by human ...
The process is aided by neutrophils, the complement system, tumor necrosis factor alpha, etc. Aetiologically, these are most ...
Overall this protein shows similarity to the complement 1Q factors (C1Q). However, when the 3-dimensional structure of the ... "The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor". Current ... A low level of adiponectin is an independent risk factor for developing: Metabolic syndrome Diabetes mellitus Lower levels of ... Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH (January 2009). "Hypoadiponectinemia: a risk factor for ...
Porins are also recognized by TLR2, they bind complement factors (C3b, C4b, factor H, and C4bp (complement factor 4b-binding ... Porins are also an important factor for complement inhibition for both pathogenic and commensal species. Porins are important ... Close contact with a carrier is the predominant risk factor. Other risk factors include a weakened general or local immune ... Factor H binding protein (fHbp) that is exhibited in N. meningitidis and some commensal species is the main inhibitor of the ...
"Entrez Gene: CFHR1 complement factor H-related 1". Zipfel PF, Skerka C (1994). "Complement factor H and related proteins: an ... Díaz-Guillén MA, Rodríguez de Córdoba S, Heine-Suñer D (1999). "A radiation hybrid map of complement factor H and factor H- ... related to complement factor H are different glycosylation forms of a single protein with no factor H-like complement ... Complement factor H-related protein 1 is a protein that in humans is encoded by the CFHR1 gene. GRCh38: Ensembl release 89: ...
CP is considered a virulence factor because it provides resistance against complement-mediated polymorphonuclear neutrophil ... The ability to adhere to medical devices and subsequently form biofilms is a major virulence factor associated with S. ... Biofilm formation is influenced by a variety of factors including carbohydrates, proteins, and extracellular DNA. Detachment ... 2007). "Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and ...
Complement C4-A is a protein that in humans is encoded by the C4A gene. This gene encodes the acidic form of complement factor ... "A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B". ... Hessing M, van 't Veer C, Hackeng TM, Bouma BN, Iwanaga S (Oct 1990). "Importance of the alpha 3-fragment of complement C4 for ... Hortin G, Sims H, Strauss AW (Feb 1986). "Identification of the site of sulfation of the fourth component of human complement ...
Stevenson B, El-Hage N, Hines MA, Miller JC, Babb K (2002). "Differential binding of host complement inhibitor factor H by ... as individual Erp proteins exhibited different binding patterns to the complement regulator factor H from different animals. ... "Borrelia burgdorferi binding of host complement regulator factor H is not required for efficient mammalian infection". Infect. ... Immune system suppression Complement inhibition, induction of anti-inflammatory cytokines such as IL-10, and the formation of ...
Opsonins include Mfge8, Gas6, Protein S, antibodies and complement factors C1q and C3b. Phagoptosis has multiple functions ... Pathogenic cells such as bacteria can be opsonised by antibodies or complement factors, enabling their phagocytosis and ...
Lee FJ, Moss J, Vaughan M (1992). "Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces ... ADP-ribosylation factor 5 is a protein that in humans is encoded by the ARF5 gene. ADP-ribosylation factor 5 (ARF5) is a member ... Shin, O H; Exton J H (August 2001). "Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1". Biochem. ... "Entrez Gene: ARF5 ADP-ribosylation factor 5". Kanoh, H; Williger B T; Exton J H (February 1997). "Arfaptin 1, a putative ...
Lee FJ, Moss J, Vaughan M (1992). "Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces ... ADP-ribosylation factor 4 is a protein that in humans is encoded by the ARF4 gene. ADP-ribosylation factor 4 (ARF4) is a member ... "ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation". J. ... "ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation". J. ...
Lee FJ, Moss J, Vaughan M (1992). "Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces ... ADP-ribosylation factor 3 is a protein that in humans is encoded by the ARF3 gene. ADP-ribosylation factor 3 (ARF3) is a member ... Williger BT, Provost JJ, Ho WT, Milstine J, Exton JH (July 1999). "Arfaptin 1 forms a complex with ADP-ribosylation factor and ... Lee CM, Haun RS, Tsai SC, Moss J, Vaughan M (1992). "Characterization of the human gene encoding ADP-ribosylation factor 1, a ...
This is a type of safeguard to the system, almost like a two-factor authentication method. First, the B cells have to encounter ... Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1 and IRF4. ... Immunology: lymphocytic adaptive immune system and complement. Lymphoid. Antigens. *Antigen *Superantigen. *Allergen ...
"Evid Based Complement Alternat Med. 7 (1): 11-28. doi:10.1093/ecam/nen023. PMC 2816378. PMID 18955327.. ... Multiple factors such as gender, age, ethnicity, education and social class are also shown to have association with prevalence ... "Who Uses CAM? A Narrative Review of Demographic Characteristics and Health Factors Associated with CAM Use" ...
CFHR5 complement factor H related 5 [Homo sapiens] CFHR5 complement factor H related 5 [Homo sapiens]. Gene ID:81494 ... complement factor H-related protein 5. Names. factor H-related protein 5. ... Studies indicate that complement factor H-related proteins (FHR1-5) may enhance complement activation, with important ... Title: Complement factor H-related hybrid protein deregulates complement in dense deposit disease. ...
Complement Factor I Antibody (Internal), Rabbit Anti Human Polyclonal Antibody validated in WB, IHC-P (ALS17749), Abgent ... Complement component factor i, Factor I, FI, KAF, I factor, I factor (complement), C3b-INA, Complement factor I, Light chain of ... Anti-CFI / Complement Factor I Antibody (Internal) is for research use only and not for use in diagnostic or therapeutic ... home , Products , Primary Antibodies , Antibody Collections , GPCR Antibodies , Anti-CFI / Complement Factor I Antibody ( ...
Complement Factor I, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene ... CFI (Complement Factor I) is a Protein Coding gene. Diseases associated with CFI include Complement Factor I Deficiency and ... Pathogenic, Complement factor I deficiency (CFI deficiency) [MIM:610984]. 109,746,398(-). TTTCC(A/T)TGAAA. reference, missense ... Pathogenic, Complement factor I deficiency (CFI deficiency) [MIM:610984]. 109,760,567(-). TGATG(A/G)TATCA. reference, missense ...
Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation ... Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation ... One of the strongest susceptibility genes for age-related macular degeneration (AMD) is complement factor H (CFH); however, its ... but not complement activation, which correlated with the AMD-like phenotype in old CFH-H/H mice. Specifically, apolipoproteins ...
... complement factor I) for ELISA, IP, RIA, WB. Anti-Factor I mAb (GTX41626) is tested in Human samples. 100% Ab-Assurance. ... complement factor I. Background. This gene encodes a serine proteinase that is essential for regulating the complement cascade ... Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to ... AHUS3 Antibody , C3BINA Antibody , IF Antibody , KAF Antibody , FI Antibody , complement factor I Antibody , C3b-INA Antibody ...
Complement factor H (CFH) is a negative regulator of the alternative pathway of complement, and properdin is the sole positive ... Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic ... Factor H (fH) and properdin both modulate complement; however, fH inhibits activation, and properdin promotes activation of the ... Complement factor H deficiency (CFHD) can manifest as several different phenotypes, including asymptomatic, recurrent bacterial ...
Definition of Cobra venom factor with photos and pictures, translations, sample usage, and additional links for more ... susceptible to factor D of the properdin system, leading to activation of C3 and other components of complement and lysis of ... Medical Definition of Cobra venom factor. 1. A component of cobra venom that renders C3 proactivator (properdin factor B) ... Cobra Venom Factor Images Lexicographical Neighbors of Cobra Venom Factor. coboose. cobooses. cobordant. cobordism. cobordisms ...
... Jean Charchaflieh,1 Julie Rushbrook,2 Samrat Worah,2 and Ming Zhang ...
Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin. in plasma, ... complement factor I". Goldberger G, Bruns GA, Rits M, Edge MD, Kwiatkowski DJ (Jul 1987). "Human complement factor I: analysis ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... Leitão MF, Vilela MM, Rutz R, Grumach AS, Condino-Neto A, Kirschfink M (Dec 1997). "Complement factor I deficiency in a family ...
Complement factor B is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ... CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). "The Ba fragment of complement factor B ... Christie DL, Gagnon J (January 1983). "Amino acid sequence of the Bb fragment from complement Factor B. Sequence of the major ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the ... C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway. UniProt ...
Schulz, T. F.; Schwaeble, W.; Stanley, K. K.; Weiss, Elisabeth H.; Dierich, Manfred P. (1986): Human complement factor H. ... kDa fragment of human complement control protein factor H using polyclonal and monoclonal antibodies to screen a human liver ...
Factor H-like 1 (FHL-1) is a splice variant of FH that also possesses complement-inhibiting function. Additional five factor H- ... In addition to its canonical role in complement regulation, several other functions of FH have been discovered and a large ... While other fluid-phase and cell membrane-bound regulators of complement have been identified, FH is essential for controlling ... Moreover, numerous pathogenic microbes and some tumor cells have developed the ability to exploit FH for complement evasion. ...
Buy our Recombinant Human Complement factor B protein (denatured). Ab174401 is a protein fragment produced in Escherichia coli ... Recombinant Human Complement factor B protein (denatured). See all Complement factor B proteins and peptides. ... Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb ... a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in ...
Complement factor H gene associations with end-stage kidney disease in African Americans.. Bonomo JA1, Palmer ND2, Hicks PJ3, ... Mutations in the complement factor H gene (CFH) region associate with renal-limited mesangial proliferative forms of ...
Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. R D Horstmann, H ... Isolated complement components were used to study the regulation of the alternative complement pathway C3 convertase (EC 3.4. ... Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H ... Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H ...
Staphylococcus aureusClumping Factor A Binds to Complement Regulator Factor I and Increases Factor I Cleavage of C3b ... Myeloperoxidase influences the complement regulatory activity of complement factor H. Su-Fang Chen, Feng-Mei Wang, Zhi-Ying Li ... Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida ... Acquisition of Complement Inhibitor Serine Protease Factor I and Its Cofactors C4b-Binding Protein and Factor H by Prevotella ...
Browse our Complement Factor H Antibodies all backed by our Guarantee+. ... Complement Factor H Antibodies available through Novus Biologicals. ... anti-H factor 1 (complement) antibody, anti-H factor 1 antibody, anti-H factor 2 (complement) antibody, anti-HF antibody, anti- ... Complement Factor H Antibodies. We offer Complement Factor H Antibodies for use in common research applications: ELISA, Flow ...
J:277202 Song D, et al., Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice. Am J ...
CRP-Induced Expression of Complement- Inhibitory Factors Protects HSVECs From Complement-Mediated Injury. To assess whether the ... 13 The effect of CRP on the expression of complement-inhibitory factors is unknown. Because complement-inhibitory proteins ... C-Reactive Protein Upregulates Complement-Inhibitory Factors in Endothelial Cells. Shu-Hong Li, Paul E. Szmitko, Richard D. ... C-Reactive Protein Upregulates Complement-Inhibitory Factors in Endothelial Cells. Shu-Hong Li, Paul E. Szmitko, Richard D. ...
Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 ... "Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D ... "Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D ... "Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D ...
... factor VIII deficiency (ortholog); FOUND IN extracellular space (inferred); secretory granule (inferred) ... INVOLVED IN complement activation, alternative pathway (inferred); ASSOCIATED WITH autistic disorder (ortholog); Experimental ... Homo sapiens (human) : CFP (complement factor properdin) HGNC Alliance Mus musculus (house mouse) : Cfp (complement factor ... Sus scrofa (pig) : CFP (complement factor properdin) Chlorocebus sabaeus (African green monkey) : CFP (complement factor ...
Since there is complement activation in all areas of tissue injury, and both C3a and C5a activate MSC, it was asked whether ... The signaling cascade responsible for the production of angiogenic factors by C3a or C5a could be defined as activation of the ... C3a caused significant up-regulation of various angiogenic factors, including VEGF, CXCL8/IL-8 and IL-6. In contrast there was ... Although C5a also caused moderate up-regulation of angiogenic factors, the effect was borderline significant. Furthermore the ...
Complement Factor H Polymorphism in Age-Related Macular Degeneration. By Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen- ... Complement Factor H Polymorphism in Age-Related Macular Degeneration. By Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen- ... Complement Factor H Polymorphism in Age-Related Macular Degeneration Message Subject. (Your Name) has forwarded a page to you ... Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) ...
Both age and smoking, two important risk factors for AMD, influence plasma levels of complement factor H (28). CFH sequences ... Complement Factor H Polymorphism in Age-Related Macular Degeneration. By Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen- ... Complement Factor H Polymorphism in Age-Related Macular Degeneration. By Robert J. Klein, Caroline Zeiss, Emily Y. Chew, Jen- ... Complement Factor H Polymorphism in Age-Related Macular Degeneration Message Subject. (Your Name) has forwarded a page to you ...
  • INDICATION: Stroke Patient sample and mouse studies suggest a factor H-CR2 conjugate that inhibits C3d deposition could help treat stroke. (biocentury.com)
  • The hydrolyzed form of C3 (C3(H 2 O)) has the potential to bind factor B, which, after cleavage to Bb by factor D, will cleave both C3 and C5. (jimmunol.org)
  • Factor H is released or modified following this cleavage. (acris-antibodies.com)
  • In vitro , complement C3 and its cleavage product C3b enhanced FVIII endocytosis by dendritic cells and presentation to a FVIII-specific CD4 + T-cell hybridoma. (haematologica.org)
  • In addition, the cleavage of deleted (C3delta727-768) iC3 to iC3b-a by factor I in the presence of CR1 was significantly reduced, whereas it remained unaltered in the presence of MCP. (nih.gov)
  • Cleavage of iC3 to iC3b-a by factor I and H was similar in all expressed C3s except C3delta727-768, whose cleavage was significantly reduced. (nih.gov)
  • These results suggest that during cleavage of iC3 by factor I and CR1, or H, CR1 and H bind to at least two sites on C3 and that the MCP binding site(s) on C3b are different from those for CR1. (nih.gov)
  • Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (rupress.org)
  • According to Apellis, complement inhibition is "the only mechanism thus far to show reductions in the growth of dry AMD", adding that "APL-2 has the same mechanism of action as Potentia's original drug compound but has a significantly improved half-life in the eye. (euretina.org)
  • We have learned much about complement since our first venture in this area a decade ago, and have great hopes that complement inhibition will be the first effective treatment for patients with dry AMD. (euretina.org)
  • In additional commentary following announcement of the acquisition, Dr. Phil Rosenfeld, MD, a physician at Bascom Palmer and an advisor to Apellis, stated: "There's overwhelming scientific and clinical evidence to suggest that complement inhibition should slow the progression of dry AMD. (euretina.org)
  • Conventional protease inhibitors do not completely inactivate Factor I but they can do so if the enzyme is pre-incubated with its substrate: this supports the proposed rearrangement of the molecule upon binding to the substrate. (wikipedia.org)
  • AP inhibitors not only prevent, but have the potential to accelerate the clearance of complement-mediated ocular injury. (antikoerper-online.de)
  • It is an exceptionally specific protease and the only known protein substrate is factor B in complex with C3.3 Factor D protease activity is regulated by reversible conformational changes, which differs from the majority of serine proteases whose regulation involves either activation by processing of the zymogens or inactivation by binding of the inhibitors. (rndsystems.com)
  • 2009) Structure-activity relationships for substrate-based inhibitors of human complement factor B. (guidetoimmunopharmacology.org)
  • However, the partnership with Alcon, which had received exclusive worldwide rights, ended in 2013, following which the company struck an agreement with Apellis to develop complement inhibitors for ocular diseases. (euretina.org)
  • Previously, we reported that a monoclonal λ-chain dimer isolated from the urine of a patient LOI with MPGN activated the AP in a manner different from C3 nephritic factors ( 21 ). (jimmunol.org)
  • the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, CR1, MCP or C4BP). (wikipedia.org)
  • Factor H (H) is a crucial fluid phase regulator of the AP, as it is an essential cofactor for factor I (C3b inactivator) in the proteolytic inactivation of C3b and C3(H 2 O) ( 6 , 7 ). (jimmunol.org)
  • The action of six different enzymes on the function and structure of Factor H was investigated by use of sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, haemagglutination, two enzyme-linked immunosorbent assay systems and an assay for Factor I cofactor activity. (semanticscholar.org)
  • Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. (jci.org)
  • In this review we discuss current concepts on the physiological and pathophysiological roles of factor H in light of new data and recent developments in our understanding of the versatile roles of factor H as an inhibitor of complement activation and inflammation, as well as a mediator of cellular interactions. (mdpi.com)
  • To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells. (biologists.org)
  • In the present study, we examined the role of complement factor 3 (C3) in the development of PM-induced AHR and airway inflammation by comparing responses between C3-deficient (C3 -/- ) and wild-type mice. (elsevier.com)
  • a circulating inhibitor of complement activation) provides evidence that inflammation in general, and complement in particular, maybe causally involved in AMD. (ucl.ac.uk)
  • Since AMD and atherosclerosis share similar pathological features and risk factors, including a link with inflammation, an important question arises: is complement factor H (fH) a shared risk factor for both AMD and CHD? (ucl.ac.uk)
  • Adverse outcomes after cardiopulmonary bypass (CPB) are often related to systemic inflammation triggered by complement and leukocyte activation. (elsevier.com)
  • Prolonged phagocytosis of POS, particularly if modified by oxidative processes as occurs in inflammation, appears to markedly impair synthesis and secretion of CFH, with potential loss of important regulatory functions in counteracting the pro-inflammatory effects of activated complement. (elsevier.com)
  • We have begun to address whether these responses reflect the same sets of conformational changes in the receptor using constitutively active mutants of the human complement factor 5a receptor (C5aR). (elsevier.com)
  • Basal and Toll-like receptor (TLR) inducible expression of mRNAs encoding the complement subcomponents C1qa, C1qb and C1qc was greatly reduced in bone marrow-derived macrophages (BMM) from ARRB2-deficient, but not ARRB1-deficient mice, while factor-independent survival of ARRB2(-/-) BMM was enhanced compared to wildtype BMM. (edu.au)
  • Here we investigated the effect of liver factor B reduction on systemic and ocular factor B levels. (molvis.org)
  • In addition to its canonical role in complement regulation, several other functions of FH have been discovered and a large number of binding partners have been identified. (frontiersin.org)
  • The species-specific pattern of viability and/or lysis is highly consistent with the pattern of reservoir competence of hosts for B. burgdorferi sensu lato, suggesting a key role of complement in the global ecology of Lyme borreliosis. (asm.org)
  • Despite its important role in innate immunity, very little is known about complement production, regulation, and function in the CNS of healthy or diseased individuals. (uiowa.edu)
  • This disease model is useful for conditions in which complement factor H plays a role. (imperialinnovations.co.uk)