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Decay-accelerating factor and membrane cofactor protein.
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Acute-phase-proteins and parameters of humoral immunity in patients with advanced Hodgkin's disease.
Serum concentrations of acute-phase-proteins C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha 1-acid glycoprotein (AGP) as well as levels of immunoglobulins G, A and M and of complement components C3 and C4 were evaluated in 15 patients with advanced (stages III and IV) Hodgkin's disease. Of these patients 9 suffered from B symptoms including pruritus, night sweats and fever. While all patients had highly increased concentrations of CRP and AAT and 11 patients also had elevated levels of AGP in their sera, these concentrations were significantly (P less than 0.001) reducible by the administration of chemotherapy. Patients with B symptoms also had significantly higher concentrations of CRP (P less than 0.02), AAT (P less than 0.05) and AGP (P less than 0.05) in their sera than patients without. Plasmapheresis which was performed in 3 patients did not achieve a long-lasting reduction of serum concentrations of any acute-phase-protein tested. Complement components C3 and C4 exhibited a similar behaviour as acute-phase-proteins in that they were elevated in patients with B symptoms and reducible by the administration of chemotherapy (P less than 0.001 and P less than 0.02, respectively). We conclude that serum concentrations of CRP, AAT and AGP can serve as useful markers for the assessment of tumour activity in patients with advanced Hodgkin's disease. Whereas the concentrations of immunoglobulins G and A in patients were comparable to normal controls, IgM was significantly (P less than 0.05) reduced in patients who had received chemotherapy, but not in those who were newly diagnosed and had not received any treatment. Thus, chemotherapy lowered serum concentrations of IgM without influencing levels of IgG and IgA.
Complement-dependent hemodynamic and hematologic changes in the rabbit.
The intravenous injection of the anticomplementary protein from cobra venom, cobra factor (CoF),2 induces decreases in mean arterial blood pressure and circulating platelets in rabbits. The changes are rapidly reversed. Both changes require the presence of C3 and occur in rabbits genetically deficient in the sixth component of complement. The hypotensive effects of CoF were blocked by the histamine H2-receptor antagonist burimamide. An acute C3-dependent change in blood pressure and circulating platelets also was demonstrated following the intravenous injection of S. marcescens endotoxin. However, abrogation of these acute changes by C3 depletion did not alter the extent of a second, prolonged fall in blood pressure and platelets induced by S. marcescens endotoxin occurring after 60--90 min. C3 depletion also did not alter the lethal effects of the S. marcescens endotoxin.
Hydroxyproline fractions in serum and urine of rats during wound healing.
Total hydroxyproline in urine and free hydroxyproline, free and peptide hydroxyproline and protein bound hydroxyproline in serum are measured during wound healing in rats. The free and free+peptide fractions vary in concert with each other and with urine hydroxyproline. Protein bound hydroxyproline fractions take a very different course and behave as an acute phase reactant. The results suggest that protein bound hydroxyproline does not mirror collagen turnover but may be more relevant to C1q or complement metabolism.
Iron-binding proteins and free iron in synovial fluids of rheumatoid arthritis patients.
Iron-binding proteins (lactoferrin, transferrin and ferritin) and free iron were measured in synovial fluid (SF) from 30 patients with rheumatoid arthritis (RA) and 20 osteoarthritis (OA) patients. The iron-binding proteins except transferrin were significantly increased in RA SF as compared with OA SF. Similarly, free iron was also significantly higher in RA SF than in OA SF, whereas the ferritin saturation index, transferrin saturation index and bound iron were more significantly decreased in RA SF than in OA SF. These results suggest that RA SF contains sufficient micromolar amounts of free iron to allow hydroxyl radical formation. Also the capacity of iron-binding proteins to bind free iron is inadequate in the presence of a large amount of iron-binding proteins which are present in RA SF.
Genetic aspects of diseases of complement: an explosion.
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Complement inhibitor(s) released from leukocytes. II. Evidence that lymphocytes release and produce an inhibitor of C2 activation.
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Schistosoma mansoni: complement-mediated cytotoxic activity in vitro and effect of decomplementation on acquired immunity in mice.
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A simplified procedure for the purification of C1-inactivator from human plasma. Interaction with complement subcomponents C1r and C1s.
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Difference in antigenic reactivity and ultrastructure between fluid-phase C5b-9 and the C5b-9 membrane attack complex of human complement.
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Protein S binding in relation to the subunit composition of human C4b-binding protein.
The human regulatory complement component C4b-binding protein (C4BP) circulates in plasma either as a free protein or in a bimolecular complex with the vitamin K-dependent protein S. The major form of C4BP is composed of 7 identical, disulfide-linked 70 kDa subunits (alpha-chains), the arrangement of which gives the C4BP molecule a spider-like appearance. Recently, we identified a unique 45 kDa subunit (beta-chain) in C4BP. We have now isolated a subpopulation of C4BP, which does not bind protein S. This C4BP species, which had a molecular weight slightly lower than that of the predominant form, was found to lack the beta-chain. Another lower molecular weight form of C4BP was also purified. It contained the beta-chain and was efficient in binding protein S. Its subunit composition was judged to comprise six alpha-chains and one beta-chain. These results indicate C4BP in plasma to be heterogeneous at a molecular level vis-a-vis subunit composition and/or protein S binding ability and provide support for the concept that the beta-chain of C4BP contains the single protein S binding site.
Purification, characterization and analysis of the mechanism of action of four anti-complementary factors in Crotalus atrox venom.
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Preliminary characterization of anticomplementary components of hydatid cyst fluid.
Sheep hydatid cyst fluid (SHCF) was fractionated on Sephacryl HR S-200 and the anticomplementary activity (alpha-C activity) determined in the fractions obtained; 67% of total alpha-C activity of SHCF was recovered in the void volume fraction (SHCF-I) which contained 61% of SHCF carbohydrates. The bulk of the activity of SHCF-I was eluted by FPLC chromatofocusing on Mono P HR at pH 5.9. After heating at 100 degrees C for 15 min, SHCF and SHCF-I conserved 74 and 54%, respectively of their alpha-C activity. In addition, 37 and 11% of SHCF and SHCF-I alpha-C activity, respectively bound to Protein A. Components not bound to Protein A (SHCFPA and SHCF-IPA) were fractionated on Con A-Sepharose; 71 and 65%, respectively of their total alpha-C activity was retained by this lectin indicating the presence of alpha-D mannoside and alpha-D glucoside residues in the active molecules. Our results suggest that SHCF could contain two classes of alpha-C components: immune complexes and thermoresistant molecules with high carbohydrate content.
Immunoglobulins and complement components in human aortic atherosclerotic intima.
Concentration and preferential retention of immunoglobulins and complement components were studied in comparison with other plasma proteins in 42 human aortae with atherosclerosis. Saline and acid extracted IgG, IgA, IgM, C1q, C3c, C4, C9, C3A, C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, albumin, transferrin and fibrinogen were quantitatively determined using the radial immunodiffusion. The fibrous plaques and their adjacent areas contained higher levels of each protein than intima with only fatty streaks. No significant differences were found between the fibrous plaques and their adjacent areas presenting intimal thickenings. Saline eluted IgG and IgA were significantly higher in the fibrous plaque intima than in intimal samples with fatty streaks and were the only proteins detected in the acid eluates. The complement components were present in all saline eluates, while C-reactive protein was found in 23 samples. Crossed immunoelectrophoretic studies showed the activation of saline C3 and C4. In 8 cases serum levels of the studied proteins were compared with their concentration in saline eluates obtained from intima and media. The immunoglobulins and complement components presented higher intima/serum and lower media/intima retention ratios than the other studied proteins suggesting their preferential retention in the intima. The presence of immune related proteins in the atherosclerotic intima and their preferential retention might be explained not only by an altered permeability but also in relation to their function.
Detection of C3bBb-stabilizing activity (C3 nephritic factor) in the serum from patients with membranoproliferative glomerulonephritis.
It is known that membranoproliferative glomerulonephritis (MPGN), hypocomplementaemia and C3 nephritic factor (C3NeF) are closely related to each other, and the presence or absence of C3NeF in the serum is important for evaluating the nature of MPGN. However, some difficulties have been encountered in detecting this factor and therefore a new assay permitting the direct detection of C3NeF without purifying IgG from the patient's serum has been devised. Using this assay method, C3bBb-stabilizing activity was observed even in sera from MPGN patients who were non-hypocomplementaemic. Furthermore, among 98 cases with hypocomplementaemia. C3NeF was found to be absent in 66 cases.
Evaluation of the possible role of serum factors in the clearance of endotoxin from blood.
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Complement abnormalities in polymyositis.
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