Decay-accelerating factor and membrane cofactor protein.
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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.
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.
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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.
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.
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Serum from patients with membranoproliferative glomerulonephritis (MPGN) and acute poststreptococcal glomerulonephritis (APSGN) accelerated the decay of the cell bound C4b2a (C42) and C4b hemolytic activity relative to pooled normal human serum (pNHS) after 5 min incubation at 30 degrees C in EDTA-GVB. The accelerated decay of the C42 hemolytic activity was heat stable (56 degrees C 30 min) and was inhibited by monoclonal antibody against human C4 binding protein (MoAb:C4BP) or C4 binding protein (C4BP) depleted serum. C4 nephritic factor (C4NeF) was employed to stabilize the labile classical pathway C3 convertase C42 complex. Serum from patients with MPGN and APSGN reduced the C4NeF stabilizing activity. Sera from 32 of 46 patients with MPGN and all of 7 patients with APSGN reduced the C42 hemolytic activity relative to 50 normal human serum (NHS) after 5 min incubation at 30 degrees C in EDTA-GVB, and there was no relationship with the serum concentration of C4BP. In vivo, accelerated decay of C42 convertase might interfere with the clearing and processing mechanism of circulating immune complexes (IC) by reducing deposition of C3b on the IC lattice.
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Daily therapy and alternate-day therapy with the attenuated androgen oxymetholone were compared in patients with hereditary angioedema (HAE). Fifteen of 16 patients who experienced at least monthly attacks of HAE without treatment were asymptomatic on administration of 5 mg oxymetholene daily. When 13 of the patients who had been maintained asymptomatically on 5 mg oxymetholone daily were advanced to a treatment schedule of 5 mg every other day, seven attacks occurred during a cummulative 50 mo of therapy. The adverse effects that occurred with daily oxymetholone therapy largely subsided when the patients received alternate-day therapy, while a significant mean rise in C4 protein and function occurred only on daily therapy. Statistically significant mean increases in serum levels of C1INH occurred with daily therapy and were maintained with alternate-day therapy. Clinical benefit can be obtained with a treatment program that does not produce a statistically significant rise in C4 protein or function and does not raise C1INH to the lower limit of normal. The finding that alternate-day therapy diminished the side effects of the drug while affording a substantial reduction in the incidence and severity of attacks indicates the feasibility of this therapeutic approach.