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Mesangial IgA glomerulonephritis. Clinicopathological study of 85 cases.

A clinicopathological study was made on 85 cases of mesangial IgA glomerulonephritis and of 49 controls. Predominant incidence of male over female was noted in IgA glomerulonephritis. The disease developed insidiously in a considerable number, and occupied 68% of chance proteinuria and/or hematuria. Macrohematuria was often experienced, but in a statistical comparison with controls, no specific features were observed clinically except that hypertensive cases were rarely encountered in this disease, which may reflect the better prognosis. Serum IgA levels were not different significantly in two groups. Histological changes were those of various natures and intensities, and no specific type of lesions were observed. The negative staining of C1q and C3PA in glomeruli of IgA glomerulonephritis offered no possibility to elucidate either of the complement pathways as active.

Adolescent↗

Circulating immune complexes containing anti-VIII antibodies in multi-transfused patients with haemophilia A.

Evidence for the presence of circulating immune complexes was found in thirty-four out of fifty-five samples from forty-seven patients with haemophilia A. In eleven patients the complexes, precipitated from the blood with polyethylene glycol, were digested with pepsin. The F(ab')2 antibody was tested, and found to have neutralizing activity against coagulant Factor VIII in two patients. In one of these no free antibody had ever been found in the plasma, while in the other the antibody was concentrated tenfold in the complex. In two other samples free without complexed antibody was found. In comparison, IgG-containing complexes were found in nine out of nineteen patients with von Willebrand's disease and no complexes were found in the sera from twelve multi-transfused thalassaemics. PEG precipitation is a useful technique for the preparation of concentrated immune complexes for further study such as antigen identification.

Adolescent↗

Killing of the S and Re forms of Salmonella minnesota via the classical pathway of complement activation in guinea-pig and human sera.

The S (wildtype) and Re form (heptose-deficient, core-defective mutant) of Salmonella minnesota were killed by treatment with normal guinea-pig serum (GPS). Using C4-deficient GPS and serum containing 0.02 M ethyleneglycol-bis-(beta-aminoethylether)-tetraacetic acid and 0.02 M MgCl2 (EGTA-Mg2+) a reduced killing rate was observed. In normal GPS diluted 1:10 containing 0.02 M EGTA-Mg2+ or in C4-deficient GPS diluted 1:10 no killing occurred, whereas the same serum dilution without EGTA-Mg2+ showed a strong bactericidal effect indicating a dependency upon C4 and Ca2+ ions. Furthermore, in contrast to normal human serum (NHS) no killing occurred in a selective complete C1q-deficient human serum. The bactericidal effect, however, could be restored by addition of highly purified C1q; this is a further indication for a dependency upon the classical pathway of C activation. The C-dependent bactericidal activity was totally abolished when phosphate buffer was used, partially reduced in the presence of veronal-buffered saline (VBS), and not affected by tris-(hydroxymethyl)-aminomethane(Tris) or thioglycollate-buffered system EGTA-Mg2+ alone slightly reduced the growth rate of the bacteria whereas disodium ethylene diaminetetraacetate (EDTA) had a bacteriostatic effect on the S-form. The inhibition of the growth of the Re-form by EDTA was amplified by the addition of serum. Pre-incubation of bacteria with serum for absorption of antibodies did not increase the killing rate of such pre-treated bacteria excluding an antibody-mediated bactericidal reaction. Furthermore, pre-treatment of the bacteria with GPS at 0 degrees reduced the serum sensitivity of both types of bacteria.

Animals↗

Partial properdin deficiency.

The action of properdin in supporting complement consumption has been investigated in the serum from two individuals with partial properdin deficiency. Our studies are in agreement with those in which serum were artificially depleted of properdin in showing that serum deficient in properdin results in less C3 consumption in the presence of activators of both the alternative and classical complement pathways. Properdin deficiency did not lessen C3 consumption by C3NeF or CoF, confirming that properdin is not necessary for the action of these substances. Our findings indicate that partial properdin deficiency is innocuous but that complete absence of properdin may severely limit one's ability amplify complement activation.

Animals↗

[Complement. Evaluation of some complement fractions in patients affected by neoplasia undergoing chemotherapy (author's transl)].

Serum complement levels (UE50, C3, C4, act. C3, C1q) were determined in 75 healthy subjects and 130 cancer patients undergoing treatment. The results were correlated with statistical analysis. The patients were divided into the following groups: a) with local tumor; b) with tumor in complete remission; c) with tumor in incomplete remission; d) stationary. Three blood samples were obtained over a period of about two months. All cancer patients had decreased UE50 levels and increased act. C3 levels compared to normal values, while C3, C4, and C1q were normal. C4 levels were not significant in any group of cancer patients, but act. C3 levels were significantly increased (as compared to those of the healthy subjects). UE50 levels appeared significantly decreased only in the group with complete remission, C3 levels were increased in incomplete remission patients and were variable in stationary patients. C1q values were always increased except in the complete remission group. The variability of complement levels was dependent on the stage of the disease and on the therapy: our results provide considerable support for this hypothesis. We found that complement activity was triggered through classic or alternative means caused by antigen-antibody complexes or inflammatory processes, according to the increase or decrease of the tumor mass.

Adult↗

Immunologic function in patients with carcinoma of the pancreas.

The immune fuction of 41 patients with duct cell adenocarcinoma of the pancreas or carcinoma of the periampullary region was studied by skin testing with 2,4-dinitrocholorobenzene and common microbial antigens, in vitro lymphocyte reactivity to mitogens, T-lymphocyte and B-lymphocyte cell counts and measurements of complement levels. Results show that a great proportion of patients had depressed immune function. Depression is particularly severe in lymphocyte reactivity. Positive response to skin tests with a microbial antigen carries a slightly better prognosis. The complement level is usually normal or elevated. Correlation between immune function, prognosis and tumor resectability in individual patients is generally poor.

Adenocarcinoma↗

A search for circulating immune complex-like material during the course of autoimmune complex glomerulonephritis in Lewis and Brown Norway rats.

Circulating immune complexes were repeatedly searched for using the C1q-binding assay and the Raji cell test in Lewis and BN rats immunized with the Fx1A fraction from convoluted proximal tubule or with kidney homogenate, mixed with various adjuvants. An autoimmune glomerulonephritis was easily induced in Lewis rats. A potent adjuvant and a booster injection were necessary to obtain such a glomerulonephritis in the BN strain which is reputedly resistant. No circulating immune complex-like material could be found in Lewis rats using the C1q-binding assay. A high C1q-binding activity was found in Bn rats including control rats. The Raji cell test was weakly positive in Lewis and BN rats including control rats. This study demonstrates that the classical resistance of BN rats can be overcome if a potent adjuvant is used. Our failure to demonstrate circulating immune complexes suggests that in situ formation of immune deposits, as recently demonstrated in passive Heymann's nephritis, may also be operative in autoimmune complex glomerulonephritis. Other factors than the antigen used can be responsible for positive C1q-binding or Raji cell tests.

Animals↗

[Determination of the alternative complement pathway in patients with amebic liver abscess].

The activation of the alternative pathway of complement in the sera of patients with amebic liver abscess was studied. Of 11 sera examined, only six showed an activation of the alternative pathway. However, all sera showed diminished levels of complement (CH50) and C3, in spite of normal levels of C1q. The results suggest that the sera of patients with invasive amebiasis have a substance capable of activating the properdin pathway. The significance of these observations is not completely clear at the present time.

Complement Activation↗

Immune complexes and antibodies to BCG in sera from patients with mycobacterial infections.

We have examined the prevalence of circulating immune complexes in sera from patients with mycobacterial infections. Sera from 68 percent of patients with active M. tuberculosis and 58 percent of patients with M. intracellulare infections had significantly elevated Clq binding activity (Clq-BA). In general there was a fall in Clq-BA with treatment. Only 15 percent of M. tuberculosis patient with a bacteriological cure, 22 percent of non-tubercular patients with chronic obstructive pulmonary disease, and 3 percent of normal individuals had an elevated Clq-BA. Antibodies to a BCG-derived antigen were demonstrated in most of the individuals studied in all groups but, significantly elevated levels were seen only in patients with mycobacterial infections. In certain patients there appeared to be an inverse relationship between Clq-BA and BCG binding, suggesting that perhaps BCG-related antigens participated in the immune complexes found. Other possible antigen-antibody complexes are discussed.

Adolescent↗

The detection of circulating immune complexes in renal transplant patients.

The Raji cell assay and radiolabelled Clq binding method were used to detect circulating immune complexes in the sera of renal transplant patients. Complexes were found in seven of twelve patients using the Raji cell assay; only one serum sample was positive by the Clq method. In five patients the complexes were detected prior to the clinical diagnosis of rejection and in those in whom treatment reversed the rejection the complexes rapidly disappeared. The presence of complexes correlated with a vascular type of rejection characterised by fibrin deposits in the glomeruli in the absence of immunoglobulin or C3 deposits. In two patients, in whom anti red cell antibodies were present, irreversible rejection occurred without the presence of detectable complexes in the sera.

Adult↗

Immunological studies of human placentae: complement components in immature and mature chorionic villi.

The localization and distribution of complement components in term and pre-term normal human placentae have been studied by using haemadsorption and immunofluorescence experiments. The components Clq, C4, C5, C6 and C9 were identified in characteristic locations. Receptors for C3 and C4 were not found. Complement was associated with certain stromal cells, areas of fibrinoid necrosis within the trophoblastic mantle, and in the walls and endothelia of foetal stem vessels. Activation of the complement system on trophoblastic basement membranes (TBM) did not appear to involve the early reacting components of the classical pathway of complement activation, because C1q, C4 and C2 could not be identified on TBM. The C6 component was identified within cytoplasmic granules of foetal stem vessel endothelia, suggesting that it may be synthesized by these cells. These findings put forward the possibility that complement may play an immunobiological role in the materno-foetal relationship during normal human pregnancy.

Basement Membrane↗

Comparison of three assays for anti-DNA with three assays for the measurement of the role of complement in systemic lupus erythematosus in adolescents.

Three assays for anti-DNA antibody were compared simultaneously with assays for Clq binding, C3 concentration, and the activation of C3 (C3c,d) on blood of children with systemic lupus erythematosus. The Farr assay and the Millipore filter assay for anti-DNA were abnormal most frequently, followed by the assay for C3c,d. Positive assays for C3c,d were closely associated with abnormal Millipore filter assays. Clq binding was elevated in 42% of samples, but was not associated with any other abnormality. The hemagglutination assay for anti-DNA and the C3 concentrations were the least frequently abnormal.

Adolescent↗

[Significance of immunocomplexes and complement in renal transplantation. Preliminary data].

The authors have measured circulating immune complexes (ic) and some components (C1q, C4, C3 and properdin factor B) in 87 serum samples obtained during the follow-up of five renal transplantation. Results showed high serum levels of ic with normal renal function of the graft especially in one patient, and an increase of the values in some rejection crises. The behaviour of the complement system was variable for the different components, while frequently low properdin factor B serum levels were noticed in some renal transplantations during the normal function of the graft and during the rejection crisis. In conclusion, the Authors report that a) high levels of ic can be seen also in grafts with normal function and their presence may be correlated with viral infections; b) an increase of ic during the rejection crisis is due to humoral immune response; c) the reduction of C3 and C1q associated to an increase of ic has been frequently seen, and finally; d) the low levels of properdin factor B show a probable intervention of the alternative complement pathway in the rejection crisis.

Antigen-Antibody Complex↗

Serial measurement of circulating immune complexes in the sera of patients with leukaemia.

The occurrence of circulating immune complexes was studied in 220 sera of 86 patients with leukaemia. Three tests were used in parallel: the 125I-C1q-binding assay, the complement consumption test and C1q solubility test. Positive results in at least two assays were found in 64% of the patients and in 88% of the 32 serially investigated patients. An association was found between the elevated immune complex level and the blastic phase of the disease. A fluctuation of the immune complex level-independent of the clinical course of leukaemia-could also be demonstrated. The peaks of these types of fluctuations obtained by the different tests did not coincide on several occasions. These findings suggest that the composition of immune complexes changes in the course of the disease.

Antigen-Antibody Complex↗

Effect of age on C1q and C3 levels in human serum and their presence in colostrum.

The initiating complement component (C1q) in the classical pathway of 730 subjects and the first essential component (C3) in the alternative pathway of 461 subjects in Japan were examined. The study population consisted of normal healthy newborns, infants, children, adults and the old (from birth up to 75 years of age). In cord sera, both C1q and C3 were about 60% to the total mean level. At 3 days of age, C1q markedly increased to the mean level which remained relatively invariable up to 40 years of age. And above 40 years, the C1q level increased steadily with age up to about 75 years of age. C3 reached the mean level at about 1 month of age, and was highest during infancy. This level declined at about puberty and then continued to increase steadily with age up to around 55 years. In normal healthy subjects, a moderate positive rank correlation was found between C1q and C3 amounts. No significant differences of C1q and C3 levels were evident between male and female. No C1q was demonstrable in the colostrum from which lipids were previously removed, but after concentration by precipitation in a chelating agent with a low ionic strength, C1q, measured immunochemically, was detectable at concentrations of 300 ng/ml of colostrum. C3 was also detected at concentrations of about 200 microgram/ml of colostrum.

Adolescent↗