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Complement activation during cardiopulmonary bypass by heparin-protamine interaction.

Circulating concentrations of split products of the third complement factor (C3c and C3d) were measured in five patients before, during and after cardiopulmonary bypass. In all patients, C3d concentrations increased significantly in samples obtained after the administration of protamine sulphate. Similarly, circulating C3c was seen only in those samples obtained immediately after protamine administration. In vitro experiments demonstrated that activation of the complement system was attributable to the heparin-protamine complex, and was dose-dependent. The activation of complement was not associated with any clinically detectable adverse effects.

Adult↗

[Circulating immune complexes in hypertrophic cardiomyopathy and ischemic heart disease].

In 32 patients (pts) with hypertrophic cardiomyopathy (HC), 20 pts with ischaemic heart disease (IHD) and 30 healthy controls, the levels of circulating immune complexes (CIC), immunoglobulins A, G and M, C3c and C4 components of the complement, as well as haemolytic activity of the complement were measured. CIC were assessed using two different methods: a) precipitation with 3% polyethylene glycol with subsequent spectrophotometric measurement of protein content in the precipitate, and b) binding with J-125 labelled staphylococcal +protein ++ A. Pts with HC showed a statistically significant increase in concentration of IgM and the immune complexes (shown with both methods) together with a decrease in C4 and hemolytic activity of the complement. In addition an analysis carried out for each individual patient showed that in some cases an increase in immune complexes concentration was paralleled by a decrease in IgG, C4 and haemolytic activity of the complement. This may suggest that in these pts activation of the complement through the classical pathway can occur. In pts with IHD an increase in immune complexes concentration was demonstrated by precipitation method only. Immune globulines and complement components were within limits for the control group. This suggests that in IHD the complement system is not engaged. Our findings indicate that in HC mechanisms other than those present in myocardial ischaemia must be engaged in inducing changes in the immune system.

Antigen-Antibody Complex↗

[Immunological aspects of pulse therapy in systemic lupus erythematosus].

Twenty SLE patients were examined against a background of pulse-therapy with methylprednisolone. The analysis showed that there was a decrease in the CIC concentration, antibodies to native DNA and an increase in the level of C3c and C4 components of the complement against a background of pulse-therapy. A more rapid time course of the CIC level was noted shortly after pulse-therapy as compared to changes in other immunological indices. A dynamic study of immunological indices in SLE against a background of pulse-therapy was appropriate for a clinical assessment and a study of the mechanisms responsible for the therapeutic efficacy of this method.

Adolescent↗

[Results of partial splenic resection and transposition to the lateral abdominal wall in portal hypertension in childhood].

Between 1977 and 1995, 19 children with portal hypertension (nine extrahepatic, ten intrahepatic) were treated by transpositioning the spleen into the left abdominal wall. Among the patients with intrahepatic portal hypertension three died. Two patients underwent secondary diminuition of the transposed spleen due to relapsed hypersplenism. In one of our first patients the transposed spleen atrophied after tangential resection. All surviving patients except one preserved hepatic function. The serum colloid osmotic pressure was stable. Plasma ammonia levels were normal. Serum immunoglobulins (IgG, IgM, IgA and IgG subclasses) and complement components (C3c, C4) were analyzed. After transposition patients had normal or slightly elevated values of these proteins compared with controls.

Abdominal Muscles↗

Serum complement levels in children in communities with different levels of air pollution in Japan.

To investigate the effects of air pollution on human health, we determined serum concentrations of complement components C3c and C4 in 1037 children who lived in 4 communities with different levels of air pollution in Japan. Serum levels of C3c and C4 were higher in children who lived in Osaka, which had a high level of air pollution, than in children who lived in areas of low air pollution. In boys, both C3c and C4 levels were increased significantly as concentrations of air pollution increased in the communities. In girls, however, the relationship was not significant. Serum levels of C3c and C4 did not differ with respect to asthma or wheezing. These findings suggest that serum C3c and C4 levels in children reflect the effects of exposure to air pollutants in urban districts. Boys appeared to be more susceptible to the effects of air pollution than girls.

Air Pollutants↗

Cellular components in peritoneal fluid in infertile patients with and without endometriosis.

Cellular components in peritoneal fluid of infertile patients with and without endometriosis were evaluated in 102 patients with Wright's-Giemsa and Papanicolaou stains. The secretory activity of these cells was studied indirectly by assaying acid phosphatase, prostaglandin (PG) F2 alpha and PGE2 and complement components C3c and C4. The results showed that macrophages and lymphocytes were the dominant cells in peritoneal fluid of these patients. These cells were significantly increased in endometriosis patients, as compared with control subjects. In addition, peritoneal fluid acid phosphatase, PGF2 alpha and PGE2, and complement components C3c and C4 were significantly increased in patients with endometriosis. These cellular changes and their activation in peritoneal fluid may explain infertility associated with endometriosis.

Acid Phosphatase↗

Serum levels of selected liver proteins following partial hepatectomy in the female rat.

Liver regeneration in the rat following partial hepatectomy (PH) is a frequently used model to study regulatory mechanisms in relation to cell growth and differentiation. In the present study, we analysed quantitative changes in the peripheral circulation of a number of important serum proteins following PH and laparotomy. Alpha-fetoprotein synthesis was induced in the PH rats and remained at very low levels in non-operated controls. Pregnancy-associated murine protein-1 levels and fibronectin levels were lower in the circulation of all operated animals compared with the intact controls. The serum levels of alpha-2 macroglobulin were elevated in all operated animals compared with the non-operated controls. Circulating complement factors C3c and C4 were present at significantly lower levels in PH animals than in rats following laparotomy. Small growth stimulating molecules (< 10 kDa) synthesized by different organs during the regenerative process have been described in the literature, but dialysates of the spleen and liver from non-operated rats and PH rats showed no significant impact on serum levels of the proteins in the present study.

Animals↗

Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura.

A double antibody sandwich enzyme linked immunosorbent assay (ELISA) was applied to quantitate platelet associated (PA) immunoglobulins G, A and M and complement factors C3c and C4. Fifteen patients with acute and 29 patients with chronic idiopathic thrombocytopenic purpura (ITP) were studied as well as 35 normal controls. Forty-three out of 44 (98%) patients had elevated platelet associated immunoglobulins. PAIgG was elevated in 95%, PAIgA in 82% and PAIgM in 74% of the patients. PAC3 was increased in 86% and PAC4 in 57% of the patients. There was strong correlation between PAC3 and PAIgG but not between PAC4 and PAIgG in acute ITP. In chronic ITP, however, PAC4 correlated strongly and even better than PAC3 with PAIgG. This strengthens the conjecture that the pathogenesis of ITP in many acute cases differs from that of chronic ITP.

Adult↗

Immunodeficiency after major trauma and selective surgery.

The posttrauma immunodeficiency syndrome and the related postsurgery immunodeficiency syndrome are essential for the infections often occurring after polytrauma and major surgery. Data are given here showing that after such events the levels of immunoglobulins; the complement factors C3C, C4 and C Factor B; and the numbers of circulating lymphocytes and of the subpopulations CD3, CD4, CD8 and natural killer cells as well as the stimulatory capacity of mononuclear cells to mitogen fall; while the levels of acute phase proteins, neopterin and interleukin 2 receptors and the spontaneous uptake of thymidine by mononuclear cells become augmented. Extent and duration of these changes and the rate of subsequent infections depend on the extent and kind of surgery (minor, major, clean, contaminated). However, crucial factors of the posttrauma and postsurgery immunodeficiency syndromes are not yet elucidated and relevant predictive parameters for infections are not at hand. These are essential prerequisites to initiate future immunomodulatory measures which should be added to the use of intravenous immunoglobulins yielding so far distinct but limited benefits for the prevention of infections after polytrauma and major surgery.

Complement C3↗

Characterization of tryptic fragments of human complement factor C3.

C3c and C3d fragments were prepared in pure form from trypsin-digested human C3, and the individual chains of tryptic C3c were isolated by gel filtration on Sepharose 4B in 6M guanidinium hydrochloride. No low mol. wt (Mr) fragments were identified. The polypeptide chains were characterized with regard to Mr, amino acid composition and N-terminal amino acid sequence. Tryptic C3c consisted of one fragment from the beta-chain (Mr 64,000) and two from the alpha'-chain (Mr 40,000 and 23,000). The beta-chain fragment was derived from the C-terminal part of the chain, and the 23,000-Mr component constituted the amino terminal end of the alpha-chain. The 40,000-Mr fragment emanated from the C-terminal end of the alpha-chain. Tryptic C3d displayed microheterogeneity on polyacrylamide gel electrophoresis in sodium dodecyl sulfate, but possessed a homogeneous N-terminal, identical to that described by Tack et al. (1980) (Proc. natn. Acad. Sci. U.S.A. 77, 5764-5768). By utilization of antisera against subunits of C3 and C3c in immunoblotting a degradation scheme for C3 by trypsin was proposed and the positions of the fragments in the intact molecule indicated.

Amino Acid Sequence↗

Significance of glomerular deposition of C3c and C3d in IgA nephropathy.

BACKGROUND: Complement activation plays an important role in the pathogenesis of IgA nephropathy. The clinico-pathological significance of the glomerular deposition of complement breakdown products, C3c and C3d in IgA nephropathy remains to be clarified. METHODS: We examined the relationship between glomerular staining patterns of C3c and C3d and clinico-pathological findings with 163 patients with IgA nephropathy. Renal biopsy specimens were stained with C3c and C3d by immunofluorescence, and patients were divided into the following two groups: the intensity of C3c deposition stronger than C3d deposition, or equal to it (group A); the intensity of C3d deposition stronger than C3c deposition (group B). RESULTS: In group A, the incidence of severe hematuria (over 20 urinary red blood cells in high-power field microscope (x400)) or of higher urinary fibrinogen degenerated products (over 0.1 microg/ml) was significantly higher than that in group B. In addition, group A showed a significant decrease in the glomerular filtration rate. Group A also showed a significantly higher incidence of glomerular endocapillary proliferation than in group B. CONCLUSION: These findings suggest that the glomerular deposition of C3c is associated with the inflammatory active phase of glomeruli in IgA nephropathy.

Adolescent↗

[Serum complement and protein metabolism in chronic dialysis patients].

1. When a so-called free diet is granted there is the danger of a protein deficit, which can be proved in a significant decrease of the serum transferrin and of the complement factor E3c, in patients in the chronic haemodialysis programme. 2. Within the group undergoing dialysis a correlation analysis did not result in a statistically ascertained connection between the complement factor C3c and the total haemolytic activity and the transferrin, respectively. 3. On the basis of a diet analysis a connection between the protein supply and the serum transferrin level could be established, which was not to be proved for the complement factor C3c and the total haemolytic activity, respectively. 4. Low transferrin values in the serum seem to be followed by a deterioration of the anaemia situation of the patient undergoing haemodialysis. 5. Compared with the total haemolytic activity and the complement factor C3c the determination of the serum transferrin allows an essentially exacter information about the protein metabolism of the patient undergoing a chronic haemodialysis.

Blood Proteins↗

Immune reactive C3d on the surface of myelin sheaths in neuropathy.

Immunofluorescence studies of sural nerve demonstrated immune reactive C3d and IgM on the surface of myelin sheaths in seven patients with neuropathy and an anti-myelin-associated glycoprotein (MAG) IgM M-protein. Similar deposits of C3d and sometimes IgM were found in four of six patients with acute or chronic inflammatory demyelinating polyneuropathy and in three of six patients with vasculitic neuropathy (including one with acquired immunodeficiency syndrome (AIDS)). C3d was not found in 80 patients with other peripheral nerve disorders except for two with metachromatic leukodystrophy. None of the C3d deposits contained immune reactive C3c implying substantial degradation of C3b. C3d is a sensitive index of complement activation in nerve and may be useful in classification of neuropathies.

Antibodies, Monoclonal↗

Glomerular CR1 express in situ cofactor activity for degradation of C3b.

Adherence of sheep erythrocytes (E) sensitized with IgM antibodies (A) and C3b (EAC3b) to C3b/C4b receptors (CR1) in cryostat sections of human renal glomeruli was studied using the closed chamber technique. The adsorption was stable for at least 3 h at 37 degrees C. In the presence of purified factor I, the indicator cells, however, detached from the sections after 30 min at 37 degrees C. Factor H was not required. The release was not due to loss of CR1 activity in the tissue. The detached indicator cells were negative in the immune adherence test and were agglutinated by antibody to C3d, but not by antibody to C3c. Western blot of the detached indicator cells revealed the presence of C3d and C3c was found in the chamber fluid. Accordingly, detachment of the indicator cells was due to degradation of C3b to C3d with the release of C3c into the chamber fluid. Protease inhibitors did not prevent the detachment of the indicator cells. EAC3b incubated with sections of renal glomeruli preincubated with anti-CR1 antibody were not degraded. The results therefore indicate that CR1 in situ in renal glomeruli can provide the necessary cofactor activity for factor I-mediated degradation of C3b to C3d and C3c.

Complement C3b↗

Hypercatabolism of complement in Crohn's disease--assessment of circulating C3c.

Split products from the main complement component 3 (C3) were investigated in untreated outpatients, 20 with Crohn's disease and 20 with ulcerative colitis. The median plasma concentration of c split product of C3 (C3c) in normals was 2 mg X 1(-1), in patients with Crohn's disease 20 mg X 1(-1) and in patients with ulcerative colitis 3 mg X 1(-1). This tenfold increase in C3c was significant at the 0.005-level. Plasma C3c exceeded the reference interval in two patients with ulcerative colitis. C3c levels did not correlate to the activity of the disease or to the occurrence of the C3 phenotypes S, FS and F. Substantially elevated plasma C3c in Crohn's disease suggests hypercatabolism of C3, that is, involvement of complement reactions. Further studies are needed to reveal the site of cascade activation and to define the role of complement for the pathogenesis of the disease.

Colitis, Ulcerative↗

Prevalence of circulating immunecomplexes and variations of complement fractions in HBV, HDV and HCV infections: statistical analysis and clinical correlations.

Increased levels of circulating immunecomplexes (CIC) have been demonstrated in the serum of patients with HBV infection and HDV superinfection. This finding appears to be correlated to the disease's activity. In this report serum levels of two fractions of CIC (CIC-Clq and CIC-C3d) were evaluated by ELISA method in a sample of 110 subjects with hepatitis infection (HBV, HCV, HDV). Reference values were obtained in a group of 45 healthy subjects (blood donors). Both the CIC fractions were increased in the patients with HCV infection. The most significant increase for both CIC-C1q and CIC-C3d was found in the cirrhotic patients. The complement fractions C3c and C4 were determined in the serum of these patients to investigate a potential pathogenic role of such immunecomplexes. C3c and C4 fractions showed a significant decrease only in the cirrhotic patients, without correlation with the viral agent. Serum levels of C1q complement fraction were not significantly decreased, thus excluding an impaired synthesis of complement fractions. No significant correlation was found between CIC and C3c and C4 fractions in patients with increased levels of CIC, except a slightly significant correlation between reduction of C3c and increase of CIC-C1q. These data suggest a pathogenic action of immunecomplexes in the course of HCV, particularly in the cirrhotic stage.

Adult↗

The quantitation of C3d by routine methods after the direct absorption of human plasma with anti-C3c.

The immunological methods for quantitating C3d in plasma require first the removal of less fragmented intermediates as well as the intact C3. We describe an alternative method for the quantitation of C3d in human plasma. The components which should be removed are absorbed (precipitated) directly in the plasma by a specific anti-C3c antiserum. It is then possible to determine the concentration of C3d by routine immunological methods.

Antibodies↗