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HLA antigens and the complement system in essential hypertension.

Heredity factors are of great importance in the pathogenesis of essential hypertension, but their role was until recently not reliably proved. It was only after research into histocompatibility antigens that it was possible to discover the genetic determination of a number of diseases. The purpose of the study was to reveal the genetic factors raising the risk of essential hypertension (EH). In the population of Russian nationality in Moscow, suffering from EH, HLA antigens and certain complement components were investigated. The results showed an increased frequency of HLA-A11, HLA-B13 and HLA-Bw22. However, blood C3c and C4 concentration was in the studied group of patients significantly elevated, which attests to a possible participation of the complement system in the development of EH as a factor causing vasoconstriction. The results confirm the need for further study of the immunogenetic profile of patients with EH in order to clarify certain aspects of the pathogenesis of EH.

Adult↗

Effect of gamma-interferon on the synthesis of the functional alternative and terminal complement pathways by human umbilical vein endothelial cells in vitro.

The cytokine gamma-interferon (gIFN) has been reported to modulate synthesis by endothelial cells (EC) of alternative pathway complement factors (H, I, and B). However, the net effect of gIFN on the synthesis and expression of the functional alternative and terminal pathways has not yet been reported. EC cultured under serum-free conditions were treated with different concentrations of gIFN and simultaneously co-incubated with agarose beads, which activate the alternative pathway. C3b and the terminal complement complex (TCC) bound to co-incubated beads were measured by radioimmunoassay using anti-human C3c and TCC antibodies. gIFN in concentrations 500-4000 U/ml increasingly reduced the amount of C3b and TCC detected on the beads. The down-regulating effect of gIFN on EC complement biosynthesis may be physiologically relevant by locally controlling complement activation.

Antibody Specificity↗

Isolation and identification of the third component of complement of Japanese quails.

The identification of the third component of complement (C3) of Japanese quails was attempted by using rabbit antiserum prepared against quail serum-treated zymosan (ZX) as an initial reagent. This antiserum (anti-ZX) had agglutinating activity on rabbit erythrocytes reacted with quail antibody and quail complement (EACq) but not on EAq, and developed two precipitin lines against quail serum at beta- and gamma-regions in crossed immunoelectrophoresis. Subsequently, monospecific antisera to each of these precipitin lines were prepared in rabbits, and quail serum proteins reactive with these antisera were purified by salt precipitation followed by Sephadex gel filtration and DEAE cellulose column chromatography. One protein with a m.w. of 184,000 (184K) resembled mammalian C3 in that: 1) monospecific antiserum (anti-184K protein serum) agglutinated EACq but not EAq; 2) treatment of fresh quail serum with either inulin or zymosan resulted in the conversion of the precipitin line developed against 184K protein from gamma to beta in crossed immunoelectrophoresis; 3) the 184K protein was shown to consist of two polypeptide chains of 110K and 73K linked by disulfide bonds. Furthermore, the 184K protein in serum was cleaved through the incubation with inulin to 174K and 140K proteins that might correspond to C3b and C3c of human complement; 4) the 184K protein bound to zymosan was eluted with hydrazine or methylamine but not with Nonidet P-40, indicating that 184K protein binds to zymosan by a covalent bond but not by a hydrophobic one; and 5) by treatment of fresh quail serum with methylamine, complement reactivity was reduced, although its activity was restored by the addition of purified 184K protein. These results suggest the 184K protein is the quail's equivalent to mammalian C3. When quail serum was reacted with cells that had complement-activating capacity, quail C3 deposited on their membrane as in mammalians; however, no conversion of quail C3 was noted by the reaction with CVF. Antibody to quail C3 failed to cross-react with that in mammals.

Animals↗

Studies on vasculitis. VII. C-reactive protein as a substance perpetuating chronic vasculitis. Occurrence in lesions and concentrations in sera.

Previous findings were confirmed that C-reactive protein (C-RP) occurs in some vasculitis lesions, particularly those infiltrated mainly by neutrophils (necrotizing vasculitis). The C-RP was usually in lesions also containing complement C1 or C3c, and in some, IgG was present. Using a procedure that reliably detected 200 ng C-RP/ml serum, C-RP was found in sera of many normal persons, and the amount was influenced by the occupation of the donor. Sera of thirty-one persons with vasculitis with mainly mononuclear cell-infiltrated lesions had about four-fold more C-RP (mean 28, 200 ng/ml serum) than found in normal persons, and sera of thirty-nine persons with mainly neutrophil-infiltrated lesions had eight times the normal amount (mean 56,400 ng C-RP/ml). The amount of C-RP was influenced by the severity, extent and duration of the disorder in most patients. Experimental data suggests that C-RP may contribute to the perpetuation of inflammation in chronic vasculitis.

Animals↗

C3 in seminal plasma has no additional informative value in the diagnosis of infection/inflammation of the male genital tract.

The objective of this study was to determine the clinical significance of complement fraction C3 (C3c) in seminal plasma. Therefore 120 samples from randomly chosen subfertile males without signs of genital tract infection were screened for C3 and for seminal leucocytes as markers for subclinical infection/inflammation. A comprehensive semen evaluation included sperm analysis, sperm migration testing, immunocytochemical round cell differentiation to determine seminal leucocyte counts and the leucocyte ratio and semen cultures, in aliquots of the same ejaculates. C3 concentrations were significantly correlated with leucocyte counts per ml (P < 0.002) and per ejaculate (P < 0.001), and with the leucocyte ratio (P < 0.001). No association of C3 concentrations with semen quality or with the bacterial colonization of semen samples was found. The significant association with seminal leucocytes suggests that C3 might be used as an additional marker for silent male genital tract infection. In comparison with semen leucocytes, C3 screening does not reveal any further information about semen quality or infection/inflammation pathogenesis of the male genital tract.

Adult↗

Immunohistopathologic findings in proliferative diabetic retinopathy.

We performed immunopathologic studies on pars plana specimens obtained by biopsy in patients with diabetes mellitus type I or II and by autopsy in diabetic patients and normal subjects. Frozen sections were treated with several antisera, including anti-IgG, complement components, and major histocompatibility complex antigens, as well as anti-factor VIII to detect vascular structures. The results showed IgG in a linear pattern at the basal pole of pigment epithelial cells and complement deposits of C3c, C3d, and C4 at the same location and in the stroma. HLA-DR expression was found at the level of the pigmented cells. These data suggest that some autoimmune processes may be involved in proliferative diabetic retinopathy at the level of the pigment epithelium, but it is unknown whether they are an epiphenomenon of neovascularization or if they play a role in its initiation.

Adult↗

Plasma prokallikrein and kininogens in burned patients.

Using specific immunological (1) and enzymatic (2) methods, we have measured prokallikrein, total, high, and low molecular weight kininogens in 36 severely burned patients. At admission to the intensive care unit, all constituents were significantly decreased when compared to previously defined reference intervals. The values remained low during the three first days after burn. The changes affecting total and low molecular weight kininogens were significantly correlated (p less than 0.05) with the severity of the burn area. Prokallikrein and kininogens levels were also closely related to the concentrations of C3c and C4 complement factors.

Adult↗

Immunopathogenic mechanisms in hypertension.

There is a growing interest in immunologically-mediated lesions in the cardiovascular system, as there has been evidence that there are antimitochondrial antibodies (AMA) in patients with hypertrophic cardiomyopathy or hypertensives with left ventricular hypertrophy (LVH). We have also very recently published findings from our laboratory that hypertensives with LVH have a considerable quantity of anticardiac antibodies (ACA) in their serum. The aim of this study was to investigate the possible involvement of autoimmune mechanisms in the pathogenesis and evolution of hypertensive disease. Three groups of subjects were included in the study. Group A comprised 37 patients (20 men, 17 women, mean age 50.5 +/- 8.5 years) with mild to moderate essential hypertension, 19 without echocardiographic evidence of LVH, and 18 with LVH. Group B comprised 10 patients (6 men, 4 women, mean age 45.1 +/- 8.7 years) with secondary hypertension. The control group (C) comprised 15 normotensive subjects (8 men, 7 women, mean age 47.7 +/- 8.7 years). Cellular immunity against arterial wall antigen was studied in all subjects by means of migration inhibitory factor (MIF) against relevant antigen preparation. Sera from Group A and C subjects were tested for the presence of autoantibodies against both specific (myocardial) and nonspecific antigens, by means of the indirect immunofluorescence technique. Eighty per cent of patients with essential hypertension showed a positive cellular response (MIF) against an arterial wall antigen compared to the patients with secondary hypertension or the control group. Moreover, patients with essential hypertension and LVH had the highest incidence of specific (anticardiac, ACA) and nonspecific autoantibodies and the highest C3c and C4 complement component levels compared to patients without LVH or the control group. Most of the ACA positive patients were also AMA positive, while the ACA negative patients were AMA negative as well. Defects in cell-mediated immunity against arterial wall antigen(s) may be the cause or the effect of hypertension. On the basis of our findings that there was no delayed type hypersensitivity response to arterial wall antigen(s) in the patients with secondary hypertension, we suggest that, in some cases of essential hypertension, delayed hypersensitivity reactions possibly contribute to the pathogenesis of hypertension. Autoimmune mechanisms are discussed on the basis of common epitopes shared between heart and arterial tissue.

Autoantibodies↗

Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs.

Recently, an acute phase (AP) protein response has been reported in major depression. In order to examine whether an AP response occurs in other psychiatric disorders, such as schizophrenia and mania, the authors measured plasma AP reactants, such as haptoglobin (Hp), immunoglobulin G (IgG), IgM, fibrinogen (Fb), complement component 3 (C3C), C4, alpha 1-antitrypsin (alpha 1 AT), alpha 1-acid-glycoprotein (alpha 1S) and hemopexin (Hpx), in 27 schizophrenic, 23 manic, 29 major depressed and 21 normal subjects. Schizophrenic patients had significantly higher plasma Hp, Fb, C3C, C4, alpha 1S and Hpx than normal controls. Manic subjects showed significantly higher plasma Hp, Fb, alpha 1S and Hpx than normal volunteers. Depressed subjects had significantly higher plasma Hp, Fb, C3C, C4 and alpha 1S than normal controls. Overall, the above disorders in AP reactants were more pronounced in schizophrenic than in depressed subjects. No significant differences in the above AP reactants could be found between normal volunteers, and schizophrenic, manic or depressed patients who underwent chronic treatment with psychotropic drugs. Plasma Hp, Fb, C3C, C4, alpha 1S, and Hpx were significantly higher in schizophrenic, manic and depressed patients who were non-medicated than in those who were treated with antidepressants, antipsychotics or lithium. The results suggest that not only major depression but also schizophrenia and mania are accompanied by an AP response, and that the latter may be suppressed by (sub)chronic treatment with psychotropic drugs.

Acute-Phase Proteins↗

Immunological findings in cigarette smokers.

The aim of our study was to assess the effects of cigarette smoking on selected indices of immunity. The study comprised 116 men divided into three groups: 37 subjects smoking for not more than 10 yr, 39 subjects smoking for more than 10 yr, and control group consisting of 40 age-matched men who never used to smoke. The following parameters were studied: total number of lymphocytes, B-cells, T-cells subpopulations: (CD3+)T-, (CD4+)T-helper, (CD8+)T-cytotoxic and (CD16+)natural killer (NK)-cells and serum concentration of immunoglobulins A, D, G and M, C3c and C4 complement components, acute phase proteins: alpha(1)-acid glycoprotein, haptoglobin, ceruloplasmin and lysozyme. The (CD4+)/(CD8+) ratio was also calculated. The suppressive effect of tobacco smoke on human immunity was seen as decreased serum concentration of immunoglobulins and lysozyme, especially in men smoking for more than 10 yr, decreased (CD16+)NK-cells absolute number and elevated population of (CD8+)T-cytotoxic lymphocytes entailing a decrease in CD4+/CD8+ ratio.

Acute-Phase Proteins↗

Subacute sclerosing panencephalitis: influence of the clinical course and treatment with isoprinosine on non-specific cell-mediated and humoral immunity.

Cell-mediated and humoral immunity were studied in 30 patients with subacute sclerosing panencephalitis (SSPE). Marked changes in cell-mediated immunity were observed, manifested as a decrease in total lymphocyte count, decrease of proportion of T cells forming late E rosettes, depression in lymphocyte blastogenesis, production of migration inhibition factor and delayed-type skin reactivity. The humoral immune responses was not so markedly changed and only increased levels of serum IgG, IgM and the C3c fragment of complement were noticed. The changes in immunity were more pronounced in patients with a more advanced stage of the disease. 19 patients were investigated 3 times at 7-week intervals during treatment with isoprinosine. In the group of patients (10 cases) whose clinical status was rapidly deteriorating, a marked decline of cell-mediated immunity was observed. In the group of patients showing a stationary course of the disease, cellular immunity was improving. The mechanism of the disturbances of non-specific immunity in SSPE and the influence of isoprinosine on the immune answer are discussed.

Adolescent↗

Investigation of protein metabolism with respect to amino acid administration.

A comparative study of the protein metabolism of two groups of patients having suffered major trauma (group I, n = 26, and group II, n = 16) and of two groups having undergone major surgery (group III, n = 10, and group IV, n = 9) was performed from the 2nd to the 11th day of treatment. All of the patients received approximately 35 kcal/kg body weight/day. In addition the patients in groups I and III received a 10% amino acid solution containing 0.24 g N/kg body weight/day whereas groups II and IV were administered a 5% solution containing only essential and semiessential amino acids amounting to 0, 12 g N/kg body weight/day. The 24-hr nitrogen output in urine, the serum free amino acid concentration as well as the serum protein fractions of transferrin and the C3c and C4 complements were contrasted. Significant differences between traumatised patients and those having had major surgery with respect to nitrogen balance and serum free amino acid concentrations were observed regardless of the pattern of nutrition. However, only slight differences in the concentrations of serum protein fractions of the two groups of patients were noted. Following amino acid solution the polytraumatized patients exhibited an average N balance of -11.9 g N/day, which is indicative of a severely catabolic metabolism. The average nitrogen loss observed in the postsurgical patients amounted to only half this amount. Following administration of the semiessential amino acid solution an appreciable difference in the nitrogen balance between comparable groups was not observed. However, the blood urea nitrogen was lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunohistological study of subretinal membranes in age-related macular degeneration.

An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.

Antibodies, Monoclonal↗

[Evaluation of acute phase proteins in hypertensive and obese patients].

UNLABELLED: The inflammatory process contributes to the development of atherosclerotic changes. The aim of this study was to evaluate concentrations of selected acute phase proteins (APP) and their glycosylation profile in hypertensive subjects. 92 hypertensive patients (53 men and 39 women, average age 45.1 yrs) were recruited to the study. Hypertension was proved to be essential, mild to moderate (mean blood pressure values were 141/87 mmHg). The control group comprised 75 healthy persons in comparable age. In all subjects assessment of C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), alpha 1-antichimotripsin (ACT), transferrin, alpha 1-antitripsin (rocket immunoelectrophoresis method) and C3c and C4c complement fractions (radial immunoelectrophoresis according to Mancini) were performed. Evaluation of glycosylation profile and reactivity coefficient (RC) for AGP were done by means of affinity immunoelectrophoresis with concanavalin A as a ligand (according to Bøg-Hansen). When compared to the control group hypertensive subjects had significantly higher C-reactive protein and interleukin 6 concentrations. Level of transferrin (negative APP--decreasing in the course of the inflammatory process) was statistically lower in the studied group. Hypertensive patients were also found to have elevated AGP-AC values proving acute character of the inflammatory reaction. The intensification of the inflammatory reaction was greater in the subgroup of hypertensive patients with unsatisfactory control of blood pressure. CONCLUSIONS: 1. Hypertension may evoke the acute phase reaction. 2. Quantitative and qualitative changes in acute phase proteins observed in hypertension prove that hypertension itself is an acute inflammatory condition. 3. Markers of acute phase response are particularly strongly expressed in smokers and subjects with insufficient control of blood pressure. The most probable factor leading to the enhanced acute phase response in hypertension is interleukin 6.

Acute-Phase Proteins↗

[Effect of hemodialysis on the concentration of beta 2-microglobulin and acute phase proteins in the serum of patients with chronic renal failure].

In 24 patients with terminal renal failure the concentrations were determined of beta 2-microglobulin, prealbumin, alpha 1-antitrypsin, ceruloplasmin, alpha 2-macroglobulin, antithrombin III, plasminogen, transferrin, C3c and Cr complement components in the serum before and after haemodialysis. A statistically significant rise of concentrations of these proteins was found. It is thought that this rise was due mainly to haemoconcentration, while the contact with dialysing membranes is less important.

Acute-Phase Proteins↗

Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer's disease.

Progressive cerebral deposition of the amyloid beta-protein (A beta P) occurs in Alzheimer's disease and during aging of certain mammals (eg, human, monkey, dog) but not others (eg, mouse, rat). The authors cloned and sequenced a full-length cDNA encoding the beta-protein precursor (beta APP) of cynomolgus monkey. The predicted amino acid sequence of the 695-residue protein is completely homologous to that of human. The alternatively transcribed exons encoding the Kunitz protease inhibitor region in monkey were cloned, showing only a single conservative amino acid substitution in the 751-residue form of beta APP and four substitutions in beta APP770. Immunoblots of cerebral cortex with antibodies to various beta APP domains showed highly similar beta APP polypeptides in human and monkey, in contrast to those of mouse and rat. The latter differences reflect sequence substitutions, transcriptional regulation, and possibly post-translational modifications that may decrease the amyloidogenic potential of rodent beta APP. Immunocytochemistry of aged cynomolgus brain showed A beta P deposited in blood vessels and diffuse and compacted plaques closely resembling those of humans, and the presence of beta-amyloid-associated proteins (alpha 1-antichymotrypsin; complements C1q and C3c) characteristic of A beta P deposits in Alzheimer's disease. The authors' findings demonstrate that cynomolgus monkey and perhaps other primates provide a close animal model for examining the early transcriptional and post-translational processing of beta APP that precedes A beta P deposition during aging and in Alzheimer's disease.

Aging↗

[Contribution of biochemical tests in the diagnosis of the nervous phase of human African trypanosomiasis].

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.

Blood Chemical Analysis↗

[Parenteral feeding after ureterosigmoidostomy: nitron balance, free plasma amino acids and state of proteins].

The postoperative protein metabolism of 11 patients who had required either a colon conduit or ureterosigmoidostomy urinary diversion was examined. From the 3rd to 10th postoperative day day, each patient received a standard parenteral alimentation (100 g amino acids and 2000 kcal/24 h). Nitrogen balance, plasma level of the free amino acids, and the C3c-, C4-complement and transferrin fraction in plasma were determined regularly. The results showed that this substitution therapy succeeded in avoiding serious alterations in the parameters measured.

Adult↗