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PubMed1984

Changes in soluble proteins in cervical mucus during midcycle in normally menstruating women.

Albumin, IgG and complement C3c were analyzed by immunonephelometry in cervical mucus collected daily at midcycle. There was a statistically significant difference in the amount of mucus recovered on the day of the luteinizing hormone (LH) surge and on the following day. Several nadirs in protein concentration could be visualized in 8 out of 14 subjects, whereas in 6 subjects, no such changes in concentration were found. In terms of soluble protein concentrations and amounts there were no differences between cycle days. For changes in soluble protein concentrations and amounts, no systematic time relation to the LH peak could be found.

Adult↗
PubMed1980

Comparison of radial immunodiffusion and laser nephelometry for quantitating some serum proteins.

After quantitating immunoglobulins G, A, and M and complement C3c and C4 in serum by using a laser nephelometer coupled with a data processor, I compared these results with values obtained by an early-readout radial immunodiffusion method. Day-to-day precision was better for nephelometry than for radial immunodiffusion for all proteins analyzed. The average coefficient of variation was 6.0% for nephelometry and 9.9% for radial immunodiffusion. Comparison of these methods gave ranked correlation coefficients of 0.945, 0.981, 0.932, 0.803, and 0.792 for IgG, IgA, IgM, C3c, and C4, respectively. Nephelometry gave significantly higher values than radial immunodiffusion for IgG, IgA, IgM, and C3c, and significantly lower values for C4 (p less than 0.001). Part of this bias was found to be due to the equation programmed in the data processor for calculating the standard curves. Within 95% limits, nephelometry gave higher normal ranges than radial immunodiffusion for IgG, IgA, and IgM. Other possible factors that can produce this bias are discussed.

Adolescent↗
PubMed1978

Immunological features of kala-azar.

Serum immunoglobulins, complement C3c, percentage of T and B cells, and skin reactivity to Leishmania were studied in ten cases of kala-azar. Immunoglobulin G was increased in a majority of these patients. The C3c level in two out of six patients tested was lower than normal. The percentage of T cells in peripheral blood of nine patients tested was reduced and in seven of these patients the percentage of B cells was elevated. After a full course of anti-kala-azar therapy the percentage of T and B cells remained the same in five patients studied. All the patients showed a negative skin reaction when they were tested with Leishmania antigen.

Adult↗
PubMed1983

Pregnancy-associated plasma protein levels at term in normal pregnancy, preeclampsia and essential hypertension.

The levels of protein associated with pregnancy (placental specific beta 1 glycoprotein, SP1, and pregnancy associated -alpha 2- globulin, alpha 2-PAG), immune function (complement, C3c) and inflammation (ceruloplasmin, C), were studied at term in groups of patients with normal and complicated primigravid and multigravid pregnancy. The levels of SP1 and C3c were similar in all the groups studied. In patients matched for parity, the levels of alpha 2-PAG were significantly lower than normal in preeclamptic primigravidas and in multigravidas with a history of preeclampsia in their first pregnancy. Ceruloplasmin levels were significantly elevated in preeclampsia patients and in patients with essential hypertension. It is suggested that reduced plasma alpha 2-PAG may be of prognostic value and have a role in the aetiology of preeclampsia whereas increased ceruloplasmin levels may be no more than an acute phase reactant resulting from pathological changes due to hypertension.

Ceruloplasmin↗
PubMed1992

The occurrence of pericapillary fibrin in venous hypertension and ischaemic leg ulcers: a histopathological study.

The presence of pericapillary fibrin and complement C3c in the ulcers of 19 patients with venous hypertension and 14 patients with ischaemic leg ulcers was investigated using histochemical and immunohistochemical techniques. There was deposition of fibrin around the capillaries in the central part of the ischaemic ulcers, and the venous hypertension ulcers, and in the non-ulcerated skin around one of the venous hypertension ulcers and two of the ischaemic leg ulcers. The deposition of fibrin is a secondary phenomenon that occurs in the area of ulcerated skin and does not play a major causal role in the formation of chronic leg ulcers.

Aged↗
PubMed1981

Antiglobulin-tests for detection of auto-immunohaemolytic anaemia during long-term treatment with ibuprofen.

Auto-immunohaemolytic anaemia is a very unusual complication during long-term treatment with ibuprofen. In order to detect the haemolytic antibodies involved, serum and erythrocytes from 87 patients were investigated after continuous treatment with an average daily dose of 1337 mg ibuprofen for some 6-47 months. Eight patients showed a weak or medium-positive antiglobulin test result with polyspecific anti-human serum. With monospecific anti-human serum, complement C3c and/or C3d were detected on the surface of 8 patients' erythrocytes, but none had biochemical parameters indicating haemolysis. None of the 87 patients had IgG, IgM or IgA on their erythrocytes. The findings neither indicated haemolysis present nor early stages in any of the four types of drug-induced auto-immunohaemolytic anaemia. The frequency of a positive antinuclear factor test (ANF) among patients treated with ibuprofen did not differ from that of healthy subjects in the same age group. The type of haemolysis associated with ibuprofen is discussed, but available data do not permit any definite classification. It is concluded that ibuprofen is a safe drug which rarely causes haemolysis and does not seem to cause induction of ANF.

Adult↗
PubMed1984

Complement in chronic secretory otitis media. C3 breakdown and C3 splitting activity.

Occurrence of in vivo C3 breakdown and in vitro C3 splitting activity was studied in serum and middle-ear effusion (MEE) samples from 30 children with chronic secretory otitis media (SOM). The MEE showed strongly elevated levels of both low- and high-molecular-weight C3 breakdown products, along with decreased factor B, C4, and C3 levels. Total hemolytic complement component activity was virtually absent from MEE. The MEE fluids were found to contain C3 splitting factors as demonstrated by their high capacity to convert C3 in vitro from fresh normal human serum. This activity was not inhibited by the classic complement pathway inhibitor, 0.01M ethylene glycol tetra-acetic acid with 0.005M magnesium chloride. The results suggest that a strong local complement activation has taken place and that the factors responsible are present in the MEE of patients with SOM.

Antigen-Antibody Complex↗
PubMed1983

Relationship of clinical findings in systemic lupus erythematosus to seroreactivity.

We have characterized 52 consecutive patients fulfilling 4 or more of the American Rheumatism Association criteria for systemic lupus erythematosus in order to provide, for the first time, a homogeneous sample for statistical comparison of antinuclear antibody (ANA)-positive and ANA-negative groups. Ten patients (19%) were seronegative. There was no significant difference in age, disease activity, organ system involvement, erythrocyte sedimentation rate, immune complex levels, or C3 levels. The ANA-negative group showed a higher incidence of involvement for whites and men. Leukopenia, lower levels of antibody to DNA, and higher C4 levels were also characteristic of the ANA-negative group.

Adult↗
PubMed1987

Inhibition of interleukin 3 function by a fragment of the third component of complement.

A C3d-like (C3d-1) fragment of 33 kDa was isolated and its biological activity studied. The fragment was generated from guinea pig C3b by porcine pancreas kallikrein and purified by fast protein liquid chromatography. The C3d-like fragment inhibited interleukin (IL) 2-dependent T lymphocyte proliferation. The suppressive activity of the described C3d-1 fragment was not restricted to lymphocytes as targets but inhibited in addition the proliferation of a nonlymphocyte mast cell line which was strictly IL3-dependent in its proliferative capacity. Kinetic studies implied early stages of cellular proliferation to be influenced. Furthermore, the C3d-1 fragment was not only an inhibitor of cellular proliferation but was also a potent inducer of leukocytosis.

Animals↗
PubMed1990

Expression of complement alternative pathway proteins by endothelial cells. Differential regulation by interleukin 1 and glucocorticoids.

We have studied the secretion of proteins of the alternative pathway of complement C3, factor B and factor H by human umbilical vein endothelial cells (HUVEC). Results showed that factor H and factor B are quantitatively secreted in abundance whereas C3 could only be detected when the cells are maintained in culture during long periods of time. Interferon-gamma stimulated factor H, factor B and, to a lesser extent, C3 secretions. Interleukin (IL) 1 had a differential effect on spontaneous C3, factor B and factor H secretions. In the presence of IL 1, there was a significant secretion of C3 occurring within a short period of culture. IL 1 also stimulated factor B secretion. There was a synergistic stimulating effect between IL 1 and interferon-gamma to bring C3 and factor B productions by HUVEC to very high levels. In contrast, factor H secretion was consistently inhibited by IL 1. Local increase in C3 and factor B secretions by endothelial cells in the presence of IL 1 may have important implications in the inflammatory reaction. In striking contrast, the glucocorticoid dexamethasone (DXM) had modulatory effects which are consistent with its anti-inflammatory properties. DXM, at therapeutic concentrations, decreased C3 and factor B secretions and increased factor H secretion. Local modulation of complement protein secretion by DXM appears to be a new mechanism by which this glucocorticoid may control inflammation.

Complement C3b Inactivator Proteins↗
PubMed1994

Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure.

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1-8 months), mid-stage hemodialysis (MS-HD, 9-69 months), and advanced-stage hemodialysis (AS-HD, 70-207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6-17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Determination of the half-life of C3 in patients and its relation to the presence of C3-breakdown products and/or circulating immune complexes.

Measurement of complement components in serum may not accurately assess the degree of activation of the complement system. An alternative approach is the measurement of conversion products of the complement components. The relation between the presence of an increased concentration of C3-conversion products and the metabolism of C3 was investigated. In a group of patients, circulating immune complexes were also measured (Clq-binding test) to see whether the combination of those markers yielded information on the C3 metabolism. In this study it is shown that static measurements of serum C3 levels is of no value for the degree of complement activation. Measurement of C3-conversion products may indicate C3 hypercatabolism (in 8 of the 11 patients with C3-conversion products), but it does not imply depressed C3 synthesis. Detection of circulating immune complexes by the C1q-binding assay did not always indicate a C3 hypercatabolism. Of 12 SLE patients studied, in 9 of them, a C3 hypercatabolism was detected, and 5 of these patients were clinically characterized by the presence of minor disease symptoms. Overall, the results indicated that detection of circulating immune complexes and/or C3-conversion products could not be used as an absolute measure for insight into the C3 metabolism.

Antigen-Antibody Complex↗
PubMed1992

Increases in immunoglobulin and complement in patients with esophageal or gastric cancer.

Based on data providing evidence that the enhancement of serum IgG and IgA is associated with the occurrence of infectious complications following surgery in patients with esophageal cancer, we examined the possible factors contributing to alterations in the serum IgG, IgA, IgM, C3, C4, and CH50 levels. A multiple linear regression analysis was made on data obtained from 71 patients with esophageal cancer and 57 with gastric cancer. In the patients with esophageal cancer, age and protein-calorie malnutrition (PCM) were related to the elevation of IgG levels while the stage of cancer was linked to that of IgA. The sex and IgM levels were also seen to be related. Age and the stage of cancer were associated with reductions in C3, C4, and CH50 levels, although in the patients with gastric cancer, the stage of cancer and elevations of these complement levels were related. Thus, age, PCM, and tumor malignancy are all factors related to the enhancement of IgG or IgA in patients with esophageal cancer.

Adenocarcinoma↗
PubMed1985

Mianserin protein binding in serum and plasma from healthy subjects and patients with depression and rheumatoid arthritis.

Mianserin protein binding was measured in serum from 43 healthy subjects and plasma from 12 elderly depressed patients and 23 patients with rheumatoid arthritis. Free fraction (mean +/- SD) was 5.5 +/- 0.7% in the healthy subjects, 5.0 +/- 0.8% in the elderly subjects and 6.0 +/- 1.0 in the patients with rheumatoid arthritis. In the group of elderly patients treated with mianserin, a high correlation (r = 0.83, P less than 0.001) between total and free concentrations of mianserin was found. In both groups a high linear correlation (r = +0.90, P less than 0.001) between the free fraction of mianserin and that of imipramine was found, the latter being about twice as high as for mianserin. In both healthy subjects and arthritis patients the degree of protein binding was positively correlated to the concentration of alpha 1-acid-glycoprotein and complement C3c, and somewhat more weakly to haptoglobin. In the healthy subjects protein binding was also highly positively correlated to the concentration of apolipoprotein B, whereas no such correlation was found in the rheumatoid arthritis patients. In the rheumatoid arthritis patients protein binding was highly correlated to the concentration of hemopexin and somewhat more weakly to ceruloplasmin and fibrinogen; a weak negative correlation to the concentration of albumin was also found. Since significant intercorrelations between the concentrations of these proteins were found, the correlation to the degree of binding of mianserin may not necessarily represent binding of the drug to the protein.

Adult↗
PubMed1985

Plasma protein binding of imipramine in patients with rheumatoid arthritis.

In 23 patients with rheumatoid arthritis the plasma protein binding of 3H-imipramine and the plasma levels of 13 proteins were measured in order to examine the significance of the proteins for the binding of imipramine. The degree of 3H-imipramine binding did not differ significantly from that in healthy controls. It was positively correlated with the concentrations of fibrinogen, alpha 1-acid-glycoprotein, ceruloplasmin, complement C3c, haptoglobin and hemopexin. Erythrocyte sedimentation rate was also highly positively correlated with binding. The concentration of several of the proteins showed a significant covariation. The 3H-imipramine binding was negatively correlated with the concentration of albumin and the latter was negatively correlated with some of the proteins mentioned-above. No correlation with the levels of apolipoproteins A and B was found. There appears to be more a qualitative than a quantitative change in 3H-imipramine binding in patients with rheumatoid arthritis.

Aging↗
PubMed1986

Effect of lithium therapy on inflammatory response.

Chemiluminescence produced by normal cells was reduced in response to zymosan which was opsonized with serum from patients on prophylactic lithium therapy, compared to control serum from normal subjects (68 +/- 3.1 vs. 93 +/- 3.4 mV/5 X 10(5) cells). Preincubation of normal cells with serum from patients also resulted in reduced chemiluminescence activity when the cells were stimulated with autologous serum-coated zymosan (47 +/- 4.5 vs. 64 +/- 6.3 mV/5 X 10(5) cells). Spontaneous complement conversion was increased in the serum of patients on lithium therapy (46.3 +/- 3.8 vs. 25.3 +/- 2.5% conversion). These studies demonstrated that lithium, at safe therapeutic levels (0.4-0.9 mmol/liter), significantly altered complement conversion and had a marked affect on chemiluminescence activity by normal cells.

Adult↗
PubMed1987

IgG binding to cytoskeletal intermediate filaments activates the complement cascade.

The cellular plasma membrane becomes permeable to macromolecules during the cell injury process. This results in exposure of the interior of the cell to plasma proteins and to high-affinity binding of the Fc part of IgG to intermediate filaments (Hansson, G K, Starkebaum, G A, Benditt, E P & Schwartz, S M, Proc natl acad sci USA 81 (1984) 3103). Such IgG binding could be an early step in a process that serves to eliminate the injured cell. We have now identified its effect on the complement system. Intermediate filaments were reconstituted in vitro from purified vimentin, and incubated with plasma proteins. Cross-linker experiments showed binding of the heavy chain of IgG to vimentin, indicating that the vimentin protein carries an Fc-binding site. In contrast, no direct binding of complement factor Clq to vimentin could be detected. Binding of both IgG and Clq could, however, be detected by immunofluorescence when cytoskeletons of cultured endothelial cells were incubated with fresh serum. Therefore, IgG binding to filaments in the presence of serum is accompanied by Clq binding to IgG. This was in turn followed by fixation of C4 and C3 to intermediate filaments in a process that was dependent on both Ca2+, Mg2+ and Clq, indicating that it was part of a complement activation via the classical pathway. Exposure of fresh serum to intermediate filaments also resulted in production of the anaphylatoxic complement cleavage fragment. C3a, with a dose-response relationship between the amount of filaments present and the amount of C3a generated. Chemotactic activity towards granulocytes and monocytes was also generated by exposure of serum to intermediate filaments, and this activity was dependent on the presence of complement factor C5 and on the classical complement activation cascade, implying that it was due to the C5a peptide. Exposure of the interior of the cell to plasma proteins thus results in binding of IgG to intermediate filaments and activation of the complement cascade via the classical pathway. This, in turn generates bioactive mediators which may recruit leukocytes to the injured cell (C5a) and have profound effects on vascular permeability (C3a, C5a). We propose that this is part of a scavenger mechanism for the elimination of damaged cells.

Binding Sites↗