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Biomedical subjects

G Füst

Publications and source records attributed to G Füst.

At least 145 records · Page 8Linked to original sources
PubMed1985

Depressed classical complement pathway activities in chronic lymphocytic leukaemia.

Haemolytic activities of the classical and alternative complement pathways, and levels of C1, C4, C3, factor B and C1 inhibitor (C1-INH) were measured in 85 serum samples from 46 patients with chronic lymphocytic leukaemia (CLL). Significantly decreased mean C1 and C4 levels were found, and the haemolytic activities of these components were low or low normal in more than 50% of the sera tested. In 15 sera from 5 patients a complement profile characteristic of acquired C1-IHN deficiency was observed. These results indicate that the depression of the activity of the classical complement pathway is a frequently occurring feature in CLL.

Antigen-Antibody Complex↗
PubMed1984

Appearance of covalently bound antigen in immune complexes formed during the activation of complement.

The effects of complement activation on the antigenic component of immune complexes have been studied, using 125I-BSA-rabbit anti-BSA-IgG complexes as models. Polyethylene glycol precipitates of 4 types of IC (those formed in native normal human serum, or NHS-containing EDTA, NHS-EDTA, and preformed soluble IC incubated in NHS or NHS-EDTA immediately after preparation) were analysed by sodium dodecyl sulphate-polyacrylamide slab gel electrophoresis. A characteristic difference in the distribution of 125I-BSA in the gel was observed between the NHS- and NHS-EDTA-treated samples. With the former type of IC, a significant part (16-23%) of the label was found in gel fractions of mol. wt. exceeding that of the antigen (80-300 kDa vs. 69 kDa), whereas with NHS-EDTA-treated IC only a minimal amount (4-5%) of the radioactivity was detected in these fractions. These findings indicate that complement activation results in the covalent binding of complement to the antigenic component of IC. The practical importance of these observations is discussed. In addition, a marked difference in precipitability was observed between IC formed in NHS and preformed IC incubated in NHS.

Antigen-Antibody Complex↗
PubMed1984

Antibodies to primate retrovirus antigens in circulating immune complexes of patients with acute myeloid leukemia.

Circulating immune complexes were isolated from sera of 8 patients with acute myeloid leukemia (AML) in relapse, and 20 healthy blood donors. F(ab')2 fragments were prepared from the isolated complexes. Using a radioimmunoassay (RIA), these F(ab')2 fragments, the undigested complexes and the original sera were examined for the presence of antibodies against a panel of primate retrovirus antigens: gp70, p15 and p30 of gibbon ape leukemia virus (GaLV) and baboon endogenous virus (BaEV). F(ab')2 fragments derived from the immune complexes of all patients reacted with one or more of the antigens tested, whereas no antibody activity was found in the sera or undigested immune complexes of the same patients. By a competitive RIA, antigens related to GaLV and/or BaEV were found in the serum of 7 out of 8 patients. No markers of these retroviruses were detected in the F(ab')2 preparations, in immune complexes or in sera of any of the 20 control subjects. Our results indicate that a part of the circulating immune complexes in AML contain antigens related to primate retroviruses and specific antibodies to these antigens.

Adult↗
PubMed1984

Regulation of Fc mu receptor-mediated functions of resident and provoked peritoneal macrophages.

Modifying and/or regulating effects on Fc mu receptor (R) mediated phagocytic and ADCC activity of both resident (r) and provoked (p) peritoneal macrophages (PM) was studied applying drugs affecting the cytoskeleton and cation transport. In addition, the effects of exogenous PGE2 and cyclic nucleotides were also examined. Fc mu-receptors appear to be functionally less significant in provoked PMs than in resident ones since both Fc mu-receptor mediated phagocytosis and ADCC were lower in the formers. The cytoskeletal system is important in the regulation of both Fc mu-receptor-mediated functions. Phagocytosis through Fc mu-receptor is decreased by Cytochalasin B and by Vinblastine treatment, whereas ADCC is enhanced by Cytochalasin B. Extracellular PGE2 and cAMP induced a higher phagocytic activity and suppressed ADCC, whereas cGMP displayed an opposite effect. The sensitivity of Fc mu R-mediated activities to ionophoric and to cytoskeleton-damaging drugs was lower in provoked than in resident PMs. In addition, the regulatory role of PGE2 and of cyclic nucleotides on the same activities was less marked on provoked PMs. In contrast, ouabain inhibits Fc mu R-dependent antigen incorporation and ADCC on provoked PM monolayers only. These findings suggest differing regulatory mechanisms for Fc mu R-mediated functions in provoked PMs as compared with resident ones.

Animals↗
PubMed1984

Ionophore-induced functional changes in macrophages.

Ca ionophore A 23187 and valinomycin known to induce Ca2+ influx, i.e. K+ efflux, appeared to induce activation-related changes in rat peritoneal macrophages (PM) at 10(-5)-10(-7) M concentrations as revealed by aggregation, nitro blue tetrazolium (NBT) reduction, superoxide anion production as well as beta glucuronidase release; however, lactate dehydrogenase (LDH) activity was measured in supernatants only after treatment with 10(-5) M of A 23187. The PM-activating effect of A 23187 was abolished in the presence of 5 mM EGTA, whereas the activating effect of K ionophore did not depend on the extracellular Ca2+. Fc receptor (FcR) mediated incorporation, intracellular killing as well as the antibody dependent cytotoxicity (ADCC) were markedly inhibited upon incubation with Ca ionophore or valinomycin. C3bR mediated phagocytosis was found to be more resistant to the cation transport affecting drugs. The impairment of effector functions was elicited by nontoxic concentrations of ionophores, however, their inhibiting effects did not require extracellular Ca2+ at the time of ionophore-exposition.

Animals↗
PubMed1984

Inhibition of the complement activation by an adrenal androgen, dehydroepiandrosterone.

The effect of dehydroepiandrosterone (DEA), an adrenal androgen successfully used for preventing attacks in hereditary angioneurotic edema (HANE) patients was studied on the activation of classical and alternative complement pathway. The steroid inhibited both the spontaneous and immune activation of the classical complement pathway (CP), the former effect, however, was found to be more marked than the latter one. DEA exerted its inhibiting effect most probably by interfering with the internal activation of C1. Because DEA rendered HANE patients symptom free but induced only a slight increase in their serum C1-INH level, our present findings suggest that inhibition of CP activation may have a significance in the therapeutic effect of DEA and possibly of other androgens as well.

Angioedema↗
PubMed1984

Serial determination of complement and specific antibody titres in Pseudomonas aeruginosa infection.

Serial examination of the complement system and specific antibody titre of 12 surviving patients and 8 lethal cases suffering from Pseudomonas aeruginosa infection showed that except the onset of infection, until the development of septic shock, the level of the complement components corresponded to or exceeded the average normal value. In reversible septic shock the complement titre decreased significantly and in irreversible shock the values were even lower. Activation of the complement system occurred on 10 occasions via the classical and on 42 occasions via the alternative pathway. The number of activations grew parallel with the severity of the infection. Activation through the classical way was generally more intensive. During the whole infectious process not the individual characteristics of the P. aeruginosa present unbroken, but the pathological events and the specific antibody level determined the mode (alternative or classical pathway) of complement activation. The specific antibody level of the surviving patients significantly surpassed the titres of the lethal cases until the development of shock. Not an insufficiency of the complement system but the relative lack of specific antibodies was mainly responsible for the fatal outcome of P. aeruginosa infections.

Antibodies, Bacterial↗
PubMed1983

Precipitability and composition of HBsAg-anti-HBs immune complexes formed in the presence of complement. A model of circulating immune complex analysis.

Immune complexes (IC) of partially purified HBsAg and human anti-HBs were prepared at different antigen/antibody ratios in the presence of complement in normal human serum (NHS), and under conditions not allowing complement activation in buffers or in NHS containing 10 mM EDTA (NHS-EDTA). Commercial preparations of the radiolabelled antigen and antibody were used. IC formed in NHS were not significantly precipitated even after incubation for 24 h at 4 degrees C, whereas a typical precipitation curve was observed with complexes formed in the absence of complement. Thus, complement activation was found to markedly and permanently inhibit precipitability of HBsAg-anti-HBs immune complexes (HBsAg-IC). HBsAg-IC were precipitated from sera with 3.5% polyethylene glycol (PEG), boiled in sodium dodecyl sulphate (SDS)-urea buffer, and analysed by SDS-polyacrylamide slab gel electrophoresis (SDS-PAGE). With complexes formed in the presence of complement, about one-sixth of the antibody activity was found in high molecular weight fractions corresponding in size to IgG oligomers. By contrast, with complexes formed without complement, no significant amount of antibody was found in these fractions. With blotting technique and radiolabelled anti-human-C3 antibody, it was demonstrated that anti-HBs was covalently bound to C3b fragments in IC formed in the presence of complement and was in the high molecular weight fractions.

Animals↗
PubMed1983

Effect of dehydroepiandrosterone on hereditary angioedema.

Hereditary angioneurotic edema (HAE) is a complement-related clinical disorder with a deficiency of the C1 esterase inhibitor protein. Eight patients with severe attacks of the disease were treated with the adrenal "androgen" dehydroepiandrosterone sulphate (DS). Steroid therapy for 3-28 months resulted in dramatic improvement in their clinical state and a moderate increase in the serum concentration of C1 inhibitor. There was a significant increase in the serum level of either unconjugated dehydroepiandrosterone (D) or of DS during treatment.

Adolescent↗
PubMed1983

Effect of low-molecular-weight lymphokine components on the Fc and C3b receptor-mediated macrophage functions.

Rat lymphokine (LK) components of 500--2500 MW separated on Sephadex G-15 column (FrA) were tested for their effect on Fc and C3b receptor activities of rat resident (rPM) and thioglycollate-provoked (pPM) peritoneal macrophages. Functions of the receptors were studied by measuring the adherence and uptake of 51Cr-labeled sheep red blood cells (SRBC) mediated by isolated rat anti-SRBC IgM or IgG2a antibodies and human C3, respectively. On rPMs mainly Fc mu receptors (Fc mu Rs) were affected by FrA; at low concentration (20 micrograms/ml) adherence was increased and phagocytosis was inhibited. At higher concentrations (40-80 micrograms/ml) a reverse effect was observed: adherence was inhibited and phagocytosis increased. On pPMs IgG2a-mediated functions were mainly affected by FrA with a concentration dependence like that observed with Fc mu Rs on rPM monolayers. A concentration-dependent enhancement of C3b receptor (C3bR)-mediated adherence by FrA was observed on both PM types. On pPms C3bR-mediated phagocytosis was enhanced as well.

Animals↗
PubMed1983

Free and complexed anti-lipoprotein antibodies in vascular diseases.

The cell-mediated immune response against low density lipoproteins (LDL) was demonstrated by the migration inhibition test in patients with various vascular diseases. Anti-high density lipoprotein2 (HDL2) cellular immune response was found only in a few patients. LDL and HDL2 binding factors were detected in about 50% of coronary patients. No significant difference in their occurrence was found between the normolipidemic and hyperlipidemic patients nor between patients with hyperlipidemia type II/b and type IV. On the assumption that lipoproteins may act as auto-antigens by forming immune complexes, the presence of anti-LDL and anti-HDL2 activity was investigated in circulating immune complexes obtained by polyethylene glycol (PEG) precipitation from the sera of coronary patients and controls. Using an ELISA technique, PEG-precipitable anti-LDL activity was detected in 23, 11 and 18% of cases with myocardial infarction, angina pectoris and healthy old subjects, respectively. In the immune complexes obtained from the sera of the healthy young donors no anti-LDL activity was found. Anti-HDL2 activity in the immune complexes was demonstrated only in a few cases from among the patients and elderly persons we investigated.

Adult↗
PubMed1983

Interaction of C3 and C3b with immunoglobulin G.

Human C3b as well as native C3 were found to bind to solid phase human and rabbit IgG. Haemolytically active C3 had significantly higher binding capacity to IgG than the C3b fragment. Inhibition experiments proved that C3 and C3b have common binding sites on the Fab and Fc part of the IgG molecule but the character of these binding sites was different. As a functional consequence of C3-IgG interaction, C3 binding was found to inhibit the specific precipitation of an IgG antibody preparation.

Animals↗
PubMed1983

The effect of oligopeptides on the C3b receptor-mediated functions of rat macrophages.

Effects of various substances known to influence macrophage functions on the adherence of C3b-coated sheep erythrocytes (E-C3b) and their phagocytosis by elicited rat peritoneal macrophages (PM) has been studied. Different oligopeptides (OP) having a chemotactic effect, such as tuftsin, angiotensin II (At II) and the OP-fraction of a lymphokine preparation (LK-OP) increased both adherence and phagocytosis of E-C3b in a concentration-dependent fashion. In contrast, neither substances influencing the membrane cation transport nor prostaglandins (PG) and cyclic nucleotides significantly changed the C3b receptor (C3bR)-dependent effector functions of macrophages. Enhanced functions of the C3bR were not associated with an increased capability of PMs for intracellular killing of Candida albicans.

Angiotensin II↗
PubMed1983

Serial complement measurements in patients with leukaemia.

Haemolytic activity of the classical and alternative pathways and the levels of C4, C3 and factor B were serially measured in 153 serum samples of 41 patients with different types of leukaemia (9 AML, 14 ALL, 10 CML and 8 CLL). In parallel, the concentration of circulating immune complexes (CIC) was estimated using two methods, the complement consumption assay and the Clq-solubility test. Different complement profiles were found in different types of leukaemia. In AML, each complement parameter tested was elevated as compared to the control values (sera of healthy blood donors). Similar results were observed in ALL, although the differences were less marked. In CML, dissociation of the classical and alternative pathway activities was found: activities of the classical pathway and C4 were significantly elevated, whereas activity of the alternative pathway as well as C3 and factor B concentration did not differ significantly from the control values. In CLL, normal or slightly depressed complement levels were found. The concentration of circulating immune complexes measured by both methods was significantly increased as compared to control values. No significant positive or negative correlations were found between the complement levels and the immune complex concentrations determined in the same sera. An association between the clinical course of acute leukaemia and the complement levels was observed: significantly elevated complement titres were found in the blastic stage of the disease, whereas in remission normal values were recorded. The results of complement measurements performed in serum samples obtained before and after combination chemotherapy were compared on 32 occasions. In parallel to a significant decrease in the absolute number of blast cells in the peripheral blood, a normalization of the increased complement levels was observed after treatment.

Acute Disease↗
PubMed1983

Clinical correlates of circulating immune complex levels in advanced lung cancer. A discrimination analysis.

Sera from 53 patients with unresectable lung cancer were tested for the presence of immune complexes by 12 assays. 5 assays (EA rosette inhibition, ADCC inhibition, platelet aggregation, IgG and C3 concentrations in PEG precipitates) could discriminate cancer patients from healthy subjects with over 80% reliability. On the basis of 3 assays (EA-I, ADCC-I and PEG-C3) a function allowing a 100% correct classification could be formulated:--(EA-I)--0.5 (ADCC-I) + 2.4 (PEG-C3) greater than 69.3, i.e., results higher than 69.3 are characteristic for cancer patients and lower than 69.3 for normal subjects. The relationship between the immune complex levels and the average survival time was not altered by sex, age, histology and treatment. None of the immune complex assays or their combination were useful for the estimation of individual life expectation.

Adult↗
PubMed1983

C3b acceptors on human peripheral blood mononuclear cells; characterization and functional role.

C3b acceptors (C3bAs) of human peripheral blood mononuclear cells (PBMC) reacting with the labile binding site of nascent C3b(C3bx) have been investigated by the immune adherence (IA) test. In non-cellular systems some conventional chemical groups (OH-, NH-2) have been reported to be the target of the covalent binding of C3bx. Thus it should be assumed that every cell can fix C3bx via its labile binding site and C3bAs are barely saturable. Contrary to this expectation, however, normal human PBMC were found to be heterogeneous from this point of view, as 57 +/- 4% of B cells and 21 +/- 2% of Null cells possess C3bAs while T cells do not. C3bAs of human PBMC are saturable and trypsin-sensitive structures. The covalent nature of the C3bx-C3bA interaction has also been proved. Studying the effect of acceptor-bound C3b on the function of other cell-surface structures, the inhibition of the Fc gamma receptor function and the abolishment of the enhancement of pokeweed mitogen-stimulated blastogenesis by immune complexes were found.

Antigen-Antibody Complex↗