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Biomedical subjects

G Füst

Publications and source records attributed to G Füst.

At least 163 records · Page 9Linked to original sources

Acquired C1-esterase inhibitor deficiency and recurrent herpes infection in a patient with chronic lymphocytic leukemia.

Profound hypocomplementemia was observed in a patient with chronic lymphocytic leukemia. On the basis of the results of complement measurements performed in nine serum samples taken in a period of 6 mo it was demonstrated that the patient had an acquired form of C1-esterase inhibitor deficiency: marked reduction of CH50, C1, C4, and C1-esterase inhibitor levels with normal alternative pathway, C3, and factor B activities were found. The patient had no typical attacks of angioneurotic edema; however, angioedema-like facial swelling was observed on several occasions in connection with recurrent severe herpes simplex eruptions. The possible association of the marked and long-lasting hypocomplementemia with the clinical course of the herpes infection is discussed.

Angioedema↗

Effect of angiotensin II on macrophage functions.

Angiotensin II (At II) has been shown to inhibit in vitro the IgG2a-mediated rosette formation of 51Cr-sheep red blood cells (SRBC) by provoked peritoneal macrophages (PM) at 10(-5)-10(-6) M concentrations. The decreased rosette formation was associated with an increased phagocytosis. It was found that the enhanced rosette formation at 10(-7) M hormone concentration was followed by diminished phagocytosis via Fc gamma receptors (R). Processes mediated through Fc microR were affected only after incubation with 10(-5) M of At II. The attachment and subsequent phagocytosis through C3bR was markedly enhanced by At II in a dose-dependent way. Thus, the relative phagocytosis (RP) through both FcRs was significantly enhanced by 10(-5), i.e. by 10(-5)-10(-6) M of At II, but lowered at 10(-7) M hormone concentration. In addition, there was no RP enhancing effect of At II after preincubation with 10(-5) M of indomethacin (IM), indicating the significance of prostaglandins (PG) in the hormone effect. The medium containing 5 mM of EGTA diminished both the RP enhancing and inhibiting effects of At II. The RP mediated by C3b was not affected by At II, IM or EGTA. The intracellular killing capability, measured by chromium release from Candida albicans, was not altered or even slightly diminished after At II treatment of PMs.

Angiotensin II↗

Complement-mediated fragmentation of soluble and insoluble immune complexes containing porcine anti-DNP antibodies.

Complement-mediated release of soluble immune complexes and immune precipitates containing DNP-PSA and precipitating or non-precipitating porcine anti-DNP antibodies was studied. A decrease in the average size of soluble immune complexes indicating their fragmentation was observed during incubation in excess human serum, the extent of the complex release was found to be in direct proportion to the time of incubation. The effect was complement-dependent. In the second part of the study, complement-dependent solubilization of the immune precipitates of the precipitating antibody preparation was compared to the solubilization of the precipitates of the non-precipitating antibody formed in the presence of PEG. Although, both types of precipitates activated complement in about the same extent, complexes of non-precipitating antibody were solubilized much slower than those of the precipitating one. As avidity of both antibody preparations to the antigen was high, the observed differences in the rate of the complex solubilization probably reflected differences in the structure of the two types of complexes.

Animals↗

Serial measurement of circulating immune complexes in healthy subjects.

Circulating immune complex (CIC) levels were serially studied in healthy subjects and in normal rats. In human 3 methods (Clq solubility, complement consumption, and granulocyte phagocytosis tests) were used for the measurement of CIC; in rats, CIC levels were determined by the modified complement consumption test. A marked fluctuation in the CIC level was observed both in healthy human subjects and in normal rats. No correlation between results of the 3 assays used for CIC detection was found indicating that not only the level but the composition of CIC changes continuously in health.

Animals↗

Circulating immune complexes in patients with IgA glomerulonephritis.

Fourty-four patients with IgA-glomerulonephritis (IgA GN) were studied for circulating immune complexes (IC) repeatedly in the course of disease on the evidence of four different methods suited for the detection of IC, viz. complement consumption assay, Clq-solubility test and two tests based on PEG-precipitation, and of indirect signs pointing to the presence of IC. Joint assessment of the direct and indirect signs (positivity of a minimum of 2 indirect signs or any of the direct signs) permitted to ascertain the presence of circulating IC in 72 per cent of the patients and in 63.3 per cent of the examined sera. There was no close relationship between the presence of IC and the clinical activity. On the other hand, in 16 patients positive for the rheumatoid factor (RF) the renal biopsy material revealed extensive vascular lesions. The findings suggest that the circulating IC, some of which contain RF, play a part in the pathomechanism of IgA GN and are involved in the production of the vascular abnormalities in this disease.

Adolescent↗

Immunogenicity of antigen complexed with antibody. I. Role of different isotypes.

IgM-, IgG1-, IgG2a-, IgG2b- and IgE-type anti-ovalbumin antibodies were isolated from rat immune sera and the complexes formed by antibodies of a defined isotype and the antigen were compared for antibody avidity and interaction with homologous complement. IgG2a-containing complexes consumed total complement with the greatest efficiency. IgG2a-, IgG2b- and IgM-containing complexes displayed similar activities in activation of the alternative pathway while IgG1 was less efficient. Reduction and alkylation of IgG2a antibodies abolished the capacity of the complex to activate the alternative pathway, but not their total complement consumption. The complement-dependent solubilization was greatest when complexes contained IgG1- or IgM-type antibodies and lowest with IgG2a-containing complexes. Inbred Long Evans rats immunized by complexes containing IgG1 or IgG2b antibodies displayed a markedly lower delayed-type hypersensitivity (DTH) compared with those immunized by antigen alone. Immunization with IgG2a- or IgE-containing complexes resulted in a slightly decreased DTH, while IgM-containing complexes induced DTH like ovalbumin alone. IgG2a-containing complexes elicited an antibody response markedly higher than that found in animals immunized by antigen alone. The same effect was found when complexes contained reduced-alkylated IgG2a. Immunization with complexes containing the other isotypes involved in the study induced an antibody response similar to the antigen in phosphate-buffered saline.

Alkylation↗

Effect of ionizing radiation on chemical and biological properties of Salmonella minnesota R595 lipopolysaccharide.

Lipopolysaccharide of the Salmonella minnesota Re mutant R595 was irradiated with 60Co gamma doses of 50, 100, 150 and 200 kGy. The irradiated preparations were less toxic, less active in the Shwartzman reaction and as activators of the complement system, but they had retained the protection activity against the lethal action of endotoxin. The irradiation resulted in a dose-dependent decrease in the amounts of constituents (glucosamine, KDO, fatty acids) of the original lipopolysaccharide. With increasing irradiation doses increasing amounts of the irradiated material became dialysable (up to 21% in the 200 kGy sample). Only 50% of total fatty acids were present in the 200 kGy preparation compared to the parent lipopolysaccharide. The degradation products formed during irradiation have not been identified.

Animals↗

Evaluation of different methods for detecting circulating immune complexes. Studies in patients with lung cancer.

In a collaborative study involving 7 laboratories, sera from 53 patients with lung cancer, 37 primary and 16 secondary tumours, and sera of 40 healthy blood donors were tested by 19 different assays or assay modifications used for detecting immune complexes. In 12 out of 19 assays, significantly higher immune complex levels were found in the cancer patients than in the healthy subjects. Assays based on interactions between immune complexes and Fc receptors of different cells (lymphocytes, macrophages of platelets) discriminated between cancer patients and health subjects and a high percentage (47-87%) of positivity was observed in such assays in patients with lung cancer. In contrast, none of the tests based on immune complex-complement interactions discriminated between cancer patients and health subjects. Immunochemical analyses of the PEG precipitates obtained from the sera tested revealed that the concentrations of IgG, IgA and C3 were significantly higher in the precipitates obtained from patients sera than from control sera, but no significant differences were seen in IgM and C1q concentrations. A 100% correct classification of individuals tested was obtained on discriminant analysis of results with 3 assays: EA rosette inhibition, ADCC inhibition and C3 concentration in PEG precipitates. Correlation between results obtained with individual sera by the different assays was very poor: significant correlation coefficients were found in only 13% of all possible paired comparisons. Our results suggest that Fc receptor-dependent assays are more suitable for detection and measurement of circulating immune complexes in lung cancer than tests based on interactions with complement.

Adenocarcinoma↗

Alpha-1-antitrypsin-induced inhibition of complement-dependent phagocytosis.

In a previous investigation, inhibition of complement-dependent rosette formation by alpha 1-antitrypsin (alpha 1-AT) was observed, and it was demonstrated that alpha 1-AT interacts through its carbohydrate portion with C3 and its fragments. In the present study, the effect of alpha 1-AT on the complement-receptor-mediated phagocytosis by human peripheral blood monocytes was examined. Purified alpha 1-AT inhibited in a dose-dependent manner phagocytosis of C3-carrying yeast particles. Inhibition was selective, concerned only C3-receptor-mediated phagocytosis, neither Fc-receptor-mediated phagocytosis nor uptake of untreated yeast particles was blocked by alpha 1-AT. It was demonstrated that alpha 1-AT towards C3 and fragments of C3 was not mediated by its antiprotease effect, but by its carbohydrate moiety. This finding suggests that alpha 1-AT may have an impact on various immune functions involving complement receptors.

Blood Donors↗

Serial measurement of circulating immune complexes in myocardial infarction.

To study the changes in the quantity of circulating immune complexes in myocardial infarction two serial investigations were performed in 45 and 63 patients, respectively. For the detection of circulating immune complexes in the first series, two methods, a complement consumption test and a Clq-solubility test were used. In the second series, a polyethylene glycol (PEG)-precipitation assay was added to these methods. The incidence of circulating immune complexes was studied on the first, third, seventh, 14th, and 21st day. On the first day the complexes were detected in 59% of the patients. Their occurrence increased in the further samplings to 77%, but from the seventh day their concentration decreased and on the 21st day they were detected in 63%. Three types of changes in the level of circulating immune complexes could be shown. In type I immune complexes were detected in the first days after the onset of the infarction, then, after a gradual decrease, the results became negative. In type II immune complexes appeared in the second to third week and their quantity did not alter during the entire observation period. In type III the circulating immune complexes could be detected throughout the whole period of the study. These changes in their concentration were frequently associated with the clinical course of the disease.

Adult↗

[Serial tests of the change in concentration of circulating immune complexes in healthy subjects and in tumor patients].

Authors performed by using various tests serial examinations of the circulating immune complex (IC) concentration in healthy persons, untreated rats, as well as in patients with multiple myeloma or leukemia, and in immunocytoma bearing rats. A characteristic fluctuation of the IC values has been observed in the untreated rats and the healthy persons. The discrepant IC values obtained in the identical sample with the different tests suggest the heterogeneity of IC components. As compared to healthy individuals a significantly higher fluctuation of IC values has been found characteristic in immunocytoma. Authors analyzed the composition of IC and discussed the possible importance of the tumor specific antigens and the natural antibodies reacting with them.

Animals↗

Plasmapheresis in patients with leukaemia, multiple myeloma and immune complex diseases.

Therapeutical partial plasma exchange was performed on 9 patients with acute leukaemia, 14 patients with monoclonal and polyclonal gammopathies and 3 with primarily immune complex disease. The procedure was effective in 21 out of the 27 courses performed on patients with gammopathies and in all cases of the primarily immune complex diseases. In acute leukaemic patients the course of the disease was favourably influenced by plasmapheresis. The results show that partial plasma exchange is an effective adjunct therapy in the treatment of patients with haematological diseases.

Acute Disease↗

Effect of soluble immune complexes of Fc and C3 receptor-dependent phagocytosis by human monocytes.

The capacity was studied of bovine serum albumin (BSA) rabbit anti-BSA and ovalbumin (OA) rabbit anti-OA immune complexes of different composition to inhibit the Fc receptor-dependent adherence and phagocytosis of sensitized sheep red blood cells by human monocytes. Parallel experiments were performed on the ability of the immune but complement-reacted complexes to inhibit the C3 receptor-dependent phagocytosis of C3-coated yeast particles. The extent of inhibition of both the Fc and C3 receptor-dependent phagocytosis was proportional to the antibody avidity of the complex used. Immune complexes made at equivalence and at moderate antibody excess markedly inhibited both types of phagocytosis, whereas those made at moderate antigen excess had only a weak inhibitory effect. These findings can be explained by the correlation between the Fc receptor-binding and complement-activating capacities of immune complexes of different composition. An alternative explanation, however, is also discussed.

Antigen-Antibody Complex↗

Classes and subclasses of rat antibodies: reaction with the antigen and interaction of the complex with the complement system.

Antibodies against the dinitroaminophenyl (DNAP) haptenic group were raised in outbred CFY rats using HSA or LPS as carrier. Antibodies isolated by immunoadsorbent techniques were resolved into fractions representing distinct isotypes, and the resulting fractions were tested for avidity. Subclass IgG2a was found to contain antibodies of an avidity index lower than those of other IgG subclasses or IgM. IgG2a was the only isotype detected when DNAP-LPS was used for immunization. Complexes containing defined isotypes were compared for their capacity to activate homologous complement. IgGl type antibody-containing complexes displayed a low complement activating capacity compared with those containing IgG2b, IgG2c or IgG2a. The latter subclass when complexed with antigen can thus induce complement-dependent processes in spite of a low avidity. Insoluble complexes of IgG antibodies were rapidly solubilized in rat serum (CRA phenomenon), except those containing predominantly IgG2c.

Animals↗