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Biomedical subjects

G Füst

Publications and source records attributed to G Füst.

At least 127 records · Page 7Linked to original sources

Safety aspects of intravenous immunoglobulins.

Seven commercially available intravenous immunoglobulins (IVIG) preparations, a gamma globulin prepared by ethanol fractionation, and an experimental IgG isolated by a chromatographic procedure were compared in several tests. Split products were present in preparations manufactured by procedures involving protease treatment and in a sulphitolysed IgG. The same preparations and another chemically modified product displayed a loss in their capacity to bind staphylococcal protein A. None of the preparations exerted a high anticomplementary activity using concentrated human serum as a complement source. No strict correlation between aggregate content and anticomplementary activity could be established. None of the commercial IVIG preparations tested displayed a sizeable hypotensive action as assessed by a rat model involving potentiation of bradykinin action by an angiotensin convertase inhibitor. The chromatographically purified IgG and an intramuscular IgG prepared by Rivanol fractionation contained high endogenous protease and prekallikrein activator (PKA) activity, respectively and both were found markedly hypotensive. Neither endogenous protease nor PKA activity was detected in the Cohngammaglobulin fraction. However, it was very strongly hypotensive even without any previous blocking of angiotensin convertase. Our data support the view that immunoglobulin preparations may affect blood pressure without inducing bradykinin generation.

Animals↗

Prevalence of HIV-antibodies in patients with haemophilia in Hungary.

Incidence of HIV antibodies have been studied in 617 patients with congenital bleeding disorders. Screening was performed with the Organon ELISA test, repeatedly positive samples were tested with four different confirmatory assays. HIV antibodies were found in 3/356 patients with haemophilia A, 21/114 patients with haemophilia B, 3/123 patients with von Willebrand disease and in 1/24 patients with other types of congenital coagulation disorders. All the 28 seropositive patients were treated with imported coagulation factor, mostly with factor IX concentrates. No patient treated exclusively with nationally produced factor preparations between 1981 and 1985 was found to be anti-HIV positive.

Acquired Immunodeficiency Syndrome↗

Screening of IgA deficiency by ELISA: population frequency in Hungary.

The probability of the development of an anaphylactic shock in IgA deficient patients following repeated blood transfusion or the administration of any other IgA containing preparation is high. Since these individuals usually show mild, if any, clinical symptoms, the detection of deficiency and/or sensitisation is very important. We have developed an ELISA system suitable for both the rapid mass screening of IgA deficiency and for the detection of anti-IgA already present in the serum. Applying these methods for screening of serum IgA deficiency in healthy Hungarian population resulted in a similar pattern to that reported for other countries. Interestingly, the prevalence of IgA deficiency among Gipsies living in Hungary was significantly higher. We could detect anti-IgA only in one of our IgA deficient patients.

Antibodies, Anti-Idiotypic↗

BSA-anti-BSA immune complexes formed in the presence of human complement do not bind to autologous red blood cells.

The binding of 125I-BSA-anti-BSA immune complexes (IC) formed in the presence of complement (nascent IC) and those that reacted with complement after their formation (preformed IC) to human erythrocytes was studied. The effect of antigen-antibody ratios and serum dilutions on IC binding to red blood cells (RBC) were also investigated. A dramatic difference was found between the behaviour of the two types of complexes: while preformed IC bound effectively to human RBC after their interaction with complement, no efficient RBC-binding was observed with nascent BSA-anti-BSA complexes formed in the presence of complement. Changing the antigen-antibody ratio or dilution of serum did not affect markedly the extent of difference between the binding of preformed and nascent IC. Our findings do not support the essential role of red blood cells in the elimination of each type of IC.

Animals↗

Enhancing effect of alpha-interferon on the C2 synthesis by cultured human monocytes.

C2 synthesis by human peripheral blood monocytes cultured in the presence of human alpha-interferon (IFN-alpha) was studied. IFN-alpha was added in different amounts (1-1000 IU/ml) to the cultures on day 3 and was removed on day 7. As control, mock interferon (m-IFN) was also tested. C2 content of the culture supernatants was measured by immunohaemolytic method. IFN-alpha was found to enhance C2 synthesis in a dose-dependent way. The enhancing effect could be observed even after the removal of IFN-alpha. C2 production by the cultured monocytes was increased by m-IFN as well; the extent of enhancement however, was found to be significantly lower than that induced by the corresponding amount of IFN-alpha. In contrast to the enhancing effect on C2 production, IFN-alpha did not influence total protein synthesis in the cultures, suggesting a selective stimulatory action on the C2 gene.

Biological Assay↗

C1 and C4 abnormalities in chronic lymphocytic leukaemia and their significance.

Clinical and laboratory correlations of low C1 and C4 levels previously found to be a characteristic feature of chronic lymphocytic leukaemia (CLL) were analysed. Abnormalities of C4 were restricted to stage 1, 2 and 3 of CLL, whereas in the more advanced disease (stage 4) only low C1 levels were found. It was demonstrated that the observed disorders were associated with an increased susceptibility of the patients for infections and impair the immune complex precipitation inhibiting capacity of the patients' sera as well.

Antigen-Antibody Complex↗

A simple method for detecting HIV antibodies hidden in circulating immune complexes.

A method previously used for studying the specificity of antibody components of circulating immune complexes in different diseases has been applied to analyse circulating immune complexes in HIV-infected patients. Antibodies against HIV antigens hidden in circulating immune complexes were studied in 14 sera from 13 patients with asymptomatic HIV infection (group 1) and in 11 sera from seven patients with HIV symptoms (group 2). HIV antigen-coated wells from the Vironostika kit as well as core and envelope antigen-coated beads from the Abbott confirmatory kit were used as solid-phase antigen. Using the Vironostika plates, HIV antibodies were demonstrated in circulating immune complexes in three and five sera in groups 1 and 2, respectively. Anti-core antibodies hidden in circulating immune complexes were present in three out of eight and two out of nine sera, respectively, in groups 1 and 2, whereas anti-envelope antibodies were present in circulating immune complexes in one out of eight and six out of nine sera in the same groups. These findings demonstrate that not only core-anti-core but also envelope-anti-envelope immune complexes are present in the sera of HIV infected patients.

Acquired Immunodeficiency Syndrome↗

Study of the immune complex precipitation-inhibiting capacity of sera of patients with chronic lymphocytic leukaemia.

Two procedures measuring the capacity of different sera to prevent the precipitation of nascent immune complexes were compared: a kinetic method with a constant immune complex/serum ratio and a new procedure--the increasing immune complex load method--using different immune complex/serum ratios. Immune complex precipitation inhibition is known to depend on complement. The sera of 25 patients with chronic lymphocytic leukaemia (CLL) and the sera of nine healthy blood donors were compared with the two procedures. The kinetic method discriminated poorly between the patients' sera and the control sera, whereas the increasing immune complex load method showed a highly significant difference between the two groups. Sera with low C4 level had the lowest immune complex precipitation-inhibiting activity. Interestingly, however, in the increasing immune complex load method not only hypocomplementaemic but also normocomplementaemic sera from CLL patients were found to be markedly defective. This finding suggests that the CLL patients' sera contain a factor which modulates complement-dependent inhibition of immune complexes.

Antigen-Antibody Complex↗

Repressed classical complement pathway activities and clinical correlations 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 137 serum samples of 69 patients with chronic lymphocytic leukaemia (CLL). In most sera IgG, IgA and IgM concentrations were determined as well. Clinical correlations of these laboratory parameters have been studied. C1 and C4 activities were found to be depressed in almost 50% of the sera tested, and hypogammaglobulinaemia was observed with a similar frequency. Low C1 and C4 levels were found mainly in the early stages of the disease. A strong association between the occurrence of infections and hypogammaglobulinaemia was observed, although low immunoglobulin levels frequently occurred in patients without a history of infections. Low C1 and C4 levels were significantly correlated with the incidence of infections, too, and this correlation was observed mostly in the early stages of the disease. The reason for this is not known. The present results suggest that not only low immunoglobulin levels but low C1 and/or C4 levels may contribute to the increased susceptibility to infections in patients with chronic lymphocytic leukaemia.

Complement Activation↗

Occurrence of anti-low density lipoprotein antibodies and circulating immune complexes in aged subjects.

The incidence of circulating immune complexes, anti-low density lipoprotein (LDL) autoantibodies and the anti-LDL activity of immune complexes was studied in healthy young and aged controls and in patients with vascular diseases. Circulating immune complexes (CIC) frequently occurred both in the young or old patient groups and in the aged healthy control groups, whereas they could not be found in the young controls. Marked differences were found in the incidence of anti-LDL antibodies between the groups tested. In both young and aged control groups such antibodies were very rarely observed (4-5%). In contrast anti-LDL antibodies were present in 35-45% in the aged, or young patients. Similarly, no anti-LDL activity was found in CIC of the controls, whereas in the patients with vascular diseases a significant CIC-associated anti-LDL activity was detected. These results suggest that the presence of anti-LDL antibodies are associated with the arteriosclerotic manifestations, while that of circulating immune complexes is connected by the ageing process itself.

Adult↗

Immunological alterations in anti-HTLV-III negative haemophiliacs and homosexual men in Hungary.

Hungary can be considered as a low risk area for AIDS since no patient with full-blown AIDS or AIDS-related complex has been found in the country. A complex clinical and immunological (T cell subsets, DNCB sensitization test, circulating immune complexes, acid-labile alpha interferon) investigation was performed between November, 1983 and June, 1984 in order to study whether alterations found in symptom-free homosexuals and haemophiliacs in the risk areas for AIDS can be observed in Hungary as well. 38 patients with mild haemophilia, 35 patients with severe haemophilia and 40 homosexual men were investigated in parallel to 37 heterosexual blood donors as controls. Anti-HTLV-III antibodies were measured later in the stored serum aliquots from the same subjects by the indirect membrane immunofluorescence assay. Although specific anti-HTLV-III antibodies were not detected in the haemophiliacs or homosexuals, immunological alterations characteristic for the members of AIDS risk groups in the high risk areas (decrease in the percentage of OKT4 cells and/or decrease of the OKT4/8 ratio) were found in one-third of the homosexuals and haemophiliacs tested. In addition, a significant part of these subjects did not develop delayed type hypersensitivity skin reaction on DNCB rechallenge. These findings indicate that an immunodeficiency independent of HTLV-III infection can be present in two major AIDS risk groups, in homosexual men and haemophiliacs.

Acquired Immunodeficiency Syndrome↗

Autoimmunity and normal immune functions in aged humans.

The high frequency of ANA, A-LDL and RF in advanced age suggests that AABs are present in the majority of aged subjects. CIC incidence determined by three methods is far below AAB incidence; only the Clq solubility test suggests an increased CIC incidence in aged as compared to young subjects. Simultaneous occurrence of AABs of different specificities or CIC determined by two or three methods is rare and both AAB and CIC levels are usually low. AAB prevalence in CIC-positive individuals seems to depend on the specificity of the AAB. CIC positivity is associated with relatively low Clq concentrations; however, usually not with Clq concentrations below the normal range. Neither ANA nor CIC positivity seems to correlate with DNA synthetic response to PHA, but ANA positivity may be associated with low responses to allogeneic cells. ANA positivity and, to a lesser extent, CIC positivity seems to be connected with enhanced killer cell activity. The concept of some AABs and CIC as autoregulatory factors of the humoral immune system compensating for the thymus-dependent regulation in old age is stressed.

Aged↗

Non-covalently bound C3 enhances lysis of rabbit erythrocytes through the alternative pathway.

Rabbit red blood cells (RaRBC, 3 x 10(7)/ml PBS) were incubated with different amounts of purified human C3 at 37 degrees for 30 min and washed twice in PBS. Different amounts of normal human serum containing 2 mM Mg2+ and 5 mM EGTA were added to the C3-treated and control RaRBC. The extent of lysis was measured after a further incubation at 37 degrees for 40 min. Enhanced lysis was observed with C3-treated RaRBC as compared to control cells. The enhancing effect was dependent on the dose of C3 used for the treatment of RaRBC. Investigation the kinetics of lysis, the lag phase was observed to be significantly shorter with the C3-treated than with the control RaRBC. No enhancement was found when RaRBC were pretreated with preformed C3b fragment. KSCN-treated C3 (C3b-like C3), however, had a lysis-enhancing effect. These results suggest that noncovalently bound C3 molecules may have a role in the initiation and/or maintenance of the alternative pathway activation on activator cells.

Animals↗