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Biomedical subjects

E Apostoloff

Publications and source records attributed to E Apostoloff.

At least 19 recordsLinked to original sources

Detection of autoantibodies to Ro(SS-A), La(SS-B) and U1RNP in different congenital heart rhythm disorders using immunoblot and enzyme immunoassay.

The aim of the study was to determine if autoantibodies have distinctive qualitative or quantitative characteristics in children with congenital heart rhythm disorders compared to unaffected infants. Sera of fifty-three infants with different heart rhythm disorders and eight unaffected children born to SLE mothers were tested for antibodies to Ro(SS-A), La(SS-B) and U1RNP (including recombinant A-, C-, 68 kD-proteins) using enzyme immunoassays and immunoblot. 21 sera from affected and 8 sera from healthy children reacted in counter-immunoelectrophoresis with Ro(SS-A). 8/8 infants with third degree atrioventricular (AV)-block, 4/8 with first degree AV-block, one with sinusbradyarrhythmia (SB) and another with SB/first degree AV-block were anti-52 kD Ro(SS-A) positive compared to 7/8 healthy infants. Infants with third degree AV-block had significantly higher anti-52 kD Ro(SS-A) levels than those with the milder heart rhythm disorders (P < 0.01) and the healthy group (P < 0.002). Anti-La(SS-B) antibodies were detected significantly (P < 0.01) and in significantly higher titres (P < 0.01) in AV III than in other types of congenital heart block. Anti-U1RNP-68 kD antibodies were positive in 3/8 healthy, 2/8 first degree AV-block and in 1/8 third degree AV-block cases. Third degree AV-block was more frequently found in female infants (P < 0.05). It was concluded that the influence of antibody levels to the 52 kD Ro(SS-A) and La(SS-B) components and the association of anti-52 kD Ro(SS-A), La(SS-B) and -60 kD Ro(SS-A) antibodies, as well as the sex, on the severity of congenital AV-conduction defects suggests involvement of these factors in the pathogenesis of these disorders.

Adult

[Multiple myeloma with antinuclear antibodies. Its course during cytostatic therapy].

A 56-year-old man complained of general malaise, diffuse bone pain, nocturnal sweating, lack of appetite and weight loss (7 kg within one year). Pain in the pelvic and lumbar regions markedly impaired movement. Roentgenologically, multiple lucencies were visualised in many skeletal areas. Examination of the bone marrow revealed an increase in the proportion of atypical plasma cells to 40%. The IgG concentration was 29.8 milligrams, mainly monoclonal immunoglobulins of the IgG-kappa type, which reacted against nuclear antigens (68-kD-U1-RNP nuclear protein) with a 1:2,000 titre. The symptoms markedly regressed under cyclical combined therapy with three times 5 mg melphalan daily for 4 days and 100 mg prednisolone daily for 7 days (a total of 24 cycles). At the same time the IgG concentration and the autoantibody titre decreased markedly and the patient became symptom-free.

Antibodies, Antinuclear

Investigations into Ro-specific antibody-associated congenital cardiac conduction defects.

Forty-two babies with different congenital cardiac conduction defects, and in 12 cases the mothers, were tested for autoantibodies to Ro, La, U1RNP and Sm. Ro-specific antibodies were detected most frequently. They were to be found in 16 sera from infants and in 8 maternal serum samples. The occurrence of anti-Ro was associated preferentially with several atrioventricular conduction blocks. The sex relation of anti-Ro associated congenital heart block did not show a typical preference (6 male/10 female). At the time of giving birth, 5 anti-Ro-positive mothers did not have any clinical symptoms of rheumatic autoimmune diseases. Three of them had a first degree atrioventricular block. Our findings indicate that all pregnant women at risk for anti-Ro like connective tissue disease or cardiac conduction defects should be tested for these autoantibodies because of the suspicion of cardiac conduction abnormalities in the offspring. Anti-Ro-positive infants should be examined for structural heart disease by echocardiography.

Antibodies, Antinuclear

[Relation between 67-gallium scintigraphy and bronchoalveolar lavage--differential cell count and superoxide anion liberation--in patients with systemic scleroderma and systemic lupus erythematosus].

The aim of the study was to determine the pulmonary 67-gallium uptake, bronchoalveolar lavage (BAL) cell differentiation and the activity of BAL cells, measured as release of superoxide anion (O2-), and to investigate the results whether there are relations. In 11 nonsmoking systemic scleroderma (SS) patients and 11 systemic lupus erythematosus (SLE) patients with lung involvement double-sided BAL were performed, mainly in regions with increased 67-gallium uptake. Release of O2- was measured by INT-assey. BAL cell differentiation was in SS and SLE pathological in 68.2% without side-difference. In contrast to SS, O2(-)-release in SLE depends on BAL cell differentiation and is most increased in normal BAL cell differentiation. There is no correlation between 67-gallium uptake and both BAL cell differentiation and O2(-)-release. The results suggest, that in contrast to SS, BAL cells in SLE with pathological differentiation are less activated than BAL cells with normal differentiation probable due to autoimmunological factors. Pulmonary 67-gallium scan and BAL seem to be independent from each other.

Adult

Development of a solid phase enzyme immunoassay for the detection of anti-Ro autoantibodies.

An enzyme immunoassay was developed to detect anti-Ro(SS-A) autoantibodies. Both Ro-antigen components (52 and 60 kD) were purified from a pig spleen extract, using fast protein liquid chromatography (FPLC). Anti-La, anti-RNP, anti-DNA and anti-Sm antibodies do not react to the purified antigen. There was a strong correlation between anti-Ro activity in EIA and the titers in counter immunoelectrophoresis (rs = 0.893). Anti-Ro antibodies were found in 54 (69.2%) of 78 SLE sera by the developed EIA.

Animals

Heterogeneity of RNP and Sm autoantigens in relation to the cell sources and the activated state of the cells.

The extracts of rabbit thymus (RTE), HeLa cells, human histiocytic lymphoma cell line U-937, human promyelocytic cell line HL-60, Ehrlich ascites tumor cells (EACs), and peripheral white blood cells (WBCs) were tested for their composition, molecular weight, and amount of Sm and RNP autoantigens on immunoblotting. The molecular weight of the so-called 68 kDa U1 RNP antigen, which is associated with mixed connective tissue disease (MCTD), was 64.5 kDa in RTE, 62.5 kDa in HeLa cells and HL-60 cells, and 59 kDa in WBCs. Surprisingly, in both WBCs and U-937 cells, the main protein band bearing the 68 kDa U1 RNP antigenic determinants was 30.5 kDa in molecular weight, which was confirmed using antibodies purified by affinity chromatography. After stimulation with phytohemagglutinin (PHA), there was in the human lymphocytes a diminished amount of the 30.5 kDa protein and simultaneously an increased synthesis of several proteins of higher molecular weight, especially the 57 kDa protein bearing the 68 kDa antigenic determinants. The concentrations of the A, B/B', C, D, and E proteins also increased with PHA stimulation. Our results indicate that the expression of Sm and RNP autoantigens may depend on the cell source as well as the activated state of cells. These differences should be taken into consideration in the detection of anti-RNP and anti-Sm antibodies by immunoblotting.

Animals

Binding of C1q and DNA to support materials by means of a new coupling procedure.

Since several years matrix-bound biologically active substances are widely used in biosciences, biotechnology and medicine. We are presenting a simple and inexpensive activation procedure for support materials which allows stable binding of C1q and DNA. We could not found a remarkable leakage of the bound ligands. In connection with the good biocompatibility of our procedure, both are important for the application in extracorporeal immunoadsorption. The method is technologically simple and represents an alternative to the activation methods applied so far.

Biocompatible Materials

Development of a DNA-adsorbent for the specific removal of anti-DNA autoantibodies in systemic lupus erythematosus (SLE).

Autoantibodies against DNA are of primary importance for the diagnosis and pathogenesis of systemic lupus erythematousus (SLE). The level of anti-DNA antibodies correlates well with the disease activity and renal involvement. In such patients the removal of anti-DNA antibodies from plasma may lead to a clinical improvement. For this reason an adsorbent was made by covalent coupling of calf thymus DNA to a solid support based on ethylene dimethacrylate cross-linked hydroxethyl methacrylate. Up to 2.5 mg of DNA were immobolized to 1 ml of the support activated chemically by aminosilane and glutaraldehyde. The incubation of 40 ml of SLE plasma with 1 ml of the adsorbent resulted in a 50% decline in anti-DNA activity. There was no release of immobilized P-32-DNA into the plasma. Biocompatibility, sterilisation, and reapplication (without loss of binding capacity) of the adsorbent could be demonstrated. We concluded that the adsorbent may be suitable for treatment.

Autoantibodies

Development of a C1q-adsorbent for the selective removal of circulating immune complexes.

In body fluids circulating immune complexes possess a substantial pathogenic effect on a variety of diseases. Thus it seems to be reasonable to influence the pathogenic mechanism of such diseases by removing the circulating immune complexes out of the body fluids. The selective adsorbent for binding immune complexes were developed as possible alternative of plasmapheresis for specific removal of immune complexes out of the blood plasma. The principle is based on the biospecific binding of immune complexes to C1q that is immobilized by a covalent binding to different solid phases. Thus: so bound immune complexes can be separated by detaching the solid phases. The adsorbent may be regenerated by non-denaturated media and can be used manyfold. This adsorbent has a high biocompatibility and offers the possibility for clinical use.

Antigen-Antibody Complex

[Antibodies to anticoagulants in rheumatic autoimmune diseases].

The systemic lupus erythematosus (SLE) and the rheumatoid arthritis (RA) as the classic autoimmune diseases exhibit a great number of autoantibodies. Some of them are anticoagulants. Besides inactivating inhibitors against single coagulation factors interfering anticoagulants are known, belonging to the group of anti-phospholipid antibodies and detected as the lupus anticoagulants or anticardiolipin antibodies. Anti-phospholipid antibodies 184 patients with SLE or RA had been checked for. An enzyme immuno assay was used for detection of the anti-cardiolipin antibodies. The relations between occurrence of the anti-cardiolipin antibodies and vascular processes as well as other immunologic parameters had been tested for clinical relevancy.

Adult

[Chemiluminescence measurements of bronchoalveolar lavage cells in patients with collagenosis].

The purpose of the study was to determine the role of reactive oxygen metabolites in the pathogenesis of interstitial lung involvement in 13 patients with collagen vascular diseases (CVD) in comparison with 10 control subjects. The cellular activity of bronchoalveolar lavage (BAL) cells was measured by means of chemiluminescence (CL), spontaneously and after challenge of the cells with opsonized zymosan (simultaneously luminol- and lucigenin-dependent). The findings show an increase of the spontaneous and stimulated CL of BAL cells in CVD, more pronounced in luminol-dependent CL. The luminol-dependent CL correlates with neutrophils in BAL cell differentiation. The results suggest that reactive oxygen metabolites take part in interstitial lung involvement in patients with CVD. Therefore the measurement CL of BAL cells is useful in addition to BAL cell differentiation in diagnostic of interstitial lung involvement in CVD.

Bronchoalveolar Lavage Fluid

[Circulating immune complexes in patients with mouth mucosa carcinoma].

In 76 patients with untreated, advanced carcinomas of the oro-facial region the immune complex titer in the serum was determined by the C1q binding test. The determination of the immune complexes, accompanying the therapy, was carried out before onset of therapy and after surgical, combined radiosurgical and radiation therapy respectively. Immune complex values did not differ significantly before and after therapy and were of no value regarding the evaluation of the effectiveness of therapeutic measures.

Antigen-Antibody Complex

A myelopeptide from unstimulated bone marrow cells with immunomodulatory activity in lymphocyte cultures from healthy donors and patients with hypogammaglobulinemia and active lupus erythematosus.

A myelopeptide (SAP) was derived from culture supernatants of unstimulated animal bone marrow. SAP consists of a group of peptides with a molecular weight of about 2000 D, having a broad variety of biological activities. Testing immunoregulatory properties of the purified factor Petrov, Mickhailova & Zacharova [(1971). Immunoglobin synthesis in syngenic cells of different lymphoid tissues. J. Immun., 106 1086-1089] found enhanced antibody production in mice (SAP-stimulator of antibody production). We show here that the substance could induce expression of activation markers on human lymphocytes (4F2, HLA-class II antigens, thermostable SE rosette formation) and potentiate their appearance in combination with mitogens (PWM, PHA, Con A). Although SAP was not mitogenic for itself, it enhanced lectin-induced 3H-thymidine incorporation and T-cell-dependent B-cell differentiation in a dose-dependent manner. The factor was able to reconstitute disturbed PWM-driven Ig synthesis in lymphocyte cultures derived from two patients with hypogammaglobulinemia and a healthy non-responder to PWM. On the other side, SAP potentiated the inhibitory activity of PWM on elevated spontaneous IgG secretion in cultures derived from patients with active SLE. Findings of this study indicate immunomodulatory capacity of SAP on human peripheral blood lymphocytes possible via T-cell activation. The results suggest a potential therapeutic application of SAP in patients with disturbances in the T-dependent B-cell differentiation.

Agammaglobulinemia