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Biomedical subjects

S Aotsuka

Publications and source records attributed to S Aotsuka.

At least 55 records · Page 3Linked to original sources

Selective removal of anti-DNA and anticardiolipin antibodies by adsorbent plasmapheresis using dextran sulfate columns in patients with systemic lupus erythematosus.

The effect of adsorbent plasmapheresis using dextran sulfate columns on anti-DNA and/or anticardiolipin antibodies (aCL) in 6 patients with systemic lupus erythematosus (SLE) was studied by multicenter clinical trials. The titers of anti-DNA (RI assay), IgG anti-dsDNA (ELISA), IgG and/or IgM anti-ssDNA, (ELISA), and IgG aCL (ELISA) significantly decreased or normalized after 4 treatments of plasmapheresis during a 2 to 4 week period. A patient with SLE with recurrent abortion and aCL who was successfully treated by adsorbent plasmapheresis is reported. We expect that adsorbent plasmapheresis will be an influential treatment for patients with not only SLE but aCL syndrome.

Adsorption↗

Cross-reactive rheumatoid factors in rheumatoid arthritis with extra-articular disease.

Rheumatoid factors (RF) have been shown to have considerable heterogeneity and bind with IgG as well as with a variety of substances such as nuclear histone, non-histone nuclear protein, nitrophenyl groups or ssDNA. We describe evidence that polyclonal RF cross-reactive with ssDNA (CRRF) are widely distributed in a variety of rheumatic diseases, and that their serum level is significantly higher in rheumatoid arthritis (RA) with extra-articular disease. Although the mechanism of the cross-reactivity is not clear, the presence of CRRF could be a serological feature of a clinical subset of RA. The high prevalence rate of CRRF in RA with extra-articular disease also suggests its pathogenetic role in the extra-articular manifestation of this disease.

Antibodies, Antinuclear↗

Adsorption of anti-dsDNA antibodies by immobilized polyanionic compounds.

Antibodies to dsDNA are characteristically present in serum from patients with systemic lupus erythematosus (SLE), and have been shown to have the capacity to react with various molecules bearing repeating negative charges. After a number of polymeric or monomeric molecules with differently charged groups and hydrophobic molecules had been coupled covalently as ligands on cellulose gel, the adsorption capacities of the ligands for anti-dsDNA antibodies were evaluated. It was found that gels coupled with polyanionic dextran sulphate (DXS) and polyacrylic acid (PA) and monoanionic sulphanilic acid (SA) absorbed anti-dsDNA antibodies effectively. DXS gel also adsorbed antibodies to ssDNA and heparan sulphate, antigens with repeating negatively charged moieties, while no ligand was able to adsorb anti-nRNP antibodies. The finding that DXS gels adsorbed anti-dsDNA antibody in proportion to their charge density, and that the interaction between anti-dsDNA and DXS gel is broken readily by an increase in ionic strength, indicated that the binding is ionic in nature. Moreover, virtually all F(ab')2 anti-dsDNA became adsorbed onto the DXS gels, suggesting that the binding occurred via specific antigen-binding sites on the antibody molecule. Binding of these polyanion-binding autoantibodies with anionic sites in the glomerular basement membrane may therefore cause the tissue damage observed in SLE.

Adsorption↗

[A case of sarcoidosis demonstrating spontaneous production of interleukin-1 alpha and beta by alveolar macrophage].

A 44-year-old man was admitted for evaluation of dyspnea on exertion and subcutaneous nodules. The chest X-ray on admission revealed bilateral hilar lymph node swelling and diffuse micronodular shadows throughout both lung fields. Ga scintigram demonstrated diffuse abnormal uptake. Serum angiotensin converting enzyme was elevated significantly (86.6 IU/I). The TBLB specimen confirmed the diagnosis of sarcoidosis. The cell numbers in bronchoalveolar lavage fluid was increased (4.4 x 10(8), the percentage of lymphocytes was elevated (64%) and the ratio of Leu 3a+/Leu 2a+ was very high (16.07). We further evaluated the spontaneous IL-1 release in vitro by alveolar macrophages obtained by bronchoalveolar lavage. The results showed that large amounts of IL-1 alpha and beta were produced spontaneously by alveolar macrophages before therapy, followed by a decrease in production after corticosteroid treatment. Previously, the authors reported that no significant amount of IL-1 alpha and beta was detected in 5 normal volunteers and 6 other active sarcoidosis cases which improved without therapy. Therefore, significant amounts of spontaneous release of IL-1 alpha and beta in vitro from alveolar macrophages in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment.

Adult↗

[Spontaneous production of interleukin-1 alpha and beta by alveolar cells from patients with sarcoidosis].

The spontaneous production of interleukin-1 alpha and beta by alveolar cells obtained by BAL from 7 active pulmonary sarcoidosis and 5 normal volunteers was evaluated. The activity of disease in one case was considered to be highly active because of the chest X-ray pattern (diffuse micronodular shadows), highly intense Ga up take in lungs, increased number of BAL cells and high level of S-ACE. The contents of IL-1 alpha and beta were measured by ELISA in the culture supernatants of alveolar cells after 24 hours culture without any stimulus. Large amounts of IL-1 alpha and beta production were found in highly active case. No significant amount of IL-1 alpha and beta, however, was detected in 6 other active sarcoidosis cases and 5 normal volunteers. Therefore, spontaneous release of IL-1 alpha and beta in vitro from alveolar cells in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment and its relationship to the spontaneous remission of sarcoidosis in Japanese patients was discussed.

Bronchoalveolar Lavage Fluid↗

Selective removal of anti-double-stranded DNA antibodies by immunoadsorption with dextran sulphate in a patient with systemic lupus erythematosus.

A dextran sulphate gel column removed anti-double-stranded DNA antibodies (anti-dsDNA) selectively, efficiently, and safely from the circulation of a patient with systemic lupus erythematosus (SLE). The mechanism of the removal is thought to be due to cross reactivity of anti-dsDNA with dextran sulphate, which has negatively charged units. Selective removal of anti-dsDNA is expected to contribute not only to the treatment but also to elucidation of the pathogenesis of SLE.

Adult↗

Lack of association of HLA-DR4 with interleukin 1 beta secretion from peripheral blood monocytes in patients with rheumatoid arthritis.

The possible association between HLA-DR4 and interleukin 1 beta (IL-1 beta) secretion from peripheral blood monocytes was analyzed using 34 female patients, with definite rheumatoid arthritis (RA). RA monocytes in serum-free medium or medium supplemented with 10% fetal calf serum secreted IL-1 spontaneously. The level of secretion was enhanced by stimulation with pyrogen-free type II collagen as determined by comparison with 30 healthy individuals matched for age and sex. No association between HLA-DR4 and spontaneous or stimulated IL-1 release from RA monocytes was observed.

Adult↗

Monocyte-mediated suppression of anti-DNA antibody production in healthy subjects.

Monocyte-depleted mononuclear cells (MNC) from healthy subjects synthesized IgM-class antibody to single-stranded DNA (anti-ssDNA) at significantly higher levels than unfractionated MNC. The increased production of IgM anti-ssDNA by monocyte-depleted normal MNC was inhibited to a greater degree than total IgM by addition of supernatants from autologous monocytes. Moreover, supernatants obtained from normal monocytes cultured with indomethacin retained this suppressive effect on IgM anti-ssDNA antibody production, suggesting that prostaglandin E2 may not be involved in the suppression. These results indicate that B cells programmed to produce IgM anti-ssDNA are present in the normal B cell repertoire, but may be suppressed by monocytes or by a soluble factor (or factors) from the monocytes.

Antibodies, Antinuclear↗

Monocyte-mediated suppression of rheumatoid factor production in normal subjects.

The regulatory role of normal monocytes in the production of rheumatoid factor (RF) was investigated. Monocyte depletion from normal mononuclear cells (MNC) resulted in an elaboration of IgM RF in 18 of 20 subjects. The increased RF production was inhibited by the addition to the cultures of adherent cells or their culture supernatants. These observations demonstrate the suppressive role of normal monocytes in the production of RF. Supernatants obtained from normal monocytes cultured with indomethacin could suppress the RF production, suggesting that prostaglandin E2 may not be involved in the regulation of IgM RF production.

Biological Products↗

Analysis of negatively charged dye-binding antibodies reactive with double-stranded DNA and heparan sulfate in serum from patients with rheumatic diseases.

Antibodies to double-stranded (ds) DNA are characteristically present in serum from patients with systemic lupus erythematosus (SLE). Recently, anti-dsDNA antibodies have been shown to have the capacity to react with a diversity of molecules with repeating negative charges. Using the anionic dye Cibacron blue F3GA, bound to crosslinked agarose, we analysed the nature of antibodies capable of reacting with this dye in serum samples from patients with various rheumatic diseases. The dye-antibody complex could easily be split by eluting with solutions of increasing ionic strength, suggesting that the interaction is ionic in nature. Pepsin-digested F(ab')2 antibodies retained the capacity to bind Cibacron blue, confirming that the binding occurred via antigen-binding sites on the antibody molecule. The eluates obtained from dye-ligand chromatography of active SLE sera contained antibodies to both dsDNA and heparan sulfate, while those of sera from patients with other non-SLE rheumatic diseases contained antibodies only against heparan sulfate. Furthermore, the dye-ligand eluates of sera from patients with active SLE and other non-SLE rheumatic diseases were found to contain increased amounts of IgG. In one patient with SLE, levels of antibodies to dsDNA and heparan sulfate, and the amounts of total IgG in dye-ligand eluates, were shown to be correlated with disease activity.

Antibodies, Antinuclear↗

Nephritogenic glycoprotein. XI. Comparison of humoral immune responses in rats injected with nephritogenoside and those given Heymann antigen.

A single footpad injection of a triglycosyl glycopeptide (nephritogenoside, NG) isolated from rat glomerular basement membrane can induce proliferative glomerulonephritis (PGN) in homologous animals, resulting in contracted kidney. On the other hand, it is well known that administration of rat tubular brush border antigen (Fx1A) causes a membranous glomerulonephritis (MG) in homologous animals. When a partially purified NG (crude NG, cNG) is injected in rats, a mixed lesion of PGN and MG resulted. To investigate the correlation between renal glomerular lesions and humoral immune responses in animals given NG and cNG, levels of antibodies to cNG and Fx1A, and those of immune complexes (ICs) are measured in sera from animals of these experimental groups using enzyme-linked immunosorbent assay. Significant levels of antibodies to cNG and Fx1A and those of ICs are detected in all groups of rats injected with cNG, Fx1A and pronase-digested Fx1A. It was revealed that antibodies to cNG in sera from rats injected with cNG, Fx1A and pronase-digested Fx1A recognize the common epitopes shared with Fx1A. On the other hand, neither antibodies nor ICs are detected in rats injected with NG, suggesting that humoral immune mechanisms may not play a leading role in the pathogenesis of NG-induced glomerulonephritis.

Animals↗

C1q solid-phase radioimmunoassay: evidence for detection of antibody directed against the collagen-like region of C1q in sera from patients with systemic lupus erythematosus.

In earlier studies we showed that the C1q-binding IgG in the sera from patients with systemic lupus erythematosus (SLE) tested by C1q solid-phase radioimmunoassay is cofractionated with monomeric IgG on gel filtration and mostly binds to C1q via the F(ab')2 region. In this study, we found that C1q, even when stripped of its immune complex-binding globular regions by pepsin digestion, retained a substantial part of its ability to bind IgG from SLE sera, suggesting that the collagen-like region of C1q is involved in binding to the SLE IgG. Heat-inactivation of C1q also failed to abolish its ability to bind IgG from SLE sera. In contrast, the binding of C1q to heat-aggregated IgG was completely abrogated by these treatments. In addition, the reaction of heat-aggregated IgG with the solid-phase C1q was markedly dependent on ionic strength whereas the binding of IgG from SLE sera with the solid-phase C1q persisted at high concentrations of salt. These findings suggest that the Clq-binding IgG in SLE sera is, at least in part, antibody directed against the collagen-like region of C1q.

Autoantibodies↗

C1q solid-phase radioimmunoassay: binding properties of solid-phase C1q and evidence that C1q-binding IgG complexes in systemic lupus erythematosus are not bound to endogenous C1q.

The binding properties of C1q solid-phase radioimmunoassay (C1q SPRIA) were examined, using heat-aggregated IgG (HAG) as the model of immune complexes (IC). The free, liquid-phase C1q, which was added to the C1q-coated tubes prior to the addition of HAG, had little inhibitory effect on binding of HAG to the solid-phase C1q, suggesting that the solid-phase C1q has a higher affinity for HAG than the liquid-phase C1q. On the other hand, more than 60% inhibition was seen when HAG was preincubated with the liquid-phase C1q. These binding properties of HAG to the solid-phase C1q in the presence of the liquid-phase C1q were not essentially altered by the heat inactivation or the addition of EDTA, suggesting that these pretreatments are not essential in C1q SPRIA. Next, in similar kinds of experiments, the binding properties of C1q-binding IgG complexes in SLE sera were investigated. In contrast to HAG, the binding capacity of IgG complexes in SLE sera to the solid-phase C1q was not inhibited by the preincubation with excess liquid-phase C1q. These findings suggest that C1q-binding IgG complexes in SLE sera detected by C1q SPRIA may not be bound to endogenous C1q in the circulation.

Antigen-Antibody Complex↗

Characterization of C1q-binding IgG complexes in systemic lupus erythematosus.

The molecular size of C1q-binding immunoglobulin (Ig) G complexes in systemic lupus erythematosus (SLE) sera was studied by gel filtration using C1q solid-phase radioimmunoassay (C1q SPRIA). All 15 SLE sera tested contained predominantly small-sized IgG complexes, cofractionating with monomeric IgG. In contrast to heat-aggregated IgG, these small-sized IgG complexes retained C1q-binding activity even after pepsin digestion, exposure to low pH, or reduction and alkylation, suggesting that the F(ab')2 region is involved in C1q-binding activity of these complexes. To see whether anti-C1q antibodies or small antigen-IgG complexes, which bind to C1q via their antigens, are responsible for C1q-binding activity via the F(ab')2 region, the pepsin-digested Ig fractions of SLE sera were fractionated at high salt. C1q-binding activity in the fractions corresponding to the F(ab')2 region increased 2.5- to 3.9-fold at high salt. These results suggest that the C1q-binding, small-sized IgG complexes may be comprised mostly of anti-C1q antibodies and that some of the antibodies, which are dissociated with their antigens at high salt, might be cross-reactive with C1q.

Adult↗

Heterogeneity of antilymphocyte antibody in SLE and its correlation with disease activity.

The cytotoxic activities of individual lupus sera were demonstrated against T gamma cells, T gamma (-) cells and B cells. Immunoglobulin classes were also determined in these antilymphocyte antibodies (ALA) in SLE. T gamma-specific ALA and B-cell-specific ALA were almost equally distributed as regards IgG-dominant type, mixed IgG and IgM type and IgM dominant type, while IgM dominant type was predominant in T gamma (-)-specific ALA. Only the IgG type of T gamma-specific ALA among these ALA was significantly associated with clinical parameters, including hypocomplementemia, elevated immune complex levels and high anti-double-stranded (ds) DNA titres. Serial studies on ALA in a typical case of SLE were performed. Active clinical signs were associated with elevated cytotoxicities of IgG type of T gamma-specific ALA and with relatively low cytotoxicities of the IgM type, whereas after massive corticosteroid therapy, these signs disappeared in tact with the reduction in cytotoxic activities of IgG type of the ALA and the relative rise in cytotoxicities of IgM type of the ALA. These results suggested that IgG class of T gamma-specific ALA seemed to play a major role among several types of ALA in SLE.

Antibodies, Antinuclear↗