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S Minota

Publications and source records attributed to S Minota.

At least 73 records · Page 4Linked to original sources
PubMed1994

Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu's arteritis.

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of aortic tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the aortic tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the aortic tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the aortic tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.

Adult↗
PubMed1994

Antiendothelial cell antibodies and their relation to pulmonary hypertension in systemic lupus erythematosus.

OBJECTIVE: Antiendothelial cell antibodies (aECA) have been demonstrated in patients with systemic lupus erythematosus (SLE), but their role in the pathogenesis of this disease remains unclear. We investigated the association of aECA and anticardiolipin antibodies (aCL) with clinical and laboratory findings in patients with active SLE. METHODS: Sera from 28 patients with active SLE and 22 healthy controls were assayed for IgG and IgM-aECA by cellular ELISA method using cultured human umbilical vein endothelial cells and IgG-aCL by ELISA method. RESULTS: Serum titers of both IgG and IgM-aECA were significantly higher in active SLE than in healthy controls. Titers of IgG-aECA were unrelated to titers of IgG-aCL. Patients with pulmonary hypertension demonstrated a marked elevation of serum titer of both IgG and IgM-aECA compared with patients without pulmonary hypertension. In addition, patients with digital vasculitis showed a significant elevation of serum titer of both IgG and IgM-aECA compared with patients without digital vasculitis. Serum titers of IgG-aECA in patients with Raynaud's phenomenon and of IgM-aECA in patients with serositis were each significantly increased compared with patients without such findings. CONCLUSION: aECA were unrelated to aCL. Serum titers of aECA are elevated in patients with active SLE, especially with pulmonary hypertension, digital vasculitis, Raynaud's phenomenon or serositis. Since pulmonary hypertension in SLE has been associated with digital vasculitis, Raynaud's phenomenon and serositis, aECA may be involved in the pathogenesis of vascular injury, leading to these manifestations.

Antibodies, Anticardiolipin↗
PubMed1994

Expression of transforming growth factor-beta 1 and its relation to endomysial fibrosis in progressive muscular dystrophy.

Progressive muscular dystrophy is characterized by muscle fiber necrosis, regeneration, and endomysial fibrosis. Although absence of dystrophin has been known as the cause of muscle fiber degeneration, pathogenesis of interstitial fibrosis is still unknown. Transforming growth factor-beta 1 (TGF-beta 1) induces accumulation of extracellular matrix in various diseases, such as liver cirrhosis and interstitial pneumonitis. To investigate its function on the pathogenesis of progressive muscular dystrophy, it was necessary to determine the degree of TGF-beta 1 expression and the site of TGF-beta 1 immunoreactivity. In Duchenne muscular dystrophy and most of Becker muscular dystrophy, high TGF-beta 1 immunoreactivity expressed on muscle fibers and extracellular space. In other myopathies with endomysial fibrosis, however, TGF-beta 1 was seldom observed. We also examined the immunoreactivity of the latent TGF-beta binding protein, which is bound to the TGF-beta precursors. In all Duchenne muscular dystrophy and half of Becker muscular dystrophy cases, high latent TGF-beta 1 binding protein immunoreactivity was seen, but in other myopathies its immunoreactivity was seldom seen on muscle fibers or extracellular space. Therefore TGF-beta 1 may play an important role in synthesis and accumulation of extracellular matrix in progressive muscular dystrophy.

Animals↗
PubMed1993

Interrelationship between autoepitope, DNA-binding domain, and CRP-binding domain on a histone H1 molecule.

The interrelationship between autoepitopes, DNA-binding domains, and C-reactive protein (CRP)-binding domains on a histone H1 molecule was examined using fusion proteins of beta-galactosidase and truncated histone H1 molecules. At least two CRP-binding sites were detected on a histone H1 molecule. Site 1 was composed of approximately 25 amino acids and calcium ion was required for the binding of CRP. Site 2, composed of approximately 20 amino acids and not requiring calcium ion, was identical or located very close to a DNA-binding domain and an epitope of anti-histone H1 autoantibodies in SLE sera. These data suggest that, at physiological ionic strength, histone H1 of either free or immune-complexed form could bind to CRP via site 1. These data are discussed with respect to the possible role of CRP in the handling and clearance of immune complexes in patients with systemic lupus erythematosus.

Autoantigens↗
PubMed1993

Changes in subset specificity of anti-T cell autoantibodies in systemic lupus erythematosus.

Relative reactivity of anti-lymphocyte autoantibodies (ALA) from patients with systemic lupus erythematosus (SLE) against CD4+ and CD8+ T cells was studied using C-dependent microcytotoxicity assay. Of 46 SLE sera screened for anti-T cell autoantibodies, 27 sera (59%) showed significant cytotoxic reactivity. Of these, positive correlation between the titer of anti-T cell antibody and CD4/CD8 killing ratio (p < 0.01) was demonstrated. In time course study of individual patients, the CD4/CD8 killing ratio increased and decreased as the disease flared and subsided and was accompanied by parallel changes in the titer of anti-T cell antibody titer. Moreover, as sera were serially diluted, the CD4/CD8 killing ratio decreased in 5 out of 10 sera. These results suggest that discrepancy among reports concerning the subset specificity of anti-T cell antibodies may be due, in part, to differences in the titer of ALA in the sera studied and to the dilution of serum used.

Animals↗
PubMed1992

Autoantibodies to nucleolin cross-react with histone H1 in systemic lupus erythematosus.

IgM autoantibodies to nucleolin and histone H1 are strongly associated in the serum of patients with systemic lupus erythematosus. IgM eluted from immobilized nucleolin specifically stained histone H1 blotted to nitrocellulose; conversely, IgM eluates prepared from immobilized histone H1 stained nucleolin blots. We conclude that the linkage of anti-nucleolin and anti-histone H1 autoantibodies in SLE is due, at least in part, to immunologic cross-reactivity between these two autoantigens, which share certain similar structural features.

Adult↗
PubMed1992

Correlation of antibodies to ribosomal P protein with psychosis in patients with systemic lupus erythematosus.

Ninety one Japanese patients with systemic lupus erythematosus (SLE) were studied to determine the clinical significance of antibodies to ribosomal P protein (anti-P). Anti-P was detected by western blotting in 38 of 91 patients (42%). Clinical symptoms of SLE were compared between patients with and without anti-P. The occurrence of lupus psychosis was significantly higher in patients with anti-P than in those without anti-P (9/38 v 1/53). No significant association was found between anti-P and other symptoms of SLE. These data strongly support the suggestion proposed by previous workers that anti-P is a marker autoantibody for the development of lupus psychosis.

Autoantibodies↗
PubMed1992

Relationship between autoepitope and DNA-binding site on a histone H1 molecule.

Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.

Autoimmunity↗
PubMed1992

Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy.

A 60-yr-old female patient with rheumatoid arthritis presented with nonsteroidal anti-inflammatory drug (NSAID)-induced ileal ulcers which caused intestinal bleeding and multiple strictures. Results of investigations, including radiological, pathological, and bacteriological examinations, were not consistent with Crohn's disease or intestinal tuberculosis. Rather, the lesion was characteristic of "diaphragm disease" caused by NSAIDs. Discontinuance of NSAIDs in combination with administration of ornoprostil (prostaglandin E1-derivative), sucralfate, and sulfasalazine put an end to the intestinal bleeding. This is a rate case of a patient with multiple strictures of the small intestine caused by NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

[Possible roles of infections and heat shock proteins in rheumatoid arthritis].

Heat shock protein, one of the most conserved proteins from prokaryotes to man, was shown to be strongly immunogenic in bacterial and helminthic infections. Evidences have accumulated suggesting that mycobacterial hsp65 plays a crucial role in the development of adjuvant arthritis induced in rats. By analogy, the pathogenetic roles of hsp were investigated in rheumatoid arthritis in man. The evidences obtained so far are highly suggestive but still circumstantial. Hsp's strong immunogenicity and high conservation, which seem to be mutually exclusive, make this molecule very mysterious. In this regard, Coutinho's new network theory or Cohen and Young's theory of immunological homunculus nicely reconciles these aspects.

Animals↗
PubMed1991

Autoantibodies to nucleolin in systemic lupus erythematosus and other diseases.

The 110-kDa intracellular phosphoprotein (110K) described previously by this laboratory as a common IgM autoantigen in SLE and certain other systemic autoimmune disorders and viral infections is identified as nucleolin in the present investigation. Using rabbit antiserum to rat nucleolin as a probe, IgM autoantibody-reactive 110K co-migrated with human lymphocyte nucleolin in one- and two-dimensional immunoblots. Rabbit anti-nucleolin also specifically depleted autoreactive 110K from detergent lysates of human cells. Because nucleolin shares amino acid sequence similarity and/or forms dynamic particles with other prominent autoantigens, the present observation raises the possibility that the nucleolin/anti-nucleolin system may be of special significance for the development of humoral autoreactivity to nuclear Ag.

Antibody Specificity↗
PubMed1991

Long-term potentiation induced by a sustained rise in the intraterminal Ca2+ in bull-frog sympathetic ganglia.

1. The mechanism of a long-term potentiation of transmitter release (pre-LTP) induced by a tetanic stimulation (33 Hz for 1-30 s) applied to the preganglionic nerve was examined by intracellularly recording the fast excitatory postsynaptic potentials (fast EPSPs) in bull-frog sympathetic ganglia. 2. Short-term facilitation induced by paired pulses was decreased during the course of pre-LTP; the extent of reduction paralleled with the magnitude of pre-LTP. 3. The frequency of miniature EPSPs increased after tetanic stimulation that produced the pre-LTP. 4. The Ca2+ ionophore, A23187, increased both the amplitude and quantal content of fast EPSPs and frequency of miniature EPSPs while it decreased short-term facilitation. 5. A Ca2+ chelating agent, Quin-2, loaded as acetoxymethyl ester, reduced the amplitude and quantal content of fast EPSPs and short-term facilitation, and blocked the generation of pre-LTP. 6. Activators of protein kinase C, phorbol 12,13-dibutyrate and 1-oleoyl-2-acetyl-rac-glycerol, and its inhibitors, H-7 and staurosporine, did not block the generation of pre-LTP, while the activators enhanced transmitter release. 7. Inhibitors of calmodulin, trifluoperazine and W-7, blocked the generation of pre-LTP, whereas the amplitude and quantal content of fast EPSPs were not influenced. 8. These results suggest that the pre-LTP results from a sustained rise in the basal level of intraterminal Ca2+ and an activation of the Ca(2+)-calmodulin-dependent process in the preganglionic nerve terminals.

Animals↗
PubMed1991

Specificity of autoantibodies to histone H1 in SLE: relationship to DNA-binding domains.

Autoantibodies in the sera of patients with systemic lupus erythematosus were examined with respect to their specificity for proteolytic fragments of histone H1 that retain, or do not retain, DNA-binding domains. 16 of 31 sera contained IgG and IgM antibodies to histone H1. IgM antibodies to H1 in 8 sera (50%) were directed at 18 kD and 20 kD alpha-chymotrypic H1 fragments that bore binding sites for DNA, as identified by staining immunoblots containing the fragments with ssDNA plus 6/0, a mouse monoclonal antibody against ssDNA, IgM with this type of histone H1 specificity did not react with comparably-sized V8 protease fragments of H1. IgM antibodies to H1 in the other patients were directed against entirely different epitopes which were preserved in V8 protease digests of H1. In serial studies of three patients during different phase of their SLE, the level of antibodies against the 18 kD and 20 kD histone H1 fragments varied in parallel with the level of anti-ssDNA antibodies in one and varied inversely in the other two. The data suggest that a significant proportion of autoantibodies to histone H1 are directed at a limited number of epitopes localized to H1 fragments containing DNA-binding sites.

Animals↗
PubMed1990

Reactivity of autoantibodies and DNA/anti-DNA complexes with a novel 110-kilodalton phosphoprotein in systemic lupus erythematosus and other diseases.

Utilizing nonionic detergent lysates of human lymphoid and non-lymphoid cells as substrate, IgM and/or IgG antibodies to a 110-kDa/isoelectric point 5.4 phosphoprotein (110K) was demonstrated in serum from patients with SLE or certain other systemic autoimmune disorders by immunoblotting and immunoprecipitation. Ig of this specificity was not demonstrable in serum from normal individuals, but, in a limited survey, was detected in serum from patients with acute hepatitis A or infectious mononucleosis. 110K shares a number of properties with nucleolin, i.e., identical Mr and isoelectric point, localization in both the nucleus and the cytosol, increased expression in rapidly dividing cells, and shown to be distinct from already defined autoantigens of similar size, i.e., topoisomerase I, PM-Scl, and RNA polymerase I. Because 110K could bind denatured DNA, as demonstrated by its specific absorption by DNA-cellulose and by its reactivity with monoclonal anti-ssDNA antibody in the presence of denatured DNA, special efforts were made to distinguish reactivity of pre-formed DNA/anti-DNA complexes in SLE serum from that due to specific anti-110K autoantibodies. Although binding to 110K could be mediated by DNA and anti-DNA in some SLE sera, the accumulated evidence supports the existence of a major new autoantibody system in SLE, other autoimmune diseases, and certain virus infections.

Antibodies, Antinuclear↗
PubMed1989

Identification of an acidic ribosomal protein reactive with anti-Sm autoantibody.

Autoantibody to Sm Ag is a highly specific marker for the diagnosis of SLE. The Sm Ag exists in the cell nucleus as part of a ribonucleoprotein complex containing five small nuclear RNA. The major immunoreactive Sm species have been reported to be three polypeptides of m.w. 28,000/29,000 (B/B') and 16,000 (D). We report here that a m.w. 21,000 peptide is another major target of anti-Sm antibody. This peptide was originally identified by Western blotting as an acidic ribosomal protein (RP21) reactive with IgG from some SLE patients. Anti-RP21 is distinct from anti-ribosomal P protein antibody (anti-P) which has been previously identified as a lupus-specific autoantibody. Cell fractionation experiments showed that RP21 existed only in the ribosomal fraction and was never detected in other cellular compartments including nuclei. However, when nuclear extracts were used as Ag sources in immunoblotting, affinity-purified anti-RP21 was found to react with m.w. 28,000 and 16,000 peptides, suggesting that anti-RP21 reactivity might be due to the cross-reaction of anti-Sm. This was further confirmed by the evidence that two kinds of murine anti-Sm mAb independently derived from MRL/lpr mouse recognized RP21. These results indicate that anti-Sm antibodies in SLE are reactive with both nuclear and ribosomal ribonucleoproteins. Previous reports have described certain similarities, i.e., antibody subclass restriction and incidence, of anti-Sm and anti-P in both humans and autoimmune mice. Our present study demonstrated a close physical association of target molecules reactive with anti-Sm and anti-P, and might, therefore, provide some clue to the origin of these two types of lupus-specific autoantibodies.

Animals↗
PubMed1989

Glycine potentiates NMDA responses in rat hippocampal CA1 neurons.

When superfused onto rat hippocampal slices, glycine (0.1-0.5 mM) potentiated the depolarization induced by pressure application of NMDA in normal Krebs solution and the synaptic discharge evoked by stimulation of the Schaffer collateral-commissural inputs to the CA1 pyramidal neurons bathed in Mg2+-free media; the effects were not prevented by strychnine. In addition, glycine partially reversed the blocking effect of D-2-amino-5-phosphonovalerate (AP5) on N-methyl-D-aspartate (NMDA)-induced depolarization. These results show that glycine at relatively high concentrations potentiates the NMDA-mediated response in hippocampal slices.

2-Amino-5-phosphonovalerate↗