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S Minota

Publications and source records attributed to S Minota.

At least 55 records · Page 3Linked to original sources
PubMed1997

Constitutive tyrosine phosphorylation of the vav proto-oncogene product in MRL/Mp-lpr/lpr mice.

MRL/Mp-lpr/lpr (lpr) mice develop autoantibodies, vasculitis, and glomerulonephritis, which are similar to human systemic lupus erythematosus, and acquire a generalized, nonmalignant, lymphoproliferative disorder. CD4- CD8- CD3+ TCR alphabeta+ (double-negative, DN) T cells accumulate in spleen and lymph nodes, and become a major T cell population in vivo. These DN T cells, however, are refractory to various stimuli, including CD3, IL-2, CD28, PMA, and PHA. Recently, the lpr gene mutation has been identified as a mutant gene for Fas, resulting in expression defects of Fas Ag. It is still unclear, however, what kinds of mechanisms cause the dysfunction of lpr DN T cells. To elucidate the pathogenic mechanisms in abnormal DN T cells, biochemical analyses were conducted for the expression and tyrosine phosphorylation of the vav proto-oncogene product (Vav) in DN T cells from lpr mice. We demonstrated that Vav, a 95-kDa cytoplasmic protein, from lpr mice was constitutively tyrosine phosphorylated several times higher than in control +/+ mice, while expression of Vav protein in lpr and +/+ mice was equal. Additionally, in contrast with +/+ T cells, tyrosine phosphorylation of Vav, which normally increases within a minute of stimulation via TCR, did not increase in lpr DN T cells following PHA or Ab activation. Taken together with the suggested roles of Vav in multiple receptor-mediated signal transductions, our findings suggest that the functional abnormalities of lpr DN T cells may be related to Vav abnormal tyrosine phosphorylation, which could lead to impaired signaling between surface receptors and G proteins in this cell population.

Animals↗
PubMed1997

Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis.

One hundred thirty-two patients with various connective tissue disorders, including 60 with rheumatoid arthritis (RA), had antibodies against human as well as Escherichia coli hsp60 in titers significantly higher than those of normal controls. There was a correlation between titers of antibody to human hsp60 and those to E. coli hsp60. Levels of antibodies against human and E. coli hsp60 were lower in joint fluids than in sera, indicating little production of antibodies in the joint. Antibodies affinity-purified with E. coli hsp60 bound strongly with the homologous hsp60, but weakly with human hsp60. However, antibodies affinity-purified with human hsp60 bound comparably with both E. coli hsp60 and human hsp60. Antibodies affinity-purified with Mycobacterium tuberculosis hsp65 bound to human hsp60 with a reactivity similar to the reactivity of those affinity-purified with human hsp60. The reactivity to the three hsp60 species was lost when sera were absorbed with E. coli hsp60, while the reactivity to E. coli hsp60 remained after extensive absorption with M. tuberculosis hsp65 or human hsp60. These results indicate that anti-hsp60 antibodies in patients with RA and other connective tissue disorders are raised by infection with intestinal microorganisms such as E. coli. They may represent another example of autoimmune responses triggered by antigenic mimicry of host proteins to microbes and suggest that the reactivity of antibodies from RA patients with M. tuberculosis hsp65 might have been a cross-reaction with the E. coli homologue.

Antibodies↗
PubMed1997

Inhibitory effects of arachidonic acid on nicotinic transmission in bullfrog sympathetic neurons.

Inhibitory effects of arachidonic acid on nicotinic transmission in bullfrog sympathetic neurons. J. Neurophysiol. 78: 2396-2401, 1997. Arachidonic acid (AA, 0.2-40 mu M) reversibly reduced the amplitude of the fast excitatory postsynaptic potentials and the underlying currents (fast EPSCs) of bullfrog sympathetic neurons evoked by preganglionic nerve stimulation in a Ca2+-deficient solution. AA reduced the acetylcholine (ACh)-induced nicotinic currents (nIACh) evoked by brief applications of ACh to the ganglion cells in a dose-related manner. AA reduced the maximum amplitude of nIACh estimated from the dose-response relationship without causing an appreciable change in the apparent dissociation constant. Indomethacin (2 mu M) and nordihydroguaiaretic acid (20 mu M), blockers of cyclooxygenase and lipoxygenase pathways, respectively, had no effect on the inhibition of fast EPSC by AA. AA did not obviously affect the preganglionic nerve terminal spike configuration, synaptic delay, facilitation, quantal content of transmitter release, or the presynaptic long-term potentiation elicited by the repetitive stimulation applied to the preganglionic nerve fibers. These results suggest that AA acts on an allosteric site of the nicotinic receptor-channel complex either directly or indirectly and in turn inhibits ion permeation through these channels without affecting the release of ACh from preganglionic nerve terminals.

Acetylcholine↗
PubMed1997

Regulation of MHC class I expression by inflammatory cytokines in rat mesangial cells.

We investigated the regulation of major histocompatibility complex (MHC) class I expression by inflammatory cytokines and nitric oxide (NO) in rat mesangial cells by enzyme-linked immunosorbent assay and flow cytometry. MHC class I molecule expression on mesangial cells was significantly stimulated by interferon gamma, tumor necrosis factor alpha and interleukin 1beta, but not by interleukin 6, in a dose-dependent manner. Addition of SIN-1, an NO donor, did not affect the expression of cytokine-induced MHC class I expression. These results suggest that under inflammatory conditions mesangial cells may act as antigen-presenting cells in response to stimulation by cytokines and may be involved in the pathogenesis of immune-mediated glomerular disease.

Animals↗
PubMed1997

[Autoimmune diseases and stress proteins].

The heat shock protein(hsp), one of the most conserved and ubiquitous proteins in a wide range of species from bacteria to mammals, is strongly immunogenic. High conservation and potent immunogenicity, taken along with the fact that hsp is the target molecule of some gamma/delta T cells place it at the interface between immunity and tolerance. The role of hsp on autoimmune and inflammatory disorders has been vigorously investigated. There are accumulated lines of evidence suggestive of the possible involvement of hsp in clinical disorders but they still remain circumstantial. Two questions must be addressed before the exact role of hsp in these settings is established: 1) Why a conserved protein such as hsp is so immunogenic? 2) Why a ubiquitous protein can be a target of an organ-specific autoimmunity? Our data indicated that antibodies against highly conserved hsp60 in the sera from patients with autoimmune diseases, highlighted by rheumatoid arthritis, were directed mainly against epitopes specific for bacteria such as E. coli. The role of intestinal flora on the pathogenesis of rheumatoid arthritis has long been pursued and our data might support these lines.

Animals↗
PubMed1997

Association of interleukin 6 release from endothelial cells and pulmonary hypertension in SLE.

OBJECTIVE: To investigate how sera from 37 patients with systemic lupus erythematosus (SLE) stimulate interleukin (IL) 6 release from IL-1beta pretreated endothelial cells and compare these effects to those of sera from 16 normal controls. METHODS: Endothelial cells pretreated 18 h with IL-1beta (5 U/ml) were incubated 2 h with sera diluted 10-fold with phosphate buffered saline (PBS). IL-6 concentrations in endothelial culture supernatants collected after incubation were measured by ELISA. RESULTS: Compared with PBS, sera from controls and 24 patients with SLE suppressed IL-6 release from IL-1beta pretreated cells. However, sera from 13 patients with SLE augmented IL-6 release. Of note, sera from 5 patients with pulmonary hypertension induced the highest level of IL-6 release. IgG from control sera suppressed IL-6 release, whereas F(ab')2 did not. Both IgG and F(ab')2 from the sera of patients with SLE with pulmonary hypertension augmented IL-6 release from IL-1beta pretreated cells. CONCLUSION: IgG antiendothelial cell antibodies from patients with SLE may be associated with the pathogenesis of SLE and pulmonary hypertension.

Adolescent↗
PubMed1997

Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: To test for the presence of colony forming cells, that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells), in the peripheral blood of patients with rheumatoid arthritis (RA) and to determine its association with the clinical and laboratory features of RA. METHODS: Peripheral blood mononuclear cells (PBMC) from 96 patients with RA and 20 healthy controls were assayed for in vitro colony formation. In addition, PBMC from 38 patients with other rheumatic diseases including systemic lupus erythematosus (SLE), progressive systemic sclerosis (SSc), and polymyositis/dermatomyositis (PM/DM); 23 patients with infectious inflammatory diseases were also assayed. RESULTS: Large macrophage colony forming cells were detected in the peripheral blood of 19% of patients with RA (18/96), but not in that of healthy controls. In addition, these cells were detected in the peripheral blood of 11 of the 38 patients with other rheumatic disease (7/13 SSc and 4/11 PM/DM), but not in the 23 patients with infectious diseases. In the patients with RA, interstitial lung disease was significantly more frequently observed among patients in whom colony forming cells were found than among those in whom they were not found (p < 0.001). CONCLUSION: Based on the size of the colonies they formed, the macrophage colony forming cells detected in patients with RA probably corresponded to primitive hematopoietic progenitor cells, defined as high proliferative potential colony forming cells (HPP-CFC). Our observations provide preliminary evidence of the appearance of HPP-CFC in the circulation during inflammation of RA, and during that in other rheumatic diseases such as SSc and PM/DM, and of the association of HPP-CFC with interstitial lung disease in patients with RA.

Adult↗
PubMed1996

Selective accumulation of anti-histone antibodies in glomeruli of lupus-prone lpr mice.

Immunoglobulins were eluted from glomeruli of 50 lupus-prone, lpr mice and their physicochemical properties and specificity were compared with those in sera pooled from the same mice. Although immunoglobulins in glomeruli had higher isoelectric points than those in sera, there were no appreciable differences in the relative contents of neutral and acidic immunoglobulins between them. The proportion of IgG3 subclass was slightly higher in glomerular than serum immunoglobulins. Both anti-single-stranded and anti double-stranded DNA antibodies were twofold higher in glomerular than serum immunoglobulins, while anti-Sm antibodies were not recovered in glomerular eluate despite their high activity in serum. Antibodies in glomerular eluate reacted most strongly with histones, especially with core histones, while those in sera bound preferentially with histone H1, Sm-B, -B', and -D antigens. Since histones are very basic, they would have a higher affinity for negatively charged glomerular constituents, leading to an in situ formation of immune complexes involving fixed histones and their binding with antibodies for the induction of nephritides. Otherwise, such immune complexes themselves might retain positive charges sufficient for an affinity with the glomerular basement membrane. These results indicate that histone-anti-histone antibody system may play a role in the perpetuation of murine lupus nephritis.

Animals↗
PubMed1996

Regulation of ICAM-1 expression by inflammatory cytokines in rat mesangial cells.

We investigated the regulation of intercellular adhesion molecule 1 (ICAM-1) expression by the inflammatory cytokines interleukin 1 beta (IL-1), IL-6 and IL-8 in rat mesangial cells by enzyme-linked immunosorbent assay, flow cytometry and Northern blot analyses. ICAM-1 expression on mesangial cells was stimulated significantly by IL-1 beta, but not by IL-6 nor IL-8, in a dose-dependent manner. Levels of ICAM-1 mRNA were very low in unstimulated mesangial cells, while its expression was markedly induced by exposure to IL-1 beta for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. These results demonstrate that IL-1 beta, but not IL-6 nor IL-8, induces ICAM-1 mRNA and protein accumulation in rat mesangial cells.

Animals↗
PubMed1996

Nitric oxide inhibits intracellular adhesion molecule-1 expression in rat mesangial cells.

This study tested whether nitric oxide modulates the expression of intercellular adhesion molecule-1 (ICAM-1) expression in glomerular mesangial cells. In an enzyme-linked immunosorbent assay, interleukin 1 beta (IL-1 beta; 10 ng/mL) increased ICAM-1 molecule expression on cultured rat mesangial cell surface in a time-dependent manner. Addition of the nitric oxide donors 3-morpholino-sydnonimine (SIN-1) or sodium nitroprusside significantly suppressed IL-1 beta-induced ICAM-1 molecule expression in a dose-dependent manner. The inhibitory effect of SIN-1 was abolished in the presence of a nitric oxide scavenger hemoglobin, but not in the presence of superoxide dismutase or pyrrolidine dithiocarbamate. Addition of 8-bromo-cyclic GMP showed no significant effect on IL-1 beta-induced ICAM-1 expression. In Northern blot analysis, the expression of ICAM-1 mRNA was barely detected in unstimulated cells, whereas ICAM-1 gene transcripts were clearly expressed after exposure to IL-1 beta for 3 h, and addition of SIN-1 decreased IL-1 beta-induced ICAM-1 mRNA accumulation. These results suggest that nitric oxide suppresses ICAM-1 expression in IL-1 beta-stimulated mesangial cells, independent of cGMP formation.

Animals↗
PubMed1996

Histiocytic cytophagic panniculitis which developed during interferon-alpha therapy.

A 59-year-old woman developed edema of the face and eyelids during interferon (IFN)-alpha-2b therapy for chronic hepatitis C with a cumulative dose of 6 million x 47 units. Despite cessation of the therapy, the edema progressed and was followed by exophthalmos, pyrexia, liver dysfunction, pancytopenia, and disseminated intravascular coagulation. Two months after initial presentation, she died of hemorrhagic shock and was diagnosed with histiocytic cytophagic panniculitis at autopsy. This may be a hitherto unrecognized adverse effect of therapeutic IFN alpha.

Antiviral Agents↗
PubMed1995

Delayed onset and slow time course of the non-M-type muscarinic current in bullfrog sympathetic neurons.

The onset and time course of the muscarinic currents induced by brief applications of acetylcholine (ACh) were examined in voltage-clamped neurons of bullfrog sympathetic ganglia bathed in a solution containing d-tubocurarine. At a potential of -40 mV, the ACh-induced current (IACh) appeared within 1.2 s and rapidly increased to its peak with a half-activation time of 2.2 s. This initial current was termed the fast IACh and was blocked by 4 mM Ba2+. At a potential more negative than -60 mV, the fast IACh disappeared and the remaining IACh activated with a delay of 3.9 s and slowly increased to its peak with a half-activation time of 8.2 s. This delayed current was termed the slow IACh and is thought to be associated with inhibition of a K+ current, or IM, as well as activation of an inward current through non-M-type muscarinic cation channels. The slow IACh was not inhibited by Ba2+, but its amplitude was reduced with depolarization (the extrapolated reversal potential was +3 mV). In Na(+)-free solution, the amplitude of the slow IACh reduced, but its polarity did not reverse in the voltage region examined (-30 to -100 mV). The slow excitatory postsynaptic current was also recorded, and was shown to have a similar delay in onset and slow time course. The results demonstrate that ACh activates the non-M-type muscarinic current three times more slowly than it inhibits IM.

Acetylcholine↗
PubMed1995

Rabbit anti-chromatin antibodies recognize similar epitopes on a histone H1 molecule as lupus autoantibodies.

Autoantibodies in systemic lupus erythematosus (SLE) are believed to be produced through an antigen-driven mechanism, i.e., autosensitization with autoantigens. If this is the case, it is conceivable that antigenic determinants reactive with SLE autoantibodies and induced antibodies raised by immunization are quite similar. To examine this issue, rabbits were immunized with purified histone H1 or chromatin. Although immunization with purified histone H1 did not produce detectable amounts of anti-histone H1 antibodies, immunization with chromatin mounted relatively good antibody responses against not only all histone subunits but also ssDNA. Epitopes on a histone H1 molecule reactive with SLE autoantibodies and rabbit antisera were determined using deletion mutants of a histone H1 molecule. At least two epitopes reactive with induced antibodies were found on a histone H1 and these were closely related to or the same as major autoepitopes in SLE. These data might indicate that B cells producing anti-histone H1 autoantibodies are quite similar to those induced by immunization and provide additional evidence that autosensitization with an autoantigen might be operative and a particulate antigen chromatin could be one of the immunogens for the production of anti-nuclear antibodies of various kinds in SLE.

Animals↗
PubMed1995

Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus.

OBJECTIVES: To clarify the pathophysiological role of endothelin-1 (ET-1) in the vascular injury associated with systemic lupus erythematosus (SLE) by investigating the effect of sera from patients with SLE on ET-1 release from cultured human umbilical vein endothelial cells. METHODS: Confluent monolayers of cultured human umbilical vein endothelial cells were incubated with serum samples (diluted 1:10) from 25 patients with SLE and 16 normal controls for two hours at 37 degrees C and ET-1 concentration in the culture supernatant was measured by enzyme immunoassay. RESULTS: The mean release of ET-1 from endothelial cells in the presence of serum from SLE patients was greater than in the presence of serum from normal controls (p < 0.005). ET-1 release from endothelial cells significantly correlated with the titre of IgM anti-endothelial cell antibodies (IgM-AECA) and immune complex concentration in sera from SLE patients (p < 0.05 and p < 0.01, respectively). After gel chromatography of the serum from an SLE patient, those fractions containing IgM-AECA or immune complex were shown to stimulate ET-1 release from endothelial cells. Heat aggregated IgG also stimulated ET-1 release from endothelial cells in a concentration dependent manner. CONCLUSIONS: IgM-AECA and immune complexes may stimulate ET-1 release from endothelial cells and ET-1 may play an important role in the initiation and development of vascular injury, such as pulmonary hypertension and lupus nephritis, in SLE.

Adolescent↗
PubMed1995

[Progressive systemic sclerosis (PSS) and cancer--increasing coincidence rate of cancer in 67 PSS patients].

The coincidence rate of cancer and PSS has been increasing according to reports from Nippon Byori Boken Shuho (Annual of Pathological Autopsy Cases in Japan), reaching 12.3% in the most recent report. Therefore we reviewed the histories of 67 PSS patients seen at our division over an 18-year period between 1974 and 1992, and found a high coincidence rate (14.6%) of cancer, reflecting the increasing tendency reported in the Nippon Byori Boken Shuho. The most frequent type of cancer was gastrointestinal cancer, including gastric and colon cancer and duodenal carcinoid. There were no significant differences in the clinical and laboratory findings between PSS patients with cancer and those without. Twenty-six of the 67 PSS patients died. Cancer was the cause of death in four, ranking second behind respiratory failure. The reason for the increasing coincidence rate of cancer and PSS is unclear at present. However, it is very important to discover cancer in PSS patients as early as possible, since it has a marked effect on prognosis.

Adult↗
PubMed1995

Quantification of antiribosomal P0 protein antibodies by ELISA with recombinant P0 fusion protein and their association with central nervous system disease in systemic lupus erythematosus.

OBJECTIVE: Using solid phase ELISA with recombinant P0 fusion protein as the antigen for detecting antiribosomal P0 protein antibody, we analyzed the association of this antibody and anticardiolipin antibody (aCL) with central nervous system (CNS) disease in patients with active systemic lupus erythematosus (SLE). METHODS: Sera from 70 randomly selected Japanese patients with active SLE were assayed for IgG and IgM antiribosomal P0 protein antibody titers and IgG aCL. RESULTS: IgG and IgM antiribosomal P0 protein antibodies were present in 29 and 12 (41.4 and 17.1%) of the 70 patients, respectively. The incidence of CNS disease, excluding lupus psychosis, was significantly higher in patients with IgG and IgM antiribosomal P0 protein antibodies than in those who lacked them (IgG antiribosomal P0 protein antibody 11/29 vs 3/41; IgM antiribosomal P0 protein antibody 7/12 vs 7/58). In addition, both IgG and IgM antiribosomal P0 protein antibody titers were significantly higher in patients with CNS disease, excluding lupus psychosis, than those without. No significant association was observed between antiribosomal P0 protein antibodies and lupus psychosis. No significant association was observed between IgG aCL and CNS disease. Serial studies of antiribosomal P0 protein antibodies and aCL in patients with transverse myelopathy also showed that IgG and IgM antiribosomal P0 protein antibodies, but not IgG aCL, were associated with CNS disease, excluding lupus psychosis. CONCLUSION: These data suggest a strong association of IgG and IgM antiribosomal P0 protein antibodies with CNS disease, excluding lupus psychosis, in SLE.

Adolescent↗