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Tsuneyo Mimori

Publications and source records attributed to Tsuneyo Mimori.

At least 37 records · Page 2Linked to original sources
PubMed2004

Systemic lupus erythematosus associated with recurrent lupus enteritis and peritonitis.

We describe the case of a 41-year-old woman with systemic lupus erythematosus (SLE) who suffered from repeated reversible lupus enteritis characterized by marked edematous thickening of the small intestine. Ultrasonography (US) and computed tomography (CT) manifested as an 'accordion-like appearance' and a 'target-like appearance', respectively. Resolution of gastrointestinal tract wall thickening was observed on follow-up US performed a week after the increase in predinosolone (PSL). We conclude that careful evaluation of sonographic and radiographic findings helps to establish the diagnosis of lupus enteritis.

Adult↗
PubMed2004

Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis.

OBJECTIVE: To clarify the in vivo function of follistatin-related protein (FRP)/TSC-36/FSTL1 in rheumatoid arthritis (RA), we investigated the roles of FRP in a mouse model of arthritis. METHODS: Arthritis was induced in BALB/c mice by injecting anti-type II collagen monoclonal antibody and lipopolysaccharide. Mice were treated with daily intraperitoneal injections of 20 microg of recombinant FRP. Development of arthritis was assessed by the clinical score and footpad swelling. Histologic examination of affected paws was performed on day 21 after the onset of arthritis. The gene expression profiles of affected paws in FRP-treated and untreated mice were compared using commercially available complementary DNA (cDNA) arrays. The difference in gene expression was confirmed by real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Treatment with recombinant FRP showed significant amelioration of the arthritis severity. Histologic analyses confirmed this finding and revealed the alleviation of cellular infiltration into the synovium as well as cartilage damage. The significant decrease in the amount of urinary deoxypyridinoline also indicated the ameliorative effect of FRP on joint destruction. Moreover, cDNA array analysis of the gene expression profile in FRP-treated arthritic lesions revealed a reduced expression of the c-fos, ets-2, IL6, MMP3, and MMP9 genes, some of which are thought to be associated with synovial inflammation and joint destruction. CONCLUSION: These findings from in vivo experiments suggest that FRP could be one of the key molecules in the treatment of inflammatory joint diseases such as RA.

Animals↗
PubMed2004

[A case of dermatomyositis associated with different types of cancers at intervals of six years].

The patient is a 56-year-old Japanese woman who suffered from breast cancer and ovarian cancer at intervals of 6 years, and was also complicated by two episodes of dermatomyositis, each of which occurred simultaneously with each of two cancers. When she was 51 years old, she developed dermatomyositis for the first time 6 months after the resection of breast cancer, whose histological type was tubular adenocarcinoma. The dermatomyositis remitted without oral corticosteroids in 2 months, and the remission had continued for 6 years. However, at the age of 56, dermatomyositis abruptly recurred with a pruritic generalized rash, Gottron's papules and elevated serum CK levels. Examination for malignancy revealed an ovarian tumor, which was diagnosed as serous papillaly adenocarcinoma, and the surgery was performed. After the resection of the ovarian cancer, skin rash was improved dramatically and CK levels were normalized again without oral corticosteroids. Since there were no evidences of recurrence of the breast cancer, it was considered that each episode of dermatomyositis was associated with each of the cancers, respectively. We report this rare and interesting case to consider the etiology of cancer-associated myositis as a paraneoplastic syndrome, since the two cancers have different histological types.

Adenocarcinoma↗
PubMed2004

Immunogenetic features in 120 Japanese patients with idiopathic inflammatory myopathy.

OBJECTIVE: To examine the role of HLA-DRB1 and tumor necrosis factor (TNF) promoter genotypes in the development and the autoantibody profiles of idiopathic inflammatory myopathy (IIM) in Japanese patients. METHODS: HLA-DRB1 and TNF promoter genotypes were determined, and serum antinuclear autoantibodies were identified in 120 adult Japanese patients with IIM [72 with dermatomyositis (DM), 30 with polymyositis (PM), 18 with myositis overlapping with other collagen vascular diseases], as well as in 265 controls. RESULTS: Forty-two patients (35%) were positive for myositis-specific autoantibodies (MSA), including 37 (31%) for anti-aminoacyl-tRNA synthetase (ARS) autoantibodies. Allele carrier frequency of HLA-DRB1*0803 was increased in the patients with IIM [p = 0.02, corrected p (pc) NS, 23% vs 14%, odds ratio (OR) = 1.9 (95% confidence interval, CI = 1.1-3.2)], with PM [p = 0.006, pc NS, 33%, OR 3.1 (95% CI 1.3-7.1)], and with anti-ARS autoantibodies [27%, p = 0.04, OR 2.3 (95% CI 1.0-5.1)] compared with controls. DRB1*0405 was increased in patients with anti-ARS autoantibodies compared with controls [41% vs 25%, p = 0.04, pc NS, OR 2.1 (95% CI 1.0-4.3)]. TNF promoter genotype was associated with the presence of interstitial lung disease (ILD). The carriage of a TNF-a haplotype formed by -1031C, -863A, and -857C was increased in the patients with ILD versus those without ILD [33% vs 18%, p = 0.05, pc NS, OR 2.3 (95% CI 0.94-5.5)]. CONCLUSION: HLA-DRB1 alleles were associated with development of IIM and MSA in a Japanese population.

Adult↗
PubMed2003

Membrane-bound form of fractalkine induces IFN-gamma production by NK cells.

Natural killer (NK) cells participate in both innate and adaptive immunity, in part by their prompt secretion of cytokines including IFN-gamma, a pro-inflammatory cytokine with an important role in Th1 polarization. To assess the involvement of fractalkine in inflammatory processes, we examined the effect of fractalkine on IFN-gamma production by NK cells. Although soluble chemokines, including MCP-1 and RANTES as well as fractalkine, had a negligible effect on IFN-gamma production, immobilized fractalkine markedly induced IFN-gamma production by NK cells in a dose-dependent manner. Pretreatment of NK cells with the phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, completely inhibited the production of IFN-gamma induced by fractalkine, and pretreatment with the protein tyrosine kinase inhibitor, herbimycin A, partially suppressed the response, suggesting that augmentation of IFN-gamma production in response to fractalkine treatment of NK cells involves signaling through PI 3-K and protein tyrosine kinases. Furthermore, co-culture of NK cells with fractalkine-transfected 293E cells markedly enhanced IFN-gamma production by NK cells compared with co-culture with control 293E cells. These findings may indicate a paracrine feedback loop system in which endothelial cells may be activated to produce more fractalkine, and also suggest a role for fractalkine expressed on endothelial cells in Th1 polarization through the stimulation of IFN-gamma production by NK cells.

Cell Division↗
PubMed2003

Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis.

We previously reported that follistatin-related protein (FRP)/TSC-36 was one of the target antigens of autoantibodies in rheumatoid arthritis (RA) and that the appearance of serum autoantibodies to FRP correlated to disease activity in RA. However, the significance of FRP in autoimmunity remained to be explained due to the unknown function of FRP. Here, we disclose in part the function of FRP. Transforming growth factor (TGF)-beta augmented FRP gene expression in synovial cells. FRP reduced synovial production of matrix metalloproteinase (MMP)-1, MMP-3 and prostaglandin E(2), potent agonists of joint destruction in RA. In contrast, autoantibodies to FRP from patients with RA increased their production by blocking FRP activity, probably in the autocrine system. Moreover, FRP down-regulated synovial expression of FOS (c-fos), which seemed responsible for the reduction in MMP-1 and MMP-3 caused by FRP. Therefore, FRP and its autoantibody can be regarded as defensive and offensive factors respectively in rheumatoid arthropathy. The major epitope of autoantibodies to FRP was mapped to the sequence LKFVEQNE (residues 169-176) and homologous sequences were found in proteins from Escherichia coli, Epstein-Barr virus, etc. FRP and its autoantibody may provide some clues to elucidate the process of disease development and a new approach to the design of therapeutics in RA.

Animals↗
PubMed2003

Effect of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis in Japanese patients with connective tissue disease: 3 year followup.

OBJECTIVE: A 3 year prospective randomized study was conducted to clarify the efficacy of intermittent cyclical etidronate therapy on corticosteroid induced osteoporosis. METHODS: A group of 102 Japanese patients were enrolled, each taking > 7.5 mg of prednisolone daily for at least 90 days. Patients were randomly divided into 2 treatment groups: Group E (etidronate) took 200 mg etidronate disodium per day for 2 weeks with 3.0 g calcium lactate and 0.75 microg alphacalcidol daily; Group C (control) took 3.0 g calcium lactate and 0.75 microg alphacalcidol daily. Outcome measurements included changes from baseline in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral fractures at 48 and 144 weeks. RESULTS: The mean (+/- SD) lumbar spine BMD increased 3.7 +/- 5.6% (p < 0.01) and 1.5 +/- 4.1% (NS) from baseline at 48 weeks and 4.8 +/- 6.9% (p < 0.005) and 0.4 +/- 5.0% (NS) from baseline at 144 weeks in Group E and Group C, respectively. The improvement of BMD in Group E was significantly greater than in Group C at 144 weeks (p < 0.01). In 3 subgroups, men and premenopausal and postmenopausal women, the postmenopausal women showed the greatest improvement. Mean percentage change in this subgroup was 10.1 +/- 8.0% and 1.35 +/- 6.4% in Group E and Group C, respectively. We noted that 2 patients in Group C had new vertebral fractures, whereas no fractures were observed in Group E. CONCLUSION: These results indicate that intermittent cyclical etidronate therapy is effective for the prevention and treatment of corticosteroid induced osteoporosis in patients with connective tissue diseases.

Adult↗
PubMed2002

Lipid rafts as the signaling scaffold for NK cell activation: tyrosine phosphorylation and association of LAT with phosphatidylinositol 3-kinase and phospholipase C-gamma following CD2 stimulation.

Natural killer (NK) cells participate in both innate and adaptive immunity through the prompt secretion of cytokines and ability to lyse virally infected cells or tumor cells. Although it has been well understood that lipid rafts (rafts) and a raft-associated linker for activation of T cells (LAT) plays a central role in TCR signal transduction, there are still great gaps in our knowledge of the molecular events involved in NK cell activation. We show here that CD2 and rafts became polarized to the site of NK cell activation by CD2 cross-linking or target cell binding using confocal microscopy, and LAT and a significant amount of CD2 colocalized in raft fractions of sucrose-density gradient from an NK cell line, NK3.3. CD2 cross-linking strongly induced tyrosine phosphorylation of LAT, resulting in increased association with phosphatidylinositol 3-kinase (PI 3-K) and phospholipase C-gamma1 (PLC-gamma1). In vitro binding studies using glutathione S-transferase fusion proteins demonstrated that a large portion of the association between LAT and PI 3-K or PLC-gamma1 was mediated through their SH2 domains in tyrosine phosphorylation-dependent manner. Furthermore, disruption of lipid rafts by cholesterol depletion from cell membranes using methyl-beta-cyclodextrin markedly reduced LAT tyrosine phosphorylation and NK cell functions, including cytotoxicity and granule exocytosis. These results document that modulation of raft integrity by aggregation of NK cell activating receptors, which leads to the formation of complexes of LAT with PI 3-K and PLC-gamma1, is essential for the NK cell lytic mechanisms.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation.

Natural killer (NK) cells participate in both innate and adaptive immunity through the prompt secretion of cytokines and ability to lyse virally infected cells or tumor cells. Triggering of NK cells requires aggregation of surface receptors such as CD2 and CD16, and NK cell activity can be augmented in vitro by stimulation with IL-2. In this study, we examined the role of adapter proteins in the increased NK activation following CD2 crosslinking and IL-2 stimulation of NK3.3 cells. NK3.3 cells lysed NK-sensitive K562 cells in a CD2-dependent manner, and IL-2 markedly enhanced lytic activity in a 4h cytotoxic assay. IL-2 also enhanced spontaneous and CD2-mediated granule exocytosis from NK3.3 cells. CD2 crosslinking markedly induced tyrosine phosphorylation of Cbl associated with Grb2 or CrkL, Shc and LAT, compared with IL-2 stimulation. However, costimulation of IL-2 with CD2 crosslinking remarkably enhanced associations of Grb2-Shc and CrkL-Cbl, compared to IL-2 stimulation or CD2 crosslinking alone. In vitro binding studies using GST-fusion proteins revealed that interactions of Grb2-Shc and CrkL-Cbl were mediated through each SH2 domain in tyrosine phosphorylation-dependent manner. Furthermore, CD2 crosslinking, but not IL-2 stimulation, markedly induced tyrosine phosphorylation of LAT. Thus, tyrosine phosphorylation of different adapter proteins and consequent interactions between signaling molecules described here may explain the molecular mechanisms of the additive effects of IL-2 stimulation and CD2 crosslinking on NK cell activation.

Adaptor Proteins, Signal Transducing↗