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Shibata, Japan

Hikami K.,University of Tsukuba | Kawasaki A.,University of Tsukuba | Ito I.,University of Tsukuba | Koga M.,University of Tsukuba | And 11 more authors.
Arthritis and Rheumatism

Objective. SPI1, also referred to as PU.1, is an Ets family transcription factor that interacts with IRF2, IRF4, and IRF8. In view of the significance of the type I interferon pathway in systemic lupus erythematosus (SLE), this study was undertaken to investigate a possible association between SPI1 polymorphisms and SLE. Methods. A case-control association study was performed using 6 tag single-nucleotide polymorphisms (SNPs), as well as a SNP located upstream of SPI1 previously found to be associated with acute myelogenous leukemia, in 400 Japanese patients with SLE and 450 healthy controls. Resequencing of all exons and known regulatory regions was performed to identify functional polymorphisms. Association of genotype and SPI1 expression was examined using the GENEVAR database and reporter assays. Results. A significant association was detected in 2 SNPs in intron 2 (rs10769258 and rs4752829) (P = 0.005 and P = 0.008, respectively, under the dominant model). The association was stronger in patients with nephropathy. Resequencing identified a potentially functional polymorphism in the 3'-untranslated region (3'-UTR), rs1057233, which was in strong linkage disequilibrium with the SNPs in intron 2. The number of risk alleles at rs1057233 was strongly correlated with SPI1 messenger RNA (mRNA) level in the database analysis (P = 0.0002), and was confirmed by a reporter assay. Interestingly, rs1057233 alters a target sequence for microRNA hsa-miR-569 (miR-569). Transfection experiments demonstrated that miR-569 inhibits expression of a reporter construct with the 3'-UTR sequence containing the nonrisk allele but not the risk allele. Conclusion. Our findings indicate that a SNP in the 3'-UTR of SPI1 is associated with elevated SPI1 mRNA level and with susceptibility to SLE. © 2011, American College of Rheumatology. Source

Suka M.,Jikei University School of Medicine | Hayashi T.,University of Tsukuba | Kobayashi S.,Juntendo University | Ito S.,Niigata Rheumatic Center | And 2 more authors.
Modern Rheumatology

Objectives To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone. Methods According to the Japanese Patients with MPOANCA- Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCAassociated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18 months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients. Results The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18 months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional. Conclusion MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL. © Japan College of Rheumatology 2012. Source

Ito S.,University of Tsukuba | Ito S.,Niigata Rheumatic Center | Ogishima H.,University of Tsukuba | Kondo Y.,University of Tsukuba | And 6 more authors.
Modern Rheumatology

Purpose To reveal how often patients with rheumatoid arthritis (RA) or any of other connective tissue diseases (CTDs) who take prednisolone (PSL) manifest postprandial hyperglycemia, and to evaluate the effects of divided daily dose administration of PSL, and of acarbose and nateglinide, on RA patients. Method The blood sugar (BS) levels of the patients were measured after meals. For in-patients who showed postprandial hyperglycemia, the daily dose of PSL was divided and nateglinide and/or acarbose were/was added if their BS levels did not improve sufficiently. The patients with BS levels that were well controlled for three months were compared with the patients with poorly controlled BS levels. Results The BS levels of 78 patients, including 16 patients with diabetes mellitus (DM), were measured after meals, and 27 of them were newly diagnosed with DM. Five of 14 patients who took a steady dose of PSL showed high BS levels after lunch (over 200 mg/dl) without elevated HbA1c. The combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia significantly. The period from the start of PSL administration to intervention was significantly longer in patients with good control at three months than the corresponding period in those with poor control. Conclusion The prevalence of postprandial hyperglycemia was high in patients with RA/CTD taking PSL; accordingly, measurement of the BS level after each meal was valuable. Combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia. © 2013 Japan College of Rheumatology. Source

Ishikawa H.,Niigata Rheumatic Center
Nihon rinsho. Japanese journal of clinical medicine

In recent years a concept of "treat to target" is introduced into a medical treatment of RA, and tight control is recommended from the early stage of the disease. However, it is difficult to relieve all patients in a true remission. Nowadays, disease activity is controlled well and a reconstructive surgery is performed at a limited number of the damaged joints in a state of good remaining of bone and soft tissue structures. The patients are highly motivated, and a newly developed disorder at the non-surgically treated joints is uncommon. Therefore, an aggressive rehabilitation is possible. Combined with a medical treatment of RA, a surgical intervention enables to acquire a higher level of ADL and an improved QOL (Japanese T2T). Source

Murasawa A.,Niigata Rheumatic Center
Nihon rinsho. Japanese journal of clinical medicine

Support system for patients with rheumatoid arthritis (RA) is a wide variety, such as the health care, the medical economy, the environment, and mental activity. Among these measures, the laws called the social security system are defined. These systems consist of social insurance (medical insurance, long-term care insurance, pension insurance), social welfare (welfare for the disabled) and public health (measures for intractable diseases). As social support under total management of RA, patients can receive mitigation measures and subsidies (physically disabled person's certificate, high-cost medical care, etc.) for high medical expenses at use of biological products, hospitalization and surgery. Furthermore long-term care insurance and disability pension can be used as a further support of home care. Source

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