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Terao C.,Kyoto University | Ohmura K.,Kyoto University | Kochi Y.,RIKEN | Ikari K.,Tokyo Womens Medical University | And 17 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Background: HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it has recently been suggested that HLA-DRB1 is only associated with patients with RA who have anticitrullinated peptide/protein antibodies (ACPA), which are specific to RA. Objective: To elucidate whether specific HLA-DR alleles are associated with ACPA-negative RA development. Methods: HLA-DRB1 typing was carried out in 368 Japanese ACPA-negative patients with RA and 1508 healthy volunteers as the first set, followed by HLA-DRB1 typing of 501 cases and 500 controls as the second set. The HLA-DRB1 allele frequency and diplotype frequency were compared in each group, and the results of the two studies were combined to detect HLA-DRB1 alleles or diplotypes associated with ACPAnegative RA. Results: HLA-DRB1*12:01 was identified as a novel susceptibility allele for ACPA-negative RA (p = 0.000088, OR=1.72, 95% CI 1.31 to 2.26). HLA-DRB1*04:05 and*14:03 showed moderate associations with ACPA-negative RA (p = 0.0063, OR=1.26, 95% CI 1.07 to 1.49 and p = 0.0043, OR=1.81, 95% CI 1.20 to 2.73, respectively). The shared epitope was weakly associated with ACPA-negative RA, but no dosage effect was detected (p = 0.016, OR=1.17, 95% CI 1.03 to 1.34). A combination of HLA-DRB1*12:01 and DRB1*09:01 showed a strong association with susceptibility to ACPA-negative RA (p = 0.00013, OR=3.62, 95% CI 1.79 to 7.30). Homozygosity for HLA-DR8 was significantly associated with ACPA-negative RA (p = 0.0070, OR=2.16, 95% CI 1.22 to 3.82). It was also found that HLA-DRB1*15:02 and*13:02 were protective against ACPA-negative RA (p = 0.00010, OR=0.68, 95% CI 0.56 to 0.83 and p = 0.00059, OR=0.66, 95% CI 0.52 to 0.84, respectively). Conclusions: In this large-scale association study multiple alleles and diplotypes were found to be associated with susceptibility to, or protection against, ACPA-negative RA.

Kanatani K.T.,University of California at San Diego | Kanatani K.T.,Kyoto University | Ito I.,Kyoto University | Al-Delaimy W.K.,University of California at San Diego | And 12 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected. Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles. Methods: A case-crossover design was used. The exposure measurement was LIDAR's nonspherical extinction coefficient. The outcome measurement was hospitalization of children aged 1 to 15 years for asthma exacerbation in eight principal hospitals in Toyama, a local area in Japan bordering the Japan Sea, during February to April, 2005 to 2009. Measurements and Main Results: During the study period, there were 620 admissions for asthma exacerbation, and 6 days with a heavy dust event (daily mineral dust concentration > 0.1 mg/m 3). Conditional logistic regression showed a statistically significant association between asthma hospitalization and a heavy dust event. The crude odds ratio (OR) of the heavy dust event for hospitalization on the day was 1.88 (95% confidence interval [CI], 1.04-3.41; P = 0.037), and the O Rof heavy dust event during the previous week was 1.83 (95% CI, 1.31-2.56; P = 0.00043). The OR adjusted by other air pollutant levels, pollen, and meteorological factors was 1.71 (95% CI, 1.18-2.48; P = 0.0050). Conclusions: Heavy dust events are associated with an increased risk of hospitalizations for asthma.

Ohmura K.,Kyoto University | Terao C.,Kyoto University | Maruya E.,HLA Laboratory | Katayama M.,Kyoto University | And 16 more authors.
Rheumatology | Year: 2010

Objectives: ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion. Methods: We genotyped HLA-DRB1 alleles for 574 ACPA-positive RA, 185 ACPA-negative RA (including 97 erosive RA) and 1508 healthy donors. We also tested whether HLA-DR SE is associated with RF-negative or ANA-negative RA. Results: ACPA-negative RA with apparent bone erosion was not associated with SE, supporting the idea that ACPA-negative RA is genetically distinct from ACPA-positive RA. We also tested whether these subsets are based on autoantibody-producing activity. In accordance with the ACPA-negative RA subset, the RF-negative RA subset showed a clearly distinct pattern of association with SE from the RF-positive RA. In contrast, ANA-negative as well as ANA-positive RA was similarly associated with SE, suggesting that the subsets distinguished by ACPA are not based simply on differences in autoantibody production. © The Author(s) 2010.

Iwata M.,University of Toyama | Matsushita Y.,National Center for Global Health and Medicine | Fukuda K.,University of Toyama | Wakura T.,University of Toyama | And 9 more authors.
Journal of Diabetes Investigation | Year: 2014

Aims/Introduction: The objective of the present study was to clarify the validity of β-cell function-related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients. Materials and Methods: In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross-sectional study examining the relationship between the homeostasis model assessment of β-cell function (HOMA-β) and C-peptide-based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several β -cell function-related indices using a receiver operating characteristic (ROC) curve analysis. Results: The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA-β, followed by the fasting serum C-peptide immunoreactivity index (CPI); the fasting serum C-peptide immunoreactivity itself (F-CPR) had the least correlation. The CPI, HOMA-β and SUIT were significantly lower in the insulin-requiring group than in the non-insulin-requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F-CPR, CPI, SUIT, and HOMA-β, respectively. The cut-off values of SUIT, CPI, and HOMA-β for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively. Conclusions: The present study shows that SUIT is the best predictor of insulin requirement among these β-cell function-related markers. © 2013 The Authors.

Shimada M.,Saiseikai Takaoka Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2013

A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

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