Molecular mechanism and regulation of Sjogrens syndrome

科学研究費助成事業 研究成果報告書：基盤研究(C)2012-2014課題番号:2459143

Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-α used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4–8, 12–16, and 20–24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12–16 and 20–24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12–16 and in five patients (50%) at weeks 20–24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics

Association of Pre-ESRD Serum Calcium With Post-ESRD Mortality Among Incident ESRD Patients: A Cohort Study.

Albumin-corrected serum calcium (cSCa) decline at late stages of chronic kidney disease and rise after dialysis initiation. Although hypercalcemia is associated with higher mortality in end-stage renal disease (ESRD), there are scarce data on the impact of pre-ESRD cSCa on post-ESRD mortality. Therefore, we used a large national cohort of 21,826 US veterans who transitioned to dialysis in all US Department of Veterans Affairs health care facilities over 2009 to 2014 to examine the associations with all-cause and cause-specific post-ESRD mortality of (1) cSCa concentrations averaged over the last 6 months and (2) its rate of decline during the last 12 months before dialysis initiation. Mean concentrations and median rate of decline of cSCa were 9.3 ± 0.7 mg/dL and -0.15 (interquartile range -0.39 to 0.07) mg/dL/year, respectively. A total of 9596 patients died during the follow-up period (mean 1.9 years; total 41,541 patient-years) with an incidence rate of 23.1 per 100 patient-years. There was an independent linear association between higher cSCa with higher mortality (ptrend < 0.001). The mortality risk associated with cSCa ≥9.0 mg/dL was attenuated among active vitamin D users (pinteraction < 0.001). Patients with faster decline in cSCa showed lower mortality irrespective of baseline cSCa concentrations. These cSCa-mortality associations were stronger for noncardiovascular versus cardiovascular death. In conclusion, lower pre-ESRD cSCa and faster decline in cSCa were consistently and linearly associated with better post-ESRD survival among US veterans, especially for noncardiovascular death. Further studies are needed to determine if correcting hypocalcemia is beneficial or harmful and which intervention is preferred when indicated among patients transitioning to ESRD. © 2018 American Society for Bone and Mineral Research

ガッコウ ソシキ カイハツ リロン ニ モトズク キョウイク カツドウ ノ ソシキテキ カイゼン ニ カンスル ジッセン ケンキュウ

本研究は，学校組織開発理論（佐古 ２００９等）にもとづく，小学校の組織的な教育活動の改善に関する実践研究である。本研究では，以下の一連のプロセスを展開した。すなわち，事例校の実態をふまえて，①児童の実態についての認識共有，②児童の育成課題（根っこの課題）の設定と学校ビジョンの可視化，③実践改善の指針の作成，④焦点化した授業研究，⑤教職員の実践交流型（学び合い型）研修，を連続的に展開した。一連の組織開発方法論の実施によって，質問紙調査の結果から以下の変化が認められた。１）教職員の協働性が増大した。２）児童の育成課題達成に向けた実践改善が促進された。３）児童の基本課題として設定された自信や自尊感情についても，上昇した。４）児童の学習態度も改善され，授業の面白さを肯定する比率も増大した。This action research was aimed to improvement organized educational activities based on Theory of School Organizational Development (Sako 2009 et al.). In this study was conducted as a set of process based on Theory of School Organizational Development. Those were 1) sharing recognition of actual condition of the pupils, 2)setting fundamental development goal of pupils and visualization of school vision, 3) making guideline for improvement of teachers\u27 educational activities, 4) implementation of lesson studies focused on school vision, 5) teachers\u27 cooperative learning about their practices.Main effects of this action research on Theory of School Organizational Development were as follows. 1) The degree of collaboration was increased. 2) Teachers\u27 improvement of educational activities was facilitated. 3) The degree of pupils\u27 self-reliance or self-esteem, which were fundamental problems of this school, was increased. 4) Pupils\u27 attitude for study was improved and the proportion of positive response for interest of lesson was increased

Efficacy and safety of abatacept in active primary Sjogren's syndrome:results of a phase III, randomised, placebo-controlled trial

Objectives To evaluate efficacy and safety of abatacept in adults with active primary Sjogren's syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial. Methods Eligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjogren's Syndrome Disease Activity Index [ESSDAI] >= 5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored. Results Of 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI - 3.2 abatacept vs -3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified. Conclusions Abatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity