MicroRNA-26aはポドサイトにおいてCTGFを標的としTGF-βによる細胞外基質産生を抑制し、糖尿病性腎症において発現低下する意義に関する研究

京都大学0048新制・課程博士博士(医学)甲第19396号医博第4047号新制||医||1012(附属図書館)32421京都大学大学院医学研究科医学専攻(主査)教授 長船 健二, 教授 野田 亮, 教授 萩原 正敏学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDGA

Generalised Acanthosis Nigricans in Childhood with Short Stature Associated with Poor Response to Growth Hormone Provocation

Acanthosis nigricans (AN) is a skin disorder characterised by skin hyperpigmentation and thickening, especially in the intertriginous regions. AN is usually classified as either malignant, benign, obesity-associated, syndromic, unilateral, acral, drug-induced and mixed (1). A generalised form of AN frequently occurs together with internal malignancy in adult patients, but it is rare in childhood (2-7). Here, we report a paediatric case of generalised AN associated with short stature accompanied with decreased growth hormone levels.ArticleACTA DERMATO-VENEREOLOGICA. 94(4):486-487 (2014)journal articl

Promotion of Secondary School Science Education Driven by Inquiry-Based Activity

This article reports fundamental researches organized for developing a novel teaching/learning system in secondary school science. A curriculum constructed by an effective integration of content-based and context-based curriculum arrangements is proposed for generating teaching/learning opportunities through various inquiry-based activities on the basis of previously acquired science knowledge and concepts. The science subjects, including physics, chemistry, biology and earth science, have different logics and methodologies of science, but those are completed by mutual interdependences. Therefore, various storylines that cover different leraning contents in science subjects can be developed. The inquiry-based activities along different storylines provide students with opportunities to correlate previous learnings in different science subjects and to experience various cognitive and scientific skills. Based on such findings of our basic researches, the merits of the science education system proposed in this study is discussed briefly.本研究は，科学研究費補助金基盤研究(A)(一般)(25242015)による

Significant survival improvement of patients with recurrent breast cancer in the periods 2001-2008 vs. 1992-2000

<p>Abstract</p> <p>Background</p> <p>It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs) and trastuzumab.</p> <p>Methods</p> <p>A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared.</p> <p>Results</p> <p>Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P < 0.001). The median overall survival (OS) times after breast cancer recurrence were 1.7 years and 4.2 years for these respective cohorts (P < 0.001). Both the time period and treatment of AIs and/or trastuzumab for recurrent disease were significant prognostic factors in multivariate analysis (cohort B vs. cohort A: HR = 0.70, P = 0.01; AIs and/or trastuzumab for recurrent disease: yes vs. no: HR = 0.46, P < 0.001). When patients were categorized into 4 subgroups by the expression of hormone receptor (HR) and HER-2 status, the median OS times of the HR-positive/HER-2-negative, HR-positive/HER-2-positive, HR-negative/HER-2-positive, and HR-negative/HER-2-negative subtypes were 2.2, 2.4, 1.6, and 1.0 years in cohort A and 4.5, 5.1, 5.0, and 1.4 years in cohort B.</p> <p>Conclusions</p> <p>The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors.</p

Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy

There is a hot debate concerning actual amount of albumin filtered through glomeruli and reabsorbed at proximal tubules in normal kidneys and diabetic conditions. To overcome current technical problems, we generated a drug-inducible megalin knockout mouse line, megalin(lox/lox);Ndrg1-CreER[T2] (or iMegKO), whose protein reabsorption can be shut off anytime by tamoxifen (Tam). After Tam administration, renal megalin protein expression was reduced by 92% compared to wild-type C57BL/6J mice, and renal reabsorption of intravenously-injected retinol binding protein was almost completely abrogated. Urinary albumin excretion increased to 175 μg/day (0.460 mg/mg-creatinine), suggesting that this was the amount of total nephron albumin filtration. Glomerular sieving coefficient of albumin was 1.7 x 10[-5]. By comparing streptozotocin-induced, Tam-treated, diabetic STZ;iMegKO mice with non-STZ;iMegKO mice, we estimated that daily albumin filtration was increased by 1.9-fold, reabsorption was increased by 1.8-fold, and reabsorption efficiency was reduced to 86% by development of diabetes (versus 96% in control). Such abnormalities were well normalized after insulin treatment. Another type 1 diabetic model of Akita;iMegKO mice showed equivalent results. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy, bringing new insights into our understanding of renal albumin dynamics in hyperfiltration status of diabetic nephropath

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels.Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation.Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels