609 research outputs found

    CREBH Regulates Systemic Glucose and Lipid Metabolism

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    The cyclic adenosine monophosphate (cAMP)-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL) activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα), has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα) in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine

    Solar thermophotovoltaic using Al2O3/Er3 Al5O12 eutectic composite selective emitter

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    科研費報告書収録論文(課題番号:11555057・基盤研究(B)(2)・H11~H13/研究代表者:湯上, 浩雄/太陽熱光起電力による高温輻射-電力直接変換システムの開発

    Coronary artery spasm—Clinical features, diagnosis, pathogenesis, and treatment

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    SummaryCoronary (artery) spasm plays an important role in the pathogenesis of ischemic heart disease, including stable angina, unstable angina, myocardial infarction, and sudden death. The prevalence of coronary spasm differs among populations, is higher in Japan and Korea than in the Western countries probably due to genetic as well as environmental factors. Coronary spasm occurs most often from midnight to early morning and is usually not induced by exercise in the daytime. The attacks of coronary spasm are associated with either ST segment elevation or depression, or negative U wave on ECG. Patients with multi-vessel coronary spasm may suffer from lethal arrhythmia, including advanced AV block, ventricular tachycardia or fibrillation, or even sudden death, and they are often resistant to conventional medical therapy including Ca-channel blockers (CCBs). Endothelial nitric oxide (NO) activity is reduced and markers of oxidative stress are elevated in patients with coronary spasm. Thrombogenesis is enhanced and plasma levels of hsCRP and P-selection are elevated in patients with coronary spasm. Thus, patients with coronary spasm have endothelial dysfunction and are suffering from a low-grade chronic inflammation. Polymorphisms of endothelial NO synthase, smoking, and low-grade inflammation are the most important risk factors for coronary spasm. Coronary spasm is a hyper-contraction of coronary smooth muscle triggered by an increase of intracellular Ca2+ in the presence of an increased Ca2+ sensitivity. It has been shown that RhoA/ROCK pathway is involved in Ca2+ sensitivity and that the reduced endothelial NO activity results in increased Ca2+ sensitivity through enhanced RhoA/ROCK pathway. Accordingly, it is possible that in addition to CCBs, RhoA/ROCK pathway blockers may prove to be useful for the treatment of coronary spasm

    Metal-binding domains and the metal selectivity of the vanadium(IV)-binding protein VBP-129 in blood plasma

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    Ascidians are well known to accumulate extremely high levels of vanadium in their blood cells. Several key proteins related to vanadium accumulation and physiological function have been isolated from vanadium-rich ascidians. Of these, vanadium(IV)-binding protein-129 (VBP-129) is a unique protein that has been identified from the blood plasma of an ascidian Ascidia sydneiensis samea, but its metal binding domains are not known. In this study, several deletion and point mutants of VBP-129 were generated, and their metal binding abilities were assessed by immobilized metal ion affinity chromatography (IMAC) and electron spin resonance spectroscopy (ESR). The internal partial protein, VBP-Int41, did not bind to VIV, but the two constructs, VBP-N52 and VBP-Int55, added with additional 11 or 14 neighboring amino acids bound to VIV. Mutations for cysteine-47 and lysine-50 in VBP-Int55 diminished VIV-binding in VBP-Int55, suggesting that these amino acid residues play important roles in binding VIV. ESR titration analysis revealed that VBP-129, VBP-N52 and VBP-Int55 could bind to 6, 3 and 2 VIV ions, respectively. ESR spectrum analysis indicated a N2O2 coordination geometry, which is similar to Vanabins. The cysteines may contribute to the maintenance of the three-dimensional structure that is necessary for binding VIV ions. VBP-129 did not have a VV-reductase activity, as expected from its tissue localization in blood plasma. This study provided the evidences that VBP-129 possesses VIV-binding domains that make a similar coordination to VIV as those by Vanabins but VBP-129 acts solely as VIV-chaperon in blood plasma.This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (nos. 20570070 and 21570077)

    Immunohistochemical Analysis of Colorectal Cancer among Atomic Bomb Survivors in Hiroshima

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    In order to elucidate the biological characteristics of colorectal cancer among atomic bomb survivors in Hiroshima, a total of 159 cases of colorectal cancers comprising 73 cases in exposed atomic bomb survivors and 86 cases in non-exposed individuals were examined histologically and immunohistochemically for various functioning proteins. No statistical differences could be demonstrated in the incidence of various marker expressions of colorectal cancers between the exposed group and control group. However, comparison by the site of colorectal cancer showed that sigmoid colon cancers in the exposed group or high dose group showed a significantly higher frequency of glycoproteins such as α1-antichymotrypsin (ACT), secretory component (SC), α1-antitrypsin (AAT), and human chorionic gonadotropin (HCG) when compared with the control group. These results correlated well with the epidemiological data that the radiation effect on the incidence of colorectal cancer in atomic bomb survivors was most remarkable in the sigmoid colon.This study was supported in part by Grants in Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan

    Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a nationwide analysis of the Japan renal biopsy registry from 2007 to 2015

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    BackgroundThe incidence and age distribution of membranoproliferative glomerulonephritis (MPGN) vary throughout the world by race and ethnicity. We sought to evaluate the clinical features, pathogenesis, and age distribution of MPGN among a large nationwide data from the Japan Renal Biopsy Registry (J-RBR).MethodsA cross-sectional survey of 593 patients with MPGN (types I and III) registered in the J-RBR between 2007 and 2015 was conducted. Clinical parameters, and laboratory findings at diagnosis were compared between children (< 20 years), adults (20–64 years), and elderly patients (≥ 65 years).ResultsThe median age of the patients was 59.0 years and mean proteinuria was 3.7 g/day. The rate of nephrotic syndrome was significantly higher in adults (40.4%) and elderly patients (54.0%) than in children (14.9%), whereas the rate of chronic glomerulonephritis was significantly higher in children (66.2%) than in adults (34.4%) and elderly patients (31.2%). According to the CGA risk classification, high-risk (red zone) cases accounted for 3.4% of children, 52.5% of adults and 84.1% of elderly patients with MPGN. As for pathogenesis, primary MPGN was most frequent (56.0%). Lupus nephritis was the most common disease among adult patients with secondary MPGN, whereas infectious disease was more common in elderly patients. Multiple regression analysis revealed that high systolic blood pressure and high proteinuria were independent factors associated with decreased estimated glomerular filtration rate (eGFR) in adults and elderly patients with MPGN.ConclusionsIn Japan, adults and elderly patients with MPGN had a lower eGFR and severer proteinuria than children
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