129 research outputs found

    Flecainide reduces ventricular arrhythmias via a mechanism that differs from that of β-blockers in catecholaminergic polymorphic ventricular tachycardia

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    AbstractBackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by episodic ventricular tachycardia induced by adrenergic stress. Although β-blockers are used as first-line therapy, their therapeutic effects are largely incomplete. Flecainide has recently been shown to modify the molecular defects in CPVT. The aim of this study was to investigate the effects of flecainide as an add-on to conventional therapy on exercise-induced ventricular arrhythmia and compare them with those of conventional therapy alone.MethodsThe study included 5 CPVT patients with a mutation in RYR2. They experienced episodic arrhythmic events despite conventional β-blocker therapy and were therefore given flecainide in addition. The effects of the addition of flecainide therapy on ventricular arrhythmia during exercise testing were compared with those of conventional therapy alone.ResultsBoth β-blockers alone and with additional flecainide increased the maximal workload attained at the onset of ventricular arrhythmia; however, only flecainide increased the sinus rate at the onset of ventricular arrhythmias. Furthermore, flecainide increased the exercise capacity by preventing exercise-induced arrhythmias. During a follow-up period of 17±2 months, 1 patient experienced recurrent arrhythmic episodes that were associated with noncompliance. All patients reported improvements in their ability to perform the activities of daily living.ConclusionFlecainide effectively reduced ventricular arrhythmias via a mechanism that differs from that of β-blockers in genotype-positive patients with CPVT. The specific effects of flecainide may be critical in the improvement noted in the patients' ability to perform daily activities

    B cell-derived GABA elicits IL-10⁺ macrophages to limit anti-tumour immunity

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    GABAを標的とする抗腫瘍免疫機構 --代謝産物を介した免疫細胞間制御の一端を解明--. 京都大学プレスリリース. 2021-11-10.Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1-3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8⁺ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses

    UNIFORM-1: First Micro-Satellite of Forest Fire Monitoring Constellation Project

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    UNIFORM Project had started in November 2010 with its vision of constructing sustainable micro-satellite constellation system via cooperation with various countries. International collaboration and actual utilization of the system are the keys of the project for realizing sustainable space industry. Forest fire monitoring was selected as the first mission. UNIFORM-1 is the first micro-satellite, weighing 50kg with 50cm cubic size, in this project and launched on May 24th, 2014 by H-IIA rocket as a secondary payload. UNIFORM-1 carries two cameras of area sensor: uncooled microbolometer camera and visible light camera. Both have GSD of less than 200[m] and swath is about 100km. These two cameras are used for localization of heat anomaly spots. The acquired image will be overlaid on global map to generate a “forest fire map” which will be released so that local fire department of the concerning country can take action promptly and extinguish forest fire. Other key features of this satellite are following: 3-axis control with reaction wheels, deployable solar array panel wings, lithium ion battery, and 10Mbps X-band transmitter for mission data. Design and test result of UNIFORM-1 flight model is explained in detail in this paper. As the result of initial operation of five days after launch, image of infrared camera was successfully acquired

    女性看護師の疲労感・生活習慣・自己効力感との関連性に関する研究

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    原著Originals 本研究は、女性看護師における生活習慣、疲労感、勤務状況および自己効力感を調査し関連性を検討することで、看護師の自己効力感を高め、疲労軽減策への基礎資料を得ることを目的としている。2施設において女性看護師を対象に意識調査を実施し、867 名を分析対象とした。調査内容は、生活習慣9項目、蓄積的疲労徴候インデックス(CFSI)、一般性セルフ・エフィカシー尺度(GSES)を使用した。 本論では、疲労感と生活習慣・自己効力感に影響する要因分析を行った。一元配置分散分析、多重比較、共分散構造分析を用いて関連性の検討の結果、疲労感に有意に影響が強かった生活習慣は、労働時間、睡眠時間、食事、喫煙であった。本研究で構築した因果モデルを分析した結果、自己効力感は疲労感に影響し、身体的疲労が精神的疲労に影響することが確認できた。健康的な生活習慣を実施する重要性と、自己効力感と疲労感の関係性が示唆された

    The Homeodomain Protein Defective Proventriculus Is Essential for Male Accessory Gland Development to Enhance Fecundity in Drosophila

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    The Drosophila male accessory gland has functions similar to those of the mammalian prostate gland and the seminal vesicle, and secretes accessory gland proteins into the seminal fluid. Each of the two lobes of the accessory gland is composed of two types of binucleate cell: about 1,000 main cells and 40 secondary cells. A well-known accessory gland protein, sex peptide, is secreted from the main cells and induces female postmating response to increase progeny production, whereas little is known about physiological significance of the secondary cells. The homeodomain transcriptional repressor Defective proventriculus (Dve) is strongly expressed in adult secondary cells, and its mutation resulted in loss of secondary cells, mononucleation of main cells, and reduced size of the accessory gland. dve mutant males had low fecundity despite the presence of sex peptide, and failed to induce the female postmating responses of increased egg laying and reduced sexual receptivity. RNAi-mediated dve knockdown males also had low fecundity with normally binucleate main cells. We provide the first evidence that secondary cells are crucial for male fecundity, and also that Dve activity is required for survival of the secondary cells. These findings provide new insights into a mechanism of fertility/fecundity
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