聴覚障害者へのソーシャルワ－クにおける専門性研究 －ろう文化視点に基づく支援をめざして－ [全文の要約]

関西大

聴覚障害者へのソーシャルワークにおける専門性研究 －ろう文化視点に基づく支援をめざして－ [論文要旨及び審査の要旨]

関西大

オレキシンニューロンのグルコース感受性機構とその生理的役割の解明

金沢大学医学系オレキシンニューロンのグルコースセンサーとしての機能に与える影響、そしてオレキシンニューロンが細胞外グルコース濃度を検出するために必要なチャネル分子を特定するために、電気生理学的手法を用いて、オレキシンニューロンのパッチクランプを行っているが、特定の分子、チャネルを特定するまでには至っていない。しかし、細胞外環境によって、オレキシンニューロンのグルコースに対する反応性が異なることがわかってきた。また計画の中の一つであるグルコース感知メカニズムに関与する可能性がある分子がオレキシンニューロンに発現しているかどうかを調べるためのマイクロアレイ解析において、電気生理で用いた個々のオレキシンニューロンを集めmRNAを調達していたが、平成22年度の報告書では、ニューロンの数が足りない状況ではあったが、今現在はmRNAを調達するための必要なニューロンを確保できたので、マイクロアレイ解析に持ち込める段階にある。行動実験については、オレキシンニューロンを特異的に欠損させたトランスジェニックマウス、orexin/ataxin-3マウス(Hara et al ; Neuron, 2001)をすでに確立しており、それを実験に用いた。このマウスを、低グルコース状態下また逆に高グルコース状態下におき、それぞれの状況下での行動パターンの測定、脳波をモニターし、睡眠・覚醒パターンを通常の状態とコントロールマウスと比べ、変化があるかどうかを調べている最中である。これが調べ終わった後に自律神経系の変化、具体的には血圧、心拍数などラジオテレメトリー装置を用いて測定したいと考えている。以上の実験系を用いて、個体レベルにおいて、オレキシンニューロンのグルコースセンサーとしての機能、関わりを明らかにしたい。研究課題/領域番号:22790205, 研究期間(年度):2010 – 2011出典：研究課題「オレキシンニューロンのグルコース感受性機構とその生理的役割の解明」課題番号22790205（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22790205/）を加工して作

Oncogenic FGFR1 mutation and amplification in common cellular origin in a composite tumor with neuroblastoma and pheochromocytoma

Neuroblastoma (NB) and pheochromocytoma (PCC) are derived from neural crest cells (NCCs); however, composite tumors with NB and PCC are rare, and their underlying molecular mechanisms remain unknown. To address this issue, we performed exome and transcriptome sequencing with formalin-fixed paraffin-embedded (FFPE) samples from the NB, PCC, and mixed lesions in a patient with a composite tumor. Whole-exome sequencing revealed that most mutations (80%) were shared by all samples, indicating that NB and PCC evolved from the same clone. Notably, all samples harbored both mutation and focal amplification in the FGFR1 oncogene, resulting in an extraordinarily high expression, likely to be the main driver of this tumor. Transcriptome sequencing revealed undifferentiated expression profiles for the NB lesions. Considering that a metastatic lesion was also composite, most likely, the primitive founding lesions should differentiate into both NB and PCC. This is the first reported case with composite-NB and PCC genetically proven to harbor an oncogenic FGFR1 alteration of a common cellular origin

半側空間無視症例の正中認知に与えるヘッドマウントディスプレイアダプテーションの即時効果

東京都立大

Nintedanib can be used safely and effectively for idiopathic pulmonary fibrosis with predicted forced vital capacity <= 50%: A multi-center retrospective analysis

Background Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. Methods This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. Results 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. Conclusions Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment

Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

金沢大学医薬保健研究域医学系Stress-induced analgesia (SIA) is a key component of the defensive behavioral "fight-or-flight" response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein-regulated inwardly rectifying K+ (GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices. Orexin/ataxin-3 mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA