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医学部 附属病院 脳神経内科 |
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Resolvin D4 mitigates lipopolysaccharide-induced lung injury in mice
Inomata R., Tsubouchi H., Takao T., Kurokawa M., Yanagi S., Sakai K., Miyazaki T.
Prostaglandins Leukotrienes and Essential Fatty Acids 203 102652 2024年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Prostaglandins Leukotrienes and Essential Fatty Acids
Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving severe lung inflammation. The excessive oxidative stress and persistent inflammation that occur in ARDS lead to decreased epithelial integrity and hypoxemia due to pulmonary edema via increased vascular permeability. Resolvin D4 (RvD4) is one of the lipid mediators that is biosynthesized from omega-3 polyunsaturated fatty acids. It plays a role in the resolution of inflammation and reduces oxidative stress and cell death. We investigated the therapeutic potential of the administration of RvD4 in a murine model of lipopolysaccharide (LPS)-induced ARDS. Concurrent with the intratracheal administration of LPS, RvD4 or saline was administered to mice via the caudal vein every 12 h. This treatment with RvD4 alleviated the LPS-induced infiltration of inflammatory cells in lungs, inhibited increased pulmonary vascular permeability, decreased the levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF), and suppressed the reduction of the expression levels of the tight junction protein, Zonula occludens-1 (Zo-1) and the NAD+-dependent deacetylase, Sirtuin-3 (Sirt3). In vitro experiments revealed that in LPS-stimulated BEAS-2B cells, treatment with RvD4 suppressed the increases in the expressions of pro-inflammatory cytokines and maintained the epithelial cell barrier function and cell viability. The silencing of SIRT3 abolished both the anti-inflammatory effect and the retention of cell integrity in BEAS-2B cells. Together these results indicate that treatment with RvD4 can (i) protect against LPS-induced lung injury by inhibiting inflammation, and (ii) maintain epithelial barrier function via a reduction in the downregulation of SIRT3.
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Ghrelin–LEAP2 interactions along the stomach–liver axis 査読あり
Sakai Katsuya, Nakazato Yuki, Shiimura Yuki, Zhang Weidong, Nakazato Masamitsu
Endocrine Journal advpub ( 0 ) 2024年
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本内分泌学会
Ghrelin produced in the stomach promotes food intake and GH secretion, and acts as an anabolic peptide during starvation. Ghrelin binds to the growth hormone secretagogue receptor, a G protein-coupled receptor (GPCR), whose high-resolution complex structures have been determined in the apo state and when bound to an antagonist. Anamorelin, a low-molecular-weight ghrelin agonist, has been launched in Japan for the treatment of cancer cachexia, and its therapeutic potential has attracted attention due to the various biological activities of ghrelin. In 2019, liver-expressed antimicrobial peptide (LEAP2), initially discovered as an antimicrobial peptide produced in the liver, was identified to be upregulated in the stomach of diet-induced obese mice after vertical sleeve gastrectomy. LEAP2 binds to the GHSR and antagonizes ghrelin’s activities. The serum concentrations of human LEAP2 are positively correlated with body mass index, body fat accumulation, and fasting serum concentrations of glucose and triglyceride. Serum LEAP2 elevated and ghrelin reduced in obesity. Ghrelin and LEAP2 regulate body weight, food intake, and GH and blood glucose concentrations, and other physiological phenomena through their interactions with the same receptor, GHSR.
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Validation and Discussion of Severity Evaluation and Disease Classification Using Tremor Video
Hayashida T., Sugiyama T., Sakai K., Ishii N., Mochizuki H., Zin T.T.
Electronics (Switzerland) 12 ( 7 ) 2023年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Electronics (Switzerland)
A tremor is a significant symptom of Parkinson’s disease, but it can also be a characteristic of essential tremor, thereby hampering even specialists’ ability to differentiate between the two. This study proposes a system that leverages a single RGB camera to evaluate tremor severity and support the differential diagnosis of Parkinson’s disease and essential tremor. The system captures motor symptoms, performs time–frequency analysis using wavelet transforms, and classifies severity and disease using linear classification models. The results showed an accuracy rate of 0.56 for disease classification and 0.50 for severity classification (with an acceptable accuracy rate of 0.96). The analysis indicated that there was a low level of correlation between disease and each feature and a moderate correlation (about 0.6) between severity and each feature. Based on these results, this study recommends classifying severity with a linear model and disease with a nonlinear model to obtain improved accuracy.
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Oda Y., Tsubouchi H., Ishii N., Kitamura A., Moriyama E., Mitsutome E., Sakai K., Shiomi K., Yanagi S., Miyazaki T.
Respiratory Medicine Case Reports 46 101930 2023年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Respiratory Medicine Case Reports
Small cell lung carcinoma (SCLC) is a neuroendocrine carcinoma with a poor prognosis and is a common cause of paraneoplastic syndromes. Paraneoplastic syndromes are characterized by neurological and endocrinological problems in patients with malignancy and are often associated with difficulty in induction of chemotherapy. Here we report the case of a patient with SCLC concomitant with two paraneoplastic syndromes, syndrome of inappropriate antidiuretic hormone secretion (SIADH) and Lambert–Eaton myasthenic syndrome (LEMS), who was treated with a platinum-doublet chemotherapy regimen. A 66-year-old male patient presented with a 1-month history of progressive proximal muscle weakness, ataxia gait and 5 kg of body weight loss. The laboratory tests revealed hyponatremia due to SIADH and the existence of antibodies against P/Q-type voltage-gated calcium channels. The nerve conduction study showed a low amplitude of compound muscle action potential (0.38 mv), a 34% decrement on 3-Hz stimulation, and a 1939% increment after maximum voluntary contraction in 10 seconds (7.75 mv). The endobronchial ultrasound transbronchial needle aspiration biopsy revealed the pathological findings of SCLC. A 2-cycle chemotherapy regimen of irinotecan plus cisplatin resulted in temporary tumor shrinkage that lasted 2 months, but the improvement of proximal muscle weakness and hyponatremia were maintained over the tumor re-progression period after chemotherapy. Although paraneoplastic syndromes accelerate the decrease in performance status, chemotherapy for SCLC may improve symptoms related to paraneoplastic syndromes and could be considered in similar cases.
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Md Nurul Islam, Weidong Zhang, Katsuya Sakai, Yuki Nakazato, Ryota Tanida, Hideyuki Sakoda, Toshiki Takei, Toshifumi Takao, Masamitsu Nakazato
Peptides 151 170763 - 170763 2022年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Ghrelin is a gastric-derived peptide that stimulates feeding, blood glucose elevation, body temperature reduction, and growth hormone (GH) secretion. Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist of the ghrelin receptor, also called growth hormone secretagogue receptor (GHSR). We studied the effects of LEAP2 administration on feeding, body weight, glycemia, body temperature, and inflammation-related genes in the liver in C57BL/6 J mice and Ghsr-knockout (Ghsr-KO) mice. We found that a single administration of LEAP2 did not abolish fasting-induced food intake in 24-h fasted C57BL/6 J mice or Ghsr-KO mice. Moreover, continuous LEAP2 administration to mice fed ad libitum for 6 days did not affect feeding, body temperature, plasma ghrelin, or blood glucose. By contrast, continuous LEAP2 administration to calorie-restricted C57BL/6 J mice and Ghsr-KO mice induced body weight loss, hypoglycemia, body temperature reduction, and upregulation of Il-6 and Il-1β mRNAs in the liver. Our findings suggest that LEAP2 functions independently of GHSR, implying that LEAP2 affects physiology beyond the ghrelin-GHSR system.
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スマートフォンを用いた振戦の定量評価
酒井 克也、石井 信之、望月 仁志
Clinical Neuroscience 40 ( 9 ) 1176 - 1177 2022年9月
記述言語：日本語 掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
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グレリンとLEAP2
酒井 克也, 中里 雅光
BIO Clinica 37 ( 4 ) 16 (326) - 20 (330) 2022年3月
掲載種別：速報，短報，研究ノート等（学術雑誌）
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本年の動向 振戦の定量解析
酒井 克也, 石井 信之, 望月 仁志
Annual Review神経 2021 109 - 115 2021年6月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(株)中外医学社
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ギラン・バレー症候群治療中に判明したツツガムシ病の1例
武田 紘昌, 杉山 崇史, 宮本 美由貴, 金丸 和樹, 酒井 克也, 中里 祐毅, 望月 仁志, 中里 雅光, 塩見 一剛
臨床神経学 61 ( 6 ) 430 - 430 2021年6月
記述言語：日本語 掲載種別：速報，短報，研究ノート等（学術雑誌） 出版者・発行元：(一社)日本神経学会
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細菌性髄膜炎における髄液中Liver-expressed microbial peptide 2 (LEAP2)の上昇
酒井克也, 望月仁志, 塩見一剛, 中里雅光
第62回日本神経学会学術大会 62nd 2021年5月
掲載種別：速報，短報，研究ノート等（学術雑誌）
講演・口頭発表等 【 表示 ／ 非表示 】
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MRIと脳波で病変伸展の過程を検出し得たhuman herpes virus-6（HHV-6）脳炎の一例
酒井 克也
第94回 日本感染症学会 西日本地方会学術集会
開催年月日： 2024年11月14日 - 2024年11月16日
会議種別：口頭発表（一般）
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「足運動解析装置」を用いたパーキンソン病の足運動の定量的評価
酒井 克也
第54回 日本臨床神経生理学会 学術大会
開催年月日： 2024年10月24日 - 2024年10月26日
会議種別：ポスター発表
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70歳以上で症状が顕在化した顔面肩甲上腕型筋ジストロフィー（FSHD）の1例
金丸和樹、宮本美由貴、酒井克也、中里祐毅、杉山崇史、望月仁志、（西野一三）、塩見一剛
第235回日本神経学会九州地方会 (ハイブリッド開催)
開催年月日： 2022年3月19日
会議種別：口頭発表（一般）
開催地：ハイブリッド開催
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緩徐進行性の不随意運動と認知機能障害を呈し，17 年の経過で死亡した40 歳女性剖検例
中里祐毅、金丸和樹、宮本美由貴、酒井克也、海老原由佳、杉山崇史、望月仁志、塩見一剛
第40回日本認知症学会学術集会 (ハイブリッド開催)
開催年月日： 2021年11月26日 - 2021年11月28日
会議種別：口頭発表（一般）
開催地：ハイブリッド開催
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コロナワクチン後に生じたと考えられる脳脊髄液減少により体位性頻脈を認めた一例
長友優菜、金丸和樹、杉山崇史、宮本美由貴、酒井克也、中里祐毅、望月仁志、塩見一剛
第233回日本神経学会九州地方会 (web開催)
開催年月日： 2021年9月18日
会議種別：口頭発表（一般）
開催地：web開催
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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担癌状態のパクリタキセルの神経毒性とグレリンシグナル活性化による神経保護の検討
研究課題/領域番号：24K10536 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
担当区分：研究分担者
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生理活性ペプチドLEAP2を用いた細菌性髄膜炎の新規診断法と治療探索研究
研究課題/領域番号：24K18646 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 若手研究
担当区分：研究代表者