研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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急性腎障害を合併した消化器疾患における尿中NGAL測定による予後予測

小島雄一, 渡邉雄介, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A393 - A393 2023年3月

消化器疾患とビッグデータインターネット普及による薬物関連有害事象報告の変遷 FDAの20年の副作用報告からの解析

上村博輝, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A40 - A40 2023年3月

十全大補湯と間葉系幹細胞の併用療法は肝硬変・急性肝障害モデルマウスにおいて効果的な抗炎症・抗線維化効果を及ぼす

野尻俊介, 土屋淳紀, 佐藤毅昂, 熊谷優, 茂木聡子, 岩澤貴宏, 小川雅裕, 竹内卓, 寺井崇二

肝臓 64 ( 3 ) 172 - 172 2023年3月

臨床応用を目指した消化器領域の再生医療研究肝硬変のエクソソーム治療を目指した基礎的検討

武田信峻, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A166 - A166 2023年3月

消化器診療とliquid biopsy 肝硬変の線維化の新たなエクソソームマーカー開発

土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A159 - A159 2023年3月

肝線維化研究の最前線と治療への展開 HMGB1部分ペプチドを用いた肝線維化改善検証と医師主導治験

土屋淳紀, 渡邉雄介, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A77 - A77 2023年3月

膵癌早期診断の最前線 cStage 0/I膵癌の臨床像膵癌病態解析に関する多施設後方視的観察研究の結果より

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A135 - A135 2023年3月

当院における膵小病変に対するEUS-FNA/Bの成績

林和直, 小川光平, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A375 - A375 2023年3月

肥満モデルマウスを用いた、脂肪細胞の機能に着目した肥満制御メカニズムの解明

坂牧僚, 阿部寛幸, 上村顕也, 寺井崇二

新潟県医師会報 ( 876 ) 12 - 13 2023年3月

肝疾患における血中セロトニン値のバイオマーカーとしての有用性の検討

薛徹, 上村顕也, 寺井崇二

肝臓 64 ( 3 ) 171 - 171 2023年3月

Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans. 国際誌

Kazuki Natsui, Atsunori Tsuchiya, Risa Imamiya, Mayuko Osada-Oka, Yui Ishii, Yohei Koseki, Nobutaka Takeda, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Riuko Ohashi, Yiwei Ling, Koji Ueda, Nobuko Moritoki, Kazuhiro Sato, Takahiro Nakajima, Yoshinori Hasegawa, Shujiro Okuda, Shinsuke Shibata, Shuji Terai

Liver international : official journal of the International Association for the Study of the Liver 43 ( 5 ) 1126 - 1140 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND & AIMS: Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer membrane vesicles (OMVs) of Escherichia coli which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. METHODS: We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from Escherichia coli in mice using mouse liver-derived cells and a mouse cirrhosis model. RESULTS: In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis, and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis. CONCLUSIONS: In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.

DOI： 10.1111/liv.15539

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Performance characteristics of 5 numerical indexes in mixing test interpretation under coexistence of lupus anticoagulant and coagulation factor deficiency. 国際誌

Masato Matsuda, Yoshiki Hoshiyama, Kazuei Ogawa, Mari Emmi, Shuji Terai, Masato Moriyama

Research and practice in thrombosis and haemostasis 7 ( 2 ) 100065 - 100065 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The mixing test is useful to investigate the cause of unexpectedly prolonged activated partial thromboplastin time (APTT). Several indexes are available for distinguishing correction from non-correction (ie, factor deficiency from inhibitors), but their performance characteristics may differ because of their different formulas. Furthermore, it is unclear how each index performs under the coexistence of factor deficiency and inhibitors. OBJECTIVES: The objective of this study was to examine the differences in indexes, depending on factor VIII activity (FVIII:C) levels and lupus anticoagulant (LA) titers in test samples. METHODS: APTT was measured in spiked samples with various FVIII:C levels and LA titers, normal pooled plasma (NPP), and their 4:1, 1:1, and 1:4 mixtures. The following 5 indexes were calculated: index of circulating anticoagulant, mixing test normalized ratio, 4:1 and 1:1 percent corrections, and an APTT difference between the 1:1 mixture and NPP. The samples with LA, showing correction, were measured for FVIII:C in a one-stage assay to check parallelism. RESULTS: All indexes showed correction under FVIII deficiency and non-correction under higher LA titers. However, under lower LA titers, some indexes showed non-correction but others showed correction because of dilution effects and variations in formulas and/or sample mix ratios. The differences among the indexes were more pronounced under coexistent FVIII deficiency and LA, even though LA titers were equal in the tested samples; samples with lower FVIII:C showed correction, whereas those with normal FVIII:C showed non-correction. The samples tested for FVIII:C showed non-parallelism. CONCLUSION: Each index had different performance characteristics to LA samples, which were pronounced under low FVIII:C levels in test samples.

DOI： 10.1016/j.rpth.2023.100065

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急性肝不全に対する治療内科,外科の立場から新潟県での急性肝不全診療ネットワークの構築とOn line HD導入への取り組み

薛徹, 上村博輝, 坂牧僚, 横尾健, 上村顕也, 土屋淳紀, 高村昌明, 寺井崇二

肝臓 64 ( 2 ) 92 - 93 2023年2月

【高齢者の消化器疾患-最新の診断と治療-】肝硬変・肝細胞癌

坂牧僚, 寺井崇二

日本臨床 81 ( 2 ) 256 - 260 2023年2月

Analysis of Genetic Relatedness between Gastric and Oral Helicobacter pylori in Patients with Early Gastric Cancer Using Multilocus Sequence Typing

Ryoko Nagata, Hiroki Sato, Shoji Takenaka, Junji Yokoyama, Shuji Terai, Hitomi Mimuro, Yuichiro Noiri

International Journal of Molecular Sciences 24 ( 3 ) 2211 - 2211 2023年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

The oral cavity is the second most colonized site of Helicobacter pylori after the stomach. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer through multilocus sequence typing (MLST) analysis using eight housekeeping genes. Gastric biopsy specimens and oral samples were collected from 21 patients with a fecal antigen test positive for H. pylori. The number of H. pylori allelic profiles ranged from zero to eight since the yield of DNA was small even when the nested PCR was performed. MLST analysis revealed that only one patient had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in six patients was similar to gastric H. pylori, implying that the two strains are related but not of the same origin, and those strains may be infected on separate occasions. It is necessary to establish a culture method for oral H. pylori to elucidate whether the oral cavity acts as the source of gastric infection, as our analysis was based on a limited number of allele sequences.

DOI： 10.3390/ijms24032211

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Analysis of drug-induced liver-related adverse event trend reporting between 1997 and 2019. 国際誌

Hiroteru Kamimura, Toru Setsu, Naruhiro Kimura, Makoto Miyazawa, Shota Kaneko, Kenya Kamimura, Atsunori Tsuchiya, Yoshihiro Uesawa, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 6 ) 556 - 568 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: This study aimed to analyze the current trends of drug-induced liver-related adverse events in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases. METHODS: The characteristics of implicated drugs were investigated by analyzing big data on drug-induced liver-related adverse events over the past 20 years in FAERS, comparing drug rankings between the JADER and FAERS databases, and calculating rankings of drugs inducing liver-related adverse events using the Medical Dictionary for Regulatory Activities Terminology. RESULTS: In the 452,272 cases registered in FAERS from 1997 to 2019, warfarin, paracetamol, and adalimumab were the drugs most related to DILI. In the 38,919 cases registered in the JADER from 2004 to 2019, sorafenib, nivolumab, and herbal extracts were the drugs most related to DILI. No associations were found between the top 30 drugs in either of the two databases. Notably, the number of drug-induced liver-related adverse event reports and total adverse events has sharply increased in recent years. CONCLUSIONS: Although liver-related adverse events are largely caused by host immunity and other constitutional factors, differences in primary diseases, countries, and historical backgrounds lead to differences in the number of reports. Securing an appropriate database and a mechanism to collect real-time information on the frequency of adverse drug reactions is warranted. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13883

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Navitoclax improves acute-on-chronic liver failure by eliminating senescent cells in mice. 国際誌

Yusuke Watanabe, Hiroyuki Abe, Naruhiro Kimura, Yoshihisa Arao, Natsuki Ishikawa, Maeda Yuichiro, Toru Setsu, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 5 ) 460 - 472 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS: Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS: Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS: Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.

DOI： 10.1111/hepr.13879

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Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study

Kubota, K., Kamisawa, T., Nakazawa, T., Tanaka, A., Naitoh, I., Kurita, Y., Takikawa, H., Unno, M., Kawa, S., Masamune, A., Nakamura, S., Okazaki, K., Furumatsu, K., Sawai, S., Goto, T., Okumura, T., Suzuki, D., Otsuka, M., Kobori, I., Tamano, M., Koizumi, M., Hiasa, Y., Kawabe, N., Hirooka, Y., Yamamoto, S., Asano, Y., Inui, K., Horiguchi, A., Watanabe, H., Toya, D., Hatayama, K., Ueki, T., Kinoshita, N., Sugimoto, M., Ohira, H., Mukai, T., Tomita, E., Iwata, K., Shimizu, S., Suetsugu, J., Shimizu, M., Tsuji, K., Ishida, R., Ito, M., Furukawa, R., Sakamoto, N., Araki, M., Tanno, S., Sakamoto, Y., Ito, T., Takai, S., Ikeya, S., Yamada, T., Kudara, N., Shimizu, A., Hanada, K., Ichiki, Y., Kitada, H., Hifumi, M., Kimura, H., Kurosaki, M., Izumi, N., Sumi, H., Haruta, J.-I., Hayashi, K., Harada, R., Inoue, M., Nakamura, S., Ito, T., Tomishima, K., Isayama, H., Oura, K., Masaki, T., Shimokawahara, N., Tanoue, S., Maemura, K., Ido, A., Mizushima, I., Kawano, M., Yoshida, K., Naganuma, M., Murata, M., Nishio, A., Fujita, Y., Teratani, T., Matsubara, S., Tamai, H., Yoshida, Y., Azemoto, R., Kamata, K., Watanabe, T., Kurosu, T., Koizumi, W., Fujita, J., Seki, H., Ueda, Y., Fukumoto, T., Kousaki, T., Uchida, K., Ochiai, T., Kawasaki, T., Tanaka, M., Ishida, E., Notohara, K., Mori, H., Mori, T., Kawabata, H., Miyata, M., Sakagami, J., Itoh, Y., Shiokawa, M., Seno, H., Watanabe, N., Kataoka, H., Aoki, T., Fujishiro, M., Niihara, T., Nishimata, H., Mitoro, A., Yoshiji, H., Yoshida, M., Ikeda, M., Tomita, K., Hokari, R., Hayasaka, K., Amano, Y., Shioji, K., Hayashi, K., Terai, S., Nakajima, M., Yamahana, J., Matsumoto, R., Kikuchi, H., Kanamori, A., Kiriyama, S., Iwatsu, S., Kato, Y., Horiguchi, S., Yagi, T., Okada, H., Ohkawa, K., Hirao, M., Hiramatsu, N., Oza, N., Imamura, H., Baba, T., Nakano, S., Shinobi, T., Ryozawa, S., Motoya, M., Nakase, H., Kinoshita, N., Ito, K., Miyake, T., Kohge, N., Tobita, H., Joshita, S., Umemura, T., Kawaguchi, S., Ohno, K., Sonobe, K., Satoh, A., Shimosegawa, T., Miura, F., Yagi, M., Sano, K., Kin, T., Katanuma, A., Koike, K., Miura, S., Kawashima, Y., Kagawa, T., Azuma, S., Watanabe, M., Honjyo, M., Itoi, T., Honda, A., Kobayashi, K., Asano, T., Mizuno, S., Koike, K., Nishino, T., Taniguchi, H., Tajiri, K., Yasuda, I., Tanaka, Y., Oe, S., Harada, M., Kurata, M., Fukasawa, M., Enomoto, N., Kawaji, Y., Kitano, M., Nishise, Y., Hirakawa, H., Ishizawa, T., Ueno, Y., Kaino, M., Fujimoto, Y., Sakaida, I.

Journal of Gastroenterology and Hepatology (Australia) 38 ( 4 ) 2023年

[Toward liver fibrosis amelioration and regenerative therapy using mesenchymal stem cells, extracellular vesicles, and peptides].

Atsunori Tsuchiya, Shuji Terai

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 120 ( 12 ) 973 - 979 2023年

Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan

Tsuchiya, A., Terai, S., Horiguchi, I., Homma, Y., Saito, A., Nakamura, N., Sato, Y., Ochiya, T., Kino-oka, M.

Regenerative Therapy 21 19 - 24 2022年12月

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