研究者詳細 - 寺井　崇二

【肝胆膵診療のNew Horizon】肝臓疾患肝硬変肝性浮腫に対するバソプレシンV2受容体拮抗剤トルバプタンの使用法の提案肝性浮腫の発生機序から考える

その他リンク： http://www.lib.yamaguchi-u.ac.jp/yunoca/handle/B030064000210

寺井崇二, 田邊規和, 五嶋敦史, 坂井田功

肝胆膵 69 ( 6 ) 955 - 960 2014年12月

造影エコーにて評価した回腸NETの1例

佐伯一成, 高見太郎, 寺井崇二, 坂井田功

超音波医学 41 ( 6 ) 908 - 908 2014年11月

Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease 査読

Takashi Oono, Takahiro Yamasaki, Junichi Zaitsu, Issei Saeki, Takuya Iwamoto, Yumiko Harima, Yoshio Marumoto, Isao Hidaka, Yohei Urata, Tsuyoshi Ishikawa, Taro Takami, Makoto Segawa, Koichi Uchida, Shuji Terai, Ichiro Kunitugu, Tsuyoshi Tanabe, Isao Sakaida

HEPATOLOGY RESEARCH 44 ( 10 ) E54 - E62 2014年10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：WILEY-BLACKWELL

Aim: Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease.
Methods: We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR).
Results: HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = -0.46, P = 0.0001) and tyrosine (r = 0.55, P < 0.0001). However, BCAA were not significantly correlated with HOMA-IR (r = -0.21, P = 0.082). In multivariate analysis, only two factors were identified as independent parameters contributing to a HOMA-IR of 2.5 or more: total cholesterol (odds ratio [OR], 6.511; 95% confidence interval [95% CI], 1.554-27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087-21.549; P = 0.039).
Conclusion: Serum tyrosine levels may be associated with IR in patients with HCV-related chronic liver disease.

DOI： 10.1111/hepr.12213

Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo 査読

Luiz Fernando Quintanilha, Taro Takami, Yoshikazu Hirose, Koichi Fujisawa, Yasuhiko Murata, Naoki Yamamoto, Regina Coeli dos Santos Goldenberg, Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 44 ( 10 ) E206 - E217 2014年10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：WILEY-BLACKWELL

Aim: To overcome current limitations of therapy for liver diseases, cell-based therapies using mesenchymal stem cells (MSC) have been attempted through basic and clinical approaches. Oxidative stress is a crucial factor in hepatology, and reactive oxygen species (ROS) are well-established molecules responsible for its deleterious effects. The antioxidant properties of MSC were recently demonstrated, and therefore we examined the antioxidant activity of canine MSC (cMSC), their effects on isolated hepatocytes in vitro and their curative potential against thioacetamide (TAA)-induced liver injury in vivo.
Methods: To evaluate the ability of cMSC to challenge oxidative stress, cell viability, cytotoxicity and ROS were measured in cultured cMSC treated with TAA. Also, cMSC were co-cultured with hepatocytes in the same injury condition, and the ROS level was measured exclusively in hepatocytes. Finally, to verify the curative potential of cMSC, 2.0 x 10(6) cells or phosphate-buffered saline were injected systemically in non-obese diabetic/severe combined immunodeficiency mice that received TAA injections twice a week for 13 weeks. We then evaluated histological parameters, serum injury markers and redox homeostasis.
Results: cMSC overcame TAA-induced oxidative stress in vitro, as shown by increased viability and lower cytotoxicity and ROS levels. Moreover, hepatocytes co-cultured with cMSC also showed decreased cellular ROS. The in vivo study showed that mice treated with cMSC presented with an ameliorated histological pattern, suppressed fibrosis, lower serum injury marker levels and better oxidative parameters.
Conclusion: We concluded that cMSC injection reduce TAA-induced liver injury through antioxidant activities and hepatoprotective effects, showing a curative potential in liver diseases.

DOI： 10.1111/hepr.12204

Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension 査読

Tsuyoshi Ishikawa, Shogo Shiratsuki, Takashi Matsuda, Takuya Iwamoto, Taro Takami, Koichi Uchida, Shuji Terai, Takahiro Yamasaki, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 49 ( 9 ) 1333 - 1341 2014年9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：SPRINGER JAPAN KK

Background Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon- occluded retrograde transvenous obliteration (BRTO) can affect glucose and insulin metabolism in patients with LC.
Methods Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh's class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure.
Results Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of beta-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure.
Conclusions Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.

DOI： 10.1007/s00535-013-0893-z

Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury 査読

Hirofumi Miyazaki, Tomoo Sawada, Miwa Kiyohira, Zhiqian Yu, Keiji Nakamura, Yuki Yasumoto, Yoshiteru Kagawa, Majid Ebrahimi, Ariful Islam, Kazem Sharifi, Saki Kawamura, Takanori Kodama, Yui Yamamoto, Yasuhiro Adachi, Nobuko Tokuda, Shuji Terai, Isao Sakaida, Toshizo Ishikawa, Yuji Owada

AMERICAN JOURNAL OF PATHOLOGY 184 ( 9 ) 2505 - 2515 2014年9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：ELSEVIER SCIENCE INC

Kupffer cells (KCs) are involved in the progression of liver diseases such as hepatitis and Liver cancer. Several members of the fatty acid binding proteins (FABPs) are expressed by tissue macrophages, and FABP7 is Localized only in KCs. To clarify the role of FABP7 in the regulation of KC function, we evaluated pathological changes of Fabp7 knockout mice during carbon tetrachloride-induced Liver injury. During liver injury in Fabp7 knockout mice, serum liver enzymes were increased, cytokine expression (tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and transforming growth factor-beta) was decreased in the Liver, and the number of KCs in the liver necrotic area was significantly decreased. Interestingly, in the FABP7-deficient KCs, phagocytosis of apoptotic cells was impaired, and expression of the scavenger receptor CD36 was markedly decreased. In chronic Liver injury, Fabp7 knockout mice showed less fibrogenic response to carbon tetrachloride compared with wild-type mice. Taken together, FABP7 is involved in the liver injury process through its regulation of KC phagocytic activity and cytokine production. Such modulation of KC function by FABP7 may provide a novel therapeutic approach to the treatment of liver diseases.

DOI： 10.1016/j.ajpath.2014.05.015

肝細胞癌(HCC)に対し肝動脈化学塞栓術(TACE)施行後に腫瘍破裂を来した1例

急性肝不全予後向上を目指す新規治療法の展望他家骨髄由来の間葉系幹細胞を用いた急性肝不全に対する肝臓再生療法の可能性

寺井崇二, 高見太郎, 坂井田功

肝臓 55 ( Suppl.2 ) A560 - A560 2014年9月

当科における肝硬変による体液貯留に対するトルバプタン投与症例の検討

田邉規和, 寺井崇二, 浦田洋平, 内田耕一, 坂井田功

肝臓 55 ( Suppl.2 ) A670 - A670 2014年9月

高齢C型慢性患者における抗ウイルス療法の効果と肝発癌について

花園忠相, 日高勲, 大野高嗣, 岩本拓也, 佐伯一成, 石川剛, 寺井崇二, 坂井田功

肝臓 55 ( Suppl.2 ) A665 - A665 2014年9月

福井悠美, 佐伯一成, 花園忠相, 田邊規和, 浦田洋平, 日高勲, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 63 ( 3 ) 228 - 228 2014年8月

田邉規和, 高見太郎, 寺井崇二, 坂井田功

最新医学 69 ( 7月増刊 ) 1438 - 1445 2014年7月

記述言語：日本語出版者・発行元：(株)最新医学社

我々は,マウス基礎研究で自己骨髄細胞投与(ABMi)が肝線維化および肝機能を改善させることを報告し,2003年11月から開始した「肝硬変症に対する自己骨髄細胞投与(ABMi)療法」の国内外での臨床研究により,その肝機能改善・修復効果を確認し論文報告してきた.本稿では,骨髄細胞を用いた肝再生治療の現状と展望について概説する.(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00516&link_issn=&doc_id=20140807130004&doc_link_id=issn%3D0370-8241%26volume%3D69%26issue%3D7%26spage%3D1438&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0370-8241%26volume%3D69%26issue%3D7%26spage%3D1438&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

【単球・マクロファージの多様性と病態】骨髄由来細胞を用いた肝線維化改善療法

寺井崇二, 高見太郎, 谷本治子, 岩本拓也, 坂井田功

血管医学 15 ( 2 ) 157 - 160 2014年7月

記述言語：日本語出版者・発行元：(株)メディカルレビュー社

われわれは肝硬変症に対する自己骨髄細胞投与療法(ABMi療法)の臨床研究を行ってきた。その結果、肝硬変症治療において骨髄細胞投与により線維化を改善することにより、それに引き続き肝前駆細胞、内在の肝細胞の活性化が起こり、その結果、肝再生が誘導され肝機能を改善することが明らかになった。さらに低侵襲な治療法を開発するため、体外で自己骨髄細胞を培養する方法を考えた。その過程で骨髄由来培養細胞のうち、どのような細胞が肝線維化改善に有効か、機序も含めて解析したので報告する。(著者抄録)

高齢者肝・胆・膵疾患の治療における諸問題当科における高齢者肝細胞癌患者の現状と治療成績についての検討

田邉規和, 佐伯一成, 浦田洋平, 寺井崇二, 坂井田功

日本高齢消化器病学会誌 17 ( 1 ) 45 - 45 2014年7月

当科における高齢C型慢性肝炎患者に対する抗ウイルス療法の特性

花園忠相, 日高勲, 佐伯一成, 岩本拓也, 石川剛, 寺井崇二, 坂井田功

日本高齢消化器病学会誌 17 ( 1 ) 79 - 79 2014年7月

Veno-occlusive diseaseを呈した薬物性肝障害の一例

石川剛, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 55 ( 7 ) 441 - 441 2014年7月

Status and Prospects of Liver Cirrhosis Treatment by Using Bone Marrow-Derived Cells and Mesenchymal Cells 査読

Shuji Terai, Taro Takami, Naoki Yamamoto, Koichi Fujisawa, Tsuyoshi Ishikawa, Yohei Urata, Haruko Tanimoto, Takuya Iwamoto, Yuko Mizunaga, Takashi Matsuda, Takashi Oono, Miho Marumoto, Guzel Burganova, Luiz Fernando Quintanilha, Isao Hidaka, Yoshio Marumoto, Issei Saeki, Koichi Uchida, Takahiro Yamasaki, Kenji Tani, Yasuho Taura, Yasuhiko Fujii, Hiroshi Nishina, Kiwamu Okita, Isao Sakaida

TISSUE ENGINEERING PART B-REVIEWS 20 ( 3 ) 206 - 210 2014年6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：MARY ANN LIEBERT, INC

In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated `` Advanced medical technology B'' for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies.

DOI： 10.1089/ten.teb.2013.0527