研究者詳細 - 寺井　崇二

Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells 査読

Shogo Shiratsuki, Shuji Terai, Yasuhiko Murata, Taro Takami, Naoki Yamamoto, Koichi Fujisawa, Guzel Burganova, Luiz Fernando Quintanilha, Isao Sakaida

HEPATOLOGY RESEARCH 45 ( 13 ) 1353 - 1359 2015年12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: Less invasive therapies using mesenchymal stem cells (MSC) are being developed to treat patients with severe liver cirrhosis. MSC constitute a promising cell source for regenerative therapy and are frequently isolated from bone marrow (BMSC) or adipose tissue (ASC). Therefore, this study assessed the characteristics of these two cell types and their safety for cell infusion.
Methods: In vitro, exhaustive genetic analysis was performed using human (h)BMSC and hASC. Subsequently, the expression of mRNA and protein was evaluated. In vivo, mouse (m) BMSC or mASC was infused into serial mice via the peripheral vein, and 24-h survival rate, prothrombin time and cause of death were analyzed.
Results: On polymerase chain reaction, western blotting, enzyme-linked immunoassay and fluorescence-activated cell sorting, tissue factor was found to be expressed at higher levels in hASC than in hBMSC. Prothrombin time in mice infused with mASC (> 120s) was markedly longer than that of untreated mice (6.5 +/- 1.7 s) and that of mice infused with BMSC (6.7 +/- 0.8 s) (P< 0.001), indicating that pro-coagulation activity was potently enhanced after ASC infusion. The 24-h survival rates in the mASC-and mBMSC-infused groups were 46.4% (13/28) and 95.5% (21/22), respectively; in the former, the rate decreased with increasing number of infused mASC. This cell number-dependent effect was not observed with mBMSC. A histopathological analysis of mice that died immediately following mASC infusion revealed multiple thrombi in the blood vessels of the lungs.
Conclusion: These results indicate that BMSC are a superior and safer cell source for regenerative therapy.

DOI： 10.1111/hepr.12507

First case of bacteremia caused by Helicobacter cinaedi in a patient with liver cirrhosis: a case report and literature review 査読

Kenya Kamimura, Daisuke Kumaki, Masashi Arita, Yuji Kobayashi, Ken-ichi Mizuno, Fumiko Kusama, Megumi Kobayashi, Hiroyuki Abe, Yoshifumi Takahashi, Kohei Ogawa, Yoko Shinagawa, Manabu Takeuchi, Yuichi Sato, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

Clinical Journal of Gastroenterology 8 ( 5 ) 306 - 317 2015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：Springer-Verlag Tokyo

Patients with liver cirrhosis are known to be immunocompromised hosts due to the dysfunction of the cellular and humoral immune systems, allowing easier bacterial translocation from the intestine to the systemic circulation via the portal vein. Sepsis can often be seen in these patients
however, approximately 10 % of patients show negative results with the standard culture period (3–4 days) and their pathogens remain undiagnosed. Here we report the first case of a patient with liver cirrhosis diagnosed with bacteremia due to Helicobacter cinaedi after gastrointestinal symptoms and review 62 cases of H. cinaedi infection in patients with other diseases. The patient showed positive results for H. cinaedi after 10 days of culture. Administration of a carbapenem was effective and clinical symptoms recovered 20 days after admission. H. cinaedi is an enterohepatic bacterial species that causes bacteremia in immunocompromised patients. Due to the difficulty of detection, few cases have been reported to date and to the best of our knowledge, this is the first published case of bacteremia due to H. cinaedi infection in a patient with liver cirrhosis. Since bacteremia in patients with liver cirrhosis can result in fatality, we recommend vigilance for H. cinaedi infection, longer periods of blood culture, polymerase chain reaction analysis, and empirical antibiotic therapy to help improve prognosis.

DOI： 10.1007/s12328-015-0600-0

Scopus

Evaluation of esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer 査読

Kazuya Takahashi, Manabu Takeuchi, Yuichi Sato, Hiroki Sato, Kenichi Mizuno, Satoru Hashimoto, Masaaki Kobayashi, Shuji Terai

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY 27 ( 10 ) 1187 - 1192 2015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：LIPPINCOTT WILLIAMS & WILKINS

IntroductionEndoscopic submucosal dissection (ESD) is a standard treatment for superficial esophageal cancer. Some patients complain of dysphagia after ESD even without any postoperative strictures. Although ineffective esophageal motility might be associated with dysphagia after ESD, its effect on esophageal motility after ESD remains unknown. Therefore, we aimed to elucidate esophageal motility after ESD and the cause of dysphagia using high-resolution manometry (HRM).Patients and methodsSeventy-six patients (men/women, 64/12; mean age, 71.2 years) who had undergone ESD for superficial esophageal cancer were enrolled. The results of ESD were retrospectively investigated using endoscopic images from the ESD and patient questionnaire for dysphagia. Each patient underwent HRM, and the results were evaluated using metrics and contraction patterns, according to the Chicago classification.ResultsData were obtained from 71 patients. The circumferential mucosal defect ratio (=0.284, P=0.017), number of ESD (=0.346, P=0.003), and number of endoscopic balloon dilatations (EBDs) (=0.416, P<0.001) were correlated with the number of weak contraction with large breaks on HRM. The circumferential mucosal defect (odds ratio=1.074, P<0.001) and number of EBDs (odds ratio=1.200, P=0.035) were also significant predictors for dysphagia after ESD.ConclusionCircumferential mucosal defect ratio, EBD, and repeated ESD were predictors for impaired esophageal motility after ESD. Because circumferential mucosal defect ratios and EBD were also correlated with dysphagia after ESD, impaired esophageal motility could explain dysphagia after ESD.

DOI： 10.1097/MEG.0000000000000431

Histological and Transcriptomic Analysis of Adult Japanese Medaka Sampled Onboard the International Space Station 査読

Yasuhiko Murata, Takako Yasuda, Tomomi Watanabe-Asaka, Shoji Oda, Akiko Mantoku, Kazuhiro Takeyama, Masahiro Chatani, Akira Kudo, Satoko Uchida, Hiromi Suzuki, Fumiaki Tanigaki, Masaki Shirakawa, Koichi Fujisawa, Yoshihiko Hamamoto, Shuji Terai, Hiroshi Mitani

PLOS ONE 10 ( 10 ) e0138799 2015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：PUBLIC LIBRARY SCIENCE

To understand how humans adapt to the space environment, many experiments can be conducted on astronauts as they work aboard the Space Shuttle or the International Space Station (ISS). We also need animal experiments that can apply to human models and help prevent or solve the health issues we face in space travel. The Japanese medaka (Oryzias latipes) is a suitable model fish for studying space adaptation as evidenced by adults of the species having mated successfully in space during 15 days of flight during the second International Microgravity Laboratory mission in 1994. The eggs laid by the fish developed normally and hatched as juveniles in space. In 2012, another space experiment ("Medaka Osteoclast") was conducted. Six-week-old male and female Japanese medaka (Cab strain osteoblast transgenic fish) were maintained in the Aquatic Habitat system for two months in the ISS. Fish of the same strain and age were used as the ground controls. Six fish were fixed with paraformaldehyde or kept in RNA stabilization reagent (n = 4) and dissected for tissue sampling after being returned to the ground, so that several principal investigators working on the project could share samples. Histology indicated no significant changes except in the ovary. However, the RNA-seq analysis of 5345 genes from six tissues revealed highly tissue-specific space responsiveness after a two-month stay in the ISS. Similar responsiveness was observed among the brain and eye, ovary and testis, and the liver and intestine. Among these six tissues, the intestine showed the highest space response with 10 genes categorized as oxidation-reduction processes (gene ontogeny term GO: 0055114), and the expression levels of choriogenin precursor genes were suppressed in the ovary. Eleven genes including klf9, klf13, odc1, hsp70 and hif3a were upregulated in more than four of the tissues examined, thus suggesting common immunoregulatory and stress responses during space adaptation.

DOI： 10.1371/journal.pone.0138799

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication 査読

Masaaki Kobayashi, Yuichi Sato, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 21 ( 37 ) 10553 - 10562 2015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：BAISHIDENG PUBLISHING GROUP INC

The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori (H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection (ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies. The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy (NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritislike" appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H. pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.

DOI： 10.3748/wjg.v21.i37.10553

Possible involvement of activating follicular helper T cells in autoimmune hepatitis 査読

Kimura Naruhiro, Yamagiwa Satoshi, Honda Hiroki, Setsu Toru, Tominaga Kentaro, Kamimura Hiroteru, Takamura Masaaki, Terai Shuji

HEPATOLOGY 62 369A - 369A 2015年10月

Site-specific impact of a regional hydrodynamic injection: Computed tomography study during hydrodynamic injection targeting the swine liver 査読

Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Kenya Kamimura, Dexi Liu, Shuji Terai

Pharmaceutics 7 ( 3 ) 334 - 343 2015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：MDPI AG

A hemodynamic study of hydrodynamic gene delivery (HGD) from the tail vein in rodents has inspired a mechanism and an approach to further improve the efficacy of this procedure. However, there is no report on the hemodynamics of a regional HGD, which is an inevitable approach in large animals. Here, we report the hemodynamics of a regional hydrodynamic injection in detail based on 3D volume data and the dynamism of tissue intensity over time by using computed tomography (CT) both during and after a regional hydrodynamic injection that targeted the liver of a pig weighing 15.6 kg. Contrast medium (CM) was injected at a steady speed of 20 mL/s for 7.5 s under the temporal balloon occlusion of the hepatic vein (HV). A retrograde flow formed a wedge-shaped strong enhancement area downstream of the corresponding HV within 2.5 s, which was followed by drainage into another HV beginning from the target area and the portal vein (PV) toward a non-target area of the liver. After the injection, the CM was readily eliminated from the PV outside the target area. These data suggest that an interventional radiology approach is effective in limiting the hydrodynamic impacts in large animals at a target area and that the burden overflowing into the PV is limited. A further investigation that simultaneously evaluates gene delivery efficiency and hemodynamics using CT is needed to establish feasible parameters for a regional HGD in large animals.

DOI： 10.3390/pharmaceutics7030334

Scopus

Nutcracker and jackhammer esophagus treatment: a three-case survey, including two novel cases of eosinophilic infiltration into the muscularis propria 査読

Hiroki Sato, Manabu Takeuchi, Kazuya Takahashi, Yuichi Sato, Satoru Hashimoto, Kenichi Mizuno, Kenji Suzuki, Masaaki Kobayashi, Terasu Honma, Haruhiro Inoue, Shuji Terai

ENDOSCOPY 47 ( 9 ) 855 - 857 2015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：GEORG THIEME VERLAG KG

Nutcracker esophagus and jackhammer esophagus are largely unknown motility disorders, also sometimes called hypertensive and hypercontractile peristalsis, respectively. There is currently no standardized diagnostic or management plan for these diseases. Here, we report on three patients with jackhammer/nutcracker esophagus who were treated with either peroral endoscopic myotomy or a systemic steroid regimen, focusing particularly on two novel presentations of nutcracker and jackhammer esophagus involving eosinophilic infiltration into the muscularis propria, and their responses to both interventions.

DOI： 10.1055/s-0034-1391985

Image-guided hydrodynamic gene delivery: Current status and future directions 査読

Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Yuji Kobayashi, Kohei Ogawa, Yoko Shinagawa, Ryosuke Inoue, Shuji Terai

Pharmaceutics 7 ( 3 ) 213 - 223 2015年8月

記述言語：英語出版者・発行元：MDPI AG

Hydrodynamics-based delivery has been used as an experimental tool to express transgene in small animals. This in vivo gene transfer method is useful for functional analysis of genetic elements, therapeutic effect of oligonucleotides, and cancer cells to establish the metastatic cancer animal model for experimental research. Recent progress in the development of image-guided procedure for hydrodynamics-based gene delivery in large animals directly supports the clinical applicability of this technique. This review summarizes the current status and recent progress in the development of hydrodynamicsbased gene delivery and discusses the future directions for its clinical application.

DOI： 10.3390/pharmaceutics7030213

Scopus

Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging (vol 10, e0129950, 2015) 査読

Koichi Fujisawa, Shuji Terai, Toshihiko Matsumoto, Taro Takami, Naoki Yamamoto, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida

PLOS ONE 10 ( 8 ) e0137156 2015年8月

臨床応用の現状非代償性肝硬変症に対する再生療法

寺井崇二, 高見太郎, 坂井田功

メディカル朝日 44 ( 8 ) 36 - 37 2015年8月

抗結核薬による昏睡型急性肝不全の一例

松田崇史, 石川剛, 岩本拓也, 佐伯一成, 日高勲, 高見太郎, 寺井崇二, 坂井田功

肝臓 56 ( 7 ) 387 - 388 2015年7月

Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging 査読

Koichi Fujisawa, Shuji Terai, Toshihiko Matsumoto, Taro Takami, Naoki Yamamoto, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida

PLOS ONE 10 ( 6 ) e0129950 2015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：PUBLIC LIBRARY SCIENCE

Maid is a helix-loop-helix protein that is involved in cell proliferation. In order to further elucidate its physiological functions, we studied Maid activity in two small fish model systems. We found that Maid expression was greatest in zebrafish liver and that it increased following partial hepatectomy. Maid levels were also high in hepatic preneoplastic foci induced by treatment of zebrafish with diethylnitrosamine (DEN), but low in hepatocellular carcinomas (HCC), mixed tumors, and cholangiocarcinomas developing in these animals. In DEN-treated transgenic medaka overexpressing Maid, hepatic BrdU uptake and proliferation were reduced. After successive breedings, Maid transgenic medaka exhibited decreased movement and a higher incidence of abnormal spine curvature, possibly due to the senescence of spinal cord cells. Taken together, our results suggest that Maid levels can influence the progression of liver cancer. In conclusion, we found that Maid is important regulator of hepatocarconogenesis and aging.

DOI： 10.1371/journal.pone.0129950

【再生医療-新たな医療を求めて-】再生医療の臨床研究・治験 C型肝炎ウイルス起因肝硬変に対する自己骨髄細胞投与療法

Autologous bone marrow cell infusion therapy for hepatitis C virus infected liver cirrhosis. 査読

Aibe Y, Takami T, Terai S, Sakaida I

Nihon rinsho. Japanese journal of clinical medicine 73 Suppl 5 499 - 503 2015年6月

相部祐希, 高見太郎, 寺井崇二, 坂井田功

日本臨床 73 ( 増刊5 再生医療 ) 499 - 503 2015年6月

特発性血小板減少性紫斑病を合併した原発性胆汁性肝硬変自己免疫性肝炎オーバーラップ症候群に部分的脾動脈塞栓術を施行した1例

仁志麻衣子, 石川剛, 相部祐希, 白築祥吾, 松田崇史, 岩本拓也, 高見太郎, 寺井崇二, 坂井田功

日本門脈圧亢進症学会雑誌 21 ( 2 ) 122 - 127 2015年6月

記述言語：日本語出版者・発行元：(一社)日本門脈圧亢進症学会

症例は50歳代女性で、吐血で近医にて食道静脈瘤破裂と診断され、内視鏡的静脈瘤結紮術が行われた。肝硬変症(LC)の精査に前医を紹介され、原発性胆汁性肝硬変症-自己免疫性肝炎のオーバーラップ症候群に起因するLCの診断でウルソデオキシコール酸とプレドニゾロン(PSL)が開始されたが、肝障害の持続と血小板減少を認め、特発性血小板減少性紫斑病(ITP)と診断され、静脈瘤再発で精査目的に当院へ入院した。検査で中等度の脾腫、門脈・脾動静脈の拡張、食道静脈瘤を認め、静脈瘤に対し内視鏡的静脈瘤硬化結紮療法(EISL)を行い、その後にLC・ITPに起因する血小板減少症に対し部分的脾動脈塞栓術(PSE)を行った。1週間後の造影CTで80.6%の脾梗塞を確認し、肺動脈楔入圧、肝静脈圧較差の改善を認め、2週間後に血小板数の上昇で軽快退院した。PSLの漸減・中止後も血小板減少・肝障害の再燃はなく、EISL後18ヵ月、PSE後16ヵ月経過で食道静脈瘤の再発は認めていない。

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J03767&link_issn=&doc_id=20150721240003&doc_link_id=10.11423%2Fjsph.21.122&url=https%3A%2F%2Fdoi.org%2F10.11423%2Fjsph.21.122&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Rheological modification of hydrodynamic gene delivery

Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Akiomi Ushida, Tomiichi Hasegawa, Kenya Kamimura, Dexi Liu, Shuji Terai

Proceedings of The 18th Annual Meeting of the American Society of Gene and Cell Therapy ( 350594 ) 140 - 141 2015年5月

早期胃癌に対するESD後に発生した遅発性穿孔の検討査読

荒生祥尚, 小林正明, 橋本哲, 水野研一, 竹内学, 本田博樹, 影向一美, 高村昌昭, 佐藤祐一, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 31 ( 1 ) 27 - 32 2015年5月

記述言語：日本語出版者・発行元：(株)癌と化学療法社

当施設で治療した早期胃癌に対するendoscopic submucosal dissection(ESD)1,611例中6例(0.37%)の遅発性穿孔について原因と治療経過を検討した。基礎疾患をもった高齢の男性に多く、2例で抗血栓薬を内服していた。局在はすべて体中部であり、術時間に一定の傾向は認めなかった。過凝固が原因と考えられた症例が4例、残胃内への胆汁の逆流が原因と考えられた症例が1例であった。手術を要した3例は穿孔径が10mm以上で、手術時期が遅れた残胃の1例では術後長期の経過をたどった。穿孔径が大きい場合や残胃症例に対しては迅速な手術を考慮するべきである。(著者抄録)