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Open Journal of Medicinal Chemistry 2017年第2期7卷 19-28页

作者： Shinya Nakamura Kazuko Shimada Genzoh Tanabe Osamu Muraoka Isao nakanishi Department of Pharmaceutical Sciences Kindai University Higashiosaka Japan

Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationships. The activity of acarbose is about ten times stronger in rat than in human, and that of neosalacinol is similar in both species. Binding affinities of acarbose and neosalacinol to four catalytic domains of alpha-glucosidases in human and rat were compared to investigate the cause of activity differences among species. Species difference was brought about complicatedly by the balance of interaction with four domains, and the result was indicated that larger ligand would show larger species difference in activity.

关键词： Homology Modeling MM/PBSA Alpha-Glucosidase Salacinol Acarbose Species Difference

Homology Modeling of Human Alpha-Glucosidase Catalytic Domains and SAR Study of Salacinol Derivatives

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Open Journal of Medicinal Chemistry 2012年第3期2卷 50-60页

作者： Shinya Nakamura Kazunori Takahira Genzoh Tanabe Osamu Muraoka Isao nakanishi Department of Pharmaceutical Sciences Kinki University Kinki Japan

Maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) belong to human intestinal alpha-glucosidase and their N-terminal side catalytic domains are called NtMGAM and NtSI, and their C-terminal side catalytic domains are called CtMGAM and CtSI. As an antidiabetic, alpha-glucosidase inhibitor is required to bind to all of these domains to inhibit disaccharides hydrolysis. Salacinol and kotalanol isolated from Salacia reticulata are novel seed compounds for al-pha-glucosidase inhibitor. Even though the complex structures of NtMGAM or NtSI have been determined experimen-tally, those of CtMGAM and CtSI have not been revealed. Thus, homology modeling for CtMGAM and CtSI has been performed to predict the binding mode of salacinol and its derivatives for each domain. The binding affinities for these compounds were also calculated to explain the experimental structure-activity relationships (SARs). After a docking study of the derivatives to each catalytic domain, the MM/PBSA method has been applied to predict the binding affinities. The predicted binding affinities were almost consistent with the experimental SARs. The comparison of the complex structures and binding affinities provided insights for designing novel compounds, which inhibit all catalytic domains.

关键词： Homology Modeling Docking Study MM/PBSA Alpha-Glucosidase Salacinol Kotalanol

Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy

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World Journal of Gastroenterology 2012年第22期18卷 2832-2836页

作者： Shuhei Komatsu Daisuke Ichikawa Kazuma Okamoto Daito Ikoma Masahiro Tsujiura Yukihisa Nishimura Yasutoshi Murayama Atsushi Shiozaki Hisashi Ikoma Yoshiaki Kuriu Masayoshi nakanishi Hitoshi Fujiwara Toshiya Ochiai Yukihito Kokuba Eigo Otsuji Division of Digestive Surgery Department of Surgery Kyoto Prefectural University of Medicine 465 Kajii-cho Kawaramachihirokoji Kamigyo-ku Kyoto 602-8566 Japan

AIM: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs. METHODS: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively. RESULTS: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-Ⅰ procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-Ⅱ reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-Ⅱ vs Billroth-Ⅰ: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-Ⅰ reconstruction. In tumor location of RGC, after Billroth-Ⅰ reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-Ⅱ reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage Ⅰ-Ⅱ tended to have been followed up almost every second year. CONCLUSION: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.

关键词：时间间隔胃癌随访远端早期阶段有限元分析早期检测切除术

Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt

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World Journal of Gastroenterology 2010年第25期16卷 3211-3214页

作者： Hiromichi Ishii Teruhisa Sonoyama Shingo Nakashima Hiroyuki Nagata Atsushi Shiozaki Yoshiaki Kuriu Hisashi Ikoma Masayoshi nakanishi Daisuke Ichikawa Hitoshi Fujiwara Kazuma Okamoto Toshiya Ochiai Yukihito Kokuba Chohei Sakakura Eigo Otsuji Division of Digestive Surgery Department of Surgery Kyoto Prefectural University of Medicine Kyoto 602-8566 Japan

We report a case of hepatocellular carcinoma (HCC) that caused a severe arterioportal shunt (APS). A 49-year-old man was admitted to hospital due to esophagogastric variceal hemorrhage and HCC, and underwent endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). He was then referred to our hospital. Abdominal computed tomography revealed a lowdensity lesion in the posterior segment of the liver and an intratumoral APS, which caused portal hypertension. Although the patient underwent EVL, EIS, Hassab’s operation, and transcatheter arterial embolization for APS, he vomited blood due to rupture of esophagogastric varices. Right hepatectomy was performed for the treatment of HCC and APS, although the indocyanine green retention value at 15 min after intravenous injection was poor (30%). The patient’s postoperative course was uneventful. Eventually, APS disappeared and the esophagogastric varices improved.

关键词： Arterioportal shunt Hepatocellular carcinoma Esophagogastric varices

Hemodynamics in the portal vein evaluated by pulse wave Doppler ultrasonography in patients with chronic hepatitis C treated with interferon

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World Journal of Gastroenterology 2005年第3期11卷 396-399页

作者： Shigeo nakanishi Katsuya Shiraki Kouji Yamamoto Mutsumi Koyama Noboru Kimura Takeshi Nakano First Department of Internal Medicine Toshiba Corporation

AIM: To employ pulse wave Doppler ultrasonography to evaluate the changes in portal blood flow velocity in patients with chronic hepatitis C (CHC) receiving interferon (IFN)***: The subjects in this study were 14 patients (13 men and 1 woman) with CHC who received IFN treatment. Portal blood flow velocity was measured in the vessels at the porta hepatis at four time points: before IFN administration (pre-IFN), 2 wk after the start of administration (wk 2), 24 wk after the start of administration (wk 24, i.e.,the end of IFN administration), and 24 wk after the end of administration (wk 48).RESULTS: The patients with CHC in whom IFN treatment resulted in complete elimination or effective elimination of viruses showed a significant increase in portal blood flow velocity at the end of IFN treatment compared with that before IFN treatment. In contrast, when IFN was ineffective, no significant increase in portal bloocl flow velocity was observed at wk 24 or 48 compared with the pre-IFN value. In addition,the patients with CHC in whom IFN was ineffective showed significantly lower portal blood flow velocity values than control subjects at all measurement time ***: Pulse wave Doppler ultrasonography is a noninvasive and easily performed method for evaluating the effects of IFN treatment in patients with CHC. This technique is useful for measuring portal blood flow velocity before and 24 wk after IFN administration in order to evaluate the changes over time, thus assessing the effectiveness of IFN treatment.

关键词：血流动力学血管入口脉搏多普勒超生诊断法慢性丙型肝炎干扰素 CHC

Characteristics of Amorphous Mn_3AlC Phases Formed by Mechanical Milling

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Journal of Materials Science & Technology 1997年第2期13卷 149-153页

作者： Fuxing YIN Nanju GU (Hebei Institute of Technology, Tianin 300132, China)T.Shigematsu N.nakanishi(Faculty of Science, Konan University Kobe 658, Japan)Y.Osawa A.Sato(National Research Institute of Metals, Tsukuba 305, Japan) Hebei Institute of Technology Tianjin 300132 China Faculty of Science Konan University Kobe 658 Japan National Research Institute of Metals Tsukuba 305 Japan

Amorphization of Mn carbides by rapid quenching method has been proved to be *** mechanical milling in the present work, amorphous phases have been formed in the perovskitetype Mn3AlC compound. The transformation process from crystalline to amorphous phase was found to be milling time controlled, and 10 h is a critical period for the macroscopically single amorphous phase to form. It has been clarified that the redistribution of C atoms is an instinctive factor for amorphous phase to nucleate, and the atomic configuration in the amorphous phase is changed much in longer milling that different crystallizing behaviours have been caused. With X-ray diffraction and differential scanning calorimetry (DSC) results, an atomic configuration transition model is considered for the structures of the amorphous phases changed during milling.

关键词： Mn Ta

Counter-Rotating Type Horizontal-Axis Bidirectional Propellers for Tidal Stream Power Unit

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Journal of Power and Energy Engineering 2017年第7期5卷 34-44页

作者： Yuki Funami Yuji nakanishi Nak-Joong Lee Bin Huang Toshiaki Kanemoto Faculty of Engineering Kanagawa University Yokohama Japan Faculty of Engineering Kyushu Institute of Technology Kitakyushu Japan Ocean College Zhejiang University Zhoushan China Institute of Ocean Energy Saga University Saga Japan

Tidal stream power units with horizontal-axis propellers are one of promising technologies for generating the renewable green energy. The ebb and flow require that the power unit must operate in bidirectional tidal streams. Hence a tidal stream power unit with counter-rotating type horizontal-axis bidirectional propellers is proposed in this paper. The blades with fully-symmetrical hydrofoils were optimized numerically. The output and flow conditions predicted by the computational fluid dynamics simulations are compared with the results of the wind tunnel experiments at the higher tip speed ratios, which are of expected usual operating conditions of this unit. The numerical and experimental results show good agreements. It is also confirmed that the flow discharged from the counter-rotating type propellers has no swirling component, though the single propeller generates the unacceptable swirling component.

关键词： Bidirectional Propellers Counter-Rotating Type Machine Tidal Stream Power Unit Computational Fluid Dynamics

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现代畲语鼻音韵尾的来历

民族语文 2007年第4期 10-20页

作者：中西裕树京都市左京区北白川京都大学人文科学研究所

文章认为畲语在历史上曾只有一个鼻音韵尾,以主要元音的前后为条件读成舌尖鼻音或舌根鼻音。后来,这两种区别逐渐固定,即使主要元音的音值发生变化,已经固定的韵尾没有受到影响。

关键词：鼻音韵尾主要元音音值

Early thrombomodulin-α administration outcome for acute disseminated intravascular coagulopathy in gastrointestinal surgery

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World Journal of Gastroenterology 2017年第5期23卷 891-898页

作者： Hirotaka Konishi Kazuma Okamoto Katsutoshi Shoda Tomohiro Arita Toshiyuki Kosuga Ryo Morimura Shuhei Komatsu Yasutoshi Murayama Atsushi Shiozaki Yoshiaki Kuriu Hisashi Ikoma Masayoshi nakanishi Daisuke Ichikawa Hitoshi Fujiwara Eigo Otsuji Division of Digestive Surgery Department of SurgeryKyoto Prefectural University of MedicineKajii-choKyoto city 6028566Japan

AIM To investigate the efficacy of thrombomodulin(TM)-α for treatment of disseminated intravascular coagulopathy(DIC) in the field of gastrointestinal surgery. METHODS Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the ini-tiation of TM-α and patient demographics were also evaluated. RESULTS Abscess formation or bacteremia was the most frequent cause of DIC(33%), followed by digestive tract perforation(31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk(81%). TM-α was most often administered within 1 d of the DIC diagnosis(72%) and was continued for more than 3 d(64%). Although bleeding tendency was observed in 7 patients(19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome(SIRS) scores, quick-sequential organ failure assessment(qS OFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk(P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration(≥ 4, ≤ 6) and improvements in DIC-associated scores(DIC, SIRS and q SOFA) at 1 wk were significantly better prognostic factors for 28-d survival(P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qS OFA scores, sepsis, shock or high lactate values(P < 0.05, for all). CONCLUSION Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

关键词：快顺序的机关失败评价 Thrombomodulin-α 胃肠的外科全身的煽动性的反应症候群尖锐传播 intravascular coagulopathy

Intracellular Localization of ABC Transporter TAPL Differs between Transient and Stable Expression

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CellBio 2014年第2期3卷 50-59页

作者： Yu Motohashi Ayako Ohashi-Kobayashi Mayumi nakanishi-Matsui Yasuyuki Fujimoto Masatomo Maeda Department of Biochemistry School of Pharmacy Iwate Medical University Shiwa-Gun Japan Department of Immunology School of Pharmacy Iwate Medical University Shiwa-Gun Japan Department of Molecular Biology School of Pharmacy Iwate Medical University Shiwa-Gun Japan Laboratory of Biochemistry and Molecular Biology Graduate School of Pharmaceutical Sciences Osaka University Suita Japan

Transporter associated with antigen processing (TAP)-like (TAPL;ABCB9) is a half-type ABC transporter with sequence similarity to TAP1 and TAP2 that function in the ER membrane. To determine the cellular localization, TAPL and truncated forms of it were tagged with GFP at their car-boxyl termini. Intracellular localization of these fusion proteins was compared between transient and stable expression in CHO-K1 cells. When they were expressed transiently, the fluorescence of the fusion proteins was detected on the intracellular membrane, mainly in the ER, and all the fusion proteins, i.e., TAPL(M1 -A766)-GFP, TAPL(M1-S275)-GFP, TAPL(M1-K182 )-GFP, TAPL(M 1-R141)-GFP and TAPL(M1-G75), were co-localized with an ER marker, PDI. However, the fluorescence of all of them except for TAPL(M1-G 75)-GFP and TAPL(M1-S275)-GFP overlapped with a lysosome marker, cathepsin D, upon stable expression. Lysosomal localization was similarly observed with TAPL(M1- A766)-DsRed, which was stably expressed. These results suggest that TAPL is sorted to the lysosomal membrane when expressed stably in CHO-K1 cells. Furthermore, the lysosomal targeting signal may comprise the N-terminal four transmembrane helices since the N-terminal two transmembrane helices may not be enough to function as such a signal.

关键词： ABCB9 Lysosome Membrane Localization Stable Expression TAPL Transfection