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World Journal of Gastroenterology 2006年第17期12卷 2793-2797页

作者： Chouhei Sakakura Akeo Hagiwara Koji Soga Koji Miyagawa Susumu nakashima Tetsuji Yoshikawa Shuichi Kin Yuenn Nakase Nobuki Yamaoka Yoshihiko Sagara Hisakazu Yamagishi Department of Digestive Surgery Kyoto Prefectural University of Medicine Kawaramachi-doriKamigyokuKyoto 602-0841Japan

Constitutive activation of KIT receptor tyrosine kinase is a critical factor in the pathogenesis of gastrointestinal stromal tumors （GISTs）. But there is little information on whether combination of imatinib mesylate （IM） and surgical treatment can prolong survival in the cases with unresectable multiple liver metastases. We report a case of postoperative recurrence of GIST treated by the tyrosine kinase inhibitor IN and surgical treatment. The initial complete response （CR） to treatment continued for 18 mo, but single liver metastasis showed regrowth in the left hepatic lobe during IN treatment. After partial resection of the recurrent tumor, postoperative course was uneventful and the patient has survived without recurrence for 24 too. Currently, imatinib is the first- line therapy for non-resectable GISTs, but a single agent therapy often leads to tumor resistance. Even if tolerance to imatinib occurs, a combination of imatinib and surgical treatment can prolong survival in some cases as reported here. However, further studies on a large number of cases of recurrent GIST are necessary to evaluate the effectiveness of IN treatment combined with surgery.

关键词： GIST Imatinib mesylate Liver metastases

Antithrombotic Effects of Different Strains of Lactic Acid Bacteria

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Health 2014年第18期6卷 2433-2443页

作者： Hiromasa Ooe Masaru Kato Kanae Hyodo Keiko nakashima hiroshi Ashigai Kyoko Kato Toshinori Sasaki Yuko Fukushima John C. Giddings Junichiro Yamamoto Research Laboratories for Health Science and Food Technologies Kirin Company Limited Yokohama Japan Research Laboratories for Brewing Technologies Kirin Company Limited Yokohama Japan Laboratory of Physiology Faculty of Nutrition Kobe Gakuin University Kobe Japan Central Laboratories for Key Technologies Kirin Company Limited Yokohama Japan Formerly Department of Haematology School of Medicine Cardiff University UK

Objective: The aim of the present study was to assess the antithrombotic properties of different strains of orally available antithrombotic lactic acid bacteria (LAB). Research Methods & Procedures: Antithrombotic activity, antiplatelet reactivity and/or thrombolytic activity, were measured in seven strains of LAB and LAB cell-free-extracts (LAB filtrates) using the shear-induced platelet reactivity/thrombolytic activity, The Global Thrombosis Test (GTT), with non-anticoagulated rat blood in vitro. Subsequently, the most potent antithrombotic strains identified in vitro were assessed in vivo after oral administration in mouse carotid arteries using a helium-neon laser-induced thrombosis model. Result: Five strains out of seven LAB (Lactobacillus paracasei KW 3100, Lactobacillus fermentum NBRC 3961, Lactobacillus pentosus JCM 8333, Leuconostoc oeni Elios 1, Pediococcus pentosaceus NK-2) promoted significant endogenous thrombolysis in vitro. In addition, one strain (Lactobacillus fermentum NBRC 3961) significantly inhibited shear-induced platelet re-activity. Three antithrombotic strains, Lactobacillus fermentum NBRC 3961, Leuconostoc oeni Elios 1, and Lactobacillus pentosus JCM 8333, were further assessed in vivo. The results demonstrated that filtrates, and the cells per se of these LAB, modulated antiplatelet activity and/or thrombolytic activity, and that the antithrombotic mechanisms were mainly influenced by protein content (60% - 70% of dry matter). Conclusion: The findings suggested that some strains of lactic acid bacteria could usefully provide the basis for the production of oral antithrombotic probiotics.

关键词： Antithrombotic Lactic Acid Bacteria Shear-Induced Thrombosis Global Thrombosis Test (GTT) Laser-Induced Thrombosis Endogenous Thrombolysis

Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease

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World Journal of Stem Cells 2018年第11期10卷 146-159页

作者： Saifun Nahar Yoshiki nakashima Chika Miyagi-Shiohira Takao Kinjo Zensei Toyoda Naoya Kobayashi Issei Saitoh Masami Watanabe Hirofumi Noguchi Jiro Fujita Department of Infectious Respiratory and Digestive Medicine Graduate School of Medicine University of the Ryukyus Okinawa 903-0215 Japan Department of Regenerative Medicine Graduate School of Medicine University of the Ryukyus Okinawa 903-0215 Japan Department of Basic Laboratory Sciences School of Health Sciences in the Faculty of Medicine University of the Ryukyus Okinawa 903-0215 Japan Okayama Saidaiji Hospital Okayama 704-8192 Japan Division of Pediatric Dentistry Graduate School of Medical and Dental Science Niigata University Niigata 951-8514 Japan Department of Urology Okayama Univer sity Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama 700-8558 Japan

Adipose-derived mesenchymal stem cells （ADSCs） are a treatment cell source for patients with chronic liver injury. ADSCs are characterized by being harvested from the patient’s own subcutaneous adipose tissue, a high cell yield （ i.e. , reduced immune rejection res-ponse）, accumulation at a disease nidus, suppression of excessive immune response, production of various growth factors and cytokines, angiogenic effects, anti-apoptotic effects, and control of immune cells via cell-cell interaction. We previously showed that conditioned medium of ADSCs promoted hepatocyte proliferation and improved the liver function in a mouse model of acute liver failure. Furthermore, as found by many other groups, the administration of ADSCs improved liver tissue fbrosis in a mouse model of liver cirrhosis. A comprehensive protein expression analysis by liquid chromatography with tandem mass spectrometry show-ed that the various cytokines and chemokines produced by ADSCs promote the healing of liver disease. In this review, we examine the ability of expressed protein com-ponents of ADSCs to promote healing in cell therapy for liver disease. Previous studies demonstrated that ADSCs are a treatment cell source for patients with chronic liver injury. This review describes the various cytokines and chemokines produced by ADSCs that promote the healing of liver disease.

关键词： Cell transplantation therapy Cytokine Hepatocytes Liquid chromatography with tandem mass spectrometry Liver cirrhosis Adipose-derived mesenchymal stem cells

Two－Dimensional　Model　of　Hydraulic　Fracturing　in　Geosciences：Effects　of　Fluid　Buoyancy

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Journal of Earth Science 1996年第2期15卷 216-222页

作者： Yoshito nakashima Mitsuhiro Toriumi(Geological Institute, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan)

Hydraulic fracturing occurs in diverse fields of geosciences. We introduce effects of fluid buoyancy into the CGDD (Christianovich-Geertsma-DeKlerk-Daneshy) model of hydranlic fracturing. In the model, a two-dimensional one-sided crack in impermeable rock propagates from a horizontally lying wellbore or fluid reservoir at depth; the crack plane is inclined at a prescribed angle to the horizontal; incompressible and Newtonian fluid less dense than the surrounding rock is injected consecutively from the wellbore or fluid reservoir into the crack at a given injection rate. A solution of the crack propagation is obtained using lubrication theory for turbulent or laminar film flow and linear elastic fracture mechanics. The solution shows the importance of the buoyancy of the fluid in the crack as a driving force or a resisting force of the crack propagation. For example,when the water injection rate into a vertical fracture is 10-2 m2/s and the vertical length of the propagating fracture exceeds 100 m, the fluid buoyancy is important (1) as a driving force if the fracture is formed by the upward propagation of a vertical crack and (2) as a resisting force if it is formed by the downward propagation.

关键词： buoyancy crack propagation dyke hydraulic fracturing hydrofracturing vein

Hyperpolarization caused by serotonin contributes to endothelium-dependent relaxations in the porcine coronary artery

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中国药理学报 1999年第12期20卷 1093-1096页

作者： Seung-Jung PARK Mikio nakashima Tetsuhiko NAGAO Paul M VANHOUTTE Center for Experimental Therapeutics Department of MedicineBaylor College of MedicineOne Baylor PlazaHoustonTX 77030USA

AIM:The present study was designed to investigate the contribution of membrane hyperpolarization to endothelium-dependent relaxations induced by serotonin in the porcine coronary ***:Rings with and without endothelium of porcine coronary arteries were suspended in conventional organ chambers for the measurement of isometric *** cell membrane potential of the vascular smooth muscle cells was measured using glass microelectrodes,in the presence of indometacin,ketanserin,and/or N^(ω)-***:Serotonin induced a transient endothelium-,and concentration-dependent relaxation in rings contracted with prostaglandin F_(2α)in the presence of N^(ω)-nitro-L-arginine(maximal relaxation;19%).The N^(ω)-nitro-L-arginine resistant relaxation was abolished by high K^(+)and tetrabutylammonium *** also caused an endothelium-,concentration-dependent membrane hyperpolarizations with a maximal amplitude *** nitro-L-arginine resistant relaxations and hyperpolarizations were abolished by methiothepin,but not by *** time course of the endothelium-dependent relaxations and hyperpolarizations was ***:These results suggest a contribution of cell membrane hyperpolarization to theendothelium-dependent relaxations induced by serotonin in the porcine coronary artery.

关键词： indomethacin ketanserin membrane potentials methiothepin nitric oxide potassium channels serotonin vascular endothelium

Synthesis and Enhanced Guest-Binding Affinities of Dendrimer-Based Cyclophane Tetramer and Octamer

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Advances in Chemical Engineering and Science 2013年第3期3卷 33-37页

作者： Osamu Hayashida Tomomi nakashima Yu Kaku Department of Chemistry Faculty of Science Fukuoka University Fukuoka Japan

Dendritic cyclophane tetramer and octamer were prepared by aminolysis of succinimidyl ester derivative of tetraaza [6.***.6.1] paracyclophane with the corresponding poly(amidoamine) dendrimers as a scaffold, followed by removal of the protecting groups. The present cyclophane tetramer and octamer showed enhanced guest-binding affinities toward fluorescent guests such as 6-p-toluidinonaphthalene-2-sulfonate and 6-anilinonaphthalene-2-sulfonate, in comparison with those of monocyclic cyclophane, reflecting multivalency effects in macrocycles.

关键词： Cyclophane Oligomer Host-Guest Chemistry Multivalency Effect

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

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World Journal of Gastroenterology 2012年第28期18卷 3673-3680页

作者： Yoshiki Naito Hironori Kusano Osamu nakashima Eiji Sadashima Satoshi Hattori Tomoki Taira Akihiko Kawahara Yoshinobu Okabe Kazuhide Shimamatsu Jun Taguchi Seiya Momosaki Koji Irie Rin Yamaguchi hiroshi Yokomizo Michiko Nagamine Seiji Fukuda Shinichi Sugiyama Naoyo Nishida Koichi Higaki Munehiro Yoshitomi Masafumi Yasunaga Koji Okuda Hisafumi Kinoshita Masayoshi Kage Masamichi Nakayama Makiko Yasumoto Jun Akiba Hirohisa Yano Departments of Pathology Kurume University School of Medicine Kurume 830-0011 Japan Biostatistics Center Kurume University Kurume 830-0011 Japan Department of Diagnostic Pathology Kurume University Hospital Kurume 830-0011 Japan Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume 830-0011 Japan Department of Pathology Omuta City General Hospital Omuta 836-8567 Japan Department of Pathology Asakura Medical Association Hospital Fukuoka 838-0069 Japan Department of Pathology National Hospital Organization Kyushu Medical Center Fukuoka 810-8563 Japan Department of Pathology Shin-Koga Hospital Tenjinkai 120 Tenjincho Kurume 830-0033 Japan Department of Pathology Kurume University Medical Center 155-1 Kokubumachi Kurume 839-0863 Japan Department of Surgery Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Department of Pathology Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Division of Surgery Saiseikai Kumamoto Hospital Kumamoto 861-4193 Japan Department of Pathology St Mary's Hospital Kurume 830-8543 Japan Department of Surgery Kurume University School of Medicine Kurume 830-0011 Japan

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

关键词： Intraductal biliary neoplasm Intraductal papillary neoplasm of the bile duct Intraductal tubular neoplasm of the bile duct Intraductal tubulopapillary neoplasm of the bile duct Mucin expression

Microstructural evaluation of Hastelloy-X transient liquid phase bonded joints:Effects of filler metal thickness and holding time

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Transactions of Nonferrous Metals Society of China 2022年第5期32卷 1548-1558页

作者： A.MALEKAN S.E.MIRSALEHI M.FARVIZI N.SAITO K.nakashima Ceramic Division Materials and Energy Research CenterP.O.Box 14155-4777TehranIran Department of Materials and Metallurgical Engineering Amirkabir University of Technology(Tehran Polytechnic)Tehran 15875-4413Iran Department of Materials Science and Engineering Kyushu University744MotookaNishi-kuFukuoka 819-0395Japan

Transient liquid phase(TLP)bonding was investigated in Hastelloy-X samples with different filler metal thicknesses(20,35,50,65,and 100μm)and holding time(5,20,80,320,and 640 min)to obtain optimum bonding *** evaluations using electron probe microanalysis(EPMA)and electron backscattered diffraction(EBSD)show that the central eutectic phases present in the athermally solidified zone(ASZ)are Ni_(3)B,Ni_(2)Si,and CrB,and the precipitates formed in the diffusion-affected zone(DAZ)are MoB,CrB_(2),and Mo_(2)B_(5).According to the results,decreasing the filler thickness as well as increasing the holding time helps realize the completion of isothermal solidification and reduction in the density of precipitates in the DAZ,leading to a joint with more uniform *** of boron and silicon to longer distances with increasing holding time causes the removal of Cr-rich borides in the DAZ and the formation of Mo-rich silicide at the joint *** in hardness of ASZ and DAZ due to the elimination of brittle phases in these zones during long holding time causes more uniform hardness distribution in the joint *** best results are obtained for the sample joined with the 35μm-thick filler metal for 640 min holding time.

关键词： Hastelloy-X transient liquid phase(TLP)bonding microstructure filler metal electron probe microanalysis(EPMA) electron backscattered diffraction(EBSD)

In vitro evaluation of the anti-diabetic potential of soymilk yogurt and identification of inhibitory compounds on the formation of advanced glycation end-products

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Food Bioscience 2022年第6期50卷 668-675页

作者： Yuki nakashima Naoki Yamamoto Ryosuke Tsukioka Hikari Sugawa Rina Ohshima Kaede Aoki Tomoyuki Hibi Kotone Onuki Yudai Fukuchi Shin Yasuda Ryoji Nagai Hideki Kinoshita Graduate School of Bioscience Tokai University9-1-1 TorokuHigashi-kuKumamoto-shiKumamotoJapan School of Agriculture Tokai University9-1-1 TorokuHigashi-kuKumamoto-shiKumamotoJapan Graduate School of Agriculture Tokai University9-1-1 TorokuHigashi-kuKumamoto-shiKumamotoJapan Probio LLC. 1330-1 FutaNishihara-muraAso-gunKumamotoJapan

In this study, we aimed to identify starter strains of lactic acid bacteria (LAB) to produce soymilk yogurt that can decrease the risk of diabetes mellitus (DM) and its complications. The inhibition assays of the dipeptidyl peptidase IV (DPP- IV) and advanced glycation end products (AGEs) formation were conducted using 70% ethanol (EtOH) extraction of freeze-dried soymilk yogurt. Soymilk yogurt produced using Weissella confusa TOKAI 2 showed the highest inhibition rate in the α-amylase inhibition assay, while soymilk yogurt produced using Lactiplantibacillus plantarum TOKAI 17 showed the highest inhibition rates in the α-glucosidase and DPP-Ⅳ inhibition assays, respectively. Soymilk yogurt produced using Streptococcus macedonicus TOKAI 4 showed the highest inhibitory activities in Nω-(carboxymethyl) arginine (CMA) and Nε-(carboxymethyl) lysine (CML) formation, respectively. Furthermore, soymilk yogurt prepared using Lb. plantarum TOKAI 17 and Lactiplantibacillus pentosus TOKAI 35 exhibited higher proportions of aglycone isoflavones than soymilk and showed a higher fluorescent AGEs inhibitory activity than that of soymilk (p < 0.05). Interestingly, the inhibition assay assessing fluorescent AGEs formation using isoflavones indicated that aglycone-type isoflavones, such as genistein and daidzein, had higher inhibitory activities than that of glycosides (p < 0.05). These results indicate that soymilk yogurt produced using Lb. plantarum TOKAI 17 and Lb. pentosus TOKAI 35 had inhibitory effects on α-glucosidase, DPP-Ⅳ, and AGEs formation in vitro, and that aglycone isoflavones might inhibit the formation of fluorescent AGEs.

关键词： Lactic acid bacteria Soymilk yogurt Diabetes Advanced glycation end products

Enhanced piezoelectric properties of (Ba_(0.3)Bi_(0.7))(Mg_(0.05)Fe_(0.6)Ti_(0.35))O_(3) piezoelectric ceramics with high Curie temperature

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Journal of Advanced Dielectrics 2014年第1期4卷 81-86页

作者： Ichiro Fujii Ryuta Mitsui Kouichi nakashima Satoshi Wada Interdisciplinary Graduate School of Medical and Engineering University of Yamanashi Kofu 400-8510Japan

(Ba_(0.3)Bi_(0.7))(Mg_(0.05)Fe_(0.6)Ti_(0.35))O_(3) ceramics were either doped with vanadium or sintered in calcined powder with the same *** to an undoped ceramic sintered without the calcined powder,both ceramics showed reduced leakage current densities(lower than 1×10^(-7) A/cm^(2))and absence of dielectric relaxation behaviors observed in frequency-and temperaturedependent dielectric *** Curie temperatures of both samples were higher than 460℃.The maximum field-induced strain over the applied field,S_(max)/E_(max),of 366 pm/V of the undoped ceramic sintered without the calcined powder increased to 455 and 799 pm/V for the V-doped ceramics and the ceramics sintered with the calcined powder,*** increase was related to a reduced concentration of bismuth vacancy-oxygen vacancy defect dipoles.

关键词： Piezoelectrics domain structure lead-free high Curie temperature dopant.