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Brain activity following esophageal acid infusion using positron emission tomography

World Journal of Gastroenterology 2010年第43期16卷 5481-5489页

作者： Shigeyuki Kobayashi Yasuhiko Abe manabu tashiro Tomoyuki Koike Katsunori Iijima Akira Imatani Shuichi Ohara Satoshi Watanabe Shin Fukudo Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine Division of Cyclotron Nuclear Medicine Cyclotron and Radioisotope Center Tohoku University Division of Behavioral Medicine Tohoku University Graduate School of Medicine

AIM: To investigate symptoms and brain activity following esophageal acid infusion. METHODS: Fifteen healthy volunteers were recruited for the study. Hydrochloric acid (pH 1 and 2) and distilled water (pH 7) were randomly and repeatedly infused into the esophagus. The brain activity was evaluated by positron emission tomography. The severity of heartburn elicited by the infusion was rated on an auditory analog scale of ***: The severity of heartburn following each infusion showed a step-wise increase with increasing acidity of the perfusate. The heartburn scores were significantly higher in the second pH 1 infusion compared with the first infusion. Acid and distilled water infusion induced activation of various brain areas such as the anterior insula, temporal gyrus, and anterior/ posterior cingulate cortex. At pH 1 or 2, in particular, activation was observed in some emotion-related brain areas such as the more anterior part of the anterior cingulate cortex, parahippocampal gyrus, or the temporal pole. Strong activation of the orbitofrontal cortex was found by subtraction analysis of the two second pH 1 infusions, with a significant increase of heartburn symptoms. CONCLUSION: Emotion-related brain areas were activated by esophageal acid stimulation. The orbitofrontal area might be involved in symptom processing, with esophageal sensitization induced by repeated acid stimulation.

关键词： Esophageal acid infusion Brain imaging Positron emission tomography

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Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance

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Oncology Research 2024年第1期32卷 139-150页

作者： SAYAKA IMATSUJI YUKIKO UJIE HIROYUKI ODAKE MASAYA IMOTO SUSUMU ITOH ETSU tashiro Department of Biosciences and Informatics Faculty of Science and TechnologyKeio UniversityYokohama223-8522Japan Department of Neurology Juntendo University Graduate School of MedicineTokyo113-8421Japan Laboratory of Biochemistry Showa Pharmaceutical UniversityTokyo194-8543Japan

Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer ***,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains *** address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell *** these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was ***,the expression of EMT-related transcription factors,including Slug,was *** the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant *** mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic ***,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene *** results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.

关键词： Cisplatin EMT Chemo-resistance TGF-β

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Numerical analysis of plasma arc physical characteristics under additional constraint of keyhole

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Chinese Physics B 2018年第3期27卷 306-313页

作者：徐斌蒋凡陈树君田中学田代真一 Nguyen Van Anh Engineering Research Center of Advanced Manufacturing Technology for Automotive Components Ministry of Education Joining and Welding Research Institute Osaka University

The physical characteristics of a plasma arc affect the stability of the keyhole and weld pool directly during keyhole plasma arc welding （KPAW）. There will be significant change for these characteristics because of the interaction between the keyhole weld pool and plasma arc after penetration. Therefore, in order to obtain the temperature field, flow field, and arc pressure of a plasma arc under the reaction of the keyhole, the physical model of a plasma arc with a pre-set keyhole was established. In addition, the tungsten and base metal were established into the calculated domain, which can reflect the effect of plasma arc to weld pool further. Based on magneto hydrodynamics and Maxwell equations, a twoSdimensional steady state mathematical model was established. Considering the heat production of anode and cathode, the distribution of temperature field, flow field, welding current density, and plasma arc pressure were solved out by the finite difference method. From the calculated results, it is found that the plasma arc was compressed a second time by the keyhole. This additional constraint results in an obvious rise of the plasma arc pressure and flow velocity at the minimum diameter place of the keyhole, while the temperature field is impacted slightly. Finally, the observational and metallographic experiments are conducted, and the shapes of plasma arc and fusion line agree with the simulated results generally.

关键词： characteristics of plasma arc interaction of keyhole and plasma arc pre-set keyhole model nu- merical analysis

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possible role of soluble fibrin monomer complex after gastroenterological surgery

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World Journal of Gastroenterology 2017年第12期23卷 2209-2216页

作者： Masatoshi Kochi manabu Shimomura Takao Hinoi Hiroyuki Egi Kazuaki Tanabe Yasuyo Ishizaki Tomohiro Adachi Hirotaka tashiro Hideki Ohdan Department of Gastroenterological and Transplant Surgery Applied Life SciencesInstitute of Biomedical and Health SciencesHiroshima University Department of Surgery National Hospital Organization Higashihiroshima Medical Center Department of Surgery Institute for Clinical ResearchNational Hospital Organization Kure Medical Center and Chu-goku Cancer Center Department of Surgery National Hospital Organization Hiroshima-nishi Medical Center

AIM To examine the role of soluble fibrin monomer complex(SFMC) in the prediction of hypercoagulable state after gastroenterological *** We collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related *** A total of 123 patients were included in the present study. There were no patients with symptomatic VTE. Thirty-five(28%) patients received postoperative anticoagulant therapy. In the multivariate analysis, a high SFMC level on POD 1 was independently associated with D-dimer elevation on POD 7(OR = 4.31, 95%CI: 1.10-18.30, P = 0.03). The cutoff SFMC level was 3.8 μg/ml(AUC = 0.78, sensitivity, 63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in high-SFMC patients who received anticoagulant therapy in comparison to highSFMC patients who did *** The SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

关键词： Hypercoagulable state Gastroenterological surgery Soluble fibrin monomer complex Venous thromboembolism Anticoagulant therapy

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STRUCTURAL PHASE TRANSITION OF ALIPHATIC NYLONS VIEWED FROM THE WAXD/SAXS AND VIBRATIONAL SPECTRAL MEASUREMENTS AND MOLECULAR DYNAMICS CALCULATION

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Chinese Journal of Polymer Science 2007年第1期25卷 73-82页

作者： Kohji tashiro Department of Future Industry-Oriented Basic Science and Materials Toyota Technological InstituteTempakuNagoya 468-8511Japan

The crystalline phase transition of aliphatic nylon 10/10 has been investigated on the basis of the simultaneous measurement of wide-angle and small-angle X-ray scatterings, the infrared spectral measurement and the molecular dynamics calculation. An interpretation of infrared spectra taken for a series of nylon samples and the corresponding model compounds was successfully made, allowing us to assign the infrared bands of the planar-zigzag methylene segments reasonably. As a result the methylene segmental parts of molecular chains were found to experience an order-to-disorder transition in the Brill transition region, where the intermolecular hydrogen bonds are kept alive although the bond strength becomes weaker at higher temperature. The small-angle X-ray scattering data revealed a slight change in lamellar stacking mode in the transition region. The crystal structure has been found to change more remarkably in the temperature region immediately below the melting point, where the conformationally disordered chains experienced drastic rotational and translational motions without any constraints by hydrogen bonds, and the lamellar thickness increased largely along the chain axis. These experimental results were reasonably reproduced by the molecular dynamics calculation performed at the various temperatures.

关键词： Aliphatic nylon Phase transition Wide-angle X-ray diffraction Small-angle X-ray scattering Computer simulation.

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Neurorehabilitation using a voluntary driven exoskeletal robot improves trunk function in patients with chronic spinal cord injury: a single-arm study

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Neural Regeneration Research 2022年第2期17卷 427-432页

作者： Hiroki Okawara Syoichi tashiro Tomonori Sawada Keiko Sugai Kohei Matsubayashi Michiyuki Kawakami Satoshi Nori Osahiko Tsuji Narihito Nagoshi Morio Matsumoto Masaya Nakamura Department of Orthopaedic Surgery Keio University School of MedicineTokyoJapan Department of Rehabilitation Medicine Keio University School of MedicineTokyoJapan Department of Orthopedic Surgery National Hospital OrganizationMurayama Medical CenterTokyoJapan

Body weight-supported treadmill training with the voluntary driven exoskeleton(VDE-BWSTT) has been shown to improve the gait function of patients with chronic spinal cord injury. However, little is known whether VDE-BWSTT can effectively improve the trunk function of patients with chronic spinal cord injury. In this open-label, single-arm study, nine patients with chronic spinal cord injury at the cervical or thoracic level(six males and three females, aged 37.8 ± 15.6 years, and time since injury 51.1 ± 31.8 months) who underwent outpatient VDE-BWSTT training program at Keio University Hospital, Japan from September 2017 to March 2019 were included. All patients underwent twenty 60-minute gait training sessions using VDE. Trunk muscular strength, i.e., the maximum force against which patient could maintain a sitting posture without any support, was evaluated in four directions: anterior, posterior, and lateral(right and left) after 10 and 20 training sessions. After intervention, lateral muscular strength significantly improved. In addition, a significant positive correlation was detected between the change in lateral trunk muscular strength after 20 training sessions relative to baseline and gait speed. The change in trunk muscular strength after 20 training sessions relative to baseline was greatly correlated with patient age. This suggests that older adult patients with chronic spinal cord injury achieved a greater improvement in trunk muscle strength following VDE-BWSTT. All these findings suggest that VDE-BWSTT can improve the trunk function of patients with chronic spinal cord injury and the effect might be greater in older adult patients. The study was approved by the Keio University of Medicine Ethics Committee(IRB No. 20150355-3) on September 26, 2017.

关键词： body weight-supported treadmill training gait disorders hybrid assistive limb neurologic neurophysiotherapy postural balance precision medicine robot-assisted gait training robotics spinal cord injury trunk

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Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway

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Acta Pharmacologica Sinica 2004年第5期25卷 149-156页

作者： Shin-ichi tashiro,Satoshi ONODERA,Takashi IKEJIMA Shenyang Pharmaceutical University Shenyang 110016 China prof Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan China-Japan Research Institute of Medical and Pharmaceutical Sciences

AIM: To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability oforidonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualizedby phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel *** activity was assayed using fluorometric protease assay. ICAD, Bcl-2, and Bax proteins expression weredetected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA andincreased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase(ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activationand down-regulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). However, pretreatment with an inhibitor of poly (ADP-ribose) polymerase (PARP), 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. Inaddition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducerBax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION:Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation ofcaspase-3/ICAD pathway.

关键词： oridonin HeLa cells apoptosis caspase 3 caspases bcl-2 genes bax genes Western blotting

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The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

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Neural Regeneration Research 2017年第1期12卷 43-46页

作者： Syoichi tashiro Masaya Nakamura Hideyuki Okano Department of Rehabilitation Medicine Keio University School of MedicineTokyoJapan Department of Orthopaedic Surgery Keio University School of MedicineTokyoJapan Department of Physiology Keio University School of MedicineTokyoJapan

Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less *** the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative *** combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to *** a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic *** though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain *** this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.

关键词： transplantation spinal cord injury regenerative medicine chronic phase rehabilitation treadmill training

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Pseudolaric acid B induces apoptosis,senescence,and mitotic arrest in human breast cancer MCF-7

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Acta Pharmacologica Sinica 2007年第12期28卷 1975-1983页

作者： Shin-ichi tashiro Satoshi ONODERA Takashi IKEJIMA Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543Japan China-Japan Research Institute of Medical Pharmaceutical Sciences Shenyang Pharmaceutical UniversityShenyang 110016China

Aim:The aim of the present study was to investigate the inhibitory effect ofpseudolaric acid B （PAB） on human breast cancer MCF-7 ***:3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide analysis,morphologicalchanges,acridine orange staining,and agarose gel electrophoresis were appliedto detect *** percentage of apoptotic and necrotic cells was calcu-lated by the lactate dehydrogenase activity-based cytotoxicity assay;senescenceassociated （SA）-β-galactosidase activity was detected to evaluate senescence;flow cytometric analysis of propidium iodide staining was carried out to investi-gate the distribution of cell cycle,and the protein expression was examined byWestern blot ***:During apoptosis,the half maximal inhibitoryconcentration IC50was 3.4 and 1.35 μmol/L at 36 and 48 h after PAB treatment,*** MCF-7 cells exposed to PAB showed typical characteristics ofapoptosis,including the morphological changes and DNA ***-7 cells treated with 4 μmol/L PAB for 36 h underwent apoptosis,but *** apoptosis induced by PAB was independent of the death *** senescent cells became larger and flatter,and the SA-β-galactosi-dase staining was *** induced obvious mitotic arrest and it precededapoptosis and *** expressions of p21 and p53 was upregulated withPAB treatment,and cyclin B 1 was upregulated and transported from the cyto-plasm to nuclei,and sustained stable ***:PAB induced mitoticarrest in the MCF-7 cells and inhibited proliferation through apoptosis *** apoptosis was independent of the death receptor pathway.

关键词： apoptosis senescence mitotic arrest human breast cancer MCF-7 pseudolaric acid B

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Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell

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Acta Pharmacologica Sinica 2006年第12期27卷 1622-1629页

作者： Takashi IKEJIMA Shin-ichi tashiro Satoshi ONODERA China-Japan Research Institute of Medical Pharmaceutical Sciences Shenyang Pharmaceutical UniversityShenyang 110016China Department of Clinical and Biomedical Sciences Showa Pharmaceutical UniversityTokyo 194-8543Japan

Aim:To study the mechanisms by which N-demethyl-clarithromycin(NDC)induces human cervical cancer HeLa cell apoptosis in ***:The viabilityof N-demethyl-clarithromycin-induced HeLa cells was measured by MTT *** cells with condensed nuclei were visualized by phase *** DNA fragmentation was assayed by agarose *** of mitochondrial transmembrane potential wasanalyzed by a FACScan ***-3,poly-(ADP-ribose)polymerase(PARP),caspase-activated DNase(ICAD),Bcl-2,Bax,p53,and SIRT1 proteinexpression and the release of cytochrome c were detected by Western blot ***:N-demethyl-clarithromycin,an anti-inflammatory substance,inhibitedHeLa cell growth in a dose-and time-dependent manner.N-demethyl-clarithro-mycin induced HeLa cell death through the apoptotic *** pan-caspaseinhibitor(z-VAD-fmk),caspase-3 inhibitor(z-DEVD-fmk)and the caspase-9 inhibi-tor(z-LEHD-fmk)partially enhanced cell viability induced by N-demethyl-clarithromycin,but the caspase-8 inhibitor(z-IETD-fmk)had almost no ***-3 was activated then followed by the degradation of caspase-3 substrates,the inhibitor of ICAD and PARE Simultaneously,mitochondrial transmembranepotential was markedly reduced and the release of cytochrome c in the cytosolwas increased.N-demethyl-clarithromycin upregulated the expression ratio ofmitochondrial Bax/Bcl-2,and significantly increased the expression of the *** also downregulated anti-apoptotic protein SIRT1 ***:N-demethyl-clarithromycin induced apoptosis in HeLa cells via themitochondrial pathway.

关键词： N-demethyl-clarithromycin HeLa cells caspase mitochondria

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