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World Journal of Gastroenterology 2006年第39期12卷 6316-6324页

作者： tetsuya shimizu Shigeki Yokomuro Yoshiaki Mizuguchi Yutaka Kawahigashi Yasuo Arima Nobuhiko Taniai Yasuhiro Mamada Hiroshi Yoshida Koho Akimaru Takashi Tajiri Surgery for Organ Function and Biological Regulation Graduate School of Medicine Nippon Medical School Tokyo 113-8603 Japan

AIM： To elucidate the biological effects of transforming growth factor-β1 （TGF-β1） on intrahepatic cholangiocarcinoma （ICC）.METHODS： We investigated the effects of TGF-β1 on human ICC cell lines （HuCCT1, MEC, and HUH-28） by monitoring the influence of TGF-β1 on tumor growth and interleukin-6 （IL-6） expression in ICC cells.RESULTS： All three human ICC cell lines produced TGF-β1 and demonstrated accelerated growth in the presence of TGF-β1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-β1-induced stimulation of the expression of TGF-β1, as well as a decrease in TGF-β1 mRNA expression induced by neutralizing anti-TGF-β1 antibody. These results indicate that TGF-β1 stimulates the production and function of TGF-β1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-β1 antibody. Experiments using HuCCT1 revealed a TGF-β1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-β1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-β1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3.CONCLUSION： ICC cells produce TGF-β1 and confer a TGF-β1-induced growth effect in an autocrine ***-β1 activates ILo6 production, and the functional interaction between TGF-β1 and IL-6 contributes to ICC cell growth by TGF-β1.

关键词： Transforming growth factor-β1 Interleukin-6 Intrahepatic cholangiocarcinoma

Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

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World Journal of Gastroenterology 2006年第21期12卷 3450-3452页

作者： tetsuya shimizu Hiroshi Yoshida Yasuhiro Mamada Nobuhiko Taniai Satoshi Matsumoto Yoshiaki Mizuguchi Shigeki Yokomuro Yasuo Arima Koho Akimaru Takashi Tajiri Graduate School of Medicine Surgery for Organ Function and Biology Regulation Nippon Medical SchoolTokyo113-8603Japan

We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct. Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct. On d 46 after surgery, a retrograde transhepatic biliary drainage （RTBD） tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative man- agement, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

关键词： Postoperative complication Bile leakage Ethanol ablation

Surgical resection of a solitary para-aortic lymph node metastasis from hepatocellular carcinoma

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World Journal of Gastroenterology 2012年第23期18卷 3027-3031页

作者： Junji Ueda Hiroshi Yoshida Yasuhiro Mamada Nobuhiko Taniai Sho Mineta Masato Yoshioka Youichi Kawano tetsuya shimizu Etsuko Hara Chiaki Kawamoto Keiko Kaneko Eiji Uchida Department of Surgery Nippon Medical School Tokyo 113-8603 Japan Divisions of Cardiology Hepatology Geriatrics and Integrated Medicine Department of Internal Medicine Nippon Medical School Tokyo 113-8603 Japan

Lymph node (LN) metastases from hepatocellular carcinoma (HCC) are considered uncommon. We describe the surgical resection of a solitary para-aortic LN metastasis from HCC. A 65-year-old Japanese man with B-type liver cirrhosis was admitted for the evaluation of a liver tumor. He had already undergone radiofrequency ablation, transcatheter arterial chemoembolization, and percutaneous ethanol injection therapy for HCC. Despite treatment, viable regions remained in segments 4 and 8. We performed a right paramedian sectionectomy with partial resection of the left paramedian section of the liver. Six months later, serum concentrations of alpha-fetoprotein (189 ng/mL) and PIVKA-2 (507 mAU/mL) increased. Enhanced com- puted tomography of the abdomen revealed a tumor (20 mm in diameter) on the right side of the abdominal aorta. Fluorine-18 fluorodeoxyglucose positron emission tomography revealed an increased standard uptake value. There was no evidence of recurrence in other regions. Esophagogastroduodenoscopy and colonoscopy revealed no malignant tumor in the gastrointestinal tract. Para-aortic LN metastasis from HCC was thus diagnosed. We performed lymphadenectomy. Histopathological examination revealed that the tumor was largely necrotic, with poorly differentiated HCC on its surface, which confirmed the suspected diagnosis. After 6 mo tumor marker levels were normal, with no evidence of recurrence. Our experience suggests that a solitary para-aortic LN metastasis from HCC can be treated surgically.

关键词： Surgical resection Lymph node metasta-sis Hepatocellular carcinoma Hepatectomy Positronemission tomography

One-step palliative treatment method for obstructive jaundice caused by unresectable malignancies by percutaneous transhepatic insertion of an expandable metallic stent

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World Journal of Gastroenterology 2006年第15期12卷 2423-2426页

作者： Hiroshi Yoshida Yasuhiro Mamada Nobuhiko Taniai Yoshiaki Mizuguchi tetsuya shimizu Shigeki Yokomuro Takayuki Aimoto Yoshiharu Nakamura Eiji Uchida Yasuo Arima Manabu Watanabe Eiichi Uchida Takashi Tajiri Department of Surgery 1 Nippon Medical School Japan Uchida Hospital Japan

AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS： Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS： One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS： One-step percutaneous transhepaticinsertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient＇s quality of life.

关键词： Expandable metallic stent Bile duct carcinoma Gall bladder carcinoma Pancreatic carcinoma Gastric carcinoma Obstructive jaundice

Disruption of neuronal actin barrier promotes the entry of disease-implicated proteins to exacerbate amyotrophic lateral sclerosis pathology

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Neural Regeneration Research 2025年第9期20卷 2589-2590页

作者： Mikio shimizu Tatsusada Okuno Department of Neurology Osaka University Graduate School of MedicineSuitaJapan Department of Neurology Osaka General Medical CenterOsakaJapan

Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal *** with ALS develop skeletal muscle weakness,resulting in death from respiratory paralysis,which usually occurs 2-4 years after clinical onset(Goutman et al.,2022).

关键词： paralysis sclerosis

Comparison of corneal biomechanical properties in normal tension glaucoma patients with different visual field progression speed

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International Journal of Ophthalmology(English edition) 2016年第7期9卷 973-978页

作者： Ying Hong Nobuyuki Shoji tetsuya Morita Kazunori Hirasawa Kazuhiro Matsumura Masayuki Kasahara Kimiya shimizu Department of Ophthalmology Peking University Third Hospital Key Laboratory of Vision Loss and RestorationMinistry of Education Beijing 100191 China Department of Rehabilitation Orthoptics and Visual Science Course Kitasato University School of Allied Health Sciences Sagamihara City 252-0373 Japan Department of Ophthalmology Kitasato University Hospital Sagamihara City 252-0373 Japan Kitasato University Sagamihara City 252-0373 Japan

AIM：To compare the corneal biomechanical properties difference by ocular response analyzer（ORA） in normal tension glaucoma（NTG） patients with different visual field（VF） progression speed. METHODS：NTG patients with well-controlled Goldmann applanation tonometer（GAT） who routinely consulted Kitasato University Hospital Glaucoma Department between January 2010 and February 2014 were *** and ORA parameters including corneal compensated intraocular pressure（lOPcc）,Goldmann estimated intraocular pressure（lOPg）,corneal hysteresis（CH）,corneal resistance factor（CRF） were *** was tested by Swedish interactive threshold algorithm（SITA）-standard 30-2 *** patients underwent VF measurement regularly and GAT did not exceed 15 mm Hg at any time during the 3y follow *** were divided into four groups according to VF change over 3y,and ORA findings were compared between the upper 25th percentile group（slow progression group） and the lower 25th percentile group（rapid progression group）.RESULTS：Eighty-two eyes of 56 patients were *** were 21 eyes（21 patients） each in rapid and slow progression groups ***,lOPcc,lOPg,CH,CRF were 12.1＋1.4 mm Hg,15.8±1.8 mm Hg,12.8±2.0 mm Hg,8.4±1.1 mm Hg,7.9±1.3 mm Hg respectively in rapid progression group and 11.5±1.3 mm Hg,13.5±2.1 mm Hg,11.2±1.6 mm Hg,9.3±1.1 mm Hg,8.2±0.9 mm Hg respectively in slow progression group（P=0.214,〈0.001,0.007,0.017,0.413,respectively）.In bivariate correlation analysis,lOPcc,lOPcc-GAT and CH were significant correlated with m△MD（r =-0.292,-0.312,0.228 respectively,P =0.008,0.004,0.039 respectively）.CONCLUSION：Relatively rapid VF progression occurred in NTG patients whose lOPcc are rather high,CH are rather low and the difference between lOPcc and GAT are relatively *** lOPcc and lower CH are associated with VF progression in NTG *** study suggests that GAT measures might underestimate the IOP in such patients.

关键词： ocular response analyzer intraocular pressure corneal biochemical properties visual field normal tension glaucoma

Nerve conduction models in myelinated and unmyelinated nerves based on three-dimensional electrostatic interaction

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Neural Regeneration Research 2018年第5期13卷 779-785页

作者： tetsuya Akaishi Department of Neurology Tohoku University Graduate School of Medicine Department of Neurology Yonezawa National Hospital

Until now, nerve conduction has been described on the basis of equivalent circuit model and cable theory, both of which supposed closed electric circuits spreading inside and outside the axoplasm. With these conventional models, we can simulate the propagating pattern of action potential along the axonal membrane based on Ohm＇s law and Kirchhoff＇s law. However, we could not fully explain the different conductive patterns in unmyelinated and myelinated nerves with these theories. Also, whether we can really suppose closed electrical circuits in the actual site of the nerves or not has not been fully discussed yet. In this report, a recently introduced new theoretical model of nerve conduction based on electrostatic molecular interactions within the axoplasm will be reviewed. With this new approach, we can explain the different conductive patterns in unmyelinated and myelinated nerves. This new mathematical conductive model based on electrostatic compressional wave in the intracellular fluid may also be able to explain the signal integration in the neuronal cell body and the back-propagation mechanism from the axons to the dendrites. With this new mathematical nerve conduction model based on electrostatic molecular interactions within the intracellular fluid, we may be able to achieve an integrated explanation for the physiological phenomena taking place in the nervous system.

关键词： nerve conduction ion channels electrostatic interactions electrostatic compressional wave saltatory conduction myelinated nerves unmyelinated nerves saltatory equations

FE FORMULATION FOR THE VISCOELASTIC BODY MODELED BY FRACTIONAL CONSTITUTIVE LAW

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Acta Mechanica Sinica 2001年第4期17卷 354-365页

作者：张卫 Nobuyuki shimizu Institute of Applied Mechanics Jinan UniversityGuangzhou 510632China Department of Mechanical Engineering Iwaki Meisei UniversityJapan

This paper presents finite element (FE) formulation of the viscoelastic materials described by fractional constitutive law. The time-domain three-dimensional constitutive equation is constructed. The FE equations are set up by treating the fractional operator as a special case of the hereditary integration. The equations are solved by numerical integration method. The numerical algorithm developed by the authors for Liouville-Riemann's fractional derivative was adopted to formulate FE procedures and extended to solve the more general case of the hereditary integration. The numerical examples were given to show the correctness and effectiveness of the integration algorithm.

关键词： viscoelasticity fractional calculus FEM polymer materials

Progress in numerical simulation of cavitating water jets

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Journal of Hydrodynamics 2013年第4期25卷 502-509页

作者： PENG Guoyi shimizu Seiji College of Engineering Nihon University

This paper reviews recent progress made toward modeling of cavitation and numerical simulation of cavitating water jets. Properties of existing cavitation models are discussed and a compressible mixture flow method for the numerical simulation of high- speed water jets accompanied by intensive cavitation is introduced. Two-phase fluids media of cavitating flow are treated as a homo- geneous bubbly mixture and the mean flow is computed by solving Reynolds-Averaged Navier-Stokes （RANS） equations for com- pressible fluid. The intensity of cavitation is evaluated by the gas volume fraction, which is governed by the compressibility of bubble-liquid mixture corresponding to the status of mean flow field. Numerical results of cavitating water jet issuing from an orifice nozzle are presented and its applicability to intensively cavitating jets is demonstrated. However, the effect of impact pressure caused by collapsing of bubbles is neglected, and effectively coupling of the present compressible mixture flow method with the dynamics of bubbles remains to be a challenge.

关键词： cavitation water jet multi-phase flow numerical simulation