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True left-sided gallbladder with variations of bile duct and cholecystic vein

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World Journal of Gastroenterology 2015年第21期21卷 6754-6758页

作者： Hiromichi Ishii Akinori Noguchi Mie Onishi Koji Takao Takahiro Maruyama Hiroaki Taiyoh Yasunobu Araki takeshi shimizu Hiroyuki Izumi Naoki Tani Masahide Yamaguchi Tetsuro Yamane Department of Surgery Matsushita Memorial Hospital

A left-sided gallbladder without a right-sided round ligament,which is called a true left-sided gallbladder,is extremely rare.A 71-year-old woman was referred to our hospital due to a gallbladder *** tomography(CT) revealed not only a gallbladder polyp but also the gallbladder located to the left of the round ligament connected to the left umbilical *** portography revealed that the main portal vein diverged into the right posterior portal vein and the common trunk of the left portal vein and right anterior portal *** cholangiography revealed that the infraportal bile duct of segment 2 joined the common bile *** cholecystectomy was performed for a gallbladder polyp,and the intraoperative finding showed that the cholecystic veins joined the round ligament.A true left-sided gallbladder is closely associated with several anomalies; therefore,surgeons encountering a true left-sided gallbladder should be aware of the potential for these anomalies.

关键词： True left-sided gallbladder Infraportal bileduct of segment 2 Anomaly of the cholecystic vein Anomaly of the portal vein Laparoscopic cholecystectomy

Identification of a dihydroorotate dehydrogenase inhibitor thatinhibits cancer cell growth by proteomic profiling

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Oncology Research 2023年第6期31卷 833-844页

作者： MAKOTO KAWATANI HARUMI AONO SAYOKO HIRANUMA takeshi shimizu MAKOTO MUROI TOSHIHIKO NOGAWA TOMOKAZU OHISHI SHUN-ICHI OHBA MANABU KAWADA KANAMI YAMAZAKI SHINGO DAN NAOSHI DOHMAE HIROYUKI OSADA Biomolecular Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Resource Development Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Biology Research Group RIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Molecular Structure Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Institute of Microbial Chemistry(BIKAKEN) NumazuMicrobial Chemistry Research FoundationShizuoka410-0301Japan Division of Molecular Pharmacology Cancer Chemotherapy CenterJapan Foundation for Cancer ResearchTokyo135-8550Japan Department of Pharmaceutical Sciences University of ShizuokaShizuoka422-8526Japan

Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune *** study presents the identification of a potent DHODH inhibitor by proteomic ***-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer *** profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic ***,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic *** results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell ***,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.

关键词： Anticancer agents Differentiating agents Drug target identification

Cell-free synthesis of stable isotope-labeled internal standards for targeted quantitative proteomics

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Synthetic and Systems Biotechnology 2018年第2期3卷 97-104页

作者： Ryohei Narumi Keiko Masuda takeshi Tomonaga Jun Adachi Hiroki RUeda Yoshihiro shimizu Laboratory of Proteome Research National Institutes of Biomedical InnovationHealth and Nutrition7-6-8Satio-AsagiIbarakiOsaka 567-0085Japan Laboratory for Single Cell Mass Spectrometry RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan Department of Systems Pharmacology Graduate School of MedicineThe University of Tokyo7-3-1 HongoBunkyo-kuTokyo 113-0033Japan Laboratory for Synthetic Biology RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan Laboratory for Cell-Free Protein Synthesis RIKEN Quantitative Biology Center(QBiC)6-2-3FuruedaiSuitaOsaka 565-0874Japan

High-sensitivity mass spectrometry approaches using selected reaction monitoring(SRM)or multiple reaction monitoring(MRM)methods are powerful tools for targeted quantitative proteomics-based investigation of dynamics in specific biological *** high-sensitivity detection of lowabundance proteins and their quantification using this technique employ stable isotope-labeled peptide internal ***,there are various ways for preparing standards,including chemical peptide synthesis,cellular protein expression,and cell-free protein or peptide ***-free protein synthesis(CFPS)or in vitro translation(IVT)systems in particular provide high-throughput and low-cost preparation methods,and various cell types and reconstituted forms are now commercially ***,we review the use of such systems for precise and reliable protein quantification.

关键词： Absolute quantification Mass spectrometry Cell-free protein synthesis system In vitro translation Targeted quantitative proteomics PURE system

1.5 Harmonic Imaging Sonography with microbubble contrast agent improves characterization of hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第36期11卷 5607-5613页

作者： Kouji Yamamoto Katsuya Shiraki Shigeo Nakanishi Hiroyuki Fuke takeshi Nakano Akira Hashimoto Atsuya shimizu Toshinobu Hamataki First Department of Internal Medicine Mie University School of Medicine Tsu Mie 514-8507 Japan Department of Internal Medicine Saiseikai Matsusaka General Hospital Matsusaka Mie 515-8557 Japan Sales Engineering Department Toshiba Medical Systems Corporation Nagoya Aichi 450-0003 Japan

AIM： TO investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma （HCC） and for the evaluation of therapeutic response. METHODS： Phantom experiments were performed to compare the contrast effects of 2^rd harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC （42 nodules） before and after the treatment and to compare against the findings obtained using other diagnostic imaging modaUties. RESULTS： In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules （85.7%） during the early phase and in all 42 nodules （100%） during the late phase using 1.5 Harmonic Imaging Sonography, in 38 nodules （90.5%） using contrast-enhanced CT, in 34 nodules （81.0%） using digital subtraction angiography （DSA）, and in 42 nodules （100%） using US CO2angiography. Following transcatheter arterial embolization, 1.5 Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules （47.6%）. However, 6 of these 20 cases were not judged in contrastenhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO2 angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%,respectively. CONCLUSION： 1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated. Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arte

关键词： 1.5 Harmonic imaging sonography Hepatocellular carcinoma Microbubble

Hydrogen promotes the activation of Cu, Zn superoxide dismutase in a rat corneal alkali-burn model

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1173-1179页

作者： takeshi Arima Tsutomu Igarashi Masaaki Uchiyama Maika Kobayashi Ikuroh Ohsawa Akira shimizu Hiroshi Takahashi Department of Ophthalmology Nippon Medical SchoolTokyo1138602Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo1138602Japan Biological Process of Aging Tokyo Metropolitan Institute of GerontologyTokyo173-0015Japan

AIM: To investigate the effects of hydrogen(H2) on Cu, Zn superoxide dismutase(SOD1) activation in a rat model of corneal alkali burn. METHODS: In each rat, one cornea was subjected to alkali exposure. Physiological saline(saline group) or H2-dissolved saline(H2 group) was instilled continuously on the cornea for 5 min before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron ***: The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H2 group(P<0.01). Furthermore, H2 treatment increased both cytoplasmic SOD1 levels(P<0.01) and activity in corneal epithelial cells(P<0.01). Notably, the SOD1 activity level in the H2 group was approximately 2.5-fold greater than that in the saline ***: H2 treatment suppresses inflammation and neovascularization in the injured cornea and indirectly suppresses oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity.

关键词： hydrogen alkali burn Cu,Zn superoxide dismutase low-vacuum scanning electron microscopy rats

Evaluation of small bowel blood flow in healthy subjects receiving low-dose aspirin

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World Journal of Gastroenterology 2011年第2期17卷 226-230页

作者： Urara Nishida Mototsugu Kato Mutsumi Nishida Go Kamada takeshi Yoshida Shouko Ono Yuichi shimizu Masahiro Asaka Department of Gastroenterology Hokkaido University Graduate School of Medicine Division of Endoscopy Hokkaido University Hospital Department of Clinical Laboratory and Transfusion Hokkaido University Hospital

AIM:To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow,and the effect of rebamipide. METHODS:Ten healthy volunteers were enrolled in this *** subjects were divided into two groups:a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 *** endoscopy and contrast-enhanced ultrasonography were performed before and after administration of *** under the curves and peak value of time-intensity curve were calculated. RESULTS:Absolute differences in areas under the curves were-1102.5(95%CI:-1980.3 to-224.7,P=0.0194) in the placebo group and-152.7(95%CI:-1604.2 to 641.6,P=0.8172) in the rebamipide group. Peak values of time intensity curves were-148.0(95% CI:-269.4 to-26.2,P=0.0225) in the placebo group and 28.3(95%CI:-269.0 to 325.6,P=0.8343) in the rebamipide *** endoscopy showed mucosal breaks only in the placebo group. CONCLUSION:Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow.

关键词： Small-intestine Capsule endoscopy Lowdose aspirin Contrast-enhanced ultrasonography Rebamipide

Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B

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World Journal of Gastroenterology 2015年第7期21卷 2116-2123页

作者： Motohiro shimizu Norihiro Furusyo Hiroaki Ikezaki Eiichi Ogawa Takeo Hayashi takeshi Ihara Yuji Harada Kazuhiro Toyoda Masayuki Murata Jun Hayashi Department of General Internal Medicine Kyushu University Hospital Kyushu General Internal Medicine Center Haradoi Hospital

AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis ***:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively *** was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal *** single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration ***:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic *** the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without *** incidence of PKTD dramatically increased after 96 mo from the start of ADV *** contrast,the SNPs were not correlated with *** regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with ***:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.

关键词： Adefovir dipivoxil Proximal kidney tubular dysfunc

An Integrated Approach for Decision Support through Multi-objective Optimization with Application to an Ill-posed Design Problem

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Computer Technology and Application 2011年第11期2卷 912-925页

作者： Yoshiaki shimizu Yasumasa Kato takeshi Kariyahara Mechanical Engineering Toyohashi University of Technology Toyohashi 441-8580 Japan

In the current scenario of global competition and short product life cycles, customer-defined satisfaction has attracted interest in artifact design. Accordingly, intelligent decision-making through multi-objective optimization has been proposed as an efficient method for human-centered manufacturing. However, previous vast researches on optimization have been mainly focused on optimization theory and optimization techniques and paid little interests on the process of problem formulation itself. In this paper, therefore, the authors present a total framework for supporting multi-objective decision making. Then, the authors try to solve the formulated multi-objective optimization problem that involves both qualitative and quantitative performance measures as a general consequence from the above procedure. Taking especially quality as a qualitative measure, the authors gave a new idea to evaluate the quality quantitatively. Additionally, to facilitate the portability of the proposed method in multidisciplinary decision-making environments, the authors implement the proposal algorithm in an Excel spreadsheet and validate the effectiveness of the approach through a case study.

关键词： Integrated systems approach optimization engineering multi-objective optimization meta-modeling value system design.

Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy

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World Journal of Gastroenterology 2004年第15期10卷 2301-2302页

作者： Daisuke shimizu Kenichi Nomura Yosuke Matsumoto Kyoji Ueda Kanji Yamaguchi Masahito Minami Yoshito Itoh Shigeo Horiike Masuji Morita Masafumi Taniwaki takeshi Okanoue Molecular Hematology and Oncology Kyoto Prefectural University of Medicine Graduate School of Medical ScienceKyoto 602-0841Japan Molecular Gastroenterology and Hepatology Kyoto Prefectural University of Medicine Graduate School of Medical ScienceKyoto 602-0841Japan School of Nursing Kyoto Prefectural University of Medicine Graduate School of Medical ScienceKyoto 602-0841Japan Molecular Hematology and Oncology Kyoto Prefectural University of Medicine Graduate School of Medical ScienceKyoto 602-0841Japan Clinical Molecular Genetics and Laboratory MedicineKyoto Prefectural University of Medicine Graduate School of Medical ScienceKyoto 602-0841Japan

A 62-year-old Japanese man who was positive for hepatitis B surface antigen (HBsAg) and anti-HBe antibody, underwent chemotherapy for non-Hodgkin's lymphoma (NHL). Mutations were detected in the precore region (nt1896) of HBV. Because steroid-containing regimen may cause reactivation of hepatitis B virus (HBV) and hepatitis may progress to be fulminant afcer its withdrawal, we administered CHO (CPA, DOX and VCR) therapy and the patient obtained complete response. However, he developed acute exacerbation of hepatitis due to HBV reactivation. Recovery was achieved with lamivudine (100 mg/d) and plasma exchange. The present case suggests that acute exacerbation of hepatitis can occur with steroid-free regimen. Because the efficacy of the prophylactic use of lamivudine has been reported and the steroid enhances curability of malignant lymphoma,the steroid containing regimen with prophylaxis of lamivudine should be evaluated further.

关键词：乙型肝炎 HBV 再生作用自由胆固醇化学疗法 CHO