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Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

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World Journal of Gastroenterology 2007年第47期13卷 6379-6384页

作者： Amane Kitasato Yoshitsugu Tajima Tamotsu Kuroki Ryuji Tsutsumi Tomohiko adachi Takehiro Mishima Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8501Japan

AIM: To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells. METHODS: Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1β,interferon-γ,and tumor necrosis factor-α. Inducible nitric oxide synthase (iNOS) expression,nitric oxide (NO) generation,and DNA damage were evaluated. RESULTS: NO generation was increased significantly following cytokine stimulation,and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore,NO-dependent DNA damage,estimated by the comet assay,was significantly increased by cytokines,and decreased to control levels by an iNOS inhibitor. CONCLUSION: Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells,which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.

关键词： Biliary carcinoma Inflammation Inflammatory cytokine Nitric oxide Inducible nitric oxide synthase DNA damage Gallbladder epithelial cell Hamster

Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer

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World Journal of Gastroenterology 2012年第22期18卷 2745-2755页

作者： Hiroyuki Yamamoto Yasushi adachi Hiroaki Taniguchi Hiroaki Kunimoto Katsuhiko Nosho Hiromu Suzuki Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of Medicine Division of Cancer Cell Research Institute of Medical Science University of Tokyo Department of Molecular Biology Sapporo Medical University School of Medicine

There is an increasing understanding of the roles that microsatellite instability （MSI） plays in Lynch syndrome （by mutations） and sporadic （by mainly epigenetic changes） gastrointestinal （GI） and other cancers. Defi- cient DNA mismatch repair （MMR） results in the strong mutator phenotype known as MSI, which is the hall- mark of cancers arising within Lynch syndrome. MSI is characterized by length alterations within simple repeated sequences called microsatellites. Lynch syn- drome occurs primarily because of germline mutations in one of the MMR genes, mainly MLH1 or MSH2, less frequently MSH6, and rarely PMS2. MSI is also observed in about 15% of sporadic colorectal, gastric, and en-dometrial cancers and in lower frequencies in a minor- ity of other cancers where it is often associated with the hypermethylation of the IVlLH1 gene. miRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level and are critical in many biological processes and cellular pathways. There is accumulating evidence to support the notion that the interrelationship between MSI and miRNA plays a key role in the pathogenesis of GI cancer. As a possible new mechanism underlying MSI, overexpression of m/R-IEE has been shown to downregulate expression of MLH1, IVlSH2, and MSH6. Thus, a subset of MSI-positive （MSI＋） cancers without known MMR defects may result from m/R-1E5 overexpression. Target genes of frameshift mutation for MSI are involved in various cellular func- tions, such as DNA repair, cell signaling, and apoptosis. A novel class of target genes that included not only epi- genetic modifier genes, such as HDAC2, but also miRNA processing machinery genes, including TARBP2 and XPO5, were found to be mutated in MSI＋ GI cancers. Thus, a subset of MSI＋ colorectal cancers （CRCs） has been proposed to exhibit a mutated miRNA machinery phenotype. Genetic, epigenetic, and transcriptomic dif- ferences exist between MSI＋ and MSI- cancers. Mo- lecular signatures of miR

关键词： Microsatellite instability MicroRNA DNA mis-match repair Frameshiff mutation MicroRNA processing

Production and Accumulation of Xylooligosaccharides with Long Chains by Growing Culture and Xylanase of a Mutant Strain of Bacillus pumilus X-6-19

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生物工程学报 2008年第7期24卷 1221-1227页

作者： Qingzhu Yuan Tsuyoshi adachi Shinji Takenaka Shuichiro Murakami Machiko Tanaka Kenji Aoki Division of Life Science Graduate School of Science and Technology Kobe University Rokko Kobe 657-8501 Japan Department of Applied Biological Chemistry Graduate school of Agricultural Science Kobe University Rokko Kobe 657-8501 Japan Research ＆ Development Department Bunsen Co. Ltd. Shingu-cho Tatsuno 679-4393 Japan

Bacillus pumilus X-6-9 isolated from soil and subsequently identified, produced xylooligosaccharides with long chains from xylan and accumulated them in the culture. By improving the culture conditions and mutating the bacterium, a 3.2-fold increase in the production of the xylooligosaccharides was established, when compared to the original culture conditions of B. pumilus X-6-19. The addition of D-glucose to the culture of the mutant strain U-3 of B. pumilus X-6-9 repressed the synthesis of β-xylosidase, but not xylanase. Thus, it was revealed that strain U-3 was a good organism for the production and accumulation of xylooligosaccharides with long chains from xylan by a microbial culture. Xylanase produced by strain U-3 was purified to homogeneity and characterized. The hydrolyzates generated by the purified xylanase contained xylobiose, xylotriose, xylotetraose, and xylopentaose, but not xylose.

关键词：木聚糖酶菌株细菌堆积作用

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

Dynamic methylation driven by neuronal activity in hippocampal neurons impacts complex behavior

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Frontiers in Biology 2015年第5期10卷 439-447页

作者： Anita E. Autry Megumi adachi Lisa M. Monteggia Department of Neuroscience The University of Texas Southwestern Medical Center Dallas TX 75390-9070 USA

Epigenetic processes are well-known to play critical roles in learning and memory. Among epigenetic processes, accumulating data suggests that DNA methylation in particular is a critical determinant of learning and memory. In vitro data have suggested that DNA methyltransferase inhibitors can trigger DNA demethylation and subsequent gene expression of the brain-derived neurotrophic factor gene in an activity dependent manner. To examine if these processes occur in vivo, we chronically infused DNMT inhibitors into the hippocampus and examined the impact on behavior. We find that chronic DNMT inhibition in the hippocampus results in increased anxiety-related behavior and deficits in context-dependent fear conditioning accompanied by an increase in BDNF expression. Gene expression changes were blocked by pretreatment with the NMDA receptor antagonist AP5, suggesting that DNMT inhibition enhances gene expression in an activity-dependent manner and that, conversely, the behavior deficits and abnormal gene expression are facilitated by NMDA receptor activity.

关键词： DNA methylation NMDA receptors learning and memory behavior hippocampus

Endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for multiple intraductal papillary mucinous adenomas

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World Journal of Gastroenterology 2006年第44期12卷 7203-7205页

作者： Tamotsu Kuroki Yoshitsugu Tajima Ryuji Tsutsumi Noritsugu Tsuneoka Amane Kitasato Tomohiko adachi Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences 1-7-1 Sakamoto Nagasaki 852-8501 Japan

In benign or low-grade malignant pancreatic tumors, complete removal of the lesion is sufficient for a cure, and thus minimal resection techniques with preservation of the pancreatic functional reserve have advantages over more extended pancreatic resections. However, a high incidence of postoperative pancreatic fistula in such procedures has been reported. Moreover, branch-type intraductal papillary mucinous neoplasms of the pancreas tend to locate in the head of the pancreas, and show less malignant potential. We describe an endoscopic naso- pancreatic stent-guided single-branch resection of the pancreas for branch-type multiple intraductal papillary mucinous adenomas, along with a gastric wall-covering method for the prevention of pancreatic leakage.

关键词： Intraductal papillary mucinous neoplasm Single-branch resection Gastric wall-covering method

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

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World Journal of Gastroenterology 2010年第46期16卷 5779-5789页

作者： Yasushi adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh Imai Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University Department of Internal Medicine Sapporo Shirakabadai Hospital Vanderbilt-Ingram Cancer Center and Departments of Medicine and Cell Biology Vanderbilt University

Advances in molecular research in cancer have brought new therapeutic strategies into clinical *** new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) *** concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new *** I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human *** this review,we focus on this promising therapeutic target,*** IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI *** studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer *** results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and *** also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical *** mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single *** summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug ***,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcino

关键词： Dominant negative Gastrointestinal cancer Insulin like growth factor-I receptor Monoclonal anti-body Tyrosine kinase inhibitor

Closed-Loop Control of an XYZ Micro-Stage and Designing of Mechanical Structure for Reduction in Motion Errors

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Nanomanufacturing and Metrology 2021年第1期4卷 53-66页

作者： Hiraku Matsukuma Keisuke adachi Takuma Sugawara Yuki Shimizu Wei Gao Eiji Niwa Yoshihiro Sasaki Department of Finemechanics Graduate School of EngineeringTohoku UniversityMiyagiSendai 980-8579Japan Research Institute for Electromagnetic Materials 9-5-1 NaritaMiyagiTomiya 981-3341.Japan

This paper presents a compact XYZ micro-stage driven by an impact driving mechanism.A moving body is translationally actuated along the X-,Y-,and Z-axes in millimeter-scale range and with nanometer-scale ***-N thin-film strain sensors are integrated into the micro-stage for closed-loop ***-loop control is also carried *** motion errors in six degrees of freedom are also investigated for this *** is clarified by analysis of finite element method that rotational motion errors around the driving axis are caused by torques due to tensions from the elastic hinges of *** mechanical structure of XYZ micro-stage to cancel out the torque generated is proposed and the second prototype is *** the rotational motion error is successfully suppressed in the second prototype,a rotational motion error of more than 0.1°remains due to remaining torque and assembly error of the elastic ***,in order to reduce the rotational motion error,the prototype is designed in which the location of elastic hinges is *** designing a mechanical structure in which torque is suppressed,all rotational motion errors are successfully reduced to less than 0.05°in the prototype with single-layer hinges.

关键词： XYZ micro-stage Cr-N thin-film displacement sensor Closed-loop positioning Impact drive Friction drive

A New Algorithm for Generalized Least Squares Factor Analysis with a Majorization Technique

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Open Journal of Statistics 2015年第3期5卷 165-172页

作者： Kohei adachi Graduate School of Human Sciences Osaka University Osaka Japan

Factor analysis (FA) is a time-honored multivariate analysis procedure for exploring the factors underlying observed variables. In this paper, we propose a new algorithm for the generalized least squares (GLS) estimation in FA. In the algorithm, a majorization step and diagonal steps are alternately iterated until convergence is reached, where Kiers and ten Berge’s (1992) majorization technique is used for the former step, and the latter ones are formulated as minimizing simple quadratic functions of diagonal matrices. This procedure is named a majorizing-diagonal (MD) algorithm. In contrast to the existing gradient approaches, differential calculus is not used and only elmentary matrix computations are required in the MD algorithm. A simuation study shows that the proposed MD algorithm recovers parameters better than the existing algorithms.

关键词： Exploratory Factor Analysis Generalized Least Squares Estimation Matrix Computations Majorization