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在1例凝胶滴样角膜营养不良的日本患者中发现新错义突变

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世界核心医学期刊文摘（眼科学分册） 2005年第6期1卷 11-12页

作者： taniguchi y. Tsujikawa M. Hibino S. 程燕

To report a novel missense mutation in TACSTD2 gene, L186P, responsible for gelatinous droplike dystrophy (GDLD). Case report and experimental study. A 10- year-old Japanese boy suffering from typical GDLD was studied. A 1.1- kbDNA fragment of the TACSTD2 gene was amplified and analyzed using a molecular biological method. cDNA from the patient’ s cornea was also analyzed to determine which allele was expressed in the patient’ s corneal epithelium. Sequence analysis revealed that the patient is a compound heterozygote for the Q118X mutation and the L186P, the first missense mutation found in Japanese GDLD. Polymerase chain reaction-restriction fragment length polymorphism analysis from cDNA of patient’ s cornea revealed that the L186P missense mutation allele is expressed in the patient’ s corneal epithelium. We describe a novel mutation in one case of Japanese GDLD. The results confirm that the missense mutation L186P in the TACSTD2 gene is also responsible for the GDLD phenotype.

关键词：角膜营养不良错义突变角膜上皮分子生物杂合体表现型序列分析试验性研究

肺动脉高压启动治疗后血流动力学指标的预后价值

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中华高血压杂志 2017年第11期25卷 1011-1011页

作者：黄洁叶鹏 Weatherald J Boucly A Chemla D Savale L Peng M Jevnikar M Ja?s X taniguchi y O'Connell C Parent F Sattler C Hervé P Simonneau G Montani D Humbert M Adir y Sitbon O

血流动力学指标，如心脏指数和右心房压力（right atrial pressure，RAP）与患者确诊肺动脉高压时的生存率持续相关。近期研究表明，肺动脉顺应性（pulmon aryarterial compliance，Pea）也可能预测肺动脉高压的预后。而在治疗开始之后... 详细信息

血流动力学指标，如心脏指数和右心房压力（right atrial pressure，RAP）与患者确诊肺动脉高压时的生存率持续相关。近期研究表明，肺动脉顺应性（pulmon aryarterial compliance，Pea）也可能预测肺动脉高压的预后。而在治疗开始之后测定的血流动力学指标对预后的价值还未确定。

关键词：血流动力学指标肺动脉高压预后价值治疗肺动脉顺应性右心房压力心脏指数生存率

Hypoxia inducible factor(HIF) in the tumor microenvironment：friend or foe？

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Science China(Life Sciences) 2017年第10期60卷 1114-1124页

作者： yanqing Huang Daniel Lin Cullen M.taniguchi The University of Texas at MD Anderson Department of Experimental Radiation Oncology MD Anderson Cancer Center Houston TX 77030 USA The University of Texas at MD Anderson Division of Radiation Oncology MD Anderson Cancer Center Houston TX 77030 USA

Hypoxia acts as an important regulator of physiological and pathological processes. Hypoxia inducible factors(HIFs) are the central players involved in the cellular adaptation to hypoxia and are regulated by oxygen sensing EGLN prolyl *** affects many aspects of cellular growth through both redox effects and through the stabilization of HIFs. The HIF isoforms likely have differential effects on tumor growth via alteration of metabolism, growth, and self-renewal and are likely highly context-dependent. In some tumors such as renal cell carcinoma, the EGLN/HIF axis appears to drive tumorigenesis,while in many others HIF1 and HIF2 may actually have a tumor suppressive role. An emerging role of HIF biology is its effects on the tumor microenvironment. The EGLN/HIF axis plays a key role in regulating the function of the various components of the tumor microenvironment, which include cancer-associated fibroblasts, endothelial cells, immune cells, and the extracellular matrix(ECM). Here, we discuss hypoxia and the diverse roles of HIFs in the setting of tumorigenesis and the maintenance of the tumor microenvironment as well as possible future directions of the field.

关键词： hypoxia HIF tumor microenvironment cellular homeostasis mouse model

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

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World Journal of Gastroenterology 2008年第37期14卷 5650-5656页

作者： Mariko Oki Hiroyuki yamamoto Hiroaki taniguchi yasushi Adachi Kohzoh Imai yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of MedicineSapporo 060-8543 Japan Sapporo Medical University Sapporo 060-8556 Japan

AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands. METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed. RESULTS: Overexpression of EphA4 mRNA expres-sion was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Over-expression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpres-sion of EphA4 plays a role in gastric cancer.

关键词： Ephrin receptor A4 Gastric cancer Ephrin Fibroblast growth factor receptor 1 Prognosis

Promising role of D-amino acids in irritable bowel syndrome

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World Journal of Gastroenterology 2022年第31期28卷 4471-4474页

作者： yuka Ikeda Kurumi taniguchi Haruka Sawamura Ai Tsuji Satoru Matsuda Department of Food Science and Nutrition Nara Women's UniversityNara 630-8506Japan

Irritable bowel syndrome(IBS)is an important health care *** in the microbiota of the gut-brain axis may be linked to the pathophysiology of *** dietary intake could contribute to produce various metabolites including Damino acids by the fermentation by the gut microbiota.D-amino acids are the enantiomeric counterparts of L-amino acids,in general,which could play key roles in cellular physiological processes against various oxidative ***,the presence of D-amino acids has been shown to be linked to the protection of several organs in the *** particular,the gut microbiota could play significant roles in the stability of emotion via the action of D-amino ***,we would like to shed light on the roles of D-amino acids,which could be used for the treatment of IBS.

关键词： Irritable bowel syndrome D-amino acid Gut microbiota Colitis Probiotics Fecal microbiota transplantation

Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma

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World Journal of Gastroenterology 2010年第28期16卷 3521-3528页

作者： Noriyuki Akutsu Hiroyuki yamamoto Shigeru Sasaki Hiroaki taniguchi yoshiaki Arimura Kohzoh Imai yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of MedicineSapporo 060-8543Japan Sapporo Medical University Sapporo 060-8556 Japan

AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or *** of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(Py siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 ***3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.

关键词： Glypican-3 Wnt Matrix metalloproteinases Sulfatase Hepatocellular carcinoma

Genetic and epigenetic characteristics of gastric cancers with JC virus T-antigen

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World Journal of Gastroenterology 2009年第44期15卷 5579-5585页

作者： Satoshi yamaoka Hiroyuki yamamoto Katsuhiko Nosho Hiroaki taniguchi yasushi Adachi Shigeru Sasaki yoshiaki Arimura Kohzoh Imai yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical UniversitySapporo 060-8543 Japan Sapporo Medical University Sapporo 060-8556 Japan

AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr virus （EBV） infection, microsatellite instability （MSI）, and genetic and epigenetic alterations in gastric cancers. Mutations in the p53,β-catenin, K/MS, BRAF, PIK3CA genes were analyzed by PCR- single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS： JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin （15 of 21, 71%） than in cancers without （42%, P = 0.018）. p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers （32%） than in TAg negative cancers （57%, P = 0.018）. TAg positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers （P = 0.008 and P = 0.003）. CONCLUSION： The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.

关键词： JC virus T-antigen Epstein-Barr virus Microsatellite instability Gastric cancer

EFFECT OF INTERPHASE LIFT FORCE ON THE FLUID FLOW IN AN AIR-STIRRED CyLINDRICAL VESSEL

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Acta Metallurgica Sinica(English Letters) 2000年第4期13卷 921-931页

作者： L.F. Zhang K.K. Cai y. Qu and y.S. Shen Postdoctoral Fellow of Japan Science Promotion Society taniguchi Lab., Department of Metallurgy, Graduate School of Engineering, Tohoku University, Sendai980-8579, Japan School of Metallurgy, University of Scien Tohoku Univ Sendai Japan

In the present paper, based on the two-phase model (Eulerian model), the two dimensional fluid flow liz air-stirred water systems is simulated, and the effect of interphase lift force on the fluid flow is specially discussed. In the Eulerian two-phase model, gas and liquid phase are considered to be two different continuous fluids interacting with each other through the finite inter-phase areas. The exchange between the phases is represented by source terms in conversation equations. Turbulence is assumed to be a property of the liquid phase, k - ε model is used to describe the behavior of the liquid phase. The dispersion of phases due to turbulence is represented by introducing a diffusion term in mass consecrvation equation. The contribution of bubble movement to the turbulent energy and its dissipation rate is taken into accounted by adding extra volumetric source terms to the equations of turbulent enemy and its dissipation rate. The comparison between the mathematical simulation and experiment data indicates that the interphase lift force has a big effect on the flow behavior, and considering both drug force and lift force as interphase forces is important to accurately simulate the gas-water two-phase fluid flow in air-stirred systems. The interphase lift force makes bubbles move away from the centerline, the gas concentration is decreased near the centerline, and increased near the wall. The lift force is smaller than drug force at the same place, especially far away from the centerline.

关键词： two-phase Eulerian model interphase lift force interphase drag force mathematical simulation

Overexpression of β3/γ2 chains of laminin-5 and MMP7 in biliary cancer

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World Journal of Gastroenterology 2009年第31期15卷 3865-3873页

作者： Toshikuni Oka Hiroyuki yamamoto Shigeru Sasaki Masanori Ii Keiichi Hizaki Hiroaki taniguchi yasushi Adachi Kohzoh Imai yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of Medicine Sapporo Medical University

AIM： To clarify the clinicopathological significance of laminin-5 y2 （LNγ2） and 133 （LNI33） chains and MMP7 expression in biliary tract cancer. METHODS： We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed. RESULTS： LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified Into two types： invasive front dominant type （38%） and diffuse type （28%）.The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in ***： Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.

关键词： Biliary tract cancer Laminin-5 Laminin γ2 Laminin β3 MMP7