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Articles by S Inoue
Total Records ( 4 ) for S Inoue
  T. a Matsuyama , T Kurita , K Suyama , H Okamura , T Noda , K Satomi , W Shimizu , N Aihara , Y Ikeda , S Inoue , S Kamakura and H. Ishibashi Ueda
 

A 68-year-old woman with idiopathic dilated cardiomyopathy suffered from drug-resistant monomorphic ventricular tachycardia (VT). Electrophysiological study revealed a re-entrant VT circuit located just beneath the inferior mitral valve annulus. The VT was considered to be related to the mitral valve isthmus and was abolished by radiofrequency ablation. The patient died 2 years after the ablation due to worsening of heart failure and an autopsy was performed. Pathological examination revealed ablation scar tissue on the localized myocardial bundle running parallel to the mitral valve annulus. Therefore, this bundle appeared to comprise the slow conduction area of the re-entrant VT in this case.

  M. T Wilhelm , A Rufini , M. K Wetzel , K Tsuchihara , S Inoue , R Tomasini , A Itie Youten , A Wakeham , M Arsenian Henriksson , G Melino , D. R Kaplan , F. D Miller and T. W. Mak
 

Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and Np73 isoforms. As part of our ongoing program to distinguish the biological functions of these isoforms, we generated mice that are selectively deficient for the Np73 isoform. Mice lacking Np73 (Np73–/– mice) are viable and fertile but display signs of neurodegeneration. Cells from Np73–/– mice are sensitized to DNA-damaging agents and show an increase in p53-dependent apoptosis. When analyzing the DNA damage response (DDR) in Np73–/– cells, we discovered a completely new role for Np73 in inhibiting the molecular signal emanating from a DNA break to the DDR pathway. We found that Np73 localizes directly to the site of DNA damage, can interact with the DNA damage sensor protein 53BP1, and inhibits ATM activation and subsequent p53 phosphorylation. This novel finding may explain why human tumors with high levels of Np73 expression show enhanced resistance to chemotherapy.

  S Inoue , C Sato and K. Kitajima
 

N-Glycolylneuraminic acid (Neu5Gc) is the second most populous sialic acid (Sia). The only known biosynthetic pathway of Neu5Gc is the hydroxylation of cytidine-5'-monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), catalyzed by CMP-Neu5Ac hydroxylase (CMAH). Neu5Gc is abundantly found in mammals except for human, in which CMAH is inactivated due to mutation in the CMAH gene. Evidence has accumulated to show occurrence of Neu5Gc-containing glycoconjugates in sera of cancer patients, human cancerous tissues and cultured human cell lines. Recently, occurrence of natural antibodies against Neu5Gc was shown in healthy humans and is a serious problem for clinical xenotransplantation and stem cell therapies. Studying human occurrence of Neu5Gc is of importance and interest in a broad area of medical sciences. In this study, using a fluorometric high performance liquid chromatography method, we performed quantitative analyses of Sias both inside and in the external environment of the cell and found that (i) incorporation of Neu5Gc was most prominent in soluble glycoproteins found both in the extracellular space and inside the cell as the major Sia compounds. (ii) Of the total Neu5Gc in the Sia compounds that the cells synthesized, 90% was found in the secreted sialoglycoproteins, whereas for Neu5Ac, 70% was found in the secreted sialoglycoproteins. (iii) The Neu5Gc ratio was higher in the secreted sialoglycoproteins (as high as 40% of total Sias) than in intracellular sialoglycoproteins. (iv) The majority of the secreted sialoglycoproteins was anchored on the culture dishes and solubilized by brief trypsin treatment. Based on these findings, a new idea on the mechanism of accumulation of Neu5Gc in cancer cells was proposed.

  T Tashiro , E Sekine Kondo , T Shigeura , R Nakagawa , S Inoue , M Omori Miyake , T Chiba , N Hongo , S. i Fujii , K Shimizu , Y Yoshiga , T Sumida , K Mori , H Watarai and M. Taniguchi
 

NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with -galactosylceramide (-GalCer), which is composed of -galactopyranose linked to ceramide (itself composed of sphingosine and fatty-acyl chains); the chain length of the ceramide varies and this affects the ability of -GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized -carba-GalCer, which has an -linked carba-galactosyl moiety; here, the 5a'-oxygen atom of the D-galactopyranose ring of -GalCer is replaced by a methylene group. The -carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN- compared with -GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The -carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was -GalCer, which has an acetal bond. Modulation of the sugar moiety in glycolipids might therefore provide optimal therapeutic reagents for protective immune responses against tumor or pathogens.

 
 
 
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