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Articles by S Ohno
Total Records ( 2 ) for S Ohno
  H Itoh , T Sakaguchi , W. G Ding , E Watanabe , I Watanabe , Y Nishio , T Makiyama , S Ohno , M Akao , Y Higashi , N Zenda , T Kubota , C Mori , K Okajima , T Haruna , A Miyamoto , M Kawamura , K Ishida , I Nagaoka , Y Oka , Y Nakazawa , T Yao , H Jo , Y Sugimoto , T Ashihara , H Hayashi , M Ito , K Imoto , H Matsuura and M. Horie

Background— Drugs with IKr-blocking action cause secondary long-QT syndrome. Several cases have been associated with mutations of genes coding cardiac ion channels, but their frequency among patients affected by drug-induced long-QT syndrome (dLQTS) and the resultant molecular effects remain unknown.

Methods and Results— Genetic testing was carried out for long-QT syndrome–related genes in 20 subjects with dLQTS and 176 subjects with congenital long-QT syndrome (cLQTS); electrophysiological characteristics of dLQTS-associated mutations were analyzed using a heterologous expression system with Chinese hamster ovary cells together with a computer simulation model. The positive mutation rate in dLQTS was similar to cLQTS (dLQTS versus cLQTS, 8 of 20 [40%] versus 91 of 176 [52%] subjects, P=0.32). The incidence of mutations was higher in patients with torsades de pointes induced by nonantiarrhythmic drugs than by antiarrhythmic drugs (antiarrhythmic versus others, 3 of 14 [21%] versus 5 of 6 [83%] subjects, P<0.05). When reconstituted in Chinese hamster ovary cells, KCNQ1 and KCNH2 mutant channels showed complex gating defects without dominant negative effects or a relatively mild decreased current density. Drug sensitivity for mutant channels was similar to that of the wild-type channel. With the Luo-Rudy simulation model of action potentials, action potential durations of most mutant channels were between those of wild-type and cLQTS.

Conclusions— dLQTS had a similar positive mutation rate compared with cLQTS, whereas the functional changes of these mutations identified in dLQTS were mild. When IKr-blocking agents produce excessive QT prolongation (dLQTS), the underlying genetic background of the dLQTS subject should also be taken into consideration, as would be the case with cLQTS; dLQTS can be regarded as a latent form of long-QT syndrome.

  S Ohno , N Terada , N Ohno , S Saitoh , Y Saitoh and Y. Fujii

Our final goal of morphological and immunohistochemical studies is that all findings examined in animal experiments should reflect the physiologically functional background. Therefore, the preservation of original components in cells and tissues of animals is necessary for describing the functional morphology of living animal organs. It is generally accepted that morphological findings of various organs were easily modified by stopping their blood supply. There had been a need to develop a new preparation technique for freezing the living animal organs in vivo and then obtaining acceptable morphology and also immunolocalization of original components in functioning cells and tissues. We already developed the ‘in vivo cryotechnique’ (IVCT) not only for their morphology, but also for immunohistochemistry of many soluble components in various living animal organs. All physiological processes of cells and tissues were immediately immobilized by IVCT, and every component in the cells and tissues was maintained in situ at the time of freezing. Thus, the ischaemic or anoxic effects on them could be minimized by IVCT. Our specially designed cryoknife with liquid cryogen has solved the morphological and immunohistochemical problems which are inevitable with the conventional preparation methods at a light or electron microscopic level. The IVCT will be extremely useful for arresting transient physiological processes and for maintaining any intracellular components in situ, such as rapidly changing signal molecules, membrane channels and receptors.

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