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Showing papers by "Shin-ichi Muramatsu published in 2001"


Journal ArticleDOI
TL;DR: Developed recombinant adeno-associated virus (rAAV) vectors using the enhanced PAI-1 promoter and were successful in transducing vascular endothelial cells to express the thrombomodulin transgene under the regulation of the enhancedPAI- 1 promoter in vitro.
Abstract: We were able to facilitate plasminogen activator inhibitor 1 (PAI-1) promoter activity approximately by 14-fold using an enhancer element. This enhanced PAI-1 promoter has a strong basal activity, comparable to CAG promoter activity, and has a response similar to the PAI-1 promoter with respect to TGFbeta 1 and TNFalpha stimulation. The characteristics of the enhanced PAI-1 promoter are thought to be suited to timely and tissue-specific expression of anticoagulant molecules in the vascular cells. Thus, we developed recombinant adeno-associated virus (rAAV) vectors using the enhanced PAI-1 promoter and were successful in transducing vascular endothelial cells to express the thrombomodulin transgene under the regulation of the enhanced PAI-1 promoter in vitro. Thromobomodulin transgene expression driven by the enhanced PAI-1 promoter in rAAV vector-transduced cultured endothelial cells was between 600- and 1000-fold higher than constitutive thrombomodulin gene expression in cultured human umbilical vein endothelial cells and was up-regulated by TGFbeta1 and TNFalpha stimulation which may down-regulate endogenous thrombomodulin gene expression in endothelial cells. The brain vascular endothelial cells of Mongolian gerbils could also be transduced by the same rAAV vector in vivo. Transduction of endothelial cells by rAAV vectors to express enhanced PAI-1 promoter-driven transgenes may be a useful gene therapy approach for vascular diseases.

17 citations


Journal ArticleDOI
TL;DR: If "sporadic" cases of cerebellar ataxia show such movements, the possibility of genetic origin of the ataxIA is high and a surveillance of various forms of hereditary spinocerebellarAtaxia including SCA1 is required.

17 citations


Journal ArticleDOI
TL;DR: This study suggests that SC is useful as an adjunct to dopaminergic drugs in PD, and shows a significant improvement in motor performance with respect to the motor scores of the UPDRS.
Abstract: Senkyu-chacho-san (SC), an herbal medicine, can modulate striatal dopamine levels, but its effects on Parkinsons disease (PD) are unclear. To evaluate the efficacy, tolerance, and safety of SC in PD, 22 patients with idiopathic PD (aged 49 to 82 years; 13 women, staging Hoehen and Yahr 3 or 4) were given SC, 5.0 or 7.5g three times per day, for eight weeks. Existing antiparkinsonian drug regimes were kept unchanged. Motor functions were assessed based on the Unified Parkinsons Disease Rating Scale (UPDRS) at baseline and at weeks four and eight. After four weeks of SC administration, 14 patients showed a significant improvement in motor performance with respect to the motor scores of the UPDRS (p<0.05). The improvement in motor function declined slightly in four patients after eight weeks of treatment. No patients became worse in motor functions during treatment, and no serious adverse events occurred. This study suggests that SC is useful as an adjunct to dopaminergic drugs in PD.

2 citations