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Articles by Y Takahashi
Total Records ( 5 ) for Y Takahashi
  Y Takahashi , A Takahashi , T Kuwahara , T Fujino , K Okubo , S Kusa , A Fujii , A Yagishita , S Miyazaki , T Nozato , H Hikita , K Hirao and M. Isobe

We sought to characterize patients with persistent atrial fibrillation (AF) who were successfully treated by ablation targeting the left atrium (LA).

Methods and Results—

Ninety-three patients (58±10 years, 79 male) undergoing ablation of persistent AF were studied. During the first procedure, ablation was performed in the LA and coronary sinus, consisting of pulmonary vein isolation, linear ablation, and electrogram-based ablation. During follow-up after the first procedure, 35 patients (38%) remained free from tachyarrhythmias, 27 patients (29%) had atrial tachycardia, and 31 patients (33%) had AF. Duration of persistent AF according to medical history and whether AF was terminated by ablation were associated with the outcome (P=0.005, P=0.004, respectively). In multivariate analysis, the duration of persistent AF was the only predictor of freedom from AF (sinus rhythm or atrial tachycardia) (odds ratio, 0.80 for a 1-year increase; 95% confidence interval, 0.67 to 0.95; P=0.01). Of 31 patients in whom AF recurred during follow-up, electrogram-based ablation was performed in the right atrium in 26 patients. Sixteen of those patients (62%) remained free from AF during follow-up. Overall, 82% of patients were free from any tachyarrhythmias at 2-year follow-up after a median of 2 procedures.


Patients with shorter duration of persistent AF were more likely to be free from AF by LA ablation. Right atrial ablation may provide incremental efficacy in patients who are refractory to LA ablation.

  N Ohoka , S Kato , Y Takahashi , H Hayashi and R. Sato

The nuclear receptor-type transcription factor retinoic acid receptor-related orphan receptor (ROR) is a multifunctional molecule involved in tissue development and cellular function, such as inflammation, metabolism, and differentiation; however, the role of ROR during adipocyte differentiation has not yet been fully understood. Here we show that ROR inhibits the transcriptional activity of CCAAT/enhancer-binding protein β (C/EBPβ) without affecting its expression, thereby blocking the induction of both PPAR and C/EBP, resulting in the suppression of C/EBPβ-dependent adipogenesis. ROR interacted with C/EBPβ so as to repress both the C/EBPβ-p300 association and the C/EBPβ-dependent recruitment of p300 to chromatin. In addition to the inhibitory effect on C/EBPβ function, ROR also prevents the expression of the lipid droplet coating protein gene perilipin by peroxisome proliferators-activated receptor (PPAR), acting through the specific mechanism of its promoter. We identified a suppressive ROR-responsive element overlapping the PPAR-responsive element in the perilipin promoter and verified that ROR competitively antagonizes the binding of PPAR. ROR inhibits PPAR-dependent adipogenesis along with the repression of perilipin induction. These findings suggest that ROR is a novel negative regulator of adipocyte differentiation that acts through dual mechanisms.

  M Shiozuka , A Wagatsuma , T Kawamoto , H Sasaki , K Shimada , Y Takahashi , Y Nonomura and R. Matsuda

To induce the readthrough of premature termination codons, aminoglycoside antibiotics such as gentamicin have attracted interest as potential therapeutic agents for diseases caused by nonsense mutations. The transdermal delivery of gentamicin is considered unfeasible because of its low permeability through the dermis. However, if the skin permeability of gentamicin could be improved, it would allow topical application without the need for systemic delivery. In this report, we demonstrated that the skin permeability of gentamicin increased with the use of a thioglycolate-based depilatory agent. After transdermal administration, the readthrough activity in skeletal muscle, as determined using a lacZ/luc reporter system, was found to be equivalent to systemic administration when measured in transgenic mice. Transdermally applied gentamicin was detected by liquid chromatography-tandem mass spectrometry in the muscles and sera of mice only after depilatory agent-treatment. In addition, expansion of the intercellular gaps in the basal and prickle-cell layers was observed by electron microscopy only in the depilatory agent-treated mice. Depilatory agent-treatment may be useful for the topical delivery of readthough-inducing drugs for the rescue of nonsense mutation-mediated genetic disorders. This finding may also be applicable for the transdermal delivery of other pharmacologically active molecules.

  Y Takahashi , S Tsuji , Y Kazuki , M Noguchi , I Arifuku , Y Umebayashi , T Nakanishi , M Oshimura and K. Sato

Bioactive substances in daily food and supplements are expected to prevent various lifestyle-related diseases. Recently, many evaluation systems for bioactive substances were developed with cell lines integrated with green fluorescence protein (GFP) reporter gene. To evaluate osteogensis activity in functional food, we developed a novel cell line that reports osteocalcin gene expression using the human artificial chromosome (HAC) vector. HAC vectors are able to avoid various problems in usual plasmid vector such as difficulty in control of transgene copy number. HAC is transmitted to cells as an independent chromosome from host chromosomes, and expresses transgenes depending on host cell circumstances. We established Chinese hamster ovary cell lines that carried GFP gene regulated by osteocalcin gene promoter on the HAC. Expression of GFP was responded to vitamin D3 [1,25(OH)2D3]. Furthermore, we constructed HAC vector bearing tandem repeats of reporter gene unit, to enhance intensity of gene expression. GFP expression in these reporter cells is related to the copy number of reporter gene units. Using the evaluation system for bioactive substances, we could show osteogenic activity in some fish oils.

  T Takahashi , N Inoue Kashino , S. i Ozawa , Y Takahashi , Y Kashino and K. Satoh

Photosystem II (PS II) complexes are membrane protein complexes that are composed of >20 distinct subunit proteins. Similar to many other membrane protein complexes, two PS II complexes are believed to form a homo-dimer whose molecular mass is ~650 kDa. Contrary to this well known concept, we propose that the functional form of PS II in vivo is a monomer, based on the following observations. Deprivation of lipids caused the conversion of PS II from a monomeric form to a dimeric form. Only a monomeric PS II was detected in solubilized cyanobacterial and red algal thylakoids using blue-native polyacrylamide gel electrophoresis. Furthermore, energy transfer between PS II units, which was observed in the purified dimeric PS II, was not detected in vivo. Our proposal will lead to a re-evaluation of many crystallographic models of membrane protein complexes in terms of their oligomerization status.

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