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Articles by R Takahashi
Total Records ( 4 ) for R Takahashi
  S Koganemaru , T Mima , M. N Thabit , T Ikkaku , K Shimada , M Kanematsu , K Takahashi , G Fawi , R Takahashi , H Fukuyama and K. Domen
 

Patients with chronic stroke often show increased flexor hypertonia in their affected upper limbs. Although an intervention strategy targeting the extensors of the affected upper limb might thus be expected to have benefits for functional recovery, conventional repetitive motor training has limited clinical utility. Recent studies have shown that repetitive transcranial magnetic stimulation could induce motor recovery. The present study tested whether 5 Hz repetitive transcranial magnetic stimulation of the upper-limb area of the primary motor cortex, combined with extensor motor training, had a greater effect on motor recovery than either intervention alone in stroke hemiparesis. Nine patients with chronic subcortical stroke and nine age-matched healthy subjects completed the crossover study. In separate sessions, we examined the single intervention effect of repetitive wrist and finger extension exercises aided by neuromuscular stimulation, the single intervention effect of 5 Hz repetitive transcranial magnetic stimulation and the combined effect of the two interventions. The motor functions were evaluated behaviourally in patients (Experiment 1) and electrophysiologically in healthy subjects (Experiment 2), both before and after the intervention. In addition, we tested the long-term effect by repeating the combined interventions 12 times in patients (Experiment 3). The motor functions were measured again 2 weeks after the end of the repetitive intervention period. In Experiment 1, the combined intervention, but neither of the single interventions, resulted in an improvement of extensor movement (P < 0.0001) and grip power (P < 0.05), along with a reduction of flexor hypertonia (P < 0.01), in their paretic upper limbs. In Experiment 2, only the combined intervention resulted in selective plastic changes of cortico-spinal excitability (P < 0.01), motor threshold (P < 0.001) and silent period (P < 0.01) for the extensors. In Experiment 3, we also confirmed long-term beneficial effects of the combined intervention in patients. These findings indicate that combining motor training with repetitive transcranial magnetic stimulation can facilitate use-dependent plasticity and achieve functional recovery of motor impairments that cannot be attained by either intervention alone. This method could be a powerful rehabilitative approach for patients with hemiparetic stroke.

  X Ji , R Takahashi , Y Hiura , G Hirokawa , Y Fukushima and N. Iwai
 

Background: MicroRNAs (miRNAs) are endogenous small RNAs of 21–25 nucleotides that can pair with sites in 3' untranslated regions in mRNAs of protein-coding genes to downregulate their expression. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. We assessed the hypothesis that miRNAs may leak into the circulating blood from injured cells and thereby serve as biomarkers for identifying the injured cell type.

Methods: We used isoproterenol-induced myocardial injury in rats as a model and miRNA array analyses to identify candidate miRNAs specifically produced in the ventricles of the heart. Individual miRNA concentrations were measured by real-time reverse-transcription PCR. Plasma cardiac troponin I (cTnI) concentrations were measured with an ELISA.

Results: Array analyses revealed miR-208 to be produced exclusively in the heart, and we selected this miRNA as a possible biomarker of myocardial injury. Plasma concentrations of miR-208 increased significantly (P < 0.0001) after isoproterenol-induced myocardial injury and showed a similar time course to the concentration of cTnI, a classic biomarker of myocardial injury.

Conclusions: The plasma concentration of miR-208 may be a useful indicator of myocardial injury. Our results suggest that profiling of circulating miRNAs may help identify promising biomarkers of various pathologic conditions.

  S Yamada , H Ishii , H Takahashi , T Aoyama , Y Morita , H Kasuga , K Kimura , Y Ito , R Takahashi , T Toriyama , Y Yasuda , M Hayashi , H Kamiya , Y Yuzawa , S Maruyama , S Matsuo , T Matsubara and T. Murohara
 

Background and objectives: Cardiac failure is directly affected by left ventricular (LV) dysfunction, and particularly LV systolic dysfunction is strongly associated with survival in ESRD patients. The aim of this study was to determine the prognostic value of reduced LV ejection fraction (LVEF) measured at the time of initiation of hemodialysis (HD) in incident HD patients.

Design, setting, participants, & measurements: 1254 consecutive ESRD patients who electively started HD therapy were screened by echocardiography within 1 month after its inception. They were divided into five groups according to LVEF levels with a decrease of 0.1 each and were followed up for up to 7 years. Survival was examined with the Kaplan-Meier method and compared using the log-rank test.

Results: Among the 1254 patients, LVEF levels ≥0.6, 0.5 to 0.6, 0.4 to 0.5, 0.3 to 0.4, and <0.3 were seen in 842 (67.1%), 247 (19.7%), 107 (8.5%), 41 (3.3%), and 17 (1.4%) patients, respectively. On Kaplan-Meier analysis, 7-year event-free rates from cardiovascular death were 84.2, 83.7, 73.6, 59.4, and 30.9% in order of groups with decreasing LVEF of 0.1 each, respectively. Seven-year event-free rates from all-cause death were 69.2, 61.7, 57.1, 45.9, and 23.1% in the respective groups. Even after adjustment for other risk factors, decreasing LVEF was a strong independent predictor for cardiovascular death.

Conclusions: Reduced LVEF on starting HD therapy could stratify risk of cardiovascular and all-cause mortality in ESRD patients. Screening by echocardiography at start of HD therapy might be recommended to predict prognosis in patients with ESRD.

  R Takahashi , S Nakamura , T Nakazawa , K Minoura , T Yoshida , Y Nishi , Y Kobayashi and T. Ohkubo
 

Nicotinamide (NM) phosphoribosyltransferase (NMPRTase) catalyzes the reaction of NM and 5'-phosphoribosyl-1'-pyrophosphate (PRPP) to form NM mononucleotide (NMN) and pyrophosphate (PPi) in the pathway of NAD-biosynthesis. Monitoring the 1H and 31P NMR spectra of the reaction mixture, we found that this reaction is reversible as dictated by the equilibrium constant K = [NMN][PPi]/([NM][PRPP]) = 0.14, which agreed well with the ratio of second-order rate constants for forward and backward reactions, K = 0.16. The crystal structures of this enzyme in the free form and bound to NM and PRPP at the resolution of 2.0–2.2 Å were essentially identical to that of the complex with NMN, except for some variations that could facilitate the substitution reaction by fixing the nucleophile and the leaving group for the requisite inversion of configuration at the C1’ carbon of the ribose ring. In the active site near the C1’ atom of the bound PRPP or NMN, there was neither negatively charged group nor waterproof environment necessary to support the feasibility of a ribo-oxocarbocation intermediate inherent in the SN1 mechanism. The structures and catalytic mechanism thus revealed are also discussed in connection with the multiple biological functions of NMPRTase.

 
 
 
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