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Articles by Y. J Lin
Total Records ( 2 ) for Y. J Lin
  H. S Liu , P. Y Hsu , M. D Lai , H. Y Chang , C. L Ho , H. L Cheng , H. T Chen , Y. J Lin , T. J Wu , T. S Tzai and N. H. Chow

Homodimerization of RON (MST1R), a receptor tyrosine kinase, usually occurs in cells stimulated by a ligand and leads to the downstream activation of signaling pathways. Here we report that bladder cancer cells, in response to physiological stress, use an alternative mechanism for signaling activation. Time-course studies indicated that RON migrated directly from the membrane to the nucleus of bladder cancer cells in response to serum starvation. Biochemical and genetic studies implied that this nuclear internalization was complexed with epidermal growth factor receptor (EGFR) and required the docking of importins. In vivo analysis confirmed that nuclear RON was present in 38.4% (28/73) of primary bladder tumors. Chromatin immunoprecipitation (ChIP) on microarray analysis further revealed that this internalized complex bound to at least 134 target genes known to participate in three stress-responsive networks: p53, stress-activated protein kinase/c-jun N-terminal kinase and phosphatidylinositol 3-kinase/Akt. These findings suggest that RON, in a complex with EGFR, acts as a transcriptional regulator in response to acute disturbances (e.g. serum starvation) imposed on cancer cells. In an attempt to re-establish homeostasis, these cells bypass regular mechanisms required by ligand stimulation and trigger the RON-directed transcriptional response, which confers a survival advantage.

  Y. J Lin , C. T Tai , T Kao , S. L Chang , L. W Lo , T. C Tuan , A. R Udyavar , W Wongcharoen , Y. F Hu , H. W Tso , W. C Tsai , C. J Chang , K. C Ueng , S Higa and S. A. Chen

Background— There is a paucity of data regarding the mechanism of maintaining atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF. The aim of this study was to examine the impact of circumferential PVI on the left atrial (LA) substrate characteristics.

Methods and Results— Seventy-two AF patients (age, 53±11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18±18% and 12±17% of the LA sites, before and after PVI, respectively, P=0.02), degree of LA fractionation (mean fractionated interval: 75.6±14.3 msec versus 87.3±16.7 msec, P=0.001), and mean LA dominant frequencies (6.92±0.88 Hz versus 6.58±0.91 Hz, P=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%, P<0.05).

Conclusions— Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.

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