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Articles by H. C Lee
Total Records ( 5 ) for H. C Lee
  D. m Zhang , T He , Z. S Katusic , H. C Lee and T. Lu
  Rationale:

Activity of the large conductance Ca2+-activated K+ (BK) channels is profoundly modulated by its β1 subunit (BK-β1). However, BK-β1 expression is downregulated in diabetic vessels. The ubiquitin–proteasome system (UPS) is a major mechanism of intracellular protein degradation. Whether UPS participates in BK-β1 downregulation in diabetic vessels is unknown.

Objective:

We hypothesize that UPS facilitates vascular BK-β1 degradation in diabetes.

Methods and Results:

Using patch clamp and molecular biological approaches, we found that BK-β1–mediated channel activation and BK-β1 protein expression were reduced in aortas of streptozotocin-induced diabetic rats and in human coronary arterial smooth muscle cells (CASMCs) cultured in high glucose. This was accompanied by upregulation of F-box only protein (FBXO)-9 and FBXO-32 (atrogin-1), the key components of the Skp1-Cullin-F-box (SCF) type ubiquitin ligase complex. BK-β1 expression was suppressed by the FBXO activator doxorubicin but enhanced by FBXO-9 small interfering RNA or by the proteasome inhibitor MG-132. Cotransfection of atrogin-1 in HEK293 cells significantly reduced Flag-hSlo-β1 expression by 2.16-fold, compared with expression of Flag-hSlo-β1V146A (a mutant without the PDZ-binding motif). After cotransfection with atrogin-1, the ubiquitination of Flag-hSlo-β1 was increased by 1.91-fold, compared with that of hSlo-β1V146A, whereas cotransfection with atrogin-1F (a nonfunctional mutant without the F-box motif) had no effect. Moreover, inhibition of Akt signaling attenuated the phosphorylation of forkhead box O transcription factor (FOXO)-3a and enhanced atrogin-1 expression, which in turn suppressed BK-β1 protein levels in human CASMCs.

Conclusions:

Downregulation of vascular BK-β1 expression in diabetes and in high-glucose culture conditions was associated with FOXO-3a/FBXO-dependent increase in BK-β1 degradation.

  S Tani ichi , H. C Lee , S. K Ye and K. Ikuta
 

The signal of the IL-7R and signal transducers and activators of transcription (STAT) 5 plays an essential role in T-cell development by inducing V–J recombination in the TCR locus. Previously, we have shown that STAT5 binds to the J promoters and controls chromatin accessibility by histone acetylation. However, little is known on control mechanism of V region by the IL-7R. To elucidate the regulation by STAT5, we first analyzed the chromatin status of V region in primary thymocytes. The levels of histone H3 acetylation are high at V5, HsA element and V2 in Rag2–/– thymocytes but low in IL-7R -chain (IL-7R)-deficient early thymocytes, suggesting that IL-7R signaling controls the accessibility of the V region. In addition, high levels of histone H3 acetylation and germ line transcription were induced at V5 and HsA by cytokine and STAT5 in cytokine-dependent Ba/F3 and other hematopoietic cell lines. Importantly, the chromatin accessibility of V5 gene is increased by cytokine signal. Furthermore, STAT5 was not recruited to a non-canonical STAT-binding motif in the endogenous chromatin of the V5 promoter by cytokine stimulation, while STAT5 binds to a consensus motif in the HsA element. In accordance with this result, STAT5 does not directly activate the V5 promoter by reporter assay. These results suggested that while STAT5 directly binds to HsA element and induces its histone acetylation, STAT5 indirectly activates the V5 promoter. Thus, this study implies a potential role of STAT5 in accessibility control of V region, especially at V5 and HsA.

  D. H Yoon , B. Y Ryoo , M. H Ryu , S. G Lee , S Hwang , D. J Suh , H. C Lee , T. W Kim , C. S Ahn , K. H Kim , D. B Moon and Y. K. Kang
  Objective

Sorafenib is the only drug that has shown a survival benefit in patients with hepatocellular carcinoma in randomized Phase 3 trials. The efficacy and safety of sorafenib in the treatment of recurrent hepatocellular carcinoma after liver transplantation, however, has not been determined.

Methods

We retrospectively analyzed 13 patients who were treated with sorafenib for recurrent hepatocellular carcinoma after liver transplantation.

Results

The median time to recurrence from liver transplantation was 12.3 months (95% confidence interval: 8.5–16.1 months). Six of 10 evaluable patients showed stable disease, which was the best response and the median duration of stabilization was 3.9 months (95% confidence interval: 1.6–6.2 months). At a median follow-up duration of 3.7 months (range: 0.3–10.9 months) in surviving patients, the median time to progression and the median overall survival from commencement of sorafenib were 2.9 months (95% confidence interval: 0.0–6.8 months) and 5.4 months (95% confidence interval: 3.7–7.0 months), respectively. Grade 3 neutropenia was observed in one patient, which was the only high-grade hematologic toxicity observed. Grade 3 hand-foot skin reactions were observed in three patients. Adverse events could be managed with dose adjustment.

Conclusions

These findings suggest that sorafenib may be a feasible treatment option regarding its efficacy and safety for recurrent hepatocellular carcinoma after liver transplantation.

  S. B Fang , H. C Lee , J. J Hu , S. Y Hou , H. L Liu and H. W. Fang
 

Beneficial effects of probiotics in acute infectious diarrhoea in children are mainly seen in watery diarrhoea and viral gastroenteritis. Lactobacillus rhamnosus, one the most extensively studied probiotic strains, is effective in shortening courses of acute diarrhoea in children. However, the dose-dependent effect of Lactobacillus upon quantification of faecal rotavirus shedding in humans remains little known. Thus, an open-label randomized trial in 23 children with acute rotaviral gastroenteritis was undertaken by randomly allocating patients to receive one of the three regimens for 3 days: daily Lactobacillus rhamnosus 35 (Lcr35) with 0 CFU/day to six patients in the control group, 2 x 108 CFU/day to nine patients in the low-dose group, and 6 x 108 CFU/day to eight patients in the high-dose group. Faecal samples were collected before and after the 3-day regimen for measurements of rotavirus concentrations by ELISA. There was no statistically significant change in faecal rotavirus concentrations in either the control group (119.2 x 105 particles/ml vs. 23.7 x 105 particles/ml, p = 0.075) or the low-dose group (36.1 x 105 particles/ml vs. 73.5 x 105 particles/ml, p = 0.859). However, the high-dose group had a significant reduction of faecal rotavirus concentration (64.2 x 105 particles/ml vs. 9.0 x 105 particles/ml, p = 0.012). Without any exception, the faecal rotavirus concentrations of all eight patients in the high-dose Lcr35 group declined by 86% after 3 days when compared with those before Lcr35 administration. In conclusion, this is the first report to provide quantitative evidence of the dose-dependent effect of Lactobacillus rhamnosus, a minimal effective dose of 6 x 108 CFU for 3 days, upon the faecal rotavirus shedding in paediatric patients.

  H. C Lee and H. C. Lin
 

Information on the relationship between characteristics of mental healthcare providers, including hospitals and psychiatrists, and postdischarge suicide is scanty. This study aims to identify the risk factors for suicide among schizophrenia patients in the 3-month postdischarge period. The study cohort comprised all patients with a principal diagnosis of schizophrenia discharged from psychiatric inpatient care from 2002 to 2004 who committed suicide within 90 days of discharge. The control cohort consisted of all surviving schizophrenia patients discharged from psychiatric inpatient care in the same period and were matched to cases for age, gender, and date of discharge. There were 87 and 348 cases in the study and control cohorts, respectively. For suicide cases, death most frequently occurred on the first day after leaving the hospital (16.1%). The adjusted hazard ratios for committing suicide during the 90-day postdischarge period were 2.639 times greater for patients without previous psychiatric admission than for those hospitalized more than 3 times in the year preceding the index hospitalization. The adjusted suicide hazard for schizophrenia patients treated by male psychiatrists was significantly higher than for patients treated by female psychiatrists, by a multiple of 5.117 (P = .032). The adjusted suicide hazard among patients treated by psychiatrists over age 44 years was 2.378 times (P = .043) that for patients treated by psychiatrists aged younger than 35 years. Risk factors related to psychiatric hospitalization, including number of psychiatric admissions in the previous year and length of stay, together with gender and age of the psychiatrist providing inpatient care, are identified.

 
 
 
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