Ming Sheng General Hospital

Taoyuan, Taiwan

Ming Sheng General Hospital

Taoyuan, Taiwan
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Hee S.-W.,National Taiwan University | Tsai S.-H.,National Taiwan University Hospital | Chang Y.-C.,National Taiwan University Hospital | Chang Y.-C.,Academia Sinica, Taiwan | And 8 more authors.
Obesity | Year: 2012

The deadenylase nocturnin (Noc, Ccrn4l) has been recently found to regulate lipid metabolism and to control preadipocyte differentiation. Here, we showed that among the five deadenylases tested, Noc and Pan2 exhibited a biphasic expression which is out of phase to each other during adipocyte differentiation of 3T3-L1 cells. The expression levels of other deadenylases, including Parn, Ccr4, and Caf1, were relatively unchanged or reduced. The immediate early expressed Noc during 3T3-L1 adipogenesis was involved in regulating mitotic clonal expansion (MCE) and cyclin D1 expression, as demonstrated in Noc-silenced 3T3-L1 cells and Noc/primary mouse embryonic fibroblasts (MEFs). Transcriptional profiling of Noc-depleted 3T3-L1 adipocytes revealed that most of the differentially expressed genes were related to cell growth and proliferation. In human adipose tissue, NOC mRNA level negatively associated with both fasting serum insulin and homeostasis model assessment of insulin resistance, and positively associated with both adiponectin mRNA levels and circulating adiponectin levels. Taken together, these results suggest the role of Noc in the modulation of early adipogenesis as well as systemic insulin sensitivity. © 2011 The Obesity Society.

Chang Y.-C.,National Taiwan University Hospital | Chang T.-J.,National Taiwan University Hospital | Lee W.-J.,Ming Sheng General Hospital | Chuang L.-M.,National Taiwan University Hospital | Chuang L.-M.,National Taiwan University
Metabolism: Clinical and Experimental | Year: 2010

Visfatin/pre-B-cell colony-enhancing factor (PBEF)/nicotinamide phosphoribosyltransferase (Nampt) has been proposed as an insulin-mimicking adipocytokine predominantly secreted from visceral adipose tissue (VAT) and correlated with obesity. However, recent evidence challenged this proposal and instead suggested visfatin/PBEF/Nampt as a proinflammatory cytokine. The study aimed to examine whether visfatin/PBEF/Nampt was predominantly expressed in VAT and was correlated with obesity. The relationship of visfatin/PBEF/Nampt gene expression in adipose tissues with proinflammatory gene expression and metabolic phenotypes was also examined. The relative messenger RNA (mRNA) levels of visfatin/PBEF/Nampt, macrophage-specific marker CD68, and proinflammatory genes were measured in paired abdominal VAT and subcutaneous adipose tissues (SAT) and from 53 nondiabetic adults using quantitative real-time polymerase chain reaction. Fasting glucose, insulin, triglyceride, cholesterol, and uric acid levels were measured; and systemic insulin sensitivity was quantified with modified insulin suppression tests. There was no difference in visfatin/PBEF/Nampt mRNA levels between VAT and SAT, and neither was associated with measures of obesity. Visfatin/PBEF/Nampt mRNA levels were strongly correlated with proinflammatory gene expression including CD68 and tumor necrosis factor-α gene in both VAT and SAT. The VAT and SAT visfatin/PBEF/Nampt mRNA expressions were positively correlated with steady-state plasma glucose concentrations measured with modified insulin suppression tests, a direct measurement of systemic insulin resistance (r = 0.42, P = .03 and r = 0.44, P = .03, respectively). The VAT visfatin/PBEF/Nampt mRNA expression was also positively correlated with fasting triglyceride (r = 0.42, P = .002) and total cholesterol levels (r = 0.37, P = .009). Visfatin/PBEF/Nampt is not predominantly secreted from VAT and is not correlated with obesity. Our findings suggest that visfatin/PBEF/Nampt is a proinflammatory marker of adipose tissue associated with systemic insulin resistance and hyperlipidemia. © 2010 Elsevier Inc. All rights reserved.

Lin S.-C.,National Central University | Tsai W.-C.,Taipei Medical University | Wu S.-S.,Taipei Medical University | Chen P.-Q.,Ming Sheng General Hospital | Chen P.-Q.,National Taiwan University
Journal of Mechanics | Year: 2010

Spinal fixation and fusion has been adopted as a common procedure in spinal surgery. However, the degeneration as a result of parafixation may produce clinically significant problems. Previous studies have already shown increased loads, mobility, and intradiscal pressure at the parafixed segments. These may hasten the degeneration and instability of the neighboring segments. However, controversy remains regarding the correlation between surgical fixation and degeneration owing to parafixation. This study tried to elucidate their relationship by analyzing the in vivo roentgenograms of the post-fusion lumbar spine to measure the motion distribution of the fixed and adjacent unfused spinal segments. In addition, a mathematical model was developed to investigate the effects of implant fixation on the kinematics and mechanics at the parafixation segments. The current radiological studies demonstrated that spinal fixation resulted in the redistribution of intersegmental mobility. The loss of flexion mobility at the fixed segments was unequally compensated for by the increased mobility at all adjacent free segments. This mechanical model can predict the redistribution patterns of mobility and stress at the parafixation segments. This redistribution depends on the fixation levels, implant rigidity, and subject predisposition. Additionally, such compensation was more marked in the tri-segmental than in the two-segment fixation, especially among patients who underwent greater spinal load. This study concluded that the increased flexural rigidity at the fixed segment leads to the compensated kinematic and mechanical demands upon the unfixed adjacent segments. Accordingly, the cumulative effects of such increased mobility and loadings on the adjacent segments could be logically postulated to be the principal causes of accelerated degeneration of the adjacent lumbar segments, both upper and lower portions, subsequent to fusion surgery.

Chen F.-T.,Far Eastern Memorial Hospital | Chen F.-T.,National Taiwan University Hospital | Liu Y.-C.,National Taiwan University Hospital | Liu Y.-C.,Ming Sheng General Hospital | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. We evaluated the anti-inflammatory effect of bortezomib (Velcade), a proteasome inhibitor, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. METHODS. EIU was induced by footpad injection of LPS into Lewis rats. MG-132 (10 mg/kg), or high-dose (0.2 mg/kg) or low-dose (0.05 mg/kg) bortezomib was given 30 minutes before LPS injection in each treatment group. The rats were sacrificed 24 hours later to observe the inflammatory response in tissues. The expression levels of fractalkine, MCP-1, ICAM-1, and iNOS were evaluated by PCR and Western blot analysis. Immunohistochemical (IHC) studies were used to demonstrate the expression of pro-inflammatory mediators and nuclear factor-kappa B (NF-κB) p65 in the iris and ciliary body. The DNA-binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay (EMSA). An in vitro study using RAW 264.7 cells was performed to verify the results. RESULTS. Pretreatment with high-dose bortezomib significantly attenuated the inflammatory response of EIU. Reduced expression of inflammatory mediators always was observed in the high-dose bortezomib and MG-132 groups, but invariably was not noted in the low-dose bortezomib group. Decreased DNA-binding activity of NF-κB was noted in those rats pretreated with high-dose bortezomib or MG-132. In vitro study demonstrated the dose-dependent anti-inflammatory effects of bortezomib in LPS-stimulated RAW cells, consistent with the results obtained in vivo. CONCLUSIONS. Bortezomib inhibits EIU, probably by inhibiting the activation of NF-κB, which in turn, down-regulates the expression of the associated inflammatory genes. Proteasome inhibition may be a potential treatment strategy for uveitis. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Chang Y.-C.,National Taiwan University Hospital | Chang Y.-C.,Academia Sinica, Taiwan | Liu P.-H.,National Taiwan University | Tsai Y.-C.,National Taiwan University Hospital | And 16 more authors.
Journal of Molecular Medicine | Year: 2012

Prostaglandins are potent modulators of insulin sensitivity. We systemically evaluated the association of 61 tag single-nucleotide polymorphisms (SNP) in 14 genes involved in prostaglandin metabolism with type 2 diabetes. Among all genotyped SNPs, rs10483032 in the CBR3 (carbonyl reductase 3) gene, which encodes for an enzyme converting prostaglandin E2 to prostaglandin F2α, was associated with type 2 diabetes in 760 type 2 diabetic cases and 760 controls (stage-1 study) (P02.0×10 -4). The association was validated in 1,615 cases and 1,162 controls (stage-2 study) (P00.009). The A allele at rs10483032 was associated with increased risk of type 2 diabetes (odds ratio01.29; 95% confidence interval01.14-1.47; combined P<0.0001). The association was externally validated in the Finland-United States Investigation of NIDDM Genetics (FUSION) study (P03.7×10 -4). The risk A allele was associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) in 1,012 non-diabetic controls and 1,138 non-diabetic subjects from the Stanford Asia- Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. CBR3 gene expression in human abdominal adipose tissue was negatively associated with fasting insulin and HOMA-IR. CBR3 gene expression increased during differentiation of 3T3-L1 preadipocytes into adipocytes. Knockdown of CBR3 in 3T3-L1 preadipocytes enhanced adipogenesis and peroxisome proliferator-activator receptor-γ response element reporter activity. Our results indicated that genetic polymorphism in the CBR3 gene conferred risk of type 2 diabetes and insulin resistance in Chinese. The association was probably mediated through modulation of adipogenesis. © Springer-Verlag 2012.

Chang Y.-C.,National Taiwan University Hospital | Chang Y.-C.,Academia Sinica, Taiwan | Chiu Y.-F.,National Health Research Institute | Liu P.-H.,Chang Gung University | And 12 more authors.
Clinical Endocrinology | Year: 2012

Background A recent genome-wide association study for type 2 diabetes in Han Chinese identified several novel genetic variants. We investigated their associations with quantitative measures to explore the mechanism by which these variants influence glucose homoeostasis. We also examined whether these variants predict progression to diabetes in a large prospective family based Chinese cohort. Methods Five single nucleotide polymorphisms (SNPs) near the protein tyrosine phosphatase, receptor type, D (PTPRD), SRR, MAF/WWOX, and KCNQ1 genes were genotyped in 1138 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance study. Results At baseline, the risk-conferring rs7192960 C allele near the MAF/WWOX genes was associated with lower homoeostasis model assessment of β-cell (HOMA-β) (P = 0·01) and second-phase insulin response in oral glucose tolerance test (OGTT) (P = 0·04). The risk-conferring rs2237897 C alleles in the KCNQ1 gene were associated with higher fasting glucose (P = 0·009), lower HOMA-β (P = 0·03), and lower first-phase insulin response in OGTT (P = 0·03). Over an average follow-up period of 5·43 years, participants with the risk-conferring rs17584499 TT genotype in the PTPRD gene were more likely to progress from nondiabetes to diabetes than were noncarriers (hazard ratio: 8·82, P = 4 × 10 -5). The risk-conferring T allele in the PTPRD gene was associated with greater increase in homoeostasis model assessment of insulin resistance (HOMA-IR) (P = 0·04) over time. PTPRD gene expression in human adipose tissues was negatively associated with fasting insulin levels and HOMA-IR. Conclusion Genetic variants near the KCNQ1 and MAF/WWOX genes are associated with reduced insulin secretion. The PTPRD genetic variant appears to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance. © 2012 Blackwell Publishing Ltd.

Chang Y.-C.,National Taiwan University Hospital | Chang L.-Y.,Tungs Taichung MetroHarbor Hospital | Chang T.-J.,National Taiwan University Hospital | Jiang Y.-D.,National Taiwan University Hospital | And 5 more authors.
Obesity | Year: 2010

The LPIN1 gene, encoding lipin-1 protein, plays critical roles in adipocyte differentiation and lipid metabolism. This study aimed to analyze the association of LPIN1 mRNA levels in human adipose tissue with metabolic phenotypes. We also examined the association of LPIN1 genetic variation with type 2 diabetes and related metabolic phenotypes in the Chinese population. The relative LPIN1 mRNA levels were measured in abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) obtained from 102 nondiabetic Chinese females. Seven single-nucleotide polymorphisms (SNPs) spanning from the 5′-upstream region to the 3′-end of the LPIN1 gene were genotyped in 1,520 Chinese (760 type 2 diabetic cases and 760 controls). LPIN1 mRNA levels in VAT were negatively correlated with BMI (r = 0.21, P = 0.03), body fat percentage (r = 0.22, P = 0.02), plasma triglycerides levels (r = 0.21, P = 0.03), and plasma leptin levels (r = 0.63, P = 0.0002). LPIN1 mRNA levels were positively correlated with PPARG and ADIPOQ mRNA levels in both VAT and SAT. No single SNP of the LPIN1 gene was associated with type 2 diabetes in our population. One rare haplotype showed a significant association with type 2 diabetes (odds ratio (OR), 4.35; 95% confidence interval, 1.86-11.75; P = 4 × 10 4). No SNP or haplotype of the LPIN1 gene was associated with quantitative metabolic traits in the nondiabetic subjects. The results confirmed the association of LPIN1 gene expression in adipose tissue with lower adiposity and favorable metabolic profiles in the Chinese population. However, the LPIN1 gene seemed not to be a major susceptibility gene for type 2 diabetes or related metabolic phenotypes in the Chinese population.

Wu C.-K.,National Taiwan University Hospital | Wu C.-K.,National Taiwan University | Chang Y.-C.,National Taiwan University Hospital | Hua S.-C.,Chia Yi Christian Hospital | And 7 more authors.
Obesity | Year: 2010

Apolipoprotein A-V (apo A-V) exerts a potent triglyceride (TG)-lowering effect through enhanced intravascular TG-hydrolysis with increased uptake of TG-derived free fatty acids into muscle and adipose tissue. Genetic variants in the APOA5 gene were strongly associated with plasma TG concentrations. The aim of this study was to examine whether APOA5 genetic variation was associated with obesity. We genotyped the missense c.553 G>T polymorphism (p.G185C) in the APOA5 gene in 1,085 Chinese (333 obese subjects and 752 nonobese controls). We analyzed the association between the c.553G>T polymorphism and obesity and related metabolic phenotypes. The T allele at the c.553G>T polymorphism was associated with higher plasma TG concentrations. Each additional T allele was associated with an increased TG concentration of 53.5mg/dl (95% confidence interval (CI) 29.6-76.0, P < 0.0001). However, the T allele was associated lower risk of obesity (odds ratio (OR), 0.48; 95% CI 0.32-0.73, P = 0.0004). Each additional copy of the T allele was associated with a BMI decrease of 0.73kg/m2 (95% CI 0.26-1.16, P = 0.002), equivalent to 2.11kg in a person 1.7m tall. We may then conclude that the TG-raising APOA5 genetic variant was associated with a decrease in BMI and reduced risk of obesity in the Chinese population. © 2010 The Obesity Society.

Chen Y.-L.,Tri Service General Hospital | Tsai S.-H.,Tri Service General Hospital | Hsu K.-C.,Ming Sheng General Hospital | Chen C.-S.,Tri Service General Hospital | And 2 more authors.
Infection | Year: 2012

Primary sternal osteomyelitis (PSO) is a rare syndrome. In adults, it usually occurs with underlying predisposing factors, such as immunodeficiency, or intravenous (IV) drug abuse. The infecting organism in these patients is usually Staphylococcus aureus or Pseudomonas aeruginosa. Peptostreptococcus species are Gram-positive anaerobic cocci and are part of the normal flora of human mucocutaneous surfaces. Peptostreptococcus infection can occur in all body sites, including the central nervous system, head, neck, chest, abdomen, pelvis, skin, bone, joint, and soft tissue. Here, we report on a 32-year-old previously healthy Chinese man who was diagnosed with PSO and P. anaerobius was yielded in the bacterial culture. He was treated empirically with antibiotics, but these failed. After additional limited surgical intervention with debridement, the PSO was cured. ©p Springer-Verlag 2011.

Chang Y.-C.,National Taiwan University Hospital | Chang Y.-C.,Academia Sinica, Taiwan | Chang Y.-C.,National Taiwan University | Chiu Y.-F.,National Health Research Institute | And 10 more authors.
PLoS ONE | Year: 2013

Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including CLOCK, BMAL1(ARNTL), PER1, PER2, CRY1, CRY2, CSNK1E, and NOC(CCRN4L) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan. Their associations with metabolic phenotypes were analyzed. We found that genetic variation in the NOC gene, rs9684900 was associated with body mass index (BMI) (P = 0.0016, Bonferroni corrected P = 0.032). Another variant, rs135764 in the CSNK1E gene was associated with fasting glucose (P = 0.0023, Bonferroni corrected P = 0.046). These associations were consistent in both Taipei and Yunlin populations. Significant epistatic and joint effects between SNPs on BMI and related phenotypes were observed. Furthermore, NOC mRNA levels in human abdominal adipose tissue were significantly increased in obese subjects compared to non-obese controls.Conclusion:Genetic variation in the NOC gene is associated with BMI in Chinese subjects. © 2013 Chang et al.

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