Tainan, Taiwan
Tainan, Taiwan

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Yeh B.-W.,National Cheng Kung University | Wu W.-J.,Kaohsiung Medical University | Li W.-M.,Kaohsiung Medical University | Li C.-C.,Kaohsiung Medical University | And 5 more authors.
American Journal of Pathology | Year: 2012

Prognostic outcome prediction would be useful for the treatment of patients with upper urinary tract urothelial carcinoma (UC). However, its prognostic biomarkers are not well established so far. According to the results of analysis of 168 human upper urinary tract UC specimens, overexpressed TG-interacting factor (TGIF) in nuclei of tumor tissues is significantly correlated with poor progression-free survival and higher cancer-related death. When both TGIF and p21 expression are altered, these patients had an even worse prognosis than those with one or no marker altered. Furthermore, to elucidate the role of TGIF in the progression of UC, overexpression of TGIF in RT4 or TSGH8301 cells was performed, and the results revealed that TGIF can significantly increase migration/invasion ability, matrix metalloproteinase expression, and invadopodia formation via the phosphatidylinositol 3-kinaseAKT pathway. In contrast, knockdown of TGIF with its specific short hairpin RNA inhibited the invasion ability of T24 cells. Besides, TGIF could inhibit p21 WAF/CIP1 expression, up-regulate cyclin D1 expression, and phosphorylate retinoblastoma to promote G1-S transition and cellular proliferation. In conclusion, we demonstrated that TGIF contributes to the progression of urothelial carcinoma via the phosphatidylinositol 3-kinaseAKT pathway. It may serve as an attractive therapeutic or prognostic target for selected patients with upper urinary tract UC. © 2012 American Society for Investigative Pathology.


Kuo Y.-C.,National Cheng Kung University | Lin Y.-H.,Fu Jen Catholic University | Chen H.-I.,National Cheng Kung University | Wang Y.-Y.,National Cheng Kung University | And 7 more authors.
Human Mutation | Year: 2012

Septins are members of the GTPase superfamily, which has been implicated in diverse cellular functions including cytokinesis and morphogenesis. Septin 12 (SEPT12) is a testis-specific gene critical for the terminal differentiation of male germ cells. We report the identification of two missense SEPT12 mutations, c.266C>T/p.Thr89Met and c.589G>A/p.Asp197Asn, in infertile men. Both mutations are located inside the GTPase domain and may alter the protein structure as suggested by in silico modeling. The p.Thr89Met mutation significantly reduced guanosine-5′-triphosphate (GTP) hydrolytic activity, and the p.Asp197Asn mutation (SEPT12 D197N) interfered with GTP binding. Both mutant SEPT12 proteins restricted the filament formation of the wild-type SEPT12 in a dose-dependent manner. The patient carrying SEPT12 D197N presented with oligoasthenozoospermia, whereas the SEPT12 T89M patient had asthenoteratozoospermia. The characteristic sperm pathology of the SEPT12 D197N patient included defective annulus with bent tail and loss of SEPT12 from the annulus of abnormal sperm. Our finding suggests loss-of-function mutations in SEPT12 disrupted sperm structural integrity by perturbing septin filament formation. © 2012 Wiley Periodicals, Inc.


Wang K.-H.,Kuo General Hospital | Kao A.-P.,Taipei Medical University Hospital | Chang C.-C.,Michigan State University | Lin T.-C.,Kuo General Hospital | Kuo T.-C.,Kuo General Hospital
Taiwanese Journal of Obstetrics and Gynecology | Year: 2013

Objective: Uterine myoma is the most common benign reproductive tract tumor in women. Despite its high prevalence, the exact pathogenesis of these benign tumors remains unknown. Toward understanding the pathogenic mechanism of these tumors, we attempted to isolate human uterine myoma mesenchymal stem cells (hUM-MSCs), which may be the target cells for tumorigenesis. Furthermore, we tested the response of these hUM-MSCs to the environmental endocrine disruptor, bisphenol A (BPA), which may mimic the action of estrogen in hormone-sensitive organs such as the uterus. Materials and Methods: The hUM-MSC lines were clonally derived from uterine myoma tissue using the MSU-1 medium supplemented with N-acetyl- l-cysteine and l-ascorbic acid-2-phosphate. These hUM-MSCs were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis for the expression of mesenchymal stem cell (MSC) surface markers (e.g., CD90 and CD105) and the transcription factor Oct-4. The proliferation potential was measured by the cumulative population doubling level and the colony-forming efficiency. Results: Putative hUM-MSC lines expressed CD90, CD105, and the stem cell marker gene, Oct-4. The cells were capable of differentiating into adipocytes, osteoblasts, and chondrocytes. Bisphenol A treatment of these hUM-MSCs enhanced cell proliferation and colony-forming efficiency in a dose-responsive manner. At an environmentally relevant concentration (10-8M), BPA moreover induced cyclooxygenase-2 (COX-2) gene expression and promoted cell migration and invasiveness. Conclusion: The hUM-MSC cell lines can be isolated from uterine myoma tissues. Bisphenol A could enhance cell proliferation and colony-forming efficiency, induce COX-2 gene expression, and promote migration and invasion of hUM-MSCs. The results imply that BPA has a detrimental effect on female health by promoting uterine tumorigenesis. © 2013, Taiwan Association of Obstetrics & Gynecology.


Lee W.-T.,Kuo General Hospital | Lee W.-T.,National Chung Hsing University | Lai M.-C.,National Chung Hsing University
Journal of Microbiology, Immunology and Infection | Year: 2015

Background/Purpose: Streptococcus agalactiae (GBS), is the most common pathogen causing infections among perinatal women and neonatal babies. Nonetheless, there are few studies on the occurrence of GBS among the pregnant women and the mechanisms of GBS resistance to quinolones and macrolides in Taiwan. Methods: GBS were isolated from vaginas of the pregnant and non-pregnant symptomatic women in Taiwan. The prevalence, antimicrobial susceptibility, and mechanisms of resistance against erythromycin and quinolone of total 188 isolates were studied. Results: The isolation rate of GBS from pregnant women was significantly higher at 21.8% compare with the non-pregnant women of 13.2%. Antibiotic susceptibility test of the 188 GBS isolates revealed a high non-susceptible rate for erythromycin (50.0%) while the rate for levofloxacin was only 4.8%. Among 94 erythromycin non-susceptible GBS isolates, ermB gene was detected 83.1% (59/71) for those GBS that were non-susceptible to both clindamycin and tetracycline, which was significantly higher than GBS that are susceptible to clindamycin but resistant to tetracycline at 43.8% (7/16). No ermA or mef gene was detected in any isolate. Mutations were detected in the parC and gyrA genes in 14 out of 18 levofloxacin non-susceptible isolates. The predominant mutation type was the combination of Ser79Tyr in parC and Ser81Leu mutations in gyrA. Conclusion: GBS is the most common isolated pathogens in vaginal infections in Taiwan, resistance to tetracycline and erythromycin is higher than the rate observed for other regions of the world, while the resistance rate for levofloxacin was relatively lower in Taiwan. © 2014.


Lee I.-W.,National Cheng Kung University | Kuo P.-H.,National Taiwan University | Kuo P.-H.,National Cheng Kung University | Su M.-T.,National Cheng Kung University | And 3 more authors.
Human Reproduction | Year: 2011

BACKGROUND: Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters. Methods We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n = 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-β), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes. Results Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-β gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-β gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect. CONCLUSIONS Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Kuan L.-C.,Kuo General Hospital | Su M.-T.,National Cheng Kung University | Kuo P.-L.,National Cheng Kung University | Kuo T.-C.,Kuo General Hospital
Andrologia | Year: 2013

Structural rearrangement in the Y chromosome is closely involved in spermatogenesis. However, several Y chromosome variants may have no deleterious effects on male reproduction. Here, we report two cases of Y chromosomal duplication from incidental findings. Their FISH analysis revealed direct duplication of large segments of short and long arms of the Y chromosome. Nearly two intact Y chromosomes were carried in these two cases with normal phenotype. © 2012 Blackwell Verlag GmbH.


Chang Y.-L.,Kuo General Hospital
Journal of Internal Medicine of Taiwan | Year: 2012

The incidence of hepatocellular carcinoma and relative death is still high in Taiwan. Surgery and local ablation therapy have good effect for treatment of early small tumors. For big tumors or tumors involving major vessels, traditional treatments such as trans-arterial embolization, chemotherapy and radiotherapy has limitation owing to these patients usually have poor performance status at the time. Besides, adverse effects of these treatments induce poor life quality. Target therapy such as Sorafenib has less adverse effect than systemic chemotherapy but its effect for treating hepatocellular carcinoma is not well for many patients. New technique, trans-arterial yttrium-90 (Y90) radioembolization, are gaining acceptance as a potential therapy for hepatocellular carcinoma and liver metastases. Via catheter-based liver-directed therapy, doctor injects micron-sized embolic particles loaded with a radioisotope into specific artery supplies tumor. Local lethal radiation kills tumors without much insult to healthy hepatocytes. With meticulous pretreatment assessment, adverse effect of this treatment is light. Trans-arterial Y90 radioembolization has been adapted in America and many countries for several years, many studies show good effect for controlling hepatocellular carcinoma and liver metastases. Several hospitals in Taiwan apply this new technique to treat proper patients. It may become a common well-tolerable treatment for hepatic tumors in future.


Chang Y.-L.,Kuo General Hospital
Journal of Internal Medicine of Taiwan | Year: 2012

Patients with chronic hepatitis C may have extrahepatic manifestations. As medicine science improves and medical service is more available, more diseases are found having relationship to hepatitis C. I reviewed journals and discussed the relationship and possible mechanisms between hepatitis C and hepatic steatosis, insulin resistance and type 2 diabetes mellitus. Hepatitis C core protein influences lipid metabolism in liver cell, so lipid accumulates in liver cell, then causes hepatic steatosis. Treating hepatitis C makes hepatic steatosis recovery. Patients with chronic hepatitis C often have insulin intolerance and often develop type 2 diabetes mellitus. Chronic hepatitis C combines with insulin resistance make hepatic cirrhosis worse. Insulin resistance impairs response of interferon treatment for hepatitis C. To control insulin resistance before or during treatment for hepatitis C with life modification or using some medicines enhance sustained virological response. Beware the relate diseases when we care patients with chronic hepatitis C, control them if they develop.


Huang S.-C.,Kuo General Hospital | Yang Y.-J.,National Cheng Kung University | Lee C.-T.,National Cheng Kung University
Pediatrics and Neonatology | Year: 2011

Pseudomembranous colitis after short-course antibiotics is rare in children. We report a 14-month-old girl who presented with rectal prolapse complicated with Clostridium difficile-associated pseudomembranous colitis after a 4-day course of oral cefuroxime for treatment of acute otitis media. Abdominal sonogram showed a pelvic mass, and computed tomography revealed thickened wall of the rectum. Sigmoidoscopy demonstrated discrete yellowish plaques adherent to an edematous mucosa. Stool cultures for C difficile were positive and C difficile toxins A and B were detected in her stool. Histological examination of colonic biopsy showed superficial erosion of the mucosa and the adherent pseudomembranes. She achieved a full recovery after discontinuing cefuroxime. Our case implied that C difficile infection should be considered in children presenting with rectal prolapse, especially when they are taking or have recently received antibiotic therapy. Supportive therapy and discontinuation of antibiotics are generally sufficient for patients with C difficile-associated pseudomembranous colitis who present with mild diarrheal illness. © 2011, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.


Huang S.-C.,Kuo General Hospital | Yang Y.-J.,National Cheng Kung University
Journal of Pediatric Gastroenterology and Nutrition | Year: 2013

OBJECTIVES:: Nonalcoholic fatty liver disease (NAFLD) is identified as a major liver disease in children. The present study aimed to identify the prevalence and predictors of pediatric NAFLD and the correlation between serum retinol-binding protein 4 (RBP4) levels and metabolic characteristics in children. METHODS:: A total of 748 schoolchildren, ages 6 to 12 years, were enrolled in 2009. The body weight and height were measured in the morning before intake. Laboratory tests included overnight fasting serum lipids, insulin, liver enzymes, and RBP4 levels. Hepatic steatosis was determined by ultrasound in 219 volunteers. RESULTS:: The rates of NAFLD were 3% in the normal-weight, 25% in the overweight, and 76% in the obese children. Twenty (22%) of obese children had abnormal alanine aminotransferase (ALT) levels. In children with NAFLD, younger age and higher body mass index (BMI), insulin/homeostasis model of assessment, and male sex rate were associated with abnormal liver function. Stepwise increments in BMI, insulin, homeostasis model of assessment, and ALT were found in children with normal livers to simple steatosis, and to steatosis with abnormal ALT. Multiple logistic regression analysis confirmed that serum RBP4 levels (P = 0.048), ALT (P = 0.048), and BMI (P < 0.001) were independently predictors of pediatric NAFLD. Moreover, multiple linear regression analysis revealed that only serum triglycerides levels were positively related to RBP4 levels (P < 0.001). CONCLUSIONS:: Higher RBP4 and ALT levels as well as BMI are independently associated with pediatric NAFLD in Taiwan. In addition, an increment in RBP4 levels was positively correlated to hypertriglyceridemia in children. Copyright © 2013 by ESPGHAN and NASPGHAN.

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