The allele frequency of two single nucleotide polymorphisms in the von Hippel-Lindau (VHL) tumor suppressor gene in the Taiwanese population.

BACKGROUND: The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations. METHODS: The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I. RESULTS: Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles. CONCLUSION: We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects.

Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan.

OBJECTIVE: This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. DESIGN: Cross-sectional study. SETTING: Freely available epidemic data in Taiwan. MAIN OUTCOME MEASURE: We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. RESULTS: With our approach, we noted that keywords ('common cold'), ('fever') and ('cough') exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query ('enterovirus') exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). CONCLUSIONS: These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.

Multiple tiny ectopic sebaceous glands discovered throughout entire esophageal tract.

A 45-year-old woman complaining of abdominal fullness was referred for endoscopic examination. She was a non-smoker and non-drinker. An endoscopic examination revealed the presence of more than 100 tiny, rounded, elevated, yellowish lesions <0.5 mm in diameter scattered throughout the upper and lower esophagus. Based on the endoscopic examination results, her stomach manifested symptoms of mildly superficial gastritis. Histopathologic examination of the esophagus biopsy specimen revealed that some of the lobules of the cells displayed typical sebaceous differentiation covered by a squamous epithelium. No evidence of inflammatory reaction, hair follicles, or malignancy was found. The patient's blood and serum findings were unremarkable. Our final diagnosis was multiple tiny ectopic sebaceous glands in the esophagus. This is an interesting and rare case of esophageal sebaceous glands distributed throughout the entire esophagus. Because there were no esophageal symptoms or/and eating problems, the patient did not require endoscopic surgery or other treatment. Follow-up examinations were recommended at intervals between 6 months and 1 year. At the 2-year follow-up, an endoscopic examination revealed no change in the size or the number of the tiny ectopic esophageal sebaceous glands.

Secondhand smoke induces hepatic apoptosis and fibrosis in hamster fetus.

Secondhand smoke (SHS) is an important health issue worldwide. Inhaling SHS during pregnancy could cause abnormalities in the internal tissues of newborns, which may then impair fetal development and even cause severe intrauterine damage and perinatal death. However, the understanding of cytopathic mechanisms of SHS by maternal passive smoking on fetus liver during pregnancy is still limited. This study analyzed the effects of high-dose SHS (SHSH) on fetus liver using a maternal passive smoking animal model. Experiments showed that hepatic matrix metalloproteinase-9 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive cells were significantly increased in livers from fetuses of hamsters treated with SHSH. Similarly, expressions of both extrinsic and intrinsic apoptotic molecules were significantly higher in livers from fetuses of hamsters exposed to SHSH. Additionally, significantly increased inflammatory proteins, including transforming growth factor ß, inducible nitric oxide synthase, and interleukin 1ß, and fibrotic signaling molecules, including phosphorylated Smad2/3, SP1, and α-smooth muscle actin, were observed in the fetus livers from hamsters treated with SHSH. This study revealed that SHSH not only increased apoptosis through intrinsic and extrinsic pathways in the livers of fetuses from hamsters exposed to SHSH but also augmented hepatic fibrosis via Smad2/3 signaling.

Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17 cM interval.

PURPOSE: The genetic basis for gastrointestinal and ampullary carcinomas remains uncertain. This study was performed to pinpoint novel chromosomal region involved in the tumorigenesis of gastrointestinal tract. METHODS: We screened the allelic status on 16 chromosomal arms in a patient with synchronous ampullary carcinoma and gastric cancer, but who had no family history of familial cancer syndrome. The significance of the shared 14q deletion was examined on clinical cohorts of sporadic gastric (n=12) and ampullary (n=10) carcinoma, respectively. Then, high-density allelotype mapping was performed on 14q32 by using 23 microsatellite markers for the synchronous tumors. RESULTS: The synchronous gastric and ampullary carcinomas had no frameshift mutations in the APC, MSH2, MSH3, and MSH6 genes. Among the microsatellite markers screened, only D14S267 showed identical loss in the synchronous tumors. The same allelic loss was also detected in one of ampullary carcinomas (10%) and two of gastric cancers (16.7%). Fine mapping of 14q determined a minimally deleted region between D14S65 and D14S1010 (17 centiMorgans) for the synchronous tumors. CONCLUSIONS: This study illustrates a paradigm using molecular genetic approach in identifying chromosome 14q32 that may harbor a tumor suppressor gene involved in the pathogenesis of a subset of gastrointestinal and ampullary malignancies.

Merkel cell carcinoma in patients with long-term ingestion of arsenic.

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, mostly occurring late in life on sun-exposed body parts. Little is known about the specific etiological factors in the pathogenesis of MCC. A previous report indicated that arsenic exposure might cause MCC, which might be another specific type of skin cancer associated with arsenic exposure. On the southwest coast of Taiwan, high arsenic levels in artesian well water have been documented, and various diseases associated with arsenic exposure have been found to be prevalent in this area. We report two pathologically confirmed cases of MCC in patients who had histories of long-term ingestion of arsenic from drinking water. The tumors were on the anterior chest wall, an area less exposed to the sun, in both cases. The literature on the dose-response relationship between arsenic exposure and MCC is limited. We estimated that the total arsenic ingested by these two cases was around 14.7 and 2.6 gm, respectively. We also tried to assess the cancer risk on the basis of the estimated doses of arsenic exposure and the cancer risk model developed by the U.S. Environmental Protection Agency (EPA). The estimated lifetime target cancer risk was 1.3 x 10(-2) in Case 1 and 2.3 x 10(-3) in Case 2. Both are much higher than the 10(-6) upper limit on lifetime cancer risk put forth by the U.S. EPA health protection standard. We believe that arsenic intoxication played an important role in the carcinogenic process of MCC in our cases.

Detecting clonal rearrangement in non-Hodgkin's lymphomas in Taiwan by polymerase chain reaction.

The detection of monoclonal expansions of the immunoglobulin heavy chain (IgH) or the T-cell receptor-gamma (TCRgamma) chain genes is an important supplement for the diagnosis of the non-Hodgkin's lymphomas (NHLs). Detection of monoclonality by polymerase chain reaction (PCR) method has offered an efficient approach for rapid diagnosis and monitoring of the therapeutic effects. Here we conducted a retrospective PCR clonality study on 49 cases of NHLs including 23 B-cell lymphomas (BCLs), 20 peripheral T-cell lymphomas (PTCLs), 6 natural killer (NK)/T-cell lymphomas and 3 reactive lymphoid tissues from southern Taiwan. Genomic DNAs from paraffin sections were extracted and analyzed by the IgH- and TCR-specific PCR reactions. The results showed that 20 of 23 (87.5%) BCLs exhibited IgH gene rearrangements and were all germline for TCRgamma. 15 of 20 (75.0%) PTCLs exhibited TCRgamma gene rearrangements while 1 case (5%) was positive for IgH gene rearrangement. The 6 NK/T-cell lymphomas and 3 reactive lymphoid tissues were all germline for either IgH or TCRgamma genes. Our results were similar to other Western reports in terms of sensitivity and cell-lineage specificity. This is the first large series of PCR clonality study of IgH and TCRgamma gene rearrangements on NHLs from Taiwan. We have confirmed that this rapid method is a sensitive diagnostic tool for NHLs.

Hepatic angiosarcoma presenting as hepatic rupture in a patient with long-term ingestion of arsenic.

Hepatic angiosarcoma (HAS) is a rare primary mesenchymal malignancy of liver with close association to arsenic intoxication. Although the southwest coastal area of Taiwan is well known for its prevalence of arsenic intoxication from drinking well water, few cases of HAS associated with arsenic ingestion have been reported. We report a case of HAS complicated by spontaneous hepatic rupture in a 68-year-old female farmer who presented with acute onset of abdominal pain and shock. The arsenic level in her drinking water had been found to be 0.12 ppm at her childhood home and 0.005 ppm at her residence from age 21 to 68 years. The total ingested arsenic was estimated to be 1.9 g, and the latent period was about 25 years with a weighted mean exposure of 0.12 mg/day. We also reviewed data collected by the National Cancer Registry Program from 1981 to 1999 and identified 25 additional reported cases. The median age of these patients was 55 years, and the male-to-female ratio was 1.9 (17:9). Whereas no case was found during this period in the blackfoot disease (BFD) endemic area, a hyperendemic area of arsenic intoxication in Taiwan, this case demonstrates the existence of cases of HAS associated with exposure to high levels of arsenic near the BFD area in Taiwan.

Skin tumor-promoting potential and systemic effects of pentachlorophenol and its major metabolite tetrachlorohydroquinone in CD-1 Mice.

The mouse skin carcinogenesis model provides a conceptual framework to study the carcinogenesis process. It has been used extensively to assess whether a chemical or physical agent carries a carcinogenic hazard to humans and to define the mechanism involved with the carcinogenic effects. We conducted a study to evaluate whether the tumor-promoting activity of pentachlorophenol (PCP) is mainly from its major metabolite tetrachlorohydroquinone (TCHQ). We applied the mouse skin model to CD-1 mice and the results showed that PCP and TCHQ are much weaker promoters than 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin during a 25-wk experiment. Both PCP and TCHQ could induce mice skin epidermal hyperplasia and proliferating cell nuclear antigen (PCNA) labeling index in the epidermis. However, TCHQ caused a more significant induction of epidermal hyperplasia and PCNA positive cells than PCP. Topical application of PCP, but not TCHQ, induced significant organ enlargement and lymphoma in mice, whereas short-term treatment of TCHQ increased tumor necrosis factor-alpha (TNF-alpha) gene expression in mouse skin. We did not observe a significant association between the carcinogenic process and serum TNF-alpha or interleukin-1 beta (IL-1 beta) levels in mice.