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Biomedical subjects

C J Chen

Publications and source records attributed to C J Chen.

At least 91 records · Page 5Linked to original sources

Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan.

Previous studies of nasopharyngeal carcinoma (NPC) have found elevated risks with higher consumption of salted fish and preserved foods, particularly during childhood. These foods can contain high levels of nitrosamines; however, most studies have not estimated exposure to nitrosamines directly. We conducted a case-control study in Taiwan to evaluate dietary intakes and NPC risk. A total of 375 cases (99% response rate) and 327 controls (88% response rate) were interviewed about their diet as an adult and at age 10 using a food-frequency questionnaire. We interviewed mothers of participants about their child's diet at age 10, age 3 and during weaning and the mother's diet while she was breast-feeding. Mothers of 96 cases and 120 controls were interviewed. Nitrosamine and nitrite levels were assigned to 66 foods based on published values. Intake of nitrosamines and nitrite as an adult was not associated with risk of NPC. High intakes of nitrosamines and nitrite during childhood and weaning were associated with increased risks of NPC for foods other than soy products. Adjusted odds ratios for the highest quartile were 2.2 [95% confidence interval (CI) 0.8-5.6] for age 10, 2.6 (95% CI 1.0-7.0) for age 3 and 3.9 (95% CI 1.4-10.4) for weaning diet. Intakes of nitrite and nitrosamines from soybean products during childhood and weaning were inversely associated with risk. Soybeans contain known inhibitors of nitrosation, and thus may explain the inverse association we observed. Our results suggest that nitrosamine and nitrite intake during childhood may play a role in the development of NPC.

Adult↗

Changes in portal venous hemodynamics in patients with severe acute hepatitis over one year.

PURPOSE: A wide range of portal vein blood flow velocity (PVV) values can be found in acute hepatitis. We studied course and medical significance of PVV changes in patients with severe acute hepatitis over a 1-year period. METHODS: Portal venous hemodynamics were studied by Doppler sonography in 90 patients at study enrollment and 3, 6, and 12 months following an episode of severe acute hepatitis. RESULTS: Forty-one survivors who had a maximum PVV at enrollment greater than or equal to the value measured at the third month were classified as the "declining PVV" group. Thirty-six survivors who had a maximum PVV at enrollment less than the value measured at the third month were classified as the "rising PVV" group. Thirteen patients died of acute hepatic failure and were classified as the fatality group. The fatality group had significantly lower maximum PVV, worse liver biochemical test results, and a higher prevalence of ascites at enrollment. In contrast, the declining PVV group showed significantly better liver biochemical test results and a lower prevalence of ascites. There was no significant difference in portal vein blood flow between the rising and declining PVV groups since portal vein diameter increased while PVV decreased. CONCLUSIONS: An initially decreased PVV can be found in some patients with severe acute hepatitis and is inversely correlated with the severity of liver damage.

Acute Disease↗

Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: a microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity.

BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been documented in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromosome 11 loci in breast cancer is a frequent event. The purpose of the present study is to examine the incidence of microsatellite alterations in in situ and invasive human breast carcinoma and to clarify their significance in regulating the dynamics of cancer progression. METHODS: Four highly polymorphic (CA)n repeat microsatellites were used to determine microsatellite alterations in ten ductal carcinoma in situ (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of p53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI, immunohistochemistry staining was applied. RESULTS: MSI were detected in 20% (2/10) of DCIS and in 47.4% (9/19) of IDC. The frequency of MSI in IDC was significantly higher than that in DCIS (P < 0.001). Also, the MSI seemed to correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not histological grade or age. In addition, we found that 27% of the tumors showed LOH at 11q23.3-24 region between loci D11S934 and D11S912. Seven of nine MSI cases demonstrated low or no expression of p53. However, there was significantly reduced expression of PR, but not ER in MSI cases. CONCLUSIONS: Our results suggest that breast cancer acquires the RER phenotype (replication-error phenotype) in the relatively late stages, and that the RER phenotype is associated with aggressiveness of IDC (infiltrative duct carcinoma). The result also implicated that mismatch repair failure can alter the expression of PR but not ER and p53.

Adult↗

CD34, CD117, and actin expression in phyllodes tumor of the breast.

BACKGROUND: This study investigated the immunophenotypic patterns of CD34, CD117 (a product of the c-kit proto-oncogene), and actin (HHF35) in benign and malignant phyllodes tumors (PTs). We correlated the expression of CD34, CD117, and actin with histopathological grade. MATERIALS AND RESULTS: We analyzed 19 cases (7 benign and 12 malignant cases) of PTs using immunohistochemical analysis. Six of 7 benign PT stromal lesions stained positively for CD34, while only 3 of 12 cases of malignant PT were focally CD34 positive (P = 0.0106). Only 1 of the 7 benign PTs stromal lesions expressed CD117. Nine of the malignant PTs were composed CD117-positive fibroblasts. This result demonstrated that CD117 expression is associated with the malignant potential of PTs (P = 0. 0106). Actin (HHF-35) expression was found in 8 of 12 cases of malignant PTs (P = 0.027), but in only 1 of 7 cases of benign PTs. Actin expression was significantly (P = 0.04) correlated to frequent mitotic activity (>5 mitoses per 10 high-power fields). The immunophenotypic markers were not related to tumor size. Additionally, we sequenced part of the juxtamembrane region of the c-kit proto-oncogene and found point mutations in two malignant PTs. CONCLUSION: Our results demonstrated that expression of CD34 was associated with benign PTs, while CD117 and actin were preferentially expressed in malignant PTs. Our results implied that these immunohistological markers might be used for the histopathological grading of PTs.

Actins↗

Unilateral congenital cerebral venous dysgenesis.

I report a 30-year-old woman with congenital cerebral venous dysgenesis with absence of the internal cerebral and basal veins and most of the cortical veins. Unlike the more common bilateral picture, she had involvement only on the left side, which delayed presentation and gave relatively mild symptoms. The embryological mechanism and differential diagnosis of unilateral absence of the internal cerebral, basal and cortical veins are discussed.

Adult↗

KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms arising in the gastrointestinal tract. GISTs express the KIT receptor tyrosine kinase, and many cases have activating mutations in the KIT juxtamembrane region. We now report an analysis of KIT cDNA and genomic sequences in eight GISTs that lack juxtamembrane region mutations. Six cases contained heterozygous exon 9 mutations in which six nucleotides, encoding Ala-Tyr, were duplicated. The other two cases contained homozygous exon 13 missense mutations, resulting in substitution of Glu for Lys(642), that were associated with constitutive KIT tyrosine phosphorylation. Sequence analysis of DNAs from nonneoplastic companion tissues revealed that both the exon 9 and exon 13 mutations were somatic. These are the first descriptions, in any tumor, of mutations in KIT exons encoding the C-terminal end of the extracellular domain and the first part of the split kinase domain. These findings indicate that KIT may be activated by mutations in at least three domains-extracellular, juxtamembrane, and kinase-in GISTs.

Amino Acid Sequence↗

Epidemiology of hepatitis B virus infection in the Asia-Pacific region.

There is a wide variation of hepatitis B virus (HBV) infection in the Asia-Pacific region. The prevalence of chronic HBV infection is lowest (<1%) in North America, Australia and New Zealand, 2-4% in Japan, 5-18% in China and highest (15-20%) in Taiwan as well as several other countries in South East Asia. Perinatal transmission is common in HBV-hyperendemic areas. Geographical clusters of horizontal HBV infection have been reported in both high- and low-risk countries. Common sources of infection, including iatrogenic and sexual transmission, have been implicated. Migrant studies indicate the importance of childhood environments in the determination of HBV infection. Rural urban and ethnic differences in the prevalence of HBV infection have also been reported. There has been a decrease in the prevalence of HBV infection after mass HBV vaccination programmes in some Asia-Pacific countries, which may be due to the intervention of possible transmission routes through the use of disposable syringes and needles, screening of HBV infection markers in blood banks, and prevention of high-risk tattooing, acupuncture, ear-piercing and sexual contact. A striking decrease in the incidence of HBV infection and hepatocellular carcinoma has been observed among children in Taiwan and other areas where mass vaccination programmes have been implemented.

Asia↗

Gliotoxic action of glutamate on cultured astrocytes.

Because of the well-documented importance of glutamate clearance by astrocytes in protecting neurons against excitotoxicity, it was interesting to examine whether L-glutamate exerts a toxic action on cultured astrocytes. Cell damage was evaluated by measuring activity of lactate dehydrogenase (LDH) released into the culture medium. Exposure of astrocyte cultures of the neonatal rat cerebral cortex to L-glutamate resulted in a concentration- and time-dependent increase in the release of LDH. L-Glutamate-induced gliotoxicity appeared to be mediated predominantly by the increase of oxidative stress because the reduced glutathione content and its effects were almost completely blocked by vitamin E and pyrrolidinedithiocarbamate. To support this notion further, the supplementation or depletion of intracellular reduced glutathione content attenuated or worsened L-glutamate toxicity, respectively. Activation of the glutamate transporter mimicked the action of L-glutamate on astrocytes. In addition, degrees of cell damage were not directly correlated to the levels of glutamate uptake. Moreover, the mechanism of this toxicity required energy and macromolecular synthesis. Taken together, brief exposure to L-glutamate resulted in glutamate uptake and cell swelling, whereas sustained exposure injured astrocytes via oxidative stress instead of the excitatory mechanism.

ATP-Binding Cassette Transporters↗

Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells.

Regulation of arachidonate metabolism in human epidermoid carcinoma A431 cells by phospholipid hydroperoxide glutathione peroxidase (PHGPx) and cytosolic glutathione peroxidase (GPx1) was studied. In order to study the effect of reduced glutathione (GSH) on the catalysis regulation of these oxygenation enzymes, diethyl maleate was used to deplete the intracellular GSH. In the presence of 13-hydroperoxyoctadecadienoic acid, the enzymatic catalysis of cyclooxygenase and 12-lipoxygenase was significantly increased in the GSH-depleted cells. In terms of the inhibitory effect on 12-lipoxygenase, PHGPx was more sensitive to GSH concentrations than GPx1. Inhibition of PHGPx activity by the treatment of cells with antisense oligonucleotide of PHGPx mRNA increased the enzymatic catalysis of both cyclooxygenase and 12-lipoxygenase. In conclusion, the results indicate that catalysis of cyclooxygenase and 12-lipoxygenase in A431 cells was regulated by redox-reaction, and PHGPx seems to play an important role in the controlling of these reactions.

Arachidonate 12-Lipoxygenase↗

Crystallization and preliminary X-ray diffraction analysis of the mitochondrial transcription factor sc-mtTFB from Saccharomyces cerevisiae.

Eukaryotic mitochondria contain a distinct mini-chromosome. In yeast, transcription of the mitochondrial genome is mediated by a nuclear-encoded RNA polymerase consisting of a single polypeptide core enzyme and a specificity factor termed sc-mtTFB which bears some similarity to bacterial sigma-factors. sc-mtTFB from Saccharomyces cerevisiae has been cloned, expressed, purified and crystallized. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 89.7, b = 44.6, c = 98.9 A, beta = 110 degrees. Based on one molecule per asymmetric unit, the solvent content is estimated to be 48%. Small crystals of dimensions 0.01 x 0.05 x 0.13 mm diffract to at least 2.7 A resolution on a rotating-anode X-ray source.

Crystallization↗

Structure of the Ca2+-regulated photoprotein obelin at 1.7 A resolution determined directly from its sulfur substructure.

The crystal structure of the photoprotein obelin (22.2 kDa) from Obelia longissima has been determined and refined to 1.7 A resolution. Contrary to the prediction of a peroxide, the noncovalently bound substrate, coelenterazine, has only a single oxygen atom bound at the C2-position. The protein-coelenterazine 2-oxy complex observed in the crystals is photo-active because, in the presence of calcium ion, bioluminescence emission within the crystal is observed. This structure represents only the second de novo protein structure determined using the anomalous scattering signal of the sulfur substructure in the crystal. The method used here is theoretically different from that used for crambin in 1981 (4.72 kDa) and represents a significant advancement in protein crystal structure determination.

Aequorin↗

Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk.

BACKGROUND: Persistent infection with hepatitis B virus (HBV) causes chronic phasic necroinflammation and regenerative proliferation in the liver. The sustained hepatocellular proliferation may render chronic HBV carriers more susceptible to the effects of environmental carcinogens. Aromatic amines are potential hepatocarcinogens in humans. N-acetyltransferase (NAT) is involved in the metabolic activation and detoxification of these compounds. AIMS: To investigate if genetic polymorphisms in N-acetylation are related to hepatocellular carcinoma (HCC) among chronic HBV carriers. METHODS: Genotyping of NAT1 and NAT2 was performed using polymerase chain reaction-restriction fragment length polymorphism on peripheral leucocyte DNA from 151 incident cases of HCC and 211 controls. All subjects were male, and were chronic HBV surface antigen carriers. RESULTS: A significant association between NAT2 genetic polymorphism and HCC was observed among chronic HBV carriers who were smokers but not among those who were non-smokers. For smoking HBV carriers, the odds ratios of developing HCC for those heterozygous and homozygous for the NAT2*4 functional allele compared with those without any copies of the functional allele (reference group) were 2.67 (95% confidence interval 1.15-6.22) and 2.58 (95% confidence interval 1.04-6.43), respectively. The interaction between cigarette smoking and the presence of the NAT2*4 allele just failed to reach statistical significance (p=0.06). No association between NAT1 genotype and HCC was evident overall or within the smoking stratified subgroups. CONCLUSIONS: Our results suggest that NAT2 activity may be particularly critical in smoking related hepatocarcinogenesis among chronic HBV carriers. Our data also indirectly support a role for tobacco smoke derived aromatic amines in the aetiology of HCC.

Acetyltransferases↗

Knowledge and perception of oral health promotion in schools among dental nurses in Sarawak, Malaysia.

In recent years, the concept of a Health-Promoting School has received much interest. In Malaysia, dental nurses are ideally placed to play a lead role in promoting Oral Health within the school setting. This study aims to provide information on the knowledge, perception and perceived role of Oral Health Promotion in schools, among dental nurses. A postal questionnaire was used to measure dental nurses' knowledge, perception and perceived role of Oral Health Promotion. The majority (60%) of dental nurses had good knowledge of Oral Health Promotion. Generally, they perceived that they play an important role in promoting Oral Health in schools. However, a sizeable proportion (25%) did not think they had a role to play in working together with school authorities to provide children with healthy food choices in school canteens. The majority (60%) of dental nurses did not perceive Oral Health Promotion to be important as a whole. They had a good perception of the concepts: it supports behaviour change, it has appropriate goals, it integrates oral health and general health and relieves anxiety. However, they had a poorer perception of the concepts; diverse educational approaches, participation, focus on prevention, early intervention, "spread of effect" of dental health education and "make healthier choices the easier choices". Years of service was not significantly associated with knowledge and perception of Oral Health Promotion. Dental nurses should be reoriented towards a more holistic practice of Oral Health Promotion. Workshops that invite active participation from dental nurses should be conducted to equip them with the necessary knowledge and skills.

Adult↗

Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1.

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.

Adult↗

Risk of internal cancers from arsenic in drinking water.

The U.S. Environmental Protection Agency is under a congressional mandate to revise its current standard for arsenic in drinking water. We present a risk assessment for cancers of the bladder, liver, and lung from exposure to arsenic in water, based on data from 42 villages in an arseniasis-endemic region of Taiwan. We calculate excess lifetime risk estimates for several variations of the generalized linear model and for the multistage-Weibull model. Risk estimates are sensitive to the model choice, to whether or not a comparison population is used to define the unexposed disease mortality rates, and to whether the comparison population is all of Taiwan or just the southwestern region. Some factors that may affect risk could not be evaluated quantitatively: the ecologic nature of the data, the nutritional status of the study population, and the dietary intake of arsenic. Despite all of these sources of uncertainty, however, our analysis suggests that the current standard of 50 microg/L is associated with a substantial increased risk of cancer and is not sufficiently protective of public health.

Adult↗

Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

Adult↗

Current seroprevalence of hepatitis A virus infection among kindergarten children and teachers in Taiwan.

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before the late 1980s. The seroprevalence of HAV infection was higher than 90% with most HAV infection occurring during childhood. This study was to estimate the seroprevalence of HAV infection among preschool children in central Taiwan. A community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas and 2 aboriginal areas randomly selected through stratified sampling. Serum samples of 2,549 healthy preschool children and 104 teachers in study kindergartens were screened for the HAV antibodies (anti-HAV) by means of a commercially available microparticle enzyme immunoassay (AxSYM HAVAB). Among aboriginal kindergarten children, more than 96% of them were anti-HAV seropositive due to a mass HAV vaccination program. In urban and rural areas, kindergarten children had a very low prevalence of anti-HAV (0.4%) in contrast to a high seroprevalence in their teachers (78%). There was no gender difference in seroprevalence of anti-HAV, while the anti-HAV seroprevalence was significantly higher in urban areas than in rural areas. Crowdedness of living in urban areas might facilitate the person-to-person transmission of infectious agents.

Adult↗