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Biomedical subjects

C S Yang

Publications and source records attributed to C S Yang.

At least 55 records · Page 3Linked to original sources
PubMed2000

Epstein-barr virus nuclear antigen 2 retards cell growth, induces p21(WAF1) expression, and modulates p53 activity post-translationally.

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) has been shown to be required for promotion of cell-cycle progression in EBV-immortalized B-lymphocytes. However, other studies have indicated that EBNA2 alone, in the absence of other EBV genes, may retard cell growth. To resolve this discrepancy, we investigated the effect of EBNA2 on the growth of various cells, including EBV target nasopharyngeal carcinoma cells, NPC-TW01 and NPC-TW04. We found that EBNA2 could retard cell growth, in stable Vero, HEp-2, and U2OS cell clones expressing EBNA2, and in Vero, 293, NPC-TW01, and NPC-TW04 cells transiently transfected with EBNA2. While investigating the mechanism underlying the growth-retarding function of EBNA2, we found that EBNA2 induced p21(WAF1) expression in these cells. This induction of p21(WAF1) expression was mediated through p53. EBNA2 was found to stimulate p53 to bind to the p53-response element within the p21(WAF1) promoter, possibly by promoting p53 phosphorylation. This enhancement of p53 sequence-specific DNA-binding activity may be the mechanism through which EBNA2 activates the expression of p53-regulated genes, including p21(WAF1) and mdm-2. Together, these studies reveal a possible intrinsic function of EBNA2 in cell-growth regulation and elucidate a novel mechanism by which EBNA2 modulates transcription.

Animals↗
PubMed2000

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. CONCLUSIONS: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Adult↗
PubMed2000

Diethylmaleate decreased ascorbic acid release induced by cerebral ischemia in cerebral cortex of the anesthetized rat.

The effect of diethylmaleate administration on ascorbic acid release following cerebral ischemia was investigated in anesthetized rat brain cortex. Cerebral ischemia, induced by ligating bilateral common carotid arteries and unilateral middle cerebral artery, significantly increased the extracellular ascorbic acid levels. Diethylmaleate (4 mmoles/kg, i.p.), which has been shown in earlier studies to decrease the ischemia-induced glutamate release, significantly reduced the ischemia-induced ascorbic acid release. The ischemia-induced ascorbic acid release was unaffected by perfusing NMDA receptor antagonist MK 801 (75 microM). Additionally, elevated extracellular glutamate levels, achieved by either externally applied glutamate solutions or by perfusing L-trans-pyrrolidine-2,4-dicarboxylate (PDC) (31.4 mM and 15.7 mM) to inhibit the glutamate uptake transporter, also significantly increased the extracellular ascorbic acid levels. These results suggested that ascorbic acid release in cerebral ischemia might be related to the elevated extracellular glutamate levels, which occurs following cerebral ischemia.

Amino Acid Transport System X-AG↗
PubMed2000

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↗
PubMed2000

An improved method for the determination of green and black tea polyphenols in biomatrices by high-performance liquid chromatography with coulometric array detection.

Tea polyphenols are strong antioxidants and are believed to have beneficial health effects. However, the blood and tissue levels of these compounds are not well characterized because of a lack of suitable analytical methods for the biological resolution of these compounds. Previously, we developed methods for the analysis of three green tea catechins. Now we report an improved method for the measurement of the levels of the different catechins and theaflavins in biological fluids and tissues. The method includes digestion of the plasma, urine, or tissue samples with beta-d-glucuronidase and sulfatase, followed by extraction with ethyl acetate and subsequent separation by reversed-phase high-performance liquid chromatography (HPLC). The polyphenols are identified on the basis of their retention times, spectral analysis, and electrochemical behavior across an array of electrodes. In a single HPLC run, it is possible to determine the major catechins and theaflavins as well as some of the catechin metabolites. The detection limits for catechins and theaflavins are from 5 to 10 ng/ml of saliva, plasma, or urine.

Adult↗
PubMed2000

Expression of the Epstein-Barr virus BHRF1 gene, a homologue of Bcl-2, in nasopharyngeal carcinoma tissue.

Epstein-Barr virus (EBV) infection is associated closely with the pathogenesis of nasopharyngeal carcinoma (NPC). The EBV gene product, BHRF1, has been demonstrated in vitro and is structurally and functionally similar to the oncogene bcl-2, that is able to protect cells from programmed cell death. To determine whether the BHRF1 gene is expressed in vivo, BHRF1 mRNA or protein were sought in tissues from NPC and non-NPC patients. BHRF1 transcripts were specifically detected in the NPC tumours (32 out of 44, 72.7%) rather than the non-NPC tissues (0 out of 25) by reverse transcription, polymerase chain reaction and Southern hybridization. Other EBV genes, such as the lytic gene BZLF1 and latent genes EBNA1 and LMP2A, were also investigated. BZLF1 transcripts also were found specifically in NPC tumours (33 out of 44, 75%). EBNA1 was expressed in 79.5% of NPC, and 28% of non- NPC, tissues and LMP2A was expressed in 70.5% of NPC, and 88% of non-NPC, tissues. BHRF1 protein was detected by immunohistochemistry in 4 metastatic NPC, of 36 NPC tissue sections available. The BHRF1 protein was distributed in both the nucleus and cytoplasm of the neoplastic epithelial cells. IgG antibody against the BHRF1 protein was detected in 6 of 17 (35. 3%) NPC plasma, but the protein and IgG were both absent from the non-NPC controls. BHRF1 DNA sequences were determined for 11 NPC and 3 non-NPC samples. No sequence was specific for the EBV isolates from NPC tissue. Amino acids 79 and 88 always appeared in the same form, however, for every tested isolate and both were valine or leucine. This particular characteristic was not present in the B95-8 strain or in the corresponding regions of homologues, Bcl-2 and Bcl-XL, and was regarded as unique to Oriental EBV strains.

Amino Acids↗
PubMed2000

Mechanisms of inhibition of carcinogenesis by tea.

Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti-proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20-100 microM) are usually higher than those observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H-ras induced milogen-activated protein kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate inhibited the phosphorylation of c-jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans.

Animals↗
PubMed2000

seco-Prezizaane-type sesquiterpenes from Illicium merrillianum.

Four seco-prezizaane sesquiterpene lactones, 14-O-n-butyrylfloridanolide, 3,4-dehydrofloridanolide, 3,6-dideoxy-10-hydroxypseudoanisatin, and 2-O-n-butyrylpseudomajucin were isolated from the pericarps of Illicium merrillianum. Their structures were determined by spectroscopic methods.

Magnetic Resonance Spectroscopy↗
PubMed2000

Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs.

Rapidly progressive fibrosing interstitial nephritis after a slimming regimen containing aristolochic acid has been identified as Chinese herbs nephropathy (CHNP). From 1995 to 1998, we observed 12 Chinese people from different areas of Taiwan who underwent renal biopsy for unexplained renal failure. Medical history gave no clue to the causes of impaired renal function except for the ingestion of traditional Chinese herbs. Although these patients ingested herbal drugs from various sources for different purposes, their renal biopsy samples showed amazingly similar histological findings, with extensive hypocellular interstitial fibrosis and atrophy and loss of tubules in all cases. Glomeruli were apparently intact. They also had similar clinical features, such as normal or mildly elevated blood pressure, early and severe anemia, low-grade proteinuria, glycosuria, and insignificant urinary sediments. Renal function deteriorated rapidly in most patients despite discontinuation of the herbal medicines. Seven patients underwent dialysis, and the remainder experienced slowly progressive renal failure. Bladder carcinoma was found in one patient. Morphologically and clinically, the nephropathy in our patients was similar to CHNP, reported in Belgium. Because of the complexity and unknown types of herbs used in different clinical situations, unidentified phytotoxins other than aristolochic acid might be responsible for this unique disease entity. We conclude that the relation of this nephropathy to the consumption of Chinese herbs is striking. Using uncontrolled herbal remedies carries a high risk for developing interstitial renal fibrosis and urothelial malignancy.

Adult↗
PubMed2000

Identification of oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin with H(2)O(2).

(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are two important antioxidants in tea. They also display some antitumor activities, and these activities are believed to be mainly due to their antioxidative effects. However, the specific mechanisms of antioxidant action of tea catechins remain unclear. In this study are isolated and identified two novel reaction products of EGCG and one product of EGC when they were reacted separately with H(2)O(2). These products are formed by the oxidation and decarboxylation of the A ring in the catechin molecule. This study provides unequivocal proof that the A ring of EGCG and EGC may also be an antioxidant site. This study also indicates an additional reaction pathway for the oxidation chemistry of tea catechins.

Antioxidants↗
PubMed2000

Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion.

Tea is a popular beverage consumed worldwide. The metabolic fate of its major constituents, catechins, however, is not well-known. In this study, two catechin metabolites were detected in the urine and plasma of human volunteers after ingestion of green tea. These metabolites were identified by LC/ESI-MS and NMR as (-)-5-(3',4', 5'-trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3', 4'-dihydroxyphenyl)-gamma-valerolactone (M6). The renal excretion of M4 and M6 had a 3 h lag time and peaked 7.5-13.5 h after ingestion of a single dose of green tea, while (-)-epigallocatechin (EGC) and (-)-epicatechin peaked at 2 h. M4 and M6 were two major tea metabolites with urinary cumulative excretions as high as 8-25 times the levels of EGC and (-)-epicatechin in some of our subjects, and accounted for 6-39% of the amounts of ingested EGC and (-)-epicatechin. Both the metabolites appeared to be produced by intestinal microorganisms, with EGC and (-)-epicatechin as the precursors of M4 and M6, respectively. Repeated ingestion of green tea produced a slight accumulative effect of the metabolites. They were also detected in the plasma, exhibiting kinetics similar to those of the urinary metabolites, and in the feces. Study on these metabolites may help us further understand the cancer chemopreventive actions and other beneficial effects of tea.

Adult↗
PubMed2000

Salivary and serum antibody response to Streptococcus mutans antigens in humans.

Humoral immunity against Streptococcus mutans infection was analyzed in caries-active and caries-free young adults by immunoblotting. All volunteers from both groups had detectable salivary immunoglobulin A (IgA) and serum IgG antibodies, with similar profiles. They could be classified on the basis of relative intensity of the immunoblot bands into categories of high or low responders. Common protein antigens with molecular weight ranging from approximately 45 to 190 kDa could be found either extracellularly or associated with the cell wall of S. mutans cultured in vitro. The predominant reactive antigens recognized by both IgA and IgG were of proteins around 63 and 60 kDa. Detection of IgA antibodies to the various antigens of S. mutans in individual saliva samples did not always correlate with serum IgG antibody profiles. In addition, distinct bands, which reacted preferentially with either IgA or IgG, could be detected by antibodies from specific subjects. Differential reactivities of salivary IgA and serum IgG antibodies to two, cell-wall associated protein antigens around 33 and 36 kDa were found in caries-active and caries-free young adults; 30.8% of caries-free subjects and 12% of caries-active subjects (P < 0.01) exhibited detectable antibody response to these antigens. This difference was not attributable to variations in antibody levels, since antibody response to these proteins were still detectable in some caries-free but not caries-active individuals whose levels of antibodies to other antigens were low. Thus, a new antibody profile which correlates with dental caries disease activity has been identified in a selected population. Differences in mucosal and systemic immune responses to S. mutans seem to be both antigen and host dependent.

Adolescent↗
PubMed2000

Trace Metals' abnormalities in hemodialysis patients: relationship with medications.

A multicenter collaborative study was performed to investigate the prevalence of abnormal blood contents of 6 trace metals, copper (Cu), zinc (Zn), aluminum (Al), lead (Pb), cadmium (Cd), and mercury (Hg), in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, Al containing phosphate-binding agents, 1,25-dihydroxy vitD3, 1-hydroxy vitD3, and erythropoietin (EPO), as well as hematocrit level, by chi-square statistics. From 6 medical centers in Taiwan, we included 456 patients in maintenance HD for more than 4 months for this study, and they had continued the previously mentioned medications for at least 3 months. Blood samples were collected before initiating HD, and atomic absorption spectrophotometry was used to measure plasma levels of Cu, Zn, and Al as well as whole blood levels of Pb, Cd, and Hg. Three hundred seventy-five (78%) of the HD patients had low plasma Zn levels, that is, <800 microg/L, and the mean (+/-SD) concentration was 705.8 (+/-128.23) microg/L in all subjects. One hundred forty-one (31%) of the HD patients had high plasma Al, that is, >50 microg/L, and the mean (+/-SD) was 44.30 (+/-28.28) microg/L in all subjects. Three hundred thirty-three (73%) of the dialysis patients had high Cd levels, that is, >2.5 microg/L, and the mean (+/-SD) was 3.32 (+/-1.49) microg/L in all subjects. The majority of HD patients had normal blood levels of Cu, PB, and Hg. Only 21 (4. 6%), 5 (1.1%), and 3 (0.06%) patients had elevated blood levels of Cu, Pb, and Hg, respectively. Their mean (+/-SD) blood concentration of Cu, Pb, and Hg were 1,049.78 (+/-233.25) microg/L, 7.45 (+/-3.95) microg/dL, and 3.17 (+/-25.56) microg/L, respectively. Three patients had elevated plasma Hg concentrations, that is, 546, 12.6, and 24.0 microg/L, respectively. In the 152 normal healthy age and sex matched control group, the blood levels of Al, Cd, and Pb were all significantly lower than the HD patients. However, the levels of Cu and Zn were higher in the control group. The Hg level was not significantly different in both groups. There was no statistical difference between patients with normal and abnormal blood levels of trace metals in various medications except Al containing phosphate binder. The Al containing phosphate binder users had significantly higher plasma Al levels (54.71 +/- 26.70 versus 41.15 +/- 28.03 microg/L, p < 0.001) and hematocrit levels (29.61 +/- 4.61 versus 27. 81 +/- 3.91, p < 0.0005). There was no statistical correlation between erythropoietin (EPO) dose and hematocrit level in these patients. In conclusion, the blood level of trace metals of these HD patients except Al was not related to their medications. However, caution must be exercised in interpreting this result as dose and duration of medication; efficiency of HD and water treatment may play an important role. Otherwise, environmental factors, diet, and the aging process may contribute to the trace metal burden in uremia. Thus, Zn and Cu are abundant in seafood, and Cd is abundant in contaminated plants such as rice.

Acetates↗
PubMed2000

Elevated expression of thyroid hormone receptor alpha 2 (c-erb A- alpha 2) in nasopharyngeal carcinoma.

Differential display was used to identify genes differentially expressed between cultured normal nasal epithelial cells and nasopharyngeal carcinoma (NPC) cell lines. A 130 bp cDNA fragment showing homology with thyroid hormone receptor alpha2 (TR-alpha2 or c-erb A-alpha2) was identified in NPC cell lines. Northern blot analysis using the 130 bp cDNA fragment and a TR-alpha2 specific cDNA containing part of the coding region as probes, we were able to detect a 2.7 kb transcript corresponding to that of TR-alpha2 in NPC cell lines but not in normal nasal epithelial cells. RNA in situ hybridization was used to detect TR-alpha2 expression in clinical biopsies obtained from NPC patients and non-tumour controls. TR-alpha2 mRNA was detected in 1 out of 24 (4.2%) normal nasopharynx epithelium biopsies, in 5 out of 27 (18.5%) primary and 15 out of 24 (62.5%) recurrent tumours. The positive rate of TR-alpha2 expression in recurrent NPC biopsies was significantly higher than that in normal nasopharynx epithelium (P<0.00001). The relevance of the elevated expression of TR-alpha2 in the pathogenesis process of NPC was discussed.

Adult↗
PubMed2000

Urgent endoscopic nasobiliary drainage without fluoroscopic guidance: A useful treatment for critically ill patients with biliary obstruction.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is routinely performed under fluoroscopic control. This is a report of our experience with urgent ENBD without fluoroscopic guidance in critically ill patients. METHODS: Twenty-six critically ill patients who underwent urgent ENBD for biliary obstruction were analyzed. ENBD was performed without fluoroscopic control because of high risk of transportation or inaccessibility of the x-ray facilities. A pig-tailed nasobiliary catheter was inserted into the bile duct with the help of a guidewire under endoscopic control to bypass the site of obstruction. Successful placement was confirmed by free flow of bile on aspiration via the nasobiliary catheter. RESULTS: A nasobiliary catheter was successfully placed in 23 patients (88%). Adequate bile drainage was achieved in 20 patients with an overall success rate of 77%. There were no procedure-related complications. The mortality rate for patients with successful biliary drainage was 10% (2 of 20), in contrast to 83% (5 of 6) for the group in which drainage was unsuccessful. CONCLUSIONS: Urgent ENBD is effective for patients with biliary obstruction. With experience, this procedure may be successfully performed in critically ill patients without fluoroscopic guidance at primary care hospitals or intensive care units where fluoroscopic facilities are not readily available.

Adult↗
PubMed2000

Effect of black and green tea polyphenols on c-jun phosphorylation and H(2)O(2) production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction.

The biological activities of theaflavin (TF), theaflavin gallate (TFG) and theaflavin digallate (TFdiG) from black tea and (-)-epigallocatechin 3-gallate (EGCG) and (-)-epigallocatechin (EGC) from green tea were investigated using SV40-immortalized (33BES) and Ha-ras gene transformed (21BES) human bronchial epithelial cell lines. Growth inhibition and cell viability were measured by trypan blue dye exclusion assay following 24 h treatment with the tea polyphenols. TFdiG, EGC and EGCG displayed comparable inhibitory effects on the growth of 21BES cells, with estimated IC(50) values of 22-24 microM. TFG exhibited a lower inhibitory activity (IC(50) 37 microM) and TF was even less effective (IC(50) 47 microM) in this cell line. A similar effect was also observed in 33BES cells. These results suggest that the gallate structure of theaflavins is important for growth inhibition. Exposure of 21BES cells to 25 microM TFdiG, EGC and EGCG for 24 h led to induction of cell apoptosis/death as determined by the Annexin V apoptosis assay. With TFdiG treatment cell death occurred early, and quickly peaked at 8-12 h. Morphological observations showed that TFdiG-treated cells appeared irregular in shape, with cytoplasmic granules, suggesting a cytotoxic effect. On the other hand, EGC and EGCG showed a lag phase before a rapid increase in apoptosis between 16 and 24 h, without any marked morphological changes, which was similar to that induced by H(2)O(2). TFdiG, EGC and EGCG induced similar amounts of H(2)O(2) formation in 21BES cells. Exogenously added catalase significantly prevented EGC- and EGCG-induced cell apoptosis, but did not prevent TFdiG-induced cell death, suggesting that H(2)O(2) is involved in the apoptosis induced by EGCG and EGC, but not in TFdiG-induced cell death. EGCG and TFdiG were shown to decrease c-jun protein phosphorylation in 21BES cells. Such inhibition is expected to result in lowered AP-1 activity, which may contribute to the growth inhibitory activity of tea polyphenols.

Antioxidants↗