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Biomedical subjects

L Y Wang

Publications and source records attributed to L Y Wang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Changing prevalence of hepatitis C virus genotypes: molecular epidemiology and clinical implications in the hepatitis C virus hyperendemic areas and a tertiary referral center in Taiwan.

To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to clarify the relationship between genotype and the pathogenesis of HCV infection, 1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center in Taiwan were studied during 1995-1997. HCV genotypes and viral loads were determined using Okamoto's method and branched DNA assay, respectively. Genotype 1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral center (47.0%). By contrast, genotype 2a was the major HCV type in Masago (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively correlated to age, regardless of study populations (P < 0.01). Based on multivariate analysis, the significant factors associated with the presence of cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C patients were genotype 1b and age. In conclusion, these results underline that independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan, concomitant with a changing relative prevalence of HCV genotypes in relation to age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic properties of HCV genotypes are probably responsible for the association between genotype and the pathogenesis of HCV infection.

Adolescent↗
PubMed2001

Association of aflatoxin B(1)-albumin adduct levels with hepatitis B surface antigen status among adolescents in Taiwan.

Chronic hepatitis B virus (HBV) infection and aflatoxin B(1) (AFB(1)) exposure interact synergetically to induce hepatocellular carcinoma. One suggested mechanism for this interaction is the enhanced activation of AFB(1) in chronically HBV-infected individuals. Whereas no associations between chronic HBV infection and AFB(1)-albumin adducts were observed in several studies in adults, hepatitis B surface antigen (HbsAg)-positive children were found to have elevated adducts in Gambia. To assess the association between chronic HBV infection and AFB(1)-albumin adduct level in Taiwan, 200 junior high school adolescents from 20 townships were assayed for HBsAg and AFB(1)-albumin adducts. The mean AFB(1)-albumin adduct level was higher in HBsAg-positive compared with HBsAg-negative subjects. The association between HBsAg status and AFB(1)-albumin adducts remained after multivariate adjustment. This finding additionally supports the synergetic interaction between HBV and AFB(1), but the mechanism remains to be elucidated.

Adolescent↗
PubMed2001

Ultrasonic characteristics of periportal collateral circulation in hepatocellular carcinoma with portal vein invasion.

Real-time ultrasound (US) was used to analyze the morphological characteristics of periportal collateral circulation (PPCC) and the hepatic artery in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). During a 5-year interval, a total of 17 HCC patients with main portal vein thrombosis and detectable periportal vessels were collected: 14 men and 3 women, aged 27 to 76 years old. We examined these patients' periportal vessels by real-time US, then differentiated PPCC from hepatic artery by duplex Doppler US. We analyzed the morphological appearances of real-time US imaging of PPCC and the hepatic artery. Our results showed that the PPCC was always torturously worm-like in appearance on real-time US, and the hepatic artery usually had a linear channel appearance on real-time US. When these two kinds of vessels were seen simultaneously along the pathway of a thrombosed portal vein, the inner vessel was always the hepatic artery with linear channel structure, and the outer vessel was always PPCC with a torturously worm-like structure. In conclusion, real-time US is a useful and reliable modality in detecting periportal vessels and differentiating PPCC from the hepatic artery.

Adult↗
PubMed2001

All-trans-retinoic acid increased the expression of integrin alpha5beta1 and induced "anoikis" in SMMC-7721 hepatocarcinoma cell.

It is extensively shown that integrin can regulate various cellular functions, including apoptosis, probably by contributing to signal transduction processes through interaction with extracellular matrix (ECM) proteins. In the present study, DNA flow cytometric analysis demonstrated that SMMC-7721 hepatocarcinoma cells treated with 80 microM all-trans-retinoic acid (atRA) showed an increased expression of the integrin alpha5beta1, which was associated with the growth inhibition of the cells. We found that atRA treated cells showed obvious apoptosis. Then, it was postulated that the enhanced content of integrin alpha5beta1 in the absence of ligation with fibronectin (Fn) would stop transducing survival signals, and lead to decreased cell growth and apoptosis. To elucidate this hypothesis, we cultured the atRA treated cell in L-poly-lysine-coated and Fn-coated flask, respectively. The results indicated that Fn binding prevented the cells from apoptosis induced by atRA, in contrast to L-poly-lysine binding. When the transfectant with enhanced expression of integrin alpha5beta1 at the same level of atRA treated cell was cultured in L-poly-lysine-coated flask, apoptosis was triggered. However, apoptotic cell was not detected when those cells were cultured in Fn-coated flask. Meanwhile, culturing the transfectant in the antibody (against integrin alpha5 subunit)-coated flask induced 18.33% of the cells into apoptosis, which is far more than the control group. Our study suggests that increased expression of integrin alpha5beta1 on the surface of SMMC 7721 hepatocarcinoma cell treated by atRA, when unbound to Fn, would stop transducing survival signals to lead to "anoikis", and can be reverted by the interaction of integrin alpha5beta1 with Fn.

Anoikis↗
PubMed2001

Prediction of bone fracture by bone mineral density in Taiwanese.

BACKGROUND AND PURPOSE: This study evaluated whether lumbar spine bone mineral density (BMDL) and the rate of change of BMDL could predict the risk of bone fracture in Taiwanese. METHODS: In 1989, a baseline survey was carried out in Lin-Kou Township. BMDL was measured using dual photon absorptiometry in 404 healthy volunteers. In 1994/95, a second survey was conducted to reexamine the BMDL and fracture history as well as the risk factors associated with fracture in these subjects. Fractures were classified according to the causes of the injury as severe or mild trauma. RESULTS: Of the 404 original examinees, 381 (79%) participated in the second survey. Twenty-six subjects had experienced a total of 32 fracture incidents during their lifetime and 10 subjects had experienced fracture during the observation period. After adjusting for the effect of body mass index, gender, and age, each standard deviation of decrease in BMDL was found to be associated with a significant 2.38-fold increase in the risk of mild trauma fracture, and a BMDL below the fracture threshold was associated with a 3.93-fold increase of fracture risk. Higher BMDL change rates were found in subjects with a history of fracture. CONCLUSION: This study indicates the importance of maintaining the BMDL above the fracture threshold (1 g/cm2). The strategy for fracture prevention should be directed at prevention of age-related bone loss.

Absorptiometry, Photon↗
PubMed2001

[GnT-V overexpression in human hepatocarcinoma cells affects its migration and expression of cell adhesion molecules].

The purpose of this paper is to study the effect of N-acetylglucosaminyltransferase V (GnT-V) overexpression on the migration of 7721 cells and its mechanism. The abilities of migration of both 7721 cells transfected with GnT-V cDNA and 7721 cells transfected with pcDNA3 was detected, the expressions of integrin and E-cadherin which are important adhesion molecules on surface membrane and closely related to the abilities of invasion and metastasis. Cell migration abilities were measured by the agarose drop explant method. Flow cytometric analysis (FACS) was applied to determine the relative amounts of integrin alpha 5 and beta 1 subunits on the cell surface while RTPCR was carried out to determine the expression of their mRNA. The expression of E-cadherin was examined by the immunocytochemical ABC method. Western blot analysis was carried out to examine the expression of beta-catenin. GnT-V overexpression enhanced evidently the migration ability of 7721 cells and increased the amount of integrin alpha 5 subunit to 2.9 times of that of control while the amount of beta 1 subunits was not significantly changed. Besides, the expressions of E-cadherin and beta-catenin were enhanced at different levels in GnT-V/7721 cells compared with mocked. The results suggested that the overexpression of GnT-V related to the production of N-linked sugar chains could promote the expressions of integrin, E-cadherin and beta-catenin on 7721 cells so that the migration ability of tumor cells was enhanced.

Cadherins↗
PubMed2000

The dynamic range for gain control of NMDA receptor-mediated synaptic transmission at a single synapse.

Although the level at which NMDA receptors (NMDARs) are activated can profoundly influence the direction and extent of long-term changes in synaptic strength, the probabilistic nature of quantal release at individual synapses makes it difficult to determine the dynamic operating range of NMDAR-mediated synaptic transmission. By continually driving glutamate release from a single high-fidelity auditory synapse with bursts of high-frequency stimuli, I show here that NMDAR-mediated EPSCs exhibited incremental summation in their amplitude and did not reach a plateau until six or seven consecutive stimuli into the train. An increase in the initial quantal output, by broadening presynaptic spikes with the potassium channel blocker tetraethylammonium (TEA, 0.2 mm), slightly increased the plateau amplitude at 200/300 Hz but shifted its peak temporally toward the earlier stimuli. These results suggest that the plateau amplitude in TEA reflects the activation of the entire population of synaptic NMDARs and hence the maximal gain of NMDAR-mediated synaptic transmission. This maximum was estimated to be 3.2-fold of the basal synaptic strength, giving a 31% occupancy of synaptic NMDARs by glutamate. Thus, synaptic NMDARs possess a broad dynamic range within which the activity-dependent control of synaptic strength and plasticity can potentially be tuned by the amount of Ca(2+) influx associated with different levels of NMDAR occupancy within the same synapse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3 on intestinal epithelial cells.

Transcription factor NF-kappaB has both pro-apoptotic and anti-apoptotic properties depending on the cell type. Its role in the intestinal epithelial cell has not been well elucidated. Trefoil factor 3 (TFF3) is an anti-apoptotic peptide secreted by intestinal goblet cells. Here we show that TFF3 activated NF-kappaB p50/p65 heterodimer within 1 h in IEC-18 cells (a nontransformed rat intestinal epithelial cell line). Moreover, we found that TFF3-treated IEC-18 cells are resistant to anoikis, an anchorage-related apoptosis in epithelium. In addition, the stable expression of a mutant form of the endogenous NF-kappaB inhibitor (IkappaBalpha(mut)) in IEC-18 cells results in a significant attenuation of anti-anoikic effect of TFF3. Taken together, these data indicate that (1) TFF3 is an endogenous gastrointestinal peptide with anti-anoikic property; (2) TFF3 activates NF-kappaB in enterocytes; and (3) TFF3-induced resistance to anoikis in intestinal epithelial cells is mediated by a distinct signaling cascade linked to NF-kappaB. Furthermore, our study implicates NF-kappaB as an important regulator in survival pathway of intestinal epithelial cells.

Animals↗
PubMed2000

TGF-beta 1 modulated the expression of alpha 5 beta 1 integrin and integrin-mediated signaling in human hepatocarcinoma cells.

Integrins are a family of cell surface adhesion molecules which mediate cell adhesion and initiate signaling pathways that regulate cell spreading, migration, differentiation, and proliferation. TGF-beta is a multifunctional factor that induces a wide variety of cellular processes. In this study, we show that, TGF-beta 1 treatment enhanced the amount of alpha 5 beta 1 integrin on cell surface, the mRNA level of alpha 5 subunit, and subsequently stimulated cell adhesion onto a fibronectin (Fn) and laminin (Ln) matrix in SMMC-7721 cells. TGF-beta 1 could also promote cell migration. Furthermore, our results showed that TGF-beta1 treatment stimulated the tyrosine phosphorylation level of FAK, which can be activated by the ligation and clustering of integrins. PTEN can directly dephosphorylate FAK, and the results that TGF-beta 1 could down-regulate PTEN at protein level suggested that TGF-beta 1 might stimulate FAK phosphorylation through increasing integrin signaling and reducing dephosphorylation of FAK. These studies indicated that TGF-beta 1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells.

Carcinoma, Hepatocellular↗
PubMed2000

Heterogeneous conductance levels of native AMPA receptors.

The single-channel properties of AMPA receptors can affect information processing in neurons by influencing the amplitude and kinetics of synaptic currents, yet little is known about the unitary properties of native AMPA receptors in situ. Using whole-cell and outside-out patch-clamp recordings from granule cells in acute cerebellar slices, we found that migrating granule cells begin to express AMPA receptors before they arrive in the internal granule cell layer and receive synaptic input. At saturating agonist concentrations, the open probability of channels in outside-out patches from migrating cells was very high, allowing us to identify patches that contained only one or two active channels. Analysis of the single-channel activity in these patches showed that individual AMPA receptors exhibit as many as four distinguishable conductance levels. The conductance levels observed varied substantially for different channels, although on average the values fell within the range of unitary conductances estimated previously for synaptic AMPA receptors. In contrast to patches from migrating granule cells, we rarely observed directly resolvable single-channel currents in patches excised from the somata of granule cells in the internal granular layer, even though these cells gave large AMPA receptor whole-cell currents. We did, however, detect AMPA receptors with apparent unitary conductances of <1 pS in patches from both migrating and mature granule cells. Our results suggest that granule cells express a heterogeneous population of AMPA receptors, a subset of which are segregated to postsynaptic sites after synaptogenesis.

Animals↗
PubMed2000

Esterase-sensitive nitric oxide donors of the diazeniumdiolate family: in vitro antileukemic activity.

We have designed a novel prodrug class that is stable in neutral aqueous media but releases bioactive nitric oxide (NO) on metabolism by esterase. Diazeniumdiolates of structure R(2)N-N(O)=N-OR', in which R' = Na, were reacted with BrCH(2)OAc to convert the spontaneously NO-releasing salts 1a (R(2)N = diethylamino) and 1b (R(2)N = pyrrolidino) to prodrugs 2a (AcOM-DEA/NO) and 2b (AcOM-PYRRO/NO), respectively, where R' = CH(2)OAc. In contrast to anions 1a and 1b (half-lives in pH 7.4 phosphate at 37 degrees C of 2 min and 3 s, respectively), 2a and 2b showed only minimal decomposition after 16 h under these conditions. Very rapid hydrolysis occurred in the presence of porcine liver esterase, however, with free anion 1a being observed as an intermediate in the esterase-induced generation of NO from 2a. The potential utility of this prodrug class is illustrated with a comparison of 1 and 2 as antiproliferative agents in NO-sensitive human leukemia cell lines HL-60 and U937. While the 72-h IC(50)'s for 1a and 1b (which generate NO throughout the medium) in HL-60 cell cultures were >600 microM, those of 2a and 2b were 8.3 and 6.4 microM, respectively. This result is consistent with our hypothesis that 2 is selectively hydrolyzed to 1 and thence to NO intracellularly. For U937 cells, the 72-h IC(50) for both 2a and 2b was 53 microM. By contrast, relatively high antiproliferative IC(50)'s (>100 microM in U937 cells) were observed for analogues in which R' = CH(2)CH(2)SC(O)Me, from which acetyl and 2-mercaptoethyl groups must be successively cleaved to free the NO-releasing diazeniumdiolate function. Within 24 h at initial concentrations of 50 microM, 2a and 2b induced apoptosis in 50% and 57% of the HL-60 cells, respectively (35% and 40% of the U937 cells, respectively). The data reveal significant in vitro antileukemic activity on the part of these novel compounds. Moreover, their substantial ease-of-handling advantages over the anionic diazeniumdiolates from which they are derived suggest their use as convenient agents for probing the biological roles of NO.

Animals↗
PubMed2000

Economic evaluation of Safer Choices: a school-based human immunodeficiency virus, other sexually transmitted diseases, and pregnancy prevention program.

OBJECTIVE: To evaluate the cost-effectiveness and cost benefit of Safer Choices, a school-based human immunodeficiency virus, other sexually transmitted diseases, and unintended pregnancy prevention intervention for high school students. METHODS: The baseline cost-effectiveness and cost benefit were derived in 4 steps: (1) estimation of intervention costs; (2) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted, and development of a model to translate increases in contraceptive use into cases of pregnancy averted; (3) translation of cases averted into medical costs and social costs averted; and (4) calculation of the net benefit of the program. Multivariable sensitivity analysis was performed to determine the robustness of the base-case results. RESULTS: Under base-case assumptions, at an intervention cost of $105,243, Safer Choices achieved a 15% increase in condom use and an 11% increase in contraceptive use within 1 year among 345 sexually active students. An estimated 0.12 cases of human immunodeficiency virus, 24.37 cases of chlamydia, 2.77 cases of gonorrhea, 5.86 cases of pelvic inflammatory disease, and 18.5 pregnancies were prevented. For every dollar invested in the program, $2.65 in total medical and social costs were saved. Results of most of the scenarios remained cost saving under a wide range of model variable estimates. CONCLUSIONS: The Safer Choices program is cost-effective and cost saving in most scenarios considered. School-based prevention programs of this type warrant careful consideration by policy makers and program planners. Program cost data should be routinely collected in evaluations of adolescent prevention programs.

Adolescent↗
PubMed2000

Sex differences in relation to serum hepatitis B e antigen and alanine aminotransferase levels among asymptomatic hepatitis B surface antigen carriers.

This study aimed to investigate sex differences in relation to hepatitis B e antigen (HBeAg) and serum alanine aminotransferase (ALT) levels in chronic asymptomatic hepatitis B virus (HBV) infection. HBeAg and ALT level were determined in 636 asymptomatic hepatitis B surface antigen carriers. There was no significant sex differences in the age-adjusted prevalence of HBeAg. Abnormal ALT level (>45 IU/l) was more frequent in carriers with HBeAg (17.5% vs 7.6%; P = 0.001). Multivariate analysis indicated that male sex (odds ratio, 2.0; 95% confidence interval, 1.1-3.6) and HBeAg (odds ratio, 2.6; 95% confidence interval, 1.6-4.3) were independent risk factors for abnormal ALT levels. Male sex and HBeAg-positivity are independent risk factors for abnormal ALT activity in chronic HBV infection. This observation may be related to sex differences in chronic HBV infection.

Adolescent↗
PubMed2000

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↗
PubMed2000

Role of serum C-reactive protein as a marker of hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: The usefulness of C-reactive protein (CRP) as a tumour marker in patients with hepatocellular carcinoma (HCC) is controversial. The purpose of this study was to determine whether CRP estimation could be used to identify patients with HCC among those with cirrhosis. METHODS: Serum levels of CRP and alpha-fetoprotein (AFP) were investigated in 122 previously untreated patients with cirrhosis and HCC. Another 76 patients with cirrhosis alone were also investigated as controls. RESULTS: Of the subjects tested, 47.5% of patients with HCC and 39.5% of controls had elevated CRP values (> 6 microg/mL). Although using elevated CRP and/or AFP (> 20 ng/mL) as a criterion showed a significant difference between controls and patients with multiple nodular, massive, or diffuse type HCC (all P < 0.005), the clinical application of this criterion was limited because of low specificity (58%) and accuracy (all < 73%). By using receiver-operating characteristic curves no valuable threshold value of CRP was found to discriminate various types of HCC, except for distinguishing the diffuse type from controls. The CRP value of 12 microg/mL could be used as the cut-off value to differentiate diffuse-type HCC from controls (sensitivity 82.4%, specificity 82%, accuracy 82.1%, P<0.005). CONCLUSIONS: Serum CRP is not a good marker for HCC. However, very high values of CRP in patients with cirrhosis may suggest the presence of a diffuse-type HCC.

Adult↗
PubMed2000

Serotyping and genotyping of hepatitis C virus in Taiwanese patients with type C chronic liver disease and uraemic patients on maintenance haemodialysis.

BACKGROUND: To evaluate a recombinant immunoblot hepatitis C virus (HCV) serotyping assay, which determines HCV serotypes 1, 2, and 3 by detecting type-specific antibodies to core-and NS-4-derived peptides. METHODS: Immunoreactivity of type-specific antibodies among 173 chronic hepatitis C patients and 43 haemodialysis patients in Taiwan was examined and the serotyping results were compared with genotyping by Okamoto's method. Serial specimens from 29 patients undergoing interferon-alpha therapy were also evaluated. RESULTS: Of the 205 specimens for which genotyping data were available, 51.2% were of serotype 1, 31.7% of serotype 2, 1.0% of serotype 3, 2.4% of either serotype 1 or 3, and the remaining 13.7% were untypable. The serotypable rate was significantly lower in haemodialysis patients than in chronic hepatitis C patients (70.0% vs 94.9%; P < 0.001). Serotyping of genotype 2b specimens was significantly more dependent on core peptide bands than other genotypes. Using genotyping as the reference, the overall sensitivity, specificity and concordance of the recombinant immunoblot HCV serotyping assay were 86.3%, 97.2% and 83.9%, respectively. However, the serotyping assay had significantly lower sensitivity (69.2%), specificity (77.8%) and concordance (53.8%) for genotype 2b specimens. Of nine HCV complete responders, one lost type-specific antibodies 6 months after the cessation of interferon-alpha treatment. CONCLUSIONS: These results suggest that, except for less than optimal performance with immunocompromised or genotype 2b patients, the HCV serotyping assay is a practical and useful method for HCV typing in the clinical setting in Taiwan.

Female↗
PubMed2000

Status and natural course of GB virus C/hepatitis G virus infection among high-risk groups and volunteer blood donors in Taiwan.

BACKGROUND: Hemophilia, thalassemia and uremia patients are at risk of parenterally transmitted infectious agents. The status and nature of the course of GB virus C/hepatitis G virus (GBV-C/HGV) infection among these groups and blood donors in Taiwan was investigated. METHODS: Serum GBV-C HGV-RNA and antibodies to GBV-C/HGV envelope-2-protein (anti-E2) were determined in 500 blood donors and in 44 hemophilia, 37 thalassemia and 85 uremia patients. Phylogenetic analysis was performed. RESULTS: The prevalence of GBV-C/HGV-RNA and anti-E2, respectively, was 38.6 and 27.3% in hemophilia patients, 27.0 and 27.3% in thalassemia patients, 14.1 and 10.6% in uremia patients and 3.4 and 7.2% in blood donors. The prevalence of GBV-C HGV exposure was 59.1 and 51.4% in hemophilia and thalassemia patients, respectively, which was significantly higher than that for uremia patients (22.4%; P < 0.01) and blood donors (10.2%; P < 0.001). The anti-E2 seroconversion rate was 66.7% in blood donors and 47.4, 36.8 and 34.6% in thalassemia, uremia (P < 0.05 compared with blood donors) and hemophilia (P < 0.01 compared with blood donors) patients, respectively. Discrepancies in the prevalence of GBV-C HGV and hepatitis C virus infection were found among the three risk groups. Phylogenetic analysis showed that 51 of 56 GBV-C HGV isolates clustered in group 3; the remaining five were of group 2a. Twelve of 39 viremic patients in the risk groups cleared the virus during the 4 year follow-up period; seven developed concomitant anti-E2 reactivity. CONCLUSIONS: GB virus C hepatitis G virus infection is epidemic among risk groups and GBV-C HGV group 3 is the major strain in Taiwan. In the risk groups, approximately 18% of infections resolve with concomitant anti-E2 seroconversion within 4 years.

5' Untranslated Regions↗