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W Chen

Publications and source records attributed to W Chen.

At least 55 records · Page 3Linked to original sources
PubMed2005

siRNA targeting the leader sequence of SARS-CoV inhibits virus replication.

SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.

5' Untranslated Regions↗
PubMed2005

The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells.

Development of novel therapeutic strategies is a continuing challenge for the treatment of acute myeloid leukemia (AML). The novel triterpenoid, C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me), induces apoptosis in myeloid leukemic cell lines and in primary AML samples. In this report, the effects of CDDO-Me on CD34(+) AML progenitor cells in vitro were examined. CDDO-Me induced apoptosis in all but one of ten AML samples. CDDO-Me is known to inhibit the activation of ERK1/2. In this series of primary AML samples, ERK was expressed and phosphorylated in all patient samples studied and CDDO-Me inhibited ERK phosphorylation in five of 10 samples. However, CDDO-Me induced apoptosis in four of five samples without decreasing pERK levels, suggesting that pERK is not the sole target of the compound. CDDO-Me induced phosphorylation of p38 in AML-derived U937 cells. Pretreatment of U937 cells with a p38 inhibitor protected cells from the cyto-toxic effects of CDDO-Me. These findings suggest a role for p38 in CDDO-Me-induced apoptosis. In preliminary studies, CDDO-Me induced p38 phosphorylation in seven of eight primary AML samples. These findings suggest that CDDO-Me treatment shifts cell signaling away from cyto-protective pathways and thus CDDO-Me may be effective for the treatment of AML.

Acute Disease↗
PubMed2005

In vitro microsomal metabolic studies on a selective mGluR5 antagonist MTEP: characterization of in vitro metabolites and identification of a novel thiazole ring opening aldehyde metabolite.

In vitro liver microsomal studies revealed that [14C] MTEP (3-[2-methyl-1,3-thiazol-4-yl)ethynyl] pyridine) was metabolized into three major oxidative metabolites. Metabolite 1 (M1) was shown to be a hydroxymethyl metabolite; M2 was shown to be a pyridine oxide. Moreover, a novel aldehyde metabolite (M3) was identified from mouse liver microsomes. The structure of the aldehyde M3 was elucidated by LC/MS/MS. In addition, methoxyamine, an aldehyde-trapping agent, and accurate mass measurement using a high-resolution quadrupole-time of flight (Q-TOF) instrument, were used to confirm the proposed thiazole ring-opening structure of M3. A mechanism for aldehyde M3 formation was postulated based on MTEP incubation studies with 18O2 and H2 18O using mouse liver microsomes. MTEP was initially oxidized at sulfur, followed by subsequent C4-C5 of thiazole epoxidation, thiozole ring opening and further oxidative desulfation. This proposed thiazole ring-opening mechanism might represent a novel metabolism pathway for xenobiotics containing a thiazole moiety. Species differences in the metabolism of MTEP were observed in mouse, rat, dog, monkey and human liver microsomes. Mouse appears to generate all three oxidative metabolites to a greater extent than other species examined.

Aldehydes↗
PubMed2005

A mutation in SART3 gene in a Chinese pedigree with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic disorder of keratinization, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, and the genetic basis and pathogenesis of this disorder have not been elucidated. OBJECTIVES: To determine the locus of DSAP and identify the candidate gene(s) of the disease. METHODS: Genome-wide scan and linkage analysis were performed in a six-generation Chinese family with DSAP. The coding exons of the candidate genes were sequenced to analyse and detect the nucleotide variations. RESULTS: Linkage analysis showed that the maximum two-point lod score of 5.56 was obtained with the marker D12S79 at a recombination fraction theta of 0.00. Haplotype analysis defined the critical region for DSAP between D12S330 and D12S1612 on 12q24.1-24.2. By sequence analysis, we found a Val591Met mutation in SART3 in all affected individuals of the family. CONCLUSION: SART3 is a candidate gene for DSAP, and is possibly involved in the pathogenesis of DSAP.

Antigens, Neoplasm↗
PubMed2005

Identification of a new HLA-A*0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587.

For the development of peptide-based cancer immunotherapies, we aimed to identify specific HLA-A*0201-restricted CTL epitopes in hepatocellular carcinoma (HCC) associated antigen HCA587, which has been identified as a member of the cancer/testis (CT) antigens highly expressed in HCC. We first combined the use of an HLA-A*0201/peptide binding algorithm and T2 binding assays with the induction of specific CD8(+) T cell lines from normal donors by in vitro priming with high-affinity peptides, then IFN-gamma release and cytotoxicity assays were employed to identify the specific HLA-A*0201 CD8(+) T cell epitope using peptide-loaded T2 cells or the HCA587 protein(+) HCC cell line HepG2. In the six candidate synthesized peptides, two peptides showed higher binding ability in T2 binding assays. No. 2 peptide, encompassing amino acid residues FLAKLNNTV (HCA587(317-325)), was able to activate a HCA587-specific CD8(+) T-cell response in human lymphocyte cultures from two normal donors and two HCC patients, and these HCA587-specific CD8(+) T cells recognized peptide-pulsed T2 cells as well as the HCA587 protein(+) HCC cell line HepG2 in IFN-gamma release and cytotoxicity assays. The results indicate that no. 2 peptide is a new HLA-A*0201-restricted CTL epitope capable of inducing HCA587-specific CTLs. Our data suggest that identification of this new HCA587/HLA-A*0201 peptide FLAKLNNTV may facilitate the design of peptide-based immunotherapies for the treatment of HCA587-bearing HCC patients.

Antigens, Neoplasm↗
PubMed2005

ES-62 is unable to modulate Toxoplasma gondii-driven Th1 responses and pathology.

ES-62, a filarial nematode-derived anti-inflammatory immunomodulator, was administered to mice in an attempt to prevent pathology associated with Toxoplasma gondii infection. The nematode product was shown to elevate mitogen and T. gondii-specific IL-10 production but was unable to inhibit Th1 responses. Consequently ES-62 could not prevent Th1 generated immunopathology.

Animals↗
PubMed2005

The prevalence of PD in a nutritionally deficient rural population in China.

OBJECTIVES: In most reports, the prevalence of PD in mainland China is lower than in western populations. To estimate PD prevalence in China, we performed a cross-sectional study in a rural population in Linxian County, China. PRIMARY OUTCOMES: Clinical diagnosis of PD. RESULTS: Among the 16,488 participants examined, the overall age- and gender-adjusted prevalence rate of PD was 522/100,000 (95% CI: 477-567) assuming no cases of PD would be found among those younger than 50 years of age. The gender-adjusted prevalence rates were 103 (95% CI: 83-123), 621 (95% CI: 572-670), 902 (95% CI: 843-961), and 1744 (95% CI: 1662-1826) per 100,000 in age groups 50-59, 60-69, 70-79, and 80 and above, respectively. CONCLUSIONS: The estimated prevalence of PD in Linxian, China is higher than most of those reported from other areas in China, and similar to those reported from non-Asian populations.

Age Distribution↗
PubMed2004

The Discriminative stimulus effects of gamma-hydroxybutyrate and related compounds in rats discriminating baclofen or diazepam: The role of GABA(B) and GABA(A) receptors.

The discriminative stimulus effects of gamma-hydroxybutyrate (GHB) can be mimicked by GABA(A) receptor-positive modulators (e.g., diazepam) and GABA(B) receptor agonists (e.g., baclofen). The purposes of this study were to see whether stimulus control could be established with baclofen and to further characterize the role of GABAergic mechanisms in the behavioral actions of GHB by evaluating GHB and related compounds in rats discriminating either diazepam or baclofen. Training criteria were satisfied with baclofen and diazepam after 69 and 44 sessions, respectively. GHB and its precursors gamma-butyrolactone and 1,4-butanediol occasioned >80% responding on the drug-associated lever in rats discriminating baclofen and <11% in rats discriminating diazepam. Diazepam and other GABA(A) receptor-positive modulators occasioned intermediate levels of responding on the baclofen lever, whereas baclofen occasioned less than 4% responding on the diazepam lever. The GABA(B) receptor antagonist CGP 35348 [(3-aminopropyl)(diethoxymethyl) phosphinic acid] partially antagonized the effects of baclofen as well as the baclofen-like effects of GHB, and flumazenil partially antagonized the effects of diazepam. This study established stimulus control with baclofen, and substitution data provided direct evidence for a role of GABAergic, especially GABA(B), mechanisms in the discriminative stimulus effects of GHB. The lack of substitution by GHB or its metabolic precursors for diazepam indicates a comparatively smaller role of GABA(A) mechanisms in these effects of GHB. The inability of CGP 35348 to completely attenuate the effects of baclofen and GHB suggests that multiple receptors could be involved in the discriminative stimulus effects of GHB.

Adjuvants, Anesthesia↗
PubMed2004

Glucocorticosteroids for primary sclerosing cholangitis.

BACKGROUND: Glucocorticosteroids have been suggested for primary sclerosing cholangitis, which is characterised by chronic inflammation and fibrosis in the intrahepatic and extrahepatic biliary tree. OBJECTIVES: To assess the beneficial and harmful effects of glucocorticosteroids for patients with primary sclerosing cholangitis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE from their inception until March 2003, and reference lists. SELECTION CRITERIA: Randomised clinical trials comparing any dose or duration of glucocorticosteroids versus placebo, no intervention, or other immunosuppressive agents. We included trials irrespective of language, blinding, or publication status. DATA COLLECTION AND ANALYSIS: Both reviewers extracted data independently and assessed the methodological quality by the generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results of the meta-analyses were presented as relative risks or weighted mean difference (WMD), both with 95% confidence intervals (CI). The primary outcome measures were mortality and liver-related morbidity. MAIN RESULTS: Two randomised clinical trials were eligible for inclusion. One trial compared biliary lavage with hydrocortisone versus saline in 17 patients. A significant number of adverse events (pancreatitis; cholangitis with septicaemia; paranoid ideas; fluid retention) and no cholangiographic improvement led to termination of the trial. The other trial compared budesonide versus prednisone in 18 patients. Patients had significantly higher serum bilirubin concentration after treatment with prednisone compared with budesonide (WMD 10.4 micro mol/litre, 95% CI 1.16 to 19.64 micro mol/litre). No other significant effects on clinical or biochemical outcomes were identified for any of the evaluated interventions. REVIEWERS' CONCLUSIONS: There is no evidence to support or refute peroral glucocorticosteroids for patients with primary sclerosing cholangitis.

Anti-Inflammatory Agents↗
PubMed2004

The pre-styloid compartment of the parapharyngeal space: a three-dimensional digitized model based on the Chinese Visible Human.

To build a digitized visible model of the parapharyngeal space of the Chinese Visible Human and to provide a sectional anatomic basis for radiological and clinical diagnosis of the parapharyngeal space, sectional anatomy data of the parapharyngeal space were selected from the Chinese Visible Human male and female to compare with MR imaging findings in the axial planes. From these data the parapharyngeal space and surrounding structures were segmented. They were then reconstructed in three dimensions on PC. In the axial planes of the sectional anatomy and MR imaging, the shape, content and relations of the parapharyngeal space were clearly displayed and the dominant plane for showing the parapharyngeal space was elicited. The three-dimensional reconstructed images displayed perfectly the anatomic relationships of the parapharyngeal space, parotid, muscles, mandible and vessels. All reconstructed structures can be displayed singly, in groups or as a whole; any diameter or angle of the reconstructed structures can be easily measured. The Chinese Visible Human male and female data set can provide complete and accurate data. The digitized model of the parapharyngeal space and its surroundings offers unique insights into the complex anatomy of the area, providing morphologic data for imaging diagnosis and surgery of the parapharyngeal space.

Anatomy, Cross-Sectional↗
PubMed2004

Correlates of carotid artery stiffness in young adults: The Bogalusa Heart Study.

Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for prevention.

Adult↗
PubMed2004

Effect of chlorpyrifos on efflux transporter gene expression and function in Caco-2 cells.

The effect of chlorpyrifos (CPF) and its metabolite, chlorpyrifos-oxon (CPO), on multidrug resistance-1 (MDR1) gene expression and efflux transporter function in Caco-2 cells was determined. The effect of CPF and CPO on gene expression in Caco-2 cells was tested as a function of time using RT-PCR and competitive PCR (compPCR) techniques. The RT-PCR results depicted a maximal effect of CPF exposure on MDR1 expression at 8 h, which decreased at 24 h. Studies with CPO displayed an initial increase in expression at 4 h only. The compPCR assays were conducted with the CPF-treated group to quantify the changes in gene expression levels. The compPCR data confirmed and quantitated the results from the time-course study using semiquantitative RT-PCR. In addition to the gene expression studies, changes in efflux transporter function were investigated using Caco-2 cells grown on semipermeable membranes in Transwell plates. The permeability of verapamil was determined in cells treated for 8 h with CPF. Efflux ratios demonstrated that verapamil was effluxed at a higher rate from the CPF-treated cells as compared to the control group, confirming the inductive action of CPF on transporter function. These results suggest that CPF has the potential to modulate the bioavailability of drugs via changes in expression and function of membrane efflux transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Sensitivity of the ultrasonic CARI technique for breast tumor detection using a FETD scheme.

The CARI (clinical amplitude/velocity reconstruction imaging) technique is a new ultrasonography for better detection of the breast cancer. The method uses the mammography-like positioning of the breast and a reference structure to assess the changes of sound velocity in the screened region. In this work, we present a first attempt to simulate the CARI technique using finite element time-domain (FETD) wave propagation. The CARI sensitivity to the size, shape and location of the tumors is investigated via the simulations on 2D and 3D breast models. Small lesions can be detectable under a suitable spatial resolution. 3D simulations agree with the quantitative results of the 2D case. Moreover, the FETD approximation is proving to be a simple, but robust tool in the CARI simulation.

Breast Neoplasms↗
PubMed2004

Aldosterone signaling modifies capillary formation by human bone marrow endothelial cells.

We investigated the regulation of the epithelial sodium channel (ENaC) in human bone marrow endothelial cells (HBMEC) responding to mineralocorticoid hormones and other accessory effectors. The message for both the mineralocorticoid receptor (MCR) and the alpha subunit of ENaC was expressed in HBMEC as predicted bands of 838 and 521 bp, respectively. In Western blots, the MCR of about 107 kDa was localized primarily in the cytoplasmic compartment but migrated to the nucleus when cell cultures were exposed to exogenous aldosterone. On the other hand, the alphaENaC was revealed as a membrane-bound protein of approximately 82 kDa, whose abundance increased after aldosterone treatment. Confocal microscopy confirmed the presence of both the MCR and ENaC as nucleocytoplasmic and membrane-bound proteins, respectively, and both colocalized with tubulin in situ. On Matrigel, the mineralocorticoid aldosterone, by itself, did not influence capillary formation by HBMEC, but the diuretic amiloride reduced the organization of HBMEC into capillary-like networks; curiously, aldosterone further exacerbated this inhibitory effect of amiloride. On the fibrin matrix, aldosterone had no influence at all on the length of the newly formed capillaries, but the capillary diameter was highly increased over the control. Aldosterone-mediated capillary swelling was totally reversed by amiloride, which, by itself, also inhibited capillary elongation by HBMEC. Thus, cell signaling by mineralocorticoid hormones in HBMEC appears to proceed in a manner very similar to that in the epithelial cell, thereby leading to an increase in the endothelial cell volume, which may underline the hypertensive state and which may also modify angiogenesis.

Aldosterone↗
PubMed2004

No evidence for links between autism, MMR and measles virus.

BACKGROUND: We examined whether, in the UK, there is an increased risk of autism (AD) following exposures, in early life, to: (1) wild measles; (2) live attenuated measles, alone or in combination as MMR; and (3) the alteration of the mumps strain within MMR. METHOD: We conducted time trend analyses of 2407 AD subjects born between 1959-93; and for comparison, 4640 Down's syndrome (DS) subjects born between 1966-93. Between 1968-86, we correlated variations in AD and DS births with wild measles incidence. Between 1959-93, we tested for abrupt changes in the long-term AD birth trend for the effects of introducing: (1) monovalent measles vaccines in 1968; (2) MMR immunization in 1988; and (3) the 'overnight switch' from mixed use of Urabe MMR to exclusive use of Jeryl-Lynn MMR in 1992. Incidence rate ratios (IRRs) were used as measures of association. RESULTS: We found no significant association between AD births and exposure (prenatal and postnatal up to 18 months age) to population rates of measles infections, and no 'step-up' increase in AD births associated with the introduction of monovalent measles and MMR vaccines, and changing mumps strain. An unexpected reduction in AD births of 21% (95% CI 6.9-33.3%; P=0.005) among the post-1987 birth cohorts was detected. CONCLUSION: No increased risk of AD following exposures to wild measles and vaccinations with monovalent measles, and Urabe or Jeryl-Lynn variants of MMR was detected. The precise meaning of the detected AD births reduction is unclear. Our study cannot exclude rare complications of MMR, given its correlational design.

Autistic Disorder↗
PubMed2004

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study.

OBJECTIVE: To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: : Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUC-baseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variance-component-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

Adolescent↗
PubMed2004

Upgrading of existing sludge treatment processes for phosphorus management serving a EBPR WWTP.

For a large-scale wastewater treatment plant to comply with phosphorus consents using enhanced biological phosphorus removal processes, its sludge and liquor treatment processes need to be carefully upgraded. In this case study, the wastewater treatment plant of interest has three different types of sludge treated by two different and independent sludge treatment processes. The task of upgrading the sludge treatment systems to serve an EBPR process while satisfying other regulatory and operational constraints in a cost effective way presents an interesting challenge. A range of process options was investigated to include P-rich surplus activated sludge treatment, raw sludge treatment, and sludge liquors treatment. Sludge pre-liming, i.e. to introduce lime slurry into raw liquid sludge before the dewatering stage, was studied in bench-scale and full-scale trials for phosphorus precipitation and pathogen reduction. It was applied to the mixture of surplus activated sludge and imported sludge. The results showed that a complete phosphorus precipitation was achieved at above pH 9 with lime addition of 7% (w/w as calcium hydroxide to sludge dry weight). A satisfactory 2-log pathogen reduction was consistently achieved at above pH 11 with lime addition of 14% (w/w). The process significantly simplified the potential upgrading work for sludge and liquor treatment, compared to other alternatives.

Calcium Compounds↗