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Biomedical subjects

Wei Zhao

Publications and source records attributed to Wei Zhao.

At least 163 records · Page 9Linked to original sources
PubMed2004

Injection drug use and crack cocaine smoking: independent and dual risk behaviors for HIV infection.

PURPOSE: Previous studies have examined the practices of injecting drugs or smoking crack cocaine as high-risk, but independent, factors for HIV transmission. To explore the independent and dual risks of injection practices and crack smoking, this study examined HIV seroprevalence rates among distinct drug user groups, based on patterns of daily administration. METHODS: A sample of 3,555 drug users and neighborhood controls in urban Miami, FL and rural Belle Glade and Immokalee, FL were partitioned into four mutually-exclusive groups: 1) injection drug users (IDUs); 2) crack-cocaine smokers; 3) dual users who both smoked crack and injected drugs; and 4) non-drug-user controls. RESULTS: HIV seroprevalence rates were 45.1% for IDUs, 30.5% for dual users, 20.1% for crack smokers and 7.3% for controls. Multivariate logistic regression analysis found that when compared with controls odds ratios for HIV seropositivity were 9.81 for IDUs, 5.27 for dual users, and 2.24 for crack smokers. CONCLUSIONS: These findings provide evidence of: 1) behavioral and structural co-factors that influence HIV exposure patterns among drug users; and 2) the substantially higher risk of HIV infection among IDUs compared with other drug users. Intervention strategies must be tailored for the specific drug use subpopulations to optimize efficacy.

Adult↗
PubMed2004

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts.

To examine the role of gap junctions in cell senescence, the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts. Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore, cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis, elevation of p53 expression, loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

Apoptosis↗
PubMed2004

X-ray imaging performance of structured cesium iodide scintillators.

Columnar structured cesium iodide (CsI) scintillators doped with Thallium (Tl) have been used extensively for indirect x-ray imaging detectors. The purpose of this paper is to develop a methodology for systematic investigation of the inherent imaging performance of CsI as a function of thickness and design type. The results will facilitate the optimization of CsI layer design for different x-ray imaging applications, and allow validation of physical models developed for the light channeling process in columnar CsI layers. CsI samples of different types and thicknesses were obtained from the same manufacturer. They were optimized either for light output (HL) or image resolution (HR), and the thickness ranged between 150 and 600 microns. During experimental measurements, the CsI samples were placed in direct contact with a high resolution CMOS optical sensor with a pixel pitch of 48 microns. The modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) of the detector with different CsI configurations were measured experimentally. The aperture function of the CMOS sensor was determined separately in order to estimate the MTF of CsI alone. We also measured the pulse height distribution of the light output from both the HL and HR CsI at different x-ray energies, from which the x-ray quantum efficiency, Swank factor and x-ray conversion gain were determined. Our results showed that the MTF at 5 cycles/mm for the HR type was 50% higher than for the HL. However, the HR layer produces approximately 36% less light output. The Swank factor below K-edge was 0.91 and 0.93 for the HR and HL types, respectively, thus their DQE(0) were essentially identical. The presampling MTF decreased as a function of thickness L. The universal MTF, i.e., MTF plotted as a function of the product of spatial frequency f and CsI thickness L, increased as a function of L. This indicates that the light channeling process in CsI improved the MTF of thicker layers more significantly than for the thinner ones.

Algorithms↗
PubMed2004

Intracellular viral processing, not single-stranded DNA accumulation, is crucial for recombinant adeno-associated virus transduction.

Adeno-associated virus (AAV) is a unique gene transfer vector which takes approximately 4 to 6 weeks to reach its expression plateau. The mechanism for this slow-rise expression profile was proposed to be inefficient second-strand DNA synthesis from the input single-stranded (ss) DNA viral genome. In order to clarify the status of ss AAV genomes, we generated AAV vectors labeled with bromodeoxyuridine (BrdU), a nucleotide analog that can be incorporated into the AAV genome and packaged into infectious virions. Since BrdU-DNA can be detected only by an anti-BrdU antibody when DNA is in an ss form, not in a double-stranded (ds) form, ss AAV genomes with BrdU can be readily tracked in situ. Although ss AAV DNA was abundant by Southern blot analysis, free ss AAV genomes were not detectable after AAV transduction by this new detection method. Further Southern blot analysis of viral DNA and virions revealed that ss AAV DNA was protected within virions. Extracted cellular fractions demonstrated that viral particles in host cells remained infectious. In addition, a significant amount of AAV genomes was degraded after AAV transduction. Therefore, we conclude that the amount of free ss DNA is not abundant during AAV transduction. AAV transduction is limited by the steps that affect AAV ss DNA release (i.e., uncoating) before second-strand DNA synthesis can occur. AAV ss DNA released from viral uncoating is either converted into ds DNA efficiently or degraded by cellular DNA repair mechanisms as damaged DNA. This study elucidates a mechanism that can be exploited to develop new strategies to improve AAV vector transduction efficiency.

Bromodeoxyuridine↗
PubMed2004

A fast algorithm for functional mapping of complex traits.

By integrating the underlying developmental mechanisms for the phenotypic formation of traits into a mapping framework, functional mapping has emerged as an important statistical approach for mapping complex traits. In this note, we explore the feasibility of using the simplex algorithm as an alternative to solve the mixture-based likelihood for functional mapping of complex traits. The results from the simplex algorithm are consistent with those from the traditional EM algorithm, but the simplex algorithm has considerably reduced computational times. Moreover, because of its nonderivative nature and easy implementation with current software, the simplex algorithm enjoys an advantage over the EM algorithm in the dynamic modeling and analysis of complex traits.

Algorithms↗
PubMed2004

A unified statistical model for functional mapping of environment-dependent genetic expression and genotype x environment interactions for ontogenetic development.

The effects of quantitative trait loci (QTL) on phenotypic development may depend on the environment (QTL x environment interaction), other QTL (genetic epistasis), or both. In this article, we present a new statistical model for characterizing specific QTL that display environment-dependent genetic expressions and genotype x environment interactions for developmental trajectories. Our model was derived within the maximum-likelihood-based mixture model framework, incorporated by biologically meaningful growth equations and environment-dependent genetic effects of QTL, and implemented with the EM algorithm. With this model, we can characterize the dynamic patterns of genetic effects of QTL governing growth curves and estimate the global effect of the underlying QTL during the course of growth and development. In a real example with rice, our model has successfully detected several QTL that produce differences in their genetic expression between two contrasting environments. These detected QTL cause significant genotype x environment interactions for some fundamental aspects of growth trajectories. The model provides the basis for deciphering the genetic architecture of trait expression adjusted to different biotic and abiotic environments and genetic relationships for growth rates and the timing of life-history events for any organism.

Chromosome Mapping↗
PubMed2004

[Effect of ventilation tube insertion on otitis media with effusion in cleft palate children].

OBJECTIVE: To explore the effect of eardrum tubing in the repair of cleft palate on alleviating the otitis media with effusion (OME) and hearing loss in cleft palate patients. METHODS: Nineteen ears of 19 cleft palate children with OME and hearing loss were treated with the ventilation tube insertion in the repair of the cleft palates, while the untreated opposite ears were selected as the control group. All patients were followed up from 2 weeks to 18 months postoperatively and their middle ear condition and hearing thresholds were reevaluated by otoscopy and pure-tone audiometry. RESULTS: Significant differences were found in the incidences of hearing loss between pre and postoperative patients in treated ears, and there are no differences in the untreated ears. Postoperative hearing thresholds become lower than that before the operation and no serious complications were found in the treated ears. CONCLUSIONS: The ventilation tube insertion in medial ear is safe and effective to restore the hearing impaired by OME in the cleft palate patients. It can be used as a regular management for OME and hearing loss in cleft palate children.

Child↗
PubMed2004

Expression and self-assembly of HCV structural proteins into virus-like particles and their immunogenicity.

BACKGROUND: The synthesis of virus-like particles (VLPs) provides an important tool to determine the structural requirements for viral particle assembly and virus-host interactions. Our purpose was to express simultaneously all three structural proteins of hepatitis C virus (HCV) in insect cells to investigate the proteins assembly into VLPs and the immunogenicity of these particles. METHODS: HCV gene sequences encoding the structural proteins C, E1, and E2 were amplified with PCR, and recombinant baculoviruses were constructed using recombinant DNA techniques. The expression of HCV structural proteins in insect cells was analyzed by immunofluorescence and SDS-PAGE. The interaction of expressed structural proteins was investigated by immunoprecipitation and immunoblotting. The VLPs in the insect cells were visualized by electron microscopy (EM). VLPs were then purified by sucrose gradient centrifugation and used to immunize BALB/c mice. Antibodies against HCV were tested for in mouse serum samples by an ELISA assay. RESULTS: The recombinant baculoviruses reBV/C and reBV/E1-E2 were constructed successfully. Insect cells co-infected with reBV/C and reBV/E1-E2 expressed HCV C, E1, and E2 proteins with the expected molecular weights of 20kD, 35kD, and 66kD, respectively. The results of immunoprecipitation and immunoblotting assays revealed the coimmunoprecipitation of C, E1, and E2 proteins, indicating association of the three structural proteins. Electron microscopy of insect cells co-infected with reBV/C and reBV/E1-E2 demonstrated spherical particles (40 to 60 nm in diameter) similar to the HCV virions from serum samples or hepatic tissue samples of HCV infected humans. The VLPs were partially purified. Antibodies to HCV were detectable in the serum of mice immunized with VLPs. CONCLUSION: HCV structural proteins simultaneously expressed in insect cells can interact with each other and assemble into HCV-like particles, which are shown to be immunogenic in mice.

Animals↗
PubMed2004

[Screening program and risk factors on pregnancy-induced hypertension syndrome].

OBJECTIVE: To study the risk factors of pregnancy-induced hypertension syndrome (PIH) and their interactions and to develop measures to prevent PIH and related obstetrical complications. METHODS: Of 3205 pregnant women, 219 cases were found to have PIH. Data were gathered through questionnaires and measurement. Non-conditional logistic regression was used to identify the risk factors of PIH. RESULTS: Single-factor logistic showed that age and family income were related to PIH. When family had history of hypertension, an increased incidence was seen. Parity and history of natural abortion increased the incidence of PIH. The risk for PIH increased significantly with factors related to heavier weight during pregnancy. Multi-factors non-conditional logistic regression showed that age (OR = 1.801, 95% CI: 1.106 - 2.934), number of natural abortion (OR = 8.955, 95% CI: 4.118 - 19.427), family history of hypertension (OR = 8.955, 95% CI: 4.118 - 19.427), weight during pregnancy (OR = 3.062, 95% CI: 1.619 - 5.905) were related to the risks of PIH. CONCLUSION: It is necessary to strengthen screening program when women with advanced age, family history of hypertension, the numbers of natural abortion, weight of pregnancy in the PIH prevention strategy.

Abortion, Spontaneous↗
PubMed2004

[A simulation facility for low temperature water surface environment].

OBJECTIVE: To simulate the water environment during floating status after astronauts returned and splashed down on the sea because of space capsule emergency in the launching stage. METHOD: Environmental temperature in the laboratory and water-temperature in the tank were auto-controlled individually according to heat charge calculation. To meet the need of maintaining the uniformity of water-temperature, the structure of the water circulation pipeline was specially designed to increase thread-conflux and laminar flow effect. RESULT: It was proved that the experimental system satisfied the requirements for medical research and evaluation by its high precision and uniformity which even exceeded the design requirements. After acceptance, its performance was further proved in the field experiment of "the medical evaluation of the soak and cold resisting garment." CONCLUSION: The equipment provides satisfactory experimental condition for medical evaluation of the space suit used in the "Shenzhou" space capsule and simulated the low-temperature water environment for studies of human reaction in the floating status and medical evaluation of relative products in the area of aerospace.

Aerospace Medicine↗
PubMed2003

Silencing effect of CpG island hypermethylation and histone modifications on O6-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer.

O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic and mutagenic O6-alkylguanine produced by alkylating agents such as chemotherapeutic agents and mutagens. Recent studies have shown that in a subset of tumors, MGMT expression is inversely linked to hypermethylation of the CpG island in the promoter region; however, how the epigenetic silencing mechanism works, as it relates to hypermethylation, was still unclear. To understand the mechanism, we examined the detailed methylation status of the whole island with bisulfite-sequencing in 19 MGMT non-expressed cancer cell lines. We found two highly methylated regions in the island. One was upstream of exon 1, including minimal promoter, and the other was downstream, including enhancer. Reporter gene assay showed that methylation of both the upstream and downstream regions suppressed luciferase activity drastically. Chromatin immunoprecipitation assay revealed that histone H3 lysine 9 was hypermethylated throughout the island in the MGMT negative line, whereas acetylation on H3 and H4 and methylation on H3 lysine 4 were at significantly high levels outside the minimal promoter in the MGMT-expressed line. Furthermore, MeCP2 preferentially bound to the CpG-methylated island in the MGMT negative line. Given these results, we propose a model for gene silencing of MGMT that is dependent on the epigenetic state in cancer.

CpG Islands↗
PubMed2003

Synthesis of two heptasaccharide analogues of the lentinan repeating unit.

beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)]-beta-D-Glcp (18) and the allyl glycoside of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)[-beta-D-Glcp-(1-->6)]-alpha-D-Glcp (29) were synthesized as the analogues of the lentinan repeating heptaose by building the pentasaccharide backbones first, followed by attaching the side chains. 4,6-O-benzylidenated mono-13 or disaccharide 8 were used as the acceptor to ensure the beta linkage in the synthesis of 18, while 4,6-O-benzylidenated disaccharides 21 and 23 were used as the donor and acceptor, respectively, to ensure the beta linkage in the synthesis of 29.

Adjuvants, Immunologic↗
PubMed2003

Loss of CpG methylation is strongly correlated with loss of histone H3 lysine 9 methylation at DMR-LIT1 in patients with Beckwith-Wiedemann syndrome.

To clarify the chromatin-based imprinting mechanism of the p57(KIP2)/LIT1 subdomain at chromosome 11p15.5 and the mouse ortholog at chromosome 7F5, we investigated the histone-modification status at a differentially CpG methylated region of Lit1/LIT1 (DMR-Lit1/LIT1), which is an imprinting control region for the subdomain and is demethylated in half of patients with Beckwith-Wiedemann syndrome (BWS). Chromatin-immunoprecipitation assays revealed that, in both species, DMR-Lit1/LIT1 with the CpG-methylated, maternally derived inactive allele showed histone H3 Lys9 methylation, whereas the CpG-unmethylated, paternally active allele was acetylated on histone H3/H4 and methylated on H3 Lys4. We have also investigated the relationship between CpG methylation and histone H3 Lys9 methylation at DMR-LIT1 in patients with BWS. In a normal individual and in patients with BWS with normal DMR-LIT1 methylation, histone H3 Lys9 methylation was detected on the maternal allele; however, it disappeared completely in the patients with the DMR-LIT1 imprinting defect. These findings suggest that the histone-modification status at DMR-Lit1/LIT1 plays an important role in imprinting control within the subdomain and that loss of histone H3 Lys9 methylation, together with CpG demethylation on the maternal allele, may lead to the BWS phenotype.

Base Sequence↗
PubMed2003

Functional mapping for quantitative trait loci governing growth rates: a parametric model.

Are there-specific quantitative trait loci (QTL) governing growth rates in biology? This is emerging as an exciting but challenging question for contemporary developmental biology, evolutionary biology, and plant and animal breeding. In this article, we present a new statistical model for mapping QTL underlying age-specific growth rates. This model is based on the mechanistic relationship between growth rates and ages established by a variety of mathematical functions. A maximum likelihood approach, implemented with the EM algorithm, is developed to provide the estimates of QTL position, growth parameters characterized by QTL effects, and residual variances and covariances. Based on our model, a number of biologically important hypotheses can be formulated concerning the genetic basis of growth. We use forest trees as an example to demonstrate the power of our model, in which a QTL for stem growth diameter growth rates is successfully mapped to a linkage group constructed from polymorphic markers. The implications of the new model are discussed.

Age Factors↗
PubMed2003

BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas.

Colorectal cancer is believed to progress through an adenoma-carcinoma sequence. However, recent evidence increasingly supports the existence of an alternative route for colorectal carcinogenesis through serrated polyps, a group that encompasses a morphological spectrum, including hyperplastic polyp (HP), admixed hyperplastic polyp/adenoma (HP/AD), and serrated adenoma (SA; the latter two manifest epithelial dysplasia). We have studied a large series of serrated polyps for BRAF and KRAS mutations. BRAF mutations were detected in 18 of 50 (36%) HPs, 2 of 10 (20%) HP/ADs, and 9 of 9 (100%) SAs. Twenty-six of 29 mutations caused amino acid substitutions at valine 599, the known hotspot. KRAS mutations were detected in 9 of 50 (18%) HPs, 6 of 10 (60%) HP/ADs, and 0 of 9 (0%) SAs. BRAF and KRAS mutations are mutually exclusive (P = 0.001). The associations of BRAF mutations with SAs (P < 0.001) and KRAS mutations with HP/ADs (P = 0.005) are statistically significant. A majority (90%) of the serrated polyps showing dysplasia had mutations in either BRAF or KRAS, significantly different from those without dysplasia (54%; P = 0.014). Our data highlight the important role of activation of the RAS-RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase-mitogen-activated protein kinase pathway in the initiation and progression of serrated neoplasms. Acquisition of a BRAF mutation appears to be associated with the progression of HP to SA, whereas progression to HP/AD is predominantly associated with acquisition of a KRAS mutation. The high incidence of BRAF mutations in HPs and SAs is consistent with the notion that the group of colorectal cancers carrying BRAF mutations may harbor most that have progressed through the HP-SA-carcinoma pathway.

Adenoma↗
PubMed2003

Efficient photoinduced conversion of an azo dye on hexachloroplatinate(IV)-modified TiO2 surfaces under visible light irradiation-A photosensitization pathway.

The titanium dioxide photocatalyst is employed to examine the influence of chemisorbed hexachloroplatinate(IV) anions (PtCl(6) (2-)) on the surface of P-25 TiO(2) particles on the photoinduced conversion of the azo dye Ethyl Orange (EO) in visible light-illuminated Pt(IV)/TiO(2) dispersions. Spin-trap electron spin resonance (ESR) spectral results, measurement of quantities of organoperoxides formed, total organic carbon (TOC) and chemical oxygen demand (COD(Cr)) assays, together with XPS evidence show that the self-sensitized transformation dynamics of the EO dye mediated by Pt(IV)/TiO(2) are much faster than those occurring on naked TiO(2) under otherwise identical conditions of visible light irradiation. X-ray photoelectron spectral data also show that under the experimental conditions used, no Pt(0) formed on the titania particles during visible light irradiation. We propose a reaction mechanism in which the more rapid conversion of EO in the presence of PtCl(6) (2-) is caused principally by photoexcitation of the dye and not by localized excitation of the tetrachloroplatinate(IV)/TiO(2) particles.

Journal Article↗