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Z Wang

Publications and source records attributed to Z Wang.

At least 91 records · Page 5Linked to original sources
PubMed2004

Quasiparticle line shape of Sr2RuO4 and its relation to anisotropic transport.

The bulk-representative low-energy spectrum of Sr2RuO4 can be directly measured by angle-resolved photoemission. We find that the quasiparticle spectral line shape of Sr2RuO4 is sensitive to both temperature and momentum. Along the (0,0)-(pi,0) direction, both gamma and beta bands develop a sharp quasiparticle peak near k(F) at low temperatures, but as the temperature increases the spectra quickly lose coherent weight and become broad backgrounds above approximately 130 K, which is the metal-nonmetal crossover temperature, T(M), in the c-axis resistivity. However, spectra along the (0,0)-(pi,pi) direction evolve smoothly across T(M). A simple transport model can describe both in-plane and c-axis resistivity in terms of the quasiparticle line shape. Comparisons are also made to the cuprates, with implications for two dimensionality, magnetic fluctuations, and superconductivity.

Journal Article↗
PubMed2004

beta2-integrins mediate a novel form of chemoresistance in cycloheximide-induced U937 apoptosis.

In this study with cycloheximide (CHX, an inhibitor of protein synthesis) and the human leukaemic cell line U937, a novel form of chemoresistance, which we termed sudden drug resistance (SDR), was identified using Hoechst33258 staining, Western blot and DNA Ladder. CHXhigh (10-100 microg/ml)-induced apoptosis can spontaneously subside after 4-6 h or can be inhibited by short-term preincubation with CHXlow (2.5 microg/ml). Unlike typical multidrug resistance, SDR is not caused by reduced drug accumulation or altered protein expression, and may be associated with a non-P-glycoprotein mechanism. To uncover this underlying mechanism, we focused on U937 cell aggregation promoted by CHX, because cell adhesion has been suggested to influence cell survival and prevent apoptosis. EDTA, or anti-CD18 monoclonal antibody, but not EGTA, acetylsalicylic acid or RGDS tetrapeptide, abrogated this homotypic aggregation and greatly increased CHX-induced apoptosis in a time-dependent manner, while fibrinogen and soluble intercellular adhesion molecule-1 exerted opposite effects. These results establish that beta2-integrin engagement is a key mediator of SDR, although it may be non-exclusive. This finding supplements the classical basis of chemoresistance and may provide another opportunity for improved leukemia therapy.

Apoptosis↗
PubMed2004

Observation of A2E oxidation products in human retinal lipofuscin.

Several retinal dystrophies are associated with the accumulation of lipofuscin in the retinal pigment epithelium (RPE). The only structurally characterized component of human retinal lipofuscin is the bis-retinoid pyridinium compound A2E. We report here on the observation of a monooxygenated product of A2E in the organic soluble portion of human retinal lipofuscin and in the organic extract of bovine RPE cells that have been fed A2E and irradiated. Liquid chromatography mass spectrometry confirms that the products are identical. This is the first observation of a photoproduct of A2E in human retinal lipofuscin.

Animals↗
PubMed2004

A mechanistic study of the photooxidation of A2E, a component of human retinal lipofuscin.

A major constituent of human retinal lipofuscin is A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-hexatrienyl]-pyridinium). Light transmitted by the lens is absorbed by A2E and the processes initiated by this absorption has been implicated in several maculopothies. The purpose of this study was to evaluate the dominant photochemical mechanisms involved in these reactions, whether through free radical or singlet oxygen intermediacy. The photodestruction of A2E occurs faster in water vs. chloroform and hydrogenated vs. perdeuterated methanol. Both results suggest a free radical mechanism. Product distributions indicate sequential oxygen addition rather than the addition of two oxygen atoms which would be expected if singlet oxygen was an intermediate. Finally, EPR trapping studies lead to the detection of superoxide as the primary intermediate in the photochemical reactions. It is concluded that if singlet oxygen is involved in these photochemical processes it is of minor importance.

Free Radicals↗
PubMed2004

The photochemical oxidation of A2E results in the formation of a 5,8,5',8'-bis-furanoid oxide.

With age and certain diseases, the retinal pigment epithelium (RPE) accumulates a complex mixture of fluorophores generally called lipofuscin. This mixture has been implicated in those diseases via several possible mechanisms including photochemically mediated damage and detergent effects. Recently, a component of that mixture has been identified, a bis-retinoid pyridinium compound called A2E. Furthermore, the photolysis of this compound has been shown to lead to a series of photooxidation products each differing by 16 amu; with the addition of up to a total of nine oxygen atoms to A2E. It has been suggested that these products consist of a series of epoxides forming along the acyclic side chains. The present study reinvestigates this hypothesis and demonstrates that the bis-oxygenated product is in fact a relatively stable 5-8 5'-8'-bis-furanoid oxide. This is in agreement with the oxidation products observed for a homologue of A2E, beta-carotene. In addition, it was found that the bis-oxygenated photoproduct of A2E contained a mixture of symmetrical and unsymmetrical oxidized products where the second oxygen was present in the cyclohexenyl ring structure in the unsymmetrical product. Most importantly, both of these oxidation products of A2E were detected in lipofuscin extracts from human RPE cells, suggesting that these processes occur in vivo.

Furans↗
PubMed2004

Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain.

Several experimental models of peripheral neuropathy show that a significant upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a common consequence of nerve injury. A genetically modified mouse strain lacking prodynorphin does not exhibit sustained neuropathic pain after nerve injury, supporting a pronociceptive role of elevated levels of spinal dynorphin. A null mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of neuropathic pain following peripheral nerve injury. The objective of this study was to extend our observations to these genetic models to test the hypothesis that elevated levels of spinal dynorphin are essential for the maintenance of abnormal pain. In PKCgamma wild-type mice and the outbred mouse strain ICR, ligation of the L5 and L6 spinal nerves (SNL) elicited both tactile hypersensitivity and thermal hyperalgesia. Both strains showed a significant elevation in dynorphin in the lumbar spinal dorsal horn following SNL. Spinal administration of an anti-dynorphin A antiserum blocked the thermal and tactile hypersensitivity in both strains of mice. However, the PKCgamma KO mice and the 129S6 mice (which express PKCgamma) did not show abnormal pain after SNL; neither strain showed elevated levels of spinal dynorphin. The multiple phenotypic deficits in PKCgamma KO mice confound the interpretation of the proposed role of PKCgamma-expressing spinal neurons in neuropathic pain states. Additionally, the data show that the regulation of spinal dynorphin expression is a common critical feature of expression of neuropathic pain.

Animals↗
PubMed2004

Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-ad antibodies.

Recombinant adenoviruses are one of the most common gene transfer vectors utilized in human clinical trials, but it is also clear that systemic administration of this virus will be met by host innate and adaptive antiviral immune responses. One element of innate immunity is the complement system, a group of proteins that has evolved to rapidly recognize foreign microbes and viruses and to clear them from the circulatory system prior to their gaining entry to vulnerable host cells. Excessive complement activation can initiate or propagate a number of deleterious inflammatory responses, by release of potent cytokines and anaphylatoxins and/or by direct cellular toxicity. These reactions can progress rapidly and are factors important in serious complications, including the systemic inflammatory response syndrome and the adult respiratory distress syndrome.

Adenoviridae↗
PubMed2004

Waist circumference, body mass index, hip circumference and waist-to-hip ratio as predictors of cardiovascular disease in Aboriginal people.

OBJECTIVE: To investigate waist circumference (WC), waist-hip ratio, hip circumference and body mass index (BMI) as risk factors for cardiovascular disease in Aboriginal Australians. METHODS: This cohort study included 836 adults aged 20-74 y in a remote Aboriginal community. WC, waist-hip ratio, hip circumference and BMI were obtained from a screening program. The participants were followed for up to 10 y for cardiovascular events. A Cox regression model was used to calculate the rate ratio (RR) and 95% confidence interval (CI) for the first-ever cardiovascular event (fatal and nonfatal). RESULTS: RRs for the first-ever cardiovascular event were 1.31 (95% CI: 1.11, 1.54), 1.29 (95% CI: 1.09,1.53), 1.28 (95% CI: 1.08, 1.52) and 1.10 (95% CI: 0.93, 1.30) per standard deviation increase in WC, BMI, hip circumference and waist-hip ratio, respectively, after adjustment for diabetes mellitus, total cholesterol, systolic blood pressure and smoking status. WC, BMI and hip circumference were significantly associated with cardiovascular risk, independent of other cardiovascular risk factors. Dividing each of the four parameters into quartiles, WC had the highest likelihood statistics (12.76) followed by BMI (11.45), hip circumference (10.57) and waist-hip ratio (3.15) for predicting first CV events. CONCLUSION: WC, BMI and hip circumference are associated with cardiovascular outcome, independent of traditional risk factors. However, WC appears to be a better predictor for cardiovascular risk than other parameters. Waist-hip ratio is not as useful as other measurements.

Adult↗
PubMed2004

Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation.

Plasmid vectors have been widely used for DNA vaccines and gene therapy. Following intramuscular injection, the plasmid that persists is extrachromosomal and integration into host DNA, if it occurs at all, is negligible. However, new technologies for improving DNA delivery could increase the frequency of integration. In the present study, we tested the effect of electroporation on plasmid uptake and potential integration following intramuscular injection in mice, using a plasmid containing the mouse erythropoietin gene. Electroporation increased plasmid tissue levels by approximately six- to 34-fold. Using a quantitative gel-purification assay for integration, electroporation was found to markedly increase the level of plasmid associated with high-molecular-weight genomic DNA. To confirm integration and identify the insertion sites, we developed a new assay - referred to as repeat-anchored integration capture (RAIC) PCR - that is capable of detecting rare integration events in a complex mixture in vivo. Using this assay, we identified four independent integration events. Sequencing of the insertion sites suggested a random integration process, but with short segments of homology between the vector breakpoint and the insertion site in three of the four cases. This is the first definitive demonstration of integration of plasmid DNA into genomic DNA following injection in vivo.

Animals↗
PubMed2004

Body size measurements as predictors of type 2 diabetes in Aboriginal people.

OBJECTIVE: To investigate waist circumference, waist-to-hip ratio, body mass index (BMI), weight and hip circumference as risk factors for type 2 diabetes in Aboriginal Australians. DESIGN: Community-based cross-sectional study. SUBJECTS: In total, 915 Australian Aboriginal adults (age: 18-74 y) from a remote Aboriginal community in the Northern Territory of Australia. MEASUREMENTS: Body size measurements included waist circumference, waist-to-hip ratio, BMI, weight and hip circumference. Diabetes status was determined according to medical history and fasting and 2-h postload plasma glucose values. Logistic regression was used to calculate odds ratio for diabetes associated with 1 standard deviation (s.d.) increase in a body size measurement. The areas under the ROC curves of five body size measurements were calculated and compared. RESULTS: Risk of diabetes increased with increasing levels of body size. ORs (95% CI) for diabetes with adjustment for age and sex were 2.16 (1.75, 2.66), 1.80 (1.49, 2.17), 1.41 (1.17, 1.71), 1.81 (1.51, 2.19) and 1.84 (1.50, 2.24) associated with 1 s.d. increase in waist circumference, BMI, weight, waist-to-hip ratio, and hip circumference, respectively. The area under the ROC curve for waist circumference was significantly higher than those for other measurements. CONCLUSION: Waist circumference is the best body size measurement in predicting diabetes in Aboriginal people.

Adolescent↗
PubMed2004

Baseline Na-Li countertransport and risk of hypertension in children: a 10-year prospective study in Hanzhong children.

Sodium-lithium countertransport (Na-Li CT) is associated with blood pressure (BP) and in many cross-sectional investigations and some longitudinal studies, essential hypertension has been proposed as a biochemical marker or predictor of hypertension risk in adults. The present study investigated prospectively whether baseline Na-Li CT rate was an index of increased risk of future development of hypertension in children. At baseline visit in 1987 of the Hanzhong Children Hypertension Study comprising 4000 school children aged 5-6 years old, 310 samples were randomly selected for measurement of baseline Na-Li CT rate; we made a 10-year follow-up of them in the same season in 1997. This cohort of children is the sample for analysis in the present report. Baseline Na-Li CT rate was positively correlated to systolic BP (SBP) both in baseline and follow-up (baseline, gamma=0.21, P<0.05; follow-up, gamma=0.32, P<0.01), and positively correlated to diastolic BP (DBP) (gamma=0.20, P<0.05) and body mass index (gamma=0.18, P<0.05) in follow-up examination. Longitudinal analysis of 10-year BP evolution, children in higher baseline Na-Li CT (ie, >260 micromoll RBC/h) had greater BP change than children in lower baseline Na-Li CT (ie, </=260 mumol/l RBC/h) (SBP, 15.8+/-12.9 vs 19.3+/-13.1, DBP 8.8+/-11.2 and 11.3+/-10.6, P<0.05). Multiple logistic regression analysis showed that children in the higher Na-Li CT (>260 mumol/l RBC/h) were associated with approximately 1.5 times greater risk of high BP) in comparison to placement in lower Na-Li CT (</=260 mumol/l RBC/h). Elevated baeline RBC Na-Li countertransport could be a risk predictor predisposing to the development of hypertension in children.

Antiporters↗
PubMed2004

A statistical model for functional mapping of quantitative trait loci regulating drug response.

Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

Algorithms↗
PubMed2004

Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.

Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal recessive trait. In this study, we reported a Chinese family with hereditary prothrombin deficiency. The proposita had a prolonged activated partial thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The coagulation factors activities were normal except that prothrombin coagulation activity was markedly reduced, and the prothrombin antigen level was moderately decreased. Nucleotide sequencing of amplified DNA revealed a novel mutation, Glu (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation within the Gla domain of prothrombin. The proposita was identified as homozygous, while her father, mother and maternal grandmother were heterozygous for the mutation. Gla29 has been demonstrated as one of the key residue for Ca2+-binding, membrane interaction and biological activity of prothrombin.

Amino Acid Substitution↗
PubMed2004

Copasetic analysis: a framework for the blind analysis of microarray imagery.

From its conception, bioinformatics has been a multidisciplinary field which blends domain expert knowledge with new and existing processing techniques, all of which are focused on a common goal. Typically, these techniques have focused on the direct analysis of raw microarray image data. Unfortunately, this fails to utilise the image's full potential and in practice, this results in the lab technician having to guide the analysis algorithms. This paper presents a dynamic framework that aims to automate the process of microarray image analysis using a variety of techniques. An overview of the entire framework process is presented, the robustness of which is challenged throughout with a selection of real examples containing varying degrees of noise. The results show the potential of the proposed framework in its ability to determine slide layout accurately and perform analysis without prior structural knowledge. The algorithm achieves approximately, a 1 to 3 dB improved peak signal-to-noise ratio compared to conventional processing techniques like those implemented in GenePix when used by a trained operator. As far as the authors are aware, this is the first time such a comprehensive framework concept has been directly applied to the area of microarray image analysis.

Artificial Intelligence↗
PubMed2004

Differences in the metabolism and pharmacokinetics of two structurally similar PPAR agonists in dogs: involvement of taurine conjugation.

1. The metabolism and pharmacokinetics of two structurally similar PPAR agonists, MRL-I, (2R)-7-[3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy]-2-ethyl-3,4-dihydro-2H-benzopyran-2-carboxylic acid, and MRL-II, (2R)-7-[3-[2-chloro-4-(2,2,2,-trifluoroethoxy)phenoxy]propoxy]-3,4-dihydro-2-methyl-2H-benzopyran-2-carboxylic acid, in dogs were investigated. 2. MRL-I was absorbed rapidly in dogs and exhibited linear pharmacokinetics over the dose range examined, 1-25mgkg(-1). In contrast, the pharmacokinetics of MRL-II were non-linear following both intravenous and oral administration. 3. The acyl glucuronide (AG) conjugate was the only radioactive component detected in bile from dogs dosed with [14C]MRL-I, whereas bile from dogs dosed with [14C]MRL-II contained varying amounts of both the AG and taurine conjugates. The percentages of the acyl glucuronide and taurine conjugates of [14C]MRL-II in dog bile were dose dependent. A higher percentage of radioactivity was associated with the taurine conjugate (about 41%) following intravenous administration at 0.2mgkg(-1) than at 0.9mgkg(-1) (about 14%) or oral administration at 5 mgkg(-1) (about 6%). The decrease in the percentage of radioactivity associated with the taurine conjugate at 0.9 mgkg(-1) was accompanied by a concomitant increase in the amount of the acyl glucuronide. 4. MRL-I, but not MRL-II, was subject to significant enterohepatic recirculation in dogs. Continuous collection of bile resulted in an 11-fold decrease in the terminal half-life of MRL-I in plasma (1.5 versus 16.6 h), and a 2.4-fold increase in its plasma clearance (4.0 versus 1.7 ml min(-1) kg(-1)) after intravenous administration at 1 mg kg(-1). 5. Collectively, the data suggest that the presence and subsequent saturation of the taurine conjugation pathway might have contributed to the non-linear pharmacokinetics of MRL-II in the dog.

Administration, Oral↗
PubMed2004

Efficient depletion of alveolar macrophages using intratracheally inhaled aerosols of liposome-encapsulated clodronate.

Rat alveolar macrophages (AMs) were depleted via intratracheal inhalation (ITIH) of clodronate-containing liposomes. AM depletion following ITIH delivery of clodronate liposomes was 33.2 +/- 14.2 on day 1, 88.1 +/- 6.2 on day 3, and 91.4 +/- 1.8 on day 4 relative to control rats given saline-containing liposomes. Almost all (approximately 99%) of the AMs remaining at the 3-day time point were peroxidase negative, suggesting that immature macrophages were not recruited from the circulation to replace those undergoing cell death on that day. Only 0.5% +/- 0.5% of bronchoalveolar lavage (BAL) cells were neutrophils at this time (normalized to controls). Whole-body inhalation did not induce as much AM depletion at 3 days (37.6% +/- 10.1%) and required larger amounts of liposome-encapsulated clodronate compared to ITIH. Intratracheal instillation (as opposed to inhalation) of clodronate liposomes produced a significant inflammatory response characterized by the influx of both polymorphonuclear neutrophils (PMNs) and macrophages. In subsequent pilot studies, the response to intratracheally instilled crystalline silica (75 microg) was found to be markedly reduced in rats depleted of AMs by the ITIH method. We conclude that ITIH of clodronate liposomes in rats is both efficient and useful for examining the role of AMs in pulmonary toxicology.

Administration, Inhalation↗
PubMed2004

Estimation of growth parameters using a nonlinear mixed Gompertz model.

In order to maximize the utility of simulation models for decision making, accurate estimation of growth parameters and associated variances is crucial. A mixed Gompertz growth model was used to account for between-bird variation and heterogeneous variance. The mixed model had several advantages over the fixed effects model. The mixed model partitioned BW variation into between- and within-bird variation, and the covariance structure assumed with the random effect accounted for part of the BW correlation across ages in the same individual. The amount of residual variance decreased by over 55% with the mixed model. The mixed model reduced estimation biases that resulted from selective sampling. For analysis of longitudinal growth data, the mixed effects growth model is recommended.

Aging↗