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Zheng Wang

Publications and source records attributed to Zheng Wang.

At least 55 records · Page 3Linked to original sources
PubMed2006

HOXB4 inhibits cell growth in a dose-dependent manner and sensitizes cells towards extrinsic cues.

Ectopic expression of the homeodomain transcription factor HOXB4 expands hematopoietic stem and progenitor cells in vivo and in vitro, making HOXB4 a highly interesting candidate for therapeutic stem cell expansion. However, when expressed at high levels, HOXB4 concomitantly perturbs differentiation and thus likely predisposes the manipulated cells for leukemogenesis. We therefore asked whether the expression level of HOXB4 may be a critical parameter that influences the growth and transformation properties of transduced cells. Using a set of retroviral vectors which covered a 40-fold range of expression levels, we studied the consequences of HOXB4 expression at different levels in the well established Rat-1 fibroblast cell system. HOXB4 transformed Rat-1 fibroblasts beyond a certain threshold level of expression. Further escalation of HOXB4 expression, however, did not enhance transformation. Instead, HOXB4 mediated a dose dependent anti-proliferative effect on Rat-1 and NIH3T3 fibroblasts. This effect was aggravated under reduced serum concentrations and was, at least partially, due to an enhanced sensitivity of HOXB4 overexpressing cells to induction of apoptosis. Based on these results we propose that HOXB4 affects cell growth in a dose-dependent manner by sensitizing cells towards extrinsic signals.

Animals↗
PubMed2006

Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.

OBJECTIVES: Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung. DESIGN: Observational clinical study. SETTING: Academic university hospital and laboratory. PATIENTS: Twenty-one patients with acute pulmonary edema plus ex vivo human lungs. INTERVENTIONS: Measurements of catecholamine levels in patient samples and controlled laboratory studies of the effects of these catecholamine levels on the rates of alveolar fluid clearance in ex vivo human lungs. MEASUREMENTS AND MAIN RESULTS: The concentrations of both epinephrine and norepinephrine in the pulmonary edema fluid and plasma were approximately 10 M (range of 1-8x10 M) in hydrostatic pulmonary edema (n=6) and acute lung injury patients (n=15). We therefore tested whether 10 M epinephrine or norepinephrine stimulated alveolar fluid clearance in isolated human lungs and found that these epinephrine or norepinephrine concentrations did not stimulate alveolar fluid clearance. However, higher concentrations of epinephrine (10 M), but not norepinephrine (10 M), significantly stimulated alveolar fluid clearance by 84% above control. Glibenclamide (10 M) and CFTRinh-172 (10 M), cystic fibrosis transmembrane conductance regulator inhibitors, completely inhibited the epinephrine-induced stimulation of alveolar fluid clearance. CONCLUSIONS: These results indicate that endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by cystic fibrosis transmembrane conductance regulator. Therefore, exogenous cyclic adenosine monophosphate-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema.

Adrenergic beta-Agonists↗
PubMed2006

Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.

OBJECTIVE: The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance. METHODS: Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H(2)O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl(-) channel inhibitors (glibenclamide and CFTR(inh)-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs. RESULTS: Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTR(inh)-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance. CONCLUSION: CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.

Adrenergic beta-Agonists↗
PubMed2006

D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure.

Activation of D1-like receptors (D1 and/or D5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D5 receptor-deficient (D5-/-) and wild-type (D5+/+) mice. NADPH oxidase protein expression (gp91(phox), p47(phox), and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D5-/- than in D5+/+ mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D5-/- mice. In HEK-293 cells that heterologously expressed human D5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91(phox)), and ROS production. The inhibitory effect of the D5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D5 receptor activation.

Animals↗
PubMed2006

Evaluation of apolipoprotein A1 and posttranslationally modified forms of transthyretin as biomarkers for ovarian cancer detection in an independent study population.

BACKGROUND: Although overall 5-year survival rates for ovarian cancer are poor (10-30%), stage I/IIa patients have a 95% 5-year survival. New biomarkers that improve the diagnostic performance of existing tumor markers are critically needed. A previous study by Zhang et al. reported identification and validation of three biomarkers using proteomic profiling that together improved early-stage ovarian cancer detection. METHODS: To evaluate these markers in an independent study population, postdiagnostic/pretreatment serum samples were collected from women hospitalized at the Mayo Clinic from 1980 to 1989 as part of the National Cancer Institute Immunodiagnostic Serum Bank. Sera from 42 women with ovarian cancer, 65 with benign tumors, and 76 with digestive diseases were included in this study. Levels of various posttranslationally forms of transthyretin and apolipoprotein A1 were measured in addition to CA125. RESULTS: Mean levels of five of the six forms of transthyretin were significantly lower in cases than in controls. The specificity of a model including transthyretin and apolipoprotein A1 alone was high [96.5%; 95% confidence interval (95% CI), 91.9-98.8%] but sensitivity was low (52.4%; 95% CI, 36.4-68.0%). A class prediction algorithm using all seven markers, CA125, and age maintained high specificity (94.3%; 95% CI, 89.1-97.5%) but had higher sensitivity (78.6%; 95% CI, 63.2-89.7%). CONCLUSIONS: We were able to replicate the findings reported by Zhang et al. in an independently conducted blinded study. These results provide some evidence that including age of patient and these markers in a model may improve specificity, especially when CA125 levels are >/=35 units/mL. Influences of sample handling, subject characteristics, and other covariates on biomarker levels require further consideration in discovery and replication or validation studies.

Adolescent↗
PubMed2006

PKC isoform-specific enhancement of capacitative calcium entry in human corneal epithelial cells.

PURPOSE: To determine in human corneal epithelial cells (HCECs) the role of protein kinase C (PKC) in mediating epidermal growth factor (EGF)-induced stimulation of store-operated channel (SOC) activity and capacitative calcium entry (CCE). METHODS: Single-cell Ca2+ fluorescence imaging of fura2-loaded HCECs was used to evaluate CCE. PKC translocation induced by EGF or PDBu was monitored by Western blot analyses of four different subcellular fractions. Plasma membrane Ca2+ influx was measured by Mn2+ quench rates of fura2-fluorescence. The whole-cell patch clamp configuration was used to determine the SOC activation induced by EGF. RESULTS: EGF-induced increases in SOC currents through PKC stimulation, since calphostin C inhibited this response. To determine which PKC isoforms mediated EGF-induced increases in CCE, the PKC isoform enrichment of a plasma membrane-containing fraction was determined. From 5 to 30 minutes, its rank order of enrichment was: delta > betaI > alpha approximately epsilon. Preferential PKCdelta and PKCbeta translocation was in accordance with other results showing that rottlerin and hispidin have the highest efficacy in suppressing EGF-induced CCE augmentation. Furthermore, after PKCbeta and PKCdelta siRNA knockdown of gene and protein expression, declines in EGF-induced increases in CCE matched those obtained after exposure to a corresponding selective PKC isoform inhibitor. CONCLUSIONS: EGF-induced PKC stimulation in HCECs mediates SOC activation. This response contributes to CCE, which preferentially depends on PKCdelta and PKCbeta isoform stimulation. This rank order is based on the findings that either selective knockdown of their expression or exposure to PKCdelta and PKCbeta isoform inhibitors elicited the largest declines in EGF-augmented CCE.

Blotting, Western↗
PubMed2006

Phosphatase-mediated crosstalk control of ERK and p38 MAPK signaling in corneal epithelial cells.

PURPOSE: To test the hypothesis that the protein phosphatases PP2A and MKP-1 are involved in controlling epidermal growth factor (EGF)-induced increases in rabbit corneal epithelial cell (RCEC) migration by mediating crosstalk between signaling pathways eliciting EGF receptor control of migration and proliferation. METHODS: Western blot analysis was used to determine the phosphorylation status of Erk1/2, p38, and the mitogen-activated protein kinase (MAPK) kinase (MEK1/2) using inhibitors of Erk1/2 or p38 and dominant-negative (d/n) Erk1 or d/n p38 cell lines. Coimmunoprecipitation was used to evaluate protein phosphatase (PP)2A and Erk1/2 interaction. Short-interfering RNA (siRNA) transfection was performed to analyze the involvement of MAPK phosphatase (MKP)-1 in crosstalk. Scratch-wound assay was used to determine EGF-dependent effects on cell migration. RESULTS: EGF (10 ng/mL) induced changes in activation of Erk1/2 and p38, which were enhanced by inhibition with 10 microM SB203580 and 10 muM PD98059, respectively. PP inhibition with sodium orthovanadate (100 microM), okadaic acid (10 nM), or Ro 31-8220 (10 microM) resulted in larger and more prolonged increases in the phosphorylation status of Erk1/2 and p38. After 1 hour, EGF induced 14-fold increases in MKP-1 protein expression. After MKP-1 siRNA transfection, EGF had induced a similar pattern of changes in the phosphorylation status in Erk1/2 and p38 following PP inhibition. EGF-induced cell migration was enhanced by Erk1/2 pathway inhibition and was accentuated after PP inhibition. Conversely, p38 pathway inhibition eliminated this response. CONCLUSIONS: EGF-induced changes in Erk1/2 and p38 phosphorylation status are dependent on PP-mediated crosstalk. This control modulates the magnitude of growth factor-induced increases in corneal epithelial cell migration.

Animals↗
PubMed2006

Identifying influenza viruses with resequencing microarrays.

Identification of genetic variations of influenza viruses is essential for epidemic and pandemic outbreak surveillance and determination of vaccine strain selection. In this study, we combined a random amplification strategy with high-density resequencing microarray technology to demonstrate simultaneous detection and sequence-based typing of 25 geographically distributed human influenza virus strains collected in 2004 and 2005. In addition to identification, this method provided primary sequence information, which suggested that distinct lineages of influenza viruses co-circulated during the 2004-2005 season, and simultaneously identified and typed all component strains of the trivalent FluMist intranasal vaccine. The results demonstrate a novel, timely, and unbiased method for the molecular epidemiologic surveillance of influenza viruses.

Amino Acid Sequence↗
PubMed2006

[Microenvironment of positive pressure powered air purifying medical protective equipment].

OBJECTIVE: To study the filtration efficiency of a positive pressure powered air purifying medical protective equipment and the effect of the flow rate on the microenvironment of the equipment. METHODS: The filtration efficiency of high efficiency particulate air (HEPA) filter was measured with the biologic aerosol of simulating virus (Escherichia coli bacteriophage f(2)). The simulation work was done at the walk rate of 4 km/h in summer. The effect of the flow rate on the oxygen content, the carbon dioxide content, the temperature and the humidity of the microenvironment of the equipment was investigated. The clinical experiments were conducted in three appointed hospital for fighting against SARS. RESULTS: The HEPA filter could filtrate 99.99% simulating viruses in the air. When the flow rate ranged from 75 to 125 L/min, the microenvironment parameters of the equipment were: the oxygen content was between 19.6% and 20.1% (the physiological safety limit is more than 14.6%); the carbon dioxide content ranged from 0.43% to 0.57% (the physiological safety limit is less than 1.0%); the temperature was between 32.0 degrees C to 32.2 degrees C; the humidity ranged from 49.7% to 59.4% (the physiological safety limit is the temperature 31 degrees C and the humidity 85% or temperature 38 degrees C and humidity 50%). Each microenvironment parameter met the demand of a healthy person under the normal workload. In the clinical experiments, the doctors wearing the equipment who performed the tracheotomy for a SARS patient in a deep coma were not infected. CONCLUSION: The medical protective equipment can protect the doctor and nurse in SARS contaminated areas effectively and improve their work conditions.

Air↗
PubMed2006

[Viral transactivation of transcription by NF-kappaB in steroid-responsive simple nephrotic syndrome].

OBJECTIVE: To investigate the path of viral transactivation of transcription by nuclear factor-kappa B (NF-kappaB) in the pathogenesis of steroid-responsive simple nephrotic syndrome (SRSNS) triggered by respiratory tract viruses. METHODS: Children with SRSNS (including active stage, convalescent and remissive stage) were examined and were analytically compared to children with nephritic nephrosis, secondary glomerular diseases and bronchiolitis; healthy children were enrolled as controls. The methods of electrophoretic mobility shift assay (EMSA), of reverse transcription-PCR (RT-PCR), and of enzyme-linked immunosorbent assay (ELISA), were used to detect the transcriptive activity of NF-kappaB, the gene expression of respiratory tract viruses (respiratory syncytial virus-RSV, influenza virus-Flu) in peripheral blood mononuclear cells (PBMC), and the levels of IL-8 and viral antibodyies in serum, respectively. RESULTS: (1) Compared with the control and SRSNS in convalescent and remissive stage, the activity of NF-kappaB in PBMC of SRSNS in active stage was statistically elevated (P<0.05). (2)The level of IL-8 in serum of SRSNS in active stage was significantly increased, compared with healthy control (P<0.001). There was a positive linear correlation between the activity of NF-kappaB and the level of IL-8 in active stage of SRSNS, and a positive correlation trend was observed between the activity of NF-kappaB and the gene expression of respiratory tract viruses. CONCLUSION: Viral transactivation of transcription by NF-kappaB may be an important path for respiratory tract viruses triggering the pathogensis of SRSNS.

Child↗
PubMed2006

[The pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits].

OBJECTIVE: To investigate the pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits applied with eye drops or subconjunctiva injections. METHODS: 42 New Zealand albino rabbits were divided into 2 groups. (1) Nanoparticle solution containing 10 microg FK506 was injected into subconjunctiva or dropped on conjunctival sac of rabbits (68 eyes in 34 cases). (2) Eye drops containing 20 or 40 microg FK506 without nanoparticles were dropped on conjunctival sac of rabbits (16 eyes in 8 cases). Aqueous humor was collected at different times after local administration and FK506 concentrations were measured by ELISA. Ocular pharmacokinetic parameters of FK506 were calculated by 3p87 software. RESULTS: In the solution containing nanoparticle, the effective FK506 concentration in aqueous humor could be kept up to 16 h in eye drops group. The range of FK506 concentration was between (15.50 +/- 3.39) - (2.59 +/- 0.83) ng/ml. FK506 in aqueous humor can be maintained for 96 h by injecting into subconjunctiva and FK506 concentration were between (9.62 +/- 2.19) - (2.60 +/- 0.21) ng/ml from 6 - 96 h. T(max) and C(max) in eye drops were (1.25 +/- 0.50) h and (15.52 +/- 2.37) ng/ml respectively; while T(max) and C(max) in subconjunctiva injection were (64.00 +/- 13.86) h and (10.16 +/- 1.37) ng/ml respectively. Each AUC(0-->t) was (152.44 +/- 16.74) ng.ml(-1).h(-1) and (612.48 +/- 54.39) ng.ml(-1).h(-1) respectively; each Ka was 3.790 +/- 0.730 and 0.040 +/- 0.004 respectively; and each MRT was (8.20 +/- 1.28) h and (58.53 +/- 5.42) h respectively. In the eye drops containing 20 microg or 40 microg FK506 but without nanoparticles applied in conjunctival sac of rabbits, all effective FK506 concentrations in aqueous humor could not be kept over 4 h. T(max) was 1 h and C(max) was (18.93 +/- 6.95) ng/ml in 20 microg FK506, while in 40 microg FK506 T(max) was 2h and C(max) was (28.33 +/- 1.31) ng/ml. CONCLUSION: Solution with FK506 nanoparticle dropping onto the eye or injecting into subconjunctiva could be sustained in rabbit aqueous humor for a longer time than non-nanoparticle FK506 solution, while with injecting of nanoparticle FK506 solution it could be detected with a relative low but longer effective concentration.

Administration, Topical↗
PubMed2006

[G protein kinase 4gammaA142V overexpression induced hypertension by downregulating D1 receptors in transgenic mice].

OBJECTIVE: Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. We investigated the role of G protein kinase (GRK) 4gamma in essential hypertension in GRK4gamma mutant A142V transgenic mice. METHODS: Blood pressure, renal sodium excretion, D(1) receptor protein expression and phosphorylation were measured in GRK4gammaA142V transgenic mice and control mice. Moreover, the effects of GRK4 inhibition by antisense oligonucleotides on D(1) receptor expressions were determined in HK-2 cells. RESULTS: As compared with their control mice, GRK4gammaA142V transgenic mice had higher blood pressure, lower D(1) receptor expression (0.6 +/- 0.2 vs. 1.5 +/- 0.2, P < 0.05), higher D(1) receptor phosphorylation [(65 +/- 7) DU vs. (35 +/- 7) DU, P < 0.05] in renal cortical membranes and the diuretic and natriuretic effects after stimulation of renal D(1) receptor were impaired in GRK4gammaA142V transgenic mice. Inhibition of GRK4 expression (0.60 +/- 0.10 vs. 1.30 +/- 0.09, P < 0.05) by GRK4 antisense oligonucleotides upregulated D(1) receptor expression (1.5 +/- 0.2 vs. 0.8 +/- 0.1, P < 0.05) in HK-2 cells. CONCLUSIONS: Our results show that GRK4gammaA142V overexpression induced hypertension is mediated by dowregulated renal D(1) receptor expressions in GRK4gammaA142V transgenic mice.

Animals↗
PubMed2006

[Research advance in slurry sample introduction for plasma emission spectrometry/mass spectrometry].

The present review is focused on the advances and applications of slurry introduction for plasma spectrometry/mass spectrometry. Preparation and characterization of the suspensions are described, including the methods for decreasing the particle size such as the bottle and bead method, mixing mill method, vibration mill method, and supersonic mill method. Dispersion of the particles can be controlled via adding dispersant and pH adjustment. Some methods for particle size measurement, namely, sedimentation, optical microscopy, photosedimentometry, laser diffraction, scanning electron microscopy and transmission electron microscopy, are also described. Effects of suspension concentration and calibration techniques, including calibration by simple aqueous standard, internal standard, correction by empirical correction factors, standard additions, intrinsic internal standardization, and standard slurries, are discussed. Fundamental study of slurry introduction and its applications to plasma spectrometry/mass spectrometry are reviewed.

English Abstract↗
PubMed2006

[Comparison the screening methods of the acute toxicity in vitro].

OBJECTIVE: To provide the proof for establishing the high throughput screening method of the acute toxicity by comparing the 4 screening methods of the acute toxicity in vitro. METHODS: HepG2 cells, plated in 96-well plates, were treated with 47 compounds and we detected the cytotoxicity using 4 methods and calculated the IC50, IC45, IC40, IC35, IC30, and these values were compared with the LD50. RESULTS: The IC45 from the neutral red method has the best relativity with the LD50. CONCLUSION: Plating HepG2 cells in 96-well plates, the cytotoxicity be detected using the neutral red method and the IC45 was calculated. It is considered to provide the proof for establishing the high throughput screening method of the acute toxicity in vitro.

Cell Survival↗
PubMed2006

[An algorithm based on deformable contour models for medical image segmentation].

This paper provides a new medical image segmentation algorithm using a deformable contour model, which integrates Fuzzy C-Means(FCM) Clustering technique and deformable contour model. An external fuzzy constrain is defined from the membership function value of FCM, which joins the external constrain of the deformable model and drives the deformable model towards the contour ideal edge of the object. Examples are presented to demonstrate the efficiency and feasibility of the approach on spinal MRI images and the results are encouraging.

Algorithms↗
PubMed2006

[Study on the performances of the positive pressure powered air-filter protective hood].

The positive pressure powered air-filter protective hood can prevent physicians and nurses from being infected by serious respiratory infections. The contaminated air is filtered by the high efficiency specific air-filter (HESA) and then transported into the hood by a blower to form about 140 +/- 10 Pa positive pressure environment, which makes the air in hood overflow out from the lower part of the hood, by which carbon dioxide and vapor can be removed, and excreted. The HESA's filters of simulative virus up to 99.9999% with the structure of double layers filtering. With going at 4 km/h pace on a walking vehicle wearing the hood, the testees' heart rate is 90-105/min oxygen saturation of the blood(SPO2) is 97%-98%. When the air flow is from 75 L/min to 125 L/min, this can meet the testees' physiological demand under heavy workload. Clinical trial results show that the hood can effectively protect the physicians and nurses from infection.

Adult↗
PubMed2006

[Effect of compound branch chain amino acid injection on nutritional support in patients after radical resection for colorectal cancer].

OBJECTIVE: To evaluate the effect of compound branch chain amino acid(BCAA) injection on nutritional support in patients after radical resection for colorectal cancer. METHODS: Fifty patients with radical resection for colorectal cancer were randomly divided into two groups, and received compound branch chain amino acid (n=25) or compound amino acid(n=25) as control per day from postoperative day(POD)1 to POD 7. The levels of total protein, albumin, pre-albumin, transferring, nitrogen balance and complications were compared between the two groups. RESULTS: On POD 8, the levels of albumin, pre- albumin, transferring were (36.12+/-3.16)g/L, (237.10+/-37.29)mg/L, and (2.18+/- 1.34)g/L in study group, and (30.61+/-3.55)g/L, (191.73+/-27.60)mg/L, and (1.71+/-0.84)g/L respectively in the control group(all P< 0.05). Nitrogen balance increased significantly from POD5, and increased to normal on POD 6 in study group, significantly higher than that in the control group (9.91+/-6.53 vs - 9.73+/-11.21, P=0.024). The complication rate of incision infection and delayed healing was 8.3% in study group, significantly lower than 38.1% in the control group(P< 0.05). CONCLUSION: Compared with compound amino acid, compound branch chain amino acid injection can reduce proteolysis, correct negative nitrogen balance and promote wound healing.

Amino Acids↗