Biomedical subjects

Weidong Zhang

Publications and source records attributed to Weidong Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity.

The TallyHo (TH) mouse strain is a polygenic model for Type 2 diabetes with obesity. Genetic analysis in backcross progeny from a cross between F1 [C57BL/6J (B6) x TH] and TH mice mapped a quantitative trait locus (QTL) named TH-associated body weight 2 (tabw2) to chromosome 6. The TH-derived allele is associated with increased body weight. As a first step to identify the molecular basis of this obesity QTL, we constructed a congenic line of mice on the B6 genetic background that carries a genomic region from TH mice containing tabw2. Congenic mice homozygous for tabw2 (B6.TH-tabw2/tabw2) fed a chow diet exhibited slightly, but significantly, higher body weight and body fat and plasma leptin levels compared with controls (B6.TH-+/+). This difference was exacerbated when the animals were maintained on a high-fat and high-sucrose (HFS) diet. The diet-induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in adipose tissue in response to insulin administration. Using F2 progeny fed a HFS diet from an intercross of B6.TH-tabw2/+ mice, we were able to refine the map position of the tabw2 obesity susceptibility locus to a 15-cM region (95% confidence interval) extending distally from the marker D6Mit102. In summary, tabw2 congenic mice are a new animal model for diet-induced obesity that will be valuable for the study of gene-diet interactions.

Alleles↗

PubMed2004

Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene.

Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. The RSV NS1 protein seems to antagonize the host interferon (IFN) response; however, its mechanism is unknown. Here, we used a plasmid-borne small interfering RNA targeting the NS1 gene (siNS1) to examine the role of NS1 in modulating RSV infection. RSV replication was reduced in A549 cells, but not IFN-deficient Vero cells, transfected with siNS1. siNS1 induced upregulated expression of IFN-beta and IFN-inducible genes in A549 cells. siNS1-transfected human dendritic cells, upon RSV infection, produced elevated type-1 IFN and induced differentiation of naive CD4+ T cells to T helper type 1 (TH1) cells. Mice treated intranasally with siNS1 nanoparticles before or after infection with RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. Thus, siNS1 nanoparticles may provide an effective inhibition of RSV infection in humans.

Antiviral Agents↗

PubMed2004

Uncertainty analysis in a mechanistic model of bacterial regrowth in distribution systems.

The first generation of mechanistic models of bacterial regrowth in distribution systems (DS) provides insight into cause-and-effect relationships. However, the state of knowledge about the processes included in these models is insufficient to warrant deterministic predictions. Even if the process descriptions are reasonable, the uncertainty in values of key system constants limits predictions of bacterial growth. A new mechanistic model was developed to incorporate the accepted knowledge of physical, chemical, and biological processes with the hydraulic features in order to capture the unsteady state behavior of the DS. Sensitivitytesting showed that the extent of bacterial regrowth was affected mainly by the rate constants for chlorine decay reactions in bulk water and on the pipe wall and by the maximum growth rate constant of attached bacteria. A simple hypothetical network was used to evaluate the effects of uncertainty in these three system constants by running 100 Monte Carlo simulations. Cumulative probability plots showed a wide range of predictions for concentrations of bacteria and chlorine in bulk water at various nodes in the DS. The magnitude of these concentrations and the range of values were greatly affected by water residence time to each node. Once the chlorine residual is depleted, bacterial growth is mainly influenced by the amount of substrate available. However, high values of the coefficients for the maximum growth rate of attached bacteria, the chlorine decay in bulk water, and the chlorine decay by wall reaction did not necessarily lead to the maximum bacterial growth at a given location.

Bacteria↗

PubMed2004

Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery.

BACKGROUND: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). METHODS: A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. RESULTS: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. CONCLUSION: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.

Journal Article↗

PubMed2004

Experimental study of adenovirus vector mediated-hVEGF165 gene on prevention of restenosis after angioplasty.

This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries. On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer. The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.

Adenoviridae↗

PubMed2004

Mechanism of bronchoprotective effects of a novel natriuretic hormone peptide.

BACKGROUND: The natriuretic hormone peptide (NHP)(99-126), a C-terminal peptide of pro-atrial natriuretic factor (proANF), induces bronchodilatory effects in people with asthma. Recently, another plasmid-encoded C-terminal peptide, pNHP(73-102), was shown to induce a long-lasting bronchoprotective effect in a mouse model of allergic asthma. OBJECTIVE: This study was carried out to determine the role of lung epithelial cells in the bronchoprotective and anti-inflammatory activity of these peptides. METHODS: Human type II alveolar epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells were transfected with pNHP(73-102) to test the effect of this peptide on activation of these cells. After transfection, cells were analyzed for changes in Ca(++) and nitric oxide (NO) levels. Also, activation of NFkappaB and the extracellularly regulated kinase (ERK) 1, 2 signaling pathway was examined by luciferase reporter assay and phosphorylation studies respectively. RESULTS: Analysis of intracellular Ca(++) levels in pNHP(73-102) -transfected A549 or NHBE showed that the peptide increases release. This Ca(++) release was accompanied by an increase in the production of NO. Also, overexpression of pNHP(73-102), but not pVAX control, in phorbol myristate acetate-activated A549 cells resulted in a significant decrease in expression of a cotransfected nuclear factorkappaB (NFkappaB)-luciferase reporter. Similarly, pNHP(73-102) decreased TNF-alpha-induced NFkappaB activation in NHBE cells. Furthermore, NHP(73-102) but not atrial natriuretic peptide decreased phosphorylation of Erk-1, 2 in A549 cells. CONCLUSIONS: Overexpression of pNHP(73-102) in epithelial cells causes increased production of intracellular Ca(++) and NO, with a concomitant decrease in activation of NFkappaB and ERK1, 2. These results suggest a bronchodilatory and anti-inflammatory activity of this peptide.

Atrial Natriuretic Factor↗

PubMed2004

The E237G polymorphism of the high-affinity IgE receptor beta chain and asthma.

BACKGROUND: The beta chain of high-affinity IgE receptor (FcepsilonRI beta) has been proposed as a candidate gene for asthma and atopic diseases. OBJECTIVES: To determine the prevalence of the E237G polymorphism of the FcepsilonRI beta gene and to investigate its association with asthma and total IgE levels in 3 Asian populations. METHODS: A total of 291 asthmatic patients (141 Chinese, 68 Malay, and 82 Indian) and 355 asymptomatic blood donors (157 Chinese, 100 Malay, and 98 Indian) were recruited. The E237G genotype was determined by allele-specific polymerase chain reaction. Total serum IgE level was measured by enzyme-linked immunosorbent assay. RESULTS: The G allele was more common in Chinese controls (17.9%) than in Malay (11.5%) (P = .05) and Indian (9.2%) (P = .01) controls. Genotypes with the G allele were more prevalent in asthmatic patients in the Chinese population (odds ratio, 1.97; 95% confidence interval, 1.05-3.77; P = .04). CONCLUSIONS: There were interethnic differences in the frequencies of the G variant among Chinese, Malay, and Indian populations. The E237G polymorphism of FcsRI beta may be a risk factor for asthma in the Chinese population.

Adult↗

PubMed2004

An efficient SNP system for mouse genome scanning and elucidating strain relationships.

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average approximately 1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608+/-136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.

Alleles↗

PubMed2003

Comparison of several well-known controllers used in process control.

In this paper, several well-known design methods, PID control, Smith predictor, inferential control, internal model control, Dahlin controller, deadbeat control, and predictive control, are studied. A suboptimal Smith predictor is derived. The relationship among these methods is investigated. It is shown that these methods are equivalent to each other on certain premises. This explains why they are widely used in process control and provides insight into the work of bringing these techniques together to control system design. Examples are given to illustrate the result.

Journal Article↗

PubMed2003

The characterisation of polycyclic aromatic hydrocarbons emissions from burning of different firewood species in Australia.

Four kinds of woods used for residential heating in Australia were selected and burned under two burning conditions in a domestic wood heater installed in a laboratory. The selected wood species included pine (Pinus radiata), red gum (Eucalvptus camaldulensis), sugar gum (Eucalyptus cladocalyx) and yellow box (Eucalyptus melliodora). The two different burning conditions represented fast burning and slow burning, with the air inlet of the combustion chamber respectively 'full open' and 'half open'. By sampling and analysing particulate and gaseous emissions from the burning of each load of wood under defined experimental conditions, PAHs emissions and their profiles in the particulate and gaseous phases were obtained. 16 species out of the 18 selected PAHs were detected. Of these, seven species were detected in the gaseous phase and most were lower molecular weight compounds.Similarly, more than 10 species of PAHs were detected in the particulate phase and these were mostly heavier molecular weight compounds. Under both burning conditions, emission levels for total PAHs and total genotoxic PAHs were the highest for pine and lowest for sugar gum, with red gum being the second highest, followed by yellow box. Using the specific sampling method, gaseous PAHs accounted for above 90% mass fraction of total PAHs in comparison to particulate PAHs (10%). The majority of the genotoxic PAHs were present in the particulate phase. PAHs emission levels in slow burning conditions were generally higher than those in fast burning conditions.

Air Pollutants↗

PubMed2003

Tumour necrosis factor-alpha (TNF-alpha) transgene-expressing dendritic cells (DCs) undergo augmented cellular maturation and induce more robust T-cell activation and anti-tumour immunity than DCs generated in recombinant TNF-alpha.

Tumour antigen presentation by dendritic cells (DCs) to T cells in lymphoid organs is crucial for induction of anti-tumour immune responses. It has been previously reported that tumour necrosis factor-alpha (TNF-alpha) is required for DC activation and subsequent induction of optimal immune responses, and thus DCs for anti-tumour vaccination are often generated by culture in exogenous TNF-alpha. In the present study, we investigated the effect on anti-tumour immunity of vaccination with Mut1 tumour peptide-pulsed DCs engineered to express a TNF-alpha transgene. Our data shows that transfection of DCs with recombinant adenovirus AdV-TNF-alpha resulted in greater maturation of the DCs than occurred with control DCs cultured in exogenous TNF-alpha, as determined by up-regulated expression of pro-inflammatory cytokines (e.g. interleukins 1beta and 18), chemokines [e.g. interferon-gamma-inducible protein-10 and macrophage inflammatory protein-1beta (MIP-1beta)], the CC chemokine receptor CCR7, and immunologically important cell surface molecules (CD40, CD86 and intercellular adhesion molecule-1). These transgenic DCs stimulated stronger allogeneic T-cell responses in vitro and T-cell activation in vivo; displayed 2.4-fold enhanced chemotactic responses to the MIP-3betain vitro (P<0.05); and, perhaps most importantly, trafficked into the draining lymph nodes dramatically (seven-fold, P<0.01) more efficiently than the control DCs. Our data also demonstrate that vaccination of mice with Mut1 peptide-pulsed, AdV-TNF-alpha-transfected DCs stimulated more efficient in vitro Mut1-specific CD8+ cytotoxic T-cell responses and solid tumour immunity in vivo, when compared to the in vitro TNF-alpha-cultivated DCs. Thus, DCs engineered to secrete TNF-alpha may offer a new strategy in DC cancer vaccines.

Adenoviridae↗

PubMed2002

Enhancing antitumor by immunization with fusion of dendritic cells and engineered tumor cells.

A novel approach for a dentritic cells (DCs)-based tumor vaccine was developed for the formation of hybrid-engineered J558 after fusion with DCs. To make the hybrid-tumor vaccine generate more efficient specific CTL cytotoxicity against wild-type tumor cells, we genetically engineered tumor cells with mIL-12 gene prior to the cell fusion. mIL-12 was detected at 870 +/- 60 pg/(10(5) cells/ml) in the culture supernatants and the fusion ratio was about 30% by the co-focal microscopic analysis. Vaccination of mice with DCs fused with engineered J558 induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. These results suggest that this approach of using DCs fused with engineered tumor cells could be applied in clinical settings of DCs-based cancer vaccines.

Animals↗

PubMed2002

H(infinity) PID controller design for runaway processes with time delay.

This paper presents an efficient method for designing proportional-integra-derivative (PID) controllers for runaway processes with time delay. The method is developed based on the H(infinity) control theory in frequency domain. The constraints imposed by the internal stability and asymptotic properties of the closed-loop system are first investigated, a new procedure is then developed for analytically designing the controller, and simple design formulas are obtained. It is shown that the new controller can be designed to meet specified time domain performances. Typical design examples are provided to illustrate the proposed method.

Computer Simulation↗

PubMed2002

A new two-degree-of-freedom level control scheme.

In this paper, a two-degree-of-freedom level control scheme for delay free processes is analyzed. The nominal performance and robustness are examined. And sufficient and necessary conditions for robust stability are derived. An alternative level control scheme is developed for processes with dead time and suboptimal controllers that can produce smooth response are derived analytically based on the internal model control. The scheme has an important feature in that it is simple and transparent in design and in the corporation of performance and robust stability issues. Numerical examples are provided to compare the proposed scheme with those developed.

Equipment Design↗

PubMed2002

Design PID controllers for desired time-domain or frequency-domain response.

Practical requirements on the design of control systems, especially process control systems, are usually specified in terms of time-domain response, such as overshoot and rise time, or frequency-domain response, such as resonance peak and stability margin. Although numerous methods have been developed for the design of the proportional-integral-derivative (PID) controller, little work has been done in relation to the quantitative time-domain and frequency-domain responses. In this paper, we study the following problem: Given a nominal stable process with time delay, we design a suboptimal PID controller to achieve the required time-domain response or frequency-domain response for the nominal system or the uncertain system. An H(infinity) PID controller is developed based on optimal control theory and the parameters are derived analytically. Its properties are investigated and compared with that of two developed suboptimal controllers: an H2 PID controller and a Maclaurin PID controller. It is shown that all three controllers can provide the quantitative time-domain and frequency-domain responses.

Computer Simulation↗

PubMed2002

Optimal solution, quantitative performance estimation, and robust tuning of the simplifying controller.

Recently, a simplifying controller has been proposed based on the principal of simplification of the control system transfer functions, which offers improved control for processes with a large time delay. It is the purpose of this complementary paper to give a comprehensive analysis on the scheme. First, the relationship among the simplifying controller, the Smith predictor, and the internal model control are discussed. Second, an analytical design procedure is developed based on internal model control (IMC) and optimal solution is derived. Third, the problem of estimating the time domain performance of the closed loop system, quantitatively, is discussed. Fourth, a simple robust tuning procedure is presented. Numerical examples are provided to illustrate the proposed method.

Computer Simulation↗

PubMed2002

Comparison of bacterial regrowth in distribution systems using free chlorine and chloramine: a statistical study of causative factors.

Bacterial regrowth was investigated over a 15-month period in distribution systems (DSs) of Durham and Raleigh in North Carolina. These two water utilities were chosen because they are adjacent to one another, have similar service area characteristics, and treat surface waters of similar characteristics with conventional processes (coagulation-sedimentation and dual-media filtration). The finished waters have similar chemical quality and regrowth potential as measured by assimilable organic carbon (AOC). The major difference in treatment is the choice of final disinfectants (chlorine in Durham and chloramine in Raleigh). Ten sampling sites (monthly sampling) were chosen in each system to give wide geographic coverage and correspondingly, a wide range of water residence times. Significant losses were observed in both chlorine and chloramine residual in the DSs that produced bacterial regrowth as measured by heterotrophic plate count (HPC). The frequency distributions for log HPC (133 observations from Durham and 135 observations from Raleigh) were statistically the same in the chlorinated and chloraminated DSs. A correlation analysis indicated that disinfectant residual is the most important factor determining HPC level. However, the resulting R2 value for a non-linear regression model that also included AOC, temperature, and pH as independent variables was less than 0.7. Bacterial regrowth as measured by HPC, is dependent upon a complex interaction of chemical, physical, and operational parameters that may not be captured by such a simple statistical relationship.

Bacteria↗

PubMed2002

Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative mature dendritic cells enhances antitumor immunity.

Dendritic cell (DC)-tumor fusion hybrid vaccine which facilitates antigen presentation represents a new powerful strategy in cancer therapy. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between wild-type J558 or engineered J558-IL-4 myeloma cells secreting cytokine interleukin-4 (IL-4) and immature DCs (DC(IMAT)) or relative mature DCs (DC(RMAT)). DC(RMAT) displayed an up-regulated expression of immune molecules (Ia(d), CD40, CD54, CD80 and CD86) and certain cytokines/chemokines, and enhanced ability of allogeneic T cell stimulation when compared to DC(IMAT). These DCs were fused with myeloma cells by polyethylene glycol (PEG). The fusion efficiency was approximately 20%. Our data showed that immunization of C57BL/6 mice with DC(RMAT)/J558 hybrids induced protective immunity against a high dose of J558 tumor challenge (1x10(6) cells) in 3 out of 10 immunized mice, compared with no protection seen in mice immunized with DC(IMAT)/J558 hybrids. Furthermore, immunization of mice with engineered DC(RMAT)/J558-IL-4 hybrids elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro and induced more efficient protective immunity (10/10 mice; tumor free) against J558 tumor challenge in vivo than DC(RMAT)/J558 hybrid vaccines. The results demonstrate the importance of DC maturation in DC-tumor hybrid vaccines and indicate that the engineered fusion hybrid vaccines which combine gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.

Animals↗