Biomedical subjects

T Zhou

Publications and source records attributed to T Zhou.

At least 19 recordsLinked to original sources

PubMed2006

Long terminal repeats are not the sole determinants of virulence for equine infectious anemia virus.

The long terminal repeats (LTRs) of equine infectious anemia virus donkey leukocyte-attenuated virus (EIAV-DLA) were substituted with those of the wild-type EIAV-L (wt EIAV-L, the parent virus of EIAV-DLA). The resulting chimeric plasmid was designated pOK-LTR DLA/L. Purified pOK-LTR DLA/L was transfected into monocyte-derived macrophage (MDM) cultures prepared from EIAV-negative, heparinized whole blood from a donkey. Eighth-passage cell cultures developed the typical cytopathogenic effects (CPE) of EIAV infection, and virions with typical EIAV profiles were observed with an electron microscope. Horses were inoculated with the chimeric virus or EIAV-DLA and challenged with the wt EIAV-L strain six months later. All of the horses inoculated with either the chimeric virus or EIAV-DLA were protected from disease, whereas the control horses died with typical EIA symptoms.

Animals↗

PubMed2006

Wavelet multiresolution analysis of the three vorticity components in a turbulent far wake.

The main objective of the present study is to examine the characteristics of the vortical structures in a turbulent far wake using the wavelet multiresolution technique by decomposing the vorticity into a number of orthogonal wavelet components based on different central frequencies. The three vorticity components were measured simultaneously using an eight-wire probe at three Reynolds numbers, namely 2000, 4000, and 6000. It is found that the dominant contributions to the vorticity variances are from the intermediate and relatively small-scale structures. The contributions from the large and intermediate-scale structures to the vorticity variances decrease with the increase of Reynolds number. The contributions from the small-scale structures to all three vorticity variances jump significantly when Reynolds number is changed from 2000 to 4000, which is connected to previous observations in the near wake that there is a significant increase in the generation of small-scale structures once the Reynolds number reaches about 5000. This result reinforces the conception that turbulence "remembers" its origin.

Journal Article↗

PubMed2006

Combination of cytosine deaminase suicide gene expression with DR5 antibody treatment increases cancer cell cytotoxicity.

Combined treatment using adenoviral-directed enzyme/prodrug therapy and immunotherapy has the potential to become a powerful alternative method of cancer therapy. We have developed adenoviral vectors encoding the cytosine deaminase gene (Ad-CD) and cytosine deaminase:uracil phosphoribosyltransferase fusion gene (Ad-CD:UPRT). A monoclonal antibody, TRA-8, specifically binds to death receptor 5, one of two death receptors bound by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The purpose of this study was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of the combination of Ad-CD:UPRT and TRA-8 against human pancreatic cancer and glioma cell lines. The present study demonstrates that Ad-CD:UPRT infection resulted in increased 5-FC-mediated cell killing, compared with Ad-CD. Furthermore, a significant increase of cytotoxicity following Ad-CD:UPRT/5-FC and TRA-8 treatment of cancer cells in vitro was demonstrated. Animal studies showed significant inhibition of tumor growth of MIA PaCa-2 pancreatic and D54MG glioma xenografts by the combination of Ad-CD:UPRT/5-FC plus TRA-8 as compared with either agent alone or no treatment. The results suggest that the combination of Ad-CD:UPRT/5-FC with TRA-8 produces an additive cytotoxic effect in cancer cells in vitro and in vivo. These data indicate that combined treatment with enzyme/prodrug therapy and TRAIL immunotherapy provides a promising approach for cancer therapy.

Adenoviridae↗

PubMed2006

Hibiscus chlorotic ringspot virus p27 and its isoforms affect symptom expression and potentiate virus movement in kenaf (Hibiscus cannabinus L.).

Hibiscus chlorotic ringspot virus (HCRSV), a member of the genus Carmovirus, encodes p27 (27-kDa protein) and two other in-frame isoforms (p25 and p22.5) that are coterminal at the carboxyl end. Only p27, which initiates at the 2570CUG codon, was detected in transfected kenaf (Hibiscus cannabinus L.) protoplasts through fusion to a Flag tag at either its N or C terminus. Subcellular localization of a p27-green fluorescent fusion protein in kenaf epidermal cells showed that it was localized to membrane structures close to cell walls. To study the functions of these proteins, a number of start codon mutants and premature translation termination mutants were constructed. Phenotypic differences were observed between the wild-type virus and these mutants during infection. Infectivity assays on plants indicated that p27 is a determinant of symptom severity. Without p25, appearance of symptoms on systemically infected kenaf leaves was delayed by 4 to 8 days. In a timecourse analysis, Western blot assays revealed that the delay corresponded to retardation in virus systemic movement, which suggested that p25 is probably involved in virus systemic movement. Mutations disrupting expression of p22.5 did not affect symptoms or virus movement.

3' Untranslated Regions↗

PubMed2006

Antimicrobial activity of essential oils and structurally related synthetic food additives towards selected pathogenic and beneficial gut bacteria.

AIMS: To assess the potential of essential oils and structurally related synthetic food additives in reducing bacterial pathogens in swine intestinal tract. METHODS AND RESULTS: The antimicrobial activity of essential oils/compounds was measured by determining the inhibition of bacterial growth. Among 66 essential oils/compounds that exhibited > or =80% inhibition towards Salmonellatyphimurium DT104 and Escherichia coli O157:H7, nine were further studied. Most of the oils/compounds demonstrated high efficacy against S. typhimurium DT104, E. coli O157:H7, and E. coli with K88 pili with little inhibition towards lactobacilli and bifidobacteria. They were also tolerant to the low pH. When mixed with pig cecal digesta, these oils/compounds retained their efficacy against E. coli O157:H7. In addition, they significantly inhibited E. coli and coliform bacteria in the digesta, but had little effect on the total number of lactobacilli and anaerobic bacteria. CONCLUSIONS: Some essential oils/compounds demonstrated good potential, including efficacy, tolerance to low pH, and selectivity towards bacterial pathogens, in reducing human and animal bacterial pathogens in swine intestinal tract. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has identified candidates of essential oils/compounds for in vivo studies to develop antibiotic substitutes for the reduction of human and animal bacterial pathogens in swine intestinal tract.

Animals↗

PubMed2005

Scaling of longitudinal and transverse velocity increments in a cylinder wake.

Longitudinal and transverse velocity increments are measured both temporally and spatially using two X-wire probes in the intermediate region of a cylinder wake over Taylor microscale Reynolds numbers in the range of 100-300. The scaling exponents of both the spatial and temporal longitudinal velocity increments agree favorably with the predictions of Kolmogorov and She and Leveque. The scaling exponents of the transverse velocity increments are considerably smaller than those of the longitudinal ones, with the values for spatial transverse velocity increments being slightly larger than the temporal ones. The difference between the scaling exponents of the longitudinal and transverse velocity increments is examined against the refined similarity hypotheses for transverse velocity increments (RSHT) proposed by Chen It is found that the RSHT can account for the difference between the scaling exponents of the longitudinal and spatial transverse velocity increments at all Reynolds numbers considered.

Journal Article↗

PubMed2005

Tetramethylpyrazine inhibits ATP-activated currents in rat dorsal root ganglion neurons.

Tetramethylpyrazine (TMP) is one of the alkaloids contained in Ligustrazine which has been used in traditional Chinese medicine as an analgesic for injury and dysmenorrhea. ATP can elicit the sensation of pain. This study observed the effects of TMP on ATP-activated current (IATP) in rat DRG neurons. TMP (0.1-1 mM) concentration-dependently inhibited ATP (100 microM)-activated current in rat DRG neurons. The inhibitory time of ATP (100 microM)-activated current appeared at 15 s after preapplication of TMP and reached its peak at about 45 s. The dose-response curves for IATP in the absence and presence of 1 mM TMP showed that TMP (1 mM) shifted the concentration-response curve of IATP downward markedly and the two EC50 values were very close (75 vs. 82 microM), while the threshold value remained unchanged. Therefore, the inhibitory effect of TMP on IATP may be noncompetitive. TMP did not alter the reversal potential (0 mV) of ATP-activated current, indicating that the site of TMP action is on or near the exterior surface of channel protein and not within the channel pore. Externally applied TMP (1 mM) increases the inhibitory effect of chelerythrine (PKC inhibitor) contained in pipette solution on IATP. The site of TMP action may be the binding of TMP to an allosteric site on the large extracellular region of ATP receptor-ion channel complex (P2X receptors) or PKC site of the N-terminus of P2X receptors. The mechanism of TMP action may be the allosteric regulation via acting on the large extracellular region of ATP receptor-ion channel complex (P2X receptors) and promoting the phosphorylation of PKC site of the N-terminus of P2X receptors.

Action Potentials↗

PubMed2005

Modeling of dispersed-drug release from two-dimensional matrix tablets.

A mathematical model was developed and analytical solutions were obtained for dispersed-drug release from two-dimensional matrix tablets in a perfect sink. This model can be used to describe kinetics of solute release from matrices with isotropic or anisotropic properties. Moving boundaries of dispersed-drug in both radial and axial directions and release kinetics were predicted by the model. Various factors influencing release kinetics were analyzed including the ratio of initial solute loading (C0) to solute solubility (Cs), the anisotropy of the matrix and the aspect ratio of tablet radius to the half-thickness. The model is also applicable to 1-D planar or 1-D cylindrical geometries when R/H is larger than 100 or smaller than 0.01.

Data Interpretation, Statistical↗

PubMed2005

Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor.

The nature of antigens and functional state of dendritic cells (DC) are important in antigen presentation. The ability of DC for the induction of T-cell responses is promoted by maturation. It has been confirmed that mannose receptors mediate highly efficient endocytosis and presentation of mannosylated proteins. In the present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli, purified and mannosylated. The maturation and functional capacity of DC induced by mannosylated L2 (mL2) protein were investigated. The results showed that L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and co-stimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non-mL2 proteins. Uptake of mL2 antigens by DC was more efficient. Furthermore, the T cells can be stimulated to proliferate in vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN-gamma and IL-10 were detected from the T cells stimulated by mL2-pulsed DC, suggesting a concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2 domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2 can induce an enhanced maturation and functional capacity of DC. It may become an effective strategy to induce anti-ErbB2 response.

Antigen Presentation↗

PubMed2004

Genome-wide identification of NBS genes in japonica rice reveals significant expansion of divergent non-TIR NBS-LRR genes.

A complete set of candidate disease resistance ( R) genes encoding nucleotide-binding sites (NBSs) was identified in the genome sequence of japonica rice ( Oryza sativaL. var. Nipponbare). These putative R genes were characterized with respect to structural diversity, phylogenetic relationships and chromosomal distribution, and compared with those in Arabidopsis thaliana. We found 535 NBS-coding sequences, including 480 non-TIR (Toll/IL-1 receptor) NBS-LRR (Leucine Rich Repeat) genes. TIR NBS-LRR genes, which are common in A. thaliana, have not been identified in the rice genome. The number of non-TIR NBS-LRR genes in rice is 8.7 times higher than that in A. thaliana, and they account for about 1% of all of predicted ORFs in the rice genome. Some 76% of the NBS genes were located in 44 gene clusters or in 57 tandem arrays, and 16 apparent gene duplications were detected in these regions. Phylogenetic analyses based both NBS and N-terminal regions classified the genes into about 200 groups, but no deep clades were detected, in contrast to the two distinct clusters found in A. thaliana. The structural and genetic diversity that exists among NBS-LRR proteins in rice is remarkable, and suggests that diversifying selection has played an important role in the evolution of R genes in this agronomically important species. (Supplemental material is available online at http://gattaca.nju.edu.cn.)

Amino Acid Sequence↗

PubMed2004

Similarity solution of temperature structure functions in decaying homogeneous isotropic turbulence.

An equilibrium similarity analysis is applied to the transport equation for <(deltatheta)(2)>, the second-order temperature structure function, for decaying homogeneous isotropic turbulence. A possible solution is that the temperature variance decays as x(n), and that the characteristic length scale, identifiable with the Taylor microscale lambda, or equivalently the Corrsin microscale lambda(theta), varies as x(1/2). The turbulent Reynolds and Péclet numbers decay as x((m+1)/2) when m<-1, where m is the exponent which characterizes the decay of the turbulent energy , viz., approximately x(m). Measurements downstream of a grid-heated mandoline combination show that, like <(deltaq)(2)>, <(deltatheta)(2)> satisfies similarity approximately over a significant range of scales r, when lambda, lambda(theta), , and are used as the normalizing scales. This approximate similarity is exploited to calculate the third-order structure functions. Satisfactory agreement is found between measured and calculated distributions of and , where deltau is the longitudinal velocity increment.

Journal Article↗

PubMed2004

Structural analysis of the epitopes on erbB2 interacted with inhibitory or non-inhibitory monoclonal antibodies.

erbB2 oncogene encodes a growth factor receptor. The overexpression of erbB2 was correlated with more aggressive tumors and a poorer prognosis. Some antibodies directed to this molecule have an antitumor effect in vivo, but some antibodies do not. In an attempt to understand the molecular basis of the anti-erbB2 antibody interaction with erbB2 ectodomain (ECD), we analyzed binding epitopes on erbB2 for inhibitory and non-inhibitory antibodies, Herceptin and HF by computer-guided protein engineering and site-directed mutagenesis. Two different interaction domains were identified by molecular docking, computer graphics and distance geometry method and confirmed through studies on a series of mutants of erbB2 ECD. Non-inhibitory antibody HF only recognized N-terminal portion of erbB2 ECD, but inhibitory antibody Herceptin bound to C-terminal portion of it exclusively. The region interacted with inhibitory antibody Herceptin can be an important target for anticancer therapies.

Antibodies, Monoclonal↗

PubMed2004

Enhanced apoptosis following treatment with TRA-8 anti-human DR5 monoclonal antibody and overexpression of exogenous Bax in human glioma cells.

Specific activation of apoptosis in tumor cells offers a promising approach for cancer therapy. Induction of apoptosis leads to activation of specific proteases. Two major pathways for caspase activation in mammalian cells have been described. One apoptotic pathway involves members of the tumor necrosis factor family of cytokine receptors (eg death receptor 5 (DR5)). The other pathway is controlled by the Bcl-2 family of proteins. The purpose of this study was to investigate whether increased apoptosis occurs in human glioma cells following infection with a recombinant adenoviral vector encoding the human Bax gene under the control of human vascular endothelial growth factor (VEGF) promoter element (AdVEGFBax) in combination with an anti-human DR5 monoclonal antibody (TRA-8). Specific overexpression of exogenous Bax protein induced apoptosis and cell death in glioma cell lines, through activation of both caspase-8 and -9, leading to activation of downstream caspase-3. The relative sensitivity to AdVEGFBax for the glioma cell lines was U251MG>U373MG>U87MG>D54MG. The recently characterized TRA-8 monoclonal antibody induces apoptosis of most TRAIL-sensitive tumor cells by specific binding to DR5 receptors on the cellular membrane. TRA-8 induced rapid apoptosis and cell death in glioma cells, but did not demonstrate detectable cytotoxicity of primary normal human astrocytes. The efficiency of TRA-8-induced apoptosis was variable in different glioma cell lines. The relative sensitivity to TRA-8 was U373MG>U87MG>U251MG>D54MG. The combination of TRA-8 treatment and overexpression of Bax overcame TRA-8 resistance of glioma cells in vitro. Cell viability of U251MG cells was 71.1% for TRA-8 (100 ng/ml) alone, 75.9% for AdVEGFBax (5 MOI) alone and 41.1% for their combination as measured by MTS assay. Similar enhanced apoptosis results were obtained for the other glioma cell lines. In vivo studies demonstrated that the combined treatment significantly (P<0.05) suppressed the growth of U251MG xenografts and produced 60% complete tumor regressions without recurrence. These data suggest that the combination of TRA-8 treatment with specific overexpression of Bax using AdVEGFBax may be an effective approach for the treatment of human malignant gliomas.

Adenoviridae↗

PubMed2004

Modelling periodic oscillation of biological systems with multiple timescale networks.

In this paper, we aim to develop a new methodology to model and design periodic oscillators of biological networks, in particular gene regulatory networks with multiple genes, proteins and time delays, by using multiple timescale networks (MTN). Fast reactions constitute a positive feedback-loop network (PFN), while slow reactions consist of a cyclic feedback-loop network (CFN), in MTN. Multiple timescales are exploited to simplify models according to singular perturbation theory. We show that a MTN has no stable equilibrium but stable periodic orbits when certain conditions are satisfied. Specifically, we first prove the basic properties of MTNs with only one PFN, and then generalise the result to MTNs with multiple PFNs. Finally, we design a biologically plausible gene regulatory network by the cI and Lac genes, to demonstrate the theoretical results. Since there is less restriction on the network structure of a MTN, it can be expected to apply to a wide variety of areas on the modelling, analysing and designing of biological systems.

Biological Clocks↗

PubMed2003

The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome.

BACKGROUND: Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: To determine the level of BLyS in serum from patients with primary's Sjögren's syndrome (SS), another autoimmune disease in which B cell activation is high. METHODS: Serum samples from 49 patients with primary SS according to the revised European criteria were assayed for BLyS, quantitative immunoglobulins, and autoantibody levels and compared with samples from 47 healthy control subjects. RESULTS: The median level of BLyS was 5.99 ng/ml (25th-75th centile range 3.20-8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range 1.96-2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients with SS, the presence of anti-SSA antibodies was associated with significantly higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS in three patients with a monoclonal gammopathy was higher than in the other patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were associated with higher levels of gammaglobulins and IgG. There was a strong correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). CONCLUSION: In human SS the level of BLyS correlates with the level of autoantibodies. Thus, BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease. These findings raise the possibility of a novel therapeutic approach in human SS.

Antibodies, Antinuclear↗

PubMed2002

Different role of Apaf-1 in positive selection, negative selection and death by neglect in foetal thymic organ culture.

Apoptotic protease-activating factor 1 (Apaf-1) is a component of the apoptosome which is required for the activation of procaspase-9. As Apaf-1 knockout (KO) (Apaf-1-/-) mice die before birth, the role of Apaf-1 during thymic selection was investigated using 5 day foetal thymic organ culture (FTOC) of thymi obtained at gestational day 15. There was a lower ratio of CD4 single-positive (SP) to CD8 SP cells and decreased apoptosis of CD4+CD8+ (DP) thymocytes from Apaf-1-/- mice compared with wild-type. To determine if these defects resulted in increased production of neglected thymocytes, the Apaf-1-/- mice were crossed with the T-cell receptor (TCR)-alpha-chain KO mice. There was no difference in thymocyte development in the thymi of TCR-alpha-/-Apaf-1-/- and TCR-alpha-/-Apaf-1+/+ mice 5 days after FTOC. To determine if Apaf-1 is involved in apoptosis during death by negative or positive selection, FTOC of the thymus of Apaf-1-/- Db/HY TCR-alphabeta transgenic (Tg) mice was carried out. There was decreased apoptosis of the HY clonal-specific M33+ thymocytes and an increased percentage of the autoreactive CD8+M33+ thymocytes in male, but not female Apaf-1-/- Db/HY TCR Tg mice. Our data suggest that Apaf-1 is not involved in positive selection or death by neglect, but may have a partial role in negative selection during early thymic T-cell development.

Animals↗

PubMed2002

Factors affecting patulin production by Penicillium expansum.

Patulin, a mycotoxin produced by Penicillium spp. during fruit spoilage, is a major concern with regard to human health because exposure can result in severe acute and chronic toxicity, including carcinogenic, mutagenic, and teratogenic effects. In this study, we investigated the effects of Penicillium expansum isolate, apple cultivar, storage temperature and time, and pH on the production of patulin. Patulin was analyzed by a previously developed micellar electrokinetic capillary electrophoresis method. P. expansum isolates originating from across Ontario produced widely differing levels of patulin, ranging from 0 to >6 mg/g by dry mycelial weight. The highest patulin levels were those for isolates displaying aggressive growth (characterized by rapidly increasing acidity) accompanied by profuse mycelial development. Distinct patterns in fungal growth rates and patulin production were evident among isolates grown in McIntosh, Empire, and Mutsu ciders. Extensive fungal growth and higher patulin levels (538 to 1,822 microg/ml on day 14) in apple ciders were associated with incubation at room temperature (25 degrees C), although potentially toxic patulin levels (75 to 396 microg/ml on day 24) were also found in refrigerated ciders (4 degrees C) inoculated with P. expansum.

Beverages↗

PubMed2001

Antimonite regulation of the ATPase activity of ArsA, the catalytic subunit of the arsenical pump.

The ArsA ATPase is the catalytic subunit of the pump protein, coupling the hydrolysis of ATP to the movement of arsenicals and antimonials through the membrane-spanning ArsB protein. Previously, we have shown the binding and hydrolysis of MgATP to ArsA to be a multi-step process in which the rate-limiting step is an isomerization between different conformational forms of ArsA. This isomerization occurs after product release, at the end of the ATPase reaction, and involves the return of the ArsA to its original conformation, which can then bind MgATP. ArsA possesses an allosteric site for antimonite [Sb(III)], the binding of which elevates the steady-state ATPase activity. We have used a transient kinetics approach to investigate the kinetics of ternary complex formation that lead to an enhancement in the ATPase activity. These studies revealed that ArsA exists in at least two conformational forms that differ in their ligand binding affinities, and that ATP favours one form and Sb(III) the other. Ternary complex formation is rate-limited by a slow transition between these conformational forms, leading to a lag in attaining maximal steady-state activity. Sb(III) enhances the steady-state ATPase activity by inducing rapid product release, allowing ArsA to adopt a conformation that can bind MgATP for the next catalytic cycle. In the presence of Sb(III), ArsA avoids the rate-limiting isomerization at the end of the ATPase reaction and ATP hydrolysis becomes rate-limiting for the reaction. The binding of Sb(III) probably results in more effective pumping of the substrates from the cell by enhancing the rate of efflux.

Adenosine Triphosphatases↗