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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 19 recordsLinked to original sources

Power analyses for longitudinal study designs with missing data.

Existing methods for power analysis for longitudinal study designs are limited in that they do not adequately address random missing data patterns. Although the pattern of missing data can be assessed during data analysis, it is unknown during the design phase of a study. The random nature of the missing data pattern adds another layer of complexity in addressing missing data for power analysis. In this paper, we model the occurrence of missing data with a two-state, first-order Markov process and integrate the modelling information into the power function to account for random missing data patterns. The Markov model is easily specified to accommodate different anticipated missing data processes. We develop this approach for the two most popular longitudinal models: the generalized estimating equations (GEE) and the linear mixed-effects model under the missing completely at random (MCAR) assumption. For GEE, we also limit our consideration to the working independence correlation model. The proposed methodology is illustrated with numerous examples that are motivated by real study designs.

Adolescent↗

Stabilization of platinum oxygen-reduction electrocatalysts using gold clusters.

We demonstrated that platinum (Pt) oxygen-reduction fuel-cell electrocatalysts can be stabilized against dissolution under potential cycling regimes (a continuing problem in vehicle applications) by modifying Pt nanoparticles with gold (Au) clusters. This behavior was observed under the oxidizing conditions of the O2 reduction reaction and potential cycling between 0.6 and 1.1 volts in over 30,000 cycles. There were insignificant changes in the activity and surface area of Au-modified Pt over the course of cycling, in contrast to sizable losses observed with the pure Pt catalyst under the same conditions. In situ x-ray absorption near-edge spectroscopy and voltammetry data suggest that the Au clusters confer stability by raising the Pt oxidation potential.

Journal Article↗

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche.

Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short- and long-term infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.

Adult↗

In vitro paclitaxel and radiation effects on the cell types responsible for vascular stenosis: a preliminary analysis.

Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.

Arteriovenous Shunt, Surgical↗

Palladium monolayer and palladium alloy electrocatalysts for oxygen reduction.

We investigated the oxygen-reduction reaction (ORR) on Pd monolayers on various surfaces and on Pd alloys to obtain a substitute for Pt and to elucidate the origin of their activity. The activity of Pd monolayers supported on Ru(0001), Rh(111), Ir(111), Pt(111), and Au(111) increased in the following order: Pd/Ru(0001) < Pd/Ir(111) < Pd/Rh(111) < Pd/Au(111) < Pd/Pt(111). Their activity was correlated with their d-band centers, which were calculated using density functional theory (DFT). We found a volcano-type dependence of activity on the energy of the d-band center of Pd monolayers, with Pd/Pt(111) at the top of the curve. The activity of the non-Pt Pd2Co/C alloy electrocatalyst nanoparticles that we synthesized was comparable to that of commercial Pt-containing catalysts. The kinetics of the ORR on this electrocatalyst predominantly involves a four-electron step reduction with the first electron transfer being the rate-determining step. The downshift of the d-band center of the Pd "skin", which constitutes the alloy surface due to the strong surface segregation of Pd at elevated temperatures, determined its high ORR activity. Additionally, it showed very high methanol tolerance, retaining very high catalytic activity for the ORR at high concentrations of methanol. Provided its stability is satisfactory, this catalyst might possibly replace Pt in fuel-cell cathodes, especially those of direct methanol oxidation fuel cells (DMFCs).

Alloys↗

Brownian motion of an ellipsoid.

We studied the Brownian motion of isolated ellipsoidal particles in water confined to two dimensions and elucidated the effects of coupling between rotational and translational motion. By using digital video microscopy, we quantified the crossover from short-time anisotropic to long-time isotropic diffusion and directly measured probability distributions functions for displacements. We confirmed and interpreted our measurements by using Langevin theory and numerical simulations. Our theory and observations provide insights into fundamental diffusive processes, which are potentially useful for understanding transport in membranes and for understanding the motions of anisotropic macromolecules.

Journal Article↗

The BCL2 major breakpoint region (mbr) regulates gene expression.

BCL2 expression is finely tuned by a variety of environmental and endogenous stimuli and regulated at both transcriptional and post-transcriptional levels. Our previous investigations demonstrated that the BCL2 major breakpoint region (mbr) in the 3'-UTR upregulates reporter gene expression, which implies that this region possessed intrinsic regulatory function. However, the effect of the mbr on BCL2 expression, and the underlying regulatory mechanisms, remain to be elucidated. To assess the direct effect of the mbr on the transcriptional activity of the BCL2 gene, we employed targeted homologous recombination to establish a mbr(+)/mbr(-) heterozygous Nalm-6 cell line and then compared the transcriptional activity and apoptotic effect on transcription between the wild type and targeted alleles. We found that deletion of the mbr significantly decreased the transcriptional activity of the corresponding allele in the mbr(+)/mbr(-) cell. The BCL2 allele deleted of the mbr had a slower response to apoptotic stimuli than did the wild type allele. The regulatory function of the mbr was mediated through SATB1. Overexpression of SATB1 increased BCL2 expression, while knockdown of SATB1 with RNAi decreased BCL2 expression. Our results clearly indicated that the mbr could positively regulate BCL2 gene expression and this regulatory function was closely related to SATB1.

3' Untranslated Regions↗

Reduced semen quality in chronic prostatitis patients that induce the release of apoptotic protein Omi/HtrA2 from spermatozoa.

The relationship between chronic prostatitis and fertility has been disputed for many years. Several groups have shown infection and autoimmune response against prostate antigens could have a deleterious effect on semen quality and fertility. This study was conducted to test the hypothesis that Omi/HtrA2-induced apoptosis in chronic prostatitis could be a mechanism underlying the observed clinical benefit. The Omi/HtrA2 serine protease is a nuclear-encoded mitochondrial protein, which can be released from mitochondria into the cytosol after apoptosis stimuli, inducing apoptosis in caspase-dependent and independent manners. Forty-one patients diagnosed as suffering from chronic prostatitis were included. Healthy normal individuals were included as controls. Human spermatozoa in the semen were purified by Percoll-gradient technique to separate the seminal plasma and other round cells. Measurements for sperm concentration, motility, morphology, proinflammatory cytokines, Omi/HtrA2 mRNA and protein levels in spermatozoa of chronic protatitis patients, were performed accordingly. Significantly increased levels of proinflammatory cytokines were detected in seminal plasma from these prostatitis patients. Omi/HtrA2 mRNA and protein levels were significantly higher in prostatitis men than in normal men. This study shows that chronic prostatitis patients present important alterations in their semen quality parameters, Omi/HtrA2 mRNA and protein levels of spermatozoa. We speculate that the inflammatory process involved may affect male fertility by release of proapoptotic protein Omi/HtrA2.

Adolescent↗

Influence of the polyelectrolyte poly(ethyleneimine) on the adsorption of surfactant mixtures of sodium dodecyl sulfate and monododecyl hexaethylene glycol at the air-solution interface.

The polyelectrolyte poly(ethylenenimine), PEI, is shown to strongly influence the adsorption of the anionic-nonionic surfactant mixture of sodium dodecyl sulfate, SDS, and monododecyl hexaethylene glycol, C(12)E(6), at the air-solution interface. In the presence of PEI, the partitioning of the mixed surfactants to the interface is highly pH-dependent. The adsorption is more strongly biased to the SDS as the pH increases, as the PEI becomes a weaker polyelectrolyte. At surfactant concentrations >10(-4) M, the strong interaction and adsorption result in multilayer formation at the interface, and this covers a more extensive range of surfactant concentrations at higher pH values. The results are consistent with a strong interaction between SDS and PEI at the surface that is not predominantly electrostatic in origin. It provides an attractive route to selectively manipulate the adsorption and composition of surfactant mixtures at interfaces.

Journal Article↗

Uptake of oxytetracycline and its phytotoxicity to alfalfa (Medicago sativa L.).

A series of experiments were conducted in a hydroponic system to investigate the uptake of oxytetracycline (OTC) and its toxicity to alfalfa (Medicago sativa L.). OTC inhibited alfalfa shoot and root growth by up to 61% and 85%, respectively. The kinetics of OTC uptake could be well described by Michaelis-Menten equation with Vmax of 2.25 micromol g-1 fresh weight h-1, and Km of 0.036 mM. The uptake of OTC by alfalfa was strongly inhibited by the metabolic inhibitor, 2,4-DNP (2,4-dinitrophenol), at pH 3.5 and 6.0, but not by the aquaporin competitors, glycerol and Ag+. OTC uptake, however, was significantly inhibited by Hg2+, suggesting that the inhibition of influx was due to general cellular stress rather than the specific action of Hg2+ on aquaporins. Results from the present study suggested that OTC uptake into alfalfa is an energy-dependent process.

Anti-Bacterial Agents↗

Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent.

High-fat (HF) feeding induces a transient increase in caloric intake and enhances energy expenditure. We hypothesized that leptin is necessary for homeostatic restoration of the HF-enhanced caloric intake and may mediate the increase in uncoupling protein-1 (UCP1) in brown adipose tissue (BAT). We employed a leptin antagonist to examine the role of leptin in these biological processes. Simultaneous central administration of leptin and increasing doses of the leptin antagonist revealed a dose-dependent inhibition of leptin-induced hypothalamic signal transducer and activator of transcription-3 phosphorylation, and 7 days of infusion of the leptin antagonist produced the predicted increase in food intake and weight gain. When delivered with exogenous leptin in a 7-day infusion, the leptin antagonist blocked leptin-mediated anorexic effects as well as the increase in BAT UCP1 protein and signal transducer and activator of transcription-3 phosphorylation. Rats were then fed an HF diet (60% kcal as fat) or chow and simultaneously infused with antagonist (25 microg/day into the lateral ventricle) for 7 days and compared with vehicle-infused chow-fed rats. Daily caloric intake of both HF groups peaked on day 2. HF feeding elevated caloric intake, which nearly normalized by day 7, whereas in the presence of the antagonist, caloric intake remained elevated. Moreover, the HF-mediated augmentation in UCP1 in BAT was prevented by the antagonist. These results demonstrate that leptin is essential for the homeostatic restoration of caloric intake after HF feeding and that this leptin antagonist is able to block central leptin signaling and leptin-mediated UCP1 elevation.

Adipose Tissue, Brown↗

Systematic review: applications and future of gastric electrical stimulation.

BACKGROUND: Over the past 20 years, gastric electrical stimulation has received increasing attention among researchers and clinicians. AIM: To give a systematic review on the effects, mechanisms and applications of gastric electrical stimulation. METHODS: Medline was used to identify the articles to be included in this review. Key words used for the search included gastric electrical stimulation, gastric pacing, electrical stimulation, stomach, gastrointestinal motility, central nervous system, gastroparesis, nausea and vomiting; obesity and weight loss. Combinational uses of these keywords were made to identify relevant articles. Most of the articles included in this review ranged from 1985 to 2006. RESULTS: Based on the general search, the review was structured as follows: (i) peripheral and central effects and mechanisms of gastric electrical stimulation; (ii) clinical applications of gastric electrical stimulation for gastroparesis and obesity and (iii) future development of gastric electrical stimulation. CONCLUSIONS: Great progress has been made during the past decades. Gastric electrical stimulation has been shown to be effective in normalizing gastric dysrhythmia, accelerating gastric emptying and improving nausea and vomiting. Implantable device has been made available for treating gastroparesis as well as obesity. However, development of a new device and controlled clinical studies are required to further prove clinical efficacy of gastric electrical stimulation.

Animals↗

Nanocrystalline silicon-based oligonucleotide chips.

A novel oligonucleotide array sensor has been developed with nanocrystalline Si (ncSi) substrates. The ncSi was prepared by electrochemical etching technique. Our study indicated that both the binding capacity and the hybridization efficiency are dependent upon the particle size of ncSi. In contrary, the chips developed with Si substrates exhibit the lower binding capacity and hybridization efficiency. The improved performances of the sensor chips are attributed to the large specific surface area of ncSi compared to the existing conventional techniques. The sensor chips with the ncSi substrate of 13 nm-sized particle can be regenerated and reused for at least 12 times. The oligonucleotide array sensor also shows high stability, which can bear relatively the stringent conditions (e.g. 80 degrees C, 75% of relative humidity and 3.6 klx of irradiation).

Nanoparticles↗

Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation.

Doublecortin (DCX) is a microtubule-associated protein expressed in migrating neuroblasts. DCX expression is increased in subventricular zone (SVZ) cells migrating to the boundary of an ischemic lesion after induction of middle cerebral artery occlusion (MCAO) in adult rats and mice. We tested the hypothesis that DCX, in addition to being a marker of migrating neuroblasts, serves to protect neuroblasts from conditions of stress, such as oxygen and glucose deprivation (OGD). Using gene transfer technology, we overexpressed DCX in rat SVZ and U-87 human glioma cells. The cells remained viable against severe OGD, up to 32 h exhibiting 1% apoptosis compared with 100% apoptosis in control. In addition, these genetically modified cells upregulated expression of E-, VE- and N-cadherin, molecules that promote endothelial survival signals via the VE-cadherin/vascular endothelial growth factor receptor-2/phosphoinositide 3-kinase (PI3-K)/AKT/beta-catenin pathway and inactivate the proapoptotic factor Bad. DCX overexpression also significantly increased cell migration in SVZ tissue explants and U-87 cells and significantly upregulated microtubule-associated protein-2 (MAP2) and nestin protein levels in SVZ and U-87 cells compared with wild-type control cells. Knocking down DCX expression in DCX overexpressing SVZ and U-87 cells with DCX small interfering RNA (siRNA), confirmed the specificity of DCX on cell survival against OGD, and the DCX induced upregulation of E-, VE- and N-cadherin, MAP2 and nestin. In NIH3T3 cells, DCX overexpression had no effect on cell survival against OGD, and indicating that the protective effects of DCX was restricted to brain cells e.g. SVZ and U-87 cells. Our data suggest a novel and an important role for DCX as a protective agent for migrating neuroblasts and tumor cells.

Analysis of Variance↗

Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells.

Recent studies indicate that the deposition of beta-amyloid (Abeta) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. The abnormal interactions of Abeta with metal ions such as copper are implicated in the process of Abeta deposition and oxidative stress in AD brains. In the present study, we established a new AD model, using which we found that copper triggered the Abeta neurotoxicity in SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw) in a concentration dependent manner. Fermented papaya preparation (FPP) has shown high free radical scavenging ability in vivo and in vitro. FPP post-treatment increased cell viability and decreased the intracellular [Ca2+]i, reactive oxygen species (ROS) generation such as hydroxyl free radical and superoxide anion and nitric oxide (NO) accumulation in the cell. Our results also show that FPP prevents the cell apoptosis through bax/bcl-2 sensitive pathway.

Amyloid beta-Peptides↗

Applied comparative physiology of the avian middle ear: the effect of static pressure changes in columellar ears.

We investigated the motion of the single ossicle found in the middle ears of four different species of birds. In the avian middle ear, the off centre attachment of the extracolumella to the tympanic membrane and the flexion of the joint between the extracolumella and columella results in rocking of the footplate rather than direct excursion in and out of the vestibule. We postulate that this is a protective mechanism to avoid excessive displacement of the footplate into the vestibule during changes in middle-ear pressure and that it is analogous to the ossicular 'decoupling' observed in the human middle ear in the same circumstances.

Animals↗

Deuterium NMR of the TGBA* phase in chiral liquid crystals.

A deuterium NMR (DNMR) study of the TGBA* (twist grain boundary smectic A*) phase in an NMR magnetic field of 9.4 T for the chiral compound 4-[4'-(1-methyl heptyloxy)] biphenyl 4-(10-undecenyloxy) benzoate (11EB1M7) is reported. The deuterium two-dimensional (2D) exchange spectra were observed for the first time in this phase. The present study allows us to learn how the helicoidal structures arrange in an external magnetic field. To derive quantitative kinetic parameters of this novel phase, both 1D and 2D experimental spectra were simulated by means of a jump diffusion model. By comparing the experimental and simulated spectra, an accurate determination of the dynamic parameters in the TGBA* phase was obtained. Furthermore, the twist angle between two neighboring smectic A blocks is found as 26 +/- 10 degrees, which is consistent with the X-ray results for similar chiral liquid crystals. The diffusion constant (D(parallel)) is estimated to be 3.2 x 10(-12) m(2)/s at 379.5 K.

Journal Article↗