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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury.

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in PO2, PCO2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

Acute Disease↗
PubMed2005

Measurements of the density-dependent many-body electron mass in two dimensional GaAs/AlGaAs heterostructures.

We determine the density-dependent electron mass m(*) in two-dimensional electron systems of GaAs/AlGaAs heterostructures by performing detailed low-temperature Shubnikov-de Haas measurements. Using very high-quality transistors with tunable electron densities we measure m(*) in single, high mobility specimens over a wide range of r(s) (6 to 0.8). Toward low densities we observe a rapid increase of m(*) by as much as 40%. For 2>r(s)>0.8 the mass values fall approximately 10% below the band mass of GaAs. Numerical calculations are in qualitative agreement with our data but differ considerably in detail.

Journal Article↗
PubMed2005

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.

Animals↗
PubMed2005

SOD-1 inhibits FAS expression in cortex of APP transgenic mice.

Peptides derived from proteolytic processing of the amyloid precursor protein (APP) are important for the pathogenesis of Alzheimer's disease (AD). In the present study, we found that transgenic mice overexpressing wild-type human APP gene (hAPP/+) displayed a much higher expression of FAS, one of the death receptor subfamily. This FAS overexpression was significantly reduced in the cortex of mice overexpressing both wild-type hAPP gene and wild-type human superoxide dismutase-1 gene (hSOD-1). Moreover hSOD-1 transgenic expression was associated with an increase of Glial fibrillary acidic protein (GFAP) production. This study indicates that SOD-1 overexpression can inhibit FAS expression, which may be beneficial in AD.

Alzheimer Disease↗
PubMed2005

Gender-specific association between pulse pressure and C-reactive protein in a Chinese population.

There is growing evidence that low-grade chronic inflammation, as reflected by the raised serum concentration of C-reactive protein, might be a risk factor for hypertension, in particular in women. We therefore investigated gender-specific associations of systolic and diastolic blood pressure and pulse pressure with serum C-reactive protein concentration in a Chinese population sample. In 463 participants, we measured serum C-reactive protein concentration using a high-sensitivity immunonephelometric latex-enhanced assay. We performed single and multiple linear regression analyses. The 224 male and 239 female subjects were of similar age (51.0 years) and had similar levels of systolic blood pressure (124.7 mmHg) and pulse pressure (47.1 mmHg), but men, compared with women, had higher diastolic blood pressure (79.6 vs 75.8 mmHg; P<0.0001) and body mass index (24.3 vs 23.4 kg/m2; P=0.003). Both before and after adjustment for age, age2, body mass index, current smoking, alcohol intake, and use of antihypertensive drugs, pulse pressure was significantly associated with serum C-reactive protein concentration in women (P< or =0.002) but not in men (P>0.10; P=0.02 for interaction between gender and serum C-reactive protein). In women, with one-fold increase in serum C-reactive protein concentration, pulse pressure was 1.94 mmHg higher. The categorical analyses confirmed our findings. With similar adjustments applied, women in the fourth quartile, compared with those in the lowest quartile, had a 7.6 mmHg higher pulse pressure (95% confidence interval 3.5-11.7 mmHg; P=0.0003). Furthermore, when women were analysed according to menopausal status, the association between pulse pressure and C-reactive protein was only significant in postmenopausal (P< or =0.04), but not in premenopausal, subjects (P> or =0.21). In conclusion, taken together with the previous gender-specific observations on carotid lesions and hypertension, our finding suggests that chronic low-grade inflammation might play a role in the widening of pulse pressure in Chinese women. This cross-sectional observation warrants further investigation in prospective studies.

Biomarkers↗
PubMed2005

Generalized linear latent variable models for repeated measures of spatially correlated multivariate data.

Observations of multiple-response variables across space and over time occur often in environmental and ecological studies. Compared to purely spatial models for a single response variable in the exponential family of distributions, fewer statistical tools are available for multiple-response variables that are not necessarily Gaussian. An exception is a common-factor model developed for multivariate spatial data by Wang and Wall (2003, Biostatistics 4, 569-582). The purpose of this article is to extend this multivariate space-only model and develop a flexible class of generalized linear latent variable models for multivariate spatial-temporal data. For statistical inference, maximum likelihood estimates and their standard deviations are obtained using a Monte Carlo EM algorithm. We also use a novel way to automatically adjust the Monte Carlo sample size, which facilitates the convergence of the Monte Carlo EM algorithm. The methodology is illustrated by an ecological study of red pine trees in response to bark beetle challenges in a forest stand of Wisconsin.

Algorithms↗
PubMed2005

Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation.

Neural stem cells (NSCs) are present not only in the developing nervous systems, but also in the adult human central nervous system (CNS). It is long thought that the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus are the main sources of human adult NSCs, which are considered to be a reservoir of new neural cells. Recently adult NSCs with potential neural capacity have been isolated from white matter and inferior prefrontal subcortex in the human brain. Rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny. However, sources of stem cells, large scale expansion, control of the differentiations, and tracking in vivo represent formidable challenges. In this paper we review the characteristics of the adult human NSCs, their potentiality in terms of proliferation and differentiation capabilities, as well as their large scale expansion for clinical needs. This review focuses on the major advances in brain stem cell-based therapy from the clinical perspective, and summarizes our work in clinical phase I-II trials with autologuous transplantation of adult NSCs for patients with open brain trauma. It also describes multiple approaches to monitor adult human NSCs labeled superparamagnetic nanoparticles after transplantation and explores the intriguing possibility of stem cell transplantation.

Animals↗
PubMed2004

An integrated genetic map and a new set of simple sequence repeat markers for pearl millet, Pennisetum glaucum.

Over the past 10 years, resources have been established for the genetic analysis of pearl millet, Pennisetum glaucum (L.) R. Br., an important staple crop of the semi-arid regions of India and Africa. Among these resources are detailed genetic maps containing both homologous and heterologous restriction fragment length polymorphism (RFLP) markers, and simple sequence repeats (SSRs). Genetic maps produced in four different crosses have been integrated to develop a consensus map of 353 RFLP and 65 SSR markers. Some 85% of the markers are clustered and occupy less than a third of the total map length. This phenomenon is independent of the cross. Our data suggest that extreme localization of recombination toward the chromosome ends, resulting in gaps on the genetic map of 30 cM or more in the distal regions, is typical for pearl millet. The unequal distribution of recombination has consequences for the transfer of genes controlling important agronomic traits from donor to elite pearl millet germplasm. The paper also describes the generation of 44 SSR markers from a (CA)n-enriched small-insert genomic library. Previously, pearl millet SSRs had been generated from BAC clones, and the relative merits of both methodologies are discussed.

Africa↗
PubMed2004

Human topoisomerase I mediates illegitimate recombination leading to DNA insertion into the ribosomal DNA locus in Saccharomyces cerevisiae.

Eukaryotic type I DNA topoisomerases catalyze the relaxation of supercoiled DNA, and play a critical role in DNA replication, transcription and recombination. They are highly conserved, both in sequence and mechanism of activity, from yeast to mammalian cells. We tested the effect of human topoisomerase I (hTOP1) on illegitimate insertion in yeast by expressing the hTOP1 gene in top1Delta yeast ( ytop1Delta) cells. hTOP1 increased the frequency of illegitimate recombination into genomic DNA by 20- to 90-fold relative to the level in ytop1Delta cells, while it had no effect on homologous integration. The addition of the topoisomerase I inhibitor camptothecin blocked this increase in the level of illegitimate insertion. The expression of hTOP1 also significantly enhanced the fraction of integration events in ribosomal DNA (rDNA)-from 16% to 60%, indicating that the rDNA is a highly preferred target for hTOP1. Integrations occurred at the consensus sequence 5' (T/A) (G/C/A) (T/A) (T/C/A) 3' in hTOP1 expressing cells. A similar preferred break-site consensus sequence was previously identified in vitro for topoisomerases from rat liver and wheat germ.

Camptothecin↗
PubMed2004

Marker-evaluated selection in rice: shifts in allele frequency among bulks selected in contrasting agricultural environments identify genomic regions of importance to rice adaptation and breeding.

Conventional methods for quantitative trait locus (QTL) mapping require the selection of particular traits to be measured based on assumptions as to their importance. We have tested an alternative approach for the location of QTLs-marker-evaluated selection-that makes no prior assumptions as to which traits are important. The results of phenotype selection were evaluated in the products of modified bulk-population breeding that was replicated across a range of rice ecosystems. Selection was carried out in close collaboration with farmers in bulk populations that were all derived from a cross between an Indian upland variety (Kalinga III) and a high-yielding semi-dwarf variety (IR64).Twenty-seven diverse bulks were produced that were screened with molecular markers in order to determine whether shifts could be detected in marker allele frequency as a result of selection and if such changes varied by genomic region across ecosystems. Marker loci linked to important traits for adaptation to specific environments were identified without making any prior assumptions about which traits might be important. Genomic regions from Kalinga III were strongly selected in the upland environments and regions from IR64 in the lowland ones.However, exceptions occurred where the upland parent contributed positively to lowland adaptation and vice versa. The results can be used as a basis for the development of second-cycle varieties, using marker-assisted selection to produce genotypic ideotypes for specific target environments. The very strong selection for genomic regions from the adapted parents of the wide(upland x lowland) cross indicates that, in non-marker-assisted breeding, where genetically distant parents have been used, modified backcross breeding should be efficient. A single backcross to the adapted parent for aspecific ecosystem will result in a higher frequency of segregants with the desired high genetic contribution from the adapted parent.

Acclimatization↗
PubMed2004

A small animal model of regional alveolar ventilation using HP 3He MRI1.

RATIONALE AND OBJECTIVES: The aim of this study was to establish a standardized procedure for the measurement of regional fractional ventilation in a healthy rat model as a baseline for further studies of pulmonary disorder models. MATERIALS AND METHODS: The lungs of five healthy male Sprague-Dawley rats were imaged using hyperpolarized helium-3 magnetic resonance imaging. From these images, regional fractional ventilation was calculated and maps generated detailing the distribution of fractional ventilation in the lung. The 1.56 mm x 1.56 mm x 4 mm regions of interest were assigned on 5 cm x 5 cm field of view lung maps. Histograms were also generated showing the frequency distribution of fractional ventilation values. To compare fractional ventilation values between animals, the ventilation procedure was standardized to results from individual pulmonary function tests. Each animal's spontaneous tidal volume, respiratory rate, and inspiration percentage (percent of total respiratory cycle in inspiration) were used in their mechanical ventilation settings. RESULTS: Results were similar among all five healthy rats based on examination of ventilation distribution maps and frequency distribution histograms. Mean (0.13) and standard deviation (0.07) were calculated for fractional ventilation in each animal. However, these values were determined to be influenced by slice selection, and therefore the maps and histograms were favored in analysis of results. CONCLUSION: This study shows consistent results in healthy rat lungs and will serve as a baseline study for future measurements in emphysematous rat lungs.

Animals↗
PubMed2004

Refinement in quantitative convergent beam electron diffraction (QCBED).

Quantitative convergent beam electronic diffraction (QCBED) method is a powerful tool for the investigation of the atomic and electronic structure of crystals. In this work, a global optimization algorithm has been adopted and a new fitting manner has been suggested in our recently developed QCBED program. A study of the charge density distribution in intermetallics is demonstrated as an example. Using the QCBED method, an investigation of lattice distortion in oxides is attempted.

Journal Article↗
PubMed2004

Cationic corticosteroid for nonviral gene delivery.

Delivery of plasmid DNA for gene therapy often provokes an inflammatory response that reduces transgene expression. Cationic lipids for lipofection lack pharmacological activity despite the hydrophobicity of many drug candidates that could be exploited. We report a one-step synthesis of a water-soluble, dexamethasone-spermine (DS) cationic lipid that has potent gene transfer capability in confluent endothelial cells when used with the neutral lipid, dioleoylphosphatidylethanolamine (DOPE). In contrast, unconjugated mixtures of dexamethasone, spermine, and/or DOPE have essentially no gene transfer activity. DS retains partial corticosteroid character as quantified by the rapid translocation of glucocorticoid receptor to the nucleus and by dose-dependent transactivation from a glucocorticoid response element. DS has anti-inflammatory activity in vivo in the mouse thioglycollate model of inflammation. In a mouse lung model, DS:DOPE resulted in significantly less interferon-gamma production at Day 1 and elevated transgene expression at Days 1 and 7 postintranasal instillation compared to DC-Chol:DOPE (sterol:DOPE:phosphate molar ratio of 1:1:1). Cationic pharmacophores such as DS represent a new approach to gene delivery and localized therapy.

Animals↗
PubMed2004

A defective nontransmissible recombinant Sendai virus mediates efficient gene transfer to airway epithelium in vivo.

Recombinant Sendai virus (SeV)-mediated gene transfer to differentiated airway epithelial cells has shown to be very efficient, because of its ability to overcome the intra- and extracellular barriers known to limit gene delivery. However, this virus is transmission competent and therefore unlikely to be suitable for use in clinical trials. A nontransmissible, replication-competent recombinant SeV has recently been developed by deleting the envelope Fusion (F) protein gene (SeV/DeltaF). Here we show that SeV/DeltaF is able to mediate beta-galactosidase reporter gene transfer to the respiratory tract of mice in vivo, as well as to human nasal epithelial cells in vitro. Further, in an ex vivo model of differentiated airway epithelium, SeV/DeltaF gene transfer was not importantly inhibited by native mucus. When compared to the transmission-competent SeV in vivo, no difference in gene expression was observed at the time of peak expression. The development of an F-defective nontransmissible SeV, which can still efficiently mediate gene transfer to the airway epithelium, represents the first important step towards the use of a cytoplasmic RNA viral vector in clinical trials of gene therapy.

Adult↗
PubMed2004

Homology modeling of lanosterol 14alpha-demethylase of Candida albicans and Aspergillus fumigatus and insights into the enzyme-substrate Interactions.

The crystal structure of 14alpha-sterol demethylase from Mycobacterium tuberculosis (MT_14DM) provides a good template for modeling the three dimensional structure of lanosterol 14alpha-demethylase, which is the target of azole antifungal agents. Homologous 3D models of lanosterol 14alpha-demethylase from Candida albicans (CA_14DM) and Aspergillus fumigatus (AF_14DM) were built on the basis of the crystal coordinates of MT_14DM in complex with 4-phenylimidazole and fluconazole. The reliability of the two models was assessed by Ramachandran plots, Profile-3D analysis, and by analyzing the consistency of the two models with the experimental data on the P450(14DM). The overall structures of the resulting CA_14DM model and AF_14DM model are similar to those of the template structures. The two models remain the core structure characteristic for cytochrome P450s and most of the insertions and deletions expose the molecular surface. The structurally and functionally important residues such as the heme binding residues, the residues lining the substrate access channel, and residues in active site were identified from the model. To explore the binding mode of the substrate with the two models, 24(28)-methylene-24,25-dihydrolanosterol was docked into the active site of the two models and hydrophobic interaction and hydrogen-bonding were found to play an important role in substrate recognition and orientation. These results provided a basis for experiments to probe structure-function relationships in the P450(14DM). Although CA_14DM and AF_14DM shared similar core structural character, the active site of the two models were quite different, thus allowing the rational design of specific inhibitors to the target enzyme and the discovery of novel antifungal agents with broad spectrum.

Amino Acid Sequence↗
PubMed2004

Simultaneous carbon and nitrogen removal in anoxic-aerobic circulating fluidized bed biological reactor (CFBBR).

Biological nutrient removal (BNR) in municipal wastewater treatment to remove carbonaceous substrates and nutrients, has recently become increasingly popular worldwide due to increasingly stringent regulations. Biological fluidized bed (BFB) technology, which could be potentially used for BNR, can provide some advantages such as high efficiency and a compact structure. This work shows the results of simultaneous elimination of organic carbon and nitrogen using a circulating fluidized bed biological reactor (CFBBR, which has been developed recently for chemical engineering processes. The CFBBR has two fluidized beds, running as anoxic and aerobic processes to accomplish simultaneous nitrification and denitrification, with continuous liquid recirculation through the anoxic bed and the aerobic bed. Soluble COD concentrations in the effluent ranging from 4 to 20 mg l(-1) were obtained at varying COD loading rates; ammonia nitrogen removal efficiencies averaged in excess of 99% at a minimum total hydraulic retention time (HRT) of 2.0 hours over a temperature range of 25 degrees C to 28 degrees C. Effluent nitrate nitrogen concentration of less than 5 mg l(-1) was achieved by increasing effluent recycle rate. No nitrite accumulation was observed either in the anoxic bed or in the aerobic bed. The system was able to treat grit chamber effluent wastewater at a HRT of 2.0 hours while achieving average effluent BOD, COD, NH3-N, TKN, nitrates, total phosphate, TSS and VSS concentrations of 10 mg l(-1), 18 mg l(-1), 1.3 mg l(-1), 1.5 mg l(-1), 7 mg l(-1), 2.0 mg l(-1), 10 mg l(-1) and 8 mg l(-1) respectively. The CFBBR appears to be not only an excellent alternative for conventional activated sludge type BNR technologies but also capable of processing much higher loadings that are suitable for industrial applications.

Bacteria, Aerobic↗
PubMed2004

Differential expression of iodothyronine deiodinase type 2 in growth plates of chickens divergently selected for incidence of tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is a genetic leg defect in broilers with a lesion of avascular, non-calcified cartilage below the growth plate of the proximal tibiatarsus. This disease is considered to result from the inability of chondrocytes to undergo terminal differentiation. Thyroid hormones are required for chondrocyte differentiation. The thyroid gland produces and secrets mostly L-thyroxine or T4 and T4 plays most of its biological activities through conversion to triiodothyronine or T3 in local tissues by iodothyronine deiodinases type 1 or type 2, which are tissue specific. In this study, no differences were found in the plasma concentrations of total T3 and T4 between two chicken lines divergently selected for the incidence of TD. Plasma T4 was higher than T3, especially in older chickens. Younger birds had much higher T3 than older birds, but there were no significant age differences in T4. The expression level of deiodinase type 2 in the growth plates of broilers with TD was one-eighth of those birds without the disease. The expression levels of deiodinase type 2 (DIO2) in commercial broilers without the disease were much higher than those with TD and lower than those without the disease in the susceptible and resistant lines, respectively. These results indicate that the inadequate expression of DIO2 in the growth plates contributes to the pathogenesis of TD in broilers and that TD is a tissue-specific hypothyroidism.

Animals↗