Search PubMed⌕ Search

Biomedical subjects

X Zhu

Publications and source records attributed to X Zhu.

At least 55 records · Page 3Linked to original sources
PubMed2004

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Base Sequence↗
PubMed2004

Haplotype block definition and its application.

We present a simple two-stage procedure to define haplotype blocks and construct a statistic to test whether a polymorphism belongs to a block. Applying this method to the data of Gabriel et al. [2002] yielded longer haplotype blocks than were originally reported with a similar average percentage of common haplotypes in blocks. Furthermore, across regions of the genome and among the four populations that were studied, we found that linkage disequilibrium between a given single nucleotide polymorphism (SNP) and the haplotype block was a monotonic function of distance. This correlation was essentially independent of the minor allele frequency of the putative causal SNP when it fell outside of the block, however it was strongly dependent on the minor allele frequency when the SNP was internal to the block. These results have direct application to the design of candidate gene or region-wide association studies.

Algorithms↗
PubMed2004

Additive blockade of beta 2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate.

Migration of human eosinophils is regulated by integrin expression, conformational change, and activation of cytosolic phospholipase A2 (cPLA2). Corticosteroids have been shown to inhibit cPLA2 hydrolysis in human eosinophils. The objective of this study was to determine the mechanisms of fluticasone propionate (FP) alone or in combination with salmeterol (SM) in blocking adhesion mediated by beta 2-integrin in human eosinophils. Human eosinophils were isolated by negative magnetic selection. beta 2-integrin-mediated eosinophil adhesion was measured by residual eosinophil peroxidase activity. Eosinophils were pretreated for 12 h to 24 h with FP and with or without SM for 30 min. Both SM alone and FP alone inhibited eosinophil adhesion in concentration- and time-dependent manner. SM alone modestly (approximately 30%) inhibited interleukin (IL)-5-induced eosinophil adhesion. Blockade of IL-5-induced eosinophil adhesion caused by 10(-7) M FP at 24 h was augmented by 10(-7) M SM from 41.5% to 72.5%. Similar blockade was also observed for eotaxin-induced eosinophil adhesion. Neither SM, FP, nor FP + SM blocked either: 1) upregulation of CD11b surface expression; or 2) phosphorylation of cPLA2. Blockade of beta 2-integrin-mediated eosinophil adhesion by fluticasone propionate is augmented by salmeterol. Decreased adhesion results from augmented blockade of nuclear translocation of cytosolic phospholipase A2 caused by addition of salmeterol to fluticasone.

Adrenergic beta-Agonists↗
PubMed2004

Mitotic and gender parallels in Alzheimer disease: therapeutic opportunities.

In this review, we discuss the role of cell cycle dysfunction in the pathogenesis of Alzheimer disease and propose that such mitotic catastrophe, as one of the earliest events in neuronal degeneration, may, in fact, be sufficient to initiate the neurodegenerative cascade. The question as to what molecule initiates cell cycle dysfunction is now beginning to become understood and, in this regard, the gender-predication, age-related penetrance and regional susceptibility of specific neuronal populations led us to consider luteinizing hormone as a key mediator of the abnormal mitotic process. As such, agents targeted toward luteinizing hormone or downstream sequelae may be of great therapeutic value in the treatment of Alzheimer disease.

Alzheimer Disease↗
PubMed2003

Measurements of GnE/GnM from the 2H(e-->,en-->)1H Reaction to Q2=1.45 (GeV/c)2.

We report new measurements of the ratio of the electric form factor to the magnetic form factor of the neutron, G(n)(E)/G(n)(M), obtained via recoil polarimetry from the quasielastic 2H(e-->,e(')n-->)1H reaction at Q2 values of 0.45, 1.13, and 1.45 (GeV/c)(2) with relative statistical uncertainties of 7.6% and 8.4% at the two higher Q2 points, which points have never been achieved in polarization measurements.

Journal Article↗
PubMed2003

High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.

High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.

Journal Article↗
PubMed2003

Thiazolidinediones, a class of anti-diabetic drugs, inhibit Id2 expression through a PPARgamma-independent pathway in human aortic smooth muscle cells.

Inhibitor of DNA binding (Id2) is a member of the helix-loop-helix family of transcription regulators that is known to play important roles in the proliferation and differentiation of many cell types. Overexpression of Id2 has been reported to result in significant enhancement of vascular smooth muscle cell growth via increased S phase entry. We hypothesized that downregulation of Id2 gene expression by thiazolidinediones (TZDs), a class of anti-diabetic drugs and peroxisome proliferator-activated receptor gamma (PPARgamma) activators, might contribute to the anti-atherosclerotic and anti-hypertensive effects of the PPARgamma. Here we document that TZDs, including troglitazone and ciglitazone, repress Id2 gene expression in a doses- and time-dependent manner. However, GW7845, a high-affinity and non-TZD PPARgamma activator, had no inhibitory effect on Id2 gene expression. In addition, PPARgamma antagonist GW9662 did not rescue TZD-induced Id2 repression. Taken together, our data suggest that TZDs repress Id2 expression through a PPARgamma-independent pathway.

Anilides↗
PubMed2003

Qualitative semi-parametric test for genetic associations in case-control designs under structured populations.

Recently, statistical methods have been proposed using genomic markers to control for population stratification in genetic association studies. However, these methods either have unacceptable low power when population stratification becomes strong or cannot control for population stratification well under admixture population models. In this paper, we propose a semiparametric association test to detect genetic association between a candidate marker and a qualitative trait of interest in case-control designs. The performance of the test is compared to other existing methods through simulations. The results show that our method gives correct type I error rate both under discrete population models and admixture population models, and our method is robust to the extent of the population stratification. In most of the cases we considered, our method has higher power and, in some cases, substantially higher power than that of existing methods.

Case-Control Studies↗
PubMed2003

Biomass accumulation patterns for removing volatile organic compounds in rotating drum biofilters.

A rotating drum biofilter (RDB) with multi-layered foam media was developed for the improvement of current biofiltration technology. The biofilter was used to investigate the effects of organic loadings and influent volatile organic compound (VOC) concentrations on VOC removal efficiency and biomass accumulation. These effects were evaluated using diethyl ether and toluene separately as model VOCs at an empty bed contact time (EBCT) of 30 s. When the toluene loading increased from 2.0 to 4.0 and 8.0 kgCOD m(-3) day(-1), toluene removal efficiency of the biofilter decreased from over 99% to 78% and 74%, respectively. The biomass distribution was found to be more even within the medium when removing toluene than when removing diethyl ether. Higher organic loading also resulted in the more even distribution of the biomass. The ratios of biomass accumulation rates in the medium of the outermost, middle and innermost layers ranged from 1:0.11:0.02 when removing diethyl ether at 2.0 kgCOD m(-3) day(-1) to 1:0.69:0.51 when removing toluene at 8.0 kgCOD m(-3) day(-1). Review of these ratios revealed three biomass accumulation patterns: surface pattern, in-depth pattern and shallow pattern. Different patterns represent different removal mechanisms in the biofiltration process. Improved biofilter design and operation should be based on the biomass accumulation pattern.

Biodegradation, Environmental↗
PubMed2002

Inheritance and fine mapping of fertility restoration for cytoplasmic male sterility in Gossypium hirsutum L.

Genetics of CMS fertility restoration was presented through the analysis of classic genetics and molecular markers. Based on F(2) segregation of the crosses between CMS and the restoring lines, the testcrosses and F(1) x F(1) populations, together with RAPD and SSR mapping, one dominant gene was identified to control the CMS fertility restoration in cotton. The strategy of genotype representation analysis (GRA) was put forward to screen the markers linked with the Rf(1) locus. Using 1,025 random decamer primers and 282 pairs of SSR primers, two RAPD and three SSR markers were identified to be closely linked to the Rf(1) gene. Among the five markers, three were co-dominantly inherited. Additionally, based on the analysis of monosomic and telesomic lines with one SSR maker, the Rf(1) locus could be located on the long arm of chromosome 4. The molecular markers available here are helpful in the development of the elite restoring lines in cotton by marker-assisted selection.

Chromosome Mapping↗
PubMed2002

[Preoperative evaluation of renal carcinoma using multi-detector CT].

When laparoscopic nephrectomy is performed, the limited visibility of many anatomical structures requires additional pre-operative information. However, most of this information can be highlighted by Multislice-CT which depicts all the vascular structures while providing an essential road mapping for the surgeon. Besides underlining arterial abnormalities, this technique allows to depict venous pathways and tumoral invasion. This review illustrates the various potential applications of Multislice-CT in the evaluation of renal tumors.

Humans↗
PubMed2002

Over-expression of beta-1,4-galactosyltransferase V increases the growth of astrocytoma cell line.

Our previous study showed that the gene expression of beta-1,4-galactosyltransferase V (beta-1,4-GalT V), preferentially galactosylating GlcNAc1-->6Man of oligosaccharides, increased in the process of astrocytoma progress, with the highest level in grade IV astrocytoma. To investigate the function of this beta-1,4-GalT in cell proliferation, the sense and antisense cDNA of beta-1,4-GalT V was constructed as pcDNA3-HA-GalT V and pcDNA3-anti-GalT V respectively and transfected into SHG cell, a kind of human astrocytoma cell line. The transfection was confirmed with Northern and Western blot assay. It was found that the growth of SHG/HA-GalT V in serum-containing medium was faster than that of mock-transfectant with the vector pcDNA3, whereas the growth of SHG/GalTV-AS was slower than that of mock-transfectant. GalTV-HA/SHG showed a stronger capability for colony formation than that of GalTV-AS/SHG as evaluated by anchorage-independent growth in soft agar assay. This result was consistent with that of the growth curve. By RCA-1 lectin assay, the galactosylation on the surface of GalTV-HA/SHG and SHG/GalTV-AS was stained stronger (P<0.001) and weaker (P<0.05) respectively compared with the mock transfectant. This indicates that beta-1,4-GalT V was involved in the malignant phenotype of astrocytoma cells, possibly causing the high galactosylation on the cell surface.

Astrocytoma↗
PubMed2001

Positive and negative modulation by AMPA- and kainate-receptors of striatal kainate injection-induced neuronal loss in rat forebrain.

We investigated the roles of ionotropic glutamate receptor subtypes in mediating striatal kainate injection-induced neuronal loss in rat forebrain, using subtype-specific antagonists and histochemical staining. Our study demonstrates that kainate injected unilaterally into the striatum induces a massive neuronal loss in the rat ipsilateral forebrain through activation of kainate receptors and, to a limited extent, a consequent involvement of M-methyl-D-aspartate (NMDA) receptors, whereas activation of alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors shows a neuroprotective effect. These and previous results suggest that three subtypes of ionotropic glutamate receptors play differential roles in mediating excitatory amino acid (EAA)-induced neurodegeneration.

Animals↗
PubMed2001

Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening.

Bcl-2 belongs to a growing family of proteins which regulates programmed cell death (apoptosis). Overexpression of Bcl-2 has been observed in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer. Thereby, Bcl-2 is an attractive new anti-cancer target. Herein, we describe the discovery of novel classes of small-molecule inhibitors targeted at the BH3 binding pocket in Bcl-2. The three-dimensional (3D) structure of Bcl-2 has been modeled on the basis of a high-resolution NMR solution structure of Bcl-X(L), which shares a high sequence homology with Bcl-2. A structure-based computer screening approach has been employed to search the National Cancer Institute 3D database of 206 876 organic compounds to identify potential Bcl-2 small-molecule inhibitors that bind to the BH3 binding site of Bcl-2. These potential Bcl-2 small-molecule inhibitors were first tested in an in vitro binding assay for their potency in inhibition of the binding of a Bak BH3 peptide to Bcl-2. Thirty-five potential inhibitors were tested in this binding assay, and seven of them were found to have a binding affinity (IC(50) value) from 1.6 to 14.0 microM. The anti-proliferative activity of these seven active compounds has been tested using a human myeloid leukemia cell line, HL-60, which expresses the highest level of Bcl-2 protein among all the cancer cell lines examined. Compound 6 was the most potent compound and had an IC(50) value of 4 microM in inhibition of cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Five other compounds had moderate activity in inhibition of cell growth. Compound 6 was further evaluated for its ability to induce apoptosis in cancer cells. It was found that 6 induces apoptosis in cancer cells with high Bcl-2 expression and its potency correlates with the Bcl-2 expression level in cancer cells. Furthermore, using NMR methods, we conclusively demonstrated that 6 binds to the BH3 binding site in Bcl-X(L). Our results showed that small-molecule inhibitors of Bcl-2 such as 6 modulate the biological function of Bcl-2, and induce apoptosis in cancer cells with high Bcl-2 expression, while they have little effect on cancer cells with low or undetectable levels of Bcl-2 expression. Therefore, compound 6 can be used as a valuable pharmacological tool to elucidate the function of Bcl-2 and also serves as a novel lead compound for further design and optimization. Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2.

Amino Acid Sequence↗
PubMed2001

Platelet-derived growth factor promotes the expression of peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells by a phosphatidylinositol 3-kinase/Akt signaling pathway.

Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), and the administration of pharmacological PPARgamma agonists attenuates vascular lesion formation. The factors that regulate PPARgamma expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPARgamma by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPARgamma mRNA and protein were increased by 2- to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20 ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50 micromol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10 micromol/L), but not affected by a p38 kinase inhibitor (SB202190, 10 micromol/L). In addition, overexpression of the dominant-negative p85 subunit of PI3-kinase or Akt proteins blocked the PDGF-induced PPARgamma expression. Taken together, our results suggest that PDGF induces PPARgamma expression in VSMCs by a PI3-kinase/Akt signaling pathway. The characterization of factors and signaling pathways that modulate PPARgamma expression in VSMCs may have important implications for understanding the pathogenesis of vascular diseases.

Aorta↗
PubMed2001

Enhanced therapeutic effect of multiple injections of HSV-TK + GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model.

PURPOSE: Standard therapies for breast cancer lack tumor specificity and have significant risk for recurrence and toxicities. Herpes simplex virus-thymidine kinase (HSV-tk) gene therapy combined with radiation therapy (XRT) may be effective because of complementary mechanisms and distinct toxicity profiles. HSV-tk gene therapy followed by systemic administration of ganciclovir (GCV) enhances radiation-induced DNA damage by generating high local concentrations of phosphorylated nucleotide analogs that increase radiation-induced DNA breaks and interfere with DNA repair mechanisms. In addition, radiation-induced membrane damage enhances the "bystander effect" by facilitating transfer of nucleotide analogs to neighboring nontransduced cells and by promoting local and systemic immune responses. This study assesses the effect of single and multiple courses of HSV-tk gene therapy in combination with ionizing radiation in a mouse mammary cancer model. METHODS AND MATERIALS: Mouse mammary TM40D tumors transplanted s.c. in syngeneic immunocompetent BALB-c mice were treated with either adenoviral-mediated HSV-tk gene therapy or local radiation or the combination of gene and radiation therapy. A vector consisting of a replication-deficient (E1-deleted) adenovirus type 5 was injected intratumorally to administer the HSV-tk gene, and GCV was initiated 24 h later for a total of 6 days. Radiation was given as a single dose of 5 Gy 48 h after the HSV-tk injection. A metastatic model was developed by tail vein injection of TM40D cells on the same day that the s.c. tumors were established. Systemic antitumor effect was evaluated by counting the number of lung nodules after treating only the primary tumors with gene therapy, radiation, or the combination of gene and radiation therapy. To assess the therapeutic efficacy of multiple courses of this combinatorial approach, one, two, and three courses of HSV-tk + GCV gene therapy, in combination with radiation, were compared to HSV-tk or XRT alone and to sham-treated animals. (Treatments were repeated at 7-day intervals from the HSV-tk injection.) RESULTS: Both single-therapy modalities reduced tumor growth by 11% compared to controls, while the combined therapy resulted in a decrease of 29%. Median survival was 36 days in the combined therapy group, compared to 33 days in the monotherapy groups and 26 days in the control group. In the metastatic model, the number of lung nodules was reduced by 59.5% after HSV-tk gene therapy, whereas radiotherapy had no effect on metastatic growth. Combined therapy led to an additional 66.7% reduction in lung colonization. Compared to controls, local tumor growth was maximally suppressed by three courses of combined therapy (51.5%), followed by two courses of combined therapy (37.2%), and three sessions of XRT alone (35.6%). Median survival was also significantly prolonged to 58 days with the three courses of combined therapy, followed by two courses, to 45 days. All other treatment groups demonstrated median survival times between 26 and 35 days, while controls had a median survival of 24 days. CONCLUSIONS: These results indicate that multiple courses of HSV-tk therapy in combination with radiation improve the therapeutic efficacy of this approach and may provide therapeutic implications for the treatment of human breast cancer and other solid tumors.

Adenoviridae↗
PubMed2001

[The effect of estrogen receptor gene Px haplotype on bone mineral density in Chinese postmenopausal women].

OBJECTIVE: To investigate the relationship among the PvuII and XbaI polymorphism of estrogen receptor (ER) gene and bone mineral density (BMD, z-score) and bone biochemical markers in Chinese postmenopausal women. METHODS: The BMD of lumbar vertebrae (L2-4) and femoral neck (FN) of 186 postmenopausal women (aged 65.0 +/- 0.6 yr) were measured by DEXA. The polymorphism of ER gene (PvuII and XbaI) was detected by PCR-RFLP method. Serum AKP, BGP and urinary Pyd were measured by ELISA. Results The polymorphism of ER receptor can be divided into two sets: PP (14.5%), Pp (50.0%), and pp (35.5%); and 3 PvulI RFLPs and XX (7.0% ), Xx (27.4%), and xx (65.6%) 3 XbaI RFLPs. The bone markers were not significantly different among the 3 groups in each of the two sets of polymorphism. The FN BMD of women of pp genotype was higher than that of Pp genotype (P = 0.02). The BMD of 12-4 was higher in women of XX genotype than those in women of Xx and xx genotypes (P = 0.0003 and 0.0002 respectively). Women without Px haplotype (PPXX, PpXX, ppxx, n=79) had higher L2-4 BMD (P = 0.02) and FN BMD (P = 0.03) and lower serum AKP (P = 0.04) than those with Px genotype (PPxx and PPXx, Ppxx, PpXx, n=107). CONCLUSION: pp and XX genotype of ER gene may play a certain role in maintaining FN and L2-4 BMD. The genotypes without Px haplotype might exert some favorable effect on BMD, while those with Px haplotype may be harmful to bone

Aged↗