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Computers & Graphics 01/2013; · 1.00 Impact Factor
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ABSTRACT: Malignant melanoma (MM) has the highest morbidity of any malignant tumour. It is known that the Wnt pathway of enhances the development of melanoma. Dickkopf (DKK)-1, an inhibitor of the canonical Wnt/β-catenin pathway, might also inhibit the development of MM.
To examine the influence of DKK-1 expression on the invasive activity of MM cells.
To detect DKK-1 expression level we performed immunohistochemistry on human tissue sections of normal skin, malignant melanoma (MM) in situ, and MM with lymph-node metastasis. To clarify the role that DDK-1 plays in the invasive activity of MM cells, we performed a scratch-wound healing assay and Transwell invasion assay for A375 cells infected with appropriate recombinant adenoviruses, then assessed the migration of these cells.
Fewer DDK1-overexpressing A375 cells than control cells migrated to the scratch-wound area or through the pores of the Transwell membrane to the lower wells. Downregulation of DKK-1 in A375 cells had the opposite effect.
In the present study, we found for the first time that DKK-1 expression inhibits the invasive activity of MM cells.
Clinical and Experimental Dermatology 03/2012; 37(4):404-10. · 1.20 Impact Factor
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L Guo,
X Luo,
A Zhao,
H Huang,
Z Wei,
L Chen,
S Qin,
L Shao,
J Xuan,
G Feng,
C Minghua,
J Luan,
L He, Q Xing
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ABSTRACT: Dowling-Degos disease (DDD; MIM 179850) is an autosomal dominant genodermatosis caused by mutations in keratin 5 gene (KRT5). KRT5 is specifically expressed in basal layer of epidermis and plays an important role in protecting epithelial cells from mechanical and non-mechanical stresses.
We analysed the molecular basis of DDD in a Chinese family.
Genomic DNA of the Chinese DDD family and a matched control cohort was isolated according to standard techniques. All exons of the KRT5 gene and adjacent exon-intron border sequences were amplified using PCR and directly sequenced.
We identified a novel keratin 5 (K5) nonsense mutation designated c.C10T (p.Gln4X) in exon 1 of the KRT5 gene.
Our data expand the spectrum of mutations in the KRT5 gene underlying DDD.
Journal of the European Academy of Dermatology and Venereology 05/2011; 26(7):908-10. · 2.98 Impact Factor
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J Du,
A Zhang,
L Wang,
J Xuan,
L Yu,
R Che,
X Li,
N Gu,
Z Lin,
G Feng, Q Xing,
L He
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ABSTRACT: In this study, we examined the relationships between plasma concentrations of risperidone and 9-hydroxyrisperidone and polymorphisms of CYP3A4. All 130 schizophrenia patients (45 men, 85 women, age 15-60 years) who met DSM-IV criteria were given risperidone for 8 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). CYP3A4*1G was found to be associated with the change in total PANSS scores (Kruskal-Wallis test, P = 0.021), which was not significant on adjusting for multiple testing. Our study has, for the first time, conducted a genetic association study of the CYP3A4 gene with risperidone response. Further studies on larger groups and on the effects of the longer term risperidone treatment are needed to confirm these results.
Journal of Psychopharmacology 05/2009; 24(7):1115-20. · 3.04 Impact Factor
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ABSTRACT: The application of pharmacogenetics is currently one of the most promising developments in anti-psychotic treatment and is attracting more and more attention. Although risperidone belongs to the first-line atypical anti-psychotics, there have been relatively few risperidone pharmacogenetic studies, especially in Asian populations. We investigated the relationship between the C825T polymorphism of GBN3 (rs5443) and the -1019 C/G polymorphism of 5-HT(1)A (rs6295) and response to risperidone treatment. One-hundred and thirty schizophrenia patients were recruited. They were treated with risperidone monotherapy for eight weeks. Clinical response was assessed on the Positive and Negative Syndrome Scale (PANSS) on the day of admission and was subsequently assessed after eight weeks following the treatment. Patients were genotyped for two functional polymorphisms: C825T of GBN3 (rs5443) and -1019 C/G of HT(1)A (rs6295). Association tests between genotypes and percentage improvement in total PANSS scores, as well as positive symptom scores and negative symptom scores, were performed using analyses of variance (ANOVA). The -1019 C/G polymorphism of HT(1)A (rs6295) was associated with negative symptom response to treatment. Patients with the CC genotype showed substantial improvement as regards negative symptom response (F = 4.177, df = 2, P = 0.019), compared with the patients with the CG and GG genotypes. No association was observed between C825T of GBN3 (rs5443) and changes in PANSS scores. The results suggest that the -1019 C/G polymorphism (rs6295) in the 5-HT(1)A gene may be a useful predictor of reduction in negative symptoms in schizophrenic patients treated with risperidone.
Journal of Psychopharmacology 03/2008; 22(8):904-9. · 3.04 Impact Factor
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J Du,
S Duan,
H Wang,
W Chen,
X Zhao,
A Zhang,
L Wang,
J Xuan,
L Yu,
S Wu,
W Tang,
X Li,
H Li,
G Feng, Q Xing,
L He
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ABSTRACT: Studies suggest that GAD1 gene is a functional candidate susceptibility gene for schizophrenia. In order to investigate the contribution of GAD1 gene to the etiology of schizophrenia in Chinese, we carried out a family-based association study between GAD1 gene and schizophrenia in 235 Chinese Han family trios. The GAD1 gene is comprehensively analyzed using a systematic mutation scan and the following-up association studies between common SNPs and schizophrenia in both single-locus and haplotype levels. Altogether, we have found 17 variants including 10 SNPs in 5'-flanking regions, 4 SNPs and one novel in-del in intronic regions and 2 SNPs (one novel SNP) in the 3'-untranslated region (UTR). Using the transmission disequilibrium test of the 9 common SNPs out of 17 variants, Significant evidence of SNP rs3791878-G allele in 5'-flanking region of GAD1 was preferentially transmitted to both the all offsprings of the trios (P = 0.0063, respectively; odds ratio = 1.83; 95% confidence interval: 1.26-2.65) and the male offsprings the trios (P = 0.0045, respectively; odds ratio = 2.21; 95% confidence interval: 1.37-3.56). Haplotype analysis suggested that rs3762556(C)-rs3791878(G)-rs6755102(C) is the major risky haplotype preferentially transmitted in both all the trios and male-offspring trios (Global P = 0.016 and 0.012, respectively). The gender-dependent of the risk of SNP rs3791878 suggest the complexity of GAD1 gene in schizophrenia. Given that the switch from G to T in SNP rs3791878 might cause the loss of ARNT and XBP1 transcriptional factor binding sites using a bioinformatics approach, our positive findings of this SNP support the hypothesis that the abruption of GAD1 gene is important to the risk of schizophrenia.
Acta Neurovegetativa 02/2008; 115(3):513-9. · 2.73 Impact Factor
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A Zhang, Q Xing,
S Qin,
J Du,
L Wang,
L Yu,
X Li,
L Xu,
M Xu,
G Feng,
L He
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ABSTRACT: Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including -3279T>G and -3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of -3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the -3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (-3279G; -3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.
The Pharmacogenomics Journal 10/2007; 7(5):333-8. · 4.54 Impact Factor
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ABSTRACT: The Chromogranin B (CHGB) gene has been proposed as a candidate gene for predisposition to schizophrenia due to its location on the genome, the evidence of genetic studies, and its functional role in schizophrenia. To investigate its association with schizophrenia using case-control analysis, we genotyped eight single nucleotide polymorphisms (SNPs) and performed transmission disequilibrium tests (TDT) using 192 Han Chinese trios. The G allele of IVS4 + 808A > G showed a trend of over-transmission from heterozygous parents to affected offspring (P = 0.06), although no significant over-transmission was found for individual markers. Furthermore, a significant transmission was observed for the common haplotype G-G-A-G-C (P = 0.0018). Overall, our results suggest that at least one locus in or close to the CHGB gene confers risk of the disorder and strengthen the evidence that CHGB is a promising susceptibility gene for schizophrenia in Chinese population.
Acta Neurovegetativa 01/2007; 114(5):641-4. · 2.73 Impact Factor
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S Duan,
J Du,
Y Xu, Q Xing,
H Wang,
S Wu,
Q Chen,
X Li,
J Shen,
G Feng,
L He
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ABSTRACT: The TRAR4 gene locates in SCZD5 (MIM 603175), which a number of studies have linked with schizophrenia. One recent study suggested that three TRAR4 variants (M1: rs4305745, P=0.0014; M2: rs6903874, P=0.0026; M3: rs6937506, P=0.0052) in the 3'-UTR were associated with schizophrenia. To replicate these findings, we conducted a family-based association study within a sample of 235 Chinese Han trios. However, we didn't find significant evidence of preferential transmission of the three variants across all the trios (all P values>0.2). Thus, we conclude that TRAR4 is not a major or independent determinant in the occurrence of schizophrenia in the Chinese Han population.
Acta Neurovegetativa 04/2006; 113(3):381-5. · 2.73 Impact Factor
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ABSTRACT: The functional supertype of HLA-A2 was investigated in the presentation of the A*0201-restricted Flu matrix p58-66 peptide to activate recall CD8+ T-cell response. In healthy Northern Chinese, the HLA-A2 supertype was mainly composed of the six alleles, A*0201 (26.4%), A*0206 (12.7%), A*0203 (8.2%), A*0207 (7.3%), A*0210 (1.8%) and A*0205 (0.9%), as analyzed by PCR using sequence specific primer (PCR-SSP) and sequence based typing (SBT). The IFN-gamma release Elispot assay was employed to assess effector CD8+ T cells. In A*0201-bearing individuals, the CD8+ T-cell response was potent when stimulated with autologous CD8- PBMCs. The frequency of the effector CD8+ T cells was 96.6% with the magnitude of effector CD8+ T cells of 225 SFC/5 x 104 CD8+ T cells and the RI of 25.7. In non-A*0201 individuals, the effector CD8+ T cells were minimally detectable while the peptide was presented by the autologous CD8- PBMCs. However, the induction of the response of CD8+ T cells obtained from non-A*0201 individuals was remarkably improved when the peptide was presented by autologous dendritic cells instead of CD8- PBMCs. The HLA-A2 alleles possessing cross-reactivity in the peptide presentation were mainly of A*0206 and non-A*0201 heterozygotes of A*0206 and A*0210. Moreover, A*0206 as the HLA-A2 functional supertype was further confirmed by tetramer assay. In two A*0206+ donors with CD8+ T-cell response to the peptide, the CD8+ T-cell frequency assessed by specific binding of peptide HLA-A*0201 tetramer was 4.62% and 1.66%, respectively. Thus, our results have substantiated the immunological relevance of the HLA-A2 supertype, which may benefit the design of peptide vaccines with the potential to be applicable in broader populations.
Tissue Antigens 11/2003; 62(4):285-95. · 2.59 Impact Factor
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ABSTRACT: To study the protective effect of exogenous pulmonary surfactant (PS) on respiratory insufficiency after cardiopulmonary bypass in children.
24 children of VSD associated with pulmonary hypertension undergoing heart surgery with cardiopulmonary bypass(CPB) were randomly divided into two groups: control group and PS group. In the PS group, exogenous natural porcine PS 150 mg/kg was dropped into the intracheal tube before opening the chest and removing the aortic clamp. Equal amount of normal saline was given in the control group. Lung dynamic compliance and oxygenate index were measured before and after operation. The plasma molondialdehyde(MDA) concentration of the lung was analysed perioperatively with ELISA methods. The intubation time of the two groups and ultrastructure of the lung also was measured.
The dynamic compliance of the PS group was higher than that of the control group (P < 0.05), and the oxygenate index was significantly lower than that of the control group (P < 0.01) after CPB. Compared to the control group, the exogenous PS was able to markedly reduce the generation of MDA(P < 0.01). The intubation time of the PS group was 8.9 hours, much shorter than 13.8 hours of the control group(P < 0.001). The histological examination confirmed that the degree of pulmonary damage was significantly ameliorated in the PS group.
Exogenous natural PS has protective effect on respiratory insufficiency after CPB in children with VSD associated with pulmonary hypertension.
Zhonghua yi xue za zhi 02/1999; 79(2):112-4.
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ABSTRACT: To study the effects of cardiopulmonary by pass(CPB) on pulmonary surfactant (PS) activity.
In 12 children with patent ductus arteriosus(PDA) and 19 patients with ventricular septal defect (VSD), saturated phosphatidylcholine (SatPC), total phospholipids (TPL), total protein (TP) and surfactant protein-A(SP-A) in sequential airway aspirates before and after operation were determined. Tetroxide osmium digestion and neutral alumina column chromatography were used for SatPC, and a modified immunoblot method with a rabbit anti-human SP-A polyclonal antibody for SP-A measurment.
In 19 VSD patients with CPB, SatPC/TPL was significantly decreased from 48% to 34% (t = 2.737, P < 0.05), SatPC/TP decreased from 64 to 33 mg/g (t = 3.011, P < 0.01), and SP-A from 23 to 11mg/g (t = 2.987, P < 0.01). In 12 patients without CPB, SatPC/TPL, SatPC/TP, SP-A/TP levels were not changed.
CPB significantly reduces pulmonary surfactant activity.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 08/1997; 20(4):225-7.
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ABSTRACT: Samples of variously-sized total suspended particles in the air of one sampling site of TaiYuan city were collected. The samples were extracted with acid and a simulated lung fluid (SLF) respectively. Both extracts mainly consisted of metallic elements. Using SOS chromotest as a means to test the gentoxity of the extracts and five metallic compounds, namely Cr6+, Ni2+, Pb2+, Mn2+ and Cd2+ were tested first. All the compounds tested could induce the SOS response to various extent, showing that the method was sensitive to metallic compounds. For the extracts of air particles, both the extracts of acid and of SLF of the smaller-sized particles could induce SOS response. This indicated the existence of metaklic genotoxicants in the smaller-sized particles. Being convenient to use fast and precise, the SOS Chromotest has its unique advantage for detecting carcinogenic metallic compounds.
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 06/1993; 27(3):141-3.
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Optics Communications - OPT COMMUN. 01/1985; 55(2):135-137.
