Biomedical subjects

X Dou

Publications and source records attributed to X Dou.

7 recordsLinked to original sources

PubMed2002

Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts.

OBJECTIVE: As an initial approach to understanding the basis of the systemic sclerosis (SSc; scleroderma) phenotype, we sought to identify genes in the transforming growth factor beta (TGF beta) signaling pathway that are up-regulated in lesional SSc fibroblasts relative to their normal counterparts. METHODS: We used gene chip, differential display, fluorescence-activated cell sorter, and overexpression analyses to assess the potential role of TGF beta signaling components in fibrosis. Fibroblasts were obtained by punch biopsy from patients with diffuse cutaneous SSc of 2-14 months' duration (mean 8 months) and from age- and sex-matched healthy control subjects. RESULTS: Unexpectedly, we found that fibroblasts from SSc patients showed elevated expression of the endothelial cell-enriched TGF beta receptor endoglin. Endoglin is a member of the nonsignaling high-affinity TGF beta receptor type III family. The expression of endoglin increased with progression of disease. Transfection of endoglin in fibroblasts suppressed the TGF beta-mediated induction of connective tissue growth factor promoter activity. CONCLUSION: SSc is characterized by overproduction of matrix; that is, genes that are targets of TGF beta signaling in normal fibroblasts. Our findings suggest that lesional SSc fibroblasts may overexpress endoglin as a negative feedback mechanism in an attempt to block further induction of profibrotic genes by TGF beta.

Antigens, CD↗

PubMed2001

DNA-binding of phenylalanyl-tRNA synthetase is accompanied by loop formation of the double-stranded DNA.

The phenylalanyl-tRNA synthetase (FRS) from Thermus thermophilus has previously been shown to bind DNA. We demonstrate that the "winged" helix-turn-helix motifs in the duplicate domains B5 are the relevant structural elements for this DNA-binding property. By altering particular amino acids in the "wing", the affinity of the FRS to DNA was significantly reduced. Based on experimental data, which indicate that the FRS prefers a certain DNA structure rather than a particular consensus sequence, we propose a novel loop model for the DNA-binding mode of the FRS. In our model we assume that two segments of the same DNA molecule are bound simultaneously by both B5 domains and are aligned in parallel, while the intervening DNA forms a loop. Due to the limited flexibility of the DNA, loop formation is only possible if the respective intervening DNA stretch exceeds a certain length. Several lines of evidence support this model. (1) We demonstrate by gel retardation assays that the DNA requires a minimal number of ca 80 base-pairs to be bound by the FRS. (2) In the presence of the FRS, DNA longer than ca 80 base-pairs has a significantly increased DNase I accessibility. This agrees well with its known preferential cleavage at positions where the minor grove is on the outside of looped-out DNA molecules. (3) The initial cleavage by DNase I of >80 bp long DNA occurs in the middle of the fragment. In a looped molecule this is the position with the highest accessibility to DNase I. The function of the FRS related to DNA binding is still unknown. Since the FRS exists in the nucleus of rapidly growing mammalian cells, and protein-induced DNA bending or looping contributes to several transcription, replication, and recombination systems in both prokaryotes and eukaryotes, it is likely that the FRS, in addition to its aminoacylation function, influences common cellular processes via DNA binding.

Acylation↗

PubMed2001

Phase shift at a turning point in a planar optical waveguide.

We present a novel matrix approach to proving that the phase shift at a turning point in a planar optical wave-guide is exactly equal to pi rather than to pi/2 or to some other value. We also show the existence of phase contributions from reflected subwaves, which to our knowledge have never been taken into account previously.

Journal Article↗

PubMed2000

Detection of type 1 cytokines in discoid lupus erythematosus.

BACKGROUND: Although multiple studies suggest a dysregulated T-cell cytokine production in systemic lupus erythematosus, the cytokine profile in discoid lupus erythematosus (DLE) lesions is unknown. OBJECTIVES: To characterize the cytokine profile in DLE by immunohistochemical and molecular methods, and to investigate the role of cytokines in the pathogenesis of DLE. DESIGN: Patients were evaluated clinically, and biopsy specimens of lesional skin were examined by light microscopy. Reverse transcriptase-polymerase chain reaction and immunohistochemical analysis were performed on 11 biopsy specimens. We investigated the presence of interleukin (IL) 2, interferon gamma (IFN-gamma), IL-4, tumor necrosis factor alpha, (TNF-alpha), and IL-1beta messenger RNA (mRNA) in 8 biopsy specimens of DLE and compared it with 3 biopsy specimens of normal skin. SETTING: Academic referral research hospital. PATIENTS: Eight consecutive patients with a clinical and histologic diagnosis of DLE. RESULTS: Localized DLE was found in 7 patients and widespread in 1. During the 4 years of the investigation, none of the patients developed systemic lupus erythematosus. We found significantly elevated levels of IL-2 and IFN-gamma mRNA in all 8 biopsy specimens of DLE; in contrast, no transcripts of IL-2 or IFN-gamma were detected in 3 biopsy specimens of normal skin (P<.01). Similarly, elevated levels of TNF-alpha mRNA were detected in 8 DLE biopsy specimens, while no TNF-alpha mRNA was detected in 3 biopsy specimens of normal skin (P<.01). No IL-4 or IL-1 beta mRNA was detected in 8 biopsy specimens of DLE lesional skin and 3 biopsy specimens of normal patient skin. Immunohistochemical analysis showed increased staining for IL-2 and IFN-gamma receptors, while no detectable IL-4 receptor was found. No cytokine mRNA or cytokine receptor protein was detected in biopsy specimens of normal skin. CONCLUSIONS: These findings suggest that DLE is associated with type 1 cytokines characterized by the expression of IL-2 and IFN-gamma. Type 1 cytokines may be critical for induction, development, and maintenance of DLE.

Adult↗

PubMed1998

[Polymorphism analysis of 4 loci of X-chromosome in a Chinese population of the Han nationality].

OBJECTIVE: To investigate the polymorphism of 4 loci of X-chromosome in the Hans. METHODS: Using PCR-SSLP, the authors analysed the polymorphism of DXS1068, DXS7132, DXS6804 and DXS6799 in the X-chromosome in 70 randomly selected female Hans. RESULTS: The number of alleles in the 4 loci were 5,5,5 and 6 respectively; there were no significant differences between the observed and estimated and genotype probabilities of the 4 loci; the estimates of heterozygosity of 4 loci were 0.6819, 0.6895, 0.7659 and 0.6483 respectively and there were no significant differences between the observed and estimated heterozygosity of the 4 loci. CONCLUSION: The distribution of alleles and genotype probabilities of 4 loci all observe the Hardy-Weinberg equilibrium.

Asian People↗

PubMed1998

[A study of genetic patterns of idiopathic epilepsy].

OBJECTIVE: To explore genetic patterns of idiopathic epilepsy (IEP). METHODS: Using familial analysis, tests for multifactorial inheritance and segregation analysis, we studied 210 pedigrees with IEP found in a population survey in Shangdong province. RESULTS: The genetic pattern of IEP is not polygenic but is mainly influenced by autosomal recessive disorders. The results of segregation analysis indicate that the genetic pattern of U*U multiplex families and U*A group is autosomal recessive. Only a few cases in U*U group may accept the assumption of autosomal recessive inheritance while the other are sporadic cases. The frequency of sporadic cases is approximately 78.5%. Genetic heterogeneity may influence U*U(f) group and U*U group. CONCLUSION: Further and careful empirical scrutiny of U*U(f) group and the sporadic cases in U*U group offers the best hope for getting a clear understanding of genetic patterns and mechanisms in IEP.

Epilepsy↗

PubMed1998

[Detection of HGV RNA in sera from patients with fulminant hepatitis in Shenyang].

HGV RNA was detected by Rt-nested PCR in sera from 49 patients with fulminant hepatitis. The results showed: a) HGV RNA positive rate was 16.3% (8/49) in patients with fulminant hepatitis including 4 subjects with HBV coinfection, 1 subject with HCV coinfection, 2 subjects with HBV and HCV coinfection and 1 subject with HGV infection alone. b) mortality in patients with fulminant hepatitis with HGV infection was 75% (6/8), suggesting that: a) both infection with HGV alone and superinfections of other types of hepatitis virus can result in fulminant hepatitis, b) clinical manifestations of fulminant hepatitis with HGV infection may appear to be more severe and with higher mortality.

Adolescent↗