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Biomedical subjects

Yan Shen

Publications and source records attributed to Yan Shen.

At least 73 records · Page 4Linked to original sources
PubMed2005

Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer.

BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, -1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and 2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(-1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G-->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer.

Adult↗
PubMed2005

Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse model of scleroderma.

Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tight-skin (Tsk/+) mice. Administration of pB-CpG20 to Tsk/+mice every 3 weeks starting at the age of 1 week reduced skin thickness and collagen content compared to that of pB or saline. The reduction was long lasting even after halting the treatment. Furthermore, this treatment partially reduced the production of anti-nuclear antibodies although it did not decrease the incidence of lung emphysema. pB-CpG20 increased the number of spleen cells secreting IFN-gamma and reduced that of the cells secreting IL-4 in vivo and in vitro compared to saline. These results suggest that repeated administration of a CpG-enriched plasmid can ameliorate scleroderma-like syndrome by biasing Th1 immunity in young Tsk/+mice.

Animals↗
PubMed2005

Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies.

Destruction of nigrostriatal dopaminergic (DA) pathway triggers various persistent responses, such as inflammation and increased synthesis of neural growth factors, both in striatum and in substantia nigra. The pathological processes involved in such responses are poorly characterized and could contribute to secondary damage and/or regeneration in the central nervous system (CNS). Cystatin C was previously implicated in the process of neurodegeneration. However, its biological role during neurodegeneration is not understood and remains controversial. The present study identified an increased cystatin C mRNA level in the DA-depleted rat striatum, starting from the second week following a 6-OHDA-induced lesion. Immunohistochemical analysis confirmed the increase in cystatin C protein level in the striatum following DA depletion. Double-labeled fluorescence immunohistochemistry revealed that nigrostriatal neurons, astrocytes, and microglia contributed to the elevated level of cystatin C. Exposure to 6-hydroxydopamine, a DA-specific neurotoxin, resulted in DA neurons loss in the fetal mesencephalic cultures, an effect which could be partially reversed by treatment with cystatin C. Moreover, in vivo DA neurons survival study showed that administration of cystatin C in rats with 6-OHDA-induced lesion partially rescued the nigral DA neurons. The results indicate that the 6-OHDA lesioning induced a relatively slow but sustained up-regulation of cystatin C expression and suggest that the inhibitor may exert a neuroprotective action on DA neurons. The findings raise the possibility that cysteine proteinase inhibitors may be new candidates for neuroprotective treatment of Parkinson's disease. Cystatin C may be useful therapeutically in limiting neuropathy in Parkinson's disease.

Animals↗
PubMed2005

Molecular cloning, expression, and purification of SARS-CoV nsp13.

The SARS-nsp13 protein was identified as an mRNA cap1 methyltransferase. In this study, the nsp13 gene was cloned from the SARS-CoV PUMC02 strain viral RNA by RT-PCR, and inserted into the expression plasmid pET30a(+). The recombinant plasmid pET30a(+)-nsp13 was confirmed by restriction enzymes and sequencing analysis, and transformed into Escherichia coli BL21(DE3). The His-tag-fused protein was expressed by induction of 0.5mM IPTG and purified by a single Ni(2+) affinity chromatography. The protein was validated by western blot and MS analysis. A large quantity of the nsp13 protein obtained with this method may be useful for further study of its structure and function.

Amino Acid Sequence↗
PubMed2005

A genetic study of two calcium-independent cytosolic PLA2 genes in schizophrenia.

The present study detected 9 single nucleotide polymorphisms (SNPs) at the PLA2G4C and PLA2G6 loci among 240 Chinese parent-offspring trios of Han descent. Of these 9 SNPs, 5 showed highly polymorphic in the Chinese population. They were then applied as genetic markers to test the genetic association of these two calcium-independent cytosolic PLA2 genes with schizophrenia. The transmission disequilibrium test (TDT) showed that rs1549637 at the PLA2G4C locus was the only SNP associated with the illness (chi(2) = 5.63, P = 0.018). The global P-value was 0.082 for 1000 permutations with the TDT analysis. Neither the conditional on allele test nor the conditional on genotype test showed a disease association for the combination of these two genes. Because the PLA2G4C association is so weak, this initial finding should be interpreted with caution.

Adult↗
PubMed2005

Serial analysis of gene expression in the silkworm, Bombyx mori.

The silkworm Bombyx mori is one of the most economically important insects and serves as a model for Lepidoptera insects. We used serial analysis of gene expression (SAGE) to derive profiles of expressed genes during the developmental life cycle of the silkworm and to create a reference for understanding silkworm metamorphosis. We generated four SAGE libraries, one from each of the four developmental stages of the silkworm. In total we obtained 257,964 SAGE tags, of which 39,485 were unique tags. Sorted by copy number, 14.1% of the unique tags were detected at a median to high level (five or more copies), 24.2% at lower levels (two to four copies), and 61.7% as single copies. Using a basic local alignment search tool on the EST database, 35% of the tags matched known silkworm expressed sequence tags. SAGE demonstrated that a number of the genes were up- or down-regulated during the four developmental phases of the egg, larva, pupa, and adult. Furthermore, we found that the generation of longer cDNA fragments from SAGE tags constituted the most efficient method of gene identification, which facilitated the analysis of a large number of unknown genes.

Animals↗
PubMed2005

CpG oligodeoxynucleotides prevent the development of scleroderma-like syndrome in tight-skin mice by stimulating a Th1 immune response.

Tight-skin (Tsk/+) mice develop a disease similar to human scleroderma, characterized by the spontaneous appearance of cutaneous hyperplasia, anti-nuclear antibodies, and emphysema. T helper (Th) 2 cells secreting interleukin (IL)-4 are known to play a critical role in the etiopathogenesis of this disease. Th2-mediated responses can be blocked by treatment with synthetic oligodeoxynucleotides (ODN) containing immunomodulatory CpG motifs. Thus, we examined whether CpG ODN might be of therapeutic benefit in Tsk/+ mice. Administering CpG ODN to Tsk/+ mice every 3 wk starting at 1 wk of age abrogated skin fibrosis. This reduction in skin thickness persisted even after the cessation of therapy, and was accompanied by increased serum levels of IL-12 and an increased ratio of T cells available to secrete interferon-gamma rather than IL-4. CpG ODN therapy also reduced autoantibody production, but did not inhibit the incidence of lung emphysema. Delaying the initiation of CpG ODN treatment until 6 wk of age failed to prevent skin disease. These results indicate that by preferentially promoting the development of a Th1-biased immune milieu in young Tsk/+ mice, CpG ODN can ameliorate Th2-driven scleroderma-like syndrome.

Adjuvants, Immunologic↗
PubMed2005

[Clinical value of three-dimensional dynamic contrast-enhanced MR angiography in diagnosis of angiostenosis after liver transplantation].

OBJECTIVE: To evaluate the clinical application of three-dimensional dynamic contrast-enhanced MR angiography (3D DCE MRA) in diagnosis of angiostenosis after liver transplantation. METHODS: Twenty recipients of liver transplantation underwent 3D DCE MRA examination. The blood vessel rating grades were accessed and the relative diameter of vascular anastomosis was measured; and the results were compared with those of US or DSA examination. RESULTS: Satisfactory angiography images were obtained in all cases by 3D DCE MRA, including 11 cases with normal and mild stenosis, 5 with moderate and 4 with severe stenosis in hepatic artery. Except one case in which 3D DCE MRA showed severe stenosis but DSA showed moderate stenosis, the results of MRA were all consistent with those of US or/and DSA in the stenosis degree of the portal vein, hepatic vein and the postcava. CONCLUSION: 3D DCE MRA is an effective technique to evaluate the degree of angiostenosis after liver transplantation.

Adult↗
PubMed2005

Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and its possible mechanisms.

BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT). However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in China. Cyclosporine A (CsA), which is routinely used to prevent the allograft rejection, is reported to have the inhibitory activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possible mechanisms of CsA on HBV replication in vitro. DATA RESOURCES: An English-language literature search was conducted using MEDLINE (1990-2004) on cyclosporine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles. RESULTS: Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cyclophilin D, then blocking the mitochondria-mediated cytosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro. CONCLUSIONS: By interacting with mitochondria, preventing the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.

Calcium Signaling↗
PubMed2005

Orthotopic liver transplantation for patients with Klatskin tumor.

BACKGROUND: It is not certain whether Klatskin tumor should be a routine indication for orthotopic liver transplantation (OLT). This study was to summarize the indication and value of orthotopic liver transplantation for patients with Klatskin tumor. METHODS: Forty patients with Klatskin tumors including 5 patients who had had liver transplantation (LTx) and 35 patients who had not undergone LTx (WLTx) from January 1992 to December 2003 were analyzed retrospectively. Their TNM stages were comparable in both groups. In the LTx group, 4 patients had Klatskin tumor including recurrent tumor after resection(1), and 1 cancerization from Carolis disease. Biliary duct anastomosis was made by Roux-en-Y choledochojejunostomy in 2, and end-to-end choledochocholedochostomy (C-C) in 3. RESULTS: In the LTx group, the total resection rate and radical resection rate were both 100%. Four patients have been surviving for 48, 38, 21 and 5 months, respectively, except one died from bile leakage at day 40 after transplantation. All 4 survivors enjoyed good life without tumors at local and distant sites, even though 2 of these patients developed biliary stricture, which was soon resolved by radiological intervention. The 1-,3-year survival rates were both 80% in this group. The total resection rate and radical resection rate in the WLTx group were 63.0%(17/27)and 40.7%(11/27)and, the 1-, 3-, 5-year survival rates were 32.2%, 8.0%, 0%, respectively. There were significant differences between the two groups in radical resection rates and survival rates(P=0.016). CONCLUSIONS: OLT is a good choice for patients with unresectable Klatskin tumor by routine modalities. The prognosis of patients undergoing OLT is encouraging.

Adult↗
PubMed2005

[T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy].

OBJECTIVE: Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). It is considered to be a hereditary disease. The possible inheritance pattern of CAE is polygenic. The genes responsible for CAE, however, have not yet been identified. The aim of this study was to further investigate based on the authors' recent work whether or not T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy. METHODS: The authors conducted the mutation screening of the exons 6-12 and the nearby partial introns of the CACNA1H gene using the method of direct sequencing of PCR products in 48 newly found CAE patients. RESULTS: The authors found 13 single nucleotide polymorphisms (SNPs). They also found 4 mutations which only existed in CAE patients. Both G773D and H515Y mutations were heterozygous. The mutation of H515Y has never been reported previously. The patient inherited the mutation from his mother. The authors found two CAE patients with the mutation of G773D previously. This is the third time that the authors found one more CAE family with this G773D mutation, and the patient with the mutation G773D inherited the mutation from his father. CONCLUSION: T-type calcium channel gene-CACNA1H might be a susceptibility gene to childhood absence epilepsy.

Amino Acid Sequence↗
PubMed2005

Detection of chromosome aberrations in Chinese children with autism using G-banding and BAC FISH.

OBJECTIVE: To detect the characteristic chromosomal changes in Chinese children with infantile autism. METHODS: Chromosome aberrations in 68 cases of infantile autism were analyzed by high-resolution G-banding and fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. RESULTS: Chromosomal changes were detected in 4 cases by high-resolution G-banding: one case with t(4;6)(q23-24;p21), one case with longer p arm of chromosome 21 (21p+), and two cases with pericentric inversion of chromosome 9 (inv(9)) which was confirmed by C-banding. BAC FISH analysis was performed to confirm these observations and changes in chromosomes 2, 7 and 15, which are often found in autistic children. There could exist the translocation of t(4;6) (q25-26;p21.1). Chromosome changes often reported previously in chromosomes 2, 7 and 15 were not detected in this study. Inv(9) and 21p+ were not confirmed with present BAC clones. CONCLUSION: Chromosomal changes were detected in four cases of infantile autism, with a detectability of 5.9% , far lower than that (10% to 48%) reported in literature. The breakpoint of translocation could be detected more accurately using BAC FISH method.

Autistic Disorder↗
PubMed2005

[Disease gene identification: opportunities and challenges].

The recent achievements of the Human Genome Project make it increasingly feasible to determine the genetic basis of human diseases, especially complex traits. Genomics will provide powerful means to discover hereditary elements that interact with environmental factors leading to diseases. However, the expected transformation toward genomics-based medicine will occur over decades, which requires the joint efforts of many scientists and physicians. Such transformation provides both opportunities and challenges to everyone involved in this field.

Genetic Diseases, Inborn↗
PubMed2005

[Detection of duplications or deletions of the PMP22 gene using real-time quantitative PCR].

OBJECTIVE: To detect the duplication or deletion of peripheral myelin protein 22(PMP22) gene in Chinese patients with Charcot-Marie-Tooth disease(CMT) or hereditary neuropathy with liability to pressure palsies(HNPP) using real-time quantitative polymerase chain reaction. METHODS: Duplications or deletions of PMP22 gene were detected in 113 CMT cases, 4 HNPP cases and 50 normal controls by using real-time quantitative PCR. RESULTS: Thirty-six of 113 CMT cases had the PMP22 duplication, 4 HNPP cases had the PMP22 deletion. No duplication or deletion was found in 50 normal controls. CONCLUSION: The PMP22 duplication rate in Chinese patients with CMT is 31.9%(36/113). PMP22 deletion is the common cause of HNPP.

Adult↗
PubMed2005

[Estimation models for vegetation water content at both leaf and canopy levels].

Based on spectral indices method, this paper utilized the water content (Cw) and reflectance data of 67 fresh different type leaves from LOPEX' 93 database to establish the statistical model between leaf Cw and spectral indices at leaf level through 47 samples, and to test the model with the other 20 samples. The results suggested that fuel moisture content (FMC) and equivalent water thickness (EWT) as Cw demonstrators were different in reflectance spectral curves. The difference between FMC and EWT was large when they were utilized to retrieve the leaf Cw. The correlation coefficient between EWT and each spectral index was higher than FMC, but the forecast precision of FMC was better than that of EWT. The 7 spectral indices could all retrieve the leaf FMC accurately, but only the Ratio975, II and SR were suitable to estimate the leaf EWT. Spectral indices linear model on the strength of optimal subset regressions had the highest precision to retrieve the leaf Cw. Ratio975 might be the universal spectral index to estimate the leaf Cw. At canopy level, the simulated canopy spectra under different leaf area index (LAI) and Cw were derived from the PROSPECT and SAILH coupling models. In order to eliminate background influence and to precisely retrieve the Cw, soil-adjusted water index (SAWI) was proposed at the first time to indicate the information of near-infrared and short-wave infrared canopy reflectance. The ratio of SAWI and other spectral indices could dramatically eliminate the soil background, and effectively retrieve the vegetation Cw at canopy level. Spectral index (Ratio975 - 0.96)/(SAWI + 0.2) as improved Ratio975 could be used to compute the canopy Cw more precisely when LAI was ranging from 0.3 to 8.0 and Cw from 0.0001 to 0. 07cm.

Ecosystem↗
PubMed2005

[Comparative study of the parameters related to type I thyroplasty measured by laryngeal specimens and computed tomography].

OBJECTIVE: To determine the consistence of the parameters related to type I thyroplasty measured by laryngeal specimens and CT scan. METHODS: The related parameters of 50 laryngeal specimens (unilateral) obtained following total laryngectomy were measured postoperative immediately, and compared with those measured by spiral CT scan with multiple plain reconstructive (MPR) technique preoperatively. Comparative results were analyzed to evaluate the statistical significance between these two methods. RESULTS: There were no significant statistical differences among the 6 parameters between two methods (P > 0.05), and the results (x +/- s) measured by CT scan and laryngeal specimens showed that the length of the thyroid notch to the inferior thyroid border were (20.7 +/- 1.7) mm and (20.6 +/- 1.7) mm; the length of the vocal cord were (17.3 +/- 1.8) mm and (17.3 +/- 1.8) mm; the length of the oblique line were (28.6 +/- 3.2) mm and (29.1 +/- 2.7) mm; the length of the presumptive horizontal line were (26.2 +/- 2.0) mm and (26.2 +/- 2.0) mm; the endolaryngeal vertical length of the anterior of the vocal cord to the presumptive horizontal line were (4.5 +/- 0.6) mm and (4.5 +/- 0.7) mm; the endolaryngeal vertical length of the vocal process to the presumptive horizontal line were (10.8 +/- 1.1) mm and (10.9 +/- 1.1) mm, respectively. As a result, the endolaryngeal anterior and posterior width of the wedge inserted in the thyroid cartilage were 4 - 5 mm and 8 - 9 mm respectively. CONCLUSIONS: MPR technique of spiral CT scan is able to design the size of the window and the prosthesis of type I thyroplasty preoperatively, which was testified to be a precise and reliable method to measure the larynx.

Adult↗
PubMed2005

[Long-term results of 84 surgically treated patients with extrahepatic bile duct carcinoma].

OBJECTIVE: Extrahepatic bile duct carcinoma is a rare but dismal malignacy. This study is conducted to show retrospective review and analysis of the correlation between the prognosis and different treatment modalities. METHODS: The data of 84 such patients treated by different modalities from January, 1992 to July, 2000 were retrospectively reviewed and analyzed using SPSS 10.0 statistical package. The survivals were estimated by the Kaplan-Meier method and the difference among groups was tested by the log-rank test. The prognostic factors were determined by Cox multivariate analysis. RESULTS: Of the 84 patients, 33 had complete resection, 19 palliative resection, 12 exploration alone, and the remaining 20 were treated by chemotherapy and/or radiotherapy. The mean follow-up time was 592 days. The overall 5-year survival rate was 13.1%. The 1-, 3- and 5-year survival rate following complete resection was 76.8%, 52.6% and 30.5% respectively, which was significantly higher than those of palliative surgery or chemotherapy/radiotherapy (P < 0.01). Multivariate analysis revealed that lymph node status (P = 0), histopathological grade (P = 0.001) and distant metastasis (P = 0.002) were significant high risk factors. CONCLUSION: The prognosis of extrahepatic bile duct carcinoma remains poor even after complete resection as shown to have a 5-year survival of 30.5%. More effective adjuvant therapy is needed. Extended resection may be helpful in improving the prognosis for carefully selected patients. Early diagnosis and early treatment is still the key to improve the long-term survival of extrahepatic bile duct carcinoma.

Adenocarcinoma↗