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Biomedical subjects

Lai Wei

Publications and source records attributed to Lai Wei.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Relationship between the quantities of peripheral dendritic cells and of serum HBV DNA and the inflammatory reaction levels in the liver].

OBJECTIVES: To investigate the relationship between the quantity of peripheral dendritic cell (DC) and of serum HBV DNA and the inflammatory level in chronic hepatitis B (CHB). METHODS: The myeloid DC (DC1) and plasmacytoid DC (DC2) in fresh peripheral blood were enumerated by using three-color flow cytometry in chronic hepatitis B patients and healthy donors. The hepatic inflammatory levels were evaluated by percutaneous liver biopsy. The serum HBV DNA levels were determined by real-time PCR. RESULTS: CHB patients with serum HBV DNA < or = 10(6) copies/ml exhibited a significant increase in the percentage of circulating DC2 in comparison with those of CHB patients with serum HBV DNA > or = 10(6) and with healthy donors (P < 0.05). The two latter groups showed no significant differences between each other. There was also no significant difference in the relative quantity of peripheral blood DC1 among the three groups mentioned above (P = 0.162). No evidence was found to support that the relative quantity of peripheral blood DC2 was associated with the clinical severity of the disease or the inflammatory level in the liver (P > 0.05). CONCLUSION: The relative quantity of peripheral blood DC2 is associated with HBV DNA level. It is suggested that DC2 may play a pivotal role in inhibiting HBV replication in CHB patients. There was no relationship found between relative quantities of DCs and the inflammatory level in the liver.

DNA, Viral↗
PubMed2005

[ISGF3, a critical factor of the IFN-alpha pathway in the antiviral action of HBV].

OBJECTIVE: To study the mechanism of signal transduction in anti-HBV action of IFN-alpha. METHODS: The HBV DNA in HepG 2.2.15 cell line supernatant with/without IFNalpha-2b were monitored by fluorescence real-time quantitive PCR. STAT1, STAT2, ISGF3-gamma, PKR, 2'5'-OAS mRNA levels from HepG 2 and HepG 2.2.15 cell lines that were treated with/without IFNalpha-2b at different times were detected by semi-quantitive RT-PCR. And the ISGF3-gamma protein was detected by Western blot. Then, these items were detected again after inhibiting the JAK-STAT pathway with genistein. RESULTS: The HBV DNA in 2215 supernatant that were treated with IFNalpha-2b for 8 hours decreased 0.72 log 10 copies/ml. But the basal levels of DNA in cells pretreated with genistein? followed by IFNalpha-2b did not decrease. The STAT1, STAT2, ISGF3-gamma, 2'5'-OAS, PKR mRNA levels were upregulated by IFNalpha-2b. The same phenomena were observed with STAT1, STAT2, ISGF3-gamma mRNA when pretreated with genistein then treated with IFNalpha-2b, but the levels of 2'5'-OAS, PKR mRNA were decreased in this situation. The expression of the protein of ISGF3-gamma was also augmented by IFNalpha-2b, and was blocked by genistein. CONCLUSION: The JAK-STAT pathway seems to be a critical pathway in IFNalpha-2b action against HBV? and ISGF3 is most probably a key factor of the route.

Antiviral Agents↗
PubMed2005

[SNaPshot technique for detection of single-nucleotide polymorphisms (SNPs) in HBV polymerase gene region of HBV gene].

OBJECTIVE: To establish a rapid specific method to identify the single-nucleotide polymorphisms (SNPs) of HBV polymerase gene region which are the methionine residue of the conserved YMDD motif. METHODS: Two specific primers were designed to amplify interested gene region involved in SNPs which were also used as HBV DNA identification. Specific primers of SNaPshot were designed to detect 741A-G (YVDD), 743G-T (YIDD). The different fluorescent dye labeled ddNTP was used to further extend the strand of PCR product and was detected by ABI PRISM 310 Genetic Analyzer. Sera from 13 patients with chronic hepatitis B after lamivudine treatment were analyzed. RESULTS: Aside from mutation of YMDD, there were mutations of 514C-A, 523C-A, 562T-A, 667C-A. The 13 samples were simultaneously tested with SNaPshot and DNA sequencing, the same results were obtained. The method of SNaPshot showed high specificity. CONCLUSION: Mutation of YMDD results in the changes of ATG codon, and there are new ATG codon in the upper strand of YMDD. SNaPshot technique is rapid, specific and accurate for the SNPs monitoring of HBV DNA mutation during lamivudine therapy. Two samples were determined by SnaPshot technique, identifying the co-existence of the mixed wild type and mutant type HBV infection.

Antiviral Agents↗
PubMed2005

[A study on stem cell mobilization after partial liver transplantation in rats].

OBJECTIVE: To explore the role of stem cell mobilization on regeneration of partially grafted livers. METHODS: Rats models with cross-sex 50% PLTx (partial liver transplantation) were established. The rats were divided into three groups: PLTx, WLTx (whole liver transplantation) and sham operation groups. Bone marrow and liver samples were collected on days 1, 3, 5, 7 postoperatively (each n = 6). The quantitative variations of the cells with stem cell markers in the bone marrow, including beta2m-/Thy-1.1+, CD45+/CD34+, Flt2/3+ and c-kit+ markers, were detected using flow cytometry. Sry gene positive cells in donor livers were detected by fluorescent in situ hybridization (FISH), and the expressions of CD34, c-kit and Thy-1.1 were detected by immunohistochemistry technique. RESULTS: Compared with the WLTx and sham operation groups, beta2m-/Thy-1.1+, CD45+/CD34+ cells in bone marrows in the PLTx group increased on the first postoperative day and decreased on the following days. The CD34, c-kit and Thy-1.1 positive cells detected in portal tract areas peaked during the 3-5 postoperative days. CD34+/CD45+ positive cells could be detected. The expressions of CD34, c-kit and Thy-1.1 positive cells were rare in the WLTx and sham operation groups. Sry+ cells could be detected in portal tract areas and few Sry+/CD34+ and Sry+/Thy-1.1+cells were detected. CONCLUSION: In the PLTx group, the stem cells in the bone marrow were mobilized and stem cells in the liver were activated.

Animals↗
PubMed2004

Hepatic differentiation capability of rat bone marrow-derived mesenchymal stem cells and hematopoietic stem cells.

AIM: To investigate the different effects of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) on hepatic differentiation. METHODS: MSCs from rat bone marrow were isolated and cultured by standard methods. HSCs from rat bone marrow were isolated and purified by magnetic activated cell sorting. Both cell subsets were induced. Morphology, RT-PCR and immunocytochemistry were used to identify the hepatic differentiation grade. RESULTS: MSCs exhibited round in shape after differentiation, instead of fibroblast-like morphology before differentiation. Albumin mRNA and protein were expressed positively in MSCs, without detection of alpha-fetoprotein (AFP). HSCs were polygonal in shape after differentiation. The expression of albumin signal decreased and AFP signal increased. The expression of CK18 was continuous in MSCs and HSCs both before and after induction. CONCLUSION: Both MSCs and HSCs have hepatic differentiation capabilities. However, their capabilities are not the same. MSCs can differentiate into mature hepatocyte-like cells, never expressing early hepatic specific genes, while Thy-1.1(+) cells are inclined to differentiate into hepatic stem cell-like cells, with an increasing AFP expression and a decreasing albumin signal. CK18 mRNA is positive in Thy-1.1(+) cells and MSCs, negative in Thy-1.1(-) cells. It seems that CK18 has some relationship with Thy-1.1 antigen, and CK18 may be a predictive marker of hepatic differentiation capability.

Animals↗
PubMed2004

Prospective study in 142 cases of hepatitis C virus infection.

AIM: There is limited information on the natural history of HCV infection in China. We investigated the outcome of HCV infection after nine-year follow-up and the risk factors in blood donors in China in order to provide the foundation for prevention and therapy. METHODS: A total of 172 cases of HCV infection with anti-HCV positive and ALT abnormality were enrolled in the archives when was screened blood in Hebei Province in 1993. In them 142 blood donors were followed up till July 2002. No antiviral treatment was applied to them during the period of infection. In the present study, anti-HCV, HCV-RNA and aminotransferase were detected and genotyping was conducted by the method of restriction fragment length polymorphism(RFLP). B-type ultrasound detection was performed in all the patients. Age, sex, alcohol consumption and clinical symptoms were questioned. RESULTS: After nine years' follow-up, 10.56% (15/142) of the cases were negative for anti-HCV and 16.42% (12/134) of them were negative for HCV-RNA. The genotypes 1b, 2a and 1b/2a were 91.07%, 6.25% and 2.68% respectively. Twelve cases (8.45%) were negative for both HCV RNA and anti-HCV. The rate of chronicity in this group was 83.58% (112/134), and the rate of viral spontaneous resolution was 16.42% (22/134). The mean level of ALT, AST, gamma-GT in HCV RNA positive cases was significantly higher than that in HCV RNA negative cases (P<0.001). The abnormal rate of ALT and/or AST in male donors was significantly higher than that in female donors (P = 0.005). The rate of progression to liver cirrhosis from chronic hepatitis C was significantly higher in the cases of super-infection with HBV than that in the cases of single HCV infection. Overdose alcohol consumption promoted the progression to chronicity. CONCLUSION: This area (Hebei Province) has a higher rate of chronicity in HCV infection, and measures should be taken to prevent its progression to serious liver diseases, especially for patients super-infected with HCV and HBV.

Adult↗
PubMed2004

Association of interleukin-12 p40 gene 3'-untranslated region polymorphism and outcome of HCV infection.

AIM: To investigate the effect of interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism on the outcome of HCV infection. METHODS: A total of 133 patients who had been infected with HCV for 12-25 (18.2+/-3.8) years, were enrolled in this study. Liver biochemical tests were performed with an automated analyzer and HCV RNA was detected by fluorogenic quantitative polymerase chain reaction. B-mode ultrasound was used for liver examination. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the detection of IL12B (1188A/C) polymorphism. RESULTS: Self-limited infection was associated with AC genotype (OR = 3.48; P = 0.001) and persistent infection was associated with AA genotype (OR = 0.34; P = 0.014) at site 1188 of IL12B. In patients with persistent HCV infection, no significant differences were found regarding the age, gender, duration of infection and biochemical characteristics (P>0.05). According to B-mode ultrasound imaging and clinical diagnosis, patients with persistent infection were divided into groups based on the severity of infection. No significant differences were found in the frequency of IL-12 genotype (1188A/C) between different groups (P>0.05). CONCLUSION: The polymorphism of IL12B (1188A/C) appears to have some influence on the outcome of HCV infection.

3' Untranslated Regions↗
PubMed2004

Gene clustering by latent semantic indexing of MEDLINE abstracts.

MOTIVATION: A major challenge in the interpretation of high-throughput genomic data is understanding the functional associations between genes. Previously, several approaches have been described to extract gene relationships from various biological databases using term-matching methods. However, more flexible automated methods are needed to identify functional relationships (both explicit and implicit) between genes from the biomedical literature. In this study, we explored the utility of Latent Semantic Indexing (LSI), a vector space model for information retrieval, to automatically identify conceptual gene relationships from titles and abstracts in MEDLINE citations. RESULTS: We found that LSI identified gene-to-gene and keyword-to-gene relationships with high average precision. In addition, LSI identified implicit gene relationships based on word usage patterns in the gene abstract documents. Finally, we demonstrate here that pairwise distances derived from the vector angles of gene abstract documents can be effectively used to functionally group genes by hierarchical clustering. Our results provide proof-of-principle that LSI is a robust automated method to elucidate both known (explicit) and unknown (implicit) gene relationships from the biomedical literature. These features make LSI particularly useful for the analysis of novel associations discovered in genomic experiments. AVAILABILITY: The 50-gene document collection used in this study can be interactively queried at http://shad.cs.utk.edu/sgo/sgo.html.

Abstracting and Indexing↗
PubMed2004

Dendritic cells from chronic hepatitis B patients can induce HBV antigen-specific T cell responses.

AIM: To determine whether dendritic cells (DCs) from chronic hepatitis B patients could induce HBV antigen-specific T cell responses or not. METHODS: DCs were generated from peripheral blood mononuclear cells of patients with chronic hepatitis B (CHB) infection and healthy donors. We compared the phenotypes of these DCs and their ability to secrete cytokines and to participate in mixed lymphocyte reactions. In addition, autologous lymphocytes were cultured with DCs loaded with HBV core region peptide HBcAg8-27, an epitope recognized by cytotoxic T lymphocytes (CTL), and bearing human leucocyte antigen (HLA)-A2 for 10 d. Cytokine secretion and lytic activity against peptide-pulsed target cells were assessed. RESULTS: DCs with typical morphology were generated successfully by culturing peripheral blood mononuclear cells (PBMCs) from CHB patients with AIM-V containing GM-CSF and IL-4. Compared with DCs from normal donors, the level of CD80 expressed in DCs from CHB patients was lower, and DCs from patients had lower capacity of stimulate T cell proliferation. When PBMCs isolated from patients with chronic or acute hepatitis B infection and from normal donors were cocultured with HBcAg18-27 peptide, the antigen-specific memory response of PBMCs from acute hepatitis B patients was stronger than that of PBMCs from chronic hepatitis B patients or normal donors. PBMCs cocultured with DCs treated with HBcAg18-27 CTL epitope peptide induced an antigen-specific T cell reaction, in which the level of secreted cytokines and lytic activity were higher than those produced by memory T cells. CONCLUSION: DCs from patients with CHB can induce HBV antigen-specific T cell reactions, including secretion of cytokines essential for HBV clearance and for killing cells infected with HBV.

Adult↗
PubMed2004

Role of nuclear factor-kappaB in the antiviral action of interferon and interferon-regulated gene expression.

Interferons (IFNs) play critical roles in host defense by modulating the expression of various genes via tyrosine phosphorylation of STAT transcription factors. IFN-alpha/beta activates another important transcription factor, nuclear factor-kappaB (NF-kappaB), but its role in IFN-mediated activity is poorly understood. Sensitivity to the antiviral and gene-inducing effects of IFN was examined in normal fibroblasts and in NF-kappaB knockout fibroblasts from p50- and p65-null mice. Antiviral assays demonstrated that NF-kappaB knockout fibroblasts were sensitized to the antiviral action of IFN. Moreover, analysis of IFN-stimulated gene expression by real-time PCR demonstrated selective effects of NF-kappaB on gene expression. Our results demonstrate that a subset of IFN-stimulated genes is regulated through an NF-kappaB-dependent pathway and that NF-kappaB may regulate the sensitivity of cells to IFN-mediated antiviral activity.

Animals↗
PubMed2004

[Nine-year follow-up of hepatitis C virus infection in a rural area of Hebei province, China].

OBJECTIVE: To investigate natural history of hepatitis C virus infection and related factors among plasma donors in China. METHODS: 172 plasma donors in a rural area of Hebei province had been diagnosed as HCV infection in 1993. No antiviral treatment was applied to them during the period of infection. In the present study, we investigated the outcome of HCV infection nine years later and related factors affecting the outcome. In fact, only 142 cases were followed up in the investigation. The mean age of 142 cases of blood donors was 46 +/- 9 and the mean age of infection was 37 +/- 9 years old. RESULTS: After nine-year follow-up, 1.2% died of end-stage liver disease. 130 (91.6%) of 142 cases under investigation were still positive for HCV RNA or anti-HCV in their blood and 12 cases (8.4%) were negative for both HCV RNA and anti-HCV. 3.1% developed liver cirrhosis among the patients with persistent infection. The mean level of ALT, AST, GGT among HCV RNA positive cases were significantly higher than that of HCV RNA negative cases (P < 0.001). The abnormal rates of ALT and/or AST in male patients were significantly higher than those of female patients (P = 0.005). The rate of progression to liver cirrhosis from chronic hepatitis C virus was significantly higher in patients co-infected with HCV/HBV than that of the cases of single HCV infection. CONCLUSION: Higher chronic rate was observed in this research. Superinfection of HBV/HCV may have worse clinical outcomes.

Adult↗
PubMed2004

[A study on the mutation of P gene region including YMDD motif in hepatitis B virus].

OBJECTIVE: To investigate the primary structure and heterogenenity of P gene region including YMDD motif in hepatitis B virus. METHODS: From serum samples collected from 4 patients who had never been treated with anti-viral drugs, DNA fragments of 1057bp long of P gene were amplified and cloned into pUC19. Twenty positive clones were chosen randomly from each sample. The YMDD motif mutation was detected by mismatched PCR-RFLP. Finally last ten positive clones of two samples were sequenced. RESULTS: Nucleotide mutation rates among clones of Sample 1 and 2 were 0.3% - 1.1%, 0.4% - 1.7%, respectively. Among 80 clones, the variations from YMDD to YMGD were revealed in two clones. CONCLUSION: There are HBV quasispecies in the P gene region including YMDD motif of hepatitis B virus and a novel mutation of YMDD motif in the sera of patients without being therapied by anti-viral drugs.

Adult↗
PubMed2004

[Impaired non-viral specific immune function of dendritic cell does not interfere with clearance and cytotoxic T lymphocyte response to HBV or HCV].

OBJECTIVE: To investigate the correlation between impaired non-viral specific immune function of dendritic cell (DC) and viral clearance and cytotoxic T lymphocyte (CTL) response to HBV or HCV in patients with HBV and HCV coinfection. METHODS: Twenty-five patients with HBV and HCV coinfection were investigated in this study. In 1994 and 2002, biochemical and virological markers and quantitative serum HBV DNA and HCV RNA levels were detected in these patients. According to the virus clearance status, these patients were divided into 4 groups: 14 patients with both HBV and HCV clearance (Group A), 6 patients with HCV clearance only (Group B), 3 patients with HBV clearance only (Group C), and 2 patients with persistent infection of HBV and HCV (Group D). Phenotypes and immune functions of monocyte-derived DCs were compared between these groups. 51Cr release assay were used to measure CTL response to epitopes derived from HBV, HCV or influenza virus (as positive control) in HLA-A2+ patients. RESULTS: Impaired non-viral specific immune functions of DCs were observed in group B, C and D compared with group A and normal donors (Group N). These impaired functions included CD86 decreasing expression and lower capacity to stimulating allogenic T cells and uptaking antigen. The specific CTL response to HBV- and HCV-derived peptides could be induced in group A (12/12). The specific CTL response to HBV-derived peptides or to HCV-derived peptides could be induced in group C (3/3) or B (5/5), respectively. But the specific CTL response to both of two HBV-derived peptides or two HCV-derived peptides could not be induced in group C (0/3) or B (0/5), respectively. And no CTL response to HBV or HCV-derived peptides could be induced in groups D (0/1) and N (0/4). CONCLUSION: 1. The results suggest that specific CTL response to HBV or HCV play a vital role in the viral clearance. 2. The DCs with impaired non-viral specific immune functions exist in chronic patients with HBV and/or HCV infection, but do not interfere with clearance and CTL response to HBV or HCV. It is reasonable to speculate that impaired functions of DCs result from viral infection.

Adult↗