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Lizhe Xu

Publications and source records attributed to Lizhe Xu.

6 recordsLinked to original sources
PubMed2004

Cloning the human betaretrovirus proviral genome from patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis (PBC) have both serologic and tissue evidence of infection. A recently identified human betaretrovirus was originally cloned from the biliary epithelium cDNA library of a patient with PBC. By conducting a BLASTN search, the initial partial pol gene fragment was found to have 95% to 97% nucleotide homology with mouse mammary tumor virus (MMTV) and with retrovirus sequences derived from human breast cancer samples. Using an anti-p27(CA) MMTV antibody, viral proteins were detected in the perihepatic lymph nodes but not in liver tissue samples from patients with PBC, suggesting a higher viral burden in lymphoid tissue. Therefore, in the current study, we used lymph node DNA to clone the proviral genome of the human betaretrovirus from two patients with PBC using a polymerase chain reaction (PCR) walking methodology with conserved primers complementary to MMTV. The human betaretrovirus genome contains five potential open reading frames (ORF) for Gag, protease (Pro), polymerase (Pol), envelope (Env), and superantigen (Sag) proteins that are collinear with their counterparts in MMTV. Alignment studies performed with characterized MMTV and human breast cancer betaretrovirus amino acid sequences revealed a 93% to 99% identity with the p27 capsid proteins, a 93% to 97% identity with the betaretrovirus envelope proteins, and a 76% to 85% identity with the more variable superantigen proteins. Phylogenetic analysis of known betaretrovirus superantigen proteins showed that the human and murine sequences did not cluster as two distinct species. In conclusion, human betaretrovirus nucleic acid sequences have been cloned from patients with PBC. They share marked homology with MMTV and human breast cancer-derived retrovirus sequences.

Amino Acid Sequence↗
PubMed2004

Comparison of different microarray data analysis programs and description of a database for microarray data management.

Data analysis and management represent a major challenge for gene expression studies using microarrays. Here, we compare different methods of analysis and demonstrate the utility of a personal microarray database. Gene expression during HIV infection of cell lines was studied using Affymetrix U-133 A and B chips. The data were analyzed using Affymetrix Microarray Suite and Data Mining Tool, Silicon Genetics GeneSpring, and dChip from Harvard School of Public Health. A small-scale database was established with FileMaker Pro Developer to manage and analyze the data. There was great variability among the programs in the lists of significantly changed genes constructed from the same data. Similarly choices of different parameters for normalization, comparison, and standardization greatly affected the outcome. As many probe sets on the U133 chip target the same Unigene clusters, the Unigene information can be used as an internal control to confirm and interpret the probe set results. Algorithms used for the determination of changes in gene expression require further refinement and standardization. The use of a personal database powered with Unigene information can enhance the analysis of gene expression data.

Database Management Systems↗
PubMed2004

Pilot studies of single and combination antiretroviral therapy in patients with primary biliary cirrhosis.

OBJECTIVE: Preliminary reports suggest that patients with primary biliary cirrhosis (PBC) have evidence of human betaretrovirus infection. The aim of this study was to determine whether antiviral therapy impacts on the disease process. METHODS: We conducted two consecutive open-labeled, nonrandomized, 1-yr pilot studies; the first with lamivudine 150 mg/day and the second with Combivir combination therapy using lamivudine 150 mg and zidovudine 300 mg twice a day. Eleven PBC patients enrolled in each study, seven patients were entered into both studies, and one patient was withdrawn from each study due to side effects. RESULTS: Evaluation of liver biopsies before and after lamivudine therapy showed a 4-5 increase in necroinflammatory score, a 1-1.5 elevation in bile duct injury, with little change in the percentage of portal tracts with bile ducts (50-52%). None of the patients in the lamivudine study normalized alkaline phosphatase. Histological assessment following Combivir therapy revealed a 6 to 4 improvement in necroinflammatory score (p < 0.03, 95% CI: 0.53-2.33), a 3 to 1 reduction in bile duct injury (p < 0.02, 95% CI: 1.08-2.07), and a 45-75% increase in portal tracts with bile ducts (p < 0.05, 95% CI: 0.02-0.29). In the Combivir cohort, five patients normalized alkaline phosphatase and four developed normal AST, ALT, and alkaline phosphatase. CONCLUSIONS: Histological and biochemical endpoints were achieved in the Combivir pilot study suggesting a larger placebo-controlled trial is required as a proof of principle to assess whether antiviral therapy impacts the PBC disease process.

Adult↗
PubMed2003

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

Autoantigens↗