Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased transgene expression per vector genome is an important goal in the optimization of viral vectors for gene therapy. Herein we demonstrate that herpes simplex virus type 1 (HSV1) thymidine kinase (TK) gene sequences (1,131 bp) fused to the 3' end of lacZ increase transgene expression from high-capacity adenoviral vectors (HCAd), but not from first-generation (Ad) vectors. The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), in contrast, increased transgene expression levels from Ad but not HCAd vectors. The differential activity of the HSV1 TK gene and WPRE sequences was detected both in vitro and in vivo and suggests potentially different mechanisms of action or the interaction of these elements with vector genomic sequences.
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PMID:Herpes simplex virus type 1 thymidine kinase sequence fused to the lacz gene increases levels of {beta}-galactosidase activity per genome of high-capacity but not first-generation adenoviral vectors in vitro and in vivo. 1907 29

A case of fulminant disseminated varicella is reported in a 28-year-old immunocompetent man. He developed hepatitis, severe pneumonia, rhabdomyolysis and disseminated intravascular coagulation, followed by encephalopathy and multiorgan failure despite acyclovir therapy. He spent a total of 3.5 months in intensive care and rehabilitation units. Real-time PCR yielded a rapid diagnosis of varicella-zoster virus (VZV) infection and was used to monitor plasma viral load for 56 days. Plasma viral load peaked at 7.1 log(10)/ml on day 4 after symptom onset, then gradually declined and became undetectable after between 1 and 2 months; viral load in lung fluid followed a similar pattern. The glycoprotein E variant associated with increased VZV virulence was not detected, and the VZV thymidine kinase gene bore no major mutations associated with acyclovir resistance. This case serves as a reminder that varicella can be life-threatening in adults and that vaccination of individuals at risk remains essential.
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PMID:Disseminated varicella with multiorgan failure in an immunocompetent adult. 1923 68

Adult stem cells may serve as powerful cellular vehicles to deliver therapeutic genes for cancer therapy. In such applications, effective and safe transduction to load stem cells with genes of interest is essential. To examine whether baculovirus can be used to fulfill this task, we tested a range of baculoviral vectors in human bone marrow mesenchymal stem cells (MSCs). A vector using the human cytomegalovirus immediate-early gene promoter to drive transgene expression and the woodchuck hepatitis virus posttranscriptional regulatory element to enhance translation was able to transduce MSCs with efficiency close to 80%. Following the observation that baculoviral transduction did not significantly affect surface marker expression of the stem cells, we tested the feasibility of using baculovirus-transduced MSCs for targeted cancer therapy. We transduced cells with a baculoviral vector harboring the herpes simplex virus thymidine kinase gene, and performed tail vein injection of the transduced cells into mice preinoculated subcutaneously with human U87 glioma cells. After ganciclovir prodrug injection, we observed inhibition of tumor growth and significantly prolonged survival of tumor-inoculated animals. Our findings suggest that baculoviral transduction of MSCs is an attractive option to generate targeting vehicles for systemic cancer therapy.
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PMID:Baculovirus-transduced bone marrow mesenchymal stem cells for systemic cancer therapy. 2053 21

The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs.
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PMID:A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections. 2414 55

Inflammation and fibrosis in human liver are often precursors to hepatocellular carcinoma (HCC), yet none of them is easily modeled in animals. We previously generated transgenic mice with hepatocyte-specific expressed herpes simplex virus thymidine kinase (HSV-tk). These mice would develop hepatitis with the administration of ganciclovir (GCV)(Zhang, 2005 #1). However, our HSV-tk transgenic mice developed hepatitis and HCC tumor as early as six months of age even without GCV administration. We analyzed the transcriptome of the HSV-tk HCC tumor and hepatitis tissue using microarray analysis to investigate the possible causes of HCC. Gene Ontology (GO) enrichment analysis showed that the up-regulated genes in the HCC tissue mainly include the immune-inflammatory and cell cycle genes. The down-regulated genes in HCC tumors are mainly concentrated in the regions related to lipid metabolism. Gene set enrichment analysis (GSEA) showed that immune-inflammatory-related signals in the HSV-tk mice are up-regulated compared to those in Notch mice. Our study suggests that the immune system and inflammation play an important role in HCC development in HSV-tk mice. Specifically, increased expression of immune-inflammatory-related genes is characteristic of HSV-tk mice and that inflammation-induced cell cycle activation maybe a precursory step to cancer. The HSV-tk mouse provides a suitable model for the study of the relationship between immune-inflammation and HCC, and their underlying mechanism for the development of therapeutic application in the future.
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PMID:A Herpes Simplex Virus Thymidine Kinase-Induced Mouse Model of Hepatocellular Carcinoma Associated with Up-Regulated Immune-Inflammatory-Related Signals. 3006 May 37


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