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)

We have induced acute hepatitis in rats with the amino sugar Galactosamine by i.p. injection. The development of the disease was controlled by measurements of several metabolites and enzymes in serum, and light and electronic microscopy. Tyrosine transaminase was induced by i.p. injection of Cortisol, that increases ten times enzyme activity in liver parenchyma of normal rats. This inductive phenomenon cannot be observed in animals with galactosamine hepatitis. We discuss the probable mechanism and their relationship with some forms of viral hepatitis in human beings.
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PMID:Induction of tyrosine aminotransferase in galactosamine hepatitis. 4 46

Efficient inhibition of human immunodeficiency virus-1 (HIV-1) replication with intracellularly expressed antiviral genes would be an important step toward clinical gene therapy for HIV-1 disease. Enzo Biochem is investigating and developing antisense genes as a potential gene therapy approach against a variety of conditions including acquired immunodeficiency syndrome (AIDS), cancer and hepatitis. The subsidiary of Enzo Biochem, Enzo Therapeutics, utilized its StealthVector technology and initiated phase I trials in July 1998 [291511,307156]. StealthVector, which is comprised of independent antisense sequences directed against two functional HIV-1 regions, is involved in regulation of gene expression soon after HIV infection, transactivation response (TAR) and tat/rev. StealthVector localizes primarily in the cell nucleus, where it could be most effective in inhibiting viral growth.
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PMID:Technology evaluation: StealthVector (HIV) Enzo. 1124 72

As major antigen-presenting cells and effectors in the maintenance of tolerance, dendritic cells (DCs) are key cells of the immune system and can thus be envisioned to have roles in immunotherapy strategies. We, and others, previously showed that simian immunodeficiency virus (SIV)-derived lentiviral vectors were able to deliver a gene into human differentiated DCs. We describe here the upgrading of the SIV vector system and the improvements of the transduction protocol, which allowed us to transduce more than 90% of human monocyte-derived DCs. We developed new SIV lentiviral vectors carrying SIV splice regulatory elements and either the woodchuck hepatitis virus regulatory element (WPRE) or the murine phosphoglycerate-kinase 1 (PGK) promoter. We show that insertion of the WPRE in the SIV vector is detrimental to gene transfer in DCs, while this sequence increases transgene expression in 293T cells. Using an optimized SIV vector, high levels of transgene expression were obtained in more than 30% of human DCs at a multiplicity of infection (MOI) of 1, and close to 100% using a MOI of 20. VSV-G pseudotyped vectors generated with only gag, pol, tat, and rev helper functions failed to transduce DCs. This defect was completely rescued when the SIV accessory gene vpx was provided in trans in vector-producing cells. Genetically modified DCs were shown to behave as bona fide DCs in both allogenic and autologous mixed leukocyte reactions. These findings allow us to propose an optimal system for efficient and safe DC transduction with improved SIV vectors.
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PMID:High levels of transduction of human dendritic cells with optimized SIV vectors. 1186 18

Gene transfer systems based on lentiviruses have emerged as promising gene delivery vehicles for human gene therapy due to their ability to efficiently transduce nondividing target cells. Both primate and nonprimate lentiviruses have been used for construction of lentiviral vectors. An early generation of gene transfer system based on bovine immunodeficiency virus (BIV) has been developed (R. D. Berkowitz, H. Ilves, W. Y. Lin, K. Eckert, A. Coward, S. Tamaki, G. Veres, and I. Plavec, 2001, J. Virol. 75, 3371-3382). In this study, we mapped the BIV Rev response element (RRE) to 312 bp of the Env coding region. Furthermore, we compared transduction efficiencies of vectors containing different portions of the BIV Gag coding region and found that the first 104 bp of gag contains a functional part of the BIV packaging signal. These findings enabled the generation of a minimal BIV-based lentiviral vector. The minimal transfer vector construct consists of a self-inactivating long terminal repeats (LTR), minimal packaging sequence, putative central polypurine tract, minimal RRE, an internal promoter driving the gene of interest, and a woodchuck hepatitis posttranscriptional regulatory element. In addition, we constructed a BIV packaging construct containing gag/pol, minimal Rev/RRE, and the accessory gene vpy. The regulatory gene tat and the accessory genes vif and vpw have been inactivated or truncated. The current system has significantly reduced regions of homologies between the transfer vector and the packaging constructs. The vectors generated from this system achieved a titer of greater than 1 x 10(6) transducing units per milliliter and are fully functional as indicated by their ability to efficiently transduce both dividing and nondividing cells. These modifications should provide improved safety features for the BIV-based gene transfer system.
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PMID:Mapping of the bovine immunodeficiency virus packaging signal and RRE and incorporation into a minimal gene transfer vector. 1249 Mar 99

RNA-based compounds are promising agents to inactivate viruses. New specific hepatitis delta virus (HDV)-derived ribozymes are natural molecules that can be engineered to specifically target a viral RNA. We have designed specific on-off adaptor (SOFA)-HDV ribozymes targeting the tat and rev sequences of the human immunodeficiency virus type 1 (HIV-1) RNA. We show that the SOFA-HDV ribozymes cleave their RNA target in vitro. They inhibit the Tat-mediated transactivation of HIV-1 from 62% to 86% in different assays. In vivo, the amount of HIV RNA was decreased by 60 and 86% with two distinct ribozymes, which indicates that the inhibition of HIV production is directly correlated to the decline in spliced and unspliced viral RNAs. These SOFAHDV- ribozymes inhibited the expression and the viral production of four HIV-1 strains, indicating an extended potential to act on multiple HIV variants. In HEK 293T and HeLa cells transfected with pNL4-3 and the SOFA-HDV-ribozymes, the reduced RNA levels consequently decreased the Gag protein expression in the cell and virus production in the supernatant. When transfected before HIV-1 infection, the ribozymes prevented the incoming virus from being expressed. The ribozymes inhibited HIV production up to 90% when transfected in combination with the HIV protease inhibitor Atazanavir. Our results strongly suggest that SOFA-HDV ribozymes have a great potential to target HIV-1 and to be used as therapeutic agents in combination therapy.
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PMID:In vitro and in vivo cleavage of HIV-1 RNA by new SOFA-HDV ribozymes and their potential to inhibit viral replication. 2142 17