A survey of physicians' awareness of drug costs.
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Anti-Bacterial Agents↗
Biomedical subjects
D R Lowy
Publications and source records attributed to D R Lowy.
Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine.
Cells of embryos of the high leukemic mouse strain AKR can be grown in culture as virus-negative cell lines. However, these lines and clonal sublines uniformly have the capacity to initiate synthesis of murine leukemia virus. Exposure of the cells to 5-iododeoxyuridine or 5-bromodeoxyuridine induced synthesis of virus in as high as 0.1 to 0.5 percent of the cells; many of the cells were producing virus as soon as 3 days after initiation of treatment. Induction of virus by these drugs is several orders of magnitude greater than that obtained with any other treatment tested. These studies indicate that the full genome of murine leukemia virus is present in an unexpressed form in all AKR cells and provide a potentially powerful technique for activating leukemia virus genomes in other cell systems.
Animals↗
Interaction of interferon with chick embryo cells.
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Animals↗
Expression and detection of endogenous mouse C-type RNA viruses.
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Animals↗
Regulation of p21ras activity.
The ras genes encode GTP/GDP-binding proteins that participate in mediating mitogenic signals from membrane tyrosine kinases to downstream targets. The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control mechanisms. GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Other cellular factors can positively regulate p21ras by stimulating GDP/GTP exchange.
Amino Acid Sequence↗
HPV infection: future prospects.
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Animals↗
The p21 ras C-terminus is required for transformation and membrane association.
The Harvey murine sarcoma virus (Ha-MuSV) transforming gene, v-rasH, encodes a 21,000 molecular weight protein (p21) that is closely related to the p21 proteins encoded by the cellular transforming genes of the ras gene family. The primary translation product (prop21), which is found in the cytosol, undergoes posttranslational modification and the mature protein subsequently becomes associated with the inner surface of the plasma membrane and binds lipid tightly. The p21 proteins have the capacity to bind guanine nucleotides non-covalently in vitro. To assess the biological relevance of these biochemical features of the protein, we have now studied a series of deletion mutants located at or near the C-terminus of the viral p21 protein. Our tissue culture studies indicate that amino acids located at or near the C-terminus are required for cellular transformation, membrane association and lipid binding.
Animals↗
An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissue.
Studies of the mutagenic action required for specific chemicals to produce benign or malignant tumours suggest that in mouse skin at least two genetic events occur before carcinoma formation. The isolation of an activated form of the c-rasH gene from skin papillomas has provided evidence that this gene may be a target for the first mutation, which could constitute the initiating mutation in skin carcinogenesis. In vitro studies indicate that the v-rasH gene of Harvey murine sarcoma virus (Ha-MSV), a replication-defective transforming retrovirus, could impart a conditional initiated phenotype on cultured keratinocytes by blocking their ability to differentiate terminally and arresting them in a late basal cell stage of maturation. We now show that when the Ha-MSV v-rasH gene is introduced into cultured keratinocytes by a defective retroviral vector, skin grafts constructed with cells carrying the mutated ras oncogene produce papillomas on athymic nude mouse recipients. Furthermore, the expression of the exogenous oncogene seems to be regulated at the transcriptional level in the differentiated portions of the benign tumour.
Animals↗
Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA.
Enhancers are cis-acting elements that activate transcription in higher eukaryotes independently of their position or orientation relative to the promoter that they activate. The mechanisms by which enhancers activate transcription are poorly understood, in part because, with the exception of the glucocorticoid receptor, the proteins that directly interact with enhancers have not been purified, nor have the genes encoding them been cloned. The upstream regulatory region (URR) that immediately precedes the early genes of the bovine papillomavirus type 1 genome (BPV) has enhancer activity when it is activated by a trans-acting gene product of the BPV E2 open reading frame (ORF) (Fig. 1). It is not known whether this enhancement represents a direct or indirect effect of E2 on the URR. We have used an E2 peptide expressed in bacteria and a DNA-protein complex immunoprecipitation assay to study E2-mediated enhancement of transcription by the URR. We show here that this peptide directly binds to four specific sites in the BPV URR, and to one site in the human papillomavirus (H)PV16 URR. All the binding sites contain a related sequence of nucleotides; a 23 base pair (bp) fragment containing this sequence can specifically prevent binding of the E2 protein to the BPV URR. The BPV E2-URR enhancer interaction may therefore represent a useful model system for studying the mechanism of transcriptional enhancement, as both an effector protein and its target enhancer can be purified and genetically manipulated.
Animals↗