Two trisomic-21 (T-21), one monosomic-21 (M-21), and three diploid (D-21) human fibroblast cell strains were compared for their sensitivity to the antiviral and anticellular activities of human type I (HuIFN-β), human type II (HuIFN-γ), murine type I (MuIFN-β), and murine type II (MuIFN-γ) interferons. Antiviral activity was monitored by the reduction of vesicular stomatitis virus yield and anticellular activity was assessed by the inhibition of [methyl-3H]thymidine uptake in proliferating cells. T-21 cells were more sensitive to the antiviral activities of HuIFN-β and MuIFN-β than either D-21 or M-21 cells. However, T-21 cells were not more sensitive to the antiviral activities of HuIFN-γ and MuIFN-γ. Neither did T-21 cells exhibit an increased sensitivity to the anticellular activity of either HuIFN-β or -γ, or MuIFN-β or -γ. A chromosome 21 dosage effect could not be observed under any of our test conditions.
SUMMARY After heating at 37° in minimal Eagle’s medium, the alternating polyriboadenylic-polyribouridylic acid [poly r(A-U)] became much more active in producing cellular resistance to virus infection and interferon production in four different cell lines (human skin fibroblasts, mouse embryo fibroblasts, mouse L 929 cells and rabbit kidney (RK 13) cells). The thermal activating effect was neutralized by pre-treatment of the cells with DEAE-dextran, which increased the antiviral activity of unheated and decreased the activity of heated poly r(A-U) to the same level. Under all conditions tested, the degree of cellular resistance to virus infection closely paralleled the amounts of interferon produced suggesting that interferon production is responsible for the antiviral resistance produced by poly r(A-U).
Abstract Novel TSAO-T analogues, in which the 3′-spiroaminooxatioledioxide moiety has been replaced by other 3′-spiro moieties bearing a NH group at the same position as the 4″-NH2 of TSAO-T have been prepared and evaluated for their inhibitory effect on HIV replication in cell culture. In contrast to the prototype compound TSAO-T, the novel TSAO derivatives were inactive at subtoxic concentrations.
Reverse transcription of human immunodeficiency virus type 1 (HIV-1) is a crucial step in the life cycle initiated by the viral-coded reverse transcriptase (RT), functioning as RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H functions to degrade the RNA strand of the RNA:DNA heteroduplex, which makes it an attractive target for rational anti-HIV-1 drug design and development. Although development of drugs targeting the DNA polymerase have been highly successful, the discovery of drugable inhibitors of HIV RNase H is still in its infancy and none of RNase H inhibitors has reached the clinical development stage currently. This review describes the recent progress in the HIV-1 RNase H inhibitors, focusing on their chemical feature, mechanism and the structure-activity relationship (SAR).
The aim is to improve the surface quality of EDMed workpieces by in-process alloying of the white layer.Two alloying methods are investigated: using compacted powder electrodes and using powder suspended dielectrics.Both methods are able to alloy the white layer of the machined workpiece if inverse polarity is used (workpiece positive, electrode negative).When using powder electrodes, the alloying percentage is inversely proportional to the density of the electrode.Alloying percentages of more than 40 % can be obtained.When using powder suspended dielectrics, the applied regimes have to be even less powerful than with the powder electrodes to enable alloying.In this case, alloying percentages of more than 10 % can be achieved.Test results show that it is possible to obtain a more corrosion resistant surface with a higher hardness and less micro cracks resulting in a longer lifetime of the workpiece.
Athymic nude (nu/nu) mice, normal NMRI (plus/plus) mice, and nu/plus heterozygotes, inoculated at birth with the Moloney strain of murine sarcoma virus (M-MSV), did not differ either in tumor growth rate or incidence or in mortality due to tumor development; neither did nude (nu/nu) and normal NMRI mice inoculated with M-MSV at 30 days of age differ in the initial tumor growth rate. However, tumors induced in adult nude mice grew progressively and eventually killed the hosts, whereas tumors induced in adult normal NMRI mice completely regressed. These results indicated that thymus-dependent immunity, though not active in M-MSV tumor induction, determined whether the tumor, once formed, would regress or kill the host.
