Keith M Dawson

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APO866 inhibits nicotinamide phosphoribosyltransferase (NMPRTase), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Intracellular NAD is essential for cell survival, and NAD depletion resulting from APO866 treatment elicits tumor cell death. Here, we determine the in vitro and in vivo(More)
Mouse embryo development is identically inhibited by raised osmolarity, whether produced by added NaCl or raffinose, demonstrating that high osmolarity is itself detrimental to embryos. In the face of increased osmolarity, cells in the brain and kidney, and likely many other cells, accumulate nonperturbing organic osmolytes in their cytoplasm. In the(More)
Mouse zygotes and early cleavage-stage embryos are sensitive to increased osmolarity. However, development can occur at higher osmolarities if any of a number of organic compounds are present. One of the most effective of these is glycine. We have found that the amount of glycine accumulated by embryos during in vitro culture from the zygote to two-cell(More)
Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin(More)
Treatment of mice with polyinosinic acid . polycytidylic acid [poly(I) . poly(C)] 6 h before infection and once daily on days 1, 2, 3, 4, 7, and 10 after infection with encephalomyocarditis virus was found to confer no additional protection as compared with a single treatment 6 h before infection. When complexed with a colloid formed between(More)
A simple colorimetric assay for estimating cell numbers has been developed based on the observation that the indicator color in cell culture medium is proportional to viable cell number. The assay is performed in multiwell plates to take advantage of the rapid color measurement and computerized data handling capabilities of multiwell scanning(More)
Three murine anti-human beta-interferon (IFN-beta) monoclonal antibodies have been isolated following adoptive transfer of immune spleen cells. Adoptive transfer was used to increase the specific efficiency of the fusion. These antibodies have been used to define two epitopes on IFN-beta; the antiviral, antiproliferative, and immunomodulatory effects of(More)
Human fibroblast interferon, designated IFN-beta 1, has been produced in E. coli by direct expression of the cloned cDNA coding for the mature polypeptide. Bacterial lysates from recombinant cultures contain a polypeptide with an apparent molecular weight of 17,500 that corresponds in size to the unglycosylated IFN-beta 1 molecule. The latter could be(More)
The protein synthesis inhibitor beta-gamma-methylene guanosine triphosphate (Gpp-CH2p) is shown here to be ineffective as a 'leaky membrane' antiviral agent against encephalomyocarditis virus infection of L cells and mice. Studies with GppCH2p in encephalomyocarditis virus-infected L cells indicate that the cells only become permeable to the inhibitor late(More)