Synergy of an IgH promoter-enhancer-driven c-myc/v-Ha-ras retrovirus and pristane in the induction of murine plasmacytomas.
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Biomedical subjects
Publications and source records attributed to J Wax.
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A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditioned mice with mean latency periods of 60-70 days. In contrast, the same vector only harboring c-myc or v-Ha-ras was virtually ineffective. RIM-induced plasmacytomas expressed retroviral myc and ras genes while their endogenous c-myc alleles were unrearranged and transcriptionally inactive. These plasmacytomas were clonal as each possessed a unique immunoglobulin heavy-chain joining region rearrangement and a single recombinant provirus. Moloney murine leukemia helper virus did not play an obligatory role in tumorigenesis since insertions of Moloney murine leukemia proviruses were found in only 6 of 24 plasmacytomas induced in adult mice. Taken together, these findings support the view that the v-Ha-ras oncogene can cooperate with an activated myc gene in pristane plasmacytomagenesis.
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A method for the comparative bioassay of nonsteroidal anti-inflammatory agents is presented which exploits the early inflammation induced by injection of adjuvant into the plantar surface of a hind paw of the rat. The inflammation reaches a peak on the 4th postinjection day. Daily treatment with nonsteroidal anti-inflammatory agents reduces paw volumes and the associated impairment of body growth with optimal improvement on the 4th postinjection day. In this model, phenylbutazone has shown significant activity at doses as low at 1.33 mg/kg/day. Statistically valid comparative assays conducted at dose levels equivalent to or below those used in human therapy yield potency ratios with relatively narrow confidence limits. Potencies relative to phenylbutazone for inhibiting primary adjuvant-induced inflammation are: aminopyrine, 0.066 (0.36-0.11)95%; aspirin, 0.087 (0.039-0.19)95%; mefenamic acid, 0.98 (0.64-1.6)95%; flufenamic acid, 13 (7.4-26)95%; meclofenamic acid, 23(16-33)95%; and indomethacin, 53 (35-82) 95%. Ancillary and sometimes quantitative information is also provided by the improvement in well being of the animals as reflected in body weight changes with treatment.
Relative anti-inflammatory potencies of aspirin, phenylbutazone, indomethacin, three fenamates and several other nonsteroidal anti-inflammatory agents were obtained in several laboratory models of acute and chronic inflammation. Relative toxicities and ulcerogenicities were determined in rats of the same source, strain and sex. The acute ulcerogenic assay measures the minimal irritation potential of these agents and leads to a sensitive index of the safety of such compounds when compared with their therapeutic potencies. By these criteria, meclofenamic acid is a highly potent, acceptably safe and exceptionally well tolerated anti-inflammatory-antipyretic agent in rats when compared with other such drugs.
The duration of antinociceptive action of alpha-l-acetylmethadol (LAM), determined in the rat tail pinch test, was 6 times that of morphine and 3 times that of methadone. Onset of activity was considerably later after LAM than after morphine or methadone.
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