Trace element binding in the copper deficient mottled mutants in the mouse.
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Biomedical subjects
Publications and source records attributed to D M Hunt.
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Estradiol-17 beta (E2-17 beta) treatment induced dose-related reduction of sperm population and eventual azoospermia, atrophy of accessory organs, and suppressed serum LH and testosterone levels. In spite of all these alterations mating behavior was not affected, although the number of implantation sites paralleled the reduction of sperm population, suggesting that the primary detectable response to E2-17 beta treatment is related to the steroidogenic components of the testis and the hypothalamic pituitary axis. The duration of treatment is more critical for the induction of azoospermia in the rat than the total dose of E2-17 beta.
The effects of medroxyprogesterone acetate (Provera), testosterone propionate (TP), ethinyl estradiol (EE), and ethynodiol diacetate (ED) treatments on sperm population in different segments of the male rat reproductive tract, reproductive organ weights, circulating androgens and fertility were studied. Ten microgram TP given for five days reduced the sperm population and organ weights. A marked reduction in the number of sperm and reproductive organ weights was observed in males orally treated with estrogens. Only long-term (20 days) treatment with Provera (1 mg/day) significantly reduced sperm population and reproductive organ weights. Combination of TP and Provera resulted in a more pronounced reduction in sperm counts and organ weights. Among steroids studied, estrogen was the only compound which suppressed fertility and circulating steroid levels.
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Induction of erythroid differentiation in ouabain-resistant murine erythroleukemia cells by ouabain is reported. Ouabain induction results in the appearance of hemoglobin-containing cells 12-24 hr earlier than induction of the same clone by dimethyl sulfoxide. The levels of globin mRNA after ouabain induction are similar in amount to the globin mRNA levels observed after induction by dimethyl sulfoxide. The concentration of ouabain required to induce hemoglobin synthesis depends upon the K+ ion levels in the culture medium. Lowering the extracellular K+ ion concentration 2-4 fold reduced by 10-40 fold the ouabain concentration necessary for the induction of hemoglobin synthesis. In low K+ medium (1.8 mM), ouabain is an effective inducer of hemoglobin synthesis at a concentration of 0.02 mM. This K+ effect is specific for ouabain induction, since induction by other inducers, such as dimethyl sulfoxide and dimethyl acetamide, does not exhibit this marked sensitivity to the levels of K+ ions in the culture medium. These results suggest that the binding of ouabain to the plasma membrane enzyme, Na/K ATPase, is required for the induction of erythroid differentiation by ouabain. A small but significant proportion of wild-type, ouabain-sensitive cells also can be induced by ouabain, below ouabain concentrations that are toxic to these cells. The observation that the binding of ouabain to the Na/K ATPase induces hemoglobin synthesis suggests that changes in the intracellular concentration of K+ ions may be involved in the control of erythroid differentiation in Friend erythroleukemic cells.
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In vitro transcriptase activity of three group I temperature-sensitive (ts) mutants of vesicular stomatitis virus restricted at 39 C was restored by L-protein fractions derived from wild-type (wt) vesicular stomatitis virion nucleo-capsids. Soluble NS protein from wt nucleocapsids did not reconstitute restricted transcriptions of the group I RNA-ts mutants. NS protein activity, but not L protein activity, was purified from the group I ts mutants; this NS fraction always displayed the wt phenotype in reconstitution assays. Neither the L nor the NS protein was capable of restoring the defective transcriptive activity of the group IV vesicular stomatitis virus mutant ts W16B.
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The in vitro activity of the ribonucleoprotein-dependent RNA transcriptase of vesicular stomatitis virions was found to be completely inhibited by low concentrations of aurintricarboxylic acid (ATA) and polyethylene sulfonic acid (PES) when these inhibitors were added before the start of the RNA polymerase reaction. However, if RNA synthesis was allowed to occur before ATA or PES was added, RNA synthesis continued for a short time (10 min or less) in the presence of either inhibitor at a concentration which completely inhibited uninitiated enzyme. The ability to continue to synthesize RNA in the presence of ATA or PES only developed if all four nucleoside triphosphates were present during the preincubation period prior to the addition of the inhibitors. The protection was apparently not due to the released products of RNA polymerization. The results are interpreted as indicating that ATA and PES probably inhibit some reaction other than elongation of RNA chains, and this reaction might be one involved at or near initiation sites.
Mice homozygous for rho-25h, a mutation at the pink-eye locus, are small, nervous and male sterile, with abnormal sperm morphology: females have very low fecundity. Evidence is presented that in both sexes the pars nervosa of the rho-25h/rho-25h pituitary contains degenerating nerve axons, that the hypothalamus has a reduced binding capacity for oestradiol-17 beta and that thyroid iodine binding is reduced. No changes were observed in the anterior pituitary. In rho-25h/rho-25h females, the uterus is threas-like and unresponsive to oestradiol, and the ovaries are small with many abnormal follicles. Possible modes of action of the rho locus are duscussed with reference to this and pre-existing data on the rho phenotype.
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The ribonucleoprotein-dependent RNA transcriptase in vesicular stomatitis B virions of four temperature-sensitive (ts) mutants belonging to complementation group I was analyzed in vitro at permissive (31 C) and restrictive (39 C) temperatures. The RNA-synthesizing activity of all four ts mutants was more labile at 39 C than was the transcriptive activity of wild-type (wt) virions. In order to locate the temperature-sensitive transcription defect in the mutants, wt and ts mutant virions were fractionated by Triton X-100-high salt solubilizer into a sedimentable ribonucleoprotein template and a nonsedimentable enzyme fraction, each of which alone had little or no transcriptive activity. The template- and enzyme-containing fractions of wt virions were then tested for their capacity to restore transcriptive activity at 39 C to corresponding template and enzyme preparations of ts mutant virions. Recombination of wt template and ts enzymes resulted in no significant restoration of capacity to synthesize RNA at restrictive temperature. In contrast, transcriptive function at 39 C was reconstituted by recombining the wt enzyme with the template component of ts mutants. It appears, therefore, that the enzyme, rather than the template, is the temperature-sensitive component of the transcription complex of group I vesicular stomatitis virus mutants.
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