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Biomedical subjects

K F Manly

Publications and source records attributed to K F Manly.

35 records · Page 2Linked to original sources
PubMed1979

Differences in pathogenicity among cloned sublines of a murine leukemia virus.

Five clones of the lymphatic leukemia virus 334C were isolated by a procedure designed to maintain homogeneity of the clones. Three of these induced leukemia in mice with the time course of the uncloned parental virus, one induced leukemia with a delayed time course, and one seemed to be biologically inactive. When the clone inducing leukemia most rapidly and the clone inducing leukemia least rapidly were subcloned, the subclones retained the leukemogenicity of the parental clones. The electrophoretic patterns of purified virion proteins and hybridization of viral RNAs with virus-specific DNA suggest that these clones are two closely related variants, not unrelated viruses. Furthermore, in mice infected with these two clones, viral RNA appears in thymuses and spleens at the same time after infection and at nearly the same concentrations. Thus, variations in leukemogenicity can be determined by a genetic property of an ecotropic leukemia virus, and this property is expressed in some manner more subtle than simple control of replication.

Animals↗
PubMed1978

Characterization of virus-like particles released from the hamster cell line CHO-K1 after treatment with 5-bromodeoxyuridine.

Simple biochemical measurements have been shown to seriously overestimate the production of C-type particles by Chinese hamster ovary (CHO) cells treated with 5-bromodeoxyuridine. First, most particle-bound DNA polymerase activity released by induced cells was associated with particles which had a different density from C-type particles. Second, when labelled with radioactive uridine, induced CHO cells released small amounts of particle-bound radioactivity. Most of the radioactivity, however, was in DNA and did not sediment with the particle-bound polymerase. Thus, few particles which had RNA, an associated DNA polymerase, and the density typical of RNA tumour viruses were released by BrdUrd-induced CHO cells. In spite of this, some immature C-type forms were observed by electron microscopy in partially purified preparations of DNA polymerase-containing particles from induced CHO cells.

Animals↗
PubMed1976

Inhibition of RNA-directed DNA polymerase by aurintricarboxylic acid.

Commercial-grade aurintricarboxylic acid (ATA) inhibits poly(A), poly(C) and viral RNA-directed DNA synthesis by detergent-disrupted virions of Moloney murine leukemia virus. Paper chromatography of crude ATA yields two active components, which appear to behave identically, and at least two inactive components. The concentration of ATA needed to inhibit polymerase activity is proportional to the concentration of viral protein. The inhibition is neither attributable to contaminating heavy metal ions in the ATA preparation nor to chelation by ATA of Mn2+ or Zn2+, the necessary co-factors. Inhibition of the polymerase reaction by ATA greatly increases the Km for the primer [oligo(T)/oligo(dG)], while it only slightly lowers the Vmax and does not affect the Km's for the template [poly(A)/poly(C)] or the substrate (TTP/dGTP). Thus, ATA seems to reduce specifically the affinity of the polymerase for the DNA primer molecule.

Aurintricarboxylic Acid↗
PubMed1974

Histones stimulate polyribonucleotide-directed polydeoxyribonucleotide synthesis by murine leukemia virus.

The rate of homoribopolymer-directed DNA synthesis by detergent-disrupted Moloney murine leukemia virus can be stimulated or inhibited by histone, depending on the ratio of histone to template. Of the fractions which can be separated from the whole histone, f1 causes both the greatest stimulation and the greatest inhibition. The effect of histone f1 is qualitatively similar whether the template is polyadenylate (poly A), polycytidylate, or polyuridylate, but the stimulation is greatest with poly A. The pattern of stimulation and inhibition differs, however, for a different polymerase; the DNA polymerase of Micrococcus luteus is inhibited by histone concentrations which stimulate the viral enzyme and stimulated by concentrations which inhibit the viral enzyme. For the viral enzyme, the optimum histone concentration is unaffected by changes in the virus or primer concentration; but it varies in proportion to the template concentration, suggesting that histone acts by combining stoichiometrically with the template. These data raise the possibility that a histone-like protein may participate in the synthesis of the provirus of RNA tumor viruses.

Animals↗
PubMed1971

Forms of deoxyribonucleic acid produced by virions of the ribonucleic acid tumor viruses.

The in vitro product of mouse leukemia virus deoxyribonucleic acid (DNA) polymerase can be separated into two fractions by sedimentation in sucrose gradients. These two fractions were analyzed for their content of single-stranded DNA, double-stranded DNA, and DNA-ribonucleic acid (RNA) hybrid by (i) digestion with enzymes of known specificity and (ii) equilibrium centrifugation in Cs(2)SO(4) gradients. The major fraction early in the reaction contained equal amounts of single-stranded DNA and DNA-RNA hybrid and little double-stranded DNA. The major fraction after extensive synthesis contained equal amounts of single-and double-stranded DNA and little hybrid. In the presence of actinomycin D, the predominant product was single-stranded DNA. To account for these various forms of DNA, we postulate the following model: the first DNA synthesis occurs in a replicative complex containing growing DNA molecules attached to an RNA molecule. Each DNA molecule is displaced as single-stranded DNA by the synthesis of the following DNA strand, and the single-stranded DNA is copied to form double-stranded DNA either before or after release of the single strand from the RNA. Actinomycin blocks this conversion of single-to double-stranded DNA.

Carbon Isotopes↗
PubMed1965

Anesthesia of Artemia larvae: method for quantitative study.

Potency of anesthetics is quantitatively measured with laboratory-hatched larvae of the brine shrimp Artemia salina. Statistical fluctuations are minimized in that 100,000 animals are used to determine a single median anesthetic dose value. The technique was developed to study molecular mechanisms of general anesthesia.

Anesthesia, General↗