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Biomedical subjects

R C Jackson

Publications and source records attributed to R C Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1977

Post-translational cleavage of presecretory proteins with an extract of rough microsomes from dog pancreas containing signal peptidase activity.

The protease(s) responsible for removing the amino-terminal extension of nascent presecretory proteins (signal peptidase) has been extracted from rough microsomes of dog pancreas with the detergent sodium deoxycholate. Preprolactin and pre-growth-hormone, prepared by in vitro translation of bovine pituitary RNA in the wheat germ system, were used to assay signal peptidase in the extract. When added to the wheat germ system during translation, the extract reduced the size of preprolactin and pre-growth-hormone to that of prolactin and growth hormone, respectively. Post-translational addition of the extract also reduced the size of preprolactin and pre-growth-hormone to that of the authentic hormones. The prolactin produced by post-translational cleavage of radiolabeled preprolactin has been shown, by partial amino-terminal sequence analysis, to have the correct amino terminus. This post-translational assay has permitted the investigation of the subcellular localization of the enzyme. Sodium deoxycholate extracts of rough microsomes were active, whereas extracts of smooth microsomes were inactive. However, without detergent treatment, neither rough nor smooth microsomes were capable of cleaving preprolactin in the post-translational assay. From this we conclude that the signal peptidase activity is confined to the rough endoplasmic reticulum and is latent. Finally, we have detected two small peptides which we believe could be the signal peptides generated by the endoproteolytic cleavage of preprolactin and pre-growth-hormone by signal peptidase.

Animals↗
PubMed1976

On the identity of nuclear membrane and non-histone nuclear proteins.

The fate of plasma and nuclear membrane polypeptides in preparations of acidic chromosomal protein from chicken erythrocytes has been investigated. It is shown that detergent extraction procedures (Nonidet P-40, Triton X-100, and saponin), commonly employed in the preparation of acidic chromosomal protein, cannot be relied upon to remove plasma and nuclear membrane polypeptides. These polypeptides persist in nuclear and chromatin preparations and subsequently fractionate as acidic chromosomal protein. In fact, the polypeptides in a preparation of erythrocyte acidic chromosomal protein are shown by gel electrophoresis in dodecyl sulfate to be almost identical to those in a preparation of erythrocyte nuclear membrane. The implication of these results for the preparation of acidic chromosomal protein is dicussed.

Animals↗
PubMed1976

The effect of trimethoprim on cellular transport of methotrexate and its cytotoxicity to human lymphoblastoid cells in vitro.

A study has been made of the effects of the antifolate drug trimethoprim (2,4-diamino-5-(3'4',5'-trimethoxybenzyl)pyrimidine) on the cellular transport of natural folates and of methotrexate in a human lymphoblastoid cell line grown in culture. The results indicated that cellular uptake of 5-methyltetrahydrofolate, folic acid and methotrexate could be inhibited by trimethoprim; the inhibition, for methotrexate at least, was competitive, but it was in every case rather weak. Calculations showed that under conditions used during therapy with methotrexate, trimethoprim could be employed as an antibacterial agent without the cellular uptake of methotrexate being impaired by more than 1%. The cytotoxic effect of trimethoprim against the cell line used was 2000 times less, on a molar basis, than that of methotrexate. However, the degree of growth inhibition caused by the two agents in combination was greater than the sum of the individual toxicities. Again, this effect was not large at clinically useful concentrations of trimethoprim.

Biological Transport↗
PubMed1976

The aerobic demands of rowing in two Olympic rowers.

The relationship between rowing speed and Vo2 was determined on two Olympic oarsmen while rowing the single, double and coxless pair shells. The speeds covered ranged from 120 to approximately 300 meters/min and resulted in oxygen demands from 1.2 to 6.45 1 O2/min. First order regression equations described the speed/Vo2 relationship for each shell. Rowing at racing speed in either shell required an aerobic expenditure of 5.8-6.0 1 O2/min.

Adult↗
PubMed1976

The reaction of Cytembena with cellular thiol compounds.

Cytembena has been shown to undergo a rapid addition reaction with a number of thiol compounds, including glutathione and cysteine, resulting in alkylation of the sulphur. Administration of Cytembena to Yoshida sarcoma cells and to L1210 leukemia cells resulted in a loss of titratable thiol groups within the cells, though the loss of thiol groups caused by pharmacologically active doses of the drug was not sufficient to account, in itself, for the observed toxicity. The addition product of Cytembena and glutathione was isolated and tested for cytotoxicity; it was much less effective than free Cytembena. It is concluded that this reaction acts as a route of detoxification of Cytembena.

Acrylates↗
PubMed1976

Enzyme pattern-directed chemotherapy: synergistic interaction of 3-deazauridine with D-galactosamine.

We tested an experimental approach in which the specialized enzymatic pattern characteristic of the tissue of origin of a tumor might be exploited to target and enhance drug selectivity. In the present work, the D-galactosamine-induced depletion of uridine 5'-triphosphate (primarily a hepatic event) was employed to enhance the growth inhibition caused by 3-deazauridine. As predicted, the drug effect was most pronounced in the slower growing, well differentiated hepatoma lines where the activities of certain hepatic metabolic pathways and enzymes, though decreased, were still operative. The interactions of D-galactosamine and cytosine arabinoside with 3-deazauridine were examined in vitro in four liver tumor cell lines and two nonhepatic lines. The effects of D-galactosamine and 3-deazauridine on the growth of the Morris hepatoma cell lines 3924A, 8999S,AND 8999R were strongly synergistic; on the Novikoff hepatoma and the nonhepatic cell lines they were only additive. The combination of 3-deazauridine with cytosine arabinoside gave approximately additive growth inhibition with all cell types, without selective toxicity towards the hepatocellular lines. Results of growth-inhibition studies with the combination of D-galactosamine and cytosine arabinoside and with combinations of all three agents are also presented. These results are analyzed in the context of the regulation of hepatic pyrimidine nucleotide metabolism and our design of enzyme pattern directed drug selectivity.

3-Deazauridine↗
PubMed1976

Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrololate reductases.

Four cultured mammalian cell lines, differing in intrinsic resistance to methotrexate over a 70-fold range, have been compared with respect to several biochemical factors that might influence response to the drug. Cellular activity of the enzymes dihydrofolate reductase and thymidylate synthetase and the total levels of folate cofactors did not vary by more than a factor of 2 among the cell lines. All the cell types were able to transport extracellular methotrexate efficiently across the cell membrane, and at comparable rates. A kinetic study of highly purified dihydrofolate reductases from the four sources revealed small differences in the Km values for dihydrofolate and reduced nicotinamide adenine dinucleotide phosphate. A study was made of the inhibition of the four dihydrofolate reductases by methotrexate, and Ki values were obtained by fitting the Zone B equation of Goldstein (Goldstein, A., J. Gen. Physiol., 27: 529-580, 1944) to the resulting data. Values Ki determined by this method correlated with intrinsic resistance of the cell lines and showed a 25-fold range from the most sensitive to the most resistant line. It is concluded that the response of a cell to methotrexate is significantly influenced by the dissociation constant of its dihydrofolate reductase-methotrexate complex.

Biological Transport↗
PubMed1975

The exterior surface of the chicken erythrocyte.

The exterior surface of mature chicken erythrocytes has been labeled with a cationic membrane impermeable reagent, rho-nitrophenyl-N,N,N-trimethy[125I]iodotyrosinate. This reagent forms stable covalent bonds with the amino groups of exposed protein and lipid companents. Two major protein components with subunit molecular weights of 100,000 and 55,000 are found on the outer surface of mature chicken erythrocytes. Both of the labeled components coincide were periodic acid-Schiff base-stained areas on sodium dodecyl sulfate polyacrylamide gel electrophoresis indicating that they may be glycoproteins.

Animals↗