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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 343 records · Page 19Linked to original sources
PubMed1982

Organization of human histone genes.

We describe the isolation and initial characterization of seven independent lambda Charon 4A recombinant phages which contain human histone genomic sequences (designated lambda HHG). Restriction maps of these clones and localization of the genes coding for histones H2A, H2B, H3, and H4 are presented. The presence of histone encoding regions in the lambda HHG clones was demonstrated by several independent criteria including hybridization with specific DNA probes, hybrid selection/in vitro translation, and hybridization of lambda HHG DNAs to reserve Southern blots containing cytoplasmic RNAs from G1-, S-, and arabinofuranosylcytosine (cytosine arabinoside)-treated S-phase cells. In addition, the lambda HHG DNAs were shown to protect in vivo labeled H4 mRNAs from S1 nuclease digestion. Based on the analysis of the lambda HHG clones, human histone genes appear to be clustered in the genome. However, gene clusters do not seem to be present in identical tandem repeats. The lambda HHG clones described in this report fall into at least three distinct types of arrangement. One of these arrangements contains two coding regions for each of the histones H3 and H4. The arrangement of histone genes in the human genome, therefore, appears to be different from that in the sea urchin and Drosophila genomes in which each of the five histone-encoding regions (H1, H2A, H2B, H3, and H4) is present only once in each tandemly repeated cluster. At least one clone, lambda HHG 41, contains, in addition to the histone genes, a region that hybridizes with a cytoplasmic RNA approximately 330 nucleotides in length. This RNA is not similar in size to known histone-encoding RNAs and is present in the cytoplasm of HeLa cells predominantly in the G1 phase of the cell cycle.

Bacteriophage lambda↗
PubMed1981

Effect of temperature on phospholipase C induced alterations in insulin binding.

Regulation of insulin-receptor affinity is at present poorly understood. In this study membrane structure was modified by exposing placental membranes to phospholipase C and the subsequent effect on insulin binding and dissociation was examined. As previously described, when insulin-receptor binding was performed at 4 degrees C, phospholipase C treated membranes showed an increase in the apparent number of insulin receptors. However, when binding was performed at 24 degrees C, the predominant effect of prior phospholipase C treatment was to increase the affinity of binding. At this temperature, phospholipase C pretreatment also increased membrane fluidity. Cytochalasin B, an agent which disrupts receptor aggregates, lowered average affinity at 24 degrees C. Phospholipase C treatment slowed the dissociation rate in 'infinite dilution' at 24 degrees C but the accelerating effect of 100 ng/ml insulin (negative cooperativity) was greatly enhanced. These studies suggest that in addition to its effect in unmasking receptor sites, increased membrane fluidity induced by phospholipase C may cause higher affinity binding by allowing greater receptor or receptor subunit aggregation. Receptor or subunit aggregation within a fluid membrane structure may determine in part the affinity of insulin-receptor binding and the kinetic phenomenon known as negative cooperativity.

Cytochalasin B↗
PubMed1980

The effects of trypsin and phospholipase C on insulin binding and action in the isolated adipocyte.

The effect of alterations to the insulin receptor on the insulin sensitivity of isolated adipocytes was studied. Receptor changes were induced by treatment of adipocytes with either phospholipase C or trypsin. After enzyme treatment, binding of insulin to insulin receptors and insulin-mediated glucose metabolism were examined. Exposure of adipocytes to phospholipase C (2 units/ml) significantly increased insulin binding to the cells, but destroyed the ability of the cells to oxidize glucose. After treatment with trypsin (500 micrograms/ml) for 5 min, insulin binding to the adipocytes was significantly increased. This was shown to be due to an increase in insulin-receptor affinity. Metabolic studies showed that trypsin treatment led to an increase in basal glucose transport but markedly decreased the response to insulin at all concentrations tested. Adipocytes treated with trypsin showed no significant difference in basal glucose oxidation rates when compared with controls, but were less sensitive to insulin at low insulin concentrations, and showed a decreased maximum response at high insulin concentrations. In conclusion, these findings indicate a dissociation between induced changes in binding of insulin to insulin receptors and subsequent hormone action. The importance of post-receptor events in the biological action of insulin is highlighted.

Adipose Tissue↗
PubMed1980

One year's study of growth and total hydroxyproline excretion in scoliotic children.

21 children with scoliosis were studied for a year during which time 24-hour urinary total hydroxyproline levels are estimated and anthropometric measurements were made on 4 occasions. The total hydroxyproline levels (using hydroxyproline centiles) and the uncorrected heights of the children were all normal. The sitting heights of the children were below average, but, although the sample was small, the findings indicate that the children's 'uncoiled' height would be greater than average.

Adolescent↗