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Biomedical subjects

H Swan

Publications and source records attributed to H Swan.

At least 55 records · Page 3Linked to original sources

Positive control of the herpes simplex virus thymidine kinase gene requires upstream DNA sequences.

We examined the ability of deleted versions of the herpes simplex virus type 1 thymidine kinase gene, present in biochemically transformed mouse cells, to be induced in trans to a higher level of expression by superinfecting herpes simplex virus immediate early gene products. The results demonstrate that sequences mapping between -200 and -80 and between -70 and -12 are required for induction. As these regions are largely coincident with the previously identified thymidine kinase gene promoter, the results suggest that herpes simplex virus immediate early gene products or their metabolic product activate thymidine kinase expression by acting at the promoter region to increase the rate of transcription.

Base Sequence↗

Extracts from the brains of hibernating and alert ground squirrels: effects on cells in culture.

Aqueous extracts were prepared from pulverized, acetone-dehydrated brains of hibernating and alert ground squirrels. Addition of these extracts to Chinese hamster ovary cells in suspension culture resulted in a decrease in the amount of [3H]thymidine incorporated into acid-precipitable material without affecting the transport or phosphorylation of the nucleoside. The inhibition was time- and dose-dependent and full recovery occurred about 2 hr after exposure of the cells to the active extract. The active factor is readily oxidized during storage at -70 degrees C but full activity can be restored by treatment with 2-mercaptoethanol. The peptide nature of the active material is indicated by its susceptibility to proteases and by loss of activity after alkylation. Fasted or cold-acclimated rats also develop increased levels of active substance in their brains; however, brains of hibernating squirrels contain 10- to 50-fold more of the active substance than brains from either alert squirrels or rats. A time-dependent increase in activity of extracts from hibernating brain incubated with a homogenate from alert brain suggests that the peptide is activated or generated in the mixture.

Animals↗

The hydroxyl-hydrogen ion concentration ratio during hypothermia.

Fundamental physicochemical characteristics of the acid-base related constituents of extracellular and intracellular fluid spaces of vertebrates in relation to changes in temperature have been reviewed. Emphasis has been placed upon the dissociation constant of water, the solubility constant of CO2, the dissociation constant of histidine imidazole, the hydroxyl-hydrogen ion ratio, the protein charge state and the alpha-imidazole regulation concept. Because pN and pKIm change in parallel when temperature varies, the OH/H ratio and the alpha-imidazole value for any sample of blood or plasma held anaerobically in vitro are invariant with changing temperature, since a constant CO2 content is maintained. Thus, when blood or plasma cools, pH increases and PCO2 decreases, but relative alkalinity and the protein charge state remain constant. These responses are solely the consequence of physical constants, that is, equilibrium constants and gas solubility, changing with temperature. In vivo, the set of PCO2 is established in each poikilothermic species by its normal ventilatory pattern designed to maintain constant CO2 content. Regulation in vivo in poikilotherms consists of adjustments of ventilation per unit metabolism (VA/VCO2) appropriate to every temperature. When the ventilatory and renal mechanisms of human beings are suppressed by anesthesia and hypothermia, their extracellular and intracellular responses mimic those of poikilotherms. Clinical management of hypothermia in humans requires ventilatory control using oxygen-augmented room air without added CO2 monitored by pH measurements of arterial blood warmed anaerobically to 37 degrees C. Finally, the need for new techniques to measure intracellular pH as temperature is lowered and some areas for further investigation are suggested.

Acid-Base Equilibrium↗

Congenital aortic stenosis: ten to 22 years after valvulotomy.

Between 1956 and 1967, 34 patients, aged 2 months to 40 years, underwent aortic valvulotomy under hypothermia for congenital aortic stenosis. There were two early and five late deaths. Twenty-seven patients were followed up for a mean of 15 years. Thirteen patients had no subsequent operation: 11 are asymptomatic, seven with mild aortic insufficiency. Ten patients have had aortic valve replacement (AVR), one revalvulotomy, three will require AVR. Three late deaths were sudden. The literature has been reviewed for data on mortality, endocarditis, aortic insufficiency, and reoperation. Operation improves longevity, but does not restore it to normal. Aortic valve replacement in children carries a poor prognosis, possibly reflecting severity of disease. The chances of reoperation after ten years are 20% to 40%. Valvulotomy must, therefore, be regarded as the first in a possibly lifelong series of operations.

Adult↗