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Biomedical subjects

H C Walker

Publications and source records attributed to H C Walker.

At least 19 recordsLinked to original sources
PubMed1993

Similar effects of NPY on energy metabolism and on plasma insulin in adrenalectomized ob/ob and lean mice.

A single intracerebroventricular (icv) injection of dexamethasone (250 ng) lowers brown adipose tissue (BAT) thermogenesis and whole body metabolic rates and raises plasma insulin concentrations within 30 min in adrenalectomized ob/ob mice with minimal effects in adrenalectomized lean mice. The present study was conducted to determine if intracerebroventricular neuropeptide Y (NPY), a neuropeptide regulated in part by glucocorticoids, would mimic effects of dexamethasone in these mice. NPY lowered BAT metabolism and whole body oxygen consumption and raised plasma insulin concentrations within 30 min in adrenalectomized ob/ob mice similarly to dexamethasone; but, unlike dexamethasone, NPY was as effective in modulating these metabolic responses in adrenalectomized lean mice as in ob/ob mice. Further, intracerebroventricular NPY increased food intake equally in both ob/ob and lean mice, whereas dexamethasone did not alter food intake during the 30 min postinjection period. These data are consistent with the hypothesis that NPY mediates some of the effects of intracerebroventricular dexamethasone action in ob/ob mice and that the divergence between ob/ob and lean mice lies in glucocorticoid control of NPY release/synthesis rather than in NPY action mechanisms.

Adipose Tissue, Brown↗
PubMed1992

Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice.

Adrenalectomy stimulates depressed brown adipose tissue (BAT) metabolism and decreases hyperinsulinemia in ob/ob mice, with minimal effects in lean mice. A single intracerebroventricular injection of dexamethasone (250 ng) into adrenalectomized ob/ob mice completely reversed the effects of adrenalectomy on BAT thermogenesis as assessed by mitochondrial GDP binding, approximately doubled plasma insulin, lowered whole body metabolic rates by 17%, and increased food intake by 19%. These responses were rapid in onset, with changes in BAT metabolism and plasma insulin occurring within 30 min of dexamethasone injection. Adrenalectomized lean mice were much less responsive to dexamethasone than their ob/ob counterparts. The dexamethasone-induced decrease in BAT thermogenesis in adrenalectomized ob/ob mice was associated with an organ-specific decrease in BAT sympathetic nerve activity as assessed by norepinephrine turnover, whereas the dexamethasone-induced increase in plasma insulin was blocked by atropine, suggesting involvement of the parasympathetic nervous system. Intracerebroventricular injection of corticotropin-releasing hormone did not affect BAT thermogenesis in dexamethasone-injected adrenalectomized ob/ob mice but markedly lowered plasma insulin concentrations, possibly by suppression of the parasympathetic nervous system. In conclusion, dexamethasone alters regulation of the autonomic nervous system in ob/ob mice.

Adipose Tissue, Brown↗
PubMed1988

Effects of cimaterol, a beta-adrenergic agonist, on energy metabolism in ob/ob mice.

Cimaterol when added to the diets for 3 or 9 wk stimulated whole animal energy expenditure and brown adipose tissue thermogenic activity comparably in genetically obese (ob/ob) and lean mice; however, ob/ob mice fed diets containing 140 or 280 micrograms cimaterol/kcal failed to increase energy intake as much as lean mice. Consequently, the efficiency of energy retention was actually lower in ob/ob mice fed diets containing cimaterol than in similarly treated lean mice. Cimaterol stimulated skeletal muscle gain in ob/ob mice, although at no point did final hindlimb muscle weight of ob/ob mice equal that of lean mice. Hyperinsulinemia was abolished in ob/ob mice fed diets containing cimaterol even though plasma corticosterone concentrations remained elevated. We conclude that cimaterol has greater effects on energy balance and plasma insulin, but not on skeletal muscle accretion, in ob/ob mice than in lean mice.

Adipose Tissue, Brown↗
PubMed1987

The importance of NPSH on the radiosensitizing effect of oxygen in Chinese hamster V-79 cells.

The radiosensitivity of Chinese hamster V-79-171B fibroblasts increased more rapidly with increasing partial pressure of oxygen when the cell cultures had low endogenous levels of non-protein sulphydryl (NPSH), about 5 mumol per cell compared with about 15 mumol per cell. There was a good correlation between initial NPSH content and sensitization by oxygen concentrations between 0.06 and 0.7 per cent.

Animals↗
PubMed1986

Radiation injury in mouse lung: dependence on oxygen levels in the inspired gas.

The relationship between radiosensitivity and the partial pressure of oxygen (PO2) in the inspired gas has been established for radiation pneumonitis as a measure of lung damage following irradiation of the mouse thorax. The radiosensitivity at low PO2 (0-1 per cent) fitted the linear transformation of the Alper, Howard-Flanders relationship giving a K value for lung tissue of 1.35 per cent oxygen with an oxygen enhancement ratio, m, of 2.13. The radiosensitivity at higher PO2 (5-21 per cent) did not fit the Alper, Howard-Flanders relationship probably because the PO2 of the inspired gas was greater than the PO2 in the alveolus. At the low PO2 levels in the inspired gas, back diffusion of oxygen from blood into the alveolus may lead to errors in the estimated value of K. If the low value of m is due to this 'contaminating' oxygen from blood then by taking a higher value for m, the amount of contaminating oxygen can be calculated (0.23 per cent) and a 'true' value for K(1.1 per cent) determined. Other uncertainties in this estimate of K due to the radiolytic consumption of oxygen and possible inadequacies in equilibration are discussed. Allowing for the uncertainties, it is concluded that the K value for lung damage lies towards the upper end of the range of K values measured for cells in vitro.

Animals↗
PubMed1985

The effect of several different anaesthetics on the blood pressure and heart rate of the mouse and on the radiation response of the mouse sarcoma RIF-1.

Several anaesthetics were tested with mice to study: (a) their ability to immobilize the animal; (b) their effect on blood pressure and heart rate; and (c) their effect on the response to X-irradiation of the mouse sarcoma RIF-1. All anaesthetics which produced adequate immobilization also caused a fall in blood pressure and some radioprotection of tumour cells. Physical restraint of the tumour-bearing leg of an unanaesthetized mouse also caused radioprotection of the tumour cells.

Anesthetics↗
PubMed1984

Constants of the Alper and Howard-Flanders oxygen equation for damage to bacterial membrane, deduced from observations on the radiation-induced penicillin-sensitive lesion.

Energy deposited in the bacterial envelope of E. coli B/r induces lesions which are lethally attacked by penicillin in concentration insufficient to affect unirradiated bacteria. The critical lesions are probably in the membrane moiety. Bacteria were irradiated in the presence of 100 per cent oxygen, oxygen-free nitrogen and mixtures of 1.01, 0.59, 0.3, 0.1 and 0.06 per cent oxygen in nitrogen. Changes in sensitivity with pO2 conformed with the Alper and Howard-Flanders equation, for bacteria treated after irradiation by penicillin as well as for the untreated ones. The values of m were respectively 4.8 and 3.3; the values of K were identical, within experimental error, i.e. 4.4 mmHg. Sensitivity to induction of the penicillin-sensitive lesion was calculated from the difference in the reciprocals of D0 values proper to untreated and treated bacteria, for every gas used. The value of m could not be directly calculated because the effect of penicillin on anoxically irradiated bacteria was not detectable. For that reason, a transformation of the oxygen equation was used which allowed estimates to be made of both m and K, provided the results conformed with the equation. Within experimental error they did so conform. The calculated values of m and K for induction of the penicillin-sensitive lesion were respectively 8 and 5.9 mmHg, but it is shown that the oxygen enhancement ratio was probably underestimated and the K value overestimated. On the assumptions that these values of m and K are specific for radiation damage to bacterial membrane, and that radiation-induced killing is attributable to lethal lesions in the membrane as well as the DNA, the results demonstrate that any interaction of oxygen with sites of energy deposition in the DNA must play a very much smaller role in radiosensitization than does interaction with sites of energy deposition in the membrane.

Cell Membrane↗
PubMed1980

Cell survival at low oxygen tension and dose build-up in argon.

Mammalian cells were exposed to 250 kVp X-irradiation in air, argon and nitrogen to determine whether cells irradiated when severely hypoxic have survival curves with lower extrapolation numbers (n) than their aerobic counterparts. Cells irradiated suspended in liquid showed no significant differences between values of 'n' irrespective of the gas used, neither was the sensitivity of cells irradiated in argon any greater than that of cells irradiated in nitrogen. In contrast, cells attached to glass dishes irradiated with the medium withdrawn were apparently much more sensitive in argon than in nitrogen. It has been demonstrated that the lower survival of cells irradiated in argon could have been caused by the greater photoelectric absorption in argon compared with nitrogen. When the dosimetric discrepancy was removed either by absorption of photoelectrons in liquid or by use of high energy radiations, there was no evidence that severe hypoxia during irradiation could lead to reduced values of 'n'.

Animals↗
PubMed1980

Correlation between the radiobiological oxygen constant, K, and the non-protein sulphydryl content of mammalian cells.

The value of the radiobiological oxygen constant K has been found to depend on the concentration of non-protein sulphydryl (NPSH) within the cell. Cells in the exponential phase of growth have a higher concentration of NPSH and a higher value of K than cells in plateau phase. Binding NPSH with N-ethylmaleimide reduced the value of K and conversely, addition of NPSH as dithioerythritol increased the value of K. K also rises with the same time course as NPSH increases, when plateau phase cells are replated into fresh medium. These results support the hypothesis that free-SH groups within the cell compete with oxygen to react with radiation damaged molecules.

Animals↗