A metabolic switch produced by enzymically interconvertible forms of an enzyme

A system of enzymically interconvertible enzyme forms (interconversion cycle) is known to increase the sensitivity to regulators. Here it is shown that this system may also provide a discrete switching mechanism in which the response is maintained when the stimulus is removed. These switches may be important in producing discontinuous metabolic changes such as those associated with cell differentiation.     

Maximal oxygen uptake in Danish adolescents 16-19 years of age

A random sample of schoolchildren, 119 boys and 153 girls, was tested in the fall of 1983. The data presented here are anthropometric data (height, weight, fat % and vital capacity) and oxygen uptake directly measured on a bicycle ergometer. The mean height and weight for boys were 179.1 cm and 67.7 kg, and those for girls were 168.0 cm and 59.6 kg. The mean fat content was 9.1% for boys and 19.1% for girls, and their mean vital capacities were 4.91 and 3.61 respectively. The boys had a high maximal oxygen uptake (51.7 ml X kg-1 X min-1) showing no reduction over the age span studied. The girls' maximal oxygen uptake was lower (overall mean 40.0 ml X kg-1 X min-1) with a small reduction from 16 to 19 years of age. When comparing maximal oxygen uptake per kg lean body mass in the two sexes, the boys had 18.4% higher values than the girls, indicating that girls of this age have the lower fitness level. The results of maximal aerobic power measurement in the boys compare well with findings from other investigations using direct measurements, indicating that the fitness of teenage boys is kept at a high level. Comparable data from various countries for girls show different pictures, but it appears that in general they have a low fitness level.     

Absent aldosterone response to metoclopramide in patients with high spinal cord transection: evidence that metoclopramide stimulates aldosterone secretion through central pathways

This study evaluates dopaminergic regulation of aldosterone secretion in 6 patients with high spinal cord transections. Administration of the dopamine antagonist metoclopramide resulted in a marked rise in plasma aldosterone and 18-hydroxycorticosterone levels in 12 normal individuals, but no change in plasma levels of these zona glomerulosa corticosteroid products in spinal cord patients. Spinal cord transected patients also did not have the rise in plasma renin activity that was observed in normals following metoclopramide administration. Basal levels of aldosterone, 18 hydroxycorticosterone, corticosterone and renin activity as well as the aldosterone responses to graded dose infusion of adrenocorticotropin were similar in the spinal cord patients and the normals. These data suggest that dopaminergic regulation of adrenal zona glomerulosa corticosteroid and renal renin secretion is absent in patients with high spinal cord transections, suggesting that intact neural pathways from the central nervous system are necessary for metoclopramide stimulation of aldosterone and renin secretion in men. Since basal plasma aldosterone levels were normal in spinal cord transected patients, it appears that the absence of dopaminergic control does not result in elevated secretion.     

Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli

Auranofin, a new oral antirheumatic gold compound, in concentrations achieved therapeutically, inhibits neutrophil phagocytosis, chemotaxis, chemiluminescence, reduction of cytochrome c, and release of lysosomal enzymes. To further characterize the mechanism by which auranofin affects neutrophils, we studied the effects of auranofin on unstimulated properties and functions of neutrophils as well as on rapidly stimulated functions. When examined by electron microscopy, 4 micrograms/ml of auranofin significantly decreased the number of visualized centriole-associated microtubules in resting cells. Furthermore, auranofin inhibited neutrophil spreading on glass and caused a decrease in negative surface charge (electrophoretic mobility). In addition, auranofin inhibited several fmet-leu-phe-stimulated responses such as shape change, increases in centriole-associated microtubules, decreases in surface charge, and elicited membrane potential changes (di-O-C5(3) dye response). Auranofin (1 micrograms/ml) inhibited fmet-leu-phe-stimulated superoxide and hydrogen peroxide production by 80% (p less than 0.05), and also increased the affinity of receptors for fmet-leu-phe (from Ka 0.035 to Ka 0.48, p less than 0.001). Auranofin also affected neutrophil responses to phorbol myristic acetate (PMA). The total amount of PMA-stimulated superoxide production was suppressed by as little as 0.4 micrograms/ml of auranofin, but the lag time for activation was shortened by low concentrations of auranofin (0.5 to 1 microgram/ml). Four micrograms per milliliter of auranofin suppressed the decrease in surface charge induced by PMA. However, auranofin did not influence superoxide production elicited by the ionophore A23187. The results indicate that auranofin affects the earliest detected responses in neutrophil activation by certain receptor-mediated stimuli.     

Flying and walking of small insects (Musca domestica) recorded differentially with a standing-wave radar actograph

ABSTRACT. An actograph is described for recording the behaviour of small insects, by using a standing-wave radar system in an enclosed metal cabinet. Experiments show that the system produces an output frequency dependent only on the speed of movement of the subject. By filtering the signal electrically into components below and above 5 Hz, walking and flying of adult Musca domestica could be separately recorded. Each filter is followed by a level-comparator with hysteresis. Activity causing signal to cross the hysteresis-band is recorded as an event on a digital counter, and also integrated or summed to be displayed as a stepped-integral or bar-chart of total distance covered by the subject in each counting period. The energy-density of the radar can be kept very low, so that possible influence on the subject is minimal. The detector is remote from the box containing the subject, giving great flexibility in container design, so that the apparatus is ideally suited to the study of environmental factors.     

Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linolenate

Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from the skin were determined. The results indicate that re-establishment of a low trans-epidermal water loss was associated with incorporation of linolenate into the two epidermal sphingolipids. Supplementation with columbinate resulted in relatively high amounts of this fatty acid in the investigated epidermal sphingolipids. Analysis of pooled skin specimens from a previous study in which weanling rats were fed a fat-free diet and supplemented orally with pure alpha-linolenate for 13 weeks (Hansen, H.S. and Jensen, B. (1983) Lipids 18, 682-690) revealed very little polyunsaturated fatty acid in the two sphingolipids. These rats showed increased evaporation which was comparable to that of essential fatty acid-deficient rats. We interpret these results as strong evidence for a very specific and essential function of linoleic acid in maintaining the integrity of the epidermal water permeability barrier. This function of linoleate is independent of its role as precursor for arachidonate and icosanoids.