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Biomedical subjects

S E Pedersen

Publications and source records attributed to S E Pedersen.

42 records · Page 3Linked to original sources

Functional reconstitution of beta-adrenergic receptors and the stimulatory GTP-binding protein of adenylate cyclase.

A procedure for the functional reconstitution of beta-adrenergic receptors and the stimulatory guanine nucleotide-binding protein (G/F) of adenylate cyclase in phospholipid vesicles is described. beta-Adrenergic receptors were solubilized from turkey erythrocyte plasma membranes and reconstituted into phospholipid vesicles by the addition of dimyristoyl phosphatidylcholine and removal of detergent by gel filtration. This procedure restored the ability to bind [125I]iodohydroxybenzylpindolol and [3H]dihydroalprenolol. Purified rabbit hepatic G/F that was added to the receptor vesicles could be stably activated by guanosine 5'-[3-thio]triphosphate at a low rate, and this activation was increased up to 4-fold in the presence of beta-adrenergic agonists. This stimulation of the activation of G/F was specific for beta-adrenergic agonists and could be specifically blocked by beta-adrenergic antagonists. Stimulation was proportional to the concentration of vesicles containing active beta-adrenergic receptor. Under optimal conditions, 5 to 6 molecules of G/F were activated per receptor, indicating that catalytic activation of G/F by receptor was reconstituted.

Adenylyl Cyclases↗

Serum concentrations of theophylline in children treated with two daily doses of a sustained-release theophylline preparation.

Over a 3-month period 22 asthmatic children were treated with a sustained-release theophylline preparation (Nuelin Retard, Riker) in twice-daily doses. During the first 2 weeks of treatment slight side-effects were observed in 14 children. Over the remaining 10-week period only four children experienced minor-side-effects. Serum theophylline levels 4 hours after tablet administration were measured three times and serum levels just before tablet administration were measured once during the observation period. The average difference between the serum levels of theophylline just before tablet administration and the corresponding serum value 4 hours afterwards was 4.2 microgram/ml. The serum values 4 hours after tablet administration showed an insignificant fall throughout the period and patient compliance was assessed as good. When the average requirements of theophylline in mg/kg found by Wyatt et al. (15) (Table 2) were used as initial doses, few dosage adjustments were necessary and no serum values were greater than 26.2 microgram/ml, but in order to avoid serum levels above 20 microgram/ml initial doses should be decreased about 10% and final adjustment made with the aid of serum theophylline measurement under steady state conditions. In children, Nuelin Retard given in two daily doses is capable of maintaining a constant therapeutic serum concentration for the whole 24-hour period.

Adolescent↗

Effects of ergotamine on isolated human vessels.

In isolated human mesenteric and crural veins, ergotamine induced long-lasting contractions. These contractions were resistant to repeated wash-out and were not affected by alpha-adrenoceptor blockade, but could be abolished by removal of extracellular calcium or by the presence of the calcium-blocker nifedipine. In contrast to its effect on human mesenteric and crural veins, ergotamine had no contractile effect, but a marked relaxant effect on mesenteric arteries mediated via blockade of alpha-receptors. The ergotamine-induced contraction was not affected by indomethacin (0.28--2.8 microM) nor was it influenced by serotonin (5-HT). In both mesenteric and crural veins, the ergotamine-induced contraction was diminished by the 5-HT blocking agent, methysergide. In veins, development of tachyphylaxis to 5-HT was demonstrated. It is concluded that ergotamine has a direct contractile effect on isolated human mesenteric and crural veins. These effects are dependent on unhindered influx of extracellular calcium and are at least partly mediated via 5-HT receptors. In mesenteric arteries, ergotamine acted as an alpha-adrenoceptor blocker, and had no contractant effect.

Adult↗

Stability of DNA/ANTI-DNA complexes. IV. Complement fixation.

We describe an in vitro assay to study complement fixation of antibody/dsDNA immune complexes formed from SLE sera and radiolabeled dsDNA. The method measures the amount of radiolabeled dsDNA which is part of an immune complex bound to red blood cells via the C3b complement component receptor. The assay is dependent upon active complement, red blood cells, and anti-dsDNA antibodies, but it is independent of the red blood cell donor (type O) and the age of the red blood cells (up to 10 days). The method has been compared in some detail with the Farr assay with respect to the antibody/dsDNA ratio in the immune complexes and the relative stability of the complexes as measured by their resistance to dissociation by excess unlabeled dsDNA. Our results indicate that multiple binding of antibodies to dsDNA is required for complement fixation, and that a significant percentage of those antibodies which fix complement are of high avidity. Finally, a double label assay using both [3H]- and [14C]-dsDNA indicates that the complement fixing potential of the anti-dsDNA antibodies in an SLE serum is strongly influenced by the order of mixing of the isotopes with the serum. The DNA isotope which is added to the serum first is considerably more effective at fixing complement than the isotope which is added 1 h later. The implications of these results with respect to the pathogenesis of SLE are discussed.

Antigen-Antibody Complex↗

Dialysis encephalopathy in a non-dialysed uraemic boy treated with aluminium hydroxide orally.

Brain aluminium concentration has been found significantly higher in patients dying with dialysis encephalopathy than in uraemic patients without this syndrome, and it has previously been reported only in haemodialysed patients. We report a case of high brain aluminium concentration in a uraemic boy showing symptoms of severe encephalopathy. He was never dialysed but only treated with aluminium hydroxide orally. Baluarte reported corresponding symptoms in nondialysed uraemic children, but brain aluminium concentrations were not reported. His patients as well as our had very high levels of parathormone which may play a role in the resorption and distribution of aluminium. Aluminium preparations should be avoided in children with renal failure.

Administration, Oral↗