Structure analysis and molecular model of the selenoenzyme glutathione peroxidase at 2.8 A resolution.
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Biomedical subjects
Publications and source records attributed to A Jones.
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Completed questionnaires were received from 208 patients on whom 245 operations for ingrowing toenails had been performed at King's College Hospital. Avulsion of a strip of nail had an 83 per cent recurrence rate, total nail avulsion 70 per cent, Zadik operations 28 per cent and wedge resections 29 per cent. It is recommended that immediate avulsion of ingrown toenails should not be a routine practice.
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The control of secretion of prolactin was studied using continuous perfusion of a column of isolated rat pituitary cells supported by Bio-Gel polyacrylamide beads. Prolactin secretion was inhibited repeatedly by dopamine and rapidly recovered in its absence. Maximum inhibition was achieved at 5 x 10(-7) M dopamine. Bromocriptine and lergotrile directly inhibited prolactin release from the pituitary cells. Bromocriptine had a longterm action in inhibiting secretion. The dopamine receptor blocking agent, metoclopramide, overcame the inhibitory effect of dopamine but had no effect on prolactin secretion in its absence.
The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.
The effects of the histamine (H2) receptor antagonist cimetidine on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol were studied in five normal males. Cimetidine, when given by infusion at the dose of 100 mg/h for 5 h, did not alter adenohypophyseal secretion either basally or after pituitary stimulation with LHRH and TRH. However, 400 mg cimetidine given intravenously as a bolus injection significantly stimulated PRL release in all subjects, without affecting any other measured hormone. A dose-reponse relationship existed, and 200 mg cimetidine seems to be the minimum PRL-releasing dose when given as an intravenous bolus injection. These results suggest that cimetidine releases PRL and that this effect is dose-related, but only when large intravenous injections are given.
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An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.
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Diplozoon homoion gracile from the southern barbel (Barbus meridionalis) displays an egg-laying and an egg hatching rhythm, the latter being more clearly defined. Egg laying continues both day and night but significantly more eggs are laid at night. The oncomiracidia hatch at dusk. If parasite eggs are eaten by the host they pass through the gut undamaged and hatch normally.
Half-hourly blood samples were taken from six clinically euthyroid men over a continuous period of 24 h. Their concentrations of total thyroxine (T4), total triiodothyronine (T3), thyrotrophin (TSH) and prolactin (PRL) were assessed together with the degree of unsaturation of thyroid hormone binding proteins as determined by the thyroid hormone uptake test (THUT). Both T3 and T4 were also measured in urine samples collected serially during the same 24 h period. Significant circadian changes in serum TSH, THUT, serum and urine T4 and serum PRL were demonstrated in all subjects. TSH showed a reciprocal pattern to serum T4, with higher levels during the evening and at night than the daytime. This TSH pattern did not coincide with PRL secretion. Further studies on the same subjects did not show any significant effect of posture, corticosteroid or T4 administration upon circadian changes in TSH. There appeared to be no consistent circadian changes in serum or urinary T3. It seems likely that the TSH circadian rhythm is centrally determined and that free T3 levels are maintained more or less constant by variation in peripheral conversion from T4.
In the presence of alpha-ketoglutarate, cell-free extracts of Streptomyces species 3022a catalysed transfer of the amino group from p-aminophenylalanine, yielding an unstable product similar to that obtained by the action of D- and L-amino acid oxidases on the amino acid. The enzyme, purified 16-fold from cell homogenates by chromatography on ion-exchange celluloses, hydroxyapatite, and cross-linked dextran gel, has a molecular weight of 90 000 and a broad pH optimum at 8.0. It is active with L-phenylalanine and L-tyrosine as well as p-amino-DL-phenylalanine as amino donors, and its relative activity towards these substrates did not change during purification. Polyacrylamide disc-gel electrophoresis of the partially purified enzyme gave single zones with identical mobility when the gels were assayed for activity with p-aminophenylalanine and tyrosine as amino donors. The results indicate that synthesis of p-aminophenylalanine en route to chloramphenicol uses a multispecific aminotransferase for aromatic amino acids. With L-phenylalanine as substrate, the preferred amino-accepting co-substrate was alpha-ketoglutarate. Some kinetic constants for the enzyme were determined, and its requirement for pyridoxal phosphate was demonstrated.
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The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.
To investigate the possibility that Hodgkin's disease (H.D.) may be transmitted from person to person, a case-control study was conducted among 87 of the 97 H.D. patients diagnosed under the age of 40 years in the period 1962-71, resident at the time of diagnosis in a defined area around Oxford. For each of the 87 H.D. patients a matched control patient was selected with a diagnosis other than that of a chronic or malignant disease. H.D. patients and controls were interviewed to determine their places of schooling and work and attempts were made to link pairs of patients who had attended the same school or work place at the same time. The findings do not support the hypothesis that H.D. patients may pass on the disease to others. Among the H.D. patients, links between 40 pairs were established, compared with 40-75 links expected, based upon the experience of all 174 persons studied. The only finding which was statistically significant (p approximately 0-04) arose when H.D. patients were considered to be "susceptible" from 10 to 5 years before diagnosis and "infective" from diagnosis to 2 years after diagnosis: 7 pairs of links were found against 2-75 expected. However, since 7 postulated periods of susceptibility and 9 postulated periods of infectivity were examined, this one "statistically significant" finding might easily have arisen by chance.