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Biomedical subjects

N Thomas

Publications and source records attributed to N Thomas.

At least 181 records · Page 10Linked to original sources
PubMed1981

Effects of somatostatin added to insulin in a glucose-controlled insulin infusion system.

Five insulin treated diabetics were studied on three consecutive days. Overnight variable intravenous insulin infusions were used before each study to maintain normoglycaemia and to calculate the optimal basal insulin infusion rate (1.1 +/- 0.1 U/h) which ws then kept constant throughout the study day. A standard 400 kCal breakfast with 25 g xylose was given at 0800 h. When the blood glucose rose above 4.1 mmol/l, an external artificial pancreas was used to infuse either extra insulin (day INS) or somatostatin for either 3h (day som) or the entire 8h experimental period (day SOM). Peak post-prandial blood glucose values were similar on all three days. The blood glucose rebounded after the cessation of the somatostatin infusion on day som. Post-prandial blood xylose peaks were lowered by somatostatin on both days but rebounded after the cessation of the somatostatin infusion on day som. The area under the plasma and urinary xylose curves was lowered by somatostatin only on day SOM. Growth hormone and glucagon levels were not statistically different on all 3 days. Thus somatostatin, when added to an optimal insulin infusion, minimised the insulin requirements by slowing intestinal absorption, but led to rebound hyperglycaemia if not feed-back controlled.

Adult↗
PubMed1981

Glucocorticoid-induced cell-size changes and nuclear fragility in rat thymocytes.

The events preceding glucocorticoid-induced lymphocytolysis have been studied in isolated rat thymocytes. Incubation of thymocytes at 37 degrees C in the presence of 1 microM dexamethasone resulted in the progressive appearance of pyknotic cells of modal diameter 4.5 mum, distinct from normal cells of diameter 5.2 mum. The rate of appearance of the pyknotic cells was determined by selective electronic cell counting, and was shown to be accompanied by increased nuclear fragility. The production of pyknotic cells was glucocorticoid-specific, dose-dependent, blocked by cycloheximide, and preceded the loss of cell viability as determined by dye exclusion. The pyknotic cells were separated from the non-pyknotic cells by density gradient centrifugation and shown to be solely responsible for the observed nuclear fragility.

Animals↗
PubMed1980

Semisynthesis and biological activity of porcine [LeuB24]insulin and [LeuB25]insulin.

Two analogs of porcine insulin with substitutions of leucine for phenylalanine in the COOH-terminal region of the insulin B chain have been prepared by a combination of solid-phase synthesis and semisynthesis. Solid-phase synthesis of the substituted octapeptides B23-B30 bearing the trifluoracetyl group on lysine-B29, enzymatic coupling of the octapeptides to bis(tertiary-butyloxycarbonyl)desoctapeptide insulin by trypsin, and deprotection of the corresponding adducts in formic acid and piperidine resulted in two insulin derivatives, one with leucine at position B24 and the other with leucine at position B25. These analogs had only about 10% and 1%, respectively, of the activity of porcine insulin in competing for the binding of [125I]iodoinsulin to both rat adipocytes and human IM-9 lymphocytes. The relative potencies of the analogs in stimulating glucose oxidation by rat adipocytes decreased in the order porcine insulin > [LeuB24]insulin > [LeuB25]insulin. However, at high concentrations both analogs had full agonists activity. Experiments in which the semisynthetic insulins were mixed with the native hormone showed that [LeuB24]insulin, but not [LeuB25]insulin, was an active antagonist of insulin action. These results suggest that the antagonistic activity of a human insulin variant having leucine at position B24 or B25 can be assigned to the molecule with the sequence Gly-Leu-Phe-Tyr (residues B23-B26) in its active site.

Adipose Tissue↗
PubMed1979

Action of gonadotropin-releasing hormone and its superactive analogues on the anterior pituitary: the mechanism of release and synthesis of gonadotropins.

The role of prostaglandins (PG), their active intermediates or the adenylcyclase-cyclic AMP system for gonadotropin release and/or synthesis was evaluated by administering gonadotropin-releasing hormone (Gn-RH) and its superactive analog to normal and aspirin-treated rats. Serum LH levels, anterior pituitary malondialdehyde (MDA) content and cyclic AMP (cAMP) levels were followed. The pituitaries stimulated with Gn-RH or its superactive analog yielded more MDA and cAMP than the controls. Stimulation of the pituitary with the releasing hormones, after aspirin treatment, yielded 40--70% less MDA and lower LH values than the nontreated animals. The cAMP levels were not significantly lowered by the aspirin treatment. These studies suggest that the activation of the PG biosynthesis and the adenyl-cyclase-cyclic AMP system are not sequential but 2 separate physiological events. The active PG intermediates may only be responsible for the release of LH. It is not clear whether the activation of cAMP initiates also the processes preparatory to the synthesis of LH in the endoplasmic reticulum. In vivo studies in rats showed that the analogs (I and II) were 30 times more potent and had a more prolonged action on the pituitary (3 h) than Gn-RH. Ultrastructural studies on the anterior pituitary after hypophyseal stalk portal vessel infusion of Gn-RH and the analog (I and II) provided ample morphological evidence for both Gn-RH and analog induced gonadotropin-release and synthesis. The prolonged action of the superactive analog (I and II) on the gonadotrophs was also indicated by ultrastructural studies.

Animals↗
PubMed1978

Identification of placental alkaline phosphatase in human sera using polyacrylamide gel electrophoresis.

Polyacrylamide gradient gel electrophoresis may be used to separate placental alkaline phosphatase from other types of serum alkaline phosphatase. This method, of which specificity is demonstrated by the thermostability and immunological reaction of the placental form, is sensitive enough to detect an activity of 0.02 mU in a sample, and seems suitable for use in investigating placental isoenzyme in serum.

Adult↗
PubMed1976

The primary enzyme defect in hereditary coproporphyria.

The activity of coproporphyrinogen oxidase (E.C. 1.3.3.3) in cultured skin fibroblasts from three patients with hereditary coproporphyria (H.C.) was approximately half that in fibroblasts from normal subjects and patients with other types of porphyria. It is suggested that this is the primary defect in H.C., which is inherited as an autosomal dominant, and that the same abnormality is present in the liver. Consideration of the probable relative activities of the enzymes of haem biosynthesis in the liver in H.C. suggests that the acute attacks of porphyria which are its major clinical manifestation occur when the activity of uroporphyrinogen-I-synthase (E.C. 4.3.1.8) becomes rate-limiting for haem synthesis.

Adult↗
PubMed1975

Potassium supplements in patients treated with corticosteroids.

1. Preliminary studies are reported on 8 patients with lung disease given prednisone both with and without potassium supplements. 2. There were no abnormalities of plasma potassium but there was a relationship between the dose of prednisone and the urinary excretion of potassium whilst off supplements: higher doses were associated with increased potassium excretion. 3. Patients who had been on treatment for a short period retained more of their supplements than did those who had been on treatment for several years. 4. It is suggested that with prolonged treatment control of potassium homeostasis may be altered, and that more detailed metabolic studies should be carried out.

Adult↗
PubMed1975

The erythroid cells of anaemic Xenopus laevis. I. Studies on cellular morphology and protein and nucleic acid synthesis during differentiation.

Phenylhydrazine has been used to induce anaemia in Xenopus laevis. The dosage used causes the complete destruction of all mature erythrocytes within twelve days. The anaemia results in the initiation of a wave of erythropoiesis and large numbers of immature erythroid cells are released into the circulation. The morphological and biosynthetic changes which these cells undergo as they differentiate in circulation are described. The origin of the circulating erythroid cells is also discussed.

Anemia↗
PubMed1975

The erythroid cells of anaemic Xenopus laevis. II. Studies on nuclear non-histone proteins.

The mass ratio of nuclear non-histone protein: DNA in the immature circulating erythroid cells of phenylhydrazine-induced anaemic Xenopus is approximately threefold higher than in mature erythrocytes. This is largely due to the presence of increased amounts of low and intermediate molecular weight proteins in the nuclei of the immature cells. There are a few qualitative differences in the components of this class of proteins between the mature and immature cells, the most notable of which is the presence of a protein of molecular weight approximately 115000 in the former which is not detectable in the latter. These changes are discussed in relation to the changing synthetic capacities of cells and to certain generalizations about the function of the nuclear non-histone protein based on studies of other differentiating systems.

Anemia↗