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Biomedical subjects

J M Potter

Publications and source records attributed to J M Potter.

At least 73 records · Page 4Linked to original sources
PubMed1984

The inhibition of glucose-stimulated insulin secretion by primary amines. A role for transglutaminase in the secretory mechanism.

Rat pancreatic islets contain a Ca2+-activated and thiol-dependent transglutaminase (EC 2.3.2.13) comparable in activity with that found in rat liver, lung and spleen. The Ca2+-dependence of this enzyme is such that half-maximal velocity was obtained in the region of 40 microM. Preincubation of rat islets with primary-amine substrates of transglutaminase (monodansylcadaverine, methylamine, ethylamine, propylamine and cystamine) led to an inhibition of glucose-stimulated insulin release by these amines. Kinetic analysis of the competitive substrates methylamine, monodansylcadaverine, propylamine and ethylamine for their ability to inhibit islet transglutaminase activity indicated a potency that matched their ability to inhibit glucose-stimulated insulin release. When these amines were tested for their effects on glucose-stimulated protein synthesis and glucose utilization, the most potent inhibitor of insulin release, monodansylcadaverine, had no effect on either process at 100 microM. The amines cystamine, ethylamine, methylamine and propylamine had variable effects on these metabolic processes. For ethylamine, methylamine and propylamine, concentrations were found which inhibited glucose-stimulated insulin release in a manner which was found to be independent of their effects on either glucose oxidation or protein synthesis. Primary amines may therefore inhibit insulin release through their incorporation by islet transglutaminase into normal cross-linking sites. A role for protein cross-linking in the secretory mechanism is suggested.

Acyltransferases↗
PubMed1984

A role for polyamines in stimulus-secretion coupling in the pancreatic beta-cell.

Measurement of the content of polyamines in pancreatic islets indicated that no significant change in their concentration took place during glucose-stimulated insulin release. The finding, together with the absence of any effect of alpha-difluoromethylornithine on glucose-stimulated insulin release suggested that rapid synthesis of polyamines is not involved in stimulus-secretion coupling in the beta-cell. The concentration of polyamines found in islets were high enough for them to act as substrates for the Ca2+-dependent islet transglutaminase during insulin release. This was further demonstrated by the ability of islet transglutaminase to incorporate [14C]putrescine into proteins from islet homogenates and by the demonstration of an increase in the covalent incorporation of [14C]putrescine into the proteins of intact islets following their challenge with glucose. Unlike monoamine substrates of transglutaminase, putrescine failed to effectively inhibit insulin release when its intracellular concentration was increased. A role for polyamines in the secretory process through their incorporation into islet proteins is suggested.

Acyltransferases↗
PubMed1984

Polymerization of human transcortin in plasma.

Using radial immunodiffusion and antiserum raised against purified transcortin, polymers of native transcortin have been identified in plasma. They are characterized by multiple precipitin bands, the size of which diminishes on dilution, consistent with reversibility of this form of polymer. Spectrophotometric scans have been used to study the time course of polymerization in purified transcortin, in which dilution reversibility can be demonstrated also, and in which disaggregation may be produced by addition of sodium dodecyl sulphate and dithiothreitol, but apparently not by cortisol.

Humans↗
PubMed1984

Purification of an anticoagulant from the body fluid of Ascaris suum.

An anticoagulant has been purified from the body fluid of Ascaris suum by sequential passage through Sephadex G-50, CM-cellulose and Sephadex G-25 columns then treated with 2 M NaCl, passaged through a Sephadex G-25 column, separated from the phosphate buffer by precipitation of the latter with the CaCl2, then passaged through a Sephadex G-10 column in water. In the body fluid of the worm, the anticoagulant is ionically-bound to a carrier substance. The complex can be split by treatment with 2 M NaCl. The molecular weight of the anticoagulant is slightly less than 1400.

Animals↗
PubMed1984

Potassium supplements and total body potassium in elderly patients.

Total body potassium (TBK) and serum potassium measurements have been obtained in nine elderly patients in controlled heart failure on differing diuretic regimens. The patients were randomly maintained on a potassium-sparing diuretic, on frusemide, and on frusemide with potassium supplements (48 mmol/day) for a minimum of one month. TBK levels increased by a mean of 128 mmol on frusemide with potassium supplements compared with no supplements (P less than 0.001), a 7% increase in TBK. Serum potassium levels increased, similarly, from 4.1 mmol/l to 4.8 mmol/l (P less than 0.01). The potassium-sparing diuretic had the same effect as frusemide with supplements in increasing TBK in six patients. However, in three cases there was no increase in TBK compared with frusemide alone. The results demonstrate that potassium supplements are effective in raising TBK levels and serum potassium levels in elderly patients with heart failure.

Aged↗
PubMed1983

Adrenal suppression following extradural steroids.

Adrenocortical function was tested in 12 patients following a single lumbar extradural injection of methylprednisolone acetate ('Depo-Medrol') 80 mg as treatment for chronic sciatica. There was no absorption of the corticosteroid into the systemic circulation, but marked suppression of plasma cortisol levels was documented for up to 3 weeks following the injection and the capacity of the adrenal cortex to secrete cortisol in response to synthetic adrenocorticotrophin (ACTH) was diminished. These results suggest that the dose and frequency of extradural steroid administration should be kept to a minimum to prevent suppression of the hypothalamic/pituitary/adrenocortical axis and that patients thus treated should be considered candidates for steroid cover during surgery and other stressful procedures.

Adrenal Cortex↗
PubMed1983

Type I hyperlipoproteinemia presenting as sudden death in infancy.

A routine post-mortem investigating sudden death in an eight week old male infant revealed gross Type I hyperlipoproteinemia (triglyceride concentration 825 mmol/L). Death was attributed to generalized cerebral anoxia. Study of the family revealed the parents were first cousins both of whom had depressed postheparin lipolytic activity, as did five out of seven of the remainder of the family members tested. This family is a notable example of deficiency of extrahepatic lipoprotein lipase.

Brain Ischemia↗
PubMed1982

Diurnal variations in blood intermediary metabolites in mild gestational diabetic patients and the effect of a carbohydrate-restricted diet.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven non-diabetic women (group A) and in two groups of mild gestational diabetics, at diagnosis (group B, seven patients) and after treatment with a 150-g carbohydrate diet (group C, seven patients). Mean 24-h blood metabolite levels (+/- SD) in groups A, B and C were: glucose: 4.65 +/- 0.82, 5.35 +/- 3.06 and 5.40 +/- 1.7 mmol/l; alanine: 1.05 +/- 0.18, 1.14 +/- 0.42 and 0.78 +/- 0.22 mmol/l; alanine: 0.31 +/- 0.03, 0.31 +/- 0.10 and 0.27 +/-0.07 mmol/l; ketone bodies: 0.11 +/- 0.04, 0.19 +/- 0.05 and 0.26 +/- 0.15 mmol/l. Glucose levels were not significantly different between the groups. Ketone body levels were elevated in the diabetics prior to treatment (p less than 0.01) and rose higher on diet. Lactate levels were reduced on the diet (0.05 less than p less than 0.10). Abnormalities in the concentrations of total blood ketone body levels in gestational diabetics may be detrimental to fetal development and therapy should be designed to minimise changes in intermediary metabolites.

Alanine↗
PubMed1982

Serum uric acid as a marker of pregnancy-induced hypertension.

A prospective longitudinal study was conducted, looking at the changes in serum uric acid during pregnancy in women who were normotensive at initial presentation. In our sample of 78 women having a total of 88 singleton pregnancies, 13 developed pregnancy-induced hypertension during labour only, whilst a further 6 developed hypertension during pregnancy. Women who developed hypertension had significantly higher uric acid levels than women who remained normotensive throughout. However, there was an appreciable overlap between the groups. Women with essential hypertension showed similar changes. We conclude that the serum uric acid level is an unreliable indicator of developing hypertension in the individual woman. However, a rapidly rising uric acid level should be viewed with caution.

Adult↗
PubMed1982

Anomalous action of tubocurarine in the tibialis anterior muscle of the cat.

Low dose infusion of tubocurarine (20 micrograms/kg per min) causes an increase in muscle contraction in tibialis anterior of the cat. Tibialis anterior muscle of 13 adult cats was indirectly stimulated via the sciatic nerve using a square wave pulse of 0.2 ms duration and supramaximal voltage at 0.06 Hz. The increase is from 5-133% of control with a mean of 36%. This is sustained for a mean of 97 min, if the infusion is ceased when maximum potentiation is achieved. Duration of potentiation is decreased by increasing the frequency of stimulation. The potentiation occurs in the presence of either rising or falling concentrations of tubocurarine, and continuing the infusion results in neuromuscular blockade. One explanation of these observations is that low dose tubocurarine may interfere with presynaptic negative feedback control of acetylcholine release.

Animals↗
PubMed1981

Purification and characterization of human transcortin.

Human transcortin was purified to apparent homogeneity from plasma by a two-step procedure involving affinity and hydroxyapatite chromatography. The affinity gel incorporated denatured bovine serum albumin as the spacer and cortisol hemisuccinate as the ligand. Although isolated transcortin showed a propensity for spontaneous polymerization according to a geometric progression (1, 3, 9) only one band was observed on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Cortisol-binding activity of the isolated protein gave an apparent association constant of 2.5 X 10(8) M-1 at 4 degree C in equilibrium dialysis. Isoelectric focusing of purified native transcortin showed six discrete bands, five between pH 3.75 and 4.15 and another, possibly desialylated, at pH 6.15. Desialylated transcortin also gave six bands on isoelectric focusing, with pI values ranging from 4.90 to 6.30.

Biopolymers↗
PubMed1981

The effect of continuous subcutaneous insulin infusion and conventional insulin regimes on 24-hour variations of blood glucose and intermediary metabolites in the third trimester of diabetic pregnancy.

Twenty-four hour metabolic profiles were performed in the third trimester of pregnancy in seven diabetic women; first when optimally controlled using conventional insulin regimes and subsequently when controlled with continuous subcutaneous insulin infusion. Seven non-diabetic women also studied. Mean +/- SD 24 h metabolite levels in the diabetics before and during continuous subcutaneous insulin infusion and in the controls were respectively: glucose-5.8 +/- 1.2;5.0 +/- 0.9;4.7 +/- 0.8 mmol/l; total ketone bodies -0.2 +/- 0.06; 0.15 +/- 0.05; 0.11 +/- 0.04 mmol/l; lactate - 0.90 +/- 0.33;0.90 +/- 0.24; 1.05 +/- 0.18 mmol/L; alanine - 0.29 +/- 0.06; 0.30 +/- 0.06; 0.31 +/- 0.03 mmol/l. Total ketone body levels were significantly elevated (p less than 0.05) on conventional therapy but not on continuous subcutaneous insulin infusion compared with controls. Variations in metabolites over 24 h, as measured by mean standard deviations, were increased for glucose (p less than 0.001) and for total ketone bodies (p less than 0.05) on the conventional regimes we employed compared with controls. On continuous subcutaneous insulin infusion variations of blood glucose were not affected whereas variations in total ketone bodies were no different from controls. The best possible maternal metabolic control is necessary for normal foetal development and continuous subcutaneous insulin infusion provides a method of achieving this.

Adult↗
PubMed1981

Rapid changes in somatomedin activity during insulin-induced hypoglycemia: possible release of an inhibitory factor.

Somatomedin activity was determined by bioassay during insulin-induced hypoglycemia in 24 patients with a variety of pituitary disorders. Initial somatomedin levels appeared to depend primarily on the state of GH secretion and were unaffected by abnormal PRL secretion. During the test, somatomedin activity fell to a minimum after 45 to 60 min and subsequently returned to initial values in those patients whose GH levels rose in response to insulin hypoglycemia, but not in patients lacking a GH response. Heat treatment of the plasma abolished the change in somatomedin activity in the majority of patients, and it is likely that the apparent fall in somatomedin was due to the presence of a heat-labile inhibitor of somatomedin action on cartilage.

Drug Stability↗