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Biomedical subjects

A McCulloch

Publications and source records attributed to A McCulloch.

26 records · Page 2Linked to original sources
PubMed1989

Metabolism of inositol 1- and 4-monophosphates in HL60 promyelocytic leukaemia cells.

The metabolism of inositol 1- and 4-monophosphates in HL60 promyelocytic leukaemia cells was studied. LiCl, BeCl2 and NaF inhibited the hydrolysis of both monophosphates with half maximal inhibition occurring at 1.2 mM, 0.3 microM, 0.25 mM (Ins 1P) and 0.14 mM, 0.56 microM, 0.28 mM (Ins 4P) respectively. Lithium was an uncompetitive inhibitor with respect to both substrates. Ins 4P inhibited the hydrolysis of Ins 1P in a concentration dependent manner, suggesting that it acts as a competing substrate for the same enzyme. Half maximal inhibition occurred at 120 microM Ins 4P. The lithium sensitive activity responsible for the metabolism of both monophosphates was present in a soluble fraction made from the cells. Taken together these data suggest that Ins 1P and Ins 4P are hydrolysed by a single soluble enzyme activity which is sensitive to inhibition by lithium, beryllium and fluoride.

Beryllium↗
PubMed1989

Vasopressin secretion in the DIDMOAD (Wolfram) syndrome.

The diabetes insipidus which accompanies the DIDMOAD (Wolfram) syndrome is thought to be hypothalamic in origin, though no formal study of vasopressin secretion in the syndrome has been published, and some data in the literature suggest a renal tubular defect. We have studied vasopressin secretion in seven patients with the Wolfram/DIDMOAD syndrome during three dynamic stimuli: an osmotic stimulus (hypertonic saline infusion), hypoglycaemia (insulin tolerance test) and a baroregulatory stimulus (trimetaphan infusion). Hypertonic saline infusion demonstrated three patients to have complete and four to have partial hypothalamic diabetes insipidus; administration of (per nasal) desmopressin excluded nephrogenic diabetes insipidus in all seven patients. Insulin hypoglycaemia failed to stimulate vasopressin release, but trimetaphan-induced hypotension produced significant though subnormal rises in plasma vasopressin in three patients with partial diabetes insipidus, though it produced a negligible rise and no rise in plasma vasopressin in two patients with complete diabetes insipidus. The data suggest a much greater frequency of hypothalamic diabetes insipidus in the Wolfram/DIDMOAD syndrome than is reported, but did not identify nephrogenic diabetes insipidus. The absence of vasopressin responses to non-osmotic stimuli in patients with complete diabetes insipidus suggests global lack of vasopressin secreting neurones, rather than an isolated osmoreceptor defect or selective vasopressin secreting neuronal loss, as the lesion producing diabetes insipidus in the DIDMOAD syndrome.

Adult↗
PubMed1987

In-vivo chemical choledocholitholysis using MTBE.

Following endoscopic sphincterotomy, it is possible to clear a large proportion of stones from the bile ducts. In a few cases, however, the stones are too large to retrieve. Mechanical lithotripsy is unpredictable and carries a substantial risk of impaction. We report a patient who had multiple large stones in the bile ducts which were successfully dissolved using MTBE. No adverse effects were noted.

Aged↗
PubMed1983

Glucose turnover and recycling in colorectal carcinoma.

Glucose metabolism is affected by various pathologic states including tumors. In this project, glucose turnover and recycling rates in 11 patients with colorectal carcinoma were measured using a double-labelled 3-3H and 1-14C glucose injection technique. Fasting blood glucose, lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate, acetoacetate, plasma cortisol, and plasma insulin concentrations were also measured. No patient in the study had a history of diabetes mellitus or endocrine disorders, nor any abnormal liver function tests. The findings demonstrated a significantly elevated glucose turnover rate in patients with Dukes C and D lesions in comparison to patients with Dukes B lesions. Cori recycling rates were not significantly different between Dukes B vs. Dukes C and D patients. There were no differences between Dukes B and Dukes C and D patients in any of the metabolites measured. Furthermore, there were no significant differences in glucose turnover or recycling rates as a function of pre-illness weight loss. These data suggest that, when colorectal carcinoma extends beyond the limits of the bowel wall, glucose metabolism is significantly altered.

Aged↗
PubMed1982

Some hormonal influences on glucose and ketone body metabolism in normal human subjects.

Control of glucose and ketone body metabolism is integrated by a variety of hormones. Insulin is the major anabolic hormone, and its actions are antagonized by rapidly acting catabolic hormones, such as glucagon and the catecholamines, and by others such as cortisol, growth hormone and the thyroid hormones, which generally have more delayed effects. In the normal human subject, the effects of catabolic hormones to raise blood glucose are limited by a compensatory increase in insulin secretion, and these effects are enhanced in insulin deficiency. Hyperketonaemic actions of the catabolic hormones may result from increased supply of non-esterified fatty acids from lipolysis, although glucagon has a major direct action to increase ketogenesis at the liver. As expected, these actions are also restricted in normal humans by the compensatory rise in insulin secretion. Hyperketonaemia does, however, occur with adrenaline (epinephrine) and noradrenaline (norepinephrine), even in the presence of mildly elevated insulin concentrations. These catecholamines may assume particular importance in mobilization of lipid fuels in milder forms of stress, when insulin secretion is normal or mildly increased. In severe stress, when there is catecholamine-induced suppression in insulin secretion, lipolytic and hyperketonaemic effects of all the catabolic hormones may be manifest. Starvation in humans also results in diminished insulin secretion and increased catabolic hormone secretion. The relative importance of individual hormones in lipid mobilization during starvation is uncertain, although glucagon, growth hormone, noradrenaline and, possibly, dopamine may all play a part.

3-Hydroxybutyric Acid↗
PubMed1982

Model of the kinetics of ketone bodies in humans.

The kinetics of ketone bodies was studied in normal humans by giving a combined bolus intravenous injection of labeled acetoacetate ([14C]AcAc) and D(--)-beta-hydroxybutyrate (beta-[14C]-OHB) to seven subjects after an overnight fast, on two different occasions, and by collecting frequent blood samples for 100 min. Kinetic data were analyzed with both noncompartmental and compartmental modeling techniques. A four-compartment model, representing AcAc and beta-OHB in blood and two equilibrating ketone body compartments, inside the liver and extrahepatic tissues, was chosen as the most reliable mathematical representation; it is physiologically plausible and was able to accurately fit the data. The model permitted evaluation of the in vivo rate of ketone body production in the liver, the individual plasma clearance rates of AcAc and beta-OHB, their initial volumes of distribution, and the transfer rate parameters among the four ketone body compartments. Moreover, the model provided estimates of the components of the rates of appearance of AcAc and beta-OHB in plasma due to newly synthesized ketone body from acetyl-CoA in the liver, and to interconversion and recycling in the liver and extrahepatic tissues. The model also was used to evaluate other methodologies currently employed in the analysis of ketone body turnover data: the conventional approach based on use of the combined specific activity of AcAc and beta-OHB required assumptions not satisfied in vivo, leading to substantial errors in key parameter estimates.

3-Hydroxybutyric Acid↗