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Biomedical subjects

M J MacDonald

Publications and source records attributed to M J MacDonald.

162 records · Page 9Linked to original sources
PubMed1979

Epidermal proteins of cultured human and bovine keratinocytes.

Bovine and human epidermal cells were cultured on mitomycin C treated fibroblasts. The cells were carried through four passages and found to synthesize fibrous proteins and insoluble cell envelopes. Acid buffer soluble fibrous protein, prekeratin, and urea soluble fibrous protein were both identified and the latter was the major component in older cultures. Some of the prekeratin polypeptides of intact tissue were not found in cultured cells, but the ones that were present corresponded to those of whole tissue. X-ray diffraction, amino acid analysis and immunological techniques were used to establish that the polypeptides were keratins. The insoluble cell envelopes had a higher proline and 1/2 cystine content than the fibrous protein, similar to what is found in whole epidermis. Histidase, a characteristic enzyme marker of whole epidermis, was not observed in cultured cells. These studies indicate that differentiation occurs in cultured cells but it may not be as complete as in intact tissue.

Adult↗
PubMed1979

Development of phosphoenolpyruvate carboxykinase ferroactivator in fetal and young rats and guinea pigs.

The development of ferroactivator, a protein that permits Fe2+ to activate the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, was compared to that of the carboxykinase in rat and guinea pig fetuses and neonates. Significant ferroactivator was present in the liver of the fetal rat and in the liver and kidney of the fetal guinea pig in the last half of gestation. The development of ferroactivator does not parallel that of the carboxykinase which does not attain maximal levels until after birth. Thus, the ferroactivator cannot be rate limiting for neonatal gluconeogenesis. It was found, unexpectedly, that the carboxykinase was increased during suckling in the guinea pig.

Age Factors↗
PubMed1978

Hyperglycaemic activity and metabolic effects of 3-aminopicolinic acid.

Administering 3-aminopicolinate to rats starved for 24h immediately initiated a progressive increase in blood glucose concentration. Hyperglycaemia was not the result of glycogenolysis, nor was it due to an inhibition of insulin release, since it caused marked hyperinsulinaemia. The rate of [6-(3)H]glucose disappearance from the blood of the intact rat was not altered by 3-aminopicolinate, indicating that it does not cause hyperglycaemia by inhibiting glucose utilization or by causing a redistribution of total body glucose. 3-Aminopicolinate increased the rate of fall in the specific radioactivity of blood [6-(3)H]-glucose, indicating dilution of the glucose pool by newly synthesized glucose. The rate of (14)C incorporation into blood glucose from [(14)C]alanine and [(14)C]lactate was increased 90 and 35% respectively, whereas that from [(14)C]glycerol and [(14)C]xylitol was either unaffected or slightly decreased by 3-aminopicolinate administration. Liver phosphoenolpyruvate of rats was increased to four to seven times the normal concentration 10min to 1h after injections of 50-300mg of 3-aminopicolinate/kg body wt. and the amounts of 2-phosphoglycerate and 3-phosphoglycerate were increased to three to four times normal. The high concentrations of liver phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate, as well as the enhancement of gluconeogenesis from lactate and alanine, but not from glycerol or xylitol, is compatible with an enhancement of gluconeogenesis at a step between pyruvate and the triose phosphates. After injections of 3-aminopicolinate, liver malate, citrate, aspartate, alanine, lactate and pyruvate were also increased, but to lesser extents than was phosphoenolpyruvate. The increases in some of these metabolites were approximated after an intravenous infusion of glucose, so their elevated concentration after 3-aminopicolinate administration could have been, in part, a consequence of the hyperglycaemia. The possibility is considered that 3-aminopicolinate stimulates gluconeogenesis in vivo by facilitating Fe(2+) activation of phosphoenolpyruvate carboxykinase as it does with the purified enzyme in vitro [MacDonald & Lardy (1978) J. Biol. Chem.253, 2300-2307]. In this effect 3-aminopicolinate may simulate the physiological role of the naturally occurring ferroactivator protein [Bentle & Lardy (1977) J. Biol. Chem.252, 1431-1440].

Animals↗
PubMed1978

Effect of Fe2+ and Mn2+ on 3-mercaptopicolinate inhibition of cytosolic and mitochondrial phosphoenolpyruvate carboxykinase of five species.

Liver cytosolic or mitochondrial fractions of five species were incubated with 30 micrometer Fe2+ or with 100 micrometer Mn2+ prior to assaying for phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) acticity in the presence of 3-mercaptopicolinate. Only the cytosolic carboxykinases were activated 3--4-fold by Fe2+ or Mn2+. Fe2+ enhanced the inhibitory potency of 3-mercaptopicolinate 10--50-fold against the cytosolic and the mitochondrial carboxykinases, but Mn2+ was ineffective. Mn2+ interfered with Fe2+ -enhancement of inhibition by 3-mercaptopicolinate in a manner competitive with Fe2+. It is hypothesized that Fe2+ and 3-mercaptopicolinate form a coordination complex that inhibits the carboxylkinases and that 3-mercaptopicolinate does not blind to a carboxykinase containing Mn2+.

Animals↗
PubMed1975

Studies of insulin release and rat pancreatic islet metabolism with diastereomers of D-glucose.

Studies of insulin release with diastereomers and other analogues of D-glucose demonstrated that only sugars which undergo oxidation to CO2 stimulated insulin release by the pancreatic islet. None of the non-metabolizable diastereomers of glucose stimulated insulin release in the presence of a sub-stimulatory concentration of glucose for fuel. Although 5.5 mM glucose formed 77% as much CO2 as 16.7 mM mannose and twice that of 16.7 mM fructose, 5.5 mM glucose did not stimulate insulin release whereas 16.7 mM mannose and fructose did stimulate insulin release. These results indicate that the important stimulus for glucose-induced insulin release involves metabolism of glucose, but that the stimulus does not involve solely a fuel function of glucose.

Animals↗
PubMedDate not supplied

Echocardiography and surgery in a dog with left atrial rupture and hemopericardium.

Endocardial splitting and left atrial rupture were diagnosed in a dog with mitral regurgitation that experienced the sudden onset of collapsing episodes, weakness, depression, labored breathing, and weak pulses. Thoracic radiographs showed a rounded cardiac silhouette with prominent left atrium consistent with hemopericardium due to left atrial rupture. Two-dimensional echocardiography confirmed the presence of severe mitral valve disease, pericardial fluid, and a laminated blood clot caudal to the left ventricle. A sterile emergency thoracotomy was performed, the hemopericardium and blood clot were removed, and the rupture site in the left atrium was repaired with reinforced sutures. The dog recovered from surgery but died the next day, presumably from a ventricular arrhythmia.

Animals↗
PubMedDate not supplied

Postexercise late-onset hypoglycemia in insulin-dependent diabetic patients.

A new clinical entity that is prevalent in young type I (insulin-dependent) diabetic patients, postexercise late-onset (PEL) hypoglycemia, is described. A prospective case-finding study suggested that PEL hypoglycemia occurred in 48 of approximately 300 diabetic type I patients who were diagnosed as diabetic before age 20 yr and who were monitored for up to 2 yr. Typically, hypoglycemia was nocturnal and occurred 6-15 h after the completion of unusually strenuous exercise or play. In more than half the cases the hypoglycemia resulted in loss of consciousness or seizures and necessitated treatment with subcutaneous glucagon or intravenous glucose and/or attendance by a health professional. The hypoglycemia was not limited to patients in good or excellent metabolic control and often occurred after a single bout of exercise in patients unaccustomed to exercise or in athletic patients who were making the transition from an untrained to a trained state. Surprisingly, 12 of the patients who experienced nocturnal PEL hypoglycemia were not using significant amounts of insulin that peaked at night. Type I diabetic patients should be made aware of the possibility of PEL hypoglycemia to enable them to make adjustments in their management plans in anticipation of unusually strenuous exercise, so that they may attempt to minimize or avoid late-onset hypoglycemia.

Adolescent↗