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Biomedical subjects

S Currie

Publications and source records attributed to S Currie.

At least 19 recordsLinked to original sources

Bombesin stimulates the rapid activation of phospholipase A2-catalyzed phosphatidylcholine hydrolysis in Swiss 3T3 cells.

In Swiss 3T3 fibroblasts bombesin stimulated the release of arachidonic acid in a time- and dose-dependent manner. Arachidonate levels were significantly elevated after only a 2-s stimulation with the agonist. Furthermore, by measuring the arachidonate content of cellular phospholipids after cell activation, it was shown that there was selective depletion from phosphatidylcholine over the same time course. The corresponding production of lysophosphatidylcholine suggested the involvement of a phosphatidylcholine-specific phospholipase A2. Initial arachidonic acid release was not dependent on the presence of extracellular calcium, not activated by treatment of the cells with thapsigargin, and was unaffected by down-regulation of protein kinase C activity, or by treatment of the cells with the protein kinase C inhibitor staurosporine. These data strongly suggest that occupation of the bombesin receptor is closely coupled to activation of phospholipase A2 which results in the rapid release of arachidonic acid from phosphatidylcholine.

3T3 Cells

Thermoregulation, plasma catecholamine and metabolite levels during submaximal work in individuals susceptible to malignant hyperpyrexia.

Measurements of body temperature, respiratory gas exchange, sweat evaporation rate and circulating levels of catecholamines, lactate, pyruvate, free fatty acids and glucose were made in seven patients susceptible to malignant hyperpyrexia (MHS) and in seven control subjects during 2 h of treadmill walking at 40% of maximum oxygen consumption. These studies took place in an ambient temperature of 22 degrees C. The MHS patients displayed the same thermoregulatory, plasma catecholamine and metabolic responses as the control subjects. The results of the present study suggest that non-competitive, low-intensity, steady-state exercise need not be contraindicated for MHS patients.

Body Temperature Regulation

A rapid startle response in larval lampreys.

Electromyography (EMG) and cinematography revealed a rapid, vibration-evoked startle response in intact larval lampreys. Vibratory stimuli produce simultaneous contraction of both sides of the body, and the response is lost after labyrinthectomy. Midbody EMGs exhibit a stimulus-response latency of 26.5 +/- 4.2 ms. Direct stimulation of the otic capsules, using an electrically driven probe applied to a semi-intact preparation, first evokes a volley of giant axon spikes in the spinal cord followed by the bilateral trunk response.

Animals

Thermoregulatory responses to cooling in patients susceptible to malignant hyperpyrexia.

The influence of 1 h of surface cooling on body temperature, variables which contribute to thermoregulation and selected hormones and metabolites has been investigated in seven patients susceptible to malignant hyperpyrexia (MH) and in seven matched control subjects. Cooling was achieved using a liquid conditioned coverall worn next to the skin. Skin temperature decreased similarly in both groups of subjects. Heat production increased in both groups, with a slightly higher heat production being seen in the MH group. Core temperature increased in both groups of subjects at the start of the cooling period, with a significantly greater increase occurring in the MH group (control: + 0.13 +/- 0.13; MH: + 0.28 +/- 0.10 degrees C, P less than 0.05). There were no significant changes in plasma lactate, or pyruvate concentrations. Plasma glucose concentrations were lower in the control group; after 30 min of cooling plasma glucose was 4.25 +/- 0.37 mmol litre-1 in the control group and 5.34 +/- 0.21 mmol litre-1 in the MH group (P less than 0.05). There were no significant changes in plasma thyroxine or adrenaline concentrations. Plasma noradrenaline increased in both groups of subjects. The increase in plasma noradrenaline of the MH patients was greater than in most of the control subjects.

Adolescent

Which behavior does the lamprey central motor program mediate?

The isolated lamprey spinal cord, when bathed in 2 millimolar D-glutamic acid, will generate a pattern of motor neuron discharge that has generally been assumed to represent the central motor program for swimming. Motion pictures of behaving lampreys were analyzed by a computer algorithm to estimate undulatory movement parameters that could be directly compared with those generated during D-glutamate--induced undulations. The D-glutamate--induced movement parameters were significantly different from those observed during normal behaviors, including swimming, but accurately predicted the undulations produced by spinally transected adult lampreys.

Animals

Thirst, resetting of the osmostat, and water intoxication following encephalitis.

A young man developed pathological thirst and hyperdipsia, hyperphagia, disordered temperature regulation, a lowered threshold for aggressive behavior, apathy, impaired memory, and seizures following encephalitis. He had marked hyponatremia. Bouts of water drinking produced water intoxication and precipitated status epilepticus. Studies of water handling with measurements of plasma osmolality and arginine vasopressin (AVP) revealed a very low thirst threshold (below 242 mOsm/kg) with resetting of the osmostat to a new level (255 mOsm/kg) but normal control of plasma osmolality at that level with adequate AVP release.

Adult

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

Animals

Evaluation of creatinine phosphokinase in screening patients for malignant hyperpyrexia.

Evidence is presented that serum creatinine phosphokinase (CPK) activity is of no direct value in screening patients for susceptibility to malignant hyperpyrexia and does not correlate with halothane-induced muscle contracture or the presence of myopathy. Widely differing CPK values were found at different times in the same people. In most "malignant hyperpyrexia" families the susceptible patients had either normal or inconsistently raised CPK values.

Creatine Kinase