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Biomedical subjects

R McGee

Publications and source records attributed to R McGee.

At least 145 records · Page 8Linked to original sources
PubMed1984

Acute elevation of cyclic AMP does not alter the ion-conducting properties of the neuronal nicotinic acetylcholine receptor of PC12 cells.

The nicotinic acetylcholine receptor of Torpedo californica has been shown to be subject to cyclic AMP-dependent phosphorylation, raising the possibility that nicotinic receptors may be regulatable by phosphorylation. To investigate this possibility for a neuronal nicotinic receptor, we have studied the effects of elevation of cyclic AMP on the ion-conducting properties of the nicotinic receptor of PC12 cells. The cyclic AMP content of the cells was altered by exposure to various concentrations of forskolin (an activator of adenylate cyclase) for periods of time ranging from 1 to 40 min. Receptor activation then was measured as agonist-induced influx of 86Rb+ into the cells. Throughout a variety of conditions, no changes in agonist-induced ion influx were detected. This was true regardless of the concentration of agonist used, the duration of receptor stimulation that was measured, the concentration of forskolin employed, or the duration of elevation of cyclic AMP prior to receptor activation. Experiments designed to measure receptor desensitization also were unable to detect any differences upon elevation of cyclic AMP. Finally, the antagonism of receptor activation by substance P also was not affected by elevation of cyclic AMP. Thus, no evidence could be obtained in these cells supporting the hypothesis that a neuronal nicotinic acetylcholine receptor can be acutely regulated by changes in cellular cyclic AMP.

Adenylyl Cyclases↗
PubMed1984

A longitudinal study of the intelligence and behavior of preterm and small for gestational age children.

A large sample of children (n = 850) from Dunedin, New Zealand, were classified into three groups, preterm (n = 31), small for gestational age (SGA; n = 71), and full-term, normal birth weight (n = 748). These groups were compared on intelligence measures taken at ages 3, 5, 7, and 9 years of age and parent and teacher behavior reports at 5, 7, and 9 years. The SGA group but not the preterm group had significantly lower IQ scores than the normal birth weight children. In addition, the mothers of the SGA children reported more behavior problems. These differences were not attributable to socioeconomic disadvantage in the SGA group. The results suggest "it is better to be born too early than too small."

Birth Weight↗
PubMed1983

Developmental language delay from three to seven years and its significance for low intelligence and reading difficulties at age seven.

A large sample of Dunedin (New Zealand) children was assessed at three, five and seven years to study the prevalence and stability of language delay, and to investigate the association between language delay at each age and low intelligence and reading problems at age seven. The prevalence of specific comprehension delay, specific expressive delay, and general language delay varied from 2.0 to 4.3 per cent. General language delays were the most stable. Every type of language delay at each age, particularly earlier, general and stable delay was associated with a significantly higher prevalence of low intelligence or reading difficulties at age seven than among the total sample.

Age Factors↗
PubMed1983

Regulation of depolarization-dependent release of neurotransmitters by adenosine: cyclic AMP-dependent enhancement of release from PC12 cells.

We have used pheochromocytoma cells, clone PC12, as a model system for studying the effects of adenosine on neurosecretion. Exposure of the cells to adenosine or 2-chloroadenosine caused immediate activation of adenylate cyclase, increases in cellular cyclic AMP content, and inhibition of SAM-dependent phospholipid N-methylation and protein carboxymethylation. However, the effects on methylation were only observed with concentrations of adenosine 100 times greater than those that elevated cyclic AMP. Exposure of the cells to adenosine and 2-chloroadenosine did not alter the release of [3H]norepinephrine [(3H]NE) in the absence of depolarization. However, depolarization-dependent release of [3H]NE was markedly elevated by short (1-20 min) pretreatments with adenosine or 2-chloroadenosine. The enhancement of release was observed irrespective of the nature of the depolarizing stimulus (elevated K+, carbamylcholine, or veratridine). Release of [3H]acetylcholine in response to elevated K+ also was increased by adenosine pretreatment. These effects of adenosine and 2-chloroadenosine on neurotransmitter release closely paralleled elevation of cellular cyclic AMP but not inhibition of methylation. Taken together, the results show that adenosine, probably acting through adenosine receptors coupled to stimulation of adenylate cyclase, is able to modulate the neurosecretory process in PC12 cells. Furthermore, the enhancement of release occurred even though the extent of depolarization (measured as 86Rb+ flux through the acetylcholine receptor channel) and the amount of 45Ca2+ which entered upon depolarization were unchanged. Therefore, the enhancement of release produced by elevated cyclic AMP appeared to reflect increased efficiency of the stimulus-secretion coupling process.

2-Chloroadenosine↗
PubMed1983

Prevalence of self-reported depressive symptoms and associated social factors in mothers in Dunedin.

A large sample of women (n = 899) from Dunedin, New Zealand, completed a self-report questionnaire on depressive symptoms. On this basis, about 8 per cent of the sample were identified as having major depressive disorder. These women tended to have a history of previously reported psychological symptoms and formal treatment for depression. A significantly high proportion of the depressed group had been young at first pregnancy and had since been separated from their partners. The depressed women also reported more behaviour problems in their children, but these reports were not confirmed by teachers' reports or by the children's self-reports, suggesting a response bias in depressed women towards reporting problems.

Adult↗
PubMed1982

Neurological dysfunction in a large sample of three year old children: a report from the Dunedin Multidisciplinary Child Development Study.

The prevalence of neurological abnormalities was examined in a large sample of Dunedin three-year-old children. About 10 percent of those assessed had one or more abnormalities at three and 2 percent had abnormalities which were judged to have an effect on the child's functioning. The presence of abnormalities at three was associated with language and motor delays at that age and predictive of later IQ deficit. However, abnormalities were not stable over time and their significance for predictive purposes with individual cases is questioned.

Child↗
PubMed1982

Behaviour problems and otitis media with effusion: a report from the Dunedin Multidisciplinary Child Development Study.

The relationship between behaviour problems at age seven and occurrence of otitis media with effusion (OME) at age five was examined in a large sample of Dunedin children. It was found that children with a significant degree of problem behaviour at seven were twice as likely to have had OME at five when compared with children without behaviour problems. Furthermore, there was a significant association between hyperactive behaviour in boys and bilateral OME.

Child↗
PubMed1982

The effects of membrane fatty acid modification of clonal pheochromocytoma cells on depolarization-dependent exocytosis.

We have begun studying the role of membrane lipids in the exocytotic release process using the pheochromocytoma clone, PC12. The phospholipid fatty acid composition of the cells was modified by growth in the presence of specific fatty acids. None of the fatty acid modifications affected K+-stimulated release of [3H] norepinephrine. This observation indicates that the individual steps of the secretion process, including the extent of depolarization produced by K+, the response of the voltage-dependent Ca2+ channels to depolarization, and the subsequent steps in Ca2+-dependent exocytosis were unaffected by the fatty acid changes. In contrast, exocytosis evoked by stimulation of nicotinic cholinergic receptors with carbamylcholine or direct activation of action potential Na+ channels with veratridine was diminished in cells enriched with unsaturated fatty acids. The diminished output of the release systems was observed at all concentrations of carbamylcholine and veratridine tested. Since the events of exocytosis subsequent to Ca2+ influx were unaffected by unsaturated fatty acids, it appears likely that the magnitude of the depolarization produced by carbamylcholine and veratridine was reduced. The loss of carbamylcholine-stimulated release did not correlate with the simple presence of the fatty acids, but paralleled closely the time and concentration-dependent changes in the phospholipid fatty acid composition. However, when oleate and arachidonate were simultaneously added to the culture medium, the inhibitory effects on carbamylcholine-stimulated release were additive, whereas the changes in fatty acid composition were antagonistic. Thus, exposure of PC12 cells to unsaturated fatty acids causes specific, reversible decreases in the activities of at least 2 stimulus/secretion systems. However, the mechanistic explanation for these changes is not readily apparent from a simple analysis of total phospholipid fatty acid composition.

Adrenal Gland Neoplasms↗
PubMed1982

Cigarette smoking and state-dependent memory.

Two experiments were carried out to investigate whether cigarette smoking could produce state-dependent learning (SDL) in humans. The first experiment was concerned with the methodological issue of choosing an appropriate control cigarette for use in an SDL design. A low nicotine content (0.2 mg) cigarette was chosen as it did not appear to affect the physiological arousal of the subjects. In Experiment 2, it was shown that cigarette smoking can produce state-dependent memory effects. The most likely basis for the results is the arousal produced by the nicotine content of the cigarette.

Adult↗
PubMed1982

Enhancement of depolarization-dependent neurosecretion from PC12 cells by forskolin-induced elevation of cyclic AMP.

The effects of elevated intracellular cyclic AMP on the release of neurotransmitters was studied using the clonal pheochromocytoma cell line, PC12, and forskolin, a direct activator of adenylate cyclase. Intracellular cyclic AMP concentrations ranging from 8 to 400 times basal levels were achieved with 0.1 to 100 uM forskolin. Unstimulated release of neurotransmitters was unchanged by any concentration of forskolin. However, K+-stimulated release of both norepinephrine (NE) and acetylcholine was enhanced by 0.1 to 10 uM forskolin. Release of NE elicited by depolarization with carbachol and veratridine also was enhanced by 1 uM forskolin. Enhancement of release was reversed by higher concentrations of forskolin, especially in the presence of a phosphodiesterase inhibitor (RO 20-1724) which caused very large increases in cyclic AMP content. The enhancement of transmitter release from the PC12 cells occurred without concomitant changes in agonist-stimulated ion flux through the acetylcholine receptor ion channel, or in depolarization-dependent uptake of 45Ca++. Thus, increasing the cyclic AMP content of PC12 cells fails to initiate neurosecretion but appears to facilitate some element in the secretion process subsequent to Ca++ influx.

Adrenal Gland Neoplasms↗
PubMed1981

Membrane fatty acid modification of the neuroblastoma x glioma hybrid, NG108-15.

As a first step in studying the effects of membrane lipid modification on complex cellular functions we have modified the membrane fatty acid composition of the neuroblastoma X glioma hybrid clone, NG108-15. These cultured cells were chosen because they exhibit many complex neuronal functions in vitro. Unsaturated fatty acids (oleate, linoleate, linolenate and arachidonate) were accumulated, metabolized and esterified by the cells. These unsaturated fatty acids stimulated cell growth, whereas saturated fatty acids were toxic to the cells. Changes as large as 40-fold in the ratio of monounsaturated/polyunsaturated fatty acids in the membrane phospholipids were produced by addition of fatty acids directly to serum-containing culture medium. As a result of the exposure of NG108-15 cells to unsaturated fatty acids the amount of phosphatidylethanolamine in the cells was increased by as much as 60%. Polyunsaturated fatty acids also caused a small decrease in the membrane cholesterol/phospholipid molar ratio. These experiments demonstrate that large changes in membrane fatty acid composition can be created in clonal cells capable of differentiated neuronal activities. Additional changes in membrane lipid composition also appear to be induced by these manipulations. The question of the importance of specific membrane lipid composition to neuronal cellular function now can be addressed.

Animals↗
PubMed1981

Alteration of the action potential of tissue cultured neuronal cells by growth in the presence of a polyunsaturated fatty acid.

The effects of alterations in membrane phospholipid fatty acid composition on the excitability of neuroblastoma X glioma hybrid cells, clone NG108-15, were examined using intracellular recording techniques. Cells were grown in the presence of arachidonate (20:4) added to the culture medium as a complex with bovine serum albumin. Exposure of the cells to 20:4 for 3-21 days produced a 40% decrease in the maximum rate of rise of the action potential (dV/dt) with a small change in its amplitude. The resting membrane potential and passive properties of the cells were unaffected. An effect of 20:4 was not observed until 24 hr after treatment and increased over the next 2 days. The phospholipid content of 20:4 and its metabolite 22:4 increased from 6.9% to 25.3% of total fatty acids during approximately the same time span. It is concluded that the action potential dV/dt can be altered by changes in membrane lipid composition.

Action Potentials↗