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P C Simpson

Publications and source records attributed to P C Simpson.

47 records · Page 3Linked to original sources
PubMed1986

Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression.

The mechanism of hormonally induced cell hypertrophy is unknown. Stimulation of cardiac myocytes by alpha 1-adrenergic agents, phorbol esters, and serum induces an increase in the cell size of nondividing cardiac myocytes in primary culture. Expression of the c-myc gene, known to be increased in growth factor-induced cell division, was studied in this model of cell hypertrophy. The alpha-adrenergic agonist norepinephrine (0.002-20 microM) increased levels of c-myc-encoded mRNA to 10-fold over control levels. This increase was detectable at 30 min, peaked at 2 hr, and returned to baseline by 6 hr after stimulation. The norepinephrine response was abolished by the alpha 1-antagonist terazosin (2 microM) but was not affected by the beta-adrenergic antagonist propranolol (2 microM) and was only slightly (25%) attenuated by the alpha 2-adrenergic antagonist yohimbine (2 microM). Serum and the phorbol ester tumor promoter phorbol 12-myristate 13-acetate also enhanced c-myc expression in cardiac myocyte cultures. These findings show that the induction of cardiac myocyte hypertrophy is associated with enhanced expression of the c-myc gene and suggest that hormonally induced cell hypertrophy and cell division share common mechanistic pathways.

Animals↗
PubMed1986

Mechanisms and time course of beta 1 adrenoceptor desensitisation in mammalian cardiac myocytes.

To study the mechanisms and time course of beta1 adrenoceptor desensitisation in mammalian heart tissue neonatal rat cardiac myocytes (greater than 90% pure) were cultured in serum free medium. Cells were exposed to 1 mumol X litre-1 (-)-isoprenaline for 30 min, 4 h, and 16 h. In myocyte membranes mean(SEM)) 125I-iodocyanopindolol binding was 167(46) pmol X litre-1 (n = 5) and did not differ at 30 min, 4 h, or 16 h in control compared with (-)-isoprenaline treated cells. The maximum number of binding sites was 84(32) fmol X mg protein-1 and was unchanged at 30 min, but (-)-isoprenaline stimulated adenylate cyclase activity significantly decreased from 221(62) to 103(37) pmol X mg protein-1 30 min-1. (-)-Isoprenaline competition curves at 30 min showed a significant increase in the proportion of low affinity binding sites from 46% to 62% (n = 5). By 4 h the maximum number of binding sites was significantly decreased by 54%, adenylate cyclase activity remained depressed, and agonist affinity decreased threefold in the (-)-isoprenaline treated cells. At 16 h (-)-isoprenaline treated cells showed alterations similar to the 4 h values in the maximum number of binding sites, adenylate cyclase activity, and affinity for (-)-isoprenaline. (-)-Isoprenaline stimulated adenylate cyclase activity took 72 h to recover after desensitisation. Overnight ultracentrifugation of the cytosol showed a significant 40% increase in beta adrenoceptor density in cells exposed to (-)-isoprenaline for 4 h (n = 5), suggesting receptor internalisation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1985

Adrenergic receptor characteristics of cardiac myocytes cultured in serum-free medium: comparison with serum-supplemented medium.

Neonatal rat ventricular myocytes cultured in serum-free medium coexpress both alpha 1 and beta 1 receptors as determined by radioligand binding studies. In cells exposed to serum for 48 hr surface area increased 3.69 fold, but the maximum number of binding sites ([125I]-iodocynanopindolol) only increased 1.5 fold from 12956 +/- 7579 to 19676 +/- 5181 sites/cell (n = 5, p less than .05) yielding a value of 2.48 sites/um2 for cells grown in serum-supplemented medium compared with 6.96 sites/um2 for cells grown in serum-free medium. Thus serum-induced hypertrophy is associated with a decrease in beta 1 receptor density relative to cell size; however, adenylate cyclase response is unaffected. This cell culture system constitutes an excellent model for studying interventions that may influence the regulation of cardiac myocyte hypertrophy by nonhemodynamic factors, particularly through the adrenergic receptor system.

Animals↗
PubMed1981

Computed tomography: a new method for diagnosing tumor of the heart.

An unsuspected metastasis of liposarcoma of the heart was detected on a computed tomographic (CT) examination of the chest. Further CT study with i.v. contrast administration gave excellent delineation of the tumor. Compared with two-dimensional echocardiography and angiocardiography, CT was best at showing the myocardial and intrapericardial extension of the tumor, but did not show movement of the tumor during the cardiac cycle. CT is a useful noninvasive method for evaluating cardiac metastasis. Its advantages and disadvantages with respect to echocardiography and angiocardiography are discussed.

Angiocardiography↗
PubMed1978

scyllo-inositol and myo-inositol levels in tissues of the skate Raja erinacea.

1. Many organs of the skate Raja erinacea have been found to contain scyllo-inositol levels that are much higher than myo-inositol, the opposite to that found in mammals. 2. Both inositols were found in all skate organs studied. 3. myo-Inosose-2 was found to accompany the inositols in many of these organs.

Animals↗
PubMedDate not supplied

Adrenergic hormones and control of cardiac myocyte growth.

The molecular mechanisms of cardiac myocyte growth are relevant to important problems in cardiovascular disease. A cell culture model has been developed to explore the role of adrenergic hormones in cardiac myocyte growth and gene expression. Activation of a cardiac myocyte alpha 1-adrenergic receptor by catecholamines induces hypertrophic growth of neonatal rat cardiac myocytes and initiates selective increases in contractile protein gene transcription. These effects on growth and gene expression do not depend on contractile activity. The cardiac myocytes contain at least two subtypes of alpha 1-adrenergic receptors and at least three isoforms of protein kinase C (PKC). A distinct alpha 1 receptor subtype may mediate hypertrophy and gene transcription. Different isoforms of PKC are translocated to different intracellular sites on activation, and there is evidence that the beta-PKC isoform may be an element in the signal transduction pathway from an alpha 1 receptor at the surface to the cardiac myocyte nucleus. Growth regulation through a beta-adrenergic receptor can also be demonstrated in the culture model. The growth response mediated through a beta-adrenergic receptor differs in several respects from that transduced through an alpha 1-adrenergic receptor.

Catecholamines↗
PubMedDate not supplied

Beta-adrenoceptor and adenylate cyclase regulation in cardiac myocyte growth.

We studied the effect of growth on beta-adrenergic receptor properties of neonatal rat heart myocytes cultured in serum-free medium with transferrin and insulin. Growth was induced by addition of 1 microM (-)-norepinephrine for two days, 200 nM of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for two days, or 30 nM T3 for six days. The Kd values for beta-receptor binding (125I-ICYP) were unaffected by growth. The maximum number of beta-receptor binding sites calculated as sites/cell was increased 1.47-fold by T3 (p less than .005), but was decreased to 54% of control values by (-)-norepinephrine (p less than .005): TPA had no effect on either Kd or Bmax values. (-)-Isoproterenol-stimulated adenylate cyclase activity was augmented only in membranes from T3-treated cells and was reduced by 69% in membranes from (-)-norepinephrine treated cells. TPA had no effect on (-)-isoproterenol-stimulated adenylate cyclase activity. We conclude that the mechanisms controlling beta-adrenergic receptor number may be distinct from those controlling growth, since receptor number does not correlate with cell enlargement. Furthermore, in (-)-norepinephrine-stimulated growth, which we have shown previously is an alpha 1-adrenoceptor mediated response, beta-adrenergic signal transduction is modulated in a directionally opposite fashion.

Adenylyl Cyclases↗