Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.

Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential.

The p53 Target Gene SIVA Enables Non-Small Cell Lung Cancer Development.

Unlabelled: Although p53 transcriptional activation potential is critical for its ability to suppress cancer, the specific target genes involved in tumor suppression remain unclear. SIVA is a p53 target gene essential for p53-dependent apoptosis, although it can also promote proliferation through inhibition of p53 in some settings. Thus, the role of SIVA in tumorigenesis remains unclear.

[Cardiovascular risk factors in France. Prevalence and association].

The object of this study was to assess the prevalence of modifiable cardiovascular risk factors and their association in 61,108 subjects over 15 years of age who volunteered for a systematic medical check-up, free of charge, and performed in a health centre in central France. The risk factors were defined as follows: hypertension, diabetes, hypercholesterolaemia, hypertriglyceridaemia: medical treatment or value above the upper limits of normal defined by national or international recommendations. obesity and android fat distribution as defined by the principal recommendations.

High blood pressure and associated cardiovascular risk factors in France.

Objective: To estimate, with respect to age and gender, the prevalence of high blood pressure (BP) in treated and non-treated subjects and its association with other cardiovascular risk factors.

Design: A cross-sectional study.

Setting: Healthcare centres in the centre of France.

Reference values for clinic pulse pressure in a nonselected population.

A wide pulse pressure (PP) may constitute an independent predictor of cardiovascular morbidity and mortality. We assessed the reference values of brachial clinic PP, according to age and gender in a nonselected population (61,724 subjects) who were undergoing a routine systematic health examination. According to mean values, 50 mm Hg is likely the reference value for clinic PP in both men and women.

Differential effects of tyrosine kinase inhibitors on contraction and relaxation of the aortas of normotensive and hypertensive rats.

The contribution of tyrosine kinase activity to vasoreactivity in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was investigated on isolated aortic preparations by the use of two tyrosine kinase inhibitors: methyl-2,5-dihydroxycinnamate (30 microM) and genistein (30 microM). The pretreatment of endothelium denuded aorta with methyl-2,5-dihydroxycinnamate reduced the sensitivity of the rings to noradrenaline to a larger extent in SHR than in WKY. The relaxing effects evoked by methyl-2,5-dihydroxycinnamate and genistein on the sustained contraction induced by endothelin-1 were also more pronounced in SHR denuded rings.

[Comparison between the effects of angiotensin-converting enzyme inhibitors and angiotensin II antagonists].

The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure regulation and fluid and electrolyte homeostasis. Angiotensin converting enzyme inhibitors (ACEI) were the first of the RAAS blocking agents to be widely used in the treatment of hypertension and congestive heart failure. Angiotensin II receptor antagonists, another class of pharmacological blockers of the RAAS, have more recently been shown to be safe and useful in hypertension and perhaps also in heart failure.

Assessment of the acute arterial effects of converting enzyme inhibition in essential hypertension: a double-blind, comparative and crossover study.

In subjects with essential hypertension, angiotensin-converting enzyme (ACE) inhibition increases arterial diameter, compliance and distensibility of peripheral muscular arteries in association with blood pressure reduction. Whether pulse pressure amplification is modified by ACE inhibition and whether changes in compliance and distensibility are due to a drug effect on the arterial wall, to the blood pressure reduction or to a combination of both factors, is largely ignored. In a randomised, double-blind crossover trial, we used the ACE inhibitor quinapril as a marker to evaluate the changes in: pulse pressure amplification (applanation tonometry), carotid compliance and distensibility (echo-tracking technique), and aortic distensibility (measured from pulse wave velocity).

Role of endothelium in the endothelin-1-mediated potentiation of the norepinephrine response in the aorta of hypertensive rats.

Objective: To investigate the role of the endothelium in the functional interaction between endothelin-1 and norepinephrine in the contractile response of aortas from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

Methods: Thoracic aorta rings with and without endothelium from SHR and from WKY rats were suspended in an organ bath to record the isometric tension. After an equilibration period of 120 min, the preparations with and without endothelin-1 were subjected to single and cumulative additions of norepinephrine in different experiments.

Influence of gender on the level of pulse pressure: the role of large conduit arteries.

The blood pressure curve may be divided into two components: a steady component represented by the mean arterial pressure, and a pulsatile component represented by the purse pressure. Whether the contribution of either these two components may be different in men and women was not yet investigated. The present study used 24 hours ambulatory brachial blood pressure monitoring and determination of casual carotid and radial pulse pressure by applanation tonometry to investigate 320 subjects (199 men and 121 women) with normal or elevated blood pressure.

Arterial distensibility and circadian blood pressure variability.

OBJECTIVE: To analyse the relationships between arterial distensibility and blood pressure level and its circadian variability assessed by non-invasive ambulatory blood pressure monitoring. DESIGN: One hundred and six patients (69 men, 37 women; aged 20-72 years) without any cardiovascular complication or treatment underwent 24 h ambulatory blood pressure monitoring. Aortic distensibility was evaluated by carotid-femoral artery pulse-wave velocity measurements performed with a validated automatic device (Complior).

[Family physicians and scientific information. Survey on hypertension and diuretics].

In order to analyse the quality of scientific communication in the field of hypertension, we have conducted a survey among French physicians. The topics of the questions were partly related to hypertension and partly to diuretics; 3,600 questions forms have been mailed: 610 answers were returned (17%). The results show that most of physicians are unsufficiently informed about primary prevention therapeutical trials and recommendations.

Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies.

Pulse wave velocity is widely used as an index of arterial distensibility. The aim of this study was to evaluate the accuracy of a new automatic device to measure it and then to analyze the major determinants of pulse wave velocity by application of this device in a large population. We evaluated the accuracy of on-line and computerized measurement of pulse wave velocity using an algorithm based on the time-shifted and repeated linear correlation calculation between the initial rise in pressure waveforms compared with the reference method (manual calculation) in 56 subjects.

Early disturbance of baroreflex control of heart rate after tail suspension in conscious rats.

Experiments were performed on conscious chronically instrumented rats maintained on tail suspension to determine the time course of changes in baroreceptor control of heart rate produced by this procedure. Pressor responses were elicited by bolus injections of graded doses of phenylephrine and sodium nitroprusside, permitting evaluation of the totality of the sigmoidal curve relating mean arterial pressure to heart rate. Compared with control rats maintained at 0 degrees, rats maintained at 20 degrees using tail suspension for 24 h showed a significant reduction in reflex gain (-3.

The nicardipine-isoprenaline interaction in human and guinea-pig isolated airways.

The effects of the dihydropyridine calcium antagonist nicardipine on the concentration-response curves of relaxant compounds acting through the adenylate-cyclase/cAMP system (isoprenaline, forskolin, adenosine and theophylline) or by the cGMP pathway (sodium nitroprusside) were studied on human isolated bronchus and guinea-pig isolated trachea. These effects were compared with those of nifedipine (a dihydropyridine derivative) and theophylline (a non-selective phosphodiesterase inhibitor). Nicardipine, in the range of 0.

Role of adrenergic tone in mechanical and functional properties of carotid artery during aging.

The present study was designed to assess the role of the adrenergic tone in the regulation of carotid arterial compliance during aging. An experimental model of in situ isolated carotid arteries has been used to evaluate the elastic properties of the arterial wall in young (3-mo-old) and older (18-mo-old) Wistar rats. Binding experiments were performed in the same strain of rats to evaluate alpha 1- and beta-adrenoceptor affinity and density.

Neuronal metabolism of catecholamines: plasma DHPG, DOMA and DOPAC.

Pre-synaptic endings of the sympathetic nervous fibers control the metabolism of catecholamines, particularly inactivating norepinephrine after its neuronal recapture. The present study was carried out to investigate this segment of the metabolism of catecholamines through measurements of DHPG, DOMA and DOPAC concentrations in plasma. A sensitive and specific radio-enzymatic assay was developed of which the major characteristic is to include the plasma sample in the incubation mixture without initial extraction of the deaminated metabolites.

Endothelin modulates dihydropyridine receptor decreased binding in hippocampal slices from normotensive and spontaneously hypertensive rats.

Previous studies in rats have demonstrated both the link between voltage-operated calcium channels and endothelin and their cerebral involvement in the pathophysiology of spontaneous hypertension. In the present study, the interaction of endothelin with specific dihydropyridine (DHP) binding sites was investigated using the brain slices model. In rat hippocampal slices, pre-incubation with Bay K 8644 decreased [3H] (+) PN 200-110 binding.

Absence of a direct coupling of a G protein to dihydropyridine binding sites in rat heart.

In rat heart membranes, the addition of guanine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), a stable GTP analogue, did not significantly modify the displacement of [3H]PN 200-110 binding by the 1,4-dihydropyridine (DHP) agonist Bay K 8644 and antagonists, nifedipine and nicardipine. These results are in agreement with some previously reported electrophysiological and pharmacological data, and they suggest that there is no direct involvement of a G protein in the modulation of DHP sensitive Ca channels in cardiac cells.

Pressor responses to endothelin-1 in normotensive and spontaneously hypertensive rats.

In freely moving rats, endothelin-1 (0.0135-4.5 nmol/kg) administered as an intravenous bolus injection, produced an immediate, short-lasting, dose-related fall in blood pressure followed by a long-lasting, dose-related increase in blood pressure.

Central 5HT1A-receptor binding in normotensive and spontaneously hypertensive rats.

Central 5HT1A-receptors have been found with a high density in brainstem and are involved in cardiovascular control. The high-affinity binding of [3H]-8-OH-DPAT, a specific 5HT1A-receptor ligand, was measured in medulla oblongata of normotensive and spontaneously hypertensive rats (SHR). The maximal number of [3H]-8-OH-DPAT binding site (Bmax) was significantly increased in SHR when compared to normotensive rats.

Central hypotensive effects of nicardipine in conscious freely moving spontaneously hypertensive rat.

The central cardiovascular effects of the calcium channel blocker nicardipine was studied in conscious freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Nicardipine was administered in a 1.5 microliters volume into the lateral ventricle of the brain (i.

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells.

Nicardipine decreases blood pressure and heart rate at nucleus tractus solitarii of spontaneously hypertensive rats.

The effects of the dihydropyridine (DHP) calcium channel antagonist, nicardipine, on central cardiovascular regulation were investigated by injecting it into the cisterna magna or directly into the nucleus tractus solitarii (NTS), in anesthetized normotensive or spontaneously hypertensive (SHR) rats. Intracisternal injections of nicardipine (1-10 micrograms/kg) dose-dependently decreased blood pressure in SHR; there was no significant change in cardiovascular parameters in normotensive rats. In SHR, nicardipine (100 ng) microinjected bilaterally into the NTS produced hypotension and bradycardia.