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P Ferraris

Publications and source records attributed to P Ferraris.

8 recordsLinked to original sources

beta1-integrin cytoplasmic subdomains involved in dominant negative function.

The beta1-integrin cytoplasmic domain consists of a membrane proximal subdomain common to the four known isoforms ("common" region) and a distal subdomain specific for each isoform ("variable" region). To investigate in detail the role of these subdomains in integrin-dependent cellular functions, we used beta1A and beta1B isoforms as well as four mutants lacking the entire cytoplasmic domain (beta1TR), the variable region (beta1COM), or the common region (beta1 deltaCOM-B and beta1 deltaCOM-A). By expressing these constructs in Chinese hamster ovary and beta1 integrin-deficient GD25 cells (Wennerberg et al., J Cell Biol 132, 227-238, 1996), we show that beta1B, beta1COM, beta1 deltaCOM-B, and beta1 deltaCOM-A molecules are unable to support efficient cell adhesion to matrix proteins. On exposure to Mn++ ions, however, beta1B, but none of the mutants, can mediate cell adhesion, indicating specific functional properties of this isoform. Analysis of adhesive functions of transfected cells shows that beta1B interferes in a dominant negative manner with beta1A and beta3/beta5 integrins in cell spreading, focal adhesion formation, focal adhesion kinase tyrosine phosphorylation, and fibronectin matrix assembly. None of the beta1 mutants tested shows this property, indicating that the dominant negative effect depends on the specific combination of common and B subdomains, rather than from the absence of the A subdomain in the beta1B isoform.

Actinin↗

Tilt test results in young and elderly patients with syncope of unknown origin.

The effects of aging on the results of prolonged drug-free tilt testing were studied in 175 consecutive patients with unexplained syncope divided into 3 groups: 59 patients < 40 years old; 57 patients between 40 and 60 years; and 59 patients > 60 years old. Tilt-induced vaso-vagal syncope occurred respectively in 17 (29%), 20 (35%), and 18 patients (31%) in the 3 age groups. Vasodepressor, mixed, and cardioinhibitory vaso-vagal syncope occurred similarly in the 3 groups; organic heart disease and systemic hypertension were more frequent in elderly patients without affecting the incidence of tilt-induced syncope. Blood pressure and heart rate variations during syncope were similar in the 3 age groups; in the first 20 minutes of tilt testing, before the appearance of the vaso-vagal reflex, elderly patients showed greater reduction in blood pressure and smaller increase in heart rate than younger patients. Our data indicate that increasing age determines a different blood pressure and heart rate behavior during tilt testing, but apparently does not influence the incidence of vaso-vagal syncope in patients with syncope of undetermined etiology. As the proportion of patients with a positive isoproterenol tilt test was reported to decline with age, our results suggest that the reduced incidence of syncope during isoproterenol tilt testing could be the expression of impaired autonomic response among elderly syncope patients.

Adult↗

Plasma active and inactive renin and fetal complications in women with high risk pregnancies.

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.

Adult↗

Time-course of the changes in blood pressure and in plasma renin activity during the first week after dilation of renal artery stenosis.

We measured arterial pressure and plasma renin activity throughout the first week after a technically successful percutaneous transluminal renal angioplasty (PTRA) in 12 patients with hypertension and unilateral renal artery stenosis. Mean arterial pressure fell from 126 +/- 4 to 105 +/- 3 mmHg within 1-2 days of PTRA and stabilized thereafter; in addition, plasma renin activity decreased sharply during the first 2 days after the angioplasty (from 5.2 +/- 2.3 to 1.3 +/- 0.3 ng/ml per h) but continued to decline, reaching 0.8 +/- 0.2 ng/ml per h at the end of the study. When the antihypertensive effect of PTRA was examined in relation to baseline values of plasma renin activity, the patients with low, intermediate and high plasma renin activity showed percentage decreases in mean arterial pressure of, respectively, 6%, 16% and 19% by the sixth day of observation after the angioplasty. No overall correlation was found between the changes in arterial pressure and those in plasma renin activity induced by PTRA. These data suggest that the beneficial effect of PTRA on blood pressure can be estimated within a few days and that the reduction in the activity of the renin system is the principal but not the sole mechanism responsible for it.

Adult↗

Dopaminergic control of aldosterone secretion is not mediated by atrial natriuretic factor in patients with essential hypertension.

Both dopamine and atrial natriuretic factor (ANF) are known to suppress aldosterone secretion. Since it is possible that dopaminergic mechanisms facilitate ANF release, we investigated the relationship between these two inhibitory systems by comparing the increases in aldosterone induced by metoclopramide, a dopaminergic antagonist, with decreases in ANF. Aldosterone, ANF, prolactin, plasma renin activity, cortisol and potassium were measured before and after the intravenous injection of 10 mg metoclopramide, blood samples being collected at 15-min intervals up to 2 h after the injection. These studies were performed in patients with essential hypertension who were maintained on a constant sodium intake (100 mmol/day), before and after 5 days of treatment with ibopamine, an orally active dopamine analogue. Before ibopamine metoclopramide induced the expected, marked increases in aldosterone and in prolactin, but only minimal, non-significant decreases in ANF. All other humoral parameters, as well as blood pressure and heart rate, were unaffected by metoclopramide. After ibopamine treatment, which caused a transient natriuretic effect, the responses of aldosterone and of ANF to metoclopramide were similar to those observed in control studies, whereas that of prolactin was enhanced. Thus, it appears that the suppressive effect exerted by the dopaminergic tone on aldosterone secretion is independent of ANF both before and after dopaminergic stimulation.

Aldosterone↗