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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 343 records · Page 19Linked to original sources
PubMed1986

Chronic treatment with tibalosine in essential hypertension.

UNLABELLED: After a run-in period on placebo, 26 patients with essential hypertension were prescribed single-blind tibalosine, 150 mg daily. On tibalosine their blood pressure decreased from 157/101 to 147/93 mm Hg (p less than 0.001) and their heart rate from 74 to 68 beats per minute (p less than 0.01), while plasma renin activity tended to fall from 0.81 to 0.65 ng/ml/hr (p = 0.06). Twelve patients, maintained on monotherapy with tibalosine for an average of 3.8 months, kept a diastolic pressure below 90 mm Hg. Ten patients, whose diastolic pressure on tibalosine alone remained equal to or higher than 90 mm Hg were continued on this drug for 6.6 months, but were additionally given in a double-blind and randomized way either placebo, or atenolol 100 mg, or chlorthalidone, 50 mg, daily. As compared to tibalosine plus placebo, blood pressure and heart rate decreased further on tibalosine plus atenolol from 148/97 to 140/90 mm Hg (p less than 0.05) and from 70 to 60 beats per minute (p less than 0.05), respectively. The additional blood pressure lowering effect of tibalosine plus chlorthalidone to a level of 143/96 mm Hg was not statistically significant. Eight of 10 patients' blood pressure responded better to tibalosine combined with atenolol than with chlorthalidone. Because of adverse reactions tibalosine was discontinued in 8 of the 26 patients (31%), namely in 4 who prematurely dropped out from the study and in another 4 patients, who remained adherent to the protocol. Somnolence, weary legs and dry mouth were reported more frequently (p less than 0.05) on tibalosine than on placebo. IN CONCLUSION: tibalosine is an effective anti-hypertensive drug, but side effects preclude its clinical use at a daily dose of 150 mg; the combination with a beta-adrenoceptor blocking drug seems therapeutically more effective than with a thiazide.

Adult↗
PubMed1986

Sodium and potassium fluxes and concentrations in erythrocytes of normal subjects during prolonged sodium depletion and repletion.

The erythrocyte concentration and fluxes of sodium and potassium were investigated in normal white male subjects during dietary sodium restriction and repletion, each period lasting for 16 weeks. During dietary sodium restriction the intra-erythrocyte sodium concentration decreased and the red cell ouabain-sensitive 86Rb-uptake increased; no significant changes were observed in the ouabain-insensitive fluxes of sodium such as the total, frusemide-resistant and frusemide-sensitive Na+-efflux and the Na+, Li+-countertransport. The decrease in the intra-erythrocyte sodium concentration could result from an increased Na+,K+-ATPase pump activity. The latter increase could be secondary to the early decrease in a digitalis-like plasma inhibitor and the late increase could be facilitated by the late rise in the intracellular ATP concentration, which is the energy supplier for this pump. During the subsequent first month of sodium repletion the intra-erythrocyte sodium concentration remained low, the red cell ouabain-sensitive 86Rb-uptake and ATP concentration remained elevated and returned to baseline only after 16 weeks. This long-term effect suggests either the involvement of a mechanism which can only be slowly reversible or a mechanism which is irreversible so that normalization takes place only when new red cells are released into the circulation.

Adult↗
PubMed1986

Intraerythrocyte sodium concentration in black families with and without hypertension.

Blood pressure and intraerythrocyte sodium and potassium concentration were investigated in 59 male inhabitants of an urban quarter of Kinshasa, aged 10 years and older. Two subjects were excluded because they were on antihypertensive treatment. Seventeen subjects were normotensive with both parents normotensive (group 1); 9 subjects were normotensive with at least one hypertensive parent (group 2); 5 subjects were untreated hypertensives (group 3) and 26 subjects could not be classified (group 4). Systolic pressure and intraerythrocyte sodium concentration (expressed in mmol/1 cells) were significantly higher in normotensive subjects with a positive family history of hypertension (group 2) than in normotensive males of comparable age, weight and height, born to normotensive parents (group 1). Untreated hypertensives (group 3) were older and their intraerythrocyte sodium concentration was higher in comparison to normotensives without positive family history of hypertension. The intraerythrocyte potassium concentration did not differ significantly among groups 1, 2 and 3. When the first three groups of participants, or all the subjects with the exclusion of treated hypertensives, were considered, no relationship could be demonstrated between the level of blood pressure and the intraerythrocyte sodium and potassium concentration. It can be concluded that parental hypertension in normotensive African blacks is associated with increased intraerythrocyte sodium concentration.

Adolescent↗
PubMed1985

Vesicular stomatitis virus produced from infected LSTRA lymphoma cells bear tyrosine protein kinase activity (p56).

Murine LSTRA lymphoma cells contain a very active tyrosine protein kinase of 56 kDa (p56) which is not related to any of the other known tyrosine kinases. In the past the purification and characterization of the p56 have been hampered because of the low amount of this protein in LSTRA membranes. In this study, we have utilized a different approach for purification which consisted of trapping the protein in the membrane of vesicular stomatitis virus. Incubation of the virions with [gamma-32P]ATP resulted in the phosphorylation of p56 on tyrosine residues. Moreover, the phosphopeptide digest profile of vesicular stomatitis virus-p56 was identical to that observed with authentic LSTRA-p56. The p56 from such virions could be resolved from other proteins by two-dimensional gels, and furthermore, such virions have been used to prepare several antisera directed against the p56.

Amino Acids↗
PubMed1985

Phosphoinositides are not phosphorylated by the very active tyrosine protein kinase from the murine lymphoma LSTRA.

We studied the ability to phosphorylate phosphoinositides by 3 different subcellular preparations, and immunopurified tyrosine protein kinase (TPK) from two murine lymphoma cell lines induced by the Moloney murine leukemia virus: LSTRA with a very active TPK and MBL2 without significant TPK activity. We could not find any difference in the phosphorylation of phosphoinositides by these preparations. The TPK purified with two antibodies which phosphorylate actively tyrosine on exogenous substrate were unable to phosphorylate phosphoinositides.

Animals↗
PubMed1985

Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.

A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.

Actuarial Analysis↗
PubMed1985

Erythrocyte concentrations and transmembrane fluxes of sodium and potassium and biochemical measurements during the menstrual cycle in normal women.

The erythrocyte concentrations and the transmembrane fluxes of sodium and potassium were investigated in 20 normal women during the two stages of the menstrual cycle. Half of the women were using oral contraceptives and the other half were not. In women with a normal menstrual cycle the erythrocyte sodium concentration and the ouabain-insensitive total potassium efflux were lower in the luteal than in the follicular phase. Intracellular potassium concentration, ouabain-sensitive rubidium 86 uptake and the furosemide-sensitive sodium and potassium efflux did not differ significantly between the two periods of the cycle. No cycle-related variation in sodium or potassium intracellular concentration was observed in women using oral contraceptives. In these women, however, the ouabain-sensitive 86Rb uptake was increased in the second part of the menstrual cycle. In each woman with a normal menstrual cycle the plasma progesterone, renin activity, angiotensin II, plasma aldosterone concentration, and urinary aldosterone excretion increased during the luteal phase. The increment in the plasma renin activity, plasma angiotensin II, and plasma and urinary aldosterone indicate a stimulation of the renin-aldosterone axis in this menstrual period. During the same phase, serum cholesterol was decreased significantly. When the women using oral contraceptives were compared to those not using them, the renin-aldosterone axis was already stimulated during the first part of the cycle; no further stimulation occurred during the second part.

Adult↗
PubMed1985

Relationship between plasma renin activity and physical fitness in normal subjects.

The relationship between plasma renin activity (PRA) at rest and physical fitness was studied in 40 normal young subjects on a liberal sodium intake. Plasma renin activity was measured in arterial blood withdrawn at the end of a 30-min period of rest in recumbency, while physical fitness was expressed by the highest oxygen uptake achieved during an uninterrupted graded exercise test performed in the sitting position on an electromagnetically braked ergometer bicycle (peak VO2). Log PRA correlated significantly and inversely with peak VO2 adjusted for body weight (r = -0.34; P less than 0.05) in single regression analysis. Using multiple regression and adjusted peak VO2, age, urinary sodium excretion and mean intra-arterial pressure as independent variables, no combination of two or more independent variables yielded significant partial correlation coefficients with log PRA. This correlation suggests that PRA at rest is inversely related to the subject's physical fitness.

Adult↗
PubMed1985

Carotid baroreflex sensitivity and physical fitness in cycling tourists.

Carotid baroreceptors were stimulated with neck suction in 47 healthy subjects. Pulse interval lengthening was measured and the time course of the response was evaluated. Eight intensities of neck chamber suction were applied to select a criterion for computing the "RR response" that gives a significant linear relationship with the magnitude of the stimuli in the highest number of individuals. The best criterion was the maximal RR prolongation within 5 seconds after the onset of the stimulus. The slope of this relationship was defined as baroreflex sensitivity. The effect of physical fitness on baroreceptor function was investigated in 24 cycling tourists with a wide range of peak oxygen uptake and training characteristics. Baroreflex sensitivity averaged 7.3 +/- 0.8 msec X mm Hg-1 and was not significantly related to age, weight, basal heart rate, peak oxygen uptake and ventilation and other training characteristics. The results suggest that in man the so defined sensitivity of the carotid baroreflex control of heart rate is not influenced by the level of physical fitness and therefore the measurement of these characteristics can be neglected in evaluating baroreflex sensitivity.

Adolescent↗
PubMed1985

Effects of angiotensin II on arterial pressure, renin and aldosterone during exercise.

To evaluate the effect of isotonic exercise on the response to angiotensin II, angiotensin II in saline solution was infused intravenously (7.5 ng X kg-1 X min-1) in seven normal sodium replete male volunteers before, during and after a graded uninterrupted exercise test on the bicycle ergometer until exhaustion. The subjects performed a similar exercise test on another day under randomized conditions when saline solution only was infused. At rest in recumbency angiotensin II infusion increased plasma angiotensin II from 17 to 162 pg X ml-1 (P less than 0.001). When the tests with and without angiotensin II are compared, the difference in plasma angiotensin II throughout the experiment ranged from 86 to 145 pg X ml-1. The difference in mean intra-arterial pressure averaged 17 mmHg at recumbent rest, 12 mmHg in the sitting position, 9 mmHg at 10% of peak work rate and declined progressively throughout the exercise test to become non-significant at the higher levels of activity. Plasma renin activity rose with increasing levels of activity but angiotensin II significantly reduced the increase. Plasma aldosterone, only measured at rest and at peak exercise, was higher during angiotensin II infusion; the difference in plasma aldosterone was significant at rest, but not at peak exercise. In conclusion, the exercise-induced elevation of angiotensin II does not appear to be an important factor in the increase of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of normal men and women.

The intracellular concentration and transmembrane fluxes of sodium and potassium were studied in the red blood cells of normal men and women in the two halves of their menstrual cycle. Compared to men, the intra-erythrocyte sodium concentration was lower in women during the second half of the menstrual cycle. These two groups were similar for Na+, K+-ATPase pump activity estimated from the ouabain-sensitive 86rubidium-uptake and for the furosemide-sensitive sodium and potassium efflux. Women in the first half of the menstrual cycle, had intra-erythrocyte sodium concentration similar to men, but their furosemide-sensitive sodium efflux was lower. A lower intra-erythrocyte sodium concentration was observed in the second half as compared to the first half of the menstrual cycle in women. No significant difference was observed in the intra-erythrocyte potassium concentration and transmembrane fluxes of potassium in men and women in either half of the menstrual cycle. Therefore one should take into account sex-related variability when studying cationic fluxes and concentrations in red blood cells of men and women.

Adult↗
PubMed1985

Familial aggregation of blood pressure, anthropometric characteristics and urinary excretion of sodium and potassium--a population study in two Belgian towns.

Blood pressure and anthropometric characteristics were measured on two separate occasions and the urinary sodium and potassium excretion determined from one 24-hr urine collection in a random population sample (n = 612) of two Belgian towns. After adjusting for confounding factors familial aggregation of these measurements was studied by computing correlation coefficients for the various intrafamilial relationships. Spouses are genetically dissimilar and share a common home environment only from adulthood on. The spouse-spouse correlations for blood pressure, body weight, body mass index and urinary sodium were therefore not significant, whereas the close spouse-spouse correlation for height (r = 0.29) may be explained by assortive marriage. Sibs not only share a common home environment, but also part of their genetic material. Significant sib-sib correlations could therefore be demonstrated for diastolic blood pressure (r = 0.21), height (r = 0.32), body mass index (r = 0.24) and urinary sodium (r = 0.34). For systolic pressure the father-son (r = 0.33) and mother-daughter (r = 0.24) correlations were significant, whereas the other parent-offspring correlations for systolic and diastolic pressure were not statistically different from zero. The tendency of the correlation coefficients for body weight and body mass index to be higher in mother-offspring than in father-offspring pairs suggests a closer maternal role in the determination of calorie intake in offspring. The parent-offspring correlations for urinary sodium were only significant in father-daughter (r = 0.24) and mother-son (r = 0.21) pairs. The fact that potassium, in contrast to sodium, is rarely used as an artificial additive in food preparation may explain why the correlations for urinary potassium were relatively high in all relationship pairs, varying from 0.20 to 0.34.

Adolescent↗
PubMed1985

Acute myeloblastic leukemia with active tyrosine protein kinase.

High level of tyrosine protein kinase activity was found in a membrane fraction isolated from an acute myeloblastic leukemia, out of 24 leukemias of different origin investigated. The major substrate for tyrosine phosphorylation in vitro was a 58 kDA protein (p58). The phosphorylation proceeded actively at 0 degrees C and was strongly stimulated by Mn2+ ions. Comparison by partial proteolysis of the p58 with similar phosphoproteins from a T-lymphoma line (KE37) and from lectin stimulated lymphocytes showed high similarity. The possible role of the tyrosine kinase activity in this leukemia is discussed.

Gastrins↗
PubMed1985

Detection of tyrosine-specific protein kinases with gastrin as exogenous substrate.

Gastrin was recently shown to be phosphorylated on its single tyrosine by the epidermal growth factor (EGF)-stimulated tyrosine protein kinase (TPK). The TPK previously detected in the murine lymphoma (LSTRA) induced by the Moloney murine leukemia virus phosphorylates gastrin, the apparent Km is 65 microM and the maximum rate 1900 pmol/min per mg; the kinase is more efficient with MnCl2 than with MgCl2, is stimulated by NaVO3 and inhibited by ZnCl2. Gastrin phosphorylation is observed only when a TPK is expressed by the cell: extracts of fibroblasts infected with a temperature-sensitive mutant of the Rous sarcoma virus had no gastrin kinase activity when grown at the non-permissive temperature whereas cells grown at the permissive temperature were transformed and disclosed a clear gastrin kinase activity. Gastrin kinases were detected in various transformed cells: human lymphomas, K562 cells, cells from a patient with acute proliferative leukemia, and normal cells: human T and B lymphocytes.

Animals↗
PubMed1985

Effects of ketanserin on the intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of normal male subjects.

The effect of acute and short-term administration of ketanserin on the intracellular concentrations and transmembrane fluxes of sodium and potassium was studied in erythrocytes of 12 sodium-replete normal male subjects. The subjects received 40 mg ketanserin three times a day for 1 week. Blood samples were drawn before and 1.5 h after the first dose, 12 h after the evening dose of the 6th day, and 1.5 h after the morning dose of the 7th day. The intraerythrocyte sodium concentration was not changed after the first dose of ketanserin, but was decreased during short-term treatment with ketanserin. The ouabain-sensitive 86Rb-uptake, an estimate of the Na+,K+-adenosine triphosphatase pump activity, was decreased after acute ketanserin administration, but not during short-term treatment. This change in intraerythrocyte sodium concentration was related to the change in ouabain-sensitive 86Rb-uptake. The red cell Na+,K+-cotransport and Na+,Li+-countertransport transport activity were not changed during acute and short-term administration of ketanserin. These results indicate that short-term ketanserin administration decreases the intraerythrocyte sodium concentration, but the flux measurements can not explain this observation.

Cell Membrane Permeability↗