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Biomedical subjects

P Barbier

Publications and source records attributed to P Barbier.

At least 37 records · Page 2Linked to original sources
PubMed1997

Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80 years old. An echo 2D colour Doppler cooperative study.

In order to find out the normal values and to evaluate the effects of age, heart rate, sex, and haemodynamic and standard echocardiographic parameters on pulmonary venous flow velocity obtained by the transthoracic approach. Doppler pulmonary venous flow parameters were measured in 143 healthy subjects aged from 20 to 80 years. Doppler pulmonary venous flow parameters which had the best correlation with age were: the peak velocity of the systolic wave (r = 0.39) and its integral (r = 0.5), the peak velocity of the diastolic wave (r = -0.6) and its integral (r = -0.44); the systolic (r = 0.68) and diastolic fractions (r = -0.68); the systolic/diastolic peak velocity ratio (r = 0.73) and the systolic/diastolic integral ratio (r = 0.7). The atrial reversal wave did not correlate with age; the atrial reversal wave was more difficult and probably less reliable to measure than the systolic and diastolic waves. The correlations of pulmonary venous flow parameters with mitral flow parameters were also examined. This study showed that, in healthy subjects, despite an increase in the early and atrial waves from the annulus to the tips of the mitral leaflets, there is a similar association between pulmonary venous flow and mitral flow measured at the annulus or at the tips of the mitral leaflets. The intra-observer reproducibility of all the pulmonary venous flow parameters considered were found to be excellent. Moderate inter-observer variability was observed for the systolic, diastolic and atrial reversal wave peak velocities and integrals; however, the systolic/diastolic ratio improved the precision of the measurements. Multivariate analysis showed that age is the principal determinant of the Doppler parameters of pulmonary venous flow: heart rate, sex, body surface area, the size of the left atrium in systole and the left ventricular ejection fraction all influence the Doppler parameters of pulmonary venous flow, even if only slightly.

Adult↗
PubMed1996

Functional role of the third cytoplasmic loop in muscarinic receptor dimerization.

By means of the expression of two chimeric receptors, alpha2/m3 and m3/alpha2, in which the carboxyl-terminal receptor portions, containing transmembrane (TM) domains VI and VII, were exchanged between the alpha2C adrenergic and the m3 muscarinic receptor, Maggio et al. (Maggio, R., Vogel, Z., and Wess, J. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 3103-31073) demonstrated that G protein-linked receptors are able to interact functionally with each other at the molecular level to form (hetero)dimers. In the present study we tested the hypothesis that interaction between receptors might depend on the presence of a long third intracellular (i3) loop and that shortening this loop could impair the capability of receptors to form dimers. To address this question, we initially created short chimeric alpha2 adrenergic/m3 muscarinic receptors in which 196 amino acids were deleted from the i3 loop (alpha2/m3-short and m3/alpha2-short). Although co-transfection of alpha2/m3 and m3/alpha2 resulted in the appearance of specific binding, the co-expression of the two short constructs (alpha2/m3-short and m3/alpha2-short), either together or in combination, respectively, with m3/alpha2 and alpha2/m3 did not result in any detectable binding activity. In another set of experiments, a mutant m3 receptor, m3/m2(16aa), containing 16 amino acids of the m2 receptor sequence at the amino terminus of the third cytoplasmic loop, which was capable of binding muscarinic ligands but was virtually unable to stimulate phosphatidylinositol hydrolysis, was also mutated in the i3 loop, resulting in the m3/m2(16aa)-short receptor. Although co-transfection of m3/m2(16aa) with a truncated form of the m3 receptor (m3-trunc, containing an in frame stop codon after amino acid codon 272 of the rat m3 sequence) resulted in a considerable carbachol-stimulated phosphatidylinositol breakdown, the co-transfection of m3/m2(16aa)-short with the truncated form of the m3 receptor did not result in any recovery of the functional activity. Thus, these data suggest that intermolecular interaction between muscarinic receptors, involving the exchange of amino-terminal (containing TM domains I-V) and carboxyl-terminal (containing TM domains VI and VII) receptor fragments depends on the presence of a long i3 loop. One may speculate that when alternative forms of receptors with a different length of the i3 loop exist, they could have a different propensity to dimerize.

Animals↗
PubMed1996

Kinetics of association and dissociation of two enantiomers, NSC 613863 (R)-(+) and NSC 613862 (S)-(-) (CI 980), to tubulin.

The kinetics of binding of R- and S-enantiomers were studied by the fluorescence stopped-flow technique. For the R-enantiomer, the time course of the increase in fluorescence is best fitted by a sum of two exponentials. In pseudo-first-order conditions, the first observed rate constant showed a linear concentration dependence whereas the second showed a hyperbolic one. The dissociation rate constants were determined independently by displacement experiments with 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC). The two exponential phases were assumed to be due to a two-step binding mechanism: an initial binding followed by a conformational change. This is different from colchicine and MTC binding, where the two phases show a hyperbolic concentration dependence and are attributed to the parallel binding to different isoforms of tubulin [Banerjee, A., & Luduena, R. F. (1992) J. Biol. Chem. 267, 13335-13339]. R-isomer binding did not discriminate between the tubulin isoforms. The temperature dependence of all the rate constants were measured, and the entire thermodynamic reaction path was constructed. For the S-isomer, the direct fluorescence stopped-flow study showed that the signals were largely imputable to the fluorescence of the binding at low-affinity sites [Leynadier, D., Peyrot, V., Sarrazin, M., Briand, C., Andreu, J. M., Rener, G. A., & Temple, C., Jr. (1993) Biochemistry 32, 10674-10682]. Therefore, we exploited the competition between R- and S-isomers to determine the binding kinetics of the S-isomer to the R-site. The observed rate constants for competitive binding showed a linear concentration dependence, thus allowing us to calculate the association rate constant of the S-isomer to the R-site. The kinetics of displacement of the S-isomer by MTC allowed the dissociation rate constant for the S-isomer to be determined. The binding of both enantiomers to tubulin in presence of tropolone methyl ether (analog of the colchicine C ring) was decreased, indicating the involvement of the C subsite.

Animals↗
PubMed1996

Intraoperative multiplane vs biplane transesophageal echocardiography for the assessment of cardiac surgery.

This study was undertaken to test whether multiplane transesophageal echocardiography (TEE) offers advantages in comparison with biplane TEE in the intraoperative monitoring during cardiac surgery. A diagnostic multiplane TEE was performed in 400 patients in the immediate preoperative and postoperative periods. We systematically acquired cardiac images from the gastric fundus, lower esophagus, and upper esophagus; complete views of the descending aorta were also recorded. Usefulness of the different views in providing essential additional clinical information compared with exclusive transverse (0 to 20 degrees) and longitudinal (70 to 110 degrees) planes of the biplane TTE was assessed assuming that with manipulation of a biplane probe, a 20 degrees are could be added to the conventional horizontal and vertical planes. A high success rate of each view was demonstrated; anatomy and pathologic condition were best visualized in oblique planes. The method proved to be particularly useful in the preoperative and postoperative phases of aortic dissection (27 cases), aortic (65 cases) and mitral (35 cases) valve replacement, mitral valve repair (38 cases), left ventricular aneurysmectomy (25 cases), bleeding from proximal suture of an aortic heterograft (2 cases), and positioning of left ventricular hemopump (2 cases). Additional regional wall motion abnormalities of the right (four cases) and left ventricle (six cases) not appreciated in 0 to 20 degrees or 70 to 110 degrees planes were detected. Multiplane TEE is a useful clinical tool during intraoperative monitoring of cardiac surgery. Most structures of the heart and great vessels lie on oblique planes, while other views are optimized with the aid of slight angle corrections. This method improves the evaluation of anatomy and pathologic condition of the heart and great vessels, of native and prosthetic valves, and of left and right ventricular function.

Adolescent↗
PubMed1995

Differential effects of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate analogs modified at position C2 on tubulin polymerization, binding, and conformational changes.

NSC 613863 (R)-(+) and NSC 613862 (S)-(-) (CI980) are two chiral isomers of ethyl 5-amino 2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate which have potent antitubulin activity. The S-isomer is a more potent antimitotic compound than the R-isomer, and the two isomers differ markedly in binding to tubulin [Leynadier, D., Peyrot, V., Sarrazin, M., Briand, C., Andreu, J. M., Rener, G. A., & Temple, C., Jr. (1993) Biochemistry 32, 10675-10682]. To understand the origin of such differences, we studied the interactions of three R- and S-isomer structural analogs which differ in C2 (the chiral carbon), i.e., C179, NSC 337238, and NSC 330770. C179 is a methylated dehydrogenated achiral compound. It bound to tubulin with an apparent affinity Ka of (2.29 +/- 0.17) x 10(4) M-1, inhibited tubulin polymerization in vitro at a half-inhibitory concentration (IC50) of 100 microM, and presented no GTPase activity. The substitution of -CH3 by -H leads to the NSC 337238 compound. It bound to tubulin with a higher affinity [Ka = (2.62 +/- 0.35) x 10(5) M-1] and inhibited tubulin polymerization at a lower concentration (IC50 = 14 microM). It presented no GTPase activity and induced the formation of abnormal polymers at a protein critical concentration (Cr) of 2 mg mL-1. NSC 330770, a demethylated hydrogenated molecule, interacted strongly with tubulin [Ka = (3.30 +/- 0.56) x 10(6) M-1].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Stereoselective inhibition of muscarinic receptor subtypes by the eight stereoisomers related to rociverine.

The chemical structure corresponding to 1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(diethylamino)-1-methylethyl ester has the classical profile of ester-type antimuscarinic drugs. The presence of three chiral carbons leads to eight stereoisomers and the substitutions on the cyclohexyl ring generate cis-isomers (1, named rociverine) and trans-isomers (2). The aim of this study was to determine the binding pattern of the eight stereoisomers and two derived compounds, (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(dimethylamino)-1-ethyl ester (3) (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid (S)-2-(diethylamino)-1-methylethyl ester methyl iodide (4), at the five cloned muscarinic receptors stably expressed in chinese hamster ovary cells, in order to define how stereochemical modifications could affect the affinity. Our data showed that cis-stereoisomers exhibited higher variations in affinity than trans-stereoisomers. Among the cis-stereoisomers, those with the (1R,2R) configuration showed considerably higher affinities (up to 240-fold) than those with the (1S,2S) configuration. The (1S,2S) configuration was important for binding selectivity; this was confirmed also by the use of the two additional compounds.

Animals↗
PubMed1995

Inhibition of nitric oxide synthase dramatically potentiates seizures induced by kainic acid and pilocarpine in rats.

We investigated whether the severity of convulsions evoked by kainic acid and pilocarpine is modified in nitric oxide synthase inhibitor-treated rats. We found that chronic treatment (4 days) with NW-nitro-L-arginine greatly potentiates seizures induced by both convulsants suggesting a potential role for nitric oxide in mechanisms regulating seizure induction and propagation.

Amino Acid Oxidoreductases↗
PubMed1995

Sodium nitroprusside induces internalization of muscarinic receptors stably expressed in Chinese hamster ovary cell lines.

We have characterized the internalization of muscarinic acetylcholine receptors induced by the nitric oxide (NO)-generating compound sodium nitroprusside. When Chinese hamster ovary cells, stably transfected with the human m4 muscarinic receptor subtype, were incubated for 1 h in the presence of 700 microM sodium nitroprusside, the number of receptors measured in intact cells with the hydrophilic ligand N-[3H]methylscopolamine was reduced by 30%. The effect was dose dependent, beginning with a concentration of sodium nitroprusside as low as 45 microM. Removal of sodium nitroprusside from the incubation medium did not result in a recovery of the binding sites. The phenomenon was temperature dependent and was blocked by the muscarinic antagonist atropine. No receptor diminution was detected when the number of binding sites was evaluated with the lipophilic antagonist [3H]quinuclidinyl benzilate. This indicates that sodium nitroprusside induces a redistribution of the muscarinic receptors between the plasma membrane and an internal compartment of the cell. Receptor loss was readily reversed by treatment with the sulfhydryl reducing agent diethyldithiocarbamate. Our data provide evidence that muscarinic receptors are internalized by sodium nitroprusside through the oxidation of sulfhydryl groups; they also suggest that NO could play a role in muscarinic receptor desensitization.

Animals↗
PubMed1995

Severe left ventricular dynamic outflow tract gradient secondary to localized septal hypertrophy and concomitant acute ischaemic parietal dyssynergy.

Localized basal septal hypertrophy (LSH) is usually an incidental echocardiographic finding and, as opposed to asymmetric hypertrophic cardiomyopathy (AHC), is of no clinical significance. We report a case of a patient with LSH who developed a severe left ventricular outflow gradient during acute myocardial ischaemia, apical akinesis and compensatory hyperkinesis of basal parietal segments.

Acute Disease↗
PubMed1995

Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old.

Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.

Adult↗
PubMed1995

Coronary flow and left ventricular diastolic function in aortic regurgitation.

BACKGROUND: An abnormal coronary perfusion pressure is probably the major determinant of altered myocardial perfusion in aortic regurgitation; ventricular hypertrophy and diastolic function may also be involved. This study was undertaken to investigate the respective roles of these two variables. METHODS: Using multiplane transesophageal echocardiography, we evaluated the coronary Doppler flow velocity in the proximal left anterior descending coronary artery in 15 patients with aortic regurgitation before and immediately after valve replacement. The ratios of diastolic:systolic velocity integral and early:late diastolic velocity integral were correlated against coronary perfusion pressure, pulmonary wedge pressure and Doppler echocardiographic indices of left ventricular diastolic function. Patients were compared with 10 subjects without valvular diseases. RESULTS: Aortic regurgitation was associated with a reduction of the coronary diastolic:systolic velocity integral ratio and increment in the early:late diastolic velocity integral ratio. The latter correlated positively with early:late diastolic ratio of mitral flow velocity, pulmonary wedge pressure and left ventricular mass index. Soon after valve replacement, a decrease in pulmonary wedge pressure and a rise in coronary perfusion pressure were seen. Both the echo-Doppler parameters related to diastolic function and the systodiastolic distribution of coronary flow returned to normal. This indicates that diastolic dysfunction rather than left ventricular mass may be related to a disordered myocardial perfusion. CONCLUSIONS: In aortic regurgitation, a relationship exists between diastolic ventricular function and coronary flow phasic distribution. Valve replacement improves the former and normalizes the latter. Echo-Doppler parameters of diastolic dysfunction identify patients with worse coronary perfusion and might represent an additional criterion in the preoperative evaluation of patients with aortic regurgitation.

Adult↗
PubMed1995

[Circulatory support with Hemopump in cardiogenic shock secondary to papillary muscle rupture].

A 71-year-old woman submitted to multiple coronary artery bypass grafts suddenly developed in the third postoperatory day cardiogenic shock. Transesophageal echocardiography examination and color Doppler showed prolapse of the anterior mitral valve leaflet and detached anterolateral papillary muscle in the left atrial cavity with severe mitral valve regurgitation and increased left ventricular wall kynesis. Maximal inotropic and vasodilator support was not effective and a mechanical circulatory assistance was deemed necessary awaiting for mitral valve replacement not performed on emergency for unavailability of operatory rooms. Hemopump pump-cannula assembly was introduced through a femoral graft and the cannula was advanced in the aorta and positioned in the left ventricle across the aortic valve. Pump rate was set at the maximal speed and as an immediate result, mean arterial pressure increased and mean pulmonary pressure decreased. Global cardiac output during 190 min of assistance was 3.48 l/min at a mean arterial pressure of 81 mmHg. The Hemopump provided 3 l/min of flow with an effective left ventricle unloading. The patient subsequently underwent mitral valve replacement and her postoperative outcome was uneventful and free from complications.

Aged↗
PubMed1995

Apomorphine continuous stimulation in Parkinson's disease: receptor desensitization as a possible mechanism of reduced motor response.

Apomorphine is a potent nonselective agonist at D1 and D2 dopamine receptors. The utility of apomorphine in Parkinson's disease (PD) is well asserted but its clinical use is reduced because of its short half-life and numerous side-effects. The disabling "on-off" fluctuations are among the most frequent and troublesome complications of chronic levodopa therapy in PD. Apomorphine is effective to reverse refractory L-dopa induced "off" periods, but a reduced motor response after repeated administrations has also been described with this drug. The loss of response to apomorphine, when the drug is administered repeatedly, is well fitted by the processes of receptor phosphorylation and down regulation. Elucidation of the molecular bases of dopaminergic receptors desensitization may lead to a better understanding of the mechanisms of dopaminergic regulation, and to a more appropriate treatment of PD.

Antiparkinson Agents↗
PubMed1994

Binding profile of the selective muscarinic receptor antagonist tripitramine.

The binding selectivity of the muscarinic antagonist tripitramine has been tested on the five cloned human muscarinic receptor subtypes (Hm1 to Hm5) expressed in chinese hamster ovary (CHO-K1) cells. The results indicate that tripitramine binds to the muscarinic Hm2 receptor with a Ki value of 0.27 +/- 0.02 nM. Tripitramine distinguishes Hm2 vs. Hm4 by a factor of 24 and vs. Hm3 and Hm5 by a factor of 142 and 125, respectively. A lower affinity ratio, about 6-fold, was found between muscarinic Hm2 and Hm1 receptors. A comparative study with the well-known selective muscarinic M2 receptor antagonist methoctramine indicates that tripitramine has gained both potency and selectivity for the muscarinic Hm2 receptor subtype.

Animals↗
PubMed1994

Left atrial function and ventricular filling in hypertensive patients with paroxysmal atrial fibrillation.

OBJECTIVES: We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation. BACKGROUND: In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias. METHODS: Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender. RESULTS: The EH and EHf groups had similar systolic arterial pressures ([mean +/- SD] group EH 185 +/- 27, group EHf 173 +/- 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 +/- 55, group EHf 131 +/- 57.8 g/m2, p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 +/- 6, group EH 37.9 +/- 4.6, group EHf 44.6 +/- 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 +/- 3.6, group EH 34.5 +/- 5, group EHf 40.4 +/- 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 +/- 4.4%, group EH 14.6 +/- 5.5%, group EHf 9.3 +/- 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals x mitral annulus area) was lower than normal in group EH (group N 2.9 +/- 2.2, group EH 1.75 +/- 0.8, group EHf 2.8 +/- 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was "normalized" in group EHf, early flow being increased in this group (group N 42 +/- 13, group EH 39 +/- 29, group EHf 60 +/- 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). CONCLUSIONS: These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and "normalization" of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined.

Aged↗