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Biomedical subjects

D Choquet

Publications and source records attributed to D Choquet.

At least 55 records · Page 3Linked to original sources

Ion channel blockers inhibit B cell activation at a precise stage of the G1 phase of the cell cycle. Possible involvement of K+ channels.

Lymphocytes express voltage-activated K+ channels in their membrane. Combining the patch-clamp techniques of recording with immunological methods, we have analyzed the expression and the involvement of these channels during defined steps of LPS-induced B cell activation. We show that the number of K+ channels increased strongly when B cells entered in the G1 phase of the cell cycle. The involvement of ion channels in B cell proliferation was assessed using channel blockers that inhibit the K+ current. It was first found that TEA, but not TMA, quinine and verapamil totally suppressed both K+ current and DNA synthesis by stimulated lymphocytes as measured by [3H]TdR uptake or propiedium iodide staining. The drugs affected neither the induction by LPS of activation markers such as Ag of the murine class II MHC and type II receptor for the Fc region of IgG nor the initial cell enlargement that occur early during activation. These data indicate that functional K+ channels are not essential for the transition from the G0 to the G1 phases. In contrast, the same channel antagonists blocked the induction of transferrin receptor expression, characteristic of the final stages of G1. These drugs acted on cells already in G1, because their addition 30 h after LPS still suppressed DNA synthesis, and because they inhibited the proliferation of purified B cell blasts. The effect of tetraethylammonium was reversible, a lag period of 12 h occurring before the cells start DNA synthesis after drug removal. Taken together, these data demonstrate that the proliferation of LPS-stimulated B cells requires functional ion channels at a critical period in the G1 phase, taking place before transferrin receptor expression and the entry into the S phase. The involvement of voltage dependent K+ channels at this particular point is suggested by the parallel effects of the drugs used on K+ currents and DNA synthesis.

4-Aminopyridine↗

Ion channels and B cell mitogenesis.

Given the presence of ionic channels at the membrane of lymphocytes, we have analyzed the effect of various channels blockers on B lymphocytes activation. TEA and 4-AP, two K+ channels blockers, quinine, a blocker of Ca2(+)-activated K+ channels, nickel and verapamil, two Ca2+ channels blockers, all inhibited LPS-induced B cell proliferation. However, these drugs neither inhibited the induction of Ia and Fc gamma RII expression nor cell enlargement and early RNA synthesis, indicating that the entry of B lymphocytes into G1 phase was not affected. In contrast, both late RNA synthesis and the induction of the TfR, which occur while the cell progress through G1, were inhibited by these blockers. These data show that TEA, quinine and verapamil block B lymphocyte activation during the G1 phase, probably between G1A and G1B. To question whether these effects were due to the block of voltage-activated K+ channels, we compared the ability of TEA, quinine, verapamil, 4-AP and nickel to block proliferation and K+ channels. A striking correlation was found for all the drugs but less for 4-AP. Moreover, TMA, a TEA analog unable to block K+ currents, did not affect B cell proliferation. Taken together, our data suggests that functional voltage-gated K+ channels are required at a precise stage of the G1 phase of the B cell cycle.

Animals↗

[Mid-term results of 50 percutaneous aortic valvuloplasties. Follow-up studies using Doppler echocardiography].

The aim of this study was to assess the results of percutaneous aortic valvuloplasty in 50 patients (29 men and 21 women, mean age 74 years) at 6 months by Doppler echocardiography performed 24 hours before, 24 hours, 3 and 6 months after the procedure. The following parameters were compared: maximum instantaneous transaortic pressure gradient; mean gradient; aortic valve area and index of valve patency. The initial results of catheterisation and valvuloplasty were very satisfactory as the peak-to-peak and mean pressure gradients decreased by 50 per cent and the aortic valve area increased from 0.55 +/- 0.2 to 0.83 +/- 0.30 cm2 and the success rate defined as a final surface area greater than 0.75 cm2 was 84 per cent. Unfortunately, these favourable results were not sustained in most cases: restenosis, defined as a valve area of less than 0.7 cm2, was observed in 18 per cent of patients at Day 1 and 71 per cent of patients at the 6th month; the natural history of disease was little affected with a global mortality rate at 6 months of 18 per cent through cardiac failure and sudden death; only 18 per cent of patients maintained an aortic valve area of over 0.75 cm2 at 6 months. These results suggest that percutaneous aortic valvuloplasty should be reserved for patients in whom surgery is formally contra-indicated.

Aged↗

[Echodoppler evaluation of the normally functioning Saint-Jude's aortic valve prosthesis].

The aims of this study were: to define Doppler echocardiographic criteria of normality of aortic St Jude Medical (SJM) valve prostheses with respect to their size and to verify the validity of the continuity equation in the determination of prosthetic valve functional surface area. Forty patients with apparently normally functioning SJM prostheses without other cardiac disease were investigated at least one month after surgery. The group consisted in 1 n. 19, 6 n. 21, 9 n. 23, 12 n. 25 and 12 n. 27 SJM prostheses. The following parameters were measured: the maximum transprosthetic velocity, maximum and mean transprosthetic pressure gradients, permeability index and the Doppler surface area calculated by the continuity equation using the method proposed by Skjaerpe. The global results were as follows: maximum velocity = 2.5 +/- 0.4 m/s (1.8-3.7 m/s); maximum gradient = 26.9 +/- 9.8 mmHg (14-53 mmHg); mean gradient = 13.7 +/- 5.6 mmHg (7-30 mmHg); permeability index = 0.41 +/- 0.09 (0.23-0.57); Doppler surface area = 1.89 +/- 0.66 cm2 (0.73-3.23 cm2). When the prostheses were considered according to their sizes a weak negative correlation was observed between the mean pressure gradients and the size of the prostheses: r = -0.43, p less than 0.05 and a positive correlation between Doppler surface area and the theoretical prosthetic surface area: r = 0.71, p less than 0.005; SD = 0.45 cm2. No significant differences were observed between the pressure gradients and velocities of each size of prosthesis except when sizes 21 + 23 were compared with the large sizes (n. 25 + 27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Doppler echocardiographic study of mitral and aortic flow at various rates and atrioventricular intervals in patients with dual chamber pacemakers].

The aim of this study was to measure the changes in mitral and aortic blood flow induced by rate changes and different atrioventricular intervals in dual chamber pacemaker patients. Ten totally pacemaker dependant patients were studied under basal conditions, in double atrial and ventricular stimulation mode, by pulsed Doppler recordings of mitral and aortic flow, at three different pacing rates (80, 100 and 120/mn) and with three different atrioventricular intervals at each rate (short, 90 or 115 ms; medium, 165 or 190 ms; and long, 240 ms). The increase in pacing rate and prolongation of the atrioventricular interval significantly shortened the duration of mitral flow. Increasing the pacing rate induced a significant fall in stroke volume measured from the aortic flow. The optimal atrioventricular interval tended to shorten when the pacing rate was increased; a long atrioventricular interval had a deleterious effect on stroke volume compared with medium and short atrioventricular intervals; however, the difference between the short and medium atrioventricular intervals was not statistically significant even at 120 mn. These observations emphasise the hemodynamic advantages of shortening of the atrioventricular interval of dual chamber pacemakers when the pacing rate increases.

Aged↗

Fc gamma RII expression in resting and activated B lymphocytes.

In this report, we analyze the expression of the type II receptor for the Fc region of IgG (Fc gamma RII) in resting and lipopolysaccharide (LPS)-activated murine B lymphocytes. Fc gamma RII is encoded by two genes, alpha and beta. The beta gene encodes two mRNA, beta 1 and beta 2, which are generated by alternative splicing. Using an S1 nuclease protection assay, we found that resting and activated B lymphocytes express predominantly the beta 1 transcript. Very low levels of the beta 2 mRNA were detected in this assay, while no expression of the alpha transcript could be detected. Quantitative Northern blot analysis showed that the amount of Fc gamma RII beta mRNA was increased 9-fold in LPS-activated B lymphocytes. The expression of Fc gamma RII during the various phases of B cell activation was then studied by immunofluorescence using the monoclonal antibody 2.4G2. LPS stimulation induced an increase of the Fc gamma RII cellular pool as well as of its expression at the surface of B lymphocytes. The rise in Fc gamma RII surface expression occurred after the induction of class II antigens (Ia) and before transferrin receptor induction. Fc gamma RII expression was found to be enhanced during the G1 phase of the cell cycle since (a) only large cells (i.e. those that had entered the G1 phase) expressed an increased amount of Fc gamma RII and (b) blocking the entry of activated cells into the S phase (with the ion channel blocker quinine) did not affect the Fc gamma RII induction by LPS. Furthermore, only B cell activators that induced cells to enter into G1 [LPS and F(ab')2 anti-IgM antibodies, but not interleukin 4] caused an increase in the expression of Fc gamma RII. These results show that the increase in the membrane expression of Fc gamma RII occurs during the early G1 phase, establishing it as a marker for the entry of B lymphocytes into the cell cycle.

Animals↗

[[Doppler echocardiography in the diagnosis of tri-atrial heart in adults].

The authors report a case of isolated and well tolerated cor triatriatum in a 38-year old man without significant history admitted for aetiological diagnosis of atrial fibrillation. Echocardiography displayed the left intra-atrial septum and the openings of the 4 pulmonary veins in the proximal chamber, but there was no evidence of associated anomaly. Colour-coded doppler examination visualized a single systolo-diastolic trans-septal jet. As the maximum velocity of the jet at pulsed doppler velocimetry was 1.1 m/s, the maximum instantaneous gradient could be estimated at 5 mmHg. The mean gradient was estimated at 2.6 mmHg, which showed that the ostium caused little stenosis. All these data were confirmed by cardiac catheterization. Since the malformation was well tolerated, both functionally and haemodynamically, it was decided not to operate.

Adult↗

Does beta-alanine activate more than one chloride channel associated receptor?

In order to define which receptor-channel complexes are activated by beta-alanine, we performed cross-desensitization experiments between this amino acid and the classical inhibitory neurotransmitters, glycine and gamma-aminobutyric acid (GABA), all of which increase chloride conductances. Using the whole-cell patch-clamp technique and cultured chick spinal neurons, we found that beta-alanine completely desensitizes the glycine response, and only partially reduces GABA evoked currents. No interaction occurred between GABA and glycine at the level of their respective receptors. Conversely, both GABA and glycine reduced the beta-alanine response. These results indicate that beta-alanine activates the glycine receptor, and also suggest that it could be a partial agonist of GABAA receptor(s).

Alanine↗

Dual effects of serotonin on a voltage-gated conductance in lymphocytes.

The effects of serotonin (5-HT), a well-known immunomodulator and neurotransmitter, on the ionic permeability of a pre-B lymphocyte cell line was investigated with the whole-cell patch-clamp technique. We found that physiological doses of this biogenic amine regulate a voltage-gated potassium channel by activating different subsets of receptors. More specifically, 5-HT induces in the recorded cells (i) increase in the maximum potassium conductance, which is due to activation of 5-HT1-like receptors, and (ii) acceleration of the inactivation process that is under the control of 5-HT3 receptors and, accordingly, is mimicked by the 5-HT3 agonist, 2-methyl-5-HT; involvement of those two distinct categories of receptors was demonstrated by using specific antagonists that block predominantly one or the other of these two actions. These two results show that hormones can affect lymphocyte physiology through modulation of their ionic conductances in a way that might help explain some of the diverse effects of 5-HT on neuronal cells.

Abelson murine leukemia virus↗

[Asymptomatic and transitory electrocardiographic changes in the 24 hours following coronary transluminal angioplasty].

Fifty patients underwent a 24-hour Holter system recording immediately after successful coronary angioplasty. Only those patients who had been "successfully" dilated and who, during the following 2 days, had remained totally symptomless and without changes in standard ECG were selected. Arrhythmias occurred in 18 patients: 12 had supraventricular arrhythmia, including 3 prolonged attacks of tachyarrhythmia due to atrial fibrillation; 6 had ventricular arrhythmia, with numerous extrasystoles in 5 cases and bursts of ventricular tachycardia in 1 case. Changes in ventricular repolarization were recorded as: (1) isolated T-wave modification (11 patients), and (2) ST-segment depression (11 patients) reaching or exceeding 2 mn in 5 cases and lasting from 4 to 33 minutes. These silent and transient electrical abnormalities were observed mostly during the 12 hours which followed transluminal angioplasty, and particularly after dilatation of the right coronary artery. The physiopathological mechanisms of these changes are uncertain, but their occurrence has no influence on mid-term results, i.e. the follow-up coronary arteriography at 6 months.

Adult↗

[Echo-Doppler diagnosis of mitral stenoses].

The Doppler spectrum diagnosis of mitral stenosis includes two stages: positive diagnosis and diagnosis of gravity. The positive diagnosis rests on the increase of the maximal velocity of the transmitral flow, the persistence of this acceleration during the entire diastole with decrease of the deceleration gradient, more marked when the stenosis is narrower, and the enlargement of the spectrum. The diagnosis of gravity rests on the measurement of the mean gradient by applying Bernouilli's equation and the point by point quadratic transformation of the transmitral velocity curve obtained by Doppler and the measurement of the mitral area either by measurement of the half-decrease time in pressure or by applying the continuity equation. This last method advocated by Nakatani is particularly interesting in case or significant aortic insufficiency which often invalidates the application of T1/2.

Echocardiography, Doppler↗

[Evaluation by Doppler ultrasound of the severity of aortic stenoses. Application of the continuity equation].

In order to assess the validity of the continuity equation applied to doppler ultrasound in the evaluation of stenotic aortic valve areas, the authors have compared the results obtained in 24 patients examined by catheterization and doppler-echocardiography. In addition, 10 patients who underwent aortic dilatation also had both types of examination, which brings up to 34 the number of comparisons. In haemodynamics, the Gorlin formula was taken as reference for valve area measurement. The doppler-echocardiographic examination, performed 48 hours before, and sometimes after catheterization, recorded sub- and trans-stenotic pressures and outflow tract diameter for application of the continuity equation. Aortic valve areas calculated from doppler data on mean velocities correlated well with areas calculated from haemodynamic data (r = 0.88, p less than 0.001, e = 14 mm2, n = 34). Correlation was even closer when maximum velocities were used (r = 0.96, p less than 0.001, e = 8 mm2, n = 34). When only tight aortic stenoses with a less than 0.75 cm2 area were considered, the correlation remained very good (r = 0.87, p less than 0.001, e = 6 mm2, n = 34). This study therefore demonstrates the reliability of the continuity equation and of the simplified method using maximum sub- and trans-stenotic pressures without having recourse to planimetry. The accuracy of the method is dependent upon 3 parameters: 1. A maximum velocity jet must be obtained, which in turn depends on the investigator's experience and on the sensitivity of the equipment. 2. The velocity recorded by pulsed doppler ultrasound must be "representative" of flow in the outflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Value of the continuous Doppler in the evaluation of gradients of aortic valvular stenosis in the adult].

The purpose of this study, performed in 80 patients with aortic valve stenosis, was to find out whether continuous wave doppler ultrasound was reliable in assessing the severity of the stenosis. Maximum mean and instantaneous transaortic pressure gradients obtained by continuous wave doppler were compared with maximum mean instantaneous and peak to peak gradients simultaneously obtained by cardiac catheterization. 35 patients who underwent aortic valve dilation were explored beforehand and afterwards, which brings up to 115 the total number of gradient comparisons. There was a correlation between maximum instantaneous gradient at doppler and peak to peak gradient (r = 0.62, n = 115, e = 22.5 mmHg, p less than 0.001). A similar correlation was found between maximum instantaneous gradients at doppler and haemodynamics (r = 0.64, n = 80, e = 24.5 mmHg), but correlation between mean gradients was weaker (r = 0.57, n = 80, e = 17.7 mmHg). Maximum and mean instantaneous gradients are underestimated by the doppler method. After exclusion of imperfect doppler curves, correlations were better, notably as regards mean gradients (r = 0.80, n = 18, e = 11.9 mmHg). There was a closer correlation between doppler maximum instantaneous gradients and haemodynamic peak to peak gradients in patients without aortic regurgitation (r = 0.71, n = 45, e = 17.2 mmHg) than in patients with aortic regurgitation (r = 0.54, n = 70, e = 24.3 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Cardiac Doppler. Gradients theory].

The authors remind of the theoretical basis which establish the validity of the Doppler method in the evaluation of valvular stenosis, and the origin of Bernouilli's formula: P1 - P2 = 1/2 p (v1-v2), in which P1 v1 represent pressure and speed proximal to the stenosis, and P2 and v2 represent pressure and speed at the level of the stenosis. This Bernouilli formula is only a particular case of the general law of preservation of mass and energy. Bernouilli's equation may only be applied under certain, well defined, conditions: isolated stenosis, short, not tunnel-shaped, exceeding 0.1-0.2 cm2: under this threshold, the trans-stenotic flow becomes spray with loss of the definition of the Doppler signal. The reliability of this equation is the basis for the reliability of the Doppler in the evaluation of all valvular stenoses by their instant and intermediate gradients.

Echocardiography, Doppler↗

[Doppler and valvular prostheses].

The principle of examination of prosthetic valves is not different from that of the original valves in terms of bioprosthesis. On the contrary, mechanical prosthesis are markedly opaque to ultrasounds and cause masking and non-flow phenomena behind the prosthesis, which are capable to completely hide abnormal retrograde flows, in traditional views (Apical 4 cavities to demonstrate a mitral leakage). Therefore, with mechanical prostheses, it is necessary to "cheat" and use atypical views which avoid interposition of the prosthesis between the ultrasound beam and the abnormal flow. The function of the prosthesis is evaluated on the following parameters: maximum transprosthetic velocity, maximum instant gradient, mean gradient and functional prosthetic area derived either from T1/2 or from the application of the continuity equation. The main factors of transprosthetic Max. V and gradients are the type and size of the prosthesis, the age of the prosthesis is only a factor for bioprostheses, and the cardiac rate and output. The golden rule is therefore to record, one month after the procedure, the Doppler characteristics of any new prosthesis, the patient being his own reference, year after year. Finally the characteristic manifestations of various dysfunctions are presented.

Aortic Valve↗

Cyclic AMP-modulated potassium channels in murine B cells and their precursors.

A voltage-dependent potassium current (the delayed rectifier) has been found in murine B cells and their precursors with the whole-cell patch-clamp technique. The type of channel involved in the generation of this current appears to be present throughout all stages of pre-B-cell differentiation, since it is detected in pre-B cell lines infected with Abelson murine leukemia virus; these cell lines represent various phases of B-cell development. Thus, the presence of this channel is not obviously correlated with B-cell differentiation. Although blocked by Co2+, the channel, or channels, does not appear to be activated by Ca2+ entry. It is, however, inactivated by high intracellular Ca2+ concentrations. In addition, elevation of intracellular adenosine 3', 5'-monophosphate induces at all potentials a rapid decrease in the peak potassium conductance and increased rates of activation and inactivation. Therefore, potassium channels can be physiologically modulated by second messengers in lymphocytes.

Animals↗

[Development of sensitivity to glycine, GABA and beta-alanine in cultured spinal neurons].

Whole cell patch-clamp recording of cultured chick spinal neurons, presumed to be motoneurons, revealed currents elicited in these cells by GABA, glycine and beta-alanine, corresponding to the opening of chloride channels. During maturation, sensitivity to all three transmitters were first detected on the day 6 of culture, and appeared in most neurons by day 8. However, at all stages of development, a fraction of the cells were sensitive only to GABA; this observation supports the notion that the GABA and the glycine receptors are distinct. On the other hand, separate activation by glycine and beta-alanine was never observed, in agreement with the postulate that these amino acids bind to the same receptor.

Alanine↗