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F Paillard

Publications and source records attributed to F Paillard.

At least 91 records · Page 5Linked to original sources

Down-regulation of lck mRNA by T cell activation involves transcriptional and post-transcriptional mechanisms.

The p56lck tyrosine kinase is most likely to be involved in signal transduction of T lymphocyte activation. After full activation through the TcR/CD3 complex lck mRNA is transiently down-modulated. This down-modulation was due to an early decrease of both transcription and stability of the lck mRNA. To study the involvement of transcriptional and post-transcriptional factors in this regulations, we have analysed the effect of cycloheximide, a protein synthesis inhibitor, on the steady-state of the lck mRNA. Cycloheximide superinduced lck mRNA by increasing its stability, although cycloheximide concomitantly decreased lck transcription. This suggests that the constitutive level of lck mRNA observed prior to activation is controlled by transcriptional activator(s) and post-transcriptional destabilizing factor(s). Second, lck mRNA down-modulation observed after full activation was inhibited by cycloheximide. It increased lck mRNA stability whereas lck transcription remained low. Therefore, full activation might increase the synthesis and/or activity of destabilizing factor(s). Cyclosporin A also inhibited the down-modulation of lck mRNA by increasing its transcription with no effect on its stability. Since, lck mRNA down-modulation was always associated with lymphokine mRNA induction, and since CsA blocks both lymphokine transcription and lck decrease of transcription, this indicates that these genes might share common regulatory pathways leading to their inverse transcriptional regulation.

Antigens, Differentiation, T-Lymphocyte↗

Chronic effects of tertatolol on renal function in hypertensive patients with mild chronic renal failure.

To assess the potential benefit of drug-induced renal haemodynamic changes in patients with chronic renal failure, we have evaluated the effects of the beta-blocking agent tertatolol on blood pressure, glomerular filtration rate, and renal plasma flow. Inulin and PAH clearances were performed before and after 3 months treatment and oral tertatolol, 5 mg daily in eight hypertensive patients with moderate chronic renal failure. After 3 months of treatment, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly by 10% and 13% respectively, whereas renal vascular resistance decreased by 16% and the filtration fraction was unchanged. These results indicate that tertatolol possesses novel renal haemodynamic properties in hypertensive patients with chronic renal failure. However, the long-term benefit of such a therapy is yet to be confirmed.

Adrenergic beta-Antagonists↗

Transcriptional and post-transcriptional regulation of TcR, CD4 and CD8 gene expression during activation of normal human T lymphocytes.

We previously showed that the turnover rates of the messengers coding for the T cell receptor (TcR) alpha, beta and gamma, CD4 and CD8 molecules composing the multireceptor complex vary in normal human mature T lymphocytes according to their state of activation. Activation by soluble anti-CD3 which does not induce proliferation, promotes a weak up-modulation of the corresponding five mRNAs. In contrast, activation signals such as anti-CD3 + PMA, which lead to lymphokine mRNA expression and T cell proliferation, promote a decrease of the TcR, CD4 and CD8 mRNA levels within 4 h post-activation, followed by their gradual re-expression. Here we show that the down-modulation of these mRNAs results from early regulation controls at transcriptional and post-transcriptional levels, i.e. through a concomitant inhibition of transcription and destabilization of the mRNA. Moreover, later re-expression of the mRNA results from recovery of transcription and marked increase of the mRNA stability. Finally, down-modulation is specific for TcR, CD4 and CD8 mRNAs, all submitted to similar regulation processes. These results strongly suggest a direct correlation between down-modulation of the multireceptor complex mRNAs, and lymphokine mRNA expression, and cellular proliferation.

Antibodies, Monoclonal↗

Dynamic electrophysiology of ventriculoatrial conduction: implications for DDD and DDDR pacing.

The behavior of ventriculoatrial conduction (VAC) during exercise remains unknown. In order to determine its characteristics and the consequences it might have on dual chamber pacemaker technology and programming, 17 patients underwent an electrophysiological study (EPS) of atrioventricular conduction (AVC) and of VAC during a protocol including three steps: supine rest, upright position, and finally during cycloergometric exercise; the measurements were done at progressively increasing pacing rates. During a preimplantation EPS, Wenckebach points AVC-W and VAC-W and conduction times, AVCT and VACT (as a function of pacing rate), were measured in ten consecutive patients using temporary leads and an external device. In another study, AVCT, VACT, AVC-W, and VAC-W were measured by telemetric recordings under identical conditions in seven patients implanted earlier with a DDD pacemaker. A 1/1 VAC was observed in 7/17 patients (41%) at rest, and in 13/17 patients (76%) at the end of the protocol; VAC was never observed in 4/17 patients (23%), but occurred in six of the ten patients initially free, three standing at rest and three on exercise. For all patients, the VAC behavior remained of "nodal" type, indicated by a progressive increase in VACT as pacing rate rose up to the VAC-W point. Neither the existence of exercise-induced VAC nor the maximal VACT-W could be predicted from AVC or VAC data obtained at rest. However, at the same pacing rates, standing up and exercise induced a shortening effect on VACT, and improved the VAC-W by an average of 33%. These results suggest that the electrophysiological behavior of VAC does not obey any general rule and cannot be predicted individually. It would thus appear unwise to base pacemaker mediated tachycardia (PMT) protection solely on long postventricular atrial refractory period (PVARP) programming in DDD patients. This work also revealed the potential risks of a rate responsive auto-adaptive PVARP algorithm as proposed in certain new devices.

Adult↗

[Myocardial infarction and massive biventricular thrombosis during thrombocytopenia induced by pentosan polysulfate and heparin].

Many cases of immuno-allergic thrombocytopenia complicated by serious thromboembolism induced by heparin or other heparinoids such as pentosan polysulphate have been reported. This case is of interest for two reasons: first of all, it was induced by pentosan polysulphate and then reactivated by secondary administration of heparin; secondly, it was complicated successively by an infero-apical myocardial infarction with probable spontaneous lysis of a coronary thrombosis because coronary arteriography performed one month later was normal, and then by massive biventricular thrombosis requiring surgical thrombectomy under cardiopulmonary bypass. Tests of platelet aggregation were positive to standard heparin and to several low molecular weight fractions. The outcome was favorable when the responsible substances were withdrawn.

Blood Coagulation Tests↗

[Benefits and limits of single chamber atrial pacing with adaptive rate].

Twelve patients with isolated symptomatic sinus node dysfunction or bradycardia-tachycardia syndrome with atrial chronotropic incompetence during exercise testing were managed by single chamber rate responsive atrial pacing (AAIR) when AV conduction was normal, or by a dual chamber DDDR pacemaker programmed in the AAIR mode when AV conduction was abnormal, and followed up for 12.5 +/- 9.8 months. The patients were assessed clinically, by 3 monthly ECG and Holter recordings and comparative exercise tests in AAI and AAIR modes at the 6th month. One patient with an AAIR system was excluded at M21 because of symptomatic AV block requiring reimplantation of a DDD pacemaker. Ten of the 11 remaining patients are asymptomatic and have an excellent quality of life; one patient had invalidating symptoms on exercise attributed to the "AAIR pacemaker syndrome" which were corrected by reprogramming the pacemaker and modifying the medical therapy. The comparative exercise stress tests showed a significantly higher heart rate in the AAIR mode compared to AAI pacing at the initial and intermediate exercise levels (30 to 70 W); on the other hand, the heart rates were not significantly different at the highest exercise levels although in the AAI mode, the terminal acceleration sometimes occurred in junctional rhythm whereas it was usually an atrial paced rhythm in the AAIR mode. The total duration of exercise was longer in the AAIR mode (+22%; p less than 0.01) when the 8/11 patients with chronotropic incompetence during the baseline study were considered. The spike-R interval adapted normally to exercise in only one case: in the other patients, the interval remained constant or, in the worst of cases (N = 4), it increased paradoxically, to result in the "AAIR pacemaker syndrome": this phenomenon is observed mainly in patients treated by antiarrhythmics and/or betablockers. The AAIR mode would therefore seem to be a simple, effective and reliable method of treating patients with sinus node dysfunction and chronotropic incompetence; however, the failure of adaptation of the PR interval is a real limitation to its use and may constitute an argument in favour of the choice of a DDR pacemaker in these patients.

Adult↗

[Auriculoventricular block disclosed in the exercise test].

Sixteen patients, 14 of whom described stress related symptoms, present a severe atrio-ventricular block (A-V B), identified during a stress test while the ECG at rest showed a 1/1 atrioventricular conduction (AV). The electrophysiological study (EPS) creates the A-B Block through atrial stimulation and specifies the location of the A-V B: intra-hissian in 8 patients (7 with small QRS an 1 with widened QRS) and infra-hissian in 8 patients (all with widened QRS). Non-invasive methods constitute the prime approach in the diagnostic work-up of stress symptoms. The ideal treatment consists of a dual-chamber cardiac stimulation.

Adult↗

Short tertatolol treatment does not impair the hormone and metabolic responses to exercise and hypoglycemia in diabetics.

Beta-blockers can precipitate hypoglycemia and mask its warning signs. Ten male insulin-dependent, otherwise healthy diabetic patients underwent two submaximal exercise tests and two insulin-induced hypoglycemic events (0.2 u/Kg short-acting insulin IV) after six days administration of placebo followed by tertatolol, a non selective beta-blocker (5 mg once daily). Tertatolol modified neither the exercise-induced changes in blood glucose, lactate and plasma unesterified fatty acid levels, nor those of counter regulatory hormones (glucagon, growth hormone, cortisol), while blood pressure, heart rate and plasma renin activity were significantly reduced, proving that tertatolol had actually been ingested, and was active. During the insulin-induced hypoglycemia, similarly tertatolol did not modify the course of the plasma fuels and hormones. Particularly, hypoglycemia was neither deeper nor more prolonged in the presence than in the absence of tertatolol. Warning symptoms were not affected except for palpitations which were not perceived. These results suggest that tertatolol did not precipitate hypoglycemia following exercise, and did not aggravate insulin-induced hypoglycemia in short term administration, and in otherwise healthy diabetic patients.

Adrenergic beta-Antagonists↗

Benefits and limits of selective right ventricular cineangiography in arrhythmogenic right ventricular dysplasia.

Cineangiographic data from patients with probable arrhythmogenic right ventricular dysplasia (ARVD) were compared with those from matched controls. Some changes previously thought to indicate ARVD did not do so in this study. The abnormalities specific for ARVD were free wall morphological and wall motion abnormalities, particularly bulges and mamillated akinetic areas.

Adolescent↗

Aseptic necrosis of bone following renal transplantation: relation with hyperparathyroidism.

Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.

Adult↗

Lymphokine mRNA and T cell multireceptor mRNA of the Ig super gene family are reciprocally modulated during human T cell activation.

The expression of genes, implicated in T cell proliferation as well as those coding for the three chains of the T cell receptor (TcR) and for the CD4 and CD8 molecules, has been investigated during activation of various T cell populations maintained in long-term culture. We show that a minimal activation signal, capable of inducing interleukin 2 (IL 2) receptor expression without the expression of IL2 and interferon-gamma, was not associated with a down-regulation of the messengers coding for the T cell multireceptor molecules. In contrast, a strong activation signal via the TcR/CD3 complex or via the CD2 molecule resulted in a reciprocal transient up-regulation of the messengers implicated in T cell proliferation and a down-regulation of the messengers encoding the molecules of the TcR complex of the immunoglobulin super gene family.

Antigens, Differentiation, T-Lymphocyte↗

Vitamin D metabolism in tuberculosis. Production of 1,25(OH)2D3 by cells recovered by bronchoalveolar lavage and the role of this metabolite in calcium homeostasis.

To investigate the extrarenal production of 1,25(OH)2D3 in tuberculosis, we extensively evaluated a patient with tuberculosis, hypercalcemia, and an elevated plasma concentration of 1,25(OH)2D3. Fresh total cells and cultured alveolar macrophages obtained by bronchoalveolar lavage were demonstrated to synthesize 1,25(OH)2D3 prior to and after nine months of successful antituberculous therapy. The continued capacity to produce 1,25(OH)2D3 was associated with a persistent lymphocytic alveolitis in this patient. This extrarenal production of 1,25(OH)2D3 probably contributed to the increased levels of plasma 1,25(OH)2D observed in our patient. Nevertheless, a close correlation between plasma 1,25(OH)2D and serum calcium was not observed. These findings suggest that although extrarenal production of 1,25(OH)2D3 occurs in tuberculosis, it need not be a predominant factor producing the abnormalities in calcium homeostasis observed in such patients.

Adult↗

[Proximal migration of a caval filter. Apropos of a case].

We are reporting of proximal migration, intracardiac, of a percutaneous caval filter (LEM type), resulting in the death of the patient. It is a true, early (1st week) migration after accurate positioning, opposite L4, and not an incident of insertion.

Aged↗

Atrial natriuretic factor during atrial fibrillation and supraventricular tachycardia.

Plasma immunoreactive atrial natriuretic factor was measured in 10 patients with chronic atrial fibrillation before and after cardioversion to sinus rhythm, and in 14 patients during electrophysiologic evaluation of paroxysmal supraventricular tachycardia. The mean plasma concentration of atrial natriuretic factor in atrial fibrillation was 138 +/- 48 pg/ml and decreased to 116 +/- 45 pg/ml 1 hour after cardioversion to sinus rhythm (p less than 0.005). The mean plasma concentration of atrial natriuretic factor increased from 117 +/- 53 pg/ml in sinus rhythm to 251 +/- 137 pg/ml during laboratory-induced supraventricular tachycardia (p less than 0.005). Right atrial pressures were recorded in 12 patients; the baseline atrial pressure was 4.3 +/- 1.9 mm Hg and increased to 7.4 +/- 3.6 mm Hg during supraventricular tachycardia (p less than 0.005). A modest but significant linear relation was noted between the changes in plasma atrial natriuretic factor and right atrial pressure measurements during induced supraventricular tachycardia (r = 0.60, p less than 0.05). In conclusion, changes in atrial rhythm and pressure may be an important factor modulating the release of atrial natriuretic factor in the circulation and raised levels of this hormone may be a contributing factor for the polyuria and the hypotension associated with paroxysmal supraventricular tachyarrhythmias.

Aged↗