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C Léon

Publications and source records attributed to C Léon.

18 recordsLinked to original sources
PubMed2006

[Attitudes towards immunization].

PURPOSE: Ever since vaccination was introduced, a minority has been opposed to this practice. Recently however, fear of adverse events and a general questioning of the usefulness of certain vaccines have led to wariness on the part of the broader public. In France, this phenomenon is particularly striking since the hepatitis B vaccination campaign. We wished to analyse the situation by drawing on the results of surveys conducted by the French Institute of Prevention and Health Education (Institut national de prévention et d'éducation pour la santé, INPES) which sought to gain a better understanding of health care professionals' and the general public's attitudes towards immunization. MAIN POINTS: Although the majority of French men and women are convinced of the overall benefit of vaccination in the past, they increasingly question vaccine safety and usefulness today. PERSPECTIVES: In order to prevent further deterioration of the situation, efforts must be made to enhance public and professional awareness as to the stakes involved in the control of vaccine preventable diseases.

Attitude of Health Personnel↗
PubMed2006

[Use of health services and treatments for major depressive episode in France].

INTRODUCTION: The depressive disorders are among the most frequent disorders in the general population. Various validated treatments exist but, according to international psychiatric epidemiologic surveys, only a minority of currently depressed people seek and receive treatment. To date, in France, few national studies have investigated these problems. OBJECTIVES: By using the data of the national French survey: "Santé mentale en population générale (SMPG)": 1) to estimate the prevalence of use of care services by depressed people in the general population, 2) to evaluate the proportion of depressive subjects who have received drug and/or psychological treatments, 3) to identify the demographic and clinical factors and representations associated with use. METHOD: SMPG was a transversal survey carried out by the WHO national collaborative center (CCOMS) and the Direction of the statistics of the ministry for Health (DREES). A representative sample of 36 105 non-institutionalised French individuals aged 18 or over was interviewed. Three main questionnaires was used: the Mini International Neuropsychiatric Interview (MINI) questionnaire was used to assess several mental disorders according to the ICD-10 classification, a questionnaire on the representations of the mental disease and the treatments, and a questionnaire on use of care services and treatments received. RESULTS: - 71.9% of depressed people sought or received a treatment and 47.1% stated claimed to be treated for depression. About 20% of people classified as having a recurrent or chronic depressive disorder have never used health care services for mental health. Only 53.4% of subjects having a mild or moderate Major Depressive Episode (MDE) already received a treatment: 42.1% had taken psychotropic drugs only, 3.2% had psychotherapy only, 8.1% had both, and 25.6% had taken antidepressants among the subjects treated by psychotropic drugs; 24% of subjects classified as having a recurrent or chronic depressive disorder have never received a treatment and about 3/4 of them have never received a minimal adequate treatment. Use of services by depressed people was associated with sociodemographic factors, the severity of the disorder and several representations. CONCLUSION: - The SMPG survey confirms the international finding concerning the treatment of depressed people. Several problems were pointed out: an important part of depressed people had never taken any treatment, less than half claimed they were stated to be treated for depression, a minority received a psychotherapy, and very few had a minimal adequate treatment. In France, more psychiatric epidemiologic surveys are needed to confirm and specify these findings.

Adolescent↗
PubMed2006

[Perceptions of hepatitis B vaccination in France. Analysis of three surveys].

BACKGROUND: The main target for hepatitis B vaccination has never been reached, since less than 30% of infants were immunized in 2000. We wished to examine what might explain this situation by surveying attitudes within the general public and among vaccinators. METHODS: We analyzed and compared the data on hepatitis B vaccination from three quantitative surveys conducted by the National Institute of Prevention and Health Education in 2003-2005. RESULTS: Even those physicians (especially pediatricians) who are favorable to hepatitis B immunization do not always apply recommendations; 95% of physicians stated their patients are rather reticent to participate. Regarding the general public, less than half of French adults would be prepared to have their infant immunized against hepatitis B. CONCLUSION: The usefulness of immunizing infants, rather than the absence of adverse events, should be put forth as the main argument in favour of hepatitis B immunization, both for physicians and the larger public.

Adolescent↗
PubMed2003

Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist.

Previous studies in experimental models revealed a role for the P2Y1 platelet ADP receptor in systemic vascular thromboembolism models. In the present work, we used models of localized arterial and venous thrombosis to assess the role of the P2Y1 receptor in these processes. Arterial thrombosis was induced in one mesenteric arteriole of a mouse using FeCl3, while venous thrombosis was studied in a Wessler model adapted to rats. P2Y1-deficient mice and mice treated with the P2Y1 antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls. Combination of P2Y1 deficiency with P2Y12 inhibition led to a significant additive effect. Venous thrombosis was slightly but significantly inhibited in MRS2179-treated rats. These results demonstrate a role for the P2Y1 receptor in both arterial and venous thrombosis, further establishing this receptor as a potential target for antithrombotic drugs.

Adenosine Diphosphate↗
PubMed2001

The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin--a phosphoinositide 3-kinase-dependent mechanism.

High concentrations of adenosine-5'-diphosphate ADP are able to induce partial aggregation without shape change of P2Y(1) receptor-deficient mouse platelets through activation of the P2Y(12) receptor. In the present work we studied the transduction pathways selectively involved in this phenomenon. Flow cytometric analyses using R-phycoerythrin-conjugated JON/A antibody (JON/A-PE), an antibody which recognizes activated mouse alpha(IIb)beta(3) integrin, revealed a low level activation of alpha(IIb)beta(3) in P2Y(1) receptor-deficient platelets in response to 100 microM ADP or 1 microM 2MeS-ADP. Adrenaline induced no such activation but strongly potentiated the effect of ADP in a dose-dependent manner. Global phosphorylation of (32)P-labeled platelets showed that P2Y(12)-mediated aggregation was not accompanied by an increase in the phosphorylation of myosin light chain (P(20)) or pleckstrin (P(47)) and was not affected by the protein kinase C (PKC) inhibitor staurosporine. On the other hand, two unrelated phosphoinositide 3-kinase inhibitors, wortmannin and LY294002, inhibited this aggregation. Our results indicate that (i) the P2Y(12) receptor is able to trigger a P2Y(1) receptor-independent inside-out signal leading to alpha(IIb)beta(3) integrin activation and platelet aggregation, (ii) ADP and adrenaline use different signaling pathways which synergize to activate the alpha(IIb)beta(3) integrin, and (iii) the transduction pathway triggered by the P2Y(12) receptor is independent of PKC but dependent on phosphoinositide 3-kinase.

Androstadienes↗
PubMed2001

Key role of the P2Y(1) receptor in tissue factor-induced thrombin-dependent acute thromboembolism: studies in P2Y(1)-knockout mice and mice treated with a P2Y(1) antagonist.

BACKGROUND: ADP plays a key role in hemostasis, acting through 2 platelet receptors: the P2Y(1) receptor and an unidentified P2 receptor, called P2cyc, coupled to adenylyl cyclase inhibition, which is the target of the antiplatelet drug clopidogrel. We showed that the P2Y(1) receptor is an essential cofactor in thrombotic states induced by intravenous infusion of collagen and epinephrine. The aim of the present study was to assess the role of this receptor in thrombin-dependent tissue factor-induced thromboembolism. METHODS AND RESULTS: Human thromboplastin was injected intravenously into wild-type or P2Y(1)-deficient mice, and the effects on platelet count and mortality were determined and plasma thrombin-antithrombin III (TAT) complexes were quantified. P2Y(1)-deficient mice were resistant to the thromboembolism induced by injection of thromboplastin. Whereas the platelet count decreased sharply in wild-type mice, there was no significant drop in platelets in P2Y(1)-knockout mice. The platelet consumption in wild-type mice was probably due to thrombin generation, because it was abolished by hirudin. Thromboplastin also led to a rise in TAT complexes in plasma, again reflecting thrombin formation. This effect, however, was less important in P2Y(1)-knockout mice than in wild-type mice, indicating that less thrombin was generated in the absence of P2Y(1). Similar results were obtained after intravenous administration of N:(6)-methyl-2'-deoxyadenosine-3':5'-bisphosphate, a selective antagonist of the P2Y(1) receptor, to wild-type mice. CONCLUSIONS: Our results demonstrate a role of the P2Y(1) receptor in thrombotic states involving thrombin generation and provide further evidence for the potential relevance of this receptor as a target for antithrombotic drugs.

Acute Disease↗
PubMed2001

Inhibition of platelet function by administration of MRS2179, a P2Y1 receptor antagonist.

The effects of a potent P2Y1 receptor antagonist, N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) on adenosine-5'-diphosphate (ADP)-induced platelet aggregation in vitro, ex vivo and on the bleeding time in vivo were determined. In suspensions of washed platelets, MRS2179 inhibited ADP-induced platelet shape change, aggregation and Ca2+ rise but had no effect on ADP-induced inhibition of adenylyl cyclase. Binding studies using the new radioligand [33P]MRS2179 showed that washed human platelets displayed 134+/-8 binding sites per platelet with an affinity (Kd) of 109+/-18 nM. Finally, intravenous injection of MRS2179 resulted in inhibition of rat platelet aggregation in response to ADP and prolonged the bleeding time, in rats or mice, as compared to controls. These results suggest this potent P2Y1 receptor antagonist to be a promising tool to evaluate the in vivo effects of pharmacologically targeting the P2Y1 receptor with a view to antithrombotic therapy.

Adenosine Diphosphate↗
PubMed2000

Desensitization of the platelet aggregation response to ADP: differential down-regulation of the P2Y1 and P2cyc receptors.

Platelets activated by ADP become refractory to restimulation, but the mechanism of this process is not well understood. A normal platelet response to ADP requires coactivation of the P2Y(1) receptor responsible for shape change and the P2cyc receptor, responsible for completion and amplification of the response. The aim of the present study was to characterize the desensitization of platelets to ADP and to determine whether or not these two receptors are desensitized simultaneously through identical pathways when platelets become refractory to ADP. It was found that full inhibition of platelet aggregation in response to restimulation by ADP required the presence of ADP in the medium or use of a high concentration (1 mM) of its non-hydrolysable analogue ADPbetaS. Platelets incubated for 1 h at 37 degrees C with 1 mM ADPbetaS and resuspended in Tyrode's buffer containing apyrase displayed a stable refractory state characterized by the inability to aggregate or change shape in response to ADP. ADPbetaS treated platelets loaded with fura-2/AM showed complete blockade of the calcium signal in response to ADP, whereas the capacity of ADP to inhibit PGE1 stimulated cAMP accumulation in these platelets was only diminished. Consequently, serotonin was able to promote ADP induced aggregation through activation of the Gq coupled 5HT(2A) receptor while adrenaline had no such effect. These results suggested that the refractory state of ADPbetaS treated platelets was entirely due to desensitization of the P2Y(1) receptor, the P2cyc receptor remaining functional. Binding studies were performed to determine whether the P2Y(1) and/or P2cyc binding sites were modified in refractory platelets. Using selective P2Y(1) and P2cyc antagonists (A3P5P and AR-C66096 respectively), we could demonstrate that the decrease in [33P]2MeSADP binding sites on refractory platelets corresponded to disappearance of the P2Y(1) sites with no change in the number of P2cyc sites, suggesting internalization of the P2Y(1) receptor. This was confirmed by flow cytometric analysis of Jurkat cells expressing an epitope-tagged P2Y(1) receptor, where ADPbetaS treatment resulted in complete loss of the receptor from the cell surface. We conclude that the P2Y(1) and P2cyc receptors are differently regulated during platelet activation.

Adenosine Diphosphate↗
PubMed1999

Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice.

ADP is a key agonist in hemostasis and thrombosis. ADP-induced platelet activation involves the purinergic P2Y(1) receptor, which is responsible for shape change through intracellular calcium mobilization. This process also depends on an unidentified P2 receptor (P2cyc) that leads to adenylyl cyclase inhibition and promotes the completion and amplification of the platelet response. P2Y(1)-null mice were generated to define the role of the P2Y(1) receptor and to determine whether the unidentified P2cyc receptor is distinct from P2Y(1). These mice are viable with no apparent abnormalities affecting their development, survival, reproduction, or the morphology of their platelets, and the platelet count in these animals is identical to that of wild-type mice. However, platelets from P2Y(1)-deficient mice are unable to aggregate in response to usual concentrations of ADP and display impaired aggregation to other agonists, while high concentrations of ADP induce platelet aggregation without shape change. In addition, ADP-induced inhibition of adenylyl cyclase still occurs, demonstrating the existence of an ADP receptor distinct from P2Y(1). P2Y(1)-null mice have no spontaneous bleeding tendency but are resistant to thromboembolism induced by intravenous injection of ADP or collagen and adrenaline. Hence, the P2Y(1) receptor plays an essential role in thrombotic states and represents a potential target for antithrombotic drugs.

Adenosine Diphosphate↗
PubMed1999

The P2Y1 receptor is normal in a patient presenting a severe deficiency of ADP-induced platelet aggregation.

ADP is a key stimulus inducing platelet shape change and aggregation, a rise in internal calcium and inhibition of adenylyl cyclase. These signaling pathways are thought to be activated by three independent receptors, but to date only the P2Y1 receptor responsible for calcium mobilization and the ionotropic P2X1 receptor have been identified. We report here the characteristics of the P2Y1 receptor in a patient presenting a selective deficiency of ADP-induced aggregation. Cloning of the P2Y1 gene revealed that the patient's DNA and mRNA were normal. Pharmacological studies showed that the P2Y1 receptor was expressed and functional in patient's platelets. Hence, the P2Y, receptor is not the cause of the impaired ADP-induced platelet aggregation in this patient. The P2X1 mRNA was also found to be present and normal. These findings add evidence to previous observations suggesting that a third P2 receptor coupled to adenylyl cyclase may be involved in ADP-induced platelet aggregation.

Adenosine Diphosphate↗
PubMed1998

The P2Y1 receptor is necessary for adenosine 5'-diphosphate-induced platelet aggregation.

The human P2Y1 receptor heterologously expressed in Jurkat cells behaves as a specific adenosine 5'-diphosphate (ADP) receptor at which purified adenosine triphosphate (ATP) is an ineffective agonist, but competitively antagonizes the action of ADP. This receptor is thus a good candidate to be the elusive platelet P2T receptor for ADP. In the present work, we examined the effects on ADP-induced platelet responses of two selective and competitive P2Y1 antagonists, adenosine-2'-phosphate-5'-phosphate (A2P5P) and adenosine-3'-phosphate-5'-phosphate (A3P5P). Results were compared with those for the native P2Y1 receptor expressed on the B10 clone of rat brain capillary endothelial cells (BCEC) and for the cloned human P2Y1 receptor expressed on Jurkat cells. A2P5P and A3P5P inhibited ADP-induced platelet shape change and aggregation (pA2 = 5) and competitively antagonized calcium movements in response to ADP in fura-2-loaded platelets, B10 cells, and P2Y1-Jurkat cells. In contrast, these compounds had no effect on ADP-induced inhibition of adenylyl cyclase in platelets or B10 cells, whereas known antagonists of platelet activation by ADP such as Sp-ATPalphaS were effective. These identical signaling responses and pharmacologic properties suggest that platelets and BCEC share a common P2Y1 receptor involved in ADP-induced aggregation and vasodilation, respectively. This P2Y1 receptor coupled to the mobilization of intracellular calcium stores was found to be necessary to trigger ADP-induced platelet aggregation. The present results, together with data from the literature, also point to the existence of another as yet unidentified ADP receptor, coupled to adenylyl cyclase and responsible for completion of the aggregation response. Thus, the term, P2T, should no longer be used to designate a specific molecular entity.

Adenosine Diphosphate↗
PubMed1998

ATP derivatives are antagonists of the P2Y1 receptor: similarities to the platelet ADP receptor.

Pharmacological properties of the human P2Y1 receptor transfected in Jurkat cells and of the endogenous receptor in rat brain capillary endothelial cells were analyzed under conditions in which the purity of adenine triphosphate nucleotides was controlled by creatine phosphate/creatine phosphokinase (CP/CPK). ATP, a partial agonist of the receptor, was inactive in the presence of CP/CPK. Results further indicated that ATP was a competitive antagonist of ADP actions. Ki values were 23.0 +/- 1.5 microM in endothelial cells and 14.3 +/- 0.3 microM in Jurkat cells. Solutions prepared from commercially available 2-methylthio-ATP (2-MeSATP) or 2-chloro-ATP (2-ClATP) contained approximately 10% of ADP derivatives. ADP derivatives were removed from the solution by treatment with CP/CPK. Purified 2-MeSATP and 2-ClATP antagonized platelet aggregation induced by ADP. They did not activate P2Y1 receptors but prevented ADP actions in a competitive manner. Ki values for 2-MeSATP were 36. 5 microM in endothelial cells and 5.7 +/- 0.4 microM in Jurkat cells, and Ki values for 2-ClATP were 27.5 microM in endothelial cells and 2.3 +/- 0.3 microM in Jurkat cells. EDTA potentiated actions of ADP and ATP on endothelial cells by 2.4- and 3.6-fold, respectively. In conclusion, the rat and human P2Y1 receptors are ADP-specific receptors that recognize ADP and 2-methylthio-ADP, whereas ATP, 2-MeSATP, and 2-ClATP are competitive antagonists. The results further point to the close pharmacological similarity of the P2Y1 receptor and the platelet ADP receptor.

Adenosine Diphosphate↗
PubMed1997

The P2Y1 receptor is an ADP receptor antagonized by ATP and expressed in platelets and megakaryoblastic cells.

The human P2Y1 purinoceptor has been expressed in Jurkat cells and the effects of HPLC purified nucleotides on calcium movements were measured. The most potent agonist was 2-methylthio-ADP followed by ADP. ATP, Sp-ATPalphaS and beta,gamma-methylene-ATP were competitive antagonists. Suramin and PPADS inhibited the effects of ADP. This pharmacological profile is the same as that of the so-called P2T purinoceptor responsible for platelet aggregation, which has not yet been identified. Using PCR we found the P2Y1 receptor to be present in blood platelets and megakaryoblastic cell lines. These data suggest that the P2Y1 receptor may be the elusive P2T receptor.

Adenosine Diphosphate↗
PubMed1997

Presence of P2X1 purinoceptors in human platelets and megakaryoblastic cell lines.

Human platelets are thought to possess at least two subtypes of purinoceptor, one of which, coupled to G-proteins, could be the P2Y1 receptor (Leon et al. 1997). However, it has been suggested that the unique rapid calcium influx induced by ADP in platelets could involve P2X1 ionotropic receptors (MacKenzie et al. 1996) and the aim of this study was thus to investigate the presence of P2X purinoceptors in platelets and megakaryoblastic cells. Using PCR experiments, we found P2X1 mRNA to be present in human platelets and megakaryoblastic cell lines. In platelets, the selective P2X1 agonist alphabetaMeATP induced a rise in intracellular calcium only in the presence of external calcium and this effect was antagonized by suramin and PPADS. Repeated addition of alphabetaMeATP desensitized the P2X1 purinoceptor but only slightly affected the ADP response, while no calcium response to alphabetaMeATP was observed in megakaryoblastic cells. These results support the existence of functional P2X1 purinoceptors on human platelets and the presence of P2X1 transcripts in megakaryoblastic cell lines.

Adenosine Triphosphate↗
PubMed1996

Cloning and sequencing of a human cDNA encoding endothelial P2Y1 purinoceptor.

We have cloned and sequenced a 3055-bp human placenta cDNA encoding a P2 purinoceptor. An identical receptor has also been found in human saphenous vein endothelial cells. Comparison of the deduced amino acid (aa) sequence to those of previously described P2Y1 purinoceptors revealed greater than 95% aa identity with the rat and mouse counterparts, and 83% with the chick P2Y1 purinoceptor. Northern blot experiments revealed two mRNAs of 7.5 and 4.6 kb whose expression varies according to the tissue examined.

Amino Acid Sequence↗
PubMed1992

Expression of cell adhesion molecules and catecholamine synthesizing enzymes in the developing rat adrenal gland.

Cell adhesion molecules play a major role in determining tissue architecture during histogenesis. This immunocytochemical study of the adrenal gland examines the embryonic and early postnatal cellular expression of two neural cell adhesion molecules, NCAM and L1, which are widely expressed in brain and have been found also to be expressed in the adult rat adrenal gland. In parallel, antibodies directed against two neuroendocrine cell markers, tyrosine hydroxylase and phenylethanolamine N-methyltransferase, were employed to verify the phenotypic nature of developing chromaffin cells in order to correlate cell adhesion molecule expression with the state of chromaffin cell differentiation. NCAM was found to be expressed by chromoblasts within extra-adrenal blastema (i.e. before their migration into the cortical primordium) at the 16th day of embryonic life. It continued to be expressed by all developing chromaffin cells after their infiltration into the developing adrenal gland at all ages. L1 was also expressed by chromoblasts in extra-adrenal sites, but was found only in a subpopulation of chromaffin cells within the cortical primordium from the 16th embryonic day onwards. Those chromoblasts which expressed L1 constituted relatively large compact cell clusters within the gland at this stage, while intra-adrenal chromaffin cells not expressing L1 were dispersed in small cell groups. L1 was also strongly expressed by nerve fibres (and their surrounding Schwann cells) which appeared to innervate cell groups as early as the 16th embryonic day. Both extra- and intra-adrenal chromoblasts expressed tyrosine hydroxylase, but the large L1-positive cell aggregates were less intensely immunoreactive for tyrosine hydroxylase than were cells in small groups. PNMT expression was restricted to L1-negative intra-adrenal chromoblasts present in small groups. Ultrastructural observations demonstrated that cells expressing L1 contained few secretory granules at the 18th embryonic day. It is concluded from these data that these chromoblasts are the precursors of the noradrenergic cells found in the mature gland. In addition, the arrangement of noradrenergic chromaffin cells in the form of homotypic cell groups throughout the course of histogenesis of the adrenal medulla is likely to be a direct consequence of the exclusive co-expression of both NCAM and L1 by this subpopulation of maturing chromaffin cells.

Adrenal Glands↗
PubMedDate not supplied

[Micro-endoscopy of the lacrimal apparatus combined with Erbium YAG laser: an anatomical study. New methods of imaging].

PURPOSE: To study the anatomic structure and the endoscopic aspect of the lacrimal drainage system and to evaluate the efficacy of the Erbium laser with microendoscope in lacrimal obstruction. METHODS: Twenty lacrimal ducts from ten fresh cadaver heads were used to lead a special rigid probe of 1.1. mm diameter (Endognost Schwind). This probe combined a flexible endoscopic probe of 500 mu, an Erbium laser fiber of 375 mu and an irrigation. The probe was introduced through the inferior canaliculus. Progressing in the lacrimal system, all the images were analysed. Then, we used the laser fiber to open the lacrimal sac mucosa and the lacrimal bone. RESULTS: The anatomo-endoscopic analysis was performed using endoscopic data. We appreciated essentially the walls of valves and sinuses that appeared only functional when increasing the irrigation flow. The laser could easily open the mucosa and the lacrimal bone but not the maxilla. DISCUSSION: The small size of the cannula allows to use the system for the diagnosis of lacrimal obstructions. The combined laser allows to treat at same time canalicular obstructions and lower obstructions. CONCLUSION: The endocanalicular study of the lacrimal drainage system can diagnose the type of obstruction and can treat it. A clinical study is requested to confirm these results.

Cadaver↗