P. Ravel | Université de Montpellier (original) (raw)

Papers by P. Ravel

Cancer research, Jul 17, 2016

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as anti-proliferati... more The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as anti-proliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma (mRCC) patients showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, high rate of Eomes+CD8+ T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift towards decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice...

European Journal of Cancer, 2015

Journal of Agricultural and Food Chemistry, 2001

Phenolics from grapes and wines can play a role against oxidation and development of atherosclero... more Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (-)-epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French varietal commercial wines taken from southern France to study the antioxidant capacity and the daily dietary intake of these compounds for the French population. The highest antioxidant capacity was obtained with red wines and ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines, Chardonnay enriched in phenolics by special wine-making was found to have an antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines classified by vintages (1996-1999) antioxidant capacities were ∼20 mmol/L and then decreased to 13.4 mmol/L for vintages 1995-1991. Sweet white wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines (1.91 mmol/L). On the basis of a still significant French wine consumption of 180 mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2, B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rosé wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic) mg/day/resident for the French population. Red wine, and particularly Pinot Noir, Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched in phenolics during wine-making for white varieties contribute to a very significant catechin dietary intake.

La Presse Médicale, 2007

ABSTRACT Objectif La prise en charge des femmes enceintes toxicomanes par une équipe multidiscipl... more ABSTRACT Objectif La prise en charge des femmes enceintes toxicomanes par une équipe multidisciplinaire permet de réduire les risques sociaux et médicaux. Le but de notre travail a été d'étudier l'évolution de la toxicodépendance des patientes suivies par la Cellule parentalité et usage de drogues (CPUD) de Montpellier. Méthodes Cette étude était prospective et descriptive, elle a duré 5 ans (mars 1997 à décembre 2002). Les critères d'inclusion étaient : dépendance aux opiacés, grossesse en cours, suivi par la CPUD au minimum pendant 15 jours, accouchement au CHU de Montpellier. Les mesures effectuées ont porté sur l'adhésion au suivi, la prise de drogue, les paramètres socioéconomiques, obstétricaux et néonataux. Résultats Cent quatorze patientes ont été incluses dans l'étude. Les médecins généralistes prescrivaient le plus souvent les traitements de substitution (64/89) et en particulier la buprénorphine haut dosage (70/105), ce traitement était mésusé dans plus d'un quart des cas (28/105) et 78 patientes mélangeaient plusieurs substances psychoactives. La consommation d'héroïne au cours du suivi a diminué significativement (p < 0,01). Le terme moyen d'accouchement était de 38,5 semaines d'aménorrhée. Un syndrome de sevrage néonatal touchait 89/103 enfants. Il n'y a eu aucun abandon de l'enfant pendant la période d'observation. Conclusion Un suivi multidisciplinaire et un soutien psychosocial ont permis de diminuer les complications de la dépendance aux opiacés, alors que le dispositif de prescription de la substitution par les médecins était peu encadré.

Journal of Biological Chemistry, 1997

The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 5.4.2.4) have been sho... more The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 5.4.2.4) have been shown to occur at a unique active site, with distinct binding sites for diphosphoglycerates and monophosphoglycerates. The physiological phosphatase activator (2-phosphoglycolate) binds to BPGM at an undetermined site. BPGM variants were constructed by site-directed mutagenesis of three amino acid residues in the active site to identify residues specifically involved in the binding of the monophosphoglycerates and 2-phosphoglycolate. Substitution of Cys22 by functionally conservative residues, Thr or Ser, caused a great decrease in 2-phosphoglycolate-stimulated phosphatase activity and in the Ka value of the activator, whereas it caused no change in other catalytic activities or in the Km values of 2,3-diphosphoglycerate (2,3-DPG) and glycerate 3-phosphate (3-PG, EC 1.1.1.12), indicating that Cys22 is specifically involved either directly or indirectly in 2-phosphoglycolate binding. Kinetic experiments showed that the Ka of the cofactor and the Km of 3-PG were affected by the substitution of Ser23 indicating that this residue is necessary for the fixation of both 3-PG and 2-phosphoglycolate. The R89K variant has previously been shown to have a modified Km value for monophosphoglycerates, however, its affinity for 2-phosphoglycolate is unaltered, suggesting that Arg89 is specifically involved in monophosphoglycerates binding. CD spectroscopic studies of substrates and cofactor binding showed that 2,3-DPG induced structural modifications of normal and mutated enzymes which could be due to protein phosphorylation. Addition of 2-phosphoglycolate to phosphorylated proteins with normal affinity for the cofactor produced spectra with the same characteristics as unphosphorylated species. In summary, monophosphoglycerates and 2-phosphoglycolate have partially distinct binding sites in human BPGM. The specific implication of the Cys22 residue in 2-phosphoglycolate binding is of great significance in the design of analogs of therapeutic benefit.

The International Journal of Life Cycle Assessment, 2013

Purpose Light-emitting diode (LED) technology is increasingly being used for general lighting. Th... more Purpose Light-emitting diode (LED) technology is increasingly being used for general lighting. Thus, it is timely to study the environmental impacts of the LED products. No life cycle assessments (LCA) of recessed LED downlight luminaires exist in the literature, and only a few assessments of any type of LED light source (component, lamp, luminaire) are available.

Comptes Rendus de l'Académie des Sciences - Series I - Mathematics, 1998

Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 1997

In red blood cells, a modulation of the level of the allosteric effector of hemoglobin, 2,3-dipho... more In red blood cells, a modulation of the level of the allosteric effector of hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) would have implications in the treatment of ischemia and sickle cell anemia. Its concentration is determined by the relative activities of the synthase and phosphatase reactions of the multifunctional bisphosphoglycerate mutase (BPGM). In this report we develop first a more direct synthase assay which uses glyceraldehyde phosphate to suppress the aldolase and triose phosphate isomerase reactions. Secondly we propose a radioactive phosphatase assay coupled to chromatographic separation and identification of the reaction products by paper electrophoresis. Such identification of these products allow us to show that the multifunctional BPGM expresses its mutase instead of its phosphatase activity in conditions of competition between the 3-phosphoglycerate and the 2-phosphoglycolate activator in the phosphatase reaction. These two more precise procedures could be used to study the effects of substrate and cofactor analogues regarding potential therapeutic approaches and could be used for clinical analyses to detect deficiency of BPGM.

Biochemical and Biophysical Research Communications, 1990

Analogues of N-formyl methionyl leucyl phenylalanine possessing three and four peptide units graf... more Analogues of N-formyl methionyl leucyl phenylalanine possessing three and four peptide units grafted onto an inert carbon skeleton were tested as activators of human polymorphonuclear leukocytes. For the two responses studied, degranulation and respiratory burst, the polymeric analogues showed two maxima of activity, one at the same concentration as the monomer, the other one at a concentration 100- to 1000-fold lower. The potency of the polymers with respect to the monomer is discussed in terms of receptor clustering. The similarity of the dose-response curves for superoxide production and lysozyme secretion indicates that the early transmembrane signalling events are identical for the two responses studied.

Biochemical and Biophysical Research Communications, 1993

... I am most grateful to WASPs Madge Rutherford Minton, Nonnie Anderson, Margaret Gilman, Bee Ha... more ... I am most grateful to WASPs Madge Rutherford Minton, Nonnie Anderson, Margaret Gilman, Bee Haydu, and Dawn Seymour who extended their ... Theatre November 22, 1993 directed by Phylis Ward Fox with music by Michael DiPaolo, Lighting Design by Megan McClung and ...

Annales de Cardiologie et d'Angéiologie, 2009

Female infertility treated by ovarian stimulation can lead to arterial thrombosis particularly wh... more Female infertility treated by ovarian stimulation can lead to arterial thrombosis particularly when ovarian hyperstimulation syndrome emerges. Myocardial infarction have been reported thrice, in one case even before artificial ovulation induction. A 25-year-old female with primary infertility underwent ovarian stimulation and eight days after ovulation induction and intra-uterine insemination suffered from a troponin positive non-ST-elevation myocardial infarction of the inferior wall. Coronary angiogram was normal and contrast-enhanced cardiovascular magnetic resonance imaging confirmed the subendocardial inferior infarct. This protocol included sole triptorelin administration followed by 23 recombinant follicle stimulating hormone injections and concluded by recombinant choriogonadotrophin. There was no ovarian hyperstimulation syndrome. Large biological screening did not retrieve any predisposition for arterial thrombosis. Clinical outcome was excellent. Despite weak causal link, we emphasize that chest pain during ovarian stimulation protocol should rise clinical concern for acute coronary syndrome.

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2013

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012

Cancer research, Jul 17, 2016

The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as anti-proliferati... more The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as anti-proliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma (mRCC) patients showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, high rate of Eomes+CD8+ T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift towards decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice...

European Journal of Cancer, 2015

Journal of Agricultural and Food Chemistry, 2001

Phenolics from grapes and wines can play a role against oxidation and development of atherosclero... more Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (-)-epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French varietal commercial wines taken from southern France to study the antioxidant capacity and the daily dietary intake of these compounds for the French population. The highest antioxidant capacity was obtained with red wines and ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines, Chardonnay enriched in phenolics by special wine-making was found to have an antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines classified by vintages (1996-1999) antioxidant capacities were ∼20 mmol/L and then decreased to 13.4 mmol/L for vintages 1995-1991. Sweet white wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines (1.91 mmol/L). On the basis of a still significant French wine consumption of 180 mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2, B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rosé wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic) mg/day/resident for the French population. Red wine, and particularly Pinot Noir, Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched in phenolics during wine-making for white varieties contribute to a very significant catechin dietary intake.

La Presse Médicale, 2007

ABSTRACT Objectif La prise en charge des femmes enceintes toxicomanes par une équipe multidiscipl... more ABSTRACT Objectif La prise en charge des femmes enceintes toxicomanes par une équipe multidisciplinaire permet de réduire les risques sociaux et médicaux. Le but de notre travail a été d'étudier l'évolution de la toxicodépendance des patientes suivies par la Cellule parentalité et usage de drogues (CPUD) de Montpellier. Méthodes Cette étude était prospective et descriptive, elle a duré 5 ans (mars 1997 à décembre 2002). Les critères d'inclusion étaient : dépendance aux opiacés, grossesse en cours, suivi par la CPUD au minimum pendant 15 jours, accouchement au CHU de Montpellier. Les mesures effectuées ont porté sur l'adhésion au suivi, la prise de drogue, les paramètres socioéconomiques, obstétricaux et néonataux. Résultats Cent quatorze patientes ont été incluses dans l'étude. Les médecins généralistes prescrivaient le plus souvent les traitements de substitution (64/89) et en particulier la buprénorphine haut dosage (70/105), ce traitement était mésusé dans plus d'un quart des cas (28/105) et 78 patientes mélangeaient plusieurs substances psychoactives. La consommation d'héroïne au cours du suivi a diminué significativement (p < 0,01). Le terme moyen d'accouchement était de 38,5 semaines d'aménorrhée. Un syndrome de sevrage néonatal touchait 89/103 enfants. Il n'y a eu aucun abandon de l'enfant pendant la période d'observation. Conclusion Un suivi multidisciplinaire et un soutien psychosocial ont permis de diminuer les complications de la dépendance aux opiacés, alors que le dispositif de prescription de la substitution par les médecins était peu encadré.

Journal of Biological Chemistry, 1997

The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 5.4.2.4) have been sho... more The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 5.4.2.4) have been shown to occur at a unique active site, with distinct binding sites for diphosphoglycerates and monophosphoglycerates. The physiological phosphatase activator (2-phosphoglycolate) binds to BPGM at an undetermined site. BPGM variants were constructed by site-directed mutagenesis of three amino acid residues in the active site to identify residues specifically involved in the binding of the monophosphoglycerates and 2-phosphoglycolate. Substitution of Cys22 by functionally conservative residues, Thr or Ser, caused a great decrease in 2-phosphoglycolate-stimulated phosphatase activity and in the Ka value of the activator, whereas it caused no change in other catalytic activities or in the Km values of 2,3-diphosphoglycerate (2,3-DPG) and glycerate 3-phosphate (3-PG, EC 1.1.1.12), indicating that Cys22 is specifically involved either directly or indirectly in 2-phosphoglycolate binding. Kinetic experiments showed that the Ka of the cofactor and the Km of 3-PG were affected by the substitution of Ser23 indicating that this residue is necessary for the fixation of both 3-PG and 2-phosphoglycolate. The R89K variant has previously been shown to have a modified Km value for monophosphoglycerates, however, its affinity for 2-phosphoglycolate is unaltered, suggesting that Arg89 is specifically involved in monophosphoglycerates binding. CD spectroscopic studies of substrates and cofactor binding showed that 2,3-DPG induced structural modifications of normal and mutated enzymes which could be due to protein phosphorylation. Addition of 2-phosphoglycolate to phosphorylated proteins with normal affinity for the cofactor produced spectra with the same characteristics as unphosphorylated species. In summary, monophosphoglycerates and 2-phosphoglycolate have partially distinct binding sites in human BPGM. The specific implication of the Cys22 residue in 2-phosphoglycolate binding is of great significance in the design of analogs of therapeutic benefit.

The International Journal of Life Cycle Assessment, 2013

Purpose Light-emitting diode (LED) technology is increasingly being used for general lighting. Th... more Purpose Light-emitting diode (LED) technology is increasingly being used for general lighting. Thus, it is timely to study the environmental impacts of the LED products. No life cycle assessments (LCA) of recessed LED downlight luminaires exist in the literature, and only a few assessments of any type of LED light source (component, lamp, luminaire) are available.

Comptes Rendus de l'Académie des Sciences - Series I - Mathematics, 1998

Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 1997

In red blood cells, a modulation of the level of the allosteric effector of hemoglobin, 2,3-dipho... more In red blood cells, a modulation of the level of the allosteric effector of hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) would have implications in the treatment of ischemia and sickle cell anemia. Its concentration is determined by the relative activities of the synthase and phosphatase reactions of the multifunctional bisphosphoglycerate mutase (BPGM). In this report we develop first a more direct synthase assay which uses glyceraldehyde phosphate to suppress the aldolase and triose phosphate isomerase reactions. Secondly we propose a radioactive phosphatase assay coupled to chromatographic separation and identification of the reaction products by paper electrophoresis. Such identification of these products allow us to show that the multifunctional BPGM expresses its mutase instead of its phosphatase activity in conditions of competition between the 3-phosphoglycerate and the 2-phosphoglycolate activator in the phosphatase reaction. These two more precise procedures could be used to study the effects of substrate and cofactor analogues regarding potential therapeutic approaches and could be used for clinical analyses to detect deficiency of BPGM.

Biochemical and Biophysical Research Communications, 1990

Analogues of N-formyl methionyl leucyl phenylalanine possessing three and four peptide units graf... more Analogues of N-formyl methionyl leucyl phenylalanine possessing three and four peptide units grafted onto an inert carbon skeleton were tested as activators of human polymorphonuclear leukocytes. For the two responses studied, degranulation and respiratory burst, the polymeric analogues showed two maxima of activity, one at the same concentration as the monomer, the other one at a concentration 100- to 1000-fold lower. The potency of the polymers with respect to the monomer is discussed in terms of receptor clustering. The similarity of the dose-response curves for superoxide production and lysozyme secretion indicates that the early transmembrane signalling events are identical for the two responses studied.

Biochemical and Biophysical Research Communications, 1993

... I am most grateful to WASPs Madge Rutherford Minton, Nonnie Anderson, Margaret Gilman, Bee Ha... more ... I am most grateful to WASPs Madge Rutherford Minton, Nonnie Anderson, Margaret Gilman, Bee Haydu, and Dawn Seymour who extended their ... Theatre November 22, 1993 directed by Phylis Ward Fox with music by Michael DiPaolo, Lighting Design by Megan McClung and ...

Annales de Cardiologie et d'Angéiologie, 2009

Female infertility treated by ovarian stimulation can lead to arterial thrombosis particularly wh... more Female infertility treated by ovarian stimulation can lead to arterial thrombosis particularly when ovarian hyperstimulation syndrome emerges. Myocardial infarction have been reported thrice, in one case even before artificial ovulation induction. A 25-year-old female with primary infertility underwent ovarian stimulation and eight days after ovulation induction and intra-uterine insemination suffered from a troponin positive non-ST-elevation myocardial infarction of the inferior wall. Coronary angiogram was normal and contrast-enhanced cardiovascular magnetic resonance imaging confirmed the subendocardial inferior infarct. This protocol included sole triptorelin administration followed by 23 recombinant follicle stimulating hormone injections and concluded by recombinant choriogonadotrophin. There was no ovarian hyperstimulation syndrome. Large biological screening did not retrieve any predisposition for arterial thrombosis. Clinical outcome was excellent. Despite weak causal link, we emphasize that chest pain during ovarian stimulation protocol should rise clinical concern for acute coronary syndrome.

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2013

Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, 2012