32 results on '"Vivat, A."'
Search Results
2. THE DOUBT OF FUTURE FOES (CIRCA 1571)
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Regina, Vivat
- Subjects
Poetry ,Education - Abstract
The doubt of future foes Exiles my present joy And wit me warns to shun such snares As threatens mine annoy. For falsehood now doth flow And subjects' faith doth [...]
- Published
- 2000
3. Antimicrobial Susceptibility and Resistance Patterns among Helicobacter pyloriStrains from The Gambia, West Africa
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Secka, Ousman, Berg, Douglas E., Antonio, Martin, Corrah, Tumani, Tapgun, Mary, Walton, Robert, Thomas, Vivat, Galano, Juan J., Sancho, Javier, Adegbola, Richard A., and Thomas, Julian E.
- Abstract
ABSTRACTHelicobacter pyloriis a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pyloristrains were tested for antibiotic susceptibility. The role of rdxAin metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P= 0.0031). Representative Mtz-resistant (Mtzr) strains were rendered Mtz susceptible (Mtzs) by transformation with a functional rdxAgene; conversely, Mtzsstrains were rendered Mtzrby rdxAinactivation. Many mutations were found by Gambian H. pylorirdxAsequencing; mutations that probably inactivated rdxAin Mtzrstrains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxAmutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.
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- 2012
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4. Retinoids as Therapeutic Agents: Today and Tomorrow
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Vivat-Hannah, Valerie and Zusi, F. Christopher
- Abstract
Retinoids have shown beneficial therapeutic effects in pre-clinical and animal models for multiple pathologic indications, however severe adverse effects, restricting dosage and efficacy of oral formulations limit their use in patients. The focus of this review includes the actual medicinal use of retinoids and chemical efforts to generate highly selective and less toxic synthetic retinoids.
- Published
- 2005
5. Application of Organometallic Chemistry on Metal Surfaces to Fine Chemicals: A New Access to Trimegestone by Chemo-, Regio-, and Diastereoselective Hydrogenation of Cetaloxopromegestone on Pt/Sn/SiO2Catalysts
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Gertosio, Valérie, Santini, Catherine C, Taoufik, Mostapha, Bayard, François, Basset, Jean-Marie, Buendia, Jean, and Vivat, Michel
- Abstract
The selective hydrogenation of cetaloxopromegestone (17α-methyl-17β-(1,2-dioxopropyl)-estra-5,9-dien-3-ketal) to the ketal precursor of Trimegestone (17α-methyl-17β-(2(S)-hydroxy-1-oxopropyl)-estra-5,9-dien-3-ketal) was carried out on various silica-supported monometallic catalysts and on bimetallic platinum–tin catalysts prepared by the interaction of Sn(CH3)4with reduced Pt/SiO2under H2at room temperature. The selective hydrogenation must occur stereoselectively at the C21ketone of cetaloxopromegestone, which possesses another ketone at C20and two conjugated olefinic double bonds at C5–C10and C9–C11. Of the various supported metals (Pd, Ru, Rh, Pt), the Pt/SiO2catalyst exhibited low chemoselectivity (52%), but the diastereoselectivity at C21reached 70%. The chemoselectivity of PtxSny/SiO2catalysts increased from 52 to 100%. At the same time, however, the d.e. at C21decreased from 70 to 30%. This inverse tendency of chemo- and diastereoselectivity upon the addition of tin can be explained by the fact that the multifunctional molecule can be coordinated to the surface either by its C21carbonyl (which leads to high chemoselectivity) or simultaneously by its C=C bonds and C21carbonyl (which leads to high diastereoselectivity). This substrate–catalyst binding, governed by the amount of tin that is added, controls the chemo- and diastereoselectivity via the coordination mode of the chiral cetaloxopromegestone.
- Published
- 2001
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6. Dimerization with Retinoid X Receptors and Phosphorylation Modulate the Retinoic Acid-induced Degradation of Retinoic Acid Receptors α and γ through the Ubiquitin-Proteasome Pathway*
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Kopf, Eliezer, Plassat, Jean-Luc, Vivat, Valérie, de Thé, Hughes, Chambon, Pierre, and Rochette-Egly, Cécile
- Abstract
In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for targeted degradation of proteins. We show that, in F9 cells and in transfected COS-1 cells, the nuclear retinoid receptors, retinoic acid receptor γ2 (RARγ2), RARα1, and retinoid X receptor α1 (RXRα1) are degraded in a retinoic acid-dependent manner through the ubiquitin-proteasome pathway. The degradation of RARγ2 is entirely dependent on its phosphorylation and on its heterodimerization with liganded RXRα1. In contrast, RARα1 degradation can occur in the absence of heterodimerization, whereas it is inhibited by phosphorylation, and heterodimerization reverses that inhibition. RXRα1 degradation is also modulated by heterodimerization. Thus, each partner of RARγ/RXRα and RARα/RXRα heterodimers modulates the degradation of the other. We conclude that the ligand-dependent degradation of RARs and RXRs by the ubiquitin-proteasome pathway, which is regulated by heterodimerization and by phosphorylation, could be important for the regulation of the magnitude and duration of the effects of retinoid signals.
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- 2000
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7. Obstructive sleep apnoea: multiple comparisons of cephalometric variables of obese and non-obese patients
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Tangugsorn, Vivat, Krogstad, Olaf, Espeland, Lisen, and Lyberg, Torstein
- Abstract
Background: Pathogenesis of obstructive sleep apnoea (OSA) is complex and not yet fully understood. Several factors contribute to OSA severity. Obesity is believed to play an important role. Nevertheless, not all OSA patients are obese. Therefore, the different features that cause nocturnal upper airway obstruction in obese and non-obese OSA patients could be expected. Purpose: To investigate the different components of cervico-craniofacial skeletal and upper airway soft tissue morphology among obese OSA, non-obese OSA patients and the controls. Patients: One hundred male OSA patients were classified into two groups on the basis of body mass index (BMI) as obese (BMI≥30 kg/m2) and non-obese (BMI<30 kg/m2). Consequently, 57 obese and 43 non-obese OSA patients were examined and compared with a control group of 36 healthy males. Study design: A comprehensive cephalometric analysis of cervico-craniofacial skeletal and upper airway soft tissue morphology was performed. Sixty-eight cephalometric variables were compared among the three groups by one way analysis of variance with Bonferroni's test. Results: Both OSA groups had aberrations of cervico-craniofacial skeletal as well as upper airway soft tissue morphology when compared with the controls. These anatomic deviations were confined to cervico-craniofacial skeletal structures in the non-obese OSA patients, whereas the obese OSA patients had more abnormalities in the upper airway soft tissue morphology, head posture and position of the hyoid bone. Conclusion: The findings imply that there should be different treatment regimens for the two subgroups of OSA patients. Cephalometric analysis together with various considerations of BMI is highly recommended as one of the most important tools in diagnosis and treatment planning for OSA patients.
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- 2000
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8. Synthesis of 10β,17α-Dimethyl-17β-(1,2-dioxopropyl)estra-5,9-diene-3-ketal
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Gertosio, Valérie, Santini, Catherine C., Basset, Jean-Marie, Bayard, François, Vivat, Michel, and Buendia, Jean
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The synthesis of a new progestomimetic steroid, analogous to the cetaloxopromegestone precursor of Trimegestone has been carried out in eight steps from 9α-hydroxyandrost-4-ene-3,17-dione. This latter compound can be obtained from the fermentation of γ-sitosterol, a sterol extracted from soya bean oil.
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- 2000
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9. An ode to Sun Valley
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Vivat, David
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Skis and skiing -- Idaho ,Sun Valley, Idaho -- Appreciation - Published
- 1990
10. Heterogeneous chemo-, regio- and diastereoselective hydrogenation of steroidic alpha-diketone
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Gertosio, V., Santini, C.C., Basset, J.M., Bayard, F., Buendia, J., and Vivat, M.
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- 1999
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11. Structural basis for engineering of retinoic acid receptor isotype-selective agonists and antagonists
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Géhin, Martine, Vivat, Valérie, Wurtz, Jean-Marie, Losson, Régine, Chambon, Pierre, Moras, Dino, and Gronemeyer, Hinrich
- Abstract
Many synthetic retinoids have been generated that exhibit a distinct pattern of agonist/antagonist activities with the three retinoic acid receptors (RARα, RARβ and RARγ). Because these retinoids are selective tools with which to dissect the pleiotropic functions of the natural pan-agonist, retinoic acid, and might constitute new therapeutic drugs, we have determined the structural basis of their receptor specificity and compared their activities in animal and yeast cells.
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- 1999
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12. Differential ligand‐dependent interactions between the AF‐2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.
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vom Baur, E., Zechel, C., Heery, D., Heine, M. J., Garnier, J. M., Vivat, V., Le Douarin, B., Gronemeyer, H., Chambon, P., and Losson, R.
- Abstract
Using a yeast two‐hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand‐ and AF‐2 activating domain (AF‐2 AD)‐dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha‐helix core of the AF‐2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF‐2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF‐2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF‐2 of nuclear receptors through different mechanisms.
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- 1996
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13. Thermal ion measurements on board Interball Auroral Probe by the Hyperboloid experiment
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Dubouloz, N., Berthelier, J.-J., Malingre, M., Girard, L., Galperin, Y., Covinhes, J., Chugunin, D., Godefroy, M., Gogly, G., Guérin, C., Illiano, J.-M., Kossa, P., Leblanc, F., Legoff, F., Mularchik, T., Paris, J., Stzepourginski, W., Vivat, F., and Zinin, L.
- Abstract
Hyperboloid is a multi-directional mass spectrometer measuring ion distribution functions in the auroral and polar magnetosphere of the Earth in the thermal and suprathermal energy range. The instrument encompasses two analyzers containing a total of 26 entrance windows, and viewing in two almost mutually perpendicular half-planes. The nominal angular resolution is defined by the field of view of individual windows ~13° × 12.5°. Energy analysis is performed using spherical electrostatic analyzers providing differential measurements between 1 and 80 eV. An ion beam emitter (RON experiment) and/or a potential bias applied to Hyperboloid entrance surface are used to counteract adverse effects of spacecraft potential and thus enable ion measurements down to very low energies. A magnetic analyzer focuses ions on one of four micro-channel plate (MCP) detectors, depending on their mass/charge ratio. Normal modes of operation enable to measure H
+ , He+ , O++ , and O+ simultaneously. An automatic MCP gain control software is used to adapt the instrument to the great flux dynamics encountered between spacecraft perigee (700 km) and apogee (20 000 km). Distribution functions in the main analyzer half-plane are obtained after a complete scan of windows and energies with temporal resolution between one and a few seconds. Three-dimensional (3D) distributions are measured in one spacecraft spin period (120 s). The secondary analyzer has a much smaller geometrical factor, but offers partial access to the 3D dependence of the distributions with a few seconds temporal resolution. Preliminary results are presented. Simultaneous, local heating of both H+ and O+ ions resulting in conical distributions below 80 eV is observed up to 3 Earth’s radii altitudes. The thermal ion signatures associated with large-scale nightside magnetospheric boundaries are investigated and a new ion outflow feature is identified associated to the polar edge of the auroral oval. Detailed distribution functions of injected magnetosheath ions and ouflowing cleft fountain ions are measured down to a few eVs in the dayside.- Published
- 1998
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14. Synthesis of Trimegestone: The First Industrial Application of Bakers' Yeast Mediated Reduction of a Ketone
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Crocq, V., Masson, C., Winter, J., Richard, C., Lemaitre, G., Lenay, J., Vivat, M., Buendia, J., and Prat, D.
- Abstract
Trimegestone (17α-methyl-17β-(2(S)-hydroxy-1-oxopropyl)estra-4,9-dien-3-one) is a new progestomimetic molecule developed by Roussel Uclaf for the treatment of postmenopausal diseases. It is produced on an industrial scale from a related 3-ketal, 17-keto norsteroid intermediate in a nine-step sequence involving hydrocyanation of the 17-keto group, alkylation of the protected cyanohydrin with ethyl magnesium bromide to give a 17α-hydroxy 20-ketone, stereospecific 17α-methylation of the corresponding 17,20-enolate, and oxidation of the 20,21-enolate with air and ketal deprotection to give 3,20,21-triketone. The key step of the synthesis is the chemo-, regio-, and almost stereospecific bioreduction of this triketone to the desired 21(S) alcohol, Trimegestone (de = 99%). This bioreduction is performed with bakers' yeast in water, thus showing the efficiency of this method at an industrial level.
- Published
- 1997
15. Differential ligand‐dependent interactions between the AF‐2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.
- Author
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Baur, E., Zechel, C., Heery, D., Heine, M. J., Garnier, J. M., Vivat, V., Le Douarin, B., Gronemeyer, H., Chambon, P., and Losson, R.
- Abstract
Using a yeast two‐hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand‐ and AF‐2 activating domain (AF‐2 AD)‐dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha‐helix core of the AF‐2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF‐2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF‐2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF‐2 of nuclear receptors through different mechanisms.
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- 1996
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16. Purification of the Human RARγ Ligand-Binding Domain and Crystallization of Its Complex with All-transRetinoic Acid
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Rochel, Natacha, Renaud, Jean-Paul, Ruff, Marc, Vivat, Valérie, Granger, Florence, Bonnier, Dominique, Lerouge, Thierry, Chambon, Pierre, Gronemeyer, Hinrich, and Moras, Dino
- Abstract
A 28-kDa fragment (residues 178–423) of the human retinoic acid receptor γ, hRARγ D3E, encompassing the ligand-binding domain (LBD) was overproduced inEscherichia coliand purified as a monomer to more than 95% purity and homogeneity. The Kdfor all-transretinoic acid binding was 0.6±0.1 nM. Crystals of the LBD complexed with all-transretinoic acid were grown at pH 7 from sodium acetate in the presence of detergents using the vapor diffusion method. They diffract to 2.0 Å using a synchrotron radiation (λ=0.91 Å) and belong to the tetragonal space group P41212 with unit cell parameters a=b=60.6 Å and c=155.3 Å, one monomer per asymmetric unit, a solvent content ofca.33%, and a Vmvalue of ≈2 Å3/dalton.
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- 1997
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17. A canonical structure for the ligand-binding domain of nuclear receptors
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Wurtz, Jean-Marie, Bourguet, William, Renaud, Jean-Paul, Vivat, Valérie, Chambon, Pierre, Moras, Dino, and Gronemeyer, Hinrich
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The ability of nuclear receptors (NRs) to activate transcription of target genes requires the binding of cognate ligands to their ligand-binding domains (LBDs). Information provided by the three-dimensional structures of the unliganded RXRα and the liganded RARγ LBDs has been incorporated into a general alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR-specif ic signature and contains most of the conserved residues that stabilize the core of the canonical fold of NR LBDs. A common ligand-binding pocket, involving predominantly hydrophobic residues, is inferred by homology modelling of the human RXRα and glucocorticoid receptor ligand-binding sites according to the RARγ holo-LBD structure. Mutant studies support these models, as well as a general mechanism for ligand-induced activation deduced from the comparison of the transcriptionally active RARγ holo- and inactive RXRα apo-LBD structures.
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- 1996
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18. Selective distribution of alpha-1 and beta adrenoceptors in pregnant rat uterus visualized by autoradiography.
- Author
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Legrand, C, Vivat, V, Rigolot, C, and Maltier, J P
- Abstract
Receptor autoradiography using (-)-3-[125I]cyanopindolol and [3H]prazosin was used to study the distribution of beta and alpha-1 adrenoceptors in the rat uterus at early and midpregnancy. The binding of [3H]prazosin to slide-mounted sections at 25 degrees C was time dependent (K1 = 3.01 x 10(7) M-1 min-1, K2 = -0.0116 min-1) and saturable (1 nM). Competition binding curves with the selective alpha-1 and alpha-2 antagonists (prazosin, yohimbine) or alpha-1 and alpha-2 agonists (phenylephrine, clonidine) showed the presence of alpha-1 adrenoceptors; autoradiographic studies revealed that this subtype is highly localized in the circular layer of the myometrium during pregnancy. (-)-3-[125I]Cyanopindolol binding to slide-mounted sections of the pregnant uterus at 25 degrees C was time dependent (K1 = 4.68 x 10(8) M-1 min-1, K2 = -0.0117 min-1) and saturable (200 pM). Competition binding curves with beta-1 or beta-2 selective agonists (dobutamine, metaproterenol) and antagonists (atenolol, ICI 118,551) revealed the presence of beta adrenoceptors in the proportion of 67% beta-2 to 33% beta-1. Hyperfilm exposed to sections of the whole pregnant uterus incubated with (-)-3-[125I]cyanopindolol with or without ICI 118,551 or atenolol showed a high density of beta-2 adrenoceptors in the longitudinal layer of the myometrium and in the placenta. A small density of beta-2 adrenoceptors was also located in the decidua basalis on day 8 of pregnancy.
- Published
- 1991
19. Sequences in the ligand-binding domains of the human androgen and progesterone receptors which determine their distinct ligand identities
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Vivat, V, Gofflo, D, Garcia, T, Wurtz, J-M, Bourguet, W, Philibert, D, and Gronemeyer, H
- Abstract
The natural ligands of the progesterone (PR) and androgen (AR) receptors, progesterone and testosterone, differ only by their 17β-substitution. To identify within the AR and PR ligand-binding domains (LBDs) the sequences responsible for the differential recognition of these ligands, chimeric LBDs assembled from five homologous AR/PR 'cassettes' linked to the GAL4-DNA binding domain were constructed, and their ligand binding and transactivation characteristics were determined. Replacing the central cassette 3 of PR by that of AR generated a progesterone- and testosterone-responsive PR LBD with the AR residues 788-RHLS-791 being specifically involved in testosterone recognition, while the introduction of the C-terminal PR cassette 5 into AR conferred progestin responsiveness onto the AR LBD. These results suggest that residues within AR 788-RHLS-791 interact with the testosterone 17β-OH, while PR cassette 5 apparently contains the amino acid(s) specifically involved in the recognition of the progesterone 17β-acetyl group. However, ligand binding and transactivation by these chimeras were significantly decreased compared with those of the parental LBDs, indicating that residues located outside of these cassettes contribute to the proper positioning of the steroids in the AR and PR ligand-binding pockets (LBPs). Indeed, certain AR/PR chimeras acquired efficient ligand binding, but were unable to transactivate, indicating that the ligand was improperly bound in the chimeric LBP and could not induce the conformational changes leading to a transcriptionally competent activation function (AF-2) within the LBD. The properties of the various LBD chimeras are discussed in view of the recently solved three-dimensional structures of the retinoid X receptor α apo- and retinoic acid receptor γ holo-LBDs.
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- 1997
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20. Pregnancy-related modifications of rat myometrial Gs proteins: ADP ribosylation, immunoreactivity and gene expression studies
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Elwardy-Mérézak, J, Maltier, J P, Cohen-Tannoudji, J, Lécrivain, J L, Vivat, V, and Legrand, C
- Abstract
Previous studies from our laboratory have suggested that post-receptor events at the level of β-adrenergic receptor—adenylate cyclase interaction could be altered in myometrium by steroid hormones or pregnancy. In this study, we have addressed this question by performing a direct evaluation of rat myometrial Gs proteins at various stages of pregnancy or 24 h after administration of progesterone. In the 50 000 gmyometrial plasma membrane fraction, in the presence of 32P-labelled NAD, cholera toxin ribosylated three predominant proteins with apparent molecular masses of 42, 47 and 55 kDa. Western blot analysis using the RM/1 antibody recognized the 42 and 47 kDa cholera toxin ADP-ribosylated bands but not the 55 kDa band. Thus, the 42 and 47 kDa immunoreactive bands were interpreted as being the small (Gsα-S) and large (Gsα-L) forms of Gs respectively. With a more purified myometrial plasma membrane fraction (105 000 g) an additional minor band of 44 kDa could be observed with both techniques. Treatment of late pregnant rats with 5 mg progesterone resulted in a significant increase in both Gsα subunits: +25% and +30% after ADP-ribosylation, +50% and +60% after Western blot analysis for Gsα-L and Gsα-S respectively. Pretreatment with the antiprogestin RU 486 completely suppressed the effect of progesterone, suggesting that the expression of Gsα subunits may be under the control of progesterone. However, changes in the myometrial content of Gs in progesterone-treated rats were not associated with concomitant variations in the steady-state levels of mRNA as demonstrated by Northern blot analysis. These data suggest a post-translational regulation of Gs expression by progesterone. Amounts of ADP-ribosylated Gs showed characteristic changes during the course of pregnancy with a fourfold or threefold increase (P<0·05) on day 15 versus day 12 or delivery respectively. During pregnancy, or after progesterone administration, myometrial alterations of Gs strongly correlated (r=0·913, P<0·01) with the cholera toxin-stimulated adenylate cyclase activity. These findings provide evidence that changes in myometrial amounts of functional Gs i) are controlled by the hormonal status of pregnancy and progesterone and ii) play an important role in the transduction pattern of adenylate cyclase activity during the course of pregnancy.
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- 1994
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21. Regulation by progesterone of the high-affinity state of myometrial β-adrenergic receptor and of adenylate cyclase activity in the pregnant rat
- Author
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Cohen-Tannoudji, J., Vivat, V., Heilmann, J., Legrand, C., and Maltier, J. P.
- Abstract
The effects of pregnancy or progesterone dominance on the β-adrenergic responsiveness of the uterus were studied in myometrial membranes from mid-and late-pregnant rats (day 15 and on the 16th h of day 22 of pregnancy respectively) or 24 h after administration of progesterone. Levels of the high (RH)- and low (RL)-affinity states of the β-adrenergic receptor were determined by competition experiments between 125I-labelled cyanopindolol binding and the selective β-agonist isoproterenol. The ratio KL/KH(respective dissociation constants) was determined since it also reflects the degree of formation of the high-affinity state of the β-adrenergic receptor. From day 15 to the 10th h of day 22 of pregnancy, two distinct affinity states were apparent: 80–55% RH(KH=0·31–0·21 μm) and 45–20% RL(KL=14–5 μm) with a ratio of KL/KHof 55–34. In the last 6 h before birth, β-adrenergic receptors underwent uncoupling which was paralleled by decreased responsiveness of myometrial adenylate cyclase to isoproterenol (maximum velocity (Vmax)=17±3 vs 44±3 fmol cyclic AMP/10 min per mg protein on day 15). At this stage of pregnancy, previous exposure to progesterone resulted in a 1·8-fold increase in 125I-labelled cyanopindolol-binding sites (Bmax) and the reappearance of the high-affinity state (67% RH, KH=0·19±0·04 (s.e.m.) μm, ratio KL/KH=81·1 ± 16·9). These results were reversed in the presence of the antiprogestin RU486 (100% RL, KL=24·6±4·1 μm, 41% reduction of Bmax). Moreover, after progesterone, adenylate cyclase activity was strongly stimulated by isoproterenol (Vmax=60±12 fmol cyclic AMP/10 min per mg protein vs 17±3 in controls). The data suggest (1) that progesterone may exert a permissive effect on β-adrenergic responsiveness of the pregnant rat myometrium and (2) that at term, both a desensitization mechanism involving uncoupling of β-adrenergic receptors and a decrease in activation of adenylate cyclase lead to a loss of myometrial response to β-agonists.
- Published
- 1991
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22. 3 Is it acceptable to use technical monitoring to assess palliative care patients’ level of consciousness? a qualitative exploration with patients and relatives
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Krooupa, Anna-Maria, Stone, Paddy, McKeever, Stephen, and Vivat, Bella
- Abstract
IntroductionBispectral Index (BIS) monitoring uses electroencephalographic data to objectively measure patients’ level of consciousness and might be a useful supplement to clinical observation when using sedative medication in palliative care. However its acceptability to UK palliative care service users is unknown.AimTo explore the acceptability of BIS technology with UK hospice patients and relatives.MethodsWe conducted focus groups and individual interviews with patients and relatives in a UK hospice and analysed data thematically.Results10 patients and 15 relatives participated in seven focus groups and three interviews. Responses from patient participants were similar to those from relatives and four themes emerged:Knowledge and experience of current monitoring of sedation/consciousnessAcceptable duration of monitoringReservations about using technological devices in palliative carePotential benefits of using BIS.Participants’ comments on potential benefits included that BIS alongside routine clinical practice might help ensure comfort at the end of life and serve to assure medical needs are being met particularly for people who cannot communicate. Participants generally felt that the duration of BIS monitoring should be informed by each patient’s individual needs while some expressed that patients and/or families should be consulted before using the monitor. Participants also noted that BIS while possibly obtrusive is not invasive.ConclusionsOur participants considered BIS acceptable for monitoring level of consciousness and possibly helpful at the end of life. We therefore initiated an observational study exploring use of this technology in the clinical care of UK hospice inpatients.
- Published
- 2018
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23. 52 What is current practice when using sedative medication at the end of life in a london hospice and teaching hospital? a mixed methods investigation for i-can-care
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Vivat, Bella, Harrington, Jane, Bemand-Qureshi, Lucy, Davis, Sarah, and Stone, Patrick
- Abstract
IntroductionThe I-CAN-CARE research programme explores care and assessment of dying patients in two under-researched areas: use of sedative medication at the end of life and prognostication. We present findings from an exploration of current practice relating to sedative use.AimsTo explore the understandings of palliative care physicians and nurses in London regarding use of sedatives, and simultaneously audit deceased patient records for documented sedative use.MethodsFocus groups with experienced palliative care physicians and nurses working in a London hospice or hospital/community-based palliative care were audio-recorded, transcribed, and analysed thematically. Deceased patient notes at both sites were audited independently, working backwards from December 2015 to obtain 25 patients at each site who had received continuous sedation at the end of life.ResultsFocus group participants (ten consultants/SpRs; seventeen senior nurses) all said they used sedative medication for managing agitation or distress; aiming for patients to be “comfortable”, “calm”, or “relaxed”, and selecting drugs and dosages as appropriate for patients’ individual needs, aiming to start with the lowest doses possible. None used structured observational tools to assess the effects of sedatives; strongly preferring clinical observation and judgement. The audit found usually low dosages: 10 mg/day median continuous dose midazolam; range 0.35–69.5, with written comments often addressing patients’ perceived comfort.ConclusionsFocus group participants considered the role of sedative medication as primarily symptom management, emphasising individualised care, and using lowest dosages possible to achieve patient comfort, assessed using clinical judgement. Data from patient records corroborated these qualitative findings.
- Published
- 2017
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24. P-107 Identification and evaluation of observational measures for monitoring sedation in adult palliative care patients: findings from a systematic review for i-can-care
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Krooupa, Anna-Maria, Vivat, Bella, Candy, Bridget, McKeever, Stephen, Marcus, Elena, Kupeli, Nuriye, and Stone, Paddy
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IntroductionPalliative sedation is sometimes used to manage refractory symptoms in adult palliative care patients in the UK. However, there is limited knowledge regarding which observational tools are most appropriate for monitoring the effects of sedative drugs. This review is a part of the I-CAN-CARE, a Marie Curie funded research programme.ObjectiveTo identify and critique primary studies describing the use of observational measures to assess the depth of sedation at the end of life.MethodsWe searched six databases (CENTRAL, Cinahl, Embase, Medline, PsychINFO, Scopus, and Web of Science) until November 2016, using search terms combining subject headings and free-text terms. Primary studies reporting on the use of observational measures to assess the effect of palliative sedation were eligible for inclusion. Two investigators independently reviewed the titles, abstracts and full-text articles retrieved, and performed the data extraction. From the included papers, a list of observational tools, their characteristics and the degree to which they have been validated, using the COSMIN checklist (Mokkink et al., 2010), will be generated.Results to-dateThe searches yielded 10 208 articles after removing duplicates. The majority of studies meeting the inclusion criteria and discussing the monitoring of sedation reported using observational measures for assessing not only depth of sedation but also symptom severity. Of the identified scales assessing management of intractable symptoms, only one had been validated for palliative care settings. Five measures assessing level of consciousness had undergone partial validation for use in palliative care. Six of the observational measures identified had been evaluated for their psychometric properties in single study populations.ConclusionsFew measures for monitoring sedation have been evaluated for their psychometric properties in palliative care. Next steps will be a detailed evaluation of the overall quality of the studies identified, and of the validity and reliability of the scales used. Definitive results will become available in February 2017.
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- 2017
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25. 23 Talking about the future with homeless people with ill health: the need for a different conversation
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Hudson, Briony F, Shulman, Caroline, Low, Joseph, Hewett, Nigel, Daley, Julian, Davis, Sarah, Brophy, Niamh, Howard, Diana, Vivat, Bella, Kennedy, Peter, and Stone, Patrick
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IntroductionHomelessness is associated with death at a young age, frequently related to physical and mental health problems complicated by drug or alcohol dependence (Stringfellow et al., 2015). Homeless people experience high symptom burden at the end-of-life (Tobey et al., 2016), yet access to palliative care services is limited (Shulman et al., In press). Conversations around future wishes and preferences with homeless people rarely take place.AimTo explore the barriers to conversations about the future with unwell homeless people and alternative approaches to these difficult conversations.MethodsFocus groups and interviews were used to explore views and experiences around palliative care with currently and formerly homeless people (n=38), healthcare professionals (n=32), hostel and outreach staff (n=39) and drug and alcohol workers (n=4), from three London boroughs. Verbatim transcripts were analysed using thematic analysis.ResultsThree themes were identified relating to the challenges of discussing future care preferences: the recovery focused nature of services; uncertainty around when and how to have conversations; fear of negative impact on the homeless person and staff.ConclusionsThere is little acknowledgement, discussion or planning around the health needs of unwell homeless people who are at risk of dying, reducing opportunities for person-centred care. An approach that considers current and continuing care needs that accommodates potential improvements and deterioration is needed. Identifying those whose health is a concern, rather than those thought to be imminently dying may help to ensure the wishes and choices of homeless people are respected, if their health deteriorates.References. Shulman C, Hudson BF, Low J, Hewett N, Daley J, Kennedy P, Davis S, Brophy N, Howard D, Vivat B, Stone P, (In press). Homelessness at the end of life: A qualitative analysis of the barriers in providing palliative care for people who are homeless. Palliative Medicine.. Stringfellow EJ, Kim TW, Pollio DE, Kertesz SG. Primary care provider experience and social support among homeless-experienced persons with tri-morbidity. Addiction science & clinical practice2015;10:A64–A64.. Tobey M, Manasson J, Decarlo K, Ciraldo-maryniuk K, Gaeta JM, Wilson E. Homeless Individuals Approaching the End of Life: Symptoms and Attitudes. Journal of Pain and Symptom Management2016; In press.
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- 2017
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26. Which measures assessing quality of death and dying and satisfaction with care at the very end of life have been psychometrically validated? A systematic review
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Kupeli, Nuriye, Candy, Bridget, Vivat, Bella, Harrington, Jane, Davis, Sarah, Sampson, Elizabeth L, Gola, Anna, Lodwick, Rebecca, and Stone, Paddy
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IntroductionThe very end of life can be associated with pain, anxiety and caregiver burden. Numerous measures seek to assess the quality of death and dying and satisfaction with care, but there is a lack of evidence and consensus on the best tools.AimsTo identify all existing tools for assessing quality of death and dying and the quality of care and satisfaction with care at the very end of life, and systematically evaluate those which have been psychometrically validated.MethodFour databases (Medline, Embase, Cinahl and Psycinfo) were searched in February 2016 using a combination of MeSH and free-text terms on end of life and satisfaction with care. Article titles, abstracts and full-text papers were reviewed to identify all papers reporting multi-item measures for assessing quality of death and dying and/or quality of care and satisfaction with care at the very end of life. Articles reporting on at least one psychometric investigation of the measures identified were then assessed for quality, using the COSMIN checklist (Mokkink, 2010).ResultsThe initial search terms identified 4136 articles after excluding any duplicates. Seventy-seven papers, reporting 48 different measures, met the initial inclusion criteria. The most commonly used measures were the Quality Of Death and Dying (QODD; Patrick, 2001) and FAMCARE (Kristjanson, 1986). Both have been validated in a variety of cultural settings and participant groups.ConclusionMany measures assess quality of death and dying and satisfaction with care, but few have been thoroughly validated. QODD and FAMCARE are the best of those assessed.ReferencesKristjanson LJ.Indicators of quality of palliative care from a family perspective. J Palliat Care1986;1(2): 8–17Mokkink LB, Terwee CB, Patrick DL, et al. The COSMIN checklist for assessing the methodological quality of studies on measurement properties of health status measurement instruments: an international Delphi study. Quality of Life Research2010;19(4):539–549Patrick DL, Engelberg RA, Curtis JR.Evaluating the quality of dying and death. J Pain Symptom Manage2001;22(3):717–726
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- 2016
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27. Untitled.
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CROWE, STEVE, VALDEZ, DENNY, MIRIZI, NICK, VIVAT, DAVID, MAY, JAMIE, and WILLIAMS, NOAH
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- 2009
28. DEVELOPMENT AND VALIDATION OF A CROSS-CULTURAL EORTC MEASURE OF SPIRITUAL WELLBEING (SWB) FOR PALLIATIVE CARE PATIENTS WITH CANCER
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Vivat, B, Young, T, Winstanley, J, Arraras, JI, Bennett, MI, Brédart, A, Costantini, A, Fisher, SE, Greimel, E, Guo, J, Irarrazaval, ME, Kobayashi, K, Kruizinga, R, Navarro, M, Omidvari, S, Rohde, GE, Serpentini, S, van Laarhoven, HWM, and Yang, G
- Abstract
IntroductionSpiritual care and spiritual wellbeing (SWB) are central to palliative care, but no measures of SWB have yet been developed cross-culturally.Aim(s) and method(s)In 2002 the EORTC Quality of Life (QL) Group began international development of an SWB measure for palliative patients. Three domains of SWB were initially hypothesised, and items developed accordingly. Data for Phase IV field-testing and validation of the measure were collected from January 2012 to July 2013. Participants completed the 36-item provisional SWB measure and a structured debriefing interview. EORTC QLQ-C15-PAL, socio-demographic and clinical data were also collected, and a sub-set of test-retest data. The scale structure was assessed using Principal Component Analysis (PCA) and Rasch analysis and further validity explored using known group comparisons.Results458 patients from 14 countries took part; 188 Christian, 50 Muslim, 23 Buddhist, and 158 with no religion. All items showed good score distribution. 275 patients (60%) found no items problematic, but small percentages indicated difficulties with 6 items. Combining patient feedback with PCA and Rasch analysis led to deletion of a few items. Four distinct domains explain 53% of the variance. No remarkable differential item functioning (DIF) was found for age, sex, geographical region or belief in God. Goodness of fit measures were within guidelines. Global SWB correlated weakly with global QL.Conclusion(s)This EORTC measure of SWB is available for use in palliative care research and practice, and has both measurement and intervention characteristics. Future studies will specifically recruit people in minority religious and/or ethnic communities under-represented in this already diverse sample.
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- 2014
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29. ChemInform Abstract: Ambient Temperature Nitrogen‐Directed Difluoroalkynylborane Carboni—Lindsey Cycloaddition Reactions.
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Vivat, Jerome F., Adams, Harry, and Harrity, Joseph P. A.
- Abstract
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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- 2010
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30. ChemInform Abstract: Synthesis of Trimegestone: The First Industrial Application of Bakers′ Yeast Mediated Reduction of a Ketone.
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CROCQ, V., MASSON, C., WINTER, J., RICHARD, C., LEMAITRE, G., LENAY, J., VIVAT, M., BUENDIA, J., and PRAT, D.
- Abstract
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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- 1997
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31. Erratum: A canonical structure for the ligand-binding domain of nuclear receptors
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Wurtz, Jean-Marie, Bourguet, William, Renaud, Jean-Paul, Vivat, Valérie, Chambon, Pierre, Moras, Dino, and Gronemeyer, Hinrich
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- 1996
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32. The Manhattan Chess Association.
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CAISSA, VIVAT
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- 1858
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