6 results on '"Wehbi V"'
Search Results
2. Dépistage du syndrome d'apnées du sommeil en entreprises: validation d'un questionnaire
- Author
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Vitoux, JF, Guerin, P, Vitoux-Thony, MC, Ben Amgar, L, Coulondre, D, Delattre, A, Delaunay, G, Dubourg, C, Lesage, F, Leton, M, Massin, N, Mur, JM, Nieuwjaer, A, Reignault, A, Tekulescu, D, and Wehbi, V
- Published
- 1995
- Full Text
- View/download PDF
3. Selective modulation of follicle-stimulating hormone signaling pathways with enhancing equine chorionic gonadotropin/antibody immune complexes.
- Author
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Wehbi V, Decourtye J, Piketty V, Durand G, Reiter E, and Maurel MC
- Subjects
- Antigen-Antibody Complex immunology, Arrestins metabolism, Cell Line, Cyclic AMP metabolism, Enzyme-Linked Immunosorbent Assay, Female, Fluorescence Resonance Energy Transfer, Humans, Isoquinolines pharmacology, Kinetics, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Phosphorylation drug effects, RNA, Small Interfering, Sulfonamides pharmacology, beta-Arrestin 1, beta-Arrestins, Antibodies immunology, Antigen-Antibody Complex pharmacology, Chorionic Gonadotropin immunology, Follicle Stimulating Hormone metabolism, Gonadotropins, Equine immunology, Signal Transduction drug effects
- Abstract
The injection of equine chorionic gonadotropin (eCG) in dairy goats induces the production of anti-eCG antibodies (Abs) in some females. We have previously shown that Abs negatively modulate the LH and FSH-like bioactivities of eCG, in most cases, compromising fertility in treated females. Surprisingly, we found out that some anti-eCG Abs improved fertility and prolificity of the treated females, in vivo. These Abs, when complexed with eCG, enhanced LH and FSH ability to induce steroidogenesis on specific target cells, in vitro. In the present study, we analyzed the impact of three eCG/anti-eCG Ab-enhancing complexes on two transduction mechanisms triggered by the FSH receptor: guanine nucleotide-binding protein alphaS-subunit/cAMP/protein kinase A (PKA) and beta-arrestin-dependent pathways, respectively. In all cases, significant enhancing effects were observed on ERK phosphorylation compared with eCG alone. However, cAMP production and PKA activation induced by eCG could be differently modulated by Abs. By using a pharmacological inhibitor of PKA and small interfering RNA-mediated knock-down of endogenous beta-arrestin 1 and 2, we demonstrated that signaling bias was induced and was clearly dependent on the complexed Ab. Together, our data show that eCG/anti-eCG Ab-enhancing complexes can differentially modulate cAMP/PKA and beta-arrestin pathways as a function of the complexed Ab. We hypothesize that enhancing Abs may change the eCG conformation, the immune complex acquiring new "biased" pharmacological properties ultimately leading to the physiological effects observed in vivo. The modulation of ligand pharmacological properties by Abs opens promising research avenues towards the optimization of glycoprotein hormone biological activities and, more generally, the development of new therapeutics.
- Published
- 2010
- Full Text
- View/download PDF
4. Partially deglycosylated equine LH preferentially activates beta-arrestin-dependent signaling at the follicle-stimulating hormone receptor.
- Author
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Wehbi V, Tranchant T, Durand G, Musnier A, Decourtye J, Piketty V, Butnev VY, Bousfield GR, Crépieux P, Maurel MC, and Reiter E
- Subjects
- Animals, Blotting, Western, Cattle, Cell Line, Cyclic AMP-Dependent Protein Kinases metabolism, Enzyme Activation drug effects, Female, Horses, Humans, Immunoprecipitation, Luteinizing Hormone chemistry, Luteinizing Hormone metabolism, Luteinizing Hormone pharmacology, Mice, Phosphorylation drug effects, Protein Binding, Protein Transport drug effects, RNA, Small Interfering, Receptors, FSH agonists, Receptors, FSH antagonists & inhibitors, Ribosomal Protein S6 metabolism, Swine, beta-Arrestins, Arrestins metabolism, Luteinizing Hormone analogs & derivatives, Receptors, FSH metabolism, Signal Transduction drug effects
- Abstract
Deglycosylated FSH is known to trigger poor Galphas coupling while efficiently binding its receptor. In the present study, we tested the possibility that a deglycosylated equine LH (eLHdg) might be able to selectively activate beta-arrestin-dependent signaling. We compared native eLH to an eLH derivative [i.e. truncated eLHbeta (Delta121-149) combined with asparagine56-deglycosylated eLHalpha (eLHdg)] previously reported as an antagonist of cAMP accumulation at the FSH receptor (FSH-R). We confirmed that, when used in conjunction with FSH, eLHdg acted as an antagonist for cAMP accumulation in HEK-293 cells stably expressing the FSH-R. Furthermore, when used alone at concentrations up to 1 nM, eLHdg had no detectable agonistic activity on cAMP accumulation, protein kinase A activity or cAMP-responsive element-dependent transcriptional activity. At higher concentrations, however, a weak agonistic action was observed with eLHdg, whereas eLH led to robust responses whatever the concentration. Both eLH and eLHdg triggered receptor internalization and led to beta-arrestin recruitment. Both eLH and eLHdg triggered ERK and ribosomal protein (rp) S6 phosphorylation at 1 nM. The depletion of endogenous beta-arrestins had only a partial effect on eLH-induced ERK and rpS6 phosphorylation. In contrast, ERK and rpS6 phosphorylation was completely abolished at all time points in beta-arrestin-depleted cells. Together, these results show that eLHdg has the ability to preferentially activate beta-arrestin-dependent signaling at the FSH-R. This finding provides a new conceptual and experimental framework to revisit the physiological meaning of gonadotropin structural heterogeneity. Importantly, it also opens a field of possibilities for the development of selective modulators of gonadotropin receptors.
- Published
- 2010
- Full Text
- View/download PDF
5. Structure-function relationships of the variable domains of monoclonal antibodies approved for cancer treatment.
- Author
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Magdelaine-Beuzelin C, Kaas Q, Wehbi V, Ohresser M, Jefferis R, Lefranc MP, and Watier H
- Subjects
- Amino Acid Sequence, Animals, Antibodies, Monoclonal genetics, Antibodies, Monoclonal physiology, Binding Sites, Antibody, Humans, Immunoglobulin Variable Region genetics, Immunotherapy, Models, Biological, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary genetics, Protein Structure, Tertiary physiology, Recombinant Fusion Proteins therapeutic use, Sequence Homology, Amino Acid, Structure-Activity Relationship, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal therapeutic use, Immunoglobulin Variable Region chemistry, Immunoglobulin Variable Region physiology, Neoplasms therapy
- Abstract
Due to their exquisite specificity for a given epitope on the target antigen, recombinant monoclonal antibodies (rmAb) can deliver "targeted therapy" in oncology. This review focuses on the structural bases of "antigen specificity" to aid clinical researchers and pharmacologists in managing these new drugs. The fine structure of the Fv (Fragment variable) module (combination of VH and VL domains) from the five unconjugated antibodies currently approved for cancer treatment, namely rituximab, cetuximab, alemtuzumab, trastuzumab and bevacizumab, is presented and analysed. Co-crystal and functional studies are reviewed to define rmAb residues contributing to antigen binding site (paratope)-epitope interfaces. The genetic origin of these recombinant monoclonal antibodies, determined through the IMGT/3Dstructure-DB database and IMGT/V-QUEST (http://imgt.cines.fr), is presented, allowing the evaluation of homologies between antibodies and their closest germline human counterparts and hence their possible immunogenicity. Overall, the IMGT standards appear as a first and crucial step in the evaluation of recombinant antibodies.
- Published
- 2007
- Full Text
- View/download PDF
6. [Action of hemocoagulase on the cicatrization of the dura mater in rabbits. Preliminary results].
- Author
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Steimle R, Oppermann A, Dakkar A, Carbillet JP, Jacquet G, Abdul Razzak A, and Wehbi V
- Subjects
- Animals, Dura Mater surgery, Male, Rabbits, Time Factors, Batroxobin, Dura Mater pathology, Peptide Hydrolases
- Abstract
The present study compares the cicatrization of the dura by administration of I.M. hemocoagulase. This study was done on 6 rabbits and 6 control animals. The authors think that the cicatrization is a little slower but of better quality. The hemocoagulase seems to favorize the vasculo-exsudative process of cicatrization. The fibrinous deposits are more important too. Perhaps the occlusion of C.S. fluid fistulas could be favorized by means of the used product. Definitive conclusions are not possible for the moment but a work on a larger scale is projected.
- Published
- 1978
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