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304. MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER’S DISEASE: DESIGN AND BASELINE DATA

Author

Vellas, B., primary, Gillette-Guyonnet, S., additional, Touchon, J., additional, Dantoine, T., additional, Dartigues, J.F., additional, Cuffi, M.N., additional, Bordes, S., additional, Gasnier, Y., additional, Robert, P., additional, Bories, L., additional, Rouaud, O., additional, Desclaux, F., additional, Sudres, K., additional, Bonnefoy, M., additional, Pesce, A., additional, Dufouil, C., additional, Lehericy, S., additional, Chupin, M., additional, Mangin, J.F., additional, Payoux, P., additional, Adel, D., additional, Legrand, P., additional, Catheline, D., additional, Kanony, C., additional, Zaim, M., additional, Molinier, L., additional, Costa, N., additional, Delrieu, J., additional, Voisin, T., additional, Faisant, C., additional, Lala, F., additional, Nourhashemi, F., additional, Rolland, Y., additional, Abellan Van Kan, G., additional, Dupuy, C., additional, Cantet, C., additional, Cestac, P., additional, Belleville, S., additional, Willis, S., additional, Cesari, M., additional, Weiner, M.W., additional, Soto, M.E., additional, Ousset, P.J., additional, Andrieu, S., additional, and Carrie, I., additional

Published
2014
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305. Particularités de la prise en charge non médicamenteuse de la BPCO chez les sujets âgés. Réhabilitation, sevrage tabagique, nutrition et éducation thérapeutique

Author

Guilleminault, L., Rolland, Y., and Didier, A.

Abstract

La bronchopneumopathie chronique obstructive (BPCO) est une pathologie respiratoire à l’origine d’une mortalité et d’un handicap important. Les sujets âgés de plus de 65 ans sont plus fréquemment touchés par cette maladie que les patients plus jeunes. Les interventions non pharmacologiques prennent une place importante dans la prise en charge de la BPCO et présentent des spécificités chez la personne âgée. Le sevrage tabagique doit être proposé quel que soit l’âge compte tenu de l’amélioration de la qualité de vie et du risque d’hospitalisation. L’augmentation de l’activité physique est également source de réduction des symptômes de dyspnée. Des tests sous-maximaux comme le « Short Physical Performance Battery » sont à privilégier. L’utilisation du test de marche de 6minutes est également incontournable. L’augmentation de l’activité physique doit se faire en association avec l’amélioration du statut nutritionnel. Un dépistage de la dénutrition par questionnaire, calcul de l’indice de masse corporelle et dosage de l’albuminémie est recommandé chez le sujet âgé. En cas de dénutrition, la supplémentation orale semble diminuer le risque de réhospitalisation. Toutes ces mesures doivent s’intégrer dans un programme d’éducation thérapeutique adapté aux difficultés présentées par les personnes âgées (surdité, isolement…).

Published
2018
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306. Phosphorylation of SOS1 on tyrosine 1196 promotes its RAC GEF activity and contributes to BCR-ABL leukemogenesis

Author

Gerboth, S, Frittoli, E, Palamidessi, A, Baltanas, F C, Salek, M, Rappsilber, J, Giuliani, C, Troglio, F, Rolland, Y, Pruneri, G, Kreutmair, S, Pallavicini, I, Zobel, M, Cinquanta, M, Minucci, S, Gomez, C, Santos, E, Illert, A L, and Scita, G

Abstract

Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. Although the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro and for platelet-derived growth factor (PDGF) activation of RAC- and RAC-dependent actin remodeling and cell migration. SOS1 is also phosphorylated on Y1196 by BCR-ABL in chronic myelogenous leukemic cells. Importantly, in these cells, SOS1 is required for BCR-ABL-mediated activation of RAC, cell proliferation and transformation in vitro and in a xenograft mouse model. Finally, genetic removal of Sos1 in the bone marrow-derived cells (BMDCs) from Sos1fl/flmice and infected with BCR-ABL causes a significant delay in the onset of leukemogenesis once BMDCs are injected into recipient, lethally irradiated mice. Thus, SOS1 is required for full transformation and critically contribute to the leukemogenic potential of BCR-ABL.

Published
2018
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315. P073 - Mise en œuvre des méthodes d’« Optimal Matching » et de Classification ascendante hiérarchique pour l’étude du parcours de soins de patients âgés hospitalisés après une chute

Author

Mounié, M., Fabre, D., Rapp, T., Blain, H., Rolland, Y., Tchalla, A., Carcaillon-Bentata, L., Nathalie, B., Assous, L., Apparitio, S., Caby, D., Reina, N., Andre, L., Demeulemeester, R., Molinier, L., and Costa, N.

Abstract

L’étude des chutes chez la personne âgée est d'un intérêt majeur en santé publique de par leur grande incidence et leurs conséquences en termes de prise en charge, de survie et de coût. Dans ce contexte, l’étude du parcours de soins suite à une chute avec hospitalisation est primordiale, permet d'identifier des profils de patients similaires et de proposer des prises en charge adaptées aux différents types de patient. L'objectif de cette étude est d’évaluer les parcours de soins deux ans après une chute avec hospitalisation, en termes de quantité et de types de soins, de caractériser des groupes de patients ayant des parcours similaires et d’étudier l'impact de ces groupes sur les coûts de prise en charge.

Published
2023
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318. Determination of appendicular muscle mass by dual energy X-ray absorptiometry method in women with sarcopenia and Alzheimer's disease

Author

Gillette-Guyonnet S, Nourhashemi F, Andrieu S, de Glisezinski I, Grandjean H, Rolland Y, Daniel Riviere, and Vellas B

Subjects
Aged, 80 and over, Anthropometry, Muscular Atrophy, Absorptiometry, Photon, Cross-Sectional Studies, Adipose Tissue, Alzheimer Disease, Case-Control Studies, Body Composition, Prevalence, Humans, Female, France, Muscle, Skeletal, Aged
Abstract

To study appendicular muscle mass in women with Alzheimer's disease (AD) to investigate the association between sarcopenia and AD. To examine the AD associated changes in body fat distribution.a cross-sectional study of 32 women with AD and 32 healthy age and bone mineral density matched women.Toulouse, France.No differences were noted in fat free soft tissue mass or Appendicular Skeletal Muscle (ASM) mass between AD women and control women. The difference of ASM (kg) /height2 (m)2, used as an index of relative skeletal muscle mass, was not statistically significative between the two groups. The prevalence of sarcopenia increased from 21.9 % in healthy elderly women to 40.6 % in AD women but the difference was not statistically significant. No statistically significant relationship emerged between sarcopenia and AD (OR= 0.41, CI 0.12-1.4). Moreover, total body fat mass was significantly lower in women with AD than in the age -, sex - and bone mineral density - matched controls.AD are not necessary linked to sarcopenia. The decrease in adipose tissue in women with AD could be one more factor involving estrogen deficiency in the etiology of the disease.

Published
2000

319. Feasibility [corrected] of regular physical exercise for patients with moderate to severe Alzheimer disease

Author

Rolland Y, Rival L, Fabien PILLARD, Lafont C, Rivére D, Albaréde J, and Vellas B

Subjects
Aged, 80 and over, Freedom, Male, Aging, Mental Disorders, Nutritional Status, Cognition, Alzheimer Disease, Feasibility Studies, Humans, Accidental Falls, Female, Exercise, Gait, Aged
Abstract

Physical activity delays loss of autonomy in the elderly. In patients with Alzheimer disease (AD), physical activity could be a useful strategy in therapeutic management by delaying loss of functional independence and the usual complications of the disease.To determine, using standardized tools, the effects on autonomy (ADL, IADL), cognitive function (MMS), nutritional status (MNA), behavioral problems (NPI) and risk of falls (Tinetti test) of a physical exercise program in patients with AD.Twenty-three subjects (13 men and 10 women, aged 71-92 years, mean 78 years) with AD (mean MMS 16, range 1-23) carried out for a mean of 7 weeks (5-12 weeks) a program of endurance exercise (walking, exercise bicycle) adapted to their individual capacities. Standardized gerontological evaluation was performed before and after the study.No significant change in autonomy (ADL, IADL) was observed. There was an improvement in the MNA (p0.001) and the MMS (p0.001). Risk of falls (p0.01) and behavioral problems (p0.05) decreased. These results were obtained without increasing family workload.We suggest that physical activity is a therapeutic option which can reduce nutritional and behavioral complications and risk of falls in subjects with AD.

Published
2000

323. Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US task force recommendations

Author

Vellas, B., primary, Pahor, M., additional, Manini, T., additional, Rooks, D., additional, Guralnik, J. M., additional, Morley, J., additional, Studenski, S., additional, Evans, W., additional, Asbrand, C., additional, Fariello, R., additional, Pereira, S., additional, Rolland, Y., additional, Abellan Van Kan, G., additional, Cesari, M., additional, Chumlea, W. M. C., additional, and Fielding, R., additional

Published
2013
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324. Tools in the Assessment of Sarcopenia

Author

Cooper, C., primary, Fielding, R., additional, Visser, M., additional, van Loon, L. J., additional, Rolland, Y., additional, Orwoll, E., additional, Reid, K., additional, Boonen, S., additional, Dere, W., additional, Epstein, S., additional, Mitlak, B., additional, Tsouderos, Y., additional, Sayer, A. A., additional, Rizzoli, R., additional, Reginster, J. Y., additional, and Kanis, J. A., additional

Published
2013
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325. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

Author

Garin, E., primary, Lenoir, L., additional, Edeline, J., additional, Laffont, S., additional, Mesbah, H., additional, Porée, P., additional, Sulpice, L., additional, Boudjema, K., additional, Mesbah, M., additional, Guillygomarc’h, A., additional, Quehen, E., additional, Pracht, M., additional, Raoul, J. L., additional, Clement, B., additional, Rolland, Y., additional, and Boucher, E., additional

Published
2013
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326. OP-02 Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: A new personalized promising concept

Author

Garin, E., primary, Lenoir, L., additional, Edeline, J., additional, Laffont, S., additional, Mesbah, H., additional, Porée, P., additional, Raoul, J.L., additional, Boudgema, K., additional, Sulpice, L., additional, Clement, B., additional, Rolland, Y., additional, and Boucher, E., additional

Published
2013
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334. Synthesis and cytotoxic and antitumor activity of esters in the 1,2-dihydroxy-1,2-dihydroacronycine series

Author

Elomri, A. Mitaku, S. Michel, S. Skaltsounis, A.-L. Tillequin, F. Koch, M. Pierré, A. Guilbaud, N. Léonce, S. Kraus-Berthier, L. Rolland, Y. Atassi, G.

Abstract

Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17, 19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.

Published
1996

335. Synthesis and anti-proliferative activity of 2-hydroxy-1,2-dihydroacronycine glycosides

Author

Mitaku, S. Skaltsounis, A.-L. Tillequin, F. Koch, M. Rolland, Y. Pierré, A. Atassi, G.

Abstract

Purpose. Combination of the acronycine pharmacophore with various sugar units appeared of interest, since numerous anticancer agents possess a sugar moiety, which strongly influence both their bioavailability and their selective toxicity towards tumor cells. Methods. A series of 2-hydroxy-1,2-dihydroacronycine glycosides were synthetized, by condensation of the racemic aglycone with appropriate glycoside donors. Their effect on the inhibition of L1210 cell proliferation were evaluated. Results. Compounds 6a, 6b, 11a, 11b, and 12a, 12b, including a halogenated sugar moiety displayed activities of the same order of magnitude as acronycine itself. Compounds 7a, 7b, and 8a, 86, bearing a 2,3,6-trideoxy-3-azido-L-lyxo- and L-arabino-hexopyranose unit respectively, were significantly more potent than acronycine in inhibiting cell proliferation. Conclusions. The activity of 2-hydroxy-1,2-dihydroacronycine glycosides seems to be related to the lipophilicity of the sugar unit.

Published
1996

343. Frailty and sarcopenia: definitions and outcome parameters

Author

Cooper, C., primary, Dere, W., additional, Evans, W., additional, Kanis, J. A., additional, Rizzoli, R., additional, Sayer, A. A., additional, Sieber, C. C., additional, Kaufman, J.-M., additional, Abellan van Kan, G., additional, Boonen, S., additional, Adachi, J., additional, Mitlak, B., additional, Tsouderos, Y., additional, Rolland, Y., additional, and Reginster, J.-Y. L., additional

Published
2012
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345. BIOMARKERS OF SARCOPENIA IN CLINICAL TRIALS RECOMMENDATIONS FROM THE INTERNATIONAL WORKING GROUP ON SARCOPENIA

Author

CESARI, M., primary, FIELDING, R.A., additional, PAHOR, M., additional, GOODPASTER, B., additional, HELLERSTEIN, M., additional, ABELLAN VAN KAN, G., additional, ANKER, S.D., additional, RUTKOVE, S., additional, VRIJBLOED, J.W., additional, ISAAC, M., additional, ROLLAND, Y., additional, M’RINI, C., additional, AUBERTIN-LEHEUDRE, M., additional, CEDARBAUM, J.M., additional, ZAMBONI, M., additional, SIEBER, C.C., additional, LAURENT, D., additional, EVANS, W.J., additional, ROUBENOFF, R., additional, MORLEY, J.E., additional, and VELLAS, B., additional

Published
2012
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347. Crustal-scale structure of South Tien Shan: implications for subduction polarity and Cenozoic reactivation

Author

Loury, C., Rolland, Y., Guillot, S., Mikolaichuk, A. V., Lanari, P., Bruguier, O., and Bosch, D.

Abstract

Based on new structural and petrological investigations, we present two crustal-scale cross-sections of the Kyrgyz South Tien Shan, and correlations of main faults and units between Kyrgyzstan and China. The overall structure corresponds to a doubly-vergent mountain belt. The Kyrgyz and Chinese areas exhibit identical structural and metamorphic histories. To the west, the Atbashi Range comprises high-pressure oceanic and continental units stacked by north-verging thrusts above a low metamorphic accretionary prism. High-pressure (HP) gneisses are bound to their south by a south-dipping detachment exhibiting mantle relicts. The high-pressure oceanic and continental units underwent similar pressure–temperature (P–T) paths with peak conditions of around 500 °C–20 kbar, followed by rapid exhumation. The overall south-dipping structure and kinematics indicate a south-dipping subduction of the Central Tien Shan Ocean at 320–310 Ma, ending with the docking of the Tarim block to the Kazakh continent. To the east, the Pobeda Massif shows a narrow push-up structure. A major north-vergent thrust exhumes deep-crustal-level granulites, constituting the highest summits, which were thrust towards the north onto low-grade Devonian–Carboniferous schists. The southern part of South Tien Shan is made up of a south-verging thrust stack that formed later during ongoing convergence, reactivated throughout post-30 Ma phases.

Published
2017
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348. Geochemistry of the Eocene magmatic rocks from the Lesser Caucasus area (Armenia): evidence of a subduction geodynamic environment

Author

Sahakyan, L., Bosch, D., Sosson, M., Avagyan, A., Galoyan, Gh., Rolland, Y., Bruguier, O., Stepanyan, Zh., Galland, B., and Vardanyan, S.

Abstract

This paper is focused on petrological and geochemical data obtained on a series of Middle and Upper Eocene magmatic rocks from the Lesser Caucasus of Armenia in order to elucidate magma sources and geodynamic processes. Middle–Upper Eocene magmatism is present in two main zones: the Amasia–Sevan–Hakari suture zone (ASHSZ) and the so-called South Armenian Microplate (SAM). Volcanic rocks from both places range from basalt to rhyolite and mostly display a calc-alkaline character. Trace element patterns from the SAM and ASHSZ samples show mobile-elements enrichment (Rb, Ba, Th) together with strong negative high field strength elements (Nb, Ta, Hf, Zr) anomalies. The (La/Sm)Nratio yields very close values for both areas. Conversely, the (La/Yb)Nratio is, on average, significantly higher for SAM than for ASHSZ, suggesting the presence of residual garnet at the source of the SAM volcanic rocks. Nevertheless, trace elements suggest partial melting from phlogopite- and amphibole-bearing spinel lherzolitic mantle sources.Neodymium and strontium isotopes yield εNd(40Ma)and 87Sr/86Sr(40Ma)ratios ranging, respectively, from –0.3 to +6.6 and from 0.70314 to 0.70531 for SAM samples, and from +3.4 to +6.8 and from 0.70393 to 0.70433 for ASHSZ samples. Initial Pb/Pb isotopic ratios yield close values for both areas but with slightly higher and more homogeneous 207Pb/204Pb and 208Pb/204Pb ratios for SAM samples. Such features concur with a more pronounced slab-component contribution in the frontal part of the volcanic belt, that is, in the SAM domain. No significant crustal contamination has been detected in the studied Eocene magmatic rocks from both the ASHSZ and SAM.Considering geodynamic and geochemical constraints, we propose that this magmatism is connected with a north-dipping Southern Neotethys subduction, in an extensional (back-arc) environment of orogenic belts. The Arabia–Eurasia collision and the closure of the Neotethys Ocean may have occurred after this magmatic event.

Published
2017
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349. From seafloor spreading to obduction: Jurassic–Cretaceous evolution of the northern branch of the Neotethys in the Northeastern Anatolian and Lesser Caucasus regions

Author

Hassig, M., Rolland, Y., and Sosson, M.

Abstract

We present arguments for an innovative tectonic set-up just prior to the Northern Neotethys obduction event in the NE Anatolian and Lesser Caucasus area. Along the Northern Neotethyan suture (the Ankara–Erzincan–Amasia–Sevan–Akera suture zone), relicts of the northern branch of the Neotethys oceanic domain outcrop as preserved unmetamorphosed slivers obducted over the northern edge of the South Armenian Block (SAB) and Taurides–Anatolides Platform (TAP) margins. Recent studies have shown that the ophiolitic bodies are formed of similar lithologies of Middle Jurassic age, all bearing mid-ocean ridge basalt chemical compositions enriched in large ion lithophile elements. This extensive database supports a model in which these ophiolites are derived from a single obducted nappe. This model is supported by the metamorphic pressure–temperature–time paths of the sole lithologies under the outcrops of the suture zone ophiolites. Palaeontological dating of sediment deposits directly under or sealing the obduction contact also support this model by temporally linking the emplacement of distant ophiolite outcrops. General emplacement during early Late Cretaceous time has been determined. A south-dipping subduction under the SAB shortly predating obduction has recently been proposed from the metamorphic and magmatic evolution preserved in the SAB crystalline basement, founding a model featuring opposite-direction subduction from at least late Middle Jurassic to Early Cretaceous times. The emplacement of alkaline pillow basalts directly on the oceanic crust is dated as Early to mid-Cretaceous. These dates argue the existence of abnormal mantle heat flows which may be responsible for a decrease in the density of the 80 Ma-old oceanic lithosphere prior to its obduction onto the SAB–TAP. We present a detailed review of recent data to further constrain the structural and geodynamic evolution of this sector and to define the tectonic set-up just prior to the obduction event.

Published
2017
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