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151. Multiplexed SPRi detection and AFM characterization of sub-populations of blood microparticles

Author

Elie-Caille, C., Zeggari, R., Mourey, G., Saas, P., Boireau, W., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])

Subjects
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics
Published
2012

152. Ultraflat Gold chips for Blood Particles Characterizations by Novel, SPRi & AFM, Hyphenated Techniques

Author

Elie-Caille, C., Bienaimé, A., Rouleau, A., Mourey, G., Zeggari, R., Remy-Martin, F., Arezki, K., jean-yves Rauch, Saas, P., Boireau, W., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), HORIBA Jobin Yvon SAS [Chili Mazarin], and HORIBA Scientific [France]

Subjects
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics
Published
2012

153. Increased gut permeability and intestinal inflammation precede arthritis onset in the adjuvant-induced model of arthritis

Author

Hecquet, Sophie, Totoson, Perle, Martin, Hélène, Algros, Marie-Paule, Saas, Philippe, Pais-de-Barros, Jean-Paul, Atchon, Alban, Valot, Benoît, Hocquet, Didier, Tournier, Maude, Prati, Clément, Wendling, Daniel, Demougeot, Céline, and Verhoeven, Frank

Abstract

• Intestinal inflammation and alterations of the intestinal barrier are not the consequence of joint damage

Published
2023
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158. Antithymocyte globulins in renal transplantation—from lymphocyte depletion to lymphocyte activation: The doubled-edged sword.

Author

Bamoulid, Jamal, Crépin, Thomas, Courivaud, Cécile, Rebibou, Jean-Michel, Saas, Philippe, and Ducloux, Didier

Abstract

Compelling data suggest that lymphocyte depletion following T cell depleting therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte activation in some patients. These profound and non-reversible immune changes in T cell pool subsets are the consequence of both impaired thymic renewal and peripheral homeostatic proliferation. Chronic viral challenges by CMV play a major role in these immune alterations. Even when the consequences of CD4 T cell lymphopenia have been now well described, recent studies shed new light on the clinical consequences of immune activation. In this review, we will first focus on the mechanisms involved in T cell pool reconstitution after T cell depletion and further consider the clinical consequences of ATG-induced T cell activation and senescence in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Published
2017
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159. IκB kinase inhibition as a potential treatment of osteoarthritis - results of a clinical proof-of-concept study.

Author

Grothe, K., Flechsenhar, K., Paehler, T., Ritzeler, O., Beninga, J., Saas, J., Herrmann, M., and Rudolphi, K.

Abstract

Objective: This publication summarizes the clinical development of the compound SAR113945, an IκB kinase inhibitor injected intra-articularly in a slow-release formulation to treat patients with symptomatic osteoarthritis (OA) of the knee.Results: In vitro experiments demonstrated a specific inhibition of the IκB kinase complex. Profiling of SAR113945 on kinases, enzymes and ion channels supported the initiation of a clinical development. Cellular assay systems also revealed an inhibition in the synthesis of interleukin 1β, tumor necrosis factor α (TNFα) and the prostaglandin E2 (PGE2). In vivo studies demonstrated positive effects of SAR113945 on thermal and mechanical hyperalgesia and even showed superiority in comparison with triamcinolone. Pharmacokinetic measurements showed a sustained release of dissolved SAR113945 locally supporting a comparably high exposure in the knee joint combined with a low systemic exposure. Three phase 1 studies with a dose-escalating design confirmed safety and tolerability of SAR113945. In those studies SAR113945 showed a positive trend on the WOMAC scores. The proof-of-concept or phase 2a study failed to show any effect in the overall group of recruited study participants for the primary endpoint, the WOMAC pain subscore at day 56, but showed a statistically significant difference in a subgroup of patients who had presented with effusion at baseline.Conclusion: Inhibiting the NFκB signaling pathway is an attractive method to treat patients with signs and symptoms of OA. The preclinical work and the results of the phase 1 studies appeared promising for a full clinical development, however, the proof-of-concept study failed to show efficacy in a larger patient sample size. [ABSTRACT FROM AUTHOR]

Published
2017
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160. In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent

Author

Angelot-Delettre, F., primary, Roggy, A., additional, Frankel, A. E., additional, Lamarthee, B., additional, Seilles, E., additional, Biichle, S., additional, Royer, B., additional, Deconinck, E., additional, Rowinsky, E. K., additional, Brooks, C., additional, Bardet, V., additional, Benet, B., additional, Bennani, H., additional, Benseddik, Z., additional, Debliquis, A., additional, Lusina, D., additional, Roussel, M., additional, Solly, F., additional, Ticchioni, M., additional, Saas, P., additional, and Garnache-Ottou, F., additional

Published
2014
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164. IL-22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versus-leukemia effect.

Author

UCL - SSS/DDUV - Institut de Duve, Couturier, M, Lamarthée, B, Arbez, J, Renauld, Jean-Christophe, Bossard, C, Malard, F, Bonnefoy, F, Mohty, M, Perruche, S, Tiberghien, P, Saas, P, Gaugler, B, UCL - SSS/DDUV - Institut de Duve, Couturier, M, Lamarthée, B, Arbez, J, Renauld, Jean-Christophe, Bossard, C, Malard, F, Bonnefoy, F, Mohty, M, Perruche, S, Tiberghien, P, Saas, P, and Gaugler, B

Abstract

Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation (allo-HCT), limiting the success of this therapy. Many proinflammatory cytokines secreted following the conditioning regimen have been linked to aGVHD initiation. Interleukin-22 (IL-22) is a cytokine related to IL-10 for its structure and is secreted by T helper type 17 (TH17) cells and innate immune cells. Given the paradoxical role of IL-22 in inflammation with both protective or proinflammatory functions, we investigated whether IL-22 could have a role in aGVHD pathophysiology in a mouse allo-HCT model. In this study, we show that IL-22 deficiency in donor T cells can decrease the severity of aGVHD, while limiting systemic and local inflammation in aGVHD target organs. In addition, we found that Foxp3+ regulatory T cells (Treg cells) were increased in recipient mice that received IL-22-deficient T cells, suggesting that Treg were involved in the reduced severity of GVHD. Finally, we found that the graft-versus-leukemia (GVL) effect mediated by donor T cells was preserved in the absence of IL-22. Overall, these data suggest that targeting of IL-22 may represent a valid approach towards decreasing aGVHD severity after allo-HCT while preserving the GVL effect.Leukemia advance online publication, 5 March 2013; doi:10.1038/leu.2013.39.

Published
2013

165. A new video-based tool to enhance teaching economics

Author

Kuhn, Christiane, Zlatkin-Troitschanskaia, Olga, Brückner, Sebastian, and Saas, Hannes

Abstract

We present a new video-based tool developed in Germany to enhance the teaching of economics. The tool consists of authentic teacher-student interactions in economics classes to which instructors need to react. With 18 videos, the tool provides an easily accessible opportunity to assess and enhance teaching performance in economics. The tool was rated by 41 highly experienced secondary school economics teachers according to different criteria relevant for curriculum design and instructional practice, including authenticity of the simulated classroom situations, and typical difficulties and misconceptions students have in learning economics. The teachers confirm the curricular and instructional sensitivity, validity, quality and innovative approach of the tool for formative assessment and enhancement of performance in teaching economics. Based on German practical experience, the use of the tool in secondary school teacher training programs in the United States is currently being investigated.

Published
2018
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169. Quantification des microparticules érythrocytaires et plaquettaires dans les concentrés globulaires : impact de la méthode de production et de la conservation

Author

Garnache-Ottou, F., primary, Biichlé, S., additional, Petitjean, R., additional, Aupet, S., additional, Naegelen, C., additional, Vivot, A., additional, König, F., additional, Lartod, N., additional, MarpauX, N., additional, Morel, P., additional, Bardiaux, L., additional, and Saas, P., additional

Published
2013
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180. Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis

Author

Ducloux, Didier, Bamoulid, Jamal, Crepin, Thomas, Rebibou, Jean-Michel, Courivaud, Cecile, and Saas, Philippe

Abstract

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

Published
2017
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182. O79 L’administration pré-greffe de leucocytes apoptotiques issus du donneur retarde le rejet dans un modèle murin de greffe d’îlots pancréatiques par un mécanisme impliquant les lymphocytes T régulateurs FoxP3+

Author

Mougel, F., primary, Bonnefoy, F., additional, Kury-Paulin, S., additional, Borot, S., additional, Perruche, S., additional, Kantelip, B., additional, Saas, P., additional, Kleinclauss, F., additional, and Penfornis, A., additional

Published
2011
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195. Abstract TP27: Data Drives Outcomes: Optimizing Smoking Cessation Education And Documentation When Transitioning To A New Electronic Medical Record

Author

Rexford, Tracy, Saas, Alissa M, Campbell, Margie L, and Lee, Jessica D

Abstract

Background and Purpose:In June 2021, the University of Kentucky transitioned to the EPIC documentation platform. With the change in electronic medical record (EMR), the documentation location of smoking cessation changed and compliance decreased. "Smoking cessation" per Get with the Guidelines (GWTG) is the percent of patients with ischemic or hemorrhagic stroke or transient ischemic attack (TIA) with a history of smoking cigarettes, who are, or whose care givers are, given smoking cessation advice or counseling during hospital stay. There is a four-month delay in GWTG data abstraction & implications. As a result, the medical center was unaware of declining smoking cessation compliance rates. In November of 2021, it was reported that smoking cessation had dropped to 69.0% compliance over 5 months starting in June 2021 with a low of 60.0% in October 2021. The mean compliance rate for smoking cessation 4 months prior to June 2021 was 93.0% with 100.0% compliance for the month of April 2021. As an accredited Comprehensive Stroke Center, sustaining the GWTG Stroke Quality Award is of utmost importance.Methods:Two initiatives were introduced in response to decreased compliance in smoking cessation education documentation from June-October 2021. First, Stroke Transfer Coordinators responsibilities were modified to include day and night shift clinical coaching with bedside staff on importance of smoking cessation education and documentation. Second, the Medical Director of the Comprehensive Stroke Center communicated the importance of smoking cessation to provider team and partnered with informatics to optimize clinical progress notes documentation in EPIC.Results:After implementation of Stroke Transfer Coordinator support along with provider communication and EPIC smart phase addition smoking cessation compliance rose to 100% in November 2021 and sustained 100% through February 2022. Current smoking cessation compliance rate for the first two quarters of 2022 is 99.1%.Conclusion:It is imperative that data continues to drive clinical initiatives in stroke care and data is analyzed frequently to improve quality practice. An interdisciplinary team approach resulted in positive outcomes for smoking cessation education.

Published
2023
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196. Plasma citrulline concentration and plasma LPS detection among critically ill patients a prospective observational study

Author

Chaignat, Claire, Lagrost, Laurent, Moretto, Karena, de Barros, Jean-Paul Pais, Winiszewski, Hadrien, Grober, Jacques, Saas, Philippe, and Piton, Gaël

Abstract

Gut can be a source of sepsis but sepsis itself can induce gut dysfunction. We aimed to study whether plasma citrulline, a marker of enterocyte mass, was correlated with plasma lipopolysaccharide, a potential marker of bacterial translocation among critically ill patients.

Published
2023
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197. Resolved Psoriasis with Abundant Oleic Acid in Stratum Corneum Exhibits Lower T-Cell–Driven IL-17 Signature

Author

El Mahi, Yasmin, Varin, Alexis, Vetter, Mathieu, Dal Zuffo, Ludivine, Mazzeo, Loïc, Pais De Barros, Jean-Paul, Aubin, François, Saas, Philippe, and Gallais Sérézal, Irène

Abstract

Relapses of psoriasis involve T cells that stem and survive in the skin. Inherited from previous flares, the tissue-resident memory T cells are epidermal IL-17–producing CD8+and IL-22–producing CD4+T cells. Because the capacity of resident memory T cells to take in fatty acids is essential for their residence and function, the surface composition of fatty acids may affect underlying T-cell populations. In patients treated with biologics, we used gas chromatography/mass spectrometry to decipher the fatty acid composition in both resolved and nonlesional sites. Skin T cells were activated by OKT-3 in explants from the same body sites to perform bulk transcriptomic analysis (Nanostring). The fatty acid composition differed between skin from healthy donors and normal-looking skin of patients with psoriasis but not further between nonlesional and resolved skin. Patients in whom the resolved skin was rich in oleic acid had lower T-cell–driven IL-17 epidermal transcriptomic signature upon activation of T cells in skin explants. The skin lipid composition is linked with the functions of the underlying epidermal T cells. Testing the modulating effect of custom fatty acids on skin resident T cells could help with coming closer to disease oblivion in inflammatory skin diseases.

Published
2023
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198. Engaging formal and informal institutions for stewardship of rockfish fisheries in the Gulf of Alaska.

Author

Gordon, Jesse Y., Beaudreau, Anne H., Saas, Emma M., and Carothers, Courtney

Subjects
STRIPED bass, SMALL-scale fisheries, FISHERIES, NETWORK governance, RESOURCE management, LOCAL mass media, FISHERY management
Abstract

Examining relationships between formal and informal institutions for governing small-scale fisheries may reveal pathways for effectively engaging resource users in management. This study explored formal and informal institutions for management of rockfish (Sebastes spp.) fisheries in the Gulf of Alaska. Forty-three experts (fishers and agency staff) were interviewed about their engagement with rockfish management. We analyzed interactions and gaps between formal and informal management institutions using the Inter-Institutional Gap (IIG) framework. Participation in the State of Alaska Board of Fisheries (BOF) process, a formal management institution, was viewed by some experts as more effective for enacting regulatory change, compared to informal institutions. However, fishers who were deterred from engaging with the BOF by complex bureaucratic processes tended to favor informal interactions with the Alaska Department of Fish and Game (ADF&G) through visits to local offices and communication with port samplers. Formal institutional gaps identified by experts included transparency issues regarding regulatory decisions and/or interpretation, underrepresentation of recreational and subsistence harvesters in the BOF process, complexity of regulations, and bureaucratic barriers to coordination between the Sport and Commercial divisions of ADF&G. Informal institutions of self-governance, such as stewardship actions taken by fishers to reduce bycatch and minimize harm to incidentally caught fish, were identified by fishers and agency staff as important to rockfish fishery sustainability. Communication gaps in rockfish management may also be addressed by strengthening informal institutions that build trust and relationships between fishers and agency staff, such as collaborative research to coproduce knowledge about rockfish ecology. • Inter-institutional gaps can inhibit fisher participation in resource management. • We interviewed Alaska fishers and agency staff about rockfish management institutions. • Fishers and agency staff value engagement with formal and informal institutions. • Institutional gaps include bureaucratic barriers and marginalization of some groups. • Informal institutions of self-governance are important for rockfish stewardship. [ABSTRACT FROM AUTHOR]

Published
2022
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199. Analysis of Differential Gene Expression in Healthy and Osteoarthritic Cartilage and Isolated Chondrocytes by Microarray Analysis.

Author

Walker, John M., Sabatini, Massimo, Pastoureau, Philippe, De Ceuninck, Frédéric, Aigner, Thomas, Saas, Joachim, Zien, Alexander, Zimmer, Ralf, Gebhard, Pia M., and Knorr, Thomas

Abstract

The regulation of chondrocytes in osteoarthritic cartilage and the expression of specific gene products by these cells during early-onset and late-stage osteoarthritis are not well characterized. With the introduction of cDNA array technology, the measurement of thousands of different genes in one small tissue sample can be carried out. Interpretation of gene expression analyses in articular cartilage is aided by the fact that this tissue contains only one cell type in both normal and diseased conditions. However, care has to be taken not to over- and misinterpret results, and some major challenges must be overcome in order to utilize the potential of this technology properly in the field of osteoarthritis. [ABSTRACT FROM AUTHOR]

Published
2004
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200. LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis

Author

Ceroi, Adam, Masson, David, Roggy, Anne, Roumier, Christophe, Chagué, Cécile, Gauthier, Thierry, Philippe, Laure, Lamarthée, Baptiste, Angelot-Delettre, Fanny, Bonnefoy, Francis, Perruche, Sylvain, Biichle, Sabeha, Preudhomme, Claude, Macintyre, Elisabeth, Lagrost, Laurent, Garnache-Ottou, Francine, and Saas, Philippe

Abstract

Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of adenosine triphosphate–binding cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with 3 signaling pathways associated with leukemic cell survival, namely: NF-κB activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor interleukin-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.

Published
2016
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