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Capucine L Grandjean, Fabricio Montalvao, Susanna Celli, David Michonneau, Beatrice Breart, Zacarias Garcia, Mario Perro, Olivier Freytag, Christian A Gerdes, Philippe Bousso
Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment...
October 4, 2016: Scientific Reports
Sebastien Bonnet, Steeve Provencher, Christophe Guignabert, Frédéric Perros, Olivier Boucherat, Ralph Theo Schermuly, Paul M Hassoun, Marlene Rabinovitch, Mark R Nicolls, Marc Humbert
Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding...
September 20, 2016: American Journal of Respiratory and Critical Care Medicine
Carol Evans, Sarah Tennant, Petros Perros
Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement...
2016: Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum
Sharon Mumby, Natalia Gambaryan, Chao Meng, Frederic Perros, Marc Humbert, S John Wort, Ian M Adcock
BACKGROUND AND OBJECTIVE: Nuclear factor kappa B (NF-kB)-mediated inflammatory gene expression and vascular endothelial cell proliferation/remodelling are implicated in the pathophysiology of the fatal disease, pulmonary arterial hypertension (PAH). Bromodomain and extra-terminal (BET) proteins are essential for the expression of a subset of NF-kB-induced inflammatory genes. BET mimics including JQ1+ prevent binding of BETs to acetylated histones and down-regulate the expression of selected genes...
August 18, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Alexis Régent, Kim Heang Ly, Sébastien Lofek, Guilhem Clary, Mathieu Tamby, Nicolas Tamas, Christian Federici, Cédric Broussard, Philippe Chafey, Emmanuelle Liaudet-Coopman, Marc Humbert, Frédéric Perros, Luc Mouthon
Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC)...
October 2016: Proteomics
C Chomette, E Duguet, S Mornet, E Yammine, V N Manoharan, N B Schade, C Hubert, S Ravaine, A Perro, M Tréguer-Delapierre
We synthesize robust clusters of gold satellites positioned with tetrahedral symmetry on the surface of a patchy silica core by adsorption and growth of gold on the patches. First we conduct emulsion polymerization of styrene in the presence of 52 nm silica seeds whose surface has been modified with methacryloxymethyltriethoxysilane (MMS). We derive four-dimple particles from the resulting silica/polystyrene tetrapods. Polystyrene chains are covalently bound to the silica surface within the dimples due to the MMS grafts and they may be thiolated to induce adsorption of 12 nm gold particles...
July 14, 2016: Faraday Discussions
Joachim Scholz, James P Rathmell, William S David, David A Chad, Alithia C Broderick, Stephen G Perros, Naomi S Shin, Jenna L Wells, John B Davis, Charles J DiMaggio, Shuang Wang, Simon N Tate
Diabetic polyneuropathy (DPN) is a major cause of neuropathic pain and a frequent target condition in analgesic treatment trials. Differences in the clinical symptoms and signs associated with DPN suggest distinct pathophysiological mechanisms underlying nerve damage and dysfunction that are likely to have therapeutic relevance. The aim of this study was to develop a tool for the bedside assessment of painful neuropathies such as DPN that captures the diversity of phenotypes. Sixty-one patients with type 2 diabetes and painful neuropathy, 19 patients with painless DPN, 25 patients with type 2 diabetes but no clinical evidence of neuropathy, and 20 healthy control subjects completed a structured interview (47 items) and a standardized physical examination (39 items)...
October 2016: Pain
Tuomas Haggren, Alexander Pyymaki Perros, Hua Jiang, Teppo Huhtio, Joona-Pekko Kakko, Veer Dhaka, Esko Kauppinen, Harri Lipsanen
A facile and scalable lithography-free technique(5) for the rapid construction of GaAs core-shell nanowires incorporating shell isolation from the substrate is reported. The process is based on interrupting NW growth and applying a thin spin-on-glass (SOG) layer to the base of the NWs and resuming core-shell NW growth. NW growth occurred in an atmospheric pressure metalorganic vapour phase epitaxy (MOVPE) system with gold nanoparticles used as catalysts for the vapour-liquid-solid growth. It is shown that NW axial core growth and radial shell growth can be resumed after interruption and even exposure to air...
July 8, 2016: Nanotechnology
Grégoire Ruffenach, Sophie Chabot, Virginie F Tanguay, Audrey Courboulin, Olivier Boucherat, Francois Potus, Jolyane Meloche, Aude Pflieger, Sandra Breuils-Bonnet, Valérie Nadeau, Renée Paradis, Eve Tremblay, Barbara Girerd, Aurélie Hautefort, David Montani, Elie Fadel, Peter Dorfmuller, Marc Humbert, Frédéric Perros, Roxane Paulin, Steeve Provencher, Sébastien Bonnet
RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This is sustained in time by the down-regulation of miR-204. In systemic vascular diseases, reduced miR-204 expression promotes vascular biomineralization by augmenting the expression of the transcription factor RUNX2. Implication of RUNX2 in PAH-related vascular remodeling and presence of calcified lesions in PAH remains unexplored. OBJECTIVES: We hypothesized that RUNX2 is up-regulated in lungs of PAH patients, contributing to vascular remodeling and calcium-related biomineralization...
May 5, 2016: American Journal of Respiratory and Critical Care Medicine
Valentina Parigi, Elodie Perros, Guillaume Binard, Céline Bourdillon, Agnès Maître, Rémi Carminati, Valentina Krachmalnicoff, Yannick De Wilde
We study the intensity spatial correlation function of optical speckle patterns above a disordered dielectric medium in the multiple scattering regime. The intensity distributions are recorded by scanning near-field optical microscopy (SNOM) with sub-wavelength spatial resolution at variable distances from the surface in a range which spans continuously from the near-field (distance ≪ λ) to the far-field regime (distance ≫ λ). The non-universal behavior at sub-wavelength distances reveals the connection between the near-field speckle pattern and the internal structure of the medium...
April 4, 2016: Optics Express
Wim Scheele, Susan Diamond, Jeremy Gale, Valerie Clerin, Nihad Tamimi, Vu Le, Rosalind Walley, Fernando Grover-Páez, Christelle Perros-Huguet, Timothy Rolph, Meguid El Nahas
Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy...
April 25, 2016: Journal of the American Society of Nephrology: JASN
Luigi Bartalena, Lelio Baldeschi, Kostas Boboridis, Anja Eckstein, George J Kahaly, Claudio Marcocci, Petros Perros, Mario Salvi, Wilmar M Wiersinga
Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients...
March 2016: European Thyroid Journal
Kurt R Stenmark, Maria Frid, Frédéric Perros
No abstract text is available yet for this article.
May 3, 2016: Circulation
David Montani, Edmund M Lau, Peter Dorfmüller, Barbara Girerd, Xavier Jaïs, Laurent Savale, Frederic Perros, Esther Nossent, Gilles Garcia, Florence Parent, Elie Fadel, Florent Soubrier, Olivier Sitbon, Gérald Simonneau, Marc Humbert
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In the current PH classification, PVOD and pulmonary capillary haemangiomatosis (PCH) are considered to be a common entity and represent varied expressions of the same disease. The recent discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD/PCH represents a major milestone in our understanding of the molecular pathogenesis of PVOD...
May 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Charbel Afif, Corinne Jambert, Vincent Michoud, Aurélie Colomb, Gregory Eyglunent, Agnès Borbon, Véronique Daële, Jean-François Doussin, Pascal Perros
NitroMAC (French acronym for continuous atmospheric measurements of nitrogenous compounds) is an instrument which has been developed for the semi-continuous measurement of atmospheric nitrous acid (HONO). This instrument relies on wet chemical sampling and detection using high performance liquid chromatography (HPLC)-visible absorption at 540 nm. Sampling proceeds by dissolution of gaseous HONO in a phosphate buffer solution followed by derivatization with sulfanilamide/N-(1-naphthyl)-ethylenediamine. The performance of this instrument was found to be as follows: a detection limit of around 3 ppt with measurement uncertainty of 10% over an analysis time of 10 min...
February 2016: Journal of Environmental Sciences (China)
Philippe Ruszniewski, Juan W Valle, Catherine Lombard-Bohas, Daniel J Cuthbertson, Petros Perros, Luboš Holubec, Gianfranco Delle Fave, Denis Smith, Patricia Niccoli, Pascal Maisonobe, Philippe Atlan, Martyn E Caplin
BACKGROUND: Lanreotide Autogel/Depot effectively controls symptoms in patients with carcinoid syndrome associated with neuroendocrine tumours. Data on patient-reported outcomes are sparse. AIM: To evaluate the effect of lanreotide on patient-reported outcomes (PROs) with carcinoid syndrome. METHODS: This was an international, open-label, observational study of adults with neuroendocrine tumours and history of diarrhoea, receiving lanreotide for >3 months for relief of carcinoid syndrome symptoms...
May 2016: Digestive and Liver Disease
Fabrice Antigny, Aurélie Hautefort, Jolyane Meloche, Milia Belacel-Ouari, Boris Manoury, Catherine Rucker-Martin, Christine Péchoux, François Potus, Valérie Nadeau, Eve Tremblay, Grégoire Ruffenach, Alice Bourgeois, Peter Dorfmüller, Sandra Breuils-Bonnet, Elie Fadel, Benoît Ranchoux, Philippe Jourdon, Barbara Girerd, David Montani, Steeve Provencher, Sébastien Bonnet, Gérald Simonneau, Marc Humbert, Frédéric Perros
BACKGROUND: Mutations in the KCNK3 gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH). KCNK3 encodes an outward rectifier K(+) channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH)...
April 5, 2016: Circulation
Joel S Finkelstein, Hang Lee, Benjamin Z Leder, Sherri-Ann M Burnett-Bowie, David W Goldstein, Christopher W Hahn, Sarah C Hirsch, Alex Linker, Nicholas Perros, Andrew B Servais, Alexander P Taylor, Matthew L Webb, Jonathan M Youngner, Elaine W Yu
BACKGROUND: Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS: One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1...
March 1, 2016: Journal of Clinical Investigation
Marina Bacac, Tanja Fauti, Johannes Sam, Sara Colombetti, Tina Weinzierl, Djamila Ouaret, Walter Bodmer, Steffi Lehmann, Thomas Hofer, Ralf J Hosse, Ekkehard Moessner, Oliver Ast, Peter Bruenker, Sandra Grau-Richards, Teilo Schaller, Annette Seidl, Christian Gerdes, Mario Perro, Valeria Nicolini, Nathalie Steinhoff, Sherri Dudal, Sebastian Neumann, Thomas von Hirschheydt, Christiane Jaeger, Jose Saro, Vaios Karanikas, Christian Klein, Pablo Umaña
PURPOSE: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcγRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB. EXPERIMENTAL DESIGN: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Isabel M Vincent, David E Ehmann, Scott D Mills, Manos Perros, Michael P Barrett
Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5'-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanidem-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime...
April 2016: Antimicrobial Agents and Chemotherapy
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