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Lili Gu, Hyun Ju Jung, Kyung Jin Kwak, Sy Nguyen Dinh, Yeon-Ok Kim, Hunseung Kang
Despite an increasing understanding of the essential role of the Mei2 gene encoding an RNA-binding protein (RBP) in premeiotic DNA synthesis and meiosis in yeasts and animals, the functional roles of the mei2-like genes in plant growth and development are largely unknown. Contrary to other mei2-like RBPs that contain three RNA-recognition motifs (RRMs), the mei2 C-terminal RRM only (MCT) is unique in that it harbors only the last C-terminal RRM. Although MCTs have been implicated to play important roles in plants, their functional roles in stress responses as well as plant growth and development are still unknown...
October 13, 2016: Plant Physiology and Biochemistry: PPB
Olivia Geisseler, Tobias Pflugshaupt, Ladina Bezzola, Katja Reuter, David Weller, Bernhard Schuknecht, Peter Brugger, Michael Linnebank
BACKGROUND: Recent studies suggest that cortical lesions in multiple sclerosis (MS) substantially contribute to clinical disease severity. The present study aimed at investigating clinical, neuroanatomical, and cognitive correlates of these cortical lesions with a novel approach, i.e. by comparing two samples of relapsing-remitting multiple sclerosis (RRMS) patients, one group with and the other without cortical lesions. METHODS: High-resolution structural MRI was acquired from 42 RRMS patients and 43 controls (HC)...
October 21, 2016: BMC Neurology
Gabriel Bsteh, Julia Feige, Rainer Ehling, Michael Auer, Harald Hegen, Franziska Di Pauli, Florian Deisenhammer, Markus Reindl, Thomas Berger
BACKGROUND: Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making. METHODS: We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation...
October 20, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Adam Stepien, Natalia L Dabrowska, Marzena Maciagowska, Renata Piusinska Macoch, Aleksandra Zolocinska, Slawomir Mazur, Katarzyna Siennicka, Emilia Frankowska, Rafał Kidzinski, Małgorzata Chalimoniuk, Zygmunt Pojda
The clinical outcome of autologous adipose stem cell (ASC) treatment of patients with multiple sclerosis (MS) was investigated following one year of observation. Methods. The clinical and MRI outcomes of 16 ASC-treated patients with RRMS and SPMS are reported after a one-year follow-up period. Results. At 18 months of follow-up, some patients showed "enticing" improvements on some exploratory efficacy measures, although a significant benefit was not observed for any measure across the entire group. Neither the progression of disability nor relapses were observed in any cases...
2016: Mediators of Inflammation
Jonatan Salzer, Rasmus Svenningsson, Peter Alping, Lenka Novakova, Anna Björck, Katharina Fink, Protik Islam-Jakobsson, Clas Malmeström, Markus Axelsson, Mattias Vågberg, Peter Sundström, Jan Lycke, Fredrik Piehl, Anders Svenningsson
OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS)...
October 19, 2016: Neurology
Alice Laroni, Davide Brogi, Vincenzo Brescia Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni Luigi Mancardi
: The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs)...
October 18, 2016: Neurological Sciences
Naeim Ehtesham, Fariborz Khorvash, Majid Kheirollahi
MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs)...
October 17, 2016: Journal of Molecular Neuroscience: MN
Sheena L Dupuy, Shahamat Tauhid, Shelley Hurwitz, Renxin Chu, Fawad Yousuf, Rohit Bakshi
INTRODUCTION: The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing-remitting (RR) MS. METHODS: We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1...
October 15, 2016: Neurology and Therapy
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4(+) T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines...
October 6, 2016: JCI Insight
Gavin Giovannoni, Jeffrey A Cohen, Alasdair J Coles, Hans-Peter Hartung, Eva Havrdova, Krzysztof W Selmaj, David H Margolin, Stephen L Lake, Susan M Kaup, Michael A Panzara, D Alastair S Compston
OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS...
October 12, 2016: Neurology
Luis Hernandez, Shien Guo, Hector Toro-Diaz, Stuart Carroll, Syed Feisal Syed Farooq
AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every two weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and personal social services perspective in Scotland...
October 12, 2016: Journal of Medical Economics
Ann Cathrine Kroksveen, Astrid Guldbrandsen, Marc Vaudel, Ragnhild Reehorst Lereim, Harald Barsnes, Kjell-Morten Myhr, Øyvind Torkildsen, Frode S Berven
In the current study, we conducted a quantitative in-depth proteome and deglycoproteome analysis of cerebrospinal fluid (CSF) from relapsing-remitting multiple sclerosis (RRMS) and neurological controls using mass spectrometry and pathway analysis. More than 2000 proteins and 1700 deglycopeptides were quantified, with 484 proteins and 180 deglycopeptides significantly changed between pools of RRMS and pools of controls. Approximately 300 of the significantly changed proteins were assigned to various biological processes, including inflammation, extracellular matrix organization, cell adhesion, immune response and neuron development...
October 11, 2016: Journal of Proteome Research
M Alba Mañé-Martínez, Bob Olsson, Laura Bau, Elisabet Matas, Álvaro Cobo-Calvo, Ulf Andreasson, Kaj Blennow, Lucia Romero-Pinel, Sergio Martínez-Yélamos, Henrik Zetterberg
In the present study, CSF concentrations of NFL, t-tau, p-tau, GFAP, S-100B, YKL-40, MCP-1, α-sAPP, β-sAPP, and Aβ38, Aβ40, Aβ42 were measured in 324 MS patients to test whether a correlation among the biomarkers exists and whether the profile of CSF biomarkers varies among the different types of MS. The CSF concentrations of NFL were significantly higher in RRMS while CSF concentrations of GFAP were higher in PPMS. CSF concentrations of NFL correlated with YKL-40 in CIS patients while CSF concentrations of GFAP correlated with YKL-40 in RRMS patients...
October 15, 2016: Journal of Neuroimmunology
Begoña M Escribano, Francisco J Medina-Fernández, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijoo, Fe I Garcia-Maceira, Rafael Lillo, Patricia Vieyra-Reyes, Ana I Giraldo, Evelio Luque, René Drucker-Colín, Isaac Túnez
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord...
October 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Sheena L Dupuy, Fariha Khalid, Brian C Healy, Sonya Bakshi, Mohit Neema, Shahamat Tauhid, Rohit Bakshi
BACKGROUND: Spinal cord atrophy occurs early in multiple sclerosis (MS) and impacts disability. The therapeutic effect of interferon beta-1a (IFNβ-1a) on spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been explored. METHODS: We retrospectively identified 16 consecutive patients receiving weekly intramuscular IFNβ-1a for 2 years [baseline age (mean ± SD) 47.7 ± 7.5 years, Expanded Disability Status Scale score median (range) 1...
October 5, 2016: BMC Medical Imaging
Maria A Rocca, Laura Vacchi, Mariaemma Rodegher, Alessandro Meani, Vittorio Martinelli, Francesca Possa, Giancarlo Comi, Andrea Falini, Massimo Filippi
Using fMRI during a face encoding (FE) task, we investigated the behavioral and fMRI correlates of FE in patients with relapse-onset multiple sclerosis (MS) at different stages of the disease and their relation with attentive-executive performance and structural MRI measures of disease-related damage. A fMRI FE task was administered to 75 MS patients (11 clinically isolated syndromes - CIS, 40 relapsing-remitting - RRMS - and 24 secondary progressive - SPMS) and 22 healthy controls (HC). fMRI activity during the face encoding condition was correlated with behavioral, clinical, neuropsychological and structural MRI variables...
October 6, 2016: Brain Imaging and Behavior
Marzieh Khoshbin Nazdik, Mohammad Taheri, Mir Davood Omrani, Elham Sajjadi, Shahram Arsang-Jang, Zeinab Kazaei Koohpar, Hidetoshi Inoko, Arezou Sayad
OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease involving the central nervous system (CNS) with unknown immunopathogenic mechanisms. Matrix metalloproteinase-9 (MMP-9) facilitates T-cell migration into the CNS while the tissue inhibitor matrix metalloproteinase-1 (TIMP-1) inhibits MMP-9 actions. The aim of this study was to evaluate the expression of TIMP-1 RNA and MMP-9/TIMP-1 RNA ratio in blood cells of Iranian patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNb...
September 22, 2016: Human Antibodies
Johanna von Gumberz, Mina Mahmoudi, Kim Young, Sven Schippling, Roland Martin, Christoph Heesen, Susanne Siemonsen, Jan-Patrick Stellmann
BACKGROUND: Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability...
2016: PeerJ
Morten Stilund, Mikkel Carstensen Gjelstrup, Tove Christensen, Holger Jon Møller, Thor Petersen
OBJECTIVES: This study aimed to examine the levels of the macrophage marker sCD163 and other biomarkers at the time of diagnosis of patients with either clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS), and assess relation to clinical indicators of prognosis, disease activity (DA), and changes in the levels of these biomarkers at follow-up. MATERIALS AND METHODS: The clinical status and MRI were reevaluated in 56 patients more than 1 year after diagnosis with a median follow-up time of 2 years...
September 2016: Brain and Behavior
Elena Herranz, Costanza Giannì, Céline Louapre, Constantina A Treaba, Sindhuja T Govindarajan, Russell Ouellette, Marco L Loggia, Jacob A Sloane, Nancy Madigan, David Izquierdo-Garcia, Noreen Ward, Gabriel Mangeat, Tobias Granberg, Eric C Klawiter, Ciprian Catana, Jacob M Hooker, Norman Taylor, Carolina Ionete, Revere P Kinkel, Caterina Mainero
Objective In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with (11) C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. Methods Fifteen secondary-progressive MS (SPMS) and 12 relapsing-remitting MS (RRMS) cases, and 14 matched healthy controls underwent (11) C-PBR28 MR-PET...
September 30, 2016: Annals of Neurology
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