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https://www.readbyqxmd.com/read/28337205/high-interferon-%C3%AE-uniquely-in-v%C3%AE-1-t-cells-correlates-with-markers-of-inflammation-and-axonal-damage-in-early-multiple-sclerosis
#1
Avadhesh Kumar Singh, Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Zetterberg, Jan Lycke, Susanna L Cardell
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28332001/ncam1-is-the-target-of-mirna-572-validation-in-the-human-oligodendroglial-cell-line
#2
Roberta Mancuso, Simone Agostini, Ivana Marventano, Ambra Hernis, Marina Saresella, Mario Clerici
The neural cell adhesion molecule 1 (NCAM1) is a fundamental protein in cell-cell interaction and in cellular developmental processes, and its dysregulation is involved in a number of diseases including multiple sclerosis. Studies in rats suggest that the modulation of NCAM1 expression is regulated by miRNA-572, but no data are available confirming such interaction in the human system. We analyzed whether this is the case using a human oligodendroglial cell line (MO3.13). MO3.13 cells were transfected with miRNA-572 mimic and inhibitor separately; NCAM1 mRNA and protein expression levels were analyzed at different time points after transfection...
March 22, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28320113/alzheimer-s-disease-elevated-pigment-epithelium-derived-factor-in-the-cerebrospinal-fluid-is-mostly-of-systemic-origin
#3
Veronika Lang, Marietta Zille, Carmen Infante-Duarte, Sven Jarius, Holger Jahn, Friedemann Paul, Klemens Ruprecht, Ana Luisa Pina
Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28302159/a-data-driven-approach-links-microglia-to-pathology-and-prognosis-in-amyotrophic-lateral-sclerosis
#4
Johnathan Cooper-Knock, Claire Green, Gabriel Altschuler, Wenbin Wei, Joanna J Bury, Paul R Heath, Matthew Wyles, Catherine Gelsthorpe, J Robin Highley, Alejandro Lorente-Pons, Tim Beck, Kathryn Doyle, Karel Otero, Bryan Traynor, Janine Kirby, Pamela J Shaw, Winston Hide
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that lacks a predictive and broadly applicable biomarker. Continued focus on mutation-specific upstream mechanisms has yet to predict disease progression in the clinic. Utilising cellular pathology common to the majority of ALS patients, we implemented an objective transcriptome-driven approach to develop noninvasive prognostic biomarkers for disease progression. Genes expressed in laser captured motor neurons in direct correlation (Spearman rank correlation, p < 0...
March 16, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28293128/exhaled-nitric-oxide-in-systemic-sclerosis-lung-disease
#5
Natalie K Kozij, John T Granton, Philip E Silkoff, John Thenganatt, Shobha Chakravorty, Sindhu R Johnson
Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls. Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection...
2017: Canadian Respiratory Journal: Journal of the Canadian Thoracic Society
https://www.readbyqxmd.com/read/28273785/cognitive-impairment-in-patients-with-multiple-sclerosis-is-associated-with-atrophy-of-the-inner-retinal-layers
#6
Danko Coric, Lisanne J Balk, Merike Verrijp, Anand Eijlers, Menno M Schoonheim, Joep Killestein, Bernard Mj Uitdehaag, Axel Petzold
BACKGROUND: Inner retinal layer (IRL) atrophy is a potential biomarker for neurodegeneration in multiple sclerosis (MS). OBJECTIVE: To investigate the relationship between cognitive impairment and IRL atrophy in MS. METHODS: Cross-sectional study design, including 217 patients and 59 healthy controls. Subjects were investigated clinically, underwent retinal optical coherence tomography (OCT) and comprehensive cognitive assessments. The association between these modalities was evaluated by regression analyses...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273770/transglutaminase-6-is-an-autoantigen-in-progressive-multiple-sclerosis-and-is-upregulated-in-reactive-astrocytes
#7
Massimiliano Cristofanilli, Daniel Gratch, Benjamin Pagano, Kelsey McDermott, Jessie Huang, Jeffrey Jian, Deneb Bates, Saud A Sadiq
BACKGROUND: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. OBJECTIVE: To investigate TGM6 involvement in multiple sclerosis (MS). METHODS: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28273645/biomarkers-of-stress-mediated-metabolic-deregulation-in-diabetes-mellitus
#8
REVIEW
Dina R Johar, Larry H Bernstein
This review illustrates the relationship of oxidative and nitrative stress to diabetes mellitus and its complications. This is of considerable interest because diabetes mellitus is a lifetime systemic metabolic disease that may have childhood or adult onset and affects not only a triad of pancreatic islet cell insulin, pituitary insulin-like growth hormone, and liver steatosis, it has a long-term association with adiposity, atherosclerosis, coronary vascular disease, kidney disease of the nature afferent arteriolar sclerosis and nodular glomerulosclerosis, cerebrovascular disease, and amyloid deposition in the pancreas and kidney...
February 24, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28264096/diagnostic-and-prognostic-biomarkers-in-amyotrophic-lateral-sclerosis-neurofilament-light-chain-levels-in-definite-subtypes-of-disease
#9
Alessandra Gaiani, Ilaria Martinelli, Luca Bello, Giorgia Querin, Marco Puthenparampil, Susanna Ruggero, Elisabetta Toffanin, Annachiara Cagnin, Chiara Briani, Elena Pegoraro, Gianni Sorarù
Importance: A clearer definition of the role of neurofilament light chain (NFL) as a biomarker in amyotrophic lateral sclerosis (ALS) is needed. Objectives: To assess the ability of NFL to serve as a diagnostic biomarker in ALS and the prognostic value of cerebrospinal fluid NFL in patients with ALS. Design, Setting, and Participants: In this single-center, retrospective, longitudinal study, disease progression was assessed by the ALS Functional Rating Score-Revised and the ALS Milano-Torino Staging system at baseline and 6, 12, 24, and 36 months...
March 6, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28253991/micrornas-as-peripheral-biomarkers-in-aging-and-age-related-diseases
#10
S Kumar, M Vijayan, J S Bhatti, P H Reddy
MicroRNAs (miRNAs) are found in the circulatory biofluids considering the important molecules for biomarker study in aging and age-related diseases. Blood or blood components (serum/plasma) are primary sources of circulatory miRNAs and can release these in cell-free form either bound with some protein components or encapsulated with microvesicle particles, called exosomes. miRNAs are quite stable in the peripheral circulation and can be detected by high-throughput techniques like qRT-PCR, microarray, and sequencing...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28239545/new-rapid-accurate-t2-quantification-detects-pathology-in-normal-appearing-brain-regions-of-relapsing-remitting-ms-patients
#11
Timothy M Shepherd, Ivan I Kirov, Erik Charlson, Mary Bruno, James Babb, Daniel K Sodickson, Noam Ben-Eliezer
INTRODUCTION: Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). METHODS: The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28235778/clinical-evoked-potentials-in-neurology-a-review-of-techniques-and-indications
#12
REVIEW
Agustina M Lascano, Patrice H Lalive, Martin Hardmeier, Peter Fuhr, Margitta Seeck
Evoked potentials (EPs) are a powerful and cost-effective tool for evaluating the integrity and function of the central nervous system. Although imaging techniques, such as MRI, have recently become increasingly important in the diagnosis of neurological diseases, over the past 30 years, many neurologists have continued to employ EPs in specific clinical applications. This review presents an overview of the recent evolution of 'classical' clinical applications of EPs in terms of early diagnosis and disease monitoring and is an extension of a previous review published in this journal in 2005 by Walsh and collaborators...
February 24, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28229303/phospholipase-d1-expression-analysis-in-relapsing-remitting-multiple-sclerosis-patients
#13
Mohammad Mahdi Eftekharian, Tahereh Azimi, Soudeh Ghafouri-Fard, Arezou Sayad, Mir Davood Omrani, Shaghayegh Sarrafzadeh, Roghayeh Abbasalipourkabir, Mehrdokht Mazdeh, Mohammad Taheri
Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including β-interferons (IFNβ) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid...
February 22, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#14
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28188915/machine-learning-based-compartment-models-with-permeability-for-white-matter-microstructure-imaging
#15
Gemma L Nedjati-Gilani, Torben Schneider, Matt G Hall, Niamh Cawley, Ioana Hill, Olga Ciccarelli, Ivana Drobnjak, Claudia A M Gandini Wheeler-Kingshott, Daniel C Alexander
Some microstructure parameters, such as permeability, remain elusive because mathematical models that express their relationship to the MR signal accurately are intractable. Here, we propose to use computational models learned from simulations to estimate these parameters. We demonstrate the approach in an example which estimates water residence time in brain white matter. The residence time τi of water inside axons is a potentially important biomarker for white matter pathologies of the human central nervous system, as myelin damage is hypothesised to affect axonal permeability, and thus τi...
February 8, 2017: NeuroImage
https://www.readbyqxmd.com/read/28188715/-multiple-sclerosis-current-immunological-aspects
#16
Carlos Cuevas-García
Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28174096/retinal-biomarkers-provide-insight-into-cortical-pharmacology-and-disease
#17
REVIEW
Christine T O Nguyen, Flora Hui, Jason Charng, Shajan Velaedan, Anna K van Koeverden, Jeremiah K H Lim, Zheng He, Vickie H Y Wong, Algis J Vingrys, Bang V Bui, Magnus Ivarsson
The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself to being a biomarker of the brain. More specifically, the presence of neuronal, vascular and blood-neural barrier parallels in the eye and brain coupled with fast and inexpensive methods to quantify retinal changes make ocular biomarkers an attractive option. This includes its utility as a biomarker for a number of cerebrovascular diseases as well as a drug pharmacology and safety biomarker for the CNS...
February 5, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28161558/neutrophil-perversion-in-demyelinating-autoimmune-diseases-mechanisms-to-medicine
#18
REVIEW
Courtney S Casserly, Julia C Nantes, Ryder F Whittaker Hawkins, Luc Vallières
Neutrophils are essential to a healthy life, yet pose a threat if improperly controlled. Neutrophil perversion is well documented in a variety of inflammatory disorders (e.g. arthritis, lupus, psoriasis), but is only beginning to be demystified in autoimmune demyelination, the most common cause of neurological disability in young adults. Using the animal model experimental autoimmune encephalomyelitis (EAE), several molecules that help neutrophils invade the central nervous system (CNS) have been identified...
March 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28128745/endothelial-dysfunction-microvascular-damage-and-ischemic-peripheral-vasculopathy-in-systemic-sclerosis
#19
Ivone Fernandes Santos da Silva, Andreia Teixeira, José Oliveira, Rui Almeida, Carlos Vasconcelos
OBJECTIVE: To evaluate endothelial dysfunction and microvascular damage in secondary Raynaud Phenomenon (SRP) and Systemic sclerosis (SSc)-associated patients as possible predictors of ischemic fingertip digital ulcers (DU) in a 3-year clinical follow-up. METHODS: Flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) were analysed in a 3-year observational cohort study of 77 SRP patients with systemic sclerosis...
January 27, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28120152/copy-number-variations-in-amyotrophic-lateral-sclerosis-piecing-the-mosaic-tiles-together-through-a-systems-biology-approach
#20
REVIEW
Giovanna Morello, Maria Guarnaccia, Antonio Gianmaria Spampinato, Valentina La Cognata, Velia D'Agata, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a devastating and still untreatable motor neuron disease. Despite the molecular mechanisms underlying ALS pathogenesis that are still far from being understood, several studies have suggested the importance of a genetic contribution in both familial and sporadic forms of the disease. In addition to single-nucleotide polymorphisms (SNPs), which account for only a limited number of ALS cases, a consistent number of common and rare copy number variations (CNVs) have been associated to ALS...
January 24, 2017: Molecular Neurobiology
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