1,721,020 research outputs found
Association between vaccines and neuroinflammation. time, risks, and benefits
No full textComment in
Association between vaccines and neuroinflammation-reply. [JAMA Neurol. 2015]
Comment on
Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. [JAMA Neurol. 2014
Varianti genotipiche del virus di Epstein Barr e loro usi come possibili predittori di rischio, biomarcatori e target terapeutici nella sclerosi multipla
No full textLa presente invenzione si riferisce ad un acido nucleico codificante per una variante dell’antigene nucleare 2 di Epstein Barr (EBNA2) per uso come biomarcatore per predire il rischio per lo sviluppo e/o la diagnosi e/o la prognosi della sclerosi multipla, e ad un metodo in vitro per predire il rischio per lo sviluppo e/o la diagnosi e/o la prognosi della sclerosi multipla in un soggetto, comprendente il rilevamento della presenza di detto acido nucleico
GENOMIC AND PROTEOMIC ANALYSIS OF CD8+ TCELL SUBSETS IN MONOZYGOTIC TWIN PAIRS DISCORDING FOR MULTIPLE SCLEROSIS.
No full textTelomeric nucleosomes are intrinsically mobile
No full textNucleosomes are no longer considered only static basic units that package eukaryotic DNA but they emerge as dynamic players in all chromosomal processes. Regulatory proteins can gain access to recognition sequences hidden by the histone octamer through the action of ATP-dependent chromatin remodeling complexes that cause nucleosome sliding. In addition, it is known that nucleosomes are able to spontaneously reposition along the DNA due to intrinsic dynamic properties, but it is not clear yet to what extent sequence-dependent dynamic properties contribute to nucleosome repositioning. Here, we study mobility of nucleosomes formed on telomeric sequences as a function of temperature and ionic strength. We find that telomeric nucleosomes are highly intrinsically mobile under physiological conditions, whereas nucleosomes formed on an average DNA sequence mostly remain in the initial position. This indicates that DNA sequence affects not only the thermodynamic stability and the positioning of nucleosomes but also their dynamic properties. Moreover, our findings suggest that the high mobility of telomeric nucleosomes may be relevant to the dynamics of telomeric chromatin. (C) 2007 Elsevier Ltd. All rights reserved
CD28 individual signals amplify pro-inflammatory cytokine production in relapse-remitting multiple sclerosis T lymphocytes.
No full textCD28 may be considered one of the most important costimulatory receptor that by binding its cognate ligands B7.1/CD80 or B7.2/CD86 on the surface of professional antigen presenting cells (APCs), lowers TCR activation threshold and leads to the augmentation of early signalling events necessary for efficient cytokine production, cell cycle progression and survival. The role of CD28 in multiple sclerosis (MS) has been often evaluated as the source of costimulatory signals integrating those delivered by TCR and blockade of CD28/B7 interaction by recombinant CTLA4-Ig, which binds B7 molecules with high affinity, is being evaluated for the use in MS patients. However, CD28 is also able to act as a unique signalling receptor and to arise TCR-independent autonomous signals. We have previously demonstrated that CD28 stimulation by agonistic antibodies or B7 expressed on APCs, in the absence of TCR engagement, is able to activate a specific NF-κB pathway in peripheral CD4+ T cells, leading to both the production of pro-inflammatory cytokine/chemokines and to the activation of survival genes.. NF-κB has been defined as a central mediator of the immune responses, by regulating the expression of over 150 genes including chemokines, cytokines and adhesion molecules involved in inflammation. Thus, CD28 stimulation may provide TCR-independent signals, which sustain the inflammatory response in MS.
By comparing the cytokine and chemokine patterns of peripheral blood CD4+ T cells isolated from relapsing-remitting MS (RRMS) patients and healthy donors (HD), we found that in RRMS but not in HD, CD28 stimulation selectively induces the expression of IL-6, IL-21 and IL-17A, all cytokines related to the Th17 cell profile phenotype. We also demonstrate that the up-regulation of all pro-inflammatory cytokines tested was dependent on CD28-mediated phosphatydilinositol 3 kinase (PI3K) activation. Therefore,CD28 could be considered as a novel receptor molecule that may contribute to amplify the inflammatory response in RRMS by favouring pro-inflammatory cytokine production and Th17 amplification
Vaccines in multiple sclerosis. The experience of BCG vaccination
No full textDespite earlier reports showing an onset of multiple sclerosis (MS) or the occurrence of relapses after vaccination, more recent large epidemiological studies did not find this association and confirmed the safety of common compulsory vaccinations in MS. Moreover, experimental and epidemiological evidence suggests benefit of exposure to microbial products (in the absence of infection, as is the case of vaccination) in MS. Along this line, Bacillus Calmette-Guerin (BCG) vaccine was tried in early MS and resulted safe and effective in reducing disease activity on magnetic resonance imaging, as well as the risk of developing persistent T1-hypointense lesions ("black holes" - expression of tissue damage). Another trial in people with clinically isolated syndromes demonstrated a benefit of BCG with respect to the conversion to clinically definite MS over 5 years. These results suggest the use of BCG immediately after disease onset. Even the possible extension to people at risk of MS might be envisioned, given that the approach is safe, inexpensive and convenient
Effects of Interferon-beta therapy on the expression of Epstein-Barr virus transcripts in PBMC of patients with Relapsing-Remitting Multiple Sclerosis
No full textMultiple sclerosis: pharmacogenomics and personalised drug treatment.
No full textMultiple sclerosis (MS) is a disorder of the central nervous system with an inflammatory and a neurodegenerative component. We do not yet have a definitive therapy for MS. Attempts to develop new treatments are long and costly and should be paralleled by studies aimed at increasing the therapeutic index of the existing treatments, interferon beta and glatiramer acetate. Pharmacogenetics and pharmacogenomics may be of use in this respect though their application may not be straightforward, particularly in MS
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