LECTURAS CIENTÍFICAS

  • HOTAIR but not ANRIL Long non-coding RNA contributes to the pathogenesis of Multiple Sclerosis.
    Related ArticlesHOTAIR but not ANRIL Long non-coding RNA contributes to the pathogenesis of Multiple Sclerosis. Immunology. 2017 Oct 14;: Authors: Pahlevan Kakhki M, Nikravesh A, Shirvani Farsani Z, Sahraian MA, Behmanesh M Abstract Different studies have revealed that dysregulation in gene expression is one of the main aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways underlying the immunomodulatory role of vitamin D (VD) in MS is not completely elucidated, VD has more recently become a topic of interest in immune regulation and is widely administrated to MS patients as an immunomodulatory supplement. Long non-coding RNAs (lncRNAs) are known to play important roles in regulation of gene expression via different mechanisms. Given that VD related genes are regulated by epigenetic mechanisms, here we aimed to evaluate the role of VD in combination with HOTAIR and ANRIL lncRNAs using in vivo, in vitro, and in silico experiments in MS pathogenesis. Our data revealed that HOTAIR but not ANRIL lncRNA is likely involved in the pathogenesis of MS and EAE through an unclear mechanism and it seems that by affecting the expression, inflammation and VD can influence HOTAIR -related mechanisms which needs to be more studied. This article is protected by copyright. All rights reserved.PMID: 29030863 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.
    Related ArticlesExercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection. Exp Neurol. 2017 Oct 11;: Authors: Einstein O, Fainstein N, Touloumi O, Lagoudaki R, Hanya E, Grigoriadis N, Katz A, Ben-Hur T Abstract BACKGROUND: Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. OBJECTIVE: We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. METHODS: Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. RESULTS: LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs.… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders.
    Related ArticlesShort delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2017 Oct 13;: Authors: Bonnan M, Valentino R, Debeugny S, Merle H, Fergé JL, Mehdaoui H, Cabre P Abstract INTRODUCTION: Severe attacks of neuromyelitis optica spectrum disorder (NMO-SD) are improved by plasma exchange (PLEX) given as an adjunctive therapy. Initial studies failed to demonstrate a delay of PLEX treatment influenced clinical outcome; however PLEX was always used late. We examine the clinical consequences of delay in PLEX initiation on severe optic neuritis and spinal cord attacks in NMO-SD. METHODS: All of our patients who suffered attacks of NMO-SD, treated in our centre by PLEX, were retrospectively considered for inclusion. Primary outcome was defined as complete improvement. Secondary poor/good outcomes were respectively defined to be the higher/lower third of Delta-Expanded Disability Status Scale (EDSS) (late minus baseline EDSS). Delays from clinical onset to PLEX initiation were categorised for multivariate analysis. RESULTS: Of the 60 patients included, NMO-SD criteria (2015) were fulfilled in 92%. One hundred and fifteen attacks were included and received PLEX with a median of 7 days (0-54) after clinical onset. The probability to regain complete improvement continuously decreased from 50% for PLEX given at day 0 to 1%-5% after day 20. Through multivariate analysis, the baseline impairment and PLEX delay were associated with the probability to complete improvement (OR 5.3; 95% CI 1.8 to 15.9). Reducing the PLEX delay also influenced the good secondary outcome… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • More evidence is needed to show any role of cytomegalovisrus and varicella zoster virus in pathogenesis of multiple sclerosis.
    Related ArticlesMore evidence is needed to show any role of cytomegalovisrus and varicella zoster virus in pathogenesis of multiple sclerosis. J Neuroimmunol. 2017 Sep 18;: Authors: Badihian S, Manouchehri N, Badihian N PMID: 29030049 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Ulk4 deficiency leads to hypomyelination in mice.
    Related ArticlesUlk4 deficiency leads to hypomyelination in mice. Glia. 2017 Oct 16;: Authors: Liu M, Xu P, Guan Z, Qian X, Dockery P, Fitzgerald U, O'Brien T, Shen S Abstract Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes. Defects in myelination are increasingly recognized as a common pathology underlying neuropsychiatric and neurodevelopmental disorders, which are associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key transcription factors have been identified for oligodendrogenesis, but little is known about their associated regulators. Here we report that Ulk4 acts as a key regulator of myelination. Myelination is reduced by half in the Ulk4(tm1a/tm1a) hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and Nefm remains unaltered. Transcriptome analyses reveal that 8 (Gfap, Mbp, Mobp, Plp1, Slc1a2, Ttr, Cnp, Scd2) of the 10 most significantly altered genes in the Ulk4(tm1a/tm1a) brain are myelination-related. Ulk4 is co-expressed in Olig2(+) (pan-oligodendrocyte marker) and CC1(+) (mature myelinated oligodendrocyte marker) cells during postnatal development. Major oligodendrogeneic transcription factors, including Olig2, Olig1, Myrf, Sox10, Sox8, Sox6, Sox17, Nkx2-2, Nkx6-2 and Carhsp1, are significantly downregulated in the mutants. mRNA transcripts enriched in oligodendrocyte progenitor cells (OPCs), the newly formed oligodendrocytes (NFOs) and myelinating oligodendrocytes (MOs), are significantly attenuated. Expression of stage-specific oligodendrocyte factors including Cspg4, Sox17, Nfasc, Enpp6, Sirt2, Cnp, Plp1, Mbp, Ugt8, Mag and Mog are markedly decreased. Indirect effects of axon caliber and neuroinflammation may also contribute to the hypomyelination, as Ulk4 mutants display smaller axons and increased neuroinflammation. This is… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens.
    Related ArticlesDiagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens. Neurol Sci. 2017 Oct;38(Suppl 2):225-229 Authors: Zuliani L, Zoccarato M, Gastaldi M, Iorio R, Evoli A, Biagioli T, Casagrande S, Bazzigaluppi E, Fazio R, Giannotta C, Nobile-Orazio E, Andreetta F, Simoncini O, Costa G, Mariotto S, Ferrari S, Galloni E, Marcon M, Franciotta D, Giometto B Abstract This document presents the guidelines for testing antibodies against neuronal surface antigens that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on autoimmune encephalitis associated with antibodies against neuronal surface antigens, indications and limits of testing for such antibodies, instructions for result interpretation, and an agreed laboratory protocol (Appendix A) are reported for the communicative community of neurologists and clinical pathologists.PMID: 29030767 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Advances in the Treatment of Paraproteinemic Neuropathy.
    Related ArticlesAdvances in the Treatment of Paraproteinemic Neuropathy. Curr Treat Options Neurol. 2017 Oct 16;19(12):43 Authors: Nobile-Orazio E, Bianco M, Nozza A Abstract Purpose of review Several advances have been made on the pathogenesis and therapy of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is important for the neurologist to understand the pathogenetic relevance of this association especially when the hematological disease does not require per se any therapy. Recent findings Treatment of the neuropathy in patients with malignant paraproteinemia is mainly addressed by the hematologist while the neurologist is mainly involved in the initial diagnosis and in deciding whether the neuropathy is caused by the disease or by the chemotherapy used for the disease. There is little evidence that the neuropathy is caused by the hematological condition in patients with IgG or IgA monoclonal gammopathy of undetermined significance (MGUS) unless there is an evidence of a reactivity of the paraprotein with nerve or evidence of its presence in the nerve. Patients with a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)-like presentation should be treated as CIDP while there is no evidence that immune or chemotherapy may be effective in the other patients. In most patients with IgM paraproteinemia, that is usually a MGUS or an indolent Waldenström's macroglobulinemia, the neuropathy is induced by an immune reactivity of the paraprotein with nerve and particularly with the myelin-associated glycoprotein. There are now consistent data also from controlled studies that the anti-CD20 monoclonal antibody rituximab may improve the neuropathy in these patients. POEMS syndrome… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Diagnostics of anti-MAG antibody polyneuropathy.
    Related ArticlesDiagnostics of anti-MAG antibody polyneuropathy. Neurol Sci. 2017 Oct;38(Suppl 2):249-252 Authors: Franciotta D, Gastaldi M, Benedetti L, Garnero M, Biagioli T, Brogi M, Costa G, Fadda E, Andreetta F, Simoncini O, Giannotta C, Bazzigaluppi E, Fazio R, Bedin R, Ferraro D, Mariotto S, Ferrari S, Galloni E, De Riva V, Zardini E, Cortese A, Nobile-Orazio E Abstract This document presents the guidelines for anti-myelin-associated glycoprotein (MAG) antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses. The main clinical information on anti-MAG antibody polyneuropathy, indications and limits of anti-MAG antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.PMID: 29030772 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • The Sequential Ultrasonographic, Electrophysiological and MRI Findings in a Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barré Syndrome from the Acute Phase to the Chronic Phase.
    Related ArticlesThe Sequential Ultrasonographic, Electrophysiological and MRI Findings in a Patient with the Pharyngeal-cervical-brachial Variant of Guillain-Barré Syndrome from the Acute Phase to the Chronic Phase. Intern Med. 2017;56(10):1225-1230 Authors: Miyagi T, Higa K, Kido M, Ishihara S, Nakachi R, Suwazono S Abstract Acute progressive weakness in bulbar, neck and limbs is included in several differential diagnoses, including the pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome (GBS). Patients with the PCB variant of GBS are reported to have localized diagnostic cervical spinal nerve abnormalities that can be examined by nerve ultrasonography (NUS) and magnetic resonance neurography (MRN). We herein report the case of a 77-year-old man with the PCB variant of GBS. Although the nerve conduction study (NCS) findings were indirect indicators for an early diagnosis, the combination of NCS and NUS was a useful complementary measure that facilitated an early diagnosis. MRN did not show any apparent diagnostic abnormalities. After early treatment, the patient was discharged and returned home.PMID: 28502941 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Natalizumab therapy is associated with changes in serum JC virus antibody indices over time.
    Related ArticlesNatalizumab therapy is associated with changes in serum JC virus antibody indices over time. J Neurol. 2017 Oct 16;: Authors: Peters J, Williamson E Abstract To examine changes in anti-JC Virus (JCV) index measurements over time in multiple sclerosis (MS) patients to better understand this test, which is used in assessing risk of progressive multifocal leukoencephalopathy (PML) with natalizumab. We aim to describe and compare seroconversion rates, variability of JCV antibody index values, and changes in index values over time between patients on natalizumab therapy and patients naïve to natalizumab. Anti-JCV index values are used to help decide whether to start, continue, or stop treatment. Assessing how index values vary over time is interpreted to allow a patient's risk of PML to be better characterized. Retrospective analysis was conducted using records of patients with multiple JCV antibody index measurements exposed to therapy with natalizumab (N = 150) or not (N = 145). Rates of seroconversion, variability of indices, and changes in index values over time were calculated and compared. Patients on natalizumab who were initially JCV antibody negative seroconverted at a significantly higher rate than patients naïve to natalizumab (23.9 vs. 9.1%, p < 0.01). Variability of anti-JCV indices was also found to be significantly higher for patients on natalizumab (p < 0.05). Patients on natalizumab additionally trended towards a larger increase in index values over time. Therapy with natalizumab was associated with higher rates of seroconversion and greater anti-JCV index variability, suggesting that therapy with natalizumab may influence this test used to assess risk of treatment… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Autoimmune Thyroid Diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH-Receptor Immune Response.
    Related ArticlesAutoimmune Thyroid Diseases in Patients Treated with Alemtuzumab for Multiple Sclerosis: An Example of Selective Anti-TSH-Receptor Immune Response. Front Endocrinol (Lausanne). 2017;8:254 Authors: Rotondi M, Molteni M, Leporati P, Capelli V, Marinò M, Chiovato L Abstract Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of active relapsing-remitting multiple sclerosis (MS). Alemtuzumab induces a rapid and prolonged depletion of lymphocytes from the circulation, which results in a profound immuno-suppression status followed by an immune reconstitution phase. Secondary to reconstitution autoimmune diseases represent the most common side effect of Alemtuzumab treatment. Among them, Graves' disease (GD) is the most frequent one with an estimated prevalence ranging from 16.7 to 41.0% of MS patients receiving Alemtuzumab. Thyrotropin (TSH) receptor (R)-reactive B cells are typically observed in GD and eventually present this autoantigen to T-cells, which, in turn, secrete several pro-inflammatory cytokines and chemokines. Given that reconstitution autoimmunity is more frequently characterized by autoantibody-mediated diseases rather than by destructive Th1-mediated disorders, it is not surprising that GD is the most commonly reported side effect of Alemtuzumab treatment in patients with MS. On the other hand, immune reconstitution GD was not observed in a large series of patients with rheumatoid arthritis treated with Alemtuzumab. This negative finding supports the view that patients with MS are intrinsically more at risk for developing Alemtuzumab-related thyroid dysfunctions and in particular of GD. From a clinical point of view, Alemtuzumab-induced GD is characterized by a surprisingly high rate of remission, both spontaneous and after antithyroid… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • CC-chemokine ligand 18 is a useful biomarker associated with disease activity in IgG4-related disease.
    Related ArticlesCC-chemokine ligand 18 is a useful biomarker associated with disease activity in IgG4-related disease. Ann Rheum Dis. 2017 Oct 13;: Authors: Akiyama M, Yasuoka H, Yoshimoto K, Takeuchi T PMID: 29030359 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • A Case of IgG4-related Lung Pseudotumor and Pleural Inflammation with Autoimmune Hepatitis.
    Related ArticlesA Case of IgG4-related Lung Pseudotumor and Pleural Inflammation with Autoimmune Hepatitis. Intern Med. 2017 Oct 16;: Authors: Nagashima K, Sano I, Kobayashi T, Eto K, Nagai K, Ninomiya R, Suzuki A, Oohata Y, Konishi K, Nakano T, Yamamoto F Abstract A 63-year-old man was admitted to our department following a secondary medical examination. Blood tests showed high levels of liver enzymes, IgG, IgG4, and antinuclear antibody. Computed tomography showed tumors in the bilateral lower lobes of the lungs and pleural thickening. After pleural and liver biopsy procedures, he was conclusively diagnosed with IgG4-related lung pseudotumor and pleural inflammation with autoimmune hepatitis. We started treatment with prednisolone 40 mg/day, and chest X-rays and blood tests showed signs of improvement. This was a rare case that suggested an association between IgG4-related disease and autoimmune hepatitis.PMID: 29033427 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents.
    Related ArticlesImmunohistochemical and serological characterization of membranous nephropathy in children and adolescents. Pediatr Nephrol. 2017 Oct 15;: Authors: Dettmar AK, Wiech T, Kemper MJ, Soave A, Rink M, Oh J, Stahl RAK, Hoxha E, Pediatric MN Study Group Abstract BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, but is less frequent in children. Antibodies against four antigens leading to MN have been described in children: phospholipase A2 receptor 1 (PLA2R1), thrombospondin type-1 domain-containing 7A (THSD7A), neutral endopeptidase (NEP), and cationic bovine serum albumin (BSA). METHODS: Twelve children with MN were included in this study. Sera of all patients were analyzed for antibodies against PLA2R1, THSD7A, NEP, and BSA. All sera were also analyzed using Western blot with human glomerular extracts (HGE) under non reducing conditions. In 5 cases renal biopsies were analyzed for PLA2R1, THSD7A, NEP, BSA, and all IgG subclasses. RESULTS: Six patients were PLA2R1-antibody-positive, whereas THSD7A, NEP, and BSA antibodies were not found in any of our 12 patients. All sera were analyzed by Western blot using human glomerular extracts; however, no further potential antigens were found. Five kidney biopsies from 2 PLA2R1-antibody-positive and 3 PLA2R1-antibody-negative patients were available for additional analyses, confirming the diagnosis of PLA2R1-associated MN in 2 cases, whereas none of the biopsies revealed enhanced staining for THSD7A, NEP or BSA. IgG2 and IgG4 stainings were positive in both patients with PLA2R1-associated MN and negative in the other biopsies. During follow-up (median 24 months), 4 children with PLA2R1-associated MN went… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Structural characterization of the Man5 glycoform of human IgG3 Fc.
    Related ArticlesStructural characterization of the Man5 glycoform of human IgG3 Fc. Mol Immunol. 2017 Oct 11;92:28-37 Authors: Shah IS, Lovell S, Mehzabeen N, Battaile KP, Tolbert TJ Abstract Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined the crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Retroperitoneal fibrosis associated with IgG4-related disease diagnosed by prostate biopsy developed with acute post-renal renal failure: A case report.
    Related ArticlesRetroperitoneal fibrosis associated with IgG4-related disease diagnosed by prostate biopsy developed with acute post-renal renal failure: A case report. Urol Case Rep. 2018 Jan;16:9-11 Authors: Inui K, Nakagawa Y, Watanabe H, Hasegawa G, Ikeda Y, Tsuchida M, Koda R, Iino N, Hoshii T, Nishiyama T, Tomita Y PMID: 29034178 [PubMed] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double-blind, placebo-controlled clinical trial.
    Related ArticlesLolium perenne peptides for treatment of grass pollen allergy: A randomized, double-blind, placebo-controlled clinical trial. J Allergy Clin Immunol. 2017 Oct 10;: Authors: Shamji MH, Ceuppens J, Bachert C, Hellings P, Placier G, Thirion G, Bovy N, Durham SR, Duchateau J, Legon T, Pirotton S PMID: 29030102 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma.
    Related ArticlesThe clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma. HPB (Oxford). 2017 Oct 09;: Authors: Pak LM, Schattner MA, Balachandran V, D'Angelica MI, DeMatteo RP, Kingham TP, Jarnagin WR, Allen PJ Abstract BACKGROUND: Elevation in the serum immunoglobulin-G4 (IgG4) level has been used as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined. This study evaluates the clinical utility of IgG4 in differentiating AIP from PDAC. METHODS: All patients evaluated in the hepatopancreaticobiliary surgery clinics with measured serum IgG4 were included. Patients were divided into normal IgG4 (<135 mg/dL) and elevated IgG4 (≥135 mg/dL) groups. The final diagnosis was determined by operative pathology when available or by clinical outcome. The sensitivity, specificity, PPV, and NPV of IgG4 for diagnosing AIP was assessed. RESULTS: Between 1997 and 2015, 298 patients were identified. Normal IgG4 levels were present in 85% of patients (254/298), while 15% (44/298) were elevated. The overall prevalence of AIP was 17% (52/298). The sensitivity and specificity of IgG4 for AIP was 67% and 96%, respectively; however, the PPV was only 80%, including a 9% occurrence of PDAC in patients with an elevated IgG4. CONCLUSION: In this study of selected patients who underwent IgG4 testing, 9% of elevated IgG4 patients had PDAC. The overreliance on IgG4 as diagnostic for AIP may lead to mis-diagnosis and delayed treatment for PDAC.PMID: 29033025 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-17
  • A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer’s Disease.
    A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease. Proteomics Clin Appl. 2017 Oct 13;: Authors: Brinkmalm G, Sjödin S, Simonsen AH, Hasselbalch SG, Zetterberg H, Brinkmalm A, Blennow K Abstract PURPOSE: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and 2-3 peptides per protein were quantified using stable isotope-labeled peptide standards. RESULTS: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin-2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal pentraxin-1, as well as neurofascin were also significantly lowered in AD (p<0.05). The other investigated proteins, β2-microglobulin, cystatin C, amyloid precursor protein, lysozyme C, neurexin-2, neurexin-3, and neurocan core protein, were not significantly altered. CONCLUSION AND CLINICAL RELEVANCE: PRM-MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders. This article is protected by copyright. All rights reserved.PMID: 29028155 [PubMed - as… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Elevated serum adipsin may predict unsuccessful treatment for cows’ milk allergy but other biomarkers do not.
    Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy but other biomarkers do not. Acta Paediatr. 2017 Oct 13;: Authors: Salmivesi S, Paassilta M, Huhtala H, Nieminen R, Moilanen E, Korppi M Abstract AIM: This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children. METHODS: The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6,10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users. RESULTS: There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study. CONCLUSION: None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome. This article is protected by copyright. All rights reserved.PMID: 29028118 [PubMed - as supplied by… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Blood lymphocyte subsets identify optimal responders to IFN-beta in MS.
    Related ArticlesBlood lymphocyte subsets identify optimal responders to IFN-beta in MS. J Neurol. 2017 Oct 12;: Authors: Alenda R, Costa-Frossard L, Alvarez-Lafuente R, Espejo C, Rodríguez-Martín E, de la Maza SS, Villarrubia N, Río J, Domínguez-Mozo MI, Montalban X, Álvarez-Cermeño JC, Villar LM Abstract Response to interferon-beta (IFN-beta) treatment is heterogeneous in multiple sclerosis (MS). We aimed to search for biomarkers predicting no evidence of disease activity (NEDA) status upon IFN-beta treatment in MS. 119 patients with relapsing-remitting MS (RRMS) initiating IFN-beta treatment were included in the study, and followed prospectively for 2 years. Neutralizing antibodies (NAb) were explored in serum samples obtained after 6 and 12 months of IFN-beta treatment. Soluble cytokines and blood lymphocytes were studied in basal samples by ELISA and flow cytometry, respectively. 9% of patients developed NAb. These antibodies were more frequent in patients receiving IFN-beta 1b than in those treated subcutaneous (p = 0.008) or intramuscular (p < 0.0001) IFN-beta 1a. No patient showing NAb remained NEDA during follow-up. Basal immunological variables are also associated with patient response. Percentages below 3% of CD19 + CD5 + cells (AUC 0.74, CI 0.63-0.84; OR 10.68, CI 3.55-32.15, p < 0.0001; Likelihood ratio 4.28) or above 2.6% of CD8 + perforin + T cells (AUC 0.79, CI 0.63-0.96; OR 6.11, CI 2.0-18.6, p = 0.0009; Likelihood ratio 5.47) increased the probability of achieving NEDA status during treatment. Basal blood immune cell subsets contribute to identify MS patients with a high probability of showing an optimal response to IFN-beta.PMID: 29027004 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis.
    The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis. Mult Scler. 2017 Oct 01;:1352458517736149 Authors: Pichler A, Khalil M, Langkammer C, Pinter D, Ropele S, Fuchs S, Bachmaier G, Enzinger C, Fazekas F Abstract BACKGROUND: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. METHODS: We identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. RESULTS: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29-54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm(3) vs 1591.2 cm(3), p = 0.001), a lower cGMV (628.5 cm(3) vs 668.6 cm(3), p = 0.002) and WMV (752.2 cm(3) vs 783.9 cm(3), p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. CONCLUSION: VRF are associated with lower brain volume already in early… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Fatigue as a symptom or comorbidity of neurological diseases.
    Fatigue as a symptom or comorbidity of neurological diseases. Nat Rev Neurol. 2017 Oct 13;: Authors: Penner IK, Paul F Abstract Fatigue, best described as an overwhelming feeling of tiredness and exhaustion, occurs in the context of various neurological diseases. The high prevalence of fatigue as either a symptom or a comorbidity of neurological disease must be taken seriously, as fatigue interferes with patients' activities of daily living, has a remarkable negative impact on quality of life, and is a major reason for early retirement. The tremendous consequences of fatigue are consistent across neurological diseases, as is the uncertainty concerning its underlying pathophysiological mechanisms. Inconsistencies in defining fatigue contribute to the present situation, in which fatigue represents one of the least-studied and least- understood conditions. Tools for assessing fatigue abound, but few can be recommended for clinical or research use. To make matters worse, evidence-based pharmacological treatment options are scarce. However, non-pharmacological approaches are currently promising and likely to become of increasing importance. In sum, fatigue is challenging for both health-care professionals and patients. The present article aims to provide a comprehensive review of the literature on fatigue in neurological disease, and to reveal its complexity, as well as weaknesses in the concept of fatigue itself.PMID: 29027539 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Male factor infertility and risk of multiple sclerosis: A register-based cohort study.
    Male factor infertility and risk of multiple sclerosis: A register-based cohort study. Mult Scler. 2017 Oct 01;:1352458517734069 Authors: Glazer CH, Tøttenborg SS, Giwercman A, Bräuner EV, Eisenberg ML, Vassard D, Magyari M, Pinborg A, Schmidt L, Bonde JP Abstract BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no studies have evaluated whether male infertility is associated with MS. OBJECTIVE: To study the association between male factor infertility and prevalent as well as incident MS. METHOD: Our cohort was established by linkage of the Danish National in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry and consisted of 51,063 men whose partners had undergone fertility treatment in all public and private fertility clinics in Denmark between 1994 and 2015. RESULTS: With a median age of 34 years at baseline, 24,011 men were diagnosed with male factor infertility and 27,052 did not have male factor infertility and made up the reference group. Men diagnosed with male factor infertility had a higher risk of prevalent (odds ratio (OR) = 1.61, 95% confidence interval (95% CI) 1.04-2.51) and incident MS (hazard ratio (HR) = 1.28, 95% CI 0.76-2.17) when compared to the reference group. CONCLUSION: This nationwide cohort study has shown, for the first time, an association between male infertility and MS which may be due to underlying common etiologies such as hypogonadism, shared genetics, or a joint autoimmune component.PMID: 29027840 [PubMed - as supplied by… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Schnitzler syndrome: A rare cause of chronic recalcitrant urticaria successfully treated with Anakinra.
    Related ArticlesSchnitzler syndrome: A rare cause of chronic recalcitrant urticaria successfully treated with Anakinra. Australas J Dermatol. 2017 Oct 12;: Authors: Sharma S, Joske D, Watson D, Caccetta T, Baltic S, Kumarasinghe SP PMID: 29027204 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • [Unexpected symptoms of monoclonal gammopathy].
    [Unexpected symptoms of monoclonal gammopathy]. Ned Tijdschr Geneeskd. 2017;161(0):D1741 Authors: Smit PM, Abrahams AC, Schutgens RGE, Notermans NC, Minnema MC Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a common haematological disorder characterized by the presence of a monoclonal protein (M-protein). MGUS is considered an asymptomatic 'innocent' pre-malignant precursor condition of - mostly - multiple myeloma, without indication for treatment. We present three cases illustrating that MGUS can lead to serious problems. The first patient, a 51-year-old female, presented with polyneuropathy due to anti-MAG antibodies related to IgM MGUS. The second patient, a 37-year-old female, presented with proteinuria due to immunotactoid glomerulopathy caused by renal monoclonal IgG deposition associated with MGUS. The third patient, a 55-year-old female, presented with severe bleeding caused by an aspecific inhibitor of the coagulation cascade as part of IgG MGUS. In conclusion, in addition to the risk of progression to an overt haematological malignancy, MGUS can lead to severe symptoms and significant organ damage by auto-antibody activity or pathological accumulation in tissues of its toxic M-protein.PMID: 29027517 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.
    Related ArticlesRegulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy. J Neuroinflammation. 2017 Mar 20;14(1):58 Authors: Maddur MS, Stephen-Victor E, Das M, Prakhar P, Sharma VK, Singh V, Rabin M, Trinath J, Balaji KN, Bolgert F, Vallat JM, Magy L, Kaveri SV, Bayry J Abstract BACKGROUND: Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. METHODS: Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. RESULTS: The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with Treg cell response. Contrary to murine study, there was no… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-15
  • Key points on Zika infection for the intensivist.
    Related ArticlesKey points on Zika infection for the intensivist. Intensive Care Med. 2016 Sep;42(9):1490-2 Authors: Bozza FA, Grinsztejn B PMID: 27172823 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-13
  • Zika virus-associated Guillain-Barré syndrome: a warning for critical care physicians.
    Related ArticlesZika virus-associated Guillain-Barré syndrome: a warning for critical care physicians. Intensive Care Med. 2016 Sep;42(9):1485-6 Authors: Thiery G, Valentino R, Meddhaoui H PMID: 27118575 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-13
  • Anti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report.
    Related ArticlesAnti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report. Medicine (Baltimore). 2017 Oct;96(40):e8228 Authors: Ju W, Qi B, Wang X, Yang Y Abstract RATIONALE: We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease. PATIENT CONCERNS: The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and δ waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma. DIAGNOSIS: A clinical diagnosis of lymphoma and PNS was made. INTERVENTIONS: The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days. LESSONS: We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2-associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case.PMID: 28984777 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-10-13