LECTURAS CIENTÍFICAS

  • Demyelinating neuropathy in a 6-year-old girl with autism spectrum disorder.
    Related ArticlesDemyelinating neuropathy in a 6-year-old girl with autism spectrum disorder. Pediatr Int. 2017 Aug;59(8):951-954 Authors: Kamata A, Muramatsu K, Sawaura N, Makioka N, Ogata T, Kuwashima M, Arakawa H Abstract Herein we report the case of a 6-year-old girl with autism spectrum disorder (ASD) and weakness in the distal portion of the right upper limb. Although difficult to perform, nerve conduction studies indicated demyelinating neuropathy. Magnetic resonance imaging (MRI) showed swelling a nd high-intensity signals in the right brachial plexus and cervical spinal roots. The symptoms recovered after a single course of i.v. immunoglobulin. Electrophysiological indices and MRI findings also improved after treatment. This case demonstrates the utility of neuroimaging in addition to electrophysiological assessments for the diagnosis of demyelinating neuropathy, particularly in young patients with ASD.PMID: 28804976 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β.
    Related ArticlesSodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β. J Immunol. 2016 Oct 15;197(8):3099-3110 Authors: Kundu M, Mondal S, Roy A, Martinson JL, Pahan K Abstract Upregulation and/or maintenance of regulatory T cells (Tregs) during autoimmune insults may have therapeutic efficacy in autoimmune diseases. Earlier we have reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders, upregulates Tregs and protects mice from experimental allergic encephalomyelitis, an animal model of multiple sclerosis. However, mechanisms by which NaB increases Tregs are poorly understood. Because TGF-β is an important inducer of Tregs, we examined the effect of NaB on the status of TGF-β. In this study, we demonstrated that NaB induced the expression of TGF-β mRNA and protein in normal as well as proteolipid protein-primed splenocytes. The presence of a consensus STAT6 binding site in the promoter of the TGF-β gene, activation of STAT6 in splenocytes by NaB, recruitment of STAT6 to the TGF-β promoter by NaB, and abrogation of NaB-induced expression of TGF-β in splenocytes by small interfering RNA knockdown of STAT6 suggest that NaB induces the expression of TGF-β via activation of STAT6. Furthermore, we demonstrated that blocking of TGF-β by neutralizing Abs abrogated NaB-mediated protection of Tregs and experimental allergic encephalomyelitis. These studies identify a new function of NaB in upregulating TGF-β via activation of STAT6, which may be beneficial in MS patients.PMID: 27605008 [PubMed - indexed… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Multiple Sclerosis and Schizophrenia.
    Multiple Sclerosis and Schizophrenia. Int J Mol Sci. 2017 Aug 12;18(8): Authors: Arneth BM Abstract The psychiatric and neurological aspects of health may present methodological challenges in the diagnosis and treatment of disease. This is especially true for patients whose symptoms indicate the coexistence of multiple sclerosis (MS) and schizophrenia (SCZ). These cases raise critical questions regarding the relationship between the mind and the brain. Studies have noted that patients with MS have an increased risk of developing SCZ or bipolar disorder (BD). It is suggested here that MS and a subgroup of SCZ have similar etiologies. Factors such as gender, ethnicity, geography and season also have an influence on the occurrence of MS and SCZ. This paper aims to examine the differences and similarities between SCZ and MS. For this purpose, scientific papers examining various factors associated with these disorders were reviewed, and similarities and differences in genetic, immunological, seasonal, geographical, and gender-related risk factors and limited similarities in ethnic factors between the two diseases were identified. The findings suggest that subgroups of these two diseases may belong to the same class of disorders.PMID: 28805697 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Daclizumab for the treatment of adults with relapsing forms of multiple sclerosis.
    Related ArticlesDaclizumab for the treatment of adults with relapsing forms of multiple sclerosis. Expert Rev Clin Pharmacol. 2017 Aug 14;: Authors: Osherov M, Milo R Abstract INTRODUCTION: The goal of the article is to review the mechanism of action and the use of daclizumab, a humanized monoclonal antibody (mAb) against the alpha subunit of the high affinity interleukin-2 (IL-2) receptor, in the treatment of Multiple Sclerosis (MS). Areas covered: PubMed was searched for the terms "daclizumab" and "multiple sclerosis". The mechanisms of action, pharmacokinetics and pharmacodynamics, major studies, side effects and drug interactions of daclizumab in MS are discussed. Expert commentary: Monthly daclizumab-beta [DAC-beta, formerly daclizumab high yield process (DAC HYP), approved as ZINBRYTA®, which has a different form and structure than an earlier form of daclizumab], is an effective and convenient treatment option for patients with relapsing forms of MS who have failed other treatment, or as a first-line option in highly active MS patients. IL-2 signaling modulation by daclizumab constitutes a novel mechanism of action which may also underlie the adverse and serious adverse events and risk profile of the drug that requires appropriate patient selection, monitoring and risk-mitigation programs.PMID: 28803486 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.
    Related ArticlesEndocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody. Mult Scler. 2017 Aug 01;:1352458517726593 Authors: Hacohen Y, Messina S, Gan HW, Wright S, Chandratre S, Leite MI, Fallon P, Vincent A, Ciccarelli O, Wassmer E, Lim M, Palace J, Hemingway C Abstract The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.PMID: 28803524 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Autoantibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNPA1) cause altered ‘ribostasis’ and neurodegeneration; the legacy of HAM/TSP as a model of progressive multiple sclerosis.
    Related ArticlesAutoantibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNPA1) cause altered 'ribostasis' and neurodegeneration; the legacy of HAM/TSP as a model of progressive multiple sclerosis. J Neuroimmunol. 2017 Mar 15;304:56-62 Authors: Levin MC, Lee S, Gardner LA, Shin Y, Douglas JN, Salapa H Abstract Several years following its discovery in 1980, infection with human T-lymphotropic virus type 1 (HTLV-1) was shown to cause HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease biologically similar to progressive forms of multiple sclerosis (MS). In this manuscript, we review some of the clinical, pathological, and immunological similarities between HAM/TSP and MS with an emphasis on how autoantibodies to an RNA binding protein, heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), might contribute to neurodegeneration in immune mediated diseases of the central nervous system.PMID: 27449854 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Estimating the reproductive number, total outbreak size, and reporting rates for Zika epidemics in South and Central America.
    Related ArticlesEstimating the reproductive number, total outbreak size, and reporting rates for Zika epidemics in South and Central America. Epidemics. 2017 Jul 13;: Authors: Shutt DP, Manore CA, Pankavich S, Porter AT, Del Valle SY Abstract As South and Central American countries prepare for increased birth defects from Zika virus outbreaks and plan for mitigation strategies to minimize ongoing and future outbreaks, understanding important characteristics of Zika outbreaks and how they vary across regions is a challenging and important problem. We developed a mathematical model for the 2015/2016 Zika virus outbreak dynamics in Colombia, El Salvador, and Suriname. We fit the model to publicly available data provided by the Pan American Health Organization, using Approximate Bayesian Computation to estimate parameter distributions and provide uncertainty quantification. The model indicated that a country-level analysis was not appropriate for Colombia. We then estimated the basic reproduction number to range between 4 and 6 for El Salvador and Suriname with a median of 4.3 and 5.3, respectively. We estimated the reporting rate to be around 16% in El Salvador and 18% in Suriname with estimated total outbreak sizes of 73,395 and 21,647 people, respectively. The uncertainty in parameter estimates highlights a need for research and data collection that will better constrain parameter ranges.PMID: 28803069 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI.
    Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler. 2017 Aug 01;:1352458517726866 Authors: Bergamaschi R, Cortese A, Pichiecchio A, Berzolari FG, Borrelli P, Mallucci G, Bollati V, Romani A, Nosari G, Villa S, Montomoli C Abstract BACKGROUND: Some environmental factors have been already associated to increased risk of multiple sclerosis (MS), but it is plausible that additional factors might play a role. OBJECTIVE: To investigate in MS patients the relationship between inflammatory activity, detected by brain magnetic resonance imaging (MRI) with gadolinium (Gd), and air pollution, namely, particulate matters with diameter less than 10 μm (PM10). METHODS: We analyzed from 52 remitting MS patients 226 brain MRIs, 34% with (Gd+MRI) and 66% without (Gd-MRI) T1-Gd-enhancing lesions. Daily recording of PM10 in the 30 days before MRI examination was obtained by monitors depending on the residence of subjects. RESULTS: PM10 levels in the 5, 10, 15, 20, and 25 days before brain MRIs were higher (plus 16%, 21%, 24%, 25%, and 21%, respectively) with reference to Gd+MRI versus Gd-MRI. There was a significant association between Gd+MRI and PM10 levels ( p = 0.013), independent of immune therapies, smoker status, and season. In patients who had two repeated MRIs with opposite outcomes (Gd-MRI and Gd+MRI), PM10 levels were strongly higher in concurrence with Gd+MRI ( p < 0.0001). CONCLUSION: Our findings suggest that air pollution may be a risk factor for MS favoring inflammatory exacerbations.PMID: 28805546 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Multiple sclerosis: Skin-induced antigen-specific immune tolerance.
    Related ArticlesMultiple sclerosis: Skin-induced antigen-specific immune tolerance. J Neuroimmunol. 2017 Aug 02;: Authors: Wildner P, Selmaj KW Abstract Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile. Several studies have been performed to evaluate highly selective, antigen-induced, therapies for experimental autoimmune encephalomyelitis (EAE) and MS. These trials have also indicated the importance of the antigen administration route. The continued efforts to develop efficient and safe MS therapy gave rise to the idea of incorporating the skin immune system in order to modulate autoimmunity in MS. Skin is the largest immunological organ of human body, and thus provides ample opportunities to modify immune responses. Skin dendritic cells have a significant ability to modulate the immune reactions, promoting either immunity or tolerance. Their capacity to induce tolerance has already been described in several experimental models of MS. In a one-year, double-blinded, placebo-controlled study assessing the effectiveness of transdermal myelin peptides patches, significant changes in the morphology of Langerhans cells (LCs) and shifts in the dendritic cell (DC) populations in the draining lymph nodes have been observed. In addition, patients treated with myelin patches showed… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • The clinical characteristics of AQP4 antibody positive NMO/SD in a large cohort of Chinese Han patients.
    Related ArticlesThe clinical characteristics of AQP4 antibody positive NMO/SD in a large cohort of Chinese Han patients. J Neuroimmunol. 2017 Jan 15;302:49-55 Authors: ZhangBao J, Zhou L, Li X, Cai T, Lu J, Lu C, Zhao C, Quan C Abstract We aim to summarize the clinical features of AQP4-ab-positive NMO/SD in a large Chinese Han cohort. The clinical data of 145 AQP4-ab-seropositive patients was retrospectively reviewed. 55.9% (81/145) of the patients were defined as NMO while 39.3% (57/145) were defined as NMOSD according to the criteria established in 2006 and 2007. The mean onset age was 34.4years and the female to male ratio was 8.7:1. The median disease duration was 57months. The median of "time to second attack" and "time to develop NMO" was 7 and 13months respectively. Ratio of monophasic to relapsing was 1:7.1. Myelitis and optic neuritis (ON) were the most common manifestations at onset, followed by postrema syndrome. The median age of patients presenting with ON at disease onset was significantly younger than patients presenting with myelitis. Only 17.2% of the patients younger than 30years presented with longitudinally extensive transverse myelitis (LETM) at onset, while 55.6% of the patients over 30years presented with LETM at onset. The patients presenting with ON at disease onset all exhibited a relapsing course, had a higher probability of subsequent involvement of other CNS regions and developing into definite NMO over time compared with those with LETM as the first attack. AQP4-ab levels were higher in patients with circulating auto-antibodies such… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Multiple sclerosis: The resolving lesion revealed.
    Related ArticlesMultiple sclerosis: The resolving lesion revealed. J Neuroimmunol. 2017 Mar 15;304:2-6 Authors: Raine CS Abstract A little studied lesion, the resolving lesion, is described in multiple sclerosis (MS). Unusual features of early resolving lesions comprised a fibrous astrogliotic parenchyma replete with lipid-laden (foamy) microglia/macrophages widely scattered throughout and lined up at the edge, separating demyelinated plaque from myelinated white matter. Ongoing myelin breakdown was absent, as was remyelination. Later resolving lesions displayed the unusual coexistence of macrophages and remyelination within the gliotic parenchyma. Collectively, these observations may provide for the first time evidence for a role in MS for mitigating factors like alternatively-activated (M2) microglia/macrophages, known to have an anti-inflammatory phenotype and to be associated with wound-healing and repair.PMID: 27265754 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Clinical outcome and predictive factors of postoperative myasthenic crisis in 173 thymomatous myasthenia gravis patients myasthenic crisis in thymomatous patients.
    Related ArticlesClinical outcome and predictive factors of postoperative myasthenic crisis in 173 thymomatous myasthenia gravis patients myasthenic crisis in thymomatous patients. Int J Neurosci. 2017 Aug 14;:1-26 Authors: Li Y, Wang H, Chen P, Chen Z, Su C, Luo C, Feng H, Liu W Abstract PURPOSE: Thymectomy is the first-line therapy for thymomatous myasthenia gravis patients. The aim of this study is to explore the clinical outcome and predictors of postoperative myasthenic crisis (POMC) in these patients. METHOD: Clinical data of 173 thymomatous myasthenia gravis patients undergoing thymectomy from January 2000 to March 2013 were retrospectively reviewed. Variables potentially affecting the occurrence of POMC were evaluated using binary logistic regression analysis. The difference in survival was determined by the log-rank test. RESULT: Fifty-one patients experienced POMC. Univariate analysis revealed that events significantly associated with increased risk of POMC include symptom duration before operation>2.75months, preoperative bulbar symptoms, incomplete resection, operation time ≥ 122.5 minutes, and advanced stages (stage III or IV). Multivariate logistic regression analysis showed that preoperative bulbar symptoms (OR = 3.207 [1.413-7.278]; P = 0.005), and incomplete resection (OR = 4.182 [1.332-13.135]; P = 0.014) were independent risk factors for POMC. Twenty-eight patients (16.9%) died during the follow-up. The log-rank test revealed survival for patients with POMC was significantly worse than that for patients without POMC (P = 0.042). CONCLUSION: The important risk factors for developing POMC in thymomatous myasthenia gravis patients include the preoperative bulbar symptoms, and incomplete resection of thymoma. Moreover, the patients with POMC had a… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging.
    Related ArticlesHeterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging. Mult Scler. 2017 Aug 01;:1352458517726382 Authors: Louapre C, Govindarajan ST, Giannì C, Madigan N, Sloane JA, Treaba CA, Herranz E, Kinkel RP, Mainero C Abstract BACKGROUND: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. OBJECTIVE: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). METHODS: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. RESULTS: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10(-2)); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10(-2)), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. CONCLUSION: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis.
    Related ArticlesIFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis. J Immunol. 2016 Oct 15;197(8):2992-3007 Authors: Wang D, Ghosh D, Islam SM, Moorman CD, Thomason AE, Wilkinson DS, Mannie MD Abstract This study introduces a flexible format for tolerogenic vaccination that incorporates IFN-β and neuroantigen (NAg) in the Alum adjuvant. Tolerogenic vaccination required all three components, IFN-β, NAg, and Alum, for inhibition of experimental autoimmune encephalomyelitis (EAE) and induction of tolerance. Vaccination with IFN-β + NAg in Alum ameliorated NAg-specific sensitization and inhibited EAE in C57BL/6 mice in pretreatment and therapeutic regimens. Tolerance induction was specific for the tolerogenic vaccine Ag PLP178-191 or myelin oligodendrocyte glycoprotein (MOG)35-55 in proteolipid protein- and MOG-induced models of EAE, respectively, and was abrogated by pretreatment with a depleting anti-CD25 mAb. IFN-β/Alum-based vaccination exhibited hallmarks of infectious tolerance, because IFN-β + OVA in Alum-specific vaccination inhibited EAE elicited by OVA + MOG in CFA but not EAE elicited by MOG in CFA. IFN-β + NAg in Alum vaccination elicited elevated numbers and percentages of FOXP3(+) T cells in blood and secondary lymphoid organs in 2D2 MOG-specific transgenic mice, and repeated boosters facilitated generation of activated CD44(high) CD25(+) regulatory T cell (Treg) populations. IFN-β and MOG35-55 elicited suppressive FOXP3(+) Tregs in vitro in the absence of Alum via a mechanism that was neutralized by anti-TGF-β and that resulted in the induction of an effector CD69(+) CTLA-4(+) IFNAR(+) FOXP3(+) Treg subset. In vitro IFN-β + MOG-induced Tregs inhibited EAE when… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Clinical Implications of Immunoglobulin G4 to Graves’ Ophthalmopathy.
    Clinical Implications of Immunoglobulin G4 to Graves' Ophthalmopathy. Thyroid. 2017 Aug 12;: Authors: Yu SH, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ, Lee SJ Abstract BACKGROUND: This study aimed to explore relation of immunoglobulin G4 (IgG4) to clinical and laboratory characteristics of patients newly diagnosed with Graves' disease (GD) without or with Graves' ophthalmopathy (GO), and to analyze association of IgG4 with development and grade of GO in GD patients. METHODS: Sixty-four GD patients and 64 sex- and age-matched euthyroid subjects were enrolled. Serum levels of thyroid hormones, thyroid autoantibodies, immunoglobulin G (IgG) and IgG4 were measured, and ophthalmological and ultrasonographical evaluation was performed. RESULTS: In GD patients compared with euthyroid subjects, levels of thyroid hormones, thyroid autoantibodies and IgG4 as well as IgG4/IgG ratio were elevated. GD patients having GO in comparison to not having GO were characterized by a female predominance, a high incidence of smoking history, high levels of T3, free T4, TSH receptor autoantibody (TRAb) and IgG4, and a high IgG4/IgG ratio after adjusting for sex. In GD patients, the IgG4 level was the independent factor associated with GO development on multivariate analysis. When severity and activity of GO were classified using the EUGOGO criteria in GD patients with GO, IgG4 levels and IgG4/IgG ratio were elevated in the moderate-to-severe group compared with the mild group and in the active group compared with the inactive group. IgG4 levels and IgG4/IgG ratio became elevated as clinical activity score increased. IgG4 levels were positively correlated… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • IgG4-Related Disease: A New Etiology Underlying Diffuse Intracranial Dilating Vasculopathy.
    Related ArticlesIgG4-Related Disease: A New Etiology Underlying Diffuse Intracranial Dilating Vasculopathy. World Neurosurg. 2017 Aug 09;: Authors: Marlin ES, Dornbos D, Ikeda DS, Lehman NL, Powers CJ Abstract BACKGROUND: Diffuse intracranial aneurysmal vasculopathy is a rare condition, previously described in patients with human immunodeficiency virus (HIV) infection. IgG4 related disease (IgG4-RD) is a recognized inflammatory disease of systemic organs, leading to fibrosis of connective tissues. It has also been linked to inflammatory dilating aortic aneurysms, coronary vascular disease, hypophysitis, orbital pseudotumor and pachymeningitis. It has not yet been described as a cause of diffuse intracranial dilating vasculopathy. Histologically, this disease is characterized by IgG4-plasma cell infiltration, fibrosis and phlebitis. CASE DESCRIPTION: This 40 year-old female presented with acute heart failure, valvular insufficiency, and mycotic coronary aneurysms, concerning for endocarditis. Infectious workup was negative. Concurrent neurovascular workup revealed intracranial aneurysms, appearing mycotic in origin. Despite aggressive treatment over five years, she suffered multiple episodes of subarachnoid hemorrhage from a progressive dilating intracranial vasculopathy. Serum IgG levels and aneurysm wall pathology were consistent with IgG4-RD. CONCLUSIONS: This is the first reported case of a diffuse intracranial dilating vasculopathy secondary to IgG4-RD. Recognition of similar pathologic findings in clinical presentation and radiologic workup should prompt further rheumatologic workup and possible immunosuppressive therapies.PMID: 28803167 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Radiosynthesis and preclinical PET evaluation of (89)Zr-nivolumab (BMS-936558) in healthy non-human primates.
    Related ArticlesRadiosynthesis and preclinical PET evaluation of (89)Zr-nivolumab (BMS-936558) in healthy non-human primates. Bioorg Med Chem. 2017 Aug 04;: Authors: Cole EL, Kim J, Donnelly DJ, Smith RA, Cohen D, Lafont V, Morin PE, Huang RY, Chow PL, Hayes W, Bonacorsi S Abstract Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types. This study reports the preparation and in vivo evaluation of (89)Zr labeled nivolumab in healthy non-human primates (NHP) as a preliminary study of biodistribution and clearance. The radiochemical and in vivo stabilities of the (89)Zr complex were shown to be acceptable for imaging. Three naïve NHPs were intravenously injected with tracer only or tracer co-injected with nivolumab followed by co-registered by positron emission tomography (PET) and magnetic resonance imaging (MRI), acquired for eight days following injection. Image-derived standardized uptake values (SUV) were quantified by region of interest (ROI) analysis. Radioactivity in the spleen was significantly reduced by addition of excess nivolumab compared to the tracer only study at all imaging time points. Liver uptake of the radiotracer was consistent as a clearance organ with minimal signal… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Noninfectious aortitis: what the cardiologist needs to know.
    Noninfectious aortitis: what the cardiologist needs to know. Curr Opin Cardiol. 2017 Aug 12;: Authors: Töpel I Abstract PURPOSE OF REVIEW: To sum up a group of noninfectious inflammatory diseases of the aorta and its branches relevant to a cardiologist's daily routine. To describe pathogenetic and clinical advances as well as modern diagnostic tools. To overview most recent treatment options and patient-tailored therapies. To provide an insight in future directions of research. RECENT FINDINGS: Pathophysiology of large vessel vasculitides (LVV) are still poorly defined. At least a certain number of patients with idiopathic periaortitis seem to part of the group of IgG4-related diseases which has implications for therapy. Modern diagnostic modalities as Positron-Emission-Tomography (PET)-computed tomography and PET-magnetic resonance tomography proof to be helpful to diagnose or excluded LVV and emerge as long-term surveillance tool. Biological therapy yields varying results but is reported to be important for patients nonresponding or relapsing under glucocorticoid therapy. SUMMARY: Owing to the multifactorial pathogenesis and the small number of cases of LVV further interdisciplinary efforts are necessary to elucidate the pathogenesis of this group of diseases. Technical progress in radiology and nuclear medicine supports clinical, histological, and laboratory findings to increase diagnostic precision. There are several therapies emerging that may have the potential to support patient-tailored treatment approaches in glucocorticoid refractory or relapsing disease.PMID: 28806184 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Unexpected Fibrosing Mediastinitis Shown on FDG PET/CT in a Patient With IgG4-Related Disease.
    Unexpected Fibrosing Mediastinitis Shown on FDG PET/CT in a Patient With IgG4-Related Disease. Clin Nucl Med. 2017 Aug 12;: Authors: Kan Y, Yuan L, Wang W, Yang J Abstract A 66-year-old man presented to our hospital because of abdominal pain for 5 days. A contrast abdominal CT raised the possibility of pancreatic carcinoma. FDG PET/CT showed increased FDG accumulation not only in the pancreas and the retroperitoneum, but also in the posterior mediastinum, which was not typical of pancreatic carcinoma. The patient was subsequently diagnosed having immunoglobulin G4-related disease following the histopathologic examination.PMID: 28806261 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-15
  • Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review.
    Related ArticlesRituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review. Neurology. 2017 Aug 11;: Authors: Hehir MK, Hobson-Webb LD, Benatar M, Barnett C, Silvestri NJ, Howard JF, Howard D, Visser A, Crum BA, Nowak R, Beekman R, Kumar A, Ruzhansky K, Chen IA, Pulley MT, LaBoy SM, Fellman MA, Greene SM, Pasnoor M, Burns TM Abstract OBJECTIVE: To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). METHODS: This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. RESULTS: Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-13
  • Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis.
    Related ArticlesDelayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis. Sci Rep. 2017 Aug 11;7(1):7998 Authors: Chaudhury S, Regules JA, Darko CA, Dutta S, Wallqvist A, Waters NC, Jongert E, Lemiale F, Bergmann-Leitner ES Abstract A recent study of the RTS,S malaria vaccine, which is based on the circumsporozoite protein (CSP), demonstrated an increase in efficacy from 50-60% to 80% when using a delayed fractional dose regimen, in which the standard 0-1-2 month immunization schedule was modified to a 0-1-7 month schedule and the third immunization was delivered at 20% of the full dose. Given the role that antibodies can play in RTS,S-induced protection, we sought to determine how the modified regimen alters IgG subclasses and serum opsonophagocytic activity (OPA). Previously, we showed that lower CSP-mediated OPA was associated with protection in an RTS,S study. Here we report that the delayed fractional dose regimen resulted in decreased CSP-mediated OPA and an enhanced CSP-specific IgG4 response. Linear regression modeling predicted that CSP-specific IgG1 promote OPA, and that CSP-specific IgG4 interferes with OPA, which we subsequently confirmed by IgG subclass depletion. Although the role of IgG4 antibodies and OPA in protection is still unclear, our findings, combined with previous results that the delayed fractional dose increases CSP-specific antibody avidity and somatic hypermutation frequency in CSP-specific B cells, demonstrate how changes in vaccine regimen alone can significantly alter the quality of antibody responses to improve vaccine efficacy.PMID: 28801554 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-13
  • Immune responses against Helicobacter pylori-specific antigens differentiate relapsing remitting from secondary progressive multiple sclerosis.
    Related ArticlesImmune responses against Helicobacter pylori-specific antigens differentiate relapsing remitting from secondary progressive multiple sclerosis. Sci Rep. 2017 Aug 11;7(1):7929 Authors: Efthymiou G, Dardiotis E, Liaskos C, Marou E, Tsimourtou V, Rigopoulou EI, Scheper T, Daponte A, Meyer W, Sakkas LI, Hadjigeorgiou G, Bogdanos DP Abstract To assess whether Helicobacter pylori (Hp) antibody (ab) reactivity against individual Hp antigens is pathogenetically relevant to multiple sclerosis (MS), we systematically investigated prevalence and clinical significance of abs against 14 immunodominant and subdominant Hp antigens by ELISA and immunoblotting in 139 consecutive MS patients with relapsing-remitting (RRMS, n = 102) or secondary progressive (SPMS, n = 37). Sera from 39 patients with Parkinson's disease (PD), 21 with Alzheimer's disease (ALZ) and 68 healthy controls (HCs), were also tested. Anti-flagellin (18.3%) and anti-p41 (25.0%) abs in MS were less frequent than in HCs (39.4%, 48.5%, respectively). Abs against 5 of the 14 antigens were less frequent in RRMS than HCs, including p41, p54-flagellin, p29-UreA, p67-FSH, and p120-CagA. Anti-VacA abs were more frequent in SPMS than in HCs (42.1 vs 12.1%, p = 0.019). Anti-p54, anti-p29-UreA and anti-p26 correlated with extended disability status scale (EDSS) (p = 0.017, p = 0.005, p = 0.002, respectively). Anti-p26 and anti-p17 correlated with the number of relapses (p = 0.037 and p = 0.047, respectively). This is the first comprehensive analysis of ab reactivities against most Hp antigens in MS patients. Ab responses differ between MS and HCs and between RRMS and SPMS, being more prevalent in SPMS than RRMS, thus suggesting an association between anti-Hp and the former type of MS.PMID: 28801580 [PubMed… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-13
  • The tension between early diagnosis and misdiagnosis of multiple sclerosis.
    Related ArticlesThe tension between early diagnosis and misdiagnosis of multiple sclerosis. Nat Rev Neurol. 2017 Aug 11;: Authors: Solomon AJ, Corboy JR PMID: 28799551 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.
    Related ArticlesThe MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability. Mult Scler. 2017 Aug 01;:1352458517723718 Authors: LaRocca NG, Hudson LD, Rudick R, Amtmann D, Balcer L, Benedict R, Bermel R, Chang I, Chiaravalloti ND, Chin P, Cohen JA, Cutter GR, Davis MD, DeLuca J, Feys P, Francis G, Goldman MD, Hartley E, Kapoor R, Lublin F, Lundstrom G, Matthews PM, Mayo N, Meibach R, Miller DM, Motl RW, Mowry EM, Naismith R, Neville J, Panagoulias J, Panzara M, Phillips G, Robbins A, Sidovar MF, Smith KE, Sperling B, Uitdehaag BM, Weaver J, Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Abstract BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. CONCLUSION: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • Programmed Death Ligand 1 Plays a Neuroprotective Role in Experimental Autoimmune Neuritis by Controlling Peripheral Nervous System Inflammation of Rats.
    Related ArticlesProgrammed Death Ligand 1 Plays a Neuroprotective Role in Experimental Autoimmune Neuritis by Controlling Peripheral Nervous System Inflammation of Rats. J Immunol. 2016 Nov 15;197(10):3831-3840 Authors: Ding Y, Han R, Jiang W, Xiao J, Liu H, Chen X, Li X, Hao J Abstract Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages. In this study, we investigated the effects of PD-L1 in EAN rats. For preventative and therapeutic management, we administered PD-L1, which successfully decreased the severity of EAN; it alleviated the neurologic course of EAN, as well as inhibited the infiltration of inflammatory cells and demyelination of sciatic nerves. Our data revealed that PD-L1 treatment inhibited lymphocyte proliferation and altered T cell differentiation by inducing decreases in IFN-γ(+)CD4(+) Th1 cells and IL-17(+)CD4(+) Th17 cells and increases in IL-4(+)CD4(+) Th2 cells and Foxp3(+)CD4(+) regulatory T cells. The expression levels of p-STAT3 and Foxp3 were significantly different in PD-L1-treated groups compared with the control group. Additionally, PD-L1 regulated the expression of Foxp3 and p-STAT3… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • [Contribution of serial neurophysiological studies in atypical Guillain-Barré syndrome].
    Related Articles[Contribution of serial neurophysiological studies in atypical Guillain-Barré syndrome]. An Pediatr (Barc). 2015 Oct;83(4):282-4 Authors: Álvarez Guerrico I, Mínguez P, Aznar Laín G, Rubio MA, Royo I PMID: 26006276 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • Monoclonal Antibodies: A Review.
    Monoclonal Antibodies: A Review. Curr Clin Pharmacol. 2017 Aug 09;: Authors: Singh S, Kumar N, Dwiwedi P, Charan J, Kaur R, Sidhu P, Chugh VK Abstract Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb, was first FDA approved therapeutic MAb for prevention of kidney transplant rejection. Since its approval in 1986, there has been decline in the further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of low grade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically. As of March 2017, FDA has approved approximately 60 therapeutic MAbs with much more currently under evaluation in various phases of clinical trials. MAbs are approved for the treatment of a diseases belonging to various system like cardiovascular, respiratory, hematology, kidney, immunology and oncology. Mab are approved for the treatment of orphan diseases or indications such as paroxysmal nocturnal hemoglobinuria as well as cancers and multiple sclerosis where hundreds of patients are treated and even diseases such as breast cancer, asthma and rheumatoid arthritis where millions are being treated. This review focuses briefly on types, molecular targets, mechanism of actions and therapeutic indications of FDA approved MAb products that are currently on the… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • Large Tumefactive IgG4-related Disease: Histologic, Cytologic, and Immunohistochemical Features of a Very Unusual Case.
    Large Tumefactive IgG4-related Disease: Histologic, Cytologic, and Immunohistochemical Features of a Very Unusual Case. Appl Immunohistochem Mol Morphol. 2017 Aug 09;: Authors: Akhtar I, Shenoy V, Khan M, Saad AG Abstract Immunoglobulin G4-related disease (IgG4-RD) is a regional or systemic multiorgan lymphoplasmacytic inflammatory disease of unknown etiology. It has been described in numerous organs and anatomic locations. Review of the literature shows that when the disease involves the retroperitoneum it causes retroperitoneal fibrosis. Tumefactive IgG4-RD of the retroperitoneum has not been previously reported. In this report, we describe the first case of a large retroperitoneal tumefactive IgG4-RD along with its histologic, cytologic, and immunohistochemical characteristics.PMID: 28800014 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • Intrachiasmatic abscess caused by IgG4-related hypophysitis.
    Related ArticlesIntrachiasmatic abscess caused by IgG4-related hypophysitis. Acta Neurochir (Wien). 2017 Aug 10;: Authors: Hadjigeorgiou GF, Lund EL, Poulsgaard L, Feldt-Rasmussen U, Rasmussen ÅK, Wegener M, Fugleholm K Abstract INTRODUCTION: Autoimmune hypophysitis is a rare disease of the pituitary, which may affect vision by inflammation and compression of the optic chiasm. However, intrachiasmatic abscess formation has not been previously reported. METHODS: In this study, we report a case of a 29-year-old female with bitemporal hemianopia due to a cystic intrasellar tumor. The patient underwent surgical decompression of the lesion, which was found to be an intrachiasmatic abscess. RESULTS: The histologic findings were consistent with IgG4 hypophysitis. CONCLUSION: This rare clinical presentation suggests that in case of a disproportionate degree of visual impairment in relation to the size of the lesion, suspicion should lead to an intrachiasmatic lesion.PMID: 28799078 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-12
  • Limit of Detection and Threshold for Positivity of the Centers for Disease Control and Prevention Assay for Factor VIII Inhibitors.
    Related ArticlesLimit of Detection and Threshold for Positivity of the Centers for Disease Control and Prevention Assay for Factor VIII Inhibitors. J Thromb Haemost. 2017 Aug 10;: Authors: Miller CH, Boylan B, Shapiro AD, Lentz SR, Wicklund BM, Hemophilia Inhibitor Research Study Investigators Abstract BACKGROUND: The Bethesda assay (BA) for measurement of factor VIII (FVIII) inhibitors called for quantitation of positive inhibitors using dilutions producing 25-75% residual activity (RA), corresponding to 0.4-2.0 Bethesda units, recommending use of "more sensitive methods" for samples with RA closer to 100%. The Nijmegen modification (NBA) changed the reagents used but not these calculations. Some specimens negative by NBA have been shown to have FVIII antibodies detectable by sensitive immunologic methods. OBJECTIVE: To examine the performance at very low inhibitor titers of the Centers for Disease Control and Prevention (CDC)-modified NBA (CDC-NBA), which includes preanalytical heat inactivation to liberate bound anti-FVIII antibodies. METHODS: Specimens with known inhibitors were tested by CDC-NBA. IgG4 anti-FVIII antibodies were measured by fluorescence immunoassay (FLI). RESULTS: Diluted inhibitors showed linearity below 0.4 Nijmegen-Bethesda units (NBU). Using 4 statistical methods, the limit of detection of the CDC-NBA was determined to be 0.2 NBU. IgG4 anti-FVIII antibodies, which correlate most strongly with functional inhibitors, were present at rates above the background rate of healthy controls in specimens with titers ≥0.2 NBU and showed an increase in frequency from 14.3% at 0.4 NBU to 67% at the established threshold for positivity of 0.5 NBU. CONCLUSIONS: The CDC-NBA can detect inhibitors down to 0.2… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-08-11