LECTURAS CIENTÍFICAS

  • Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability.
    Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability. Neuron. 2018 Feb 01;: Authors: Dawes JM, Weir GA, Middleton SJ, Patel R, Chisholm KI, Pettingill P, Peck LJ, Sheridan J, Shakir A, Jacobson L, Gutierrez-Mecinas M, Galino J, Walcher J, Kühnemund J, Kuehn H, Sanna MD, Lang B, Clark AJ, Themistocleous AC, Iwagaki N, West SJ, Werynska K, Carroll L, Trendafilova T, Menassa DA, Giannoccaro MP, Coutinho E, Cervellini I, Tewari D, Buckley C, Leite MI, Wildner H, Zeilhofer HU, Peles E, Todd AJ, McMahon SB, Dickenson AH, Lewin GR, Vincent A, Bennett DL Abstract Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/-) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2-/- mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Seroepidemiological Study of Epstein-Barr Virus in Different Population Groups in Croatia.
    Seroepidemiological Study of Epstein-Barr Virus in Different Population Groups in Croatia. Isr Med Assoc J. 2018 Feb;20(2):86-90 Authors: Beader N, Kolarić B, Slačanac D, Tabain I, Vilibić-Čavlek T Abstract BACKGROUND: The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population. OBJECTIVES: To analyze the seroprevalence of EBV infection in different population groups in Croatia. METHODS: During a 2 year period (2015-2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity. RESULTS: The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age < 9 years to 98.3% in 30-39 year olds, and remained stable thereafter (P < 0.001). The IgG seroprevalence differed significantly among groups: 68.1% in children/adolescents and 95.9% in adults; multiple sclerosis (100%), hemodialysis patients (97.7%), heart transplant recipients (93.8%), hematological malignancies (91.2%), and Crohn's disease (88.5%), P < 0.001. IgM antibodies were detected in 9% of participants. Using IgG avidity, recent primary EBV infection was documented in 83.8% of IgM-positive subjects < 9 years old, 69.2% age 10-19, 33.3% age 20-29, and 3.6-4.2% > 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Expression and replication of virus-like circular DNA in human cells.
    Expression and replication of virus-like circular DNA in human cells. Sci Rep. 2018 Feb 12;8(1):2851 Authors: Eilebrecht S, Hotz-Wagenblatt A, Sarachaga V, Burk A, Falida K, Chakraborty D, Nikitina E, Tessmer C, Whitley C, Sauerland C, Gunst K, Grewe I, Bund T Abstract The consumption of bovine milk and meat is considered a risk factor for colon- and breast cancer formation, and milk consumption has also been implicated in an increased risk for developing Multiple Sclerosis (MS). A number of highly related virus-like DNAs have been recently isolated from bovine milk and sera and from a brain sample of a MS patient. As a genetic activity of these Acinetobacter-related bovine milk and meat factors (BMMFs) is unknown in eukaryotes, we analyzed their expression and replication potential in human HEK293TT cells. While all analyzed BMMFs show transcriptional activity, the MS brain isolate MSBI1.176, sharing homology with a transmissible spongiform encephalopathy-associated DNA molecule, is transcribed at highest levels. We show expression of a replication-associated protein (Rep), which is highly conserved among all BMMFs, and serological tests indicate a human anti-Rep immune response. While the cow milk isolate CMI1.252 is replication-competent in HEK293TT cells, replication of MSBI1.176 is complemented by CMI1.252, pointing at an interplay during the establishment of persistence in human cells. Transcriptome profiling upon BMMF expression identified host cellular gene expression changes related to cell cycle progression and cell viability control, indicating potential pathways for a pathogenic involvement of BMMFs.PMID: 29434270 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • MOG Antibodies in Pediatric Neurology.
    Related ArticlesMOG Antibodies in Pediatric Neurology. Neuropediatrics. 2018 02;49(1):1-2 Authors: Huppke P PMID: 28915516 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • A Rare Presentation of Neuromyelitis Optica Spectrum Disorders.
    A Rare Presentation of Neuromyelitis Optica Spectrum Disorders. Clin Med Insights Case Rep. 2018;11:1179547617752685 Authors: Singh NK, Sweidan AJ, Strube S, Carrillo-Nunez I Abstract Neuromyelitis optica spectrum disorders (NMOSDs) are a set of demyelinating disorders that primarily target the optic nerves and the spinal cord. Previously thought to be a subset of multiple sclerosis (MS), now is recognized as a distinct entity. We present a 59-year-old female patient who was admitted for acute upper and lower extremity weakness. The patient had woken up from sleep with sudden onset of weakness. Patient was initially diagnosed with a right hemispheric stroke; however, magnetic resonance imaging of the cervical spine later performed showed abnormal enhancement from C2-C4, representing transverse myelitis. Cerebrospinal fluid was negative for organisms and inflammatory biomarkers. An anti-aquaporin-4 receptor antibody titer was found to be elevated with titers >80 units/mL. The patient was treated with high-dose steroids and plasmapheresis. The NMOSD is a rare entity and, here, we present a rare presentation of the disease. Since its description in 1870, it was confused with MS for years. The advent of anti-aquaporin-4 antibody has been instrumental in differentiating the disease process from MS. This distinction is important, in terms of agents used for treatment and prognostication. The NMOSD is a set of debilitating disease, which requires prompt recognition and appropriate treatment, to avoid the disabling sequelae. Future prospects of the disease include development of novel biological treatment modalities which focus on restoring the loss of immune tolerance which is key to the… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up.
    Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up. Neurotherapeutics. 2018 Feb 12;: Authors: Härtig F, Ross M, Dammeier NM, Fedtke N, Heiling B, Axer H, Décard BF, Auffenberg E, Koch M, Rattay TW, Krumbholz M, Bornemann A, Lerche H, Winter N, Grimm A Abstract As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r2 = 0.397 and r2 = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r2 = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scores INCAT r2 = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r2 = 0.272-0.414, p < 0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in > 50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Miller Fisher syndrome with acute angle-closure glaucoma as the first manifestation: A case report.
    Related ArticlesMiller Fisher syndrome with acute angle-closure glaucoma as the first manifestation: A case report. Medicine (Baltimore). 2017 Dec;96(50):e9201 Authors: Han J, Ji Y, Cao D, Kang Z, Zhu J Abstract RATIONALE: There were no reports of Miller Fisher syndrome (MFS) with acute angle-closure glaucoma as the first manifestation. PATIENT CONCERNS: A 78-year-old female patient was admitted to our hospital with pain in her left eye, blurred vision along with nausea, and vomiting for 2 days. It was extremely rare that ophthalmoplegia, loss of tendon reflexes, and ataxia, did not occur in the early stages of MFS, and initial presentation was only dilated pupis and an increase in intraocular pressure. DIAGNOSES: The final diagnosis of the patient was MFS. INTERVENTIONS: Intravenous immunoglobulins were administered. OUTCOMES: Ophthalmoplegia, walking instability, and ataxia gradually improved. At 3 months follow-up, there was no neurological deficit, and the patient could completely self-care. LESSONS: This is the first report of MFS patient with acute angle closure glaucoma as the first manifestation. Consideration should be given to the possibility of incorporating autonomic nervous system dysfunction, or even MFS, in patients with acute angle-closure glaucoma in order to reduce missed diagnosis rate.PMID: 29390338 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Outcome of Guillain-Barre syndrome patients with respiratory paralysis.
    Related ArticlesOutcome of Guillain-Barre syndrome patients with respiratory paralysis. QJM. 2016 May;109(5):319-23 Authors: Kalita J, Ranjan A, Misra UK Abstract BACKGROUND AND AIMS: To evaluate the outcome of patients with Guillain -: Barre syndrome (GBS) having respiratory failure treated with modified intubation policy. DESIGN AND METHODS: Consecutive patients with GBS having single breath count below 12 and respiratory rate >30/min were included and their clinical details noted. The patients were intubated and mechanically ventilated (MV) if their PaO2 was <60 mmHg on venturi mask, PaCo2 > 50 mmHg or pH < 7.3. Their electrophysiological subtypes and complications were noted. The hospital mortality and 3 months outcome were compared in MV and those could be managed without MV even with respiratory compromise. RESULTS: Out of 369 patients, 102 (27.6%) patients had respiratory compromise who were included in this study. Of the patients with respiratory compromise, 44 (43.1%) were intubated and mechanically ventilated after a median of 4 days of hospitalization. The median duration of MV was 21 (range 1-88) days. The patients with autonomic dysfunction (56.8% vs. 19%), facial weakness (78% vs. 36.2%), bulbar weakness (81.8% vs. 31%), severe weakness (63.8% vs. 31%) and high transaminase level (47.7% vs. 25.9%) needed MV more frequently. In our study, 6.8% patients died and 26.6% had poor outcome which was similar between MV and non-MV patients. The MV patients had longer hospitalization and more complications compared with non-MV group. CONCLUSION: In GBS patients with respiratory compromise, conservative intubation does not increase mortality and disability.PMID: 26475599 [PubMed - indexed… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • [IgG4-related sclerosing disease with initial ear symptom: a case report].
    [IgG4-related sclerosing disease with initial ear symptom: a case report]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Feb 07;53(2):140-143 Authors: Hu M, Wang W, Cheng Y PMID: 29429186 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Clinical and pathological characteristics of IgG4-related interstitial lung disease.
    Clinical and pathological characteristics of IgG4-related interstitial lung disease. Exp Ther Med. 2018 Feb;15(2):1465-1473 Authors: Lv X, Gao F, Liu Q, Zhang S, Huang Z, Zhu Y, Zong H, Li Q, Li S Abstract IgG4-related interstitial lung disease (IgG4-RILD), which is characterized by increased IgG4 levels, IgG4+ plasma cell infiltration and irregular whorled fibrosis, is a recently described lung disorder that belongs to the group of systemic fibroinflammatory IgG4-related diseases (IgG4-RD). The aim of the present study was to improve the current knowledge regarding the specific clinical and histopathological characteristics of IgG4-RILD and to investigate its underlying immune mechanism in vivo. A total of 7 patients newly diagnosed with IgG4-RILD were enrolled in the present study (4 men and 3 women; mean age, 57 years; range, 29-71 years). Patients' clinical history was collected and serological indicators, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANAs) and tumor markers were measured. Serum immunoglobulin G (IgG), IgE and IgG4 levels were also evaluated. In addition, computed tomographic (CT) images and pathological examinations were used to determine the characteristics of lung lesions in all patients. The majority of patients presented with symptoms of fever, cough and dyspnea, while allergic symptoms were also encountered. The laboratory examination results revealed different degrees of increased CRP, ESR, tumor markers, ANA, serum IgE and IgG4. The CT images revealed diffuse ground glass opacities, bronchiectasis and thickened bronchovascular bundles. Histologically, the lung lesions were characterized by dense IgG4+ lymphoplasmacytic infiltrates intermixed with extensive fibrous tissue hyperplasia… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Clinical analysis of liver transplantation in autoimmune liver diseases.
    Clinical analysis of liver transplantation in autoimmune liver diseases. Hepatobiliary Pancreat Dis Int. 2018 Feb;17(1):27-31 Authors: Zhong CP, Xi ZF, Xia Q Abstract BACKGROUND: Autoimmune liver diseases (ALDs) consist of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), IgG4-associated cholangitis and overlap syndromes. Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation. METHODS: The clinical data of 80 patients with ALD (24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIH-PBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan-Meier method. Recurrence and other complications were also analyzed. RESULTS: Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease (MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3- and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed (3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients (12.5%). The new onset of tumor was observed in 1 patient (1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively. CONCLUSION:… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region.
    Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region. Proc Natl Acad Sci U S A. 2018 Feb 05;: Authors: van de Bovenkamp FS, Derksen NIL, Ooijevaar-de Heer P, van Schie KA, Kruithof S, Berkowska MA, van der Schoot CE, IJspeert H, van der Burg M, Gils A, Hafkenscheid L, Toes REM, Rombouts Y, Plomp R, Wuhrer M, van Ham SM, Vidarsson G, Rispens T Abstract A hallmark of B-cell immunity is the generation of a diverse repertoire of antibodies from a limited set of germline V(D)J genes. This repertoire is usually defined in terms of amino acid composition. However, variable domains may also acquire N-linked glycans, a process conditional on the introduction of consensus amino acid motifs (N-glycosylation sites) during somatic hypermutation. High levels of variable domain glycans have been associated with autoantibodies in rheumatoid arthritis, as well as certain follicular lymphomas. However, the role of these glycans in the humoral immune response remains poorly understood. Interestingly, studies have reported both positive and negative effects on antibody affinity. Our aim was to elucidate the role of variable domain glycans during antigen-specific antibody responses. By analyzing B-cell repertoires by next-generation sequencing, we demonstrate that N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we subsequently show that this process is subject to selection during antigen-specific antibody… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease.
    Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease. Mod Pathol. 2018 Feb 12;: Authors: Iguchi T, Takaori K, Mii A, Sato Y, Suzuki Y, Yoshifuji H, Seno H, Ogawa O, Omori K, Bessho K, Kondo S, Yoshizaki T, Nakashima H, Saito T, Mimori T, Haga H, Kawano M, Yanagita M Abstract Immunoglobulin G4-related disease is a rare immune-mediated disease characterized by the infiltration of IgG4-positive plasma cells and unique storiform fibrosis of multiple organs. The majority of IgG4-related disease patients respond to glucocorticoids, yet the precise mechanism of their action remains unclear. Pathological sections of the submaxillary gland, kidney, and retroperitoneum from 20 patients in total diagnosed with IgG4-related disease were analyzed for glucocorticoid receptor expression and the cell types expressing glucocorticoid receptor. Strong and abundant expression of glucocorticoid receptor was observed in the submaxillary gland, kidney, and retroperitoneum of IgG4-related disease patients, while glucocorticoid receptor was rarely or only faintly observed in the submaxillary gland of patients with Sjögren's syndrome, radicular cysts and sialolithiasis or in the healthy kidney. Glucocorticoid receptor was mainly expressed in fibro/myofibroblasts, CD4-positive T cells and IgG4-positive plasma cells in the submandibular glands and kidneys of IgG4-related disease patients. The abundant expression of glucocorticoid receptor in various types of cells, including resident fibro/myofibroblasts in IgG4-related disease patients might provide clues to the mechanism of steroid responsiveness in IgG4-related disease patients.PMID: 29434340 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • 18F-FDG PET/CT Findings in a Patient With IgG4-Related Sclerosing Mesenteritis.
    18F-FDG PET/CT Findings in a Patient With IgG4-Related Sclerosing Mesenteritis. Clin Nucl Med. 2018 Feb 09;: Authors: Fu Z, Chen G, Liu M, Li Z, Li Q Abstract A large mass in the abdomen was revealed by ultrasonography on a 68-year-old woman presenting with abdominal pain and weight loss. To exclude the malignancy, an F-FDG PET/CT was performed, which showed a solitary soft tissue mass with heterogeneous F-FDG avidity at the root of small bowel mesentery. Because of the elevation of inflammatory markers and serum IgG4 level, IgG4-related sclerosing mesenteritis was suspected, which was proved by the subsequent biopsy. The mass gradually shrunk and ultimately disappeared in 6 months after a low-dose steroid therapy.PMID: 29432345 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis.
    Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis. Tohoku J Exp Med. 2018;244(2):113-117 Authors: Hamada S, Masamune A, Nabeshima T, Shimosegawa T Abstract Host-derived factors alter gut microenvironment, and changes in gut microbiota also affect biological functions of host. Alterations of gut microbiota have been reported in a wide variety of diseases, but the whole picture of alterations in pancreatic diseases remains to be clarified. In particular, the gut microbiota may be affected by malnutrition or impaired exocrine pancreas function that is associated with pancreatic diseases. We here conducted comprehensive analysis of gut microbiota in patients with type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of the systemic IgG4-related disease, and chronic pancreatitis (CP). The two diseases were selected, because altered immune reactions in AIP and/or long-standing malnutrition in CP may influence the gut microbiota. Fecal samples were obtained from 12 patients with AIP before the steroid therapy and 8 patients with CP. Metagenome DNA was extracted, and microbiota was analyzed by next generation sequencing. Gut microbiota profiles were different between patients with AIP and those with CP; namely, the proportions of Bacteroides, Streptococcus and Clostridium species were higher in patients with CP. The reasons for the increased proportion of these bacterial species remain unknown, but may reflect malabsorption and/or decreased pancreatic enzymes, both of which are associated with CP. Incidentally, the identified Streptococcus species are oral cavity inhabitants and also known as pathogens for endocarditis. Despite the small sample size, this study has shown the differences… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era.
    Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era. Neurology. 2018 Feb 02;: Authors: Alroughani R, Alowayesh MS, Ahmed SF, Behbehani R, Al-Hashel J Abstract OBJECTIVE: To determine the rate of relapse occurrence during pregnancy and postpartum. METHODS: In a cross-sectional study using the national multiple sclerosis (MS) registry, pregnant women with relapsing MS were identified. Data on demographics, clinical characteristics, and disease-modifying therapies (DMTs), including washout periods, were collected. Timings and durations of relapses were extracted. A multivariate logistic regression was used to assess the relationship between relapses and prior use of different DMTs. RESULTS: Completed data were available for 99 pregnancies (87 patients). Mean age and mean age at onset were 31.8 ± 5 and 24.4 ± 5.6 years, respectively, while the mean disease duration was 7.4 ± 4.6 years. Most pregnancies (89.9%) occurred in patients who were on DMTs in the year preceding pregnancy with a mean treatment duration of 63.4 ± 29 months. The rates of occurrence of relapses during pregnancy and postpartum were 17.2% and 13.7%, respectively. Most of the relapses occurred during the first (n = 6) and third (n = 7) trimesters. Rate of relapse was highest among patients receiving natalizumab and fingolimod before pregnancy. A longer washout period was significantly associated with relapse occurrence. CONCLUSION: The relapse occurrence during pregnancy is higher than the previously published rates. The use of high-efficacy therapies with long washout periods before conception was associated with an increased risk of relapses during… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Prognosis of Ocular Myasthenia Gravis in an Argentinian Population.
    Prognosis of Ocular Myasthenia Gravis in an Argentinian Population. Eur Neurol. 2018 Feb 09;79(3-4):113-117 Authors: Aguirre F, Villa AM Abstract BACKGROUND: We investigated the prognosis of patients with myasthenia gravis (MG) initially presenting with only ocular symptoms in an Argentinian population. SUMMARY: We performed a retrospective analysis of 61 patients with MG with pure ocular involvement at onset. Generalized MG (gMG) developed in 73.7% of patients, while the rest only exhibited ocular symptoms throughout the course of the disease (ocular MG [oMG]). The AChR antibody (AChR-ab) was found in 81.4% of the gMG and 50% of the oMG cases. AChR-ab titers were also significantly higher in the gMG than in the oMG group. Patients with oMG more frequently required treatment only with acetylcholinesterase inhibitors and showed more remissions. Key Messages: Our study showed high generalization in patients with MG debuting with ocular symptoms. Patients with AChR seropositivity and higher AChR-ab titers had an increased risk for gMG, while patients with oMG showed lower corticosteroid requirements and a higher remission rate.PMID: 29428956 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Endocytosis as a stabilizing mechanism for tissue homeostasis.
    Endocytosis as a stabilizing mechanism for tissue homeostasis. Proc Natl Acad Sci U S A. 2018 Feb 02;: Authors: Adler M, Mayo A, Zhou X, Franklin RA, Jacox JB, Medzhitov R, Alon U Abstract Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in which cells stimulate each other and grow without control. Feedback can be obtained in at least two ways: endocytosis in which a cell removes its cognate GF by internalization and cross-inhibition in which a GF down-regulates the production of another GF. Here we ask whether there are design principles for cell circuits to achieve tissue homeostasis. We develop an analytically solvable framework for circuits with multiple cell types and find that feedback by endocytosis is far more robust to parameter variation and has faster responses than cross-inhibition. Endocytosis, which is found ubiquitously across tissues, can even provide homeostasis to three and four communicating cell types. These design principles form a conceptual basis for how tissues maintain a healthy balance of cell types and how balance may be disrupted in diseases such as degeneration and fibrosis.PMID: 29429964 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-13
  • Inclusion body myositis and human immunodeficiency virus type 1: A new case report and literature review.
    Inclusion body myositis and human immunodeficiency virus type 1: A new case report and literature review. Neuromuscul Disord. 2018 Jan 10;: Authors: Couture P, Malfatti E, Morau G, Mathian A, Cohen-Aubart F, Nielly H, Amoura Z, Cherin P Abstract Prevalence of muscle disease in human immunodeficiency virus (HIV) infection is less than 1% of patients with acquired immune deficiency syndrome. Sporadic inclusion body myositis (IBM) is observed in a few cases of patients infected by retroviruses such as HIV-1. A Caucasian man was diagnosed with HIV when he was 30 years old. The viral load was undetectable and CD4 cell count was 600/mm3 when the diagnosis of inclusion body myositis was confirmed. Histological findings were typical of IBM. The treatment consisted of immunoglobulin therapy for three years without effect. Twenty-two patients were found in the English and French literature. They are younger than those who suffer from IBM without HIV (median age = 47, range: 30 to 59), and they are mostly men with considerable serum creatine kinase (CK) elevation (median CK level = 1322 IU/L, range: 465 to 10270), most of them were treated with Zidovudine.PMID: 29426734 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-11
  • High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease.
    High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease. Immunity. 2018 Feb 06;: Authors: Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP, Lelios I, Heppner FL, Kipnis J, Merkler D, Greter M, Becher B Abstract Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS. Using this approach, we revealed that microglia, several subsets of border-associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease-specific transformations in the immune microenvironment during aging and in models of Alzheimer's disease and multiple sclerosis. Together, these data and the described framework provide a resource for the study of disease mechanisms, potential biomarkers, and therapeutic targets in CNS disease.PMID: 29426702 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-11
  • Comment on the article entitled “Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome” (Autoimmunity Reviews 16 (2017) 1036-1043).
    Comment on the article entitled "Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome" (Autoimmunity Reviews 16 (2017) 1036-1043). Autoimmun Rev. 2018 Feb 07;: Authors: Goulabchand R, Delicques J, Gallo M, Le Quellec A, Guilpain P PMID: 29427824 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-11
  • Turning the tables on cytomegalovirus: targeting viral Fc receptors by CARs containing mutated CH2-CH3 IgG spacer domains.
    Turning the tables on cytomegalovirus: targeting viral Fc receptors by CARs containing mutated CH2-CH3 IgG spacer domains. J Transl Med. 2018 Feb 08;16(1):26 Authors: Proff J, Brey CU, Ensser A, Holter W, Lehner M Abstract BACKGROUND: During infection with human cytomegalovirus (HCMV) several viral proteins occur on cell surfaces in high quantity. We thus pursue an HLA-independent approach for immunotherapy of HCMV using chimeric antigen receptors (CARs) and bispecific BiTE® antibody constructs. In this context, HCMV-encoded proteins that mediate viral immune evasion and bind human IgG might represent particularly attractive target antigens. Unlike in observations of similar approaches for HIV and hepatitis B and C viruses, however, HCMV-infected cells develop a striking resistance to cytotoxic effector functions at later stages of the replication cycle. In our study we therefore wanted to test two hypotheses: (1) CAR T cells can efficiently inhibit HCMV replication independently from cytotoxic effector functions, and (2) HCMV can be targeted by CH2-CH3 IgG spacer domains that contain mutations previously reported to prevent exhaustion and to rescue CAR T cell function in vivo. METHODS: Replication of GFP-encoding recombinant HCMV in fibroblasts in the presence and absence of supernatants from T cell co-cultures plus/minus cytokine neutralizing antibodies was analyzed by flow cytometry. CARs with wild type and mutated CH2-CH3 domains were expressed in human T cells by mRNA electroporation, and the function of the CARs was assessed by quantifying T cell cytokine secretion. RESULTS: We confirm and extend previous evidence of antiviral cytokine effects and demonstrate that CAR… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • An animal model of Miller Fisher syndrome: Mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann cells.
    Related ArticlesAn animal model of Miller Fisher syndrome: Mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann cells. Neurobiol Dis. 2016 Dec;96:95-104 Authors: Rodella U, Scorzeto M, Duregotti E, Negro S, Dickinson BC, Chang CJ, Yuki N, Rigoni M, Montecucco C Abstract The neuromuscular junction is a tripartite synapse composed of the presynaptic nerve terminal, the muscle and perisynaptic Schwann cells. Its functionality is essential for the execution of body movements and is compromised in a number of disorders, including Miller Fisher syndrome, a variant of Guillain-Barré syndrome: this autoimmune peripheral neuropathy is triggered by autoantibodies specific for the polysialogangliosides GQ1b and GT1a present in motor axon terminals, including those innervating ocular muscles, and in sensory neurons. Their binding to the presynaptic membrane activates the complement cascade, leading to a nerve degeneration that resembles that caused by some animal presynaptic neurotoxins. Here we have studied the intra- and inter-cellular signaling triggered by the binding and complement activation of a mouse monoclonal anti-GQ1b/GT1a antibody to primary cultures of spinal cord motor neurons and cerebellar granular neurons. We found that a membrane attack complex is rapidly assembled following antibody binding, leading to calcium accumulation, which affects mitochondrial functionality. Consequently, using fluorescent probes specific for mitochondrial hydrogen peroxide, we found that this reactive oxygen species is rapidly produced by mitochondria of damaged neurons, and that it triggers the activation of the MAP kinase pathway in Schwann cells. These results throw light on the molecular… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Guillain-Barré Syndrome and Healthcare Needs during Zika Virus Transmission, Puerto Rico, 2016.
    Related ArticlesGuillain-Barré Syndrome and Healthcare Needs during Zika Virus Transmission, Puerto Rico, 2016. Emerg Infect Dis. 2017 01;23(1):134-136 Authors: Dirlikov E, Kniss K, Major C, Thomas D, Virgen CA, Mayshack M, Asher J, Mier-Y-Teran-Romero L, Salinas JL, Pastula DM, Sharp TM, Sejvar J, Johansson MA, Rivera-Garcia B Abstract To assist with public health preparedness activities, we estimated the number of expected cases of Zika virus in Puerto Rico and associated healthcare needs. Estimated annual incidence is 3.2-5.1 times the baseline, and long-term care needs are predicted to be 3-5 times greater than in years with no Zika virus.PMID: 27779466 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy.
    Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy. J Neurol. 2018 Feb 08;: Authors: Dressler D, Bhidayasiri R, Bohlega S, Chana P, Chien HF, Chung TM, Colosimo C, Ebke M, Fedoroff K, Frank B, Kaji R, Kanovsky P, Koçer S, Micheli F, Orlova O, Paus S, Pirtosek Z, Relja M, Rosales RL, Sagástegui-Rodríguez JA, Schoenle PW, Shahidi GA, Timerbaeva S, Walter U, Saberi FA Abstract Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Thymus imaging in myasthenia gravis – the relevance in clinical practice.
    Thymus imaging in myasthenia gravis - the relevance in clinical practice. Muscle Nerve. 2018 Feb 09;: Authors: Klimiec E, Quirke M, Leite MI, Hilton-Jones D Abstract INTRODUCTION: The ability to distinguish between normal thymus, thymic hyperplasia and thymoma should aid clinical management and decision making in patients with myasthenia gravis. We aimed to determine the accuracy of routine imaging in predicting thymic pathology. METHODS: We retrospectively analyzed records of patients with myasthenia gravis from the Oxford Myasthenia Centre registry who underwent thymectomy. Each patient received one radiological diagnosis and one histological diagnosis. RESULTS: We included 106 patients. Radiological and histological diagnoses agreed in 73 patients (68.9%). Sensitivity and specificity were calculated for each radiological diagnosis as follows: thymoma 90% and 95.5%; hyperplasia 17.6% and 98.6%; and normal 96.9% and 60.8% respectively. DISCUSSION: Routine chest CT and MRI can effectively identify thymoma. However, they are not reliable tools to differentiate between thymic hyperplasia and normal thymus in MG patients. This article is protected by copyright. All rights reserved.PMID: 29424940 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Up-to-date knowledge about the association between multiple sclerosis and the reactivation of human endogenous retrovirus infections.
    Up-to-date knowledge about the association between multiple sclerosis and the reactivation of human endogenous retrovirus infections. J Neurol. 2018 Feb 08;: Authors: Arneth B Abstract BACKGROUND: Although existing studies show that reactivation of the human endogenous retrovirus (HERVs) plays a leading role in multiple sclerosis (MS) progression, the practitioners are yet to establish effective approaches for managing MS without jeopardizing the patients' immune systems. AIM: To provide up-to-date knowledge on the specific roles played by the reactivation of the HERVs in the pathogenesis of MS. MATERIALS AND METHODS: A systematic review of 70 peer-reviewed journals accessed via PubMed was conducted. The searches generated more than 600 sources that were evaluated based on three step in and exclusion criteria. The selected sources were critically analyzed vis-à-vis the paper's hypothesis which posits that the HERVs reactivation does not directly cause the MS, but triggers a demyelination process by promoting the pathogenic effects of the retroviruses. The paper further documents the advancements in the therapeutic applications resulting from the immunohistological analysis and pathological studies aimed at minimizing the adverse consequences of the HERVs reactivation. RESULTS AND DISCUSSIONS: Only three out of the 70 reviewed sources did not find provide evidence linking the reactivation of HERV and MS progression. On the other hand, overwhelming pieces of evidence confirm that the reactivations often drive the demyelinating plaques by initiating microglial inflammation. Pathological examinations reveal that the inflammatory monocytes (Ly6ChiCCR2 + CX3CR1lo) trigger the reactivation of the malignant T cells that are responsible for the progression of MS.… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein.
    MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein. J Neurol. 2018 Feb 08;: Authors: Baumann M, Grams A, Djurdjevic T, Wendel EM, Lechner C, Behring B, Blaschek A, Diepold K, Eisenkölbl A, Fluss J, Karenfort M, Koch J, Konuşkan B, Leiz S, Merkenschlager A, Pohl D, Schimmel M, Thiels C, Kornek B, Schanda K, Reindl M, Rostásy K Abstract Antibodies against the myelin oligodendrocyte glycoprotein (MOG-Ab) can be detected in various pediatric acquired demyelinating syndromes (ADS). Here, we analyze the spectrum of neuroradiologic findings in children with MOG-Ab and a first demyelinating event. The cerebral and spinal MRI of 69 children with different ADS was assessed in regard to the distribution and characteristics of lesions. Children with acute disseminated encephalomyelitis (n = 36) or neuromyelitis optica spectrum disorder (n = 5) presented an imaging pattern characterized predominantly by poorly demarcated lesions with a wide supra- and infratentorial distribution. Younger children also tended to have poorly defined and widespread lesions. The majority of patients with an isolated optic neuritis (n = 16) only presented small non-specific brain lesions or none at all. A longitudinally extensive transverse myelitis mainly affecting the cervical, and less often so the thoracic, lumbar, and conus regions, was detected in 31 children. The three children of our cohort who were then finally diagnosed with multiple sclerosis had at onset already demarcated white matter lesions as well as transverse myelitis. In conclusion, children with MOG seropositive ADS present disparate, yet characteristic imaging patterns. These patterns have… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.
    Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59. Mult Scler. 2018 Feb 01;:1352458518758927 Authors: Zelek WM, Watkins LM, Howell OW, Evans R, Loveless S, Robertson NP, Beenes M, Willems L, Brandwijk R, Morgan BP Abstract BACKGROUND: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). OBJECTIVES: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. METHODS: sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. RESULTS: CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CONCLUSION: CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10
  • Smoking is not associated with higher prevalence of JC virus in MS patients.
    Smoking is not associated with higher prevalence of JC virus in MS patients. Eur J Clin Microbiol Infect Dis. 2018 Feb 08;: Authors: Auer M, Bsteh G, Hegen H, Di Pauli F, Wurth S, Berger T, Deisenhammer F Abstract John Cunningham virus (JCV) causes rare, but potentially life-threatening progressive multifocal leukoencephalopathy (PML) in natalizumab-treated multiple sclerosis (MS) patients. Beside JCV index, there is currently no other factor for further risk stratification. Because smoking was reported as potential risk factor for several viral and bacterial infections, we aimed to investigate whether smoking could increase the risk for JCV infection in MS patients. We screened our database of the MS Clinic of the Department of Neurology, Medical University of Innsbruck, Austria, for patients with known smoking status and test result for anti-JCV antibody index as determined by two-step ELISA at Unilabs, Copenhagen, Denmark. In a representative cohort of 200 MS patients with a rate of 36% current smokers plus 6% former smokers, we were not able to detect any association between smoking and JCV status. Furthermore, there was no association between smoking status and anti-JCV antibody index. Smoking does not seem to be a risk factor for JCV infection in MS patients and, therefore, does not represent a suitable marker for PML-risk stratification under treatment with natalizumab.PMID: 29423619 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-10