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Cns diseases

Sindhu R Johnson, Dinesh Khanna, David Daikh, Ricard Cervera, Nathalie Costedoat-Chalumeau, Dafna D Gladman, Bevra H Hahn, Falk Hiepe, Jorge Sánchez-Guerrero, Elena Massarotti, Dimitrios T Boumpas, Karen H Costenbader, David Jayne, Thomas Dörner, Diane L Kamen, Marta Mosca, Rosalind Ramsey-Goldman, Josef S Smolen, David Wofsy, Martin Aringer
OBJECTIVE: Given the complexity and heterogeneity of systemic lupus erythematosus (SLE), high performing classification criteria are critical to advancing research and clinical care. A collaborative effort by EULAR and ACR was undertaken to generate candidate criteria, and then to reduce them to a smaller set. The objective of the current study was to select a set of criteria that maximizes the likelihood of accurate classification of SLE, particularly early disease. METHODS: An independent panel of international SLE experts and the SLE classification criteria steering committee (conducting SLE research in Canada, Mexico, United States, Austria, Germany, Greece, France, Italy, and Spain) ranked 43 candidate criteria...
December 15, 2018: Journal of Rheumatology
Maureen A Mealy, Sarah E Mossburg, Su-Hyun Kim, Silvia Messina, Nadja Borisow, Reydmar Lopez-Gonzalez, Juan Pablo Ospina, Michael Scheel, Anusha K Yeshokumar, Amine Awad, M Isabel Leite, JorgeA Jimenez Arango, Friedemann Paul, Jacqueline Palace, Ho Jin Kim, Michael Levy
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that preferentially targets the spinal cord and optic nerves. Increasing disability is accrued with each inflammatory attack. Disability has been shown to be an independent predictor of poor quality of life in those with NMOSD. Factors associated with increasing disability need further systematic investigation. METHODS: We performed a multi-center retrospective chart analysis of aquaporin-4 (AQP4) seropositive NMOSD patients with a history of myelitis seen at five large referral centers for patients with NMOSD worldwide for whom thorough records including relapse history and corresponding imaging were available...
December 9, 2018: Multiple Sclerosis and related Disorders
Carme Costa, Herena Eixarch, Elena Martínez-Sáez, Laura Calvo-Barreiro, Maite Calucho, Zoraida Castro, Arantxa Ortega-Aznar, Santiago Ramón Y Cajal, Xavier Montalban, Carmen Espejo
Bone morphogenetic proteins (BMPs) are secreted proteins that belong to the transforming growth factor-beta superfamily. In the adult brain, they modulate neurogenesis, favor astrogliogenesis, and inhibit oligodendrogenesis. As BMPs may be involved in the failure of remyelination in multiple sclerosis (MS), we characterized the expression of BMP-2, -4, -5, and -7; BMP type II receptor (BMPRII); and phosphorylated (p)SMAD 1/5/8 in lesions of MS and other demyelinating diseases. Forty-two MS lesions, 12 acute ischemic lesions, eight progressive multifocal leucoencephalopathy lesions, and 10 CNS areas from four non-neuropathological patients were included...
December 13, 2018: American Journal of Pathology
Ruturaj Masvekar, Tianxia Wu, Peter Kosa, Christopher Barbour, Valentina Fossati, Bibiana Bielekova
BACKGROUND: Once multiple sclerosis (MS) reaches the progressive stage, immunomodulatory treatments have limited efficacy. This suggests that processes other than activation of innate immunity may at least partially underlie disability progression during late stages of MS. Pathology identified these alternative processes as aberrant activation of astrocytes and microglia, and subsequent degeneration of oligodendrocytes and neurons. However, we mostly lack biomarkers that could measure central nervous system (CNS) cell-specific intrathecal processes in living subjects...
December 5, 2018: Multiple Sclerosis and related Disorders
D Hepnar, P Adam, H Žáková, M Krušina, P Kalvach, J Kasík, I Karpowicz, J Nasler, K Bechyně, T Fiala, M Mamiňák, I Malíková, J Mareš, V Šigut, Z Tokár, J Vránová
Diseases of the central nervous system (CNS) mean for the human organism a potentially dangerous situation. An investigation of cerebrospinal fluid (CSF) provides important information about a character of CNS impairment in the decision-making diagnostic and therapeutic algorithm. The authors present a brief overview of available cerebrospinal fluid assays, shortened indication criteria, a recommended algorithm of CSF assessment in different suspected diseases, and a view of the external quality system. The whole portfolio of obtainable CSF methodology is further subdivided according to the adequate choice into the first and inevitable basic routine panel, and following complicated analyses of highly specialized character...
December 14, 2018: Folia Microbiologica
Yuqing Yan, Jiezhong Yu, Ye Gao, Gajendra Kumar, Minfang Guo, Yijin Zhao, Qingli Fang, Huiyu Zhang, Jingwen Yu, Yuqiang Jiang, Han-Ting Zhang, Cun-Gen Ma
Multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and other neurodegenerative diseases of central nervous system (CNS) disorders are serious human health problems. Rho-kinase (ROCK) is emerging as a potentially important therapeutic target relevant to inflammatory neurodegeneration diseases. This is supported by studies showing the beneficial effects of fasudil, a ROCK inhibitor, in inflammatory neurodegeneration diseases. MS is an autoimmune disease resulting from inflammation and demyelination in the white matter of the CNS...
December 14, 2018: Metabolic Brain Disease
Jiun-I Lai, Daniel Nachun, Lina Petrosyan, Benjamin Throesch, Erica Campau, Fuying Gao, Kristin K Baldwin, Giovanni Coppola, Joel M Gottesfeld, Elisabetta Soragni
Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by transcriptional silencing of the FXN gene, resulting in loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA•TTC  repeat expansion in the first intron of FXN induces heterochromatin, we previously showed that 2-aminobenzamide-type histone deacetylase inhibitors (HDACi) increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neurons and in circulating lymphocytes from patients after HDACi oral administration...
December 14, 2018: Journal of Biological Chemistry
Nicolas Marcoux, Scott N Gettinger, Grainne O'Kane, Kathryn C Arbour, Joel W Neal, Hatim Husain, Tracey L Evans, Julie R Brahmer, Alona Muzikansky, Philip D Bonomi, Salvatore Del Prete, Anna Wurtz, Anna F Farago, Dora Dias-Santagata, Mari Mino-Kenudson, Karen L Reckamp, Helena A Yu, Heather A Wakelee, Frances A Shepherd, Zofia Piotrowska, Lecia V Sequist
PURPOSE: Approximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non-small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical course is poorly characterized. METHODS: We retrospectively identified patients with EGFR-mutant SCLC and other high-grade neuroendocrine carcinomas seen at our eight institutions. Demographics, disease features, and outcomes were analyzed. RESULTS: We included 67 patients-38 women and 29 men; EGFR mutations included exon 19 deletion (69%), L858R (25%), and other (6%)...
December 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Qiao-Qiao Yang, Jia-Wei Zhou
Neuroinflammation in the central nervous system (CNS) is an important subject of neuroimmunological research. Emerging evidence suggests that neuroinflammation is a key player in various neurological disorders, including neurodegenerative diseases and CNS injury. Neuroinflammation is a complex and well-orchestrated process by various groups of glial cells in CNS and peripheral immune cells. The cross-talks between various groups of glial cells in CNS neuroinflammation is an extremely complex and dynamic process which resembles a well-orchestrated symphony...
December 11, 2018: Glia
Claudia Cicognola, Gunnar Brinkmalm, Jessica Wahlgren, Erik Portelius, Johan Gobom, Nicholas C Cullen, Oskar Hansson, Lucilla Parnetti, Radu Constantinescu, Kristin Wildsmith, Hsu-Hsin Chen, Thomas G Beach, Tammaryn Lashley, Henrik Zetterberg, Kaj Blennow, Kina Höglund
Tau is an axonal microtubule-binding protein. Tau pathology in brain and increased tau concentration in the cerebrospinal fluid (CSF) are hallmarks of Alzheimer's disease (AD). Most of tau in CSF is present as fragments. We immunoprecipitated tau from CSF and identified several endogenous peptides ending at amino acid (aa) 123 or 224 using high-resolution mass spectrometry. We raised neo-epitope-specific antibodies against tau fragments specifically ending at aa 123 and 224, respectively. With these antibodies, we performed immunohistochemistry on brain tissue and designed immunoassays measuring N-123, N-224, and x-224 tau...
December 13, 2018: Acta Neuropathologica
Justyna Magdalena Przystal, Nabil Hajji, Combiz Khozoie, Alexander Renziehausen, Qingyu Zeng, Fernando Abaitua, Amin Hajitou, Keittisak Suwan, Elizabeth Want, John Bomalaski, Peter Szlosarek, Kevin O'Neill, Tim Crook, Nelofer Syed
Glioblastoma multiforme (GBM) remains a cancer with a poor prognosis and few effective therapeutic options. Successful medical management of GBM is limited by the restricted access of drugs to the central nervous system (CNS) caused by the blood brain barrier (BBB). We previously showed that a subset of GBM are arginine auxotrophic because of transcriptional silencing of ASS1 and/or ASL and are sensitive to pegylated arginine deiminase (ADI-PEG20). However, it is unknown whether depletion of arginine in peripheral blood in vivo has therapeutic activity against intracranial disease...
December 13, 2018: Cell Death & Disease
Fabíola Reis de Oliveira, Marina Zilio Fantucci, Leidiane Adriano, Valéria Valim, Thiago Mattar Cunha, Paulo Louzada-Junior, Eduardo Melani Rocha
For decades, neurological, psychological, and cognitive alterations, as well as other glandular manifestations (EGM), have been described and are being considered to be part of Sjögren's syndrome (SS). Dry eye and dry mouth are major findings in SS. The lacrimal glands (LG), ocular surface (OS), and salivary glands (SG) are linked to the central nervous system (CNS) at the brainstem and hippocampus. Once compromised, these CNS sites may be responsible for autonomic and functional disturbances that are related to major and EGM in SS...
December 8, 2018: International Journal of Molecular Sciences
Shu Hui Lye, Stanislava Chtarbanova
Innate immunity is the first line of defense against invading pathogens and plays an essential role in defending the brain against infection, injury, and disease. It is currently well recognized that central nervous system (CNS) infections can result in long-lasting neurological sequelae and that innate immune and inflammatory reactions are highly implicated in the pathogenesis of neurodegeneration. Due to the conservation of the mechanisms that govern neural development and innate immune activation from flies to mammals, the lack of a classical adaptive immune system and the availability of numerous genetic and genomic tools, the fruit fly Drosophila melanogaster presents opportunities to investigate the cellular and molecular mechanisms associated with immune function in brain tissue and how they relate to infection, injury and neurodegenerative diseases...
December 7, 2018: International Journal of Molecular Sciences
Karolina Skonieczna-Żydecka, Wojciech Marlicz, Agata Misera, Anastasios Koulaouzidis, Igor Łoniewski
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors...
December 7, 2018: Journal of Clinical Medicine
Kuerbanjiang Abuduxikuer, Ling-Juan Fang, Li-Ting Li, Jing-Yu Gong, Jian-She Wang
To retrospectively analyze and quantitatively correlate UGT1A1 (bilirubin UDP- glucuronosyltransferase gene) genotypes and unconjugated hyperbilirubinemia (UCH) phenotypes among Chinese children.We retrospectively reviewed UCH patients, quantitatively analyzed genotype-phenotype correlation by comparing with healthy controls. Pfam database, SWISS-model, and Pymol were used for UGT1A1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on protein structure.Seventy four cases, including 21 prolonged unconjugated hyperbilirubinemia (PUCH), 30 Gilbert syndrome (GS), 22 Crigler-Najjar syndrome type II (CNS-II), and 1 Crigler-Najjar syndrome type I (CNS-I) phenotypes were analyzed...
December 2018: Medicine (Baltimore)
Chang-An Geng, Tong-Hua Yang, Xiao-Yan Huang, Yun-Bao Ma, Xue-Mei Zhang, Ji-Jun Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) are fascinating sources for natural drug candidates. Uncaria rhynchophylla (Gouteng) is a famous TCM used for alleviating central nervous system (CNS) disorders, while its antidepressant constituents are still disputed. AIM OF THE STUDY: The present study was designed to assess the antidepressant property of U. rhynchophylla and characterize the active constituents targeting melatonin receptors which are closely related to CNS diseases...
December 10, 2018: Journal of Ethnopharmacology
Qingjun Cao, Xueyan Liu, Fenghua Yang, Hua Wang
Epilepsy is a chronic brain disease caused by abnormal discharging in the brain, which induces momentary brain dysfunction. Cannabinoid 2 receptor (CB2R) is expressed in central nervous system (CNS) and serves an important role in the pathogenesis of CNS diseases. The aim of the present study was to explore the effects of CB2R activation on phosphoinositide 3-kinase (PI3K) 110α-protein kinase B (AKT) signaling in an astrocyte model of epilepsy. Rat CTX TNA2 astrocytes were treated with Mg free solution to establish a cell model of epilepsy and were subsequently treated with a CB2R agonist (JWH133) and antagonist (AM630)...
December 2018: Experimental and Therapeutic Medicine
Sara Hurvitz, Rashi Singh, Brad Adams, Julie A Taguchi, David Chan, Robert A Dichmann, Aurelio Castrellon, Eddie Hu, Jonathan Berkowitz, Aruna Mani, Brian DiCarlo, Rena Callahan, Ira Smalberg, Xiaoyan Wang, Ivana Meglar, Diego Martinez, Evthokia Hobbs, Dennis J Slamon
Background: Improving outcomes for patients with human epidermal growth factor 2-positive (HER2+) central nervous system (CNS) metastases remains an unmet clinical need. This trial evaluated a novel combination of everolimus, lapatinib and capecitabine for this disease. Methods: Patients with trastuzumab-pretreated, HER2+ breast cancer brain metastasis without prior therapy with a mammalian target of rapamycin (mTOR) inhibitor were eligible. Patients received lapatinib and everolimus daily (continuously) and capecitabine twice daily (d1-14) in 21-d cycles...
2018: Therapeutic Advances in Medical Oncology
Patrizia LoPresti
Central nervous system (CNS) degeneration occurs during multiple sclerosis (MS) following several years of reversible autoimmune demyelination. Progressive CNS degeneration appears later during the course of relapsing-remitting MS (RRMS), although it starts insidiously at disease onset. We propose that there is an early subclinical phase also for primary-progressive (PP) MS. Consensus exists that many different cell types are involved during disease onset. Furthermore, the response to the initial damage, which is specific for each individual, would result in distinct pathological pathways that add complexity to the disease and the mechanisms underlying progressive CNS degeneration...
2018: Frontiers in Neurology
Yingying Cai, Cuixia Yang, Xiaohan Yu, Jie Qian, Min Dai, Yan Wang, Chaoyan Qin, Weiming Lai, Shuai Chen, Tingting Wang, Jinfeng Zhou, Ningjia Ma, Yue Zhang, Ru Zhang, Nan Shen, Xin Xie, Changsheng Du
Altered migration and immune responses of dendritic cells (DCs) lead to inflammatory and autoimmune diseases. Our studies demonstrated that β-arrestin 2 deficiency promoted migration and cytokine production of mouse bone marrow-derived DCs. We further found that β-arrestin 2 directly interacted with Zbtb46, a DC-specific transcription factor. What's more, our results suggested that the interaction between β-arrestin 2 and Zbtb46 might negatively regulate DC migration. Using RNA sequencing, we indicated that genes CD74, NR4A1, and ZFP36 might be the target genes regulated by the interaction between β-arrestin 2 and Zbtb46...
December 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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