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Katarzyna Modzelewska, Elena F Boer, Timothy L Mosbruger, Daniel Picard, Daniela Anderson, Rodney R Miles, Mitchell Kroll, William Oslund, Theodore J Pysher, Joshua D Schiffman, Randy Jensen, Cicely A Jette, Annie Huang, Rodney A Stewart
Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway...
October 25, 2016: Cell Reports
Michael J Boivin, Horacio Ruiseñor-Escudero, Itziar Familiar-Lopez
There is growing concern that although the more severe forms of HIV-associated neurologic deficits are reduced following highly active anti-retroviral therapy (HAART), mild to moderate cognitive disorders may persist for years after HAART initiation and this may occur despite complete plasma viral suppression. According to the UNAIDS 2014 report, there were 3.2 million children living with HIV around the world at the end of 2013 and 91 % of these resided in sub-Saharan Africa. In the same year, only 24 % of children who needed antiretroviral treatment (ART) received it and 190,000 children died of AIDS-related illnesses...
October 25, 2016: Current HIV/AIDS Reports
Chao Zhang, Chendan Wang, Jianbo Ren, Xiangjie Guo, Keming Yun
Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes...
October 24, 2016: International Journal of Molecular Sciences
Ruchi Malik, Bhanwar Singh Choudhary, Shubham Srivastava, Pakhuri Mehta, Manish Sharma
Alzheimer's disease (AD), a progressive neurodegenerative disorder is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine via inhibiting acetylcholinesterase (AChE). The present study involves identification of newer AChE inhibitors by dual approach of e-pharmacophore and structure based virtual screening of Asinex library. Robustness of docking protocol was validated by enrichment calculation with ROC value 0...
October 26, 2016: Journal of Biomolecular Structure & Dynamics
Mohammad A Kaisar, Ravi K Sajja, Shikha Prasad, Vinay V Abhyankar, Taylor Liles, Luca Cucullo
The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered: This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies...
October 26, 2016: Expert Opinion on Drug Discovery
E C F Wagenaar, P van Wijngaarden, C M Verduin, D Beelen, R W van Etten
Staphylococcus lugdunensis (SL) is a species belonging to the group of coagulase-negative staphylococci (CNS). It can cause severe infections such as endocarditis. Three cases of endocarditis caused by SL are presented. The first case describes a 71-year-old man with a fever and endogenous endophthalmitis. The second case describes delirium in an 87-year-old woman, thought to be due to pneumonia. The third case describes a 76-year-old man with an infection of unknown origin. In all cases, the first blood cultures drawn were positive for CNS and considered to be contaminated...
2016: Nederlands Tijdschrift Voor Geneeskunde
Torsten Pietsch, Christine Haberler
The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma...
October 26, 2016: Clinical Neuropathology
Jinglan Liu, Matthew P Keisling, Ayman Samkari, Gregory Halligan, Judy M Pascasio, Christos D Katsetos
Central nervous system (CNS) tumors exhibiting dual features of malignant glioma (MG) and primitive neuroectodermal tumor (PNET) are rare and diagnostically challenging. Previous studies have shown that MG-PNET carry MYCN or MYC gene amplifications within the PNET component concomitant with glioma-associated alterations, most commonly 10q loss, in both components [9]. Here we confirm and extend the profile of molecular genetic findings in a MG-PNET involving the left frontal lobe of a 12-year-old male. Histologically, the PNET-like component showed morphological features akin to anaplastic medulloblastoma highlighted by widespread immunoreactivity for βIII-tubulin (TUBB3) and nonphosphorylated neurofilament protein, and to a lesser degree, Neu-N, synaptophysin, and CD99, whereas the gliomatous component was demarcated by glial fibrillary acidic protein (GFAP) labeling...
October 26, 2016: Clinical Neuropathology
A J Page, S J Kentish
The vagal link between the gastrointestinal tract and the central nervous system (CNS) has numerous vital functions for maintaining homeostasis. The regulation of energy balance is one which is attracting more and more attention due to the potential for exploiting peripheral hormonal targets as treatments for conditions such as obesity. While physiologically, this system is well tuned and demonstrated to be effective in the regulation of both local function and promoting/terminating food intake the neural connection represents a susceptible pathway for disruption in various disease states...
October 25, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Aggeliki Giannakopoulou, George A Lyras, Nikolaos Grigoriadis
Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of chronic inflammation remains controversial. In this study the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis was used to investigate the long-term effects of T cell-mediated central nervous system inflammation on hippocampal neurogenesis. 5-Bromodeoxyuridine (BrdU)-labeled subpopulations of hippocampal cells in EAE and control mice (coexpressing GFAP, doublecortin, NeuN, calretinin, and S100) were quantified at the recovery phase, 21 days after BrdU administration, to estimate alterations on the rate and differentiation pattern of the neurogenesis process...
October 26, 2016: Journal of Neuroscience Research
Yun Jung Choi, Hyangmin Park, Ji Sung Lee, Ju-Yeon Lee, Shin Kim, Tae Won Kim, Jung Sun Park, Jeong Eun Kim, Dok Hyun Yoon, Cheolwon Suh
The genetic association of the methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism with methotrexate (MTX)-associated toxicity has been evaluated and conflicting results have been reported. The substantial heterogeneity of the studied population was suggested to be a possible explanation because ethnicity, MTX dose, coadministered chemotherapeutic agents, and folinate rescue dosage regimen could alter the MTX toxicity profile. The patient population was homogenized by limiting the cancer type to primary central nervous system lymphoma and chemotherapy protocol to a high-dose MTX monotherapy regimen...
October 25, 2016: Hematological Oncology
Amanda J Pickard, Albert S W Sohn, Thomas F Bartenstein, Shan He, Yi Zhang, James M Gallo
The prevalence of mutant isocitrate dehydrogenase 1 (IDH1) brain tumors has generated significant efforts to understand the role of the mutated enzyme product d-2-hydroxyglutarate (D2HG), an oncometabolite, in tumorigenesis, as well as means to eliminate it. Glymphatic clearance was proposed as a pathway that could be manipulated to accelerate D2HG clearance and dictated the study design that consisted of two cohorts of mice bearing U87/mutant IDH1 intracerebral tumors that underwent two microdialysis - providing D2HG interstitial fluid concentrations - sampling periods of awake and asleep (activate glymphatic clearance) in a crossover manner...
2016: Frontiers in Oncology
Jeymohan Joseph, Paola Cinque, Deborah Colosi, Ameet Dravid, Luminita Ene, Howard Fox, Dana Gabuzda, Magnus Gisslen, Sarah Beth Joseph, Scott Letendre, Shibani S Mukerji, Avindra Nath, Ignacio Perez-Valero, Deborah Persaud, Richard W Price, Vasudev R Rao, Ned Sacktor, Ronald Swanstrom, Alan Winston, Valerie Wojna, Edwina Wright, Serena Spudich
CSF HIV escape is a recently recognised phenomenon that suggests that despite suppressive treatment, HIV RNA may be detected in the CNS compartment in some individuals. In rare cases this is associated with clinical neurological disease, while in most cases, neurological consequences are not apparent. Attempts at characterising the biological substrates of CSF escape and further investigating the neurological consequences need to be made to better understand the implications of this condition for the HIV cure agenda as well as for clinical outcomes...
October 5, 2016: Journal of Virus Eradication
Sharon R Lewin, John W Mellors
No abstract text is available yet for this article.
October 5, 2016: Journal of Virus Eradication
Ying Bai, Jun Zhu, Yan-Min Yang, Yan Liang, Hui-Qiong Tan, Juan Wang, Bi Huang, Han Zhang, Xing-Hui Shao
BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) often coexist, however, the clinical characteristics and the impact of stable CAD on the outcomes in Chinese patients with AF has not been well understood. METHODS: Consecutive AF patients in 20 hospitals in China from November 2008 to October 2011 were enrolled. The primary endpoints included 1-year all-cause mortality, stroke, non-central nervous system (non-CNS) embolism, and major bleeding...
August 2016: Journal of Geriatric Cardiology: JGC
Ni Chen, Tianpin Yu, Jing Gong, Ling Nie, Xueqin Chen, Mengni Zhang, Miao Xu, Junya Tan, Zhengzheng Su, Jinjing Zhong, Qiao Zhou
Mutations of isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes have been identified as early molecular events in the development of astrocytomas and oligodendrogliomas. Data regarding the status and prevalence of IDH1/2 mutations in Chinese patients are limited. Herein we report our data from West China Hospital, a major Chinese medical centre. IDH1(R132H) mutation was analysed by immunohistochemistry with the mutation-specific IDH1(R132H) antibody in 1011 patients, including 922 central nervous system (CNS) tumours and 89 non-neoplastic CNS lesions, and PCR-based direct sequencing of IDH1/2 gene mutation in 570 of these samples...
October 22, 2016: Pathology
L P Mesquita, F R P Bruhn, P C Maiorka, E W Howerth
The vesicular stomatitis virus (VSV) causes encephalitis in mice when inoculated intranasally. The deer mouse (Peromyscus maniculatus), a native New World rodent, is also susceptible to VSV infection and develops similar central nervous system (CNS) lesions to those observed in other rodent species. Chemokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES; CCL-5) and monocyte chemoattractant protein (MCP)-1 (CCL-2), which are important for chemotaxis and activation of inflammatory cells, are expressed during the course of VSV encephalitis...
October 22, 2016: Journal of Comparative Pathology
Virginie Avrillon, Maurice Pérol
Alectinib is a highly selective second-generation ALK inhibitor that is active against most crizotinib ALK resistance mutations, with a good penetration in CNS and a good safety profile. Thanks to the positive results of Phase II trials, alectinib was approved in Japan and by the US FDA for ALK-positive non-small-cell lung cancer (NSCLC) patients pretreated with crizotinib. Recently, the Phase III J-ALEX study demonstrated superiority of alectinib over crizotinib in crizotinib naive ALK-positive NSCLC, with an impressive improvement of progression-free survival...
October 26, 2016: Future Oncology
Petra D Cravens, Rehana Z Hussain, William A Miller-Little, Li-Hong Ben, Benjamin M Segal, Emily Herndon, Olaf Stüve
BACKGROUND: Interleukin (IL)-12 and IL-23 are heterodimers that share the p40 subunit, and both cytokines are critical in the differentiation of T helper (Th)1 and Th17 cells, respectively. Th1 and Th17 effector cells have been implicated in the pathogenesis of experimental autoimmune encephalitis (EAE), an animal model of the human central nervous system (CNS) autoimmune demyelinating disorder multiple sclerosis (MS). However, ustekinumab, a monoclonal antibody (mAb) against p40 failed to show efficacy over placebo in a phase II clinical trial in patients with MS...
2016: PloS One
Teresa T Vo, Sheeba Varghese Gupta
For treatment-naïve patients with human immunodeficiency virus infection, efavirenz (EFV) together with tenofovir and emtricitabine were once widely prescribed given its efficacy and ease of administration in a combination pill. However, the high rate of central nervous system toxicities from EFV prompted the United States Department of Health and Human Services to move the EFV-based regimen from the recommended to the alternative category. For patients who do meet the criteria for newer recommended antiretroviral treatments, EFV is a viable option and is often the mainstay of treatment outside the United States, as newer antiretroviral treatments are more expensive...
October 25, 2016: Pharmacotherapy
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