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Brain Pathology

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https://www.readbyqxmd.com/read/29226988/cns-high-grade-neuroepithelial-tumor-with-bcor-internal-tandem-duplication-a-comparison-with-its-counterparts-in-the-kidney-and-soft-tissue
#1
Yuka Yoshida, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Yoshiki Arakawa, Yohei Mineharu, Yasuo Sugita, Takako Yoshioka, Asuka Araki, Yuichiro Sato, Hideo Takeshima, Masahiko Okada, Akira Nishi, Tatsuya Yamazaki, Kenichi Kohashi, Yoshinao Oda, Junko Hirato, Hideaki Yokoo
Central nervous system high-grade neuroepithelial tumors with BCOR alteration (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so-called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3' end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to share similar pathological features...
December 11, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29222823/dominant-role-of-microglial-and-macrophage-innate-immune-responses-in-human-ischemic-infarcts
#2
Tobias Zrzavy, Joana Machado-Santos, Sheren Christine, Christoph Baumgartner, Howard L Weiner, Oleg Butovsky, Hans Lassmann
Inflammatory mechanisms, involving granulocytes, T-cells, B-cells, macrophages and activated microglia, have been suggested to play a pathogenic role in experimental models of stroke and may be targets for therapeutic intervention. However, knowledge on the inflammatory response in human stroke lesions is limited. Here, we performed a quantitative study on the inflammatory reaction in human ischemic infarct lesions. We found increased numbers of T-lymphocytes, mainly CD8+ cells, but not of B-lymphocytes. Their number was very low in comparison to that seen in inflammatory diseases of the central nervous system and they did not show signs of activation...
December 8, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29222813/reln-signaling-modulates-glioblastoma-growth-and-substrate-dependent-migration
#3
Markus Schulze, Christ Violonchi, Stefan Swoboda, Tobias Welz, Eugen Kerkhoff, Sabine Hoja, Susanne Brüggemann, Johann Simbürger, Jörg Reinders, Markus J Riemenschneider
Glioblastoma (GBM) represents the most common and most malignant type of primary brain tumor and significantly contributes to cancer morbidity and mortality. Invasion into the healthy brain parenchyma is a major feature of glioblastoma aggressiveness. Reelin (RELN) is a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning in the developing brain and sustains functionality in the adult brain. We here show that both RELN and its main downstream effector DAB1 are silenced in glioblastoma as compared to non-neoplastic tissue and mRNA expression is inversely correlated with malignancy grade...
December 8, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29105198/braf-v600e-tert-promoter-mutations-and-cdkn2a-b-homozygous-deletions-are-frequent-in-epithelioid-glioblastomas-a-histological-and-molecular-analysis-focusing-on-intratumoral-heterogeneity
#4
Nozomi Nakajima, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Tatsuya Yamazaki, Nozomi Matsumura, Kenichi Harada, Hadzki Matsuda, Nobuaki Funata, Shoichi Nagai, Hideo Nakamura, Atsushi Sasaki, Jiro Akimoto, Junko Hirato, Hideaki Yokoo
Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported...
November 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29027761/oxidative-stress-and-mitochondrial-dynamics-malfunction-are-linked-in-pelizaeus-merzbacher-disease
#5
Montserrat Ruiz, Mélina Bégou, Nathalie Launay, Pablo Ranea-Robles, Patrizia Bianchi, Jone López-Erauskin, Laia Morató, Cristina Guilera, Bérengère Petit, Catherine Vaurs-Barriere, Céline Guéret-Gonthier, Marie-Noëlle Bonnet-Dupeyron, Stéphane Fourcade, Johan Auwerx, Odile Boespflug-Tanguy, Aurora Pujol
Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD...
October 13, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29027727/downregulated-apoptosis-and-autophagy-after-anti-a%C3%AE-immunotherapy-in-alzheimer-s-disease
#6
Claire Paquet, James Ar Nicoll, Seth Love, François Mouton-Liger, Clive Holmes, Jacques Hugon, Delphine Boche
Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35...
October 13, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28990708/astroblastoma-a-distinct-tumor-entity-characterized-by-alterations-of-the-x-chromosome-and-mn1-rearrangement
#7
Takanori Hirose, Sumihito Nobusawa, Kazuhiko Sugiyama, Vishwa J Amatya, Naomi Fujimoto, Atsushi Sasaki, Yoshiki Mikami, Akiyoshi Kakita, Shinya Tanaka, Hideaki Yokoo
Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement...
October 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28990704/epithelioid-glioblastomas-stratify-into-established-diagnostic-subsets-upon-integrated-molecular-analysis
#8
Andrey Korshunov, Lukas Chavez, Tanvi Sharma, Marina Ryzhova, Daniel Schrimpf, Damian Stichel, David Capper, Dominik Sturm, Marcel Kool, Antje Habel, Bette K Kleinschmidt-DeMasters, Marc Rosenblum, Oksana Absalyamova, Andrey Golanov, Peter Lichter, Stefan M Pfister, David T W Jones, Arie Perry, Andreas von Deimling
Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM". Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort...
October 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28987033/trem2-expression-in-the-human-brain-a-marker-of-monocyte-recruitment
#9
Marie Fahrenhold, Sonja Rakic, John Classey, Carol Brayne, Paul G Ince, James A R Nicoll, Delphine Boche
Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68...
October 7, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28976058/diffuse-gliomas-with-fgfr3-tacc3-fusion-have-characteristic-histopathological-and-molecular-features
#10
Franck Bielle, Anna-Luisa Di Stefano, David Meyronnet, Alberto Picca, Chiara Villa, Michèle Bernier, Yohann Schmitt, Marine Giry, Audrey Rousseau, Dominique Figarella-Branger, Claude-Alain Maurage, Emmanuelle Uro-Coste, Anna Lasorella, Antonio Iavarone, Marc Sanson, Karima Mokhtari
Adult glioblastomas, IDH-wildtype represent a heterogeneous group of diseases. They are resistant to conventional treatment by concomitant radiochemotherapy and carry a dismal prognosis. The discovery of oncogenic gene fusions in these tumors has led to prospective targeted treatments, but identification of these rare alterations in practice is challenging. Here, we report a series of 30 adult diffuse gliomas with an in frame FGFR3-TACC3 oncogenic fusion (n=27 WHO grade IV and n=3 WHO grade II) as well as their histological and molecular features...
October 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28960623/multimodal-molecular-analysis-of-astroblastoma-enables-reclassification-of-most-cases-into-more-specific-molecular-entities
#11
Matthew D Wood, Tarik Tihan, Arie Perry, Geeta Chacko, Clinton Turner, Cunfeng Pu, Christopher Payne, Alexander Yu, Serguei I Bannykh, David A Solomon
Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1)...
September 28, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28960595/spinal-lewy-body-pathology-in-older-adults-without-an-antemortem-diagnosis-of-parkinson-s-disease
#12
Aron S Buchman, Sukriti Nag, Sue E Leurgans, Jared Miller, Veronique G J M VanderHorst, David A Bennett, Julie A Schneider
To test the hypothesis that Lewy body pathology (LBs) is present in the spinal cord of older community-dwelling adults without a clinical diagnosis of Parkinson's disease (PD). We studied 162 prospective autopsies from older adults with PD (N = 6) and without PD (N = 156). We documented the presence of LBs in cerebrum and brainstem structures from each of the six regions used for Braak PD staging and four spinal cord levels (C5/6, T7, L4/5 and S4/5). Parkinsonism proximate to death was based on a previously validated measure present if two or more of the four signs of parkinsonism were present based on a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS)...
September 28, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28960571/neuronal-rho-gtpase-rac1-elimination-confers-neuroprotection-in-a-mice-model-of-permanent-ischemic-stroke
#13
Cansu Karabiyik, Rui Fernandes, Francisco Rosário Figueiredo, Renato Socodato, Cord Brakebusch, Kate Lykke Lambertsen, João Bettencourt Relvas, Sofia Duque Santos
The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress...
September 28, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28960710/optineurin-pathology-in-the-spinal-cord-of-amyotrophic-lateral-sclerosis-parkinsonism-dementia-complex-patients-in-kii-peninsula-japan
#14
LETTER
Satoru Morimoto, Hiroyuki Hatsuta, Rie Motoyama, Yasumasa Kokubo, Hiroyuki Ishiura, Shoji Tsuji, Shigeki Kuzuhara, Shigeo Murayama
No abstract text is available yet for this article.
September 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29076287/corrigendum
#15
(no author information available yet)
No abstract text is available yet for this article.
November 2017: Brain Pathology
https://www.readbyqxmd.com/read/28378357/h3-k27m-mutation-in-gangliogliomas-can-be-associated-with-poor-prognosis
#16
LETTER
B K Kleinschmidt-DeMasters, Andrew Donson, Nicholas K Foreman, Kathleen Dorris
No abstract text is available yet for this article.
November 2017: Brain Pathology
https://www.readbyqxmd.com/read/28100023/frontotemporal-lobar-degeneration-pathogenesis-pathology-and-pathways-to-phenotype
#17
REVIEW
David M A Mann, Julie S Snowden
Frontotemporal Lobar Degeneration (FTLD) is a clinically, pathologically and genetically heterogeneous group of disorders that affect principally the frontal and temporal lobes of the brain. There are three major associated clinical syndromes, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA); three principal histologies, involving tau, TDP-43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations...
November 2017: Brain Pathology
https://www.readbyqxmd.com/read/27997995/cimpact-now-the-consortium-to-inform-molecular-and-practical-approaches-to-cns-tumor-taxonomy-a-new-initiative-in-advancing-nervous-system-tumor-classification
#18
David N Louis, Ken Aldape, Daniel J Brat, David Capper, David W Ellison, Cynthia Hawkins, Werner Paulus, Arie Perry, Guido Reifenberger, Dominique Figarella-Branger, Pieter Wesseling, Tracy T Batchelor, J Gregory Cairncross, Stefan M Pfister, Stefan Rutkowski, Michael Weller, Wolfgang Wick, Andreas von Deimling
No abstract text is available yet for this article.
November 2017: Brain Pathology
https://www.readbyqxmd.com/read/27936516/neuroprotection-of-hypoxic-postconditioning-against-global-cerebral-ischemia-through-influencing-posttranslational-regulations-of-heat-shock-protein-27-in-adult-rats
#19
Lixuan Zhan, Liu Liu, Kongping Li, Baoxing Wu, Dandan Liu, Donghai Liang, Haixia Wen, Yanmei Wang, Weiwen Sun, Weiping Liao, En Xu
We previously reported that hypoxic postconditioning (HPC) ameliorated hippocampal neuronal death induced by transient global cerebral ischemia (tGCI) in adult rats. However, the mechanism of HPC-induced neuroprotection is still elusive. Notably, heat shock protein 27 (Hsp27) has recently emerged as a potent neuroprotectant in cerebral ischemia. Although its robust protective effect on stroke has been recognized, the mechanism of Hsp27-mediated neuroprotection is largely unknown. Here, we investigated the potential molecular mechanism by which HPC modulates the posttranslational regulations of Hsp27 after tGCI...
November 2017: Brain Pathology
https://www.readbyqxmd.com/read/27864854/igg4-related-hypophysitis-is-highly-prevalent-among-cases-of-histologically-confirmed-hypophysitis
#20
Christian Bernreuther, Christopher Illies, Jörg Flitsch, Michael Buchfelder, Rolf Buslei, Markus Glatzel, Wolfgang Saeger
IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41...
November 2017: Brain Pathology
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