MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Brain Pathology' source. Wed, 08 Feb 2012 20:42:59 +0100 http://www.medworm.com/index.php?rid=5649978&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00571.x AbstractGliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in gliosarcomas is due to extensive genomic instability and/or to a mechanism similar to epithelial–mesenchymal transition (EMT). In the present study, we assessed 40 gliosarcomas for immunoreactivity of Slug, Twist, MMP‐2, and MMP‐9, which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) gliosarcomas, but not in glial areas (P < 0.0001). Nuclear Twist expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) gliosarcomas, but glial tumor areas were largely negative ex... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5649978 Mon, 30 Jan 2012 05:00:00 +0100 5649978 http://www.medworm.com/index.php?rid=5610975&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00565.x AbstractNeuroendocrine, metabolic and autonomic nervous system dysfunction are prevalent among patients with Huntington's disease (HD) and may underlie symptoms such as depression, weight loss and autonomic failure. Using post‐mortem paraffin embedded tissue, we assessed the integrity of the major neuropeptide populations in the paraventricular nucleus (PVN) ‐ the hypothalamic neuroendocrine and autonomic integration center ‐ in HD patients. The number corticotropin‐releasing hormone, cocaine‐ and amphetamine‐ regulated transcript, arginine vasopressin and oxytocin immunoreactive neurons did not differ between HD patients and control subjects. However, the significant positive correlation between arginine vasopressin and oxytocin immunoreactive neurons in control subjects (P = ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5610975 Wed, 18 Jan 2012 05:00:00 +0100 5610975 http://www.medworm.com/index.php?rid=5660858&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00573.x AbstractGlioblastoma is the most common type of primary brain tumor in adults and are among the most lethal and least successfully treated solid tumors. Recently, research into the area of stem cells in brain tumors has gained momentum. However, due to the relatively new and novel hypothesis that a subpopulation of cancer cells in each malignancy has the potential for tumor initiation and repopulation, the data in this area of research is still in its infancy. This review article is aimed at attempting to bring together research carried out so far in order to build an understanding of glioblastoma stem cells (GSCs). Initially, we consider GSCs at a morphological and cellular level, and then discuss important cell markers, signaling pathways and genetics. Furthermore, we highlight the diffi... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5660858 Sun, 01 Jan 2012 05:00:00 +0100 5660858 http://www.medworm.com/index.php?rid=5649977&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00572.x AbstractIn Creutzfeldt‐Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease‐associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico‐pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as Sporadic Fatal Insomnia.We observed two young patients with MM2‐thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nuc... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5649977 Sun, 01 Jan 2012 05:00:00 +0100 5649977 http://www.medworm.com/index.php?rid=5610974&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00566.x In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB‐inducing agents while sparing non‐stem cells. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5610974 Sun, 01 Jan 2012 05:00:00 +0100 5610974 http://www.medworm.com/index.php?rid=5599276&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2012.00564.x AbstractThe elaboration of novel pathogenic aspects of multiple sclerosis (MS) requires the analysis of well defined stages of lesion development. However, specimens of certain stages and lesion types are either present in small brain biopsies, insufficient in size for further molecular studies or available as formalin fixed and paraffin embedded (FFPE) material only. Therefore, application of current molecular biology techniques to FFPE tissue is warranted. We compared FFPE and frozen tissue by using quantitative PCR and report: (1) FFPE material is highly heterogeneous regarding the utility for transcript profiling of mRNAs; well preserved FFPE samples had about a hundred‐fold reduced sensitivity compared to frozen tissue, but gave similar results for genes of sufficient abundance. (... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5599276 Sun, 01 Jan 2012 05:00:00 +0100 5599276 http://www.medworm.com/index.php?rid=5526915&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00561.x Conclusion: A primitive non‐rhabdoid histophenotype is common amongst ATRTs and highlights the diagnostic importance of INI‐1 IHC. Epigenetically, the MGMT promoter is usually unmethylated in ATRT, suggesting that potential temozolomide ‐based chemotherapy may be of limited efficacy. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5526915 Thu, 22 Dec 2011 13:15:30 +0100 5526915 http://www.medworm.com/index.php?rid=5599277&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00560.x AbstractDouble‐transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mice express a chimeric mouse/human APP bearing the Swedish mutation (Mo/HuAPP695swe) and a mutant human PS1‐dE9 both causative of familial Alzheimer's disease (FAD). Transgenic mice show impaired memory and learning performance from the age of 6 months onwards. Double‐transgenic APP/PS1 mice express altered APP and PS1 mRNAs and proteins, reduced β‐secretase 1 (BACE1) mRNA and normal BACE1 protein, all of which suggest a particular mechanism of amyloidogenesis when compared with sporadic AD. The first β‐amyloid plaques in APP/PS1 mice appear at 3 months, and they increase in number and distribution with disease progression in parallel with increased levels of brain soluble β‐amyloid 1–42 and 1–40... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5599277 Tue, 20 Dec 2011 05:00:00 +0100 5599277 http://www.medworm.com/index.php?rid=5526916&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00560.x AbstractDouble‐transgenic APP/PS1 mice express a chimeric mouse/human amyloid precursor protein (APP) bearing the Swedish mutation (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1‐dE9) both causative of familial Alzheimer disease (FAD). Transgenic mice show impaired memory and learning performance from the age of six months onwards. Double‐transgenic APP/PS1 mice express altered APP and PS1 mRNAs and proteins, reduced BACE1 mRNA and normal BACE1 protein, all of which suggest a particular mechanism of amyloidogenesis when compared with sporadic AD. The first β‐amyloid plaques in APP/PS1 mice appear at three months and they increase in number and distribution with disease progression in parallel with increased levels of brain soluble β‐amyloid 1‐42 and 1‐40, but also wit... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5526916 Tue, 20 Dec 2011 05:00:00 +0100 5526916 http://www.medworm.com/index.php?rid=5488444&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00553.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488444 Sat, 10 Dec 2011 14:02:15 +0100 5488444 http://www.medworm.com/index.php?rid=5488443&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00556.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488443 Sat, 10 Dec 2011 14:02:14 +0100 5488443 http://www.medworm.com/index.php?rid=5488442&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00549.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488442 Sat, 10 Dec 2011 14:02:12 +0100 5488442 http://www.medworm.com/index.php?rid=5488441&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00555.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488441 Sat, 10 Dec 2011 14:02:10 +0100 5488441 http://www.medworm.com/index.php?rid=5488440&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00554.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488440 Sat, 10 Dec 2011 14:02:08 +0100 5488440 http://www.medworm.com/index.php?rid=5488438&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00546.x AbstractAutophagy is an intracellular lysosomal degradation process, which plays an important role in cell growth and development, and keeping cellular homeostasis in all eukaryotes. Autophagy has multiple physiological functions, including protein degradation, organelle turnover and response to stress. Emerging evidences support the notion that dysregulation of autophagy might be critical for pathogenesis of amyotrophic lateral sclerosis (ALS). The autophagy dysregulation in motor neurons of ALS may occur in different steps of the autophagic process. Recent studies have shown that two ALS associated proteins, TDP‐43 and superoxide dismutase 1 (SOD1), are involved in the abnormal autophagy regulation. Furthermore, it is reported that several genetic mutations in ALS disturb the autophagi... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488438 Sat, 10 Dec 2011 14:02:06 +0100 5488438 http://www.medworm.com/index.php?rid=5488437&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00545.x AbstractDementias are a varied group of disorders typically associated with memory loss, impaired judgment and/or language and by symptoms affecting other cognitive and social abilities to a degree that interferes with daily functioning. Alzheimer's disease (AD) is the most common cause of a progressive dementia, followed by dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), (VaD) and HIV‐associated neurocognitive disorders (HAND). The pathogenesis of this group of disorders has been linked to the abnormal accumulation of proteins in the brains of affected individuals, which in turn has been related to deficits in protein clearance. Autophagy is a key cellular protein clearance pathway with proteolytic cleavage and degradation via the ubiquitin–proteasome pathway represent... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488437 Sat, 10 Dec 2011 14:02:04 +0100 5488437 http://www.medworm.com/index.php?rid=5488436&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00544.x AbstractThe role of autophagy, traditionally considered a cellular homeostatic and recycling mechanism, has expanded dramatically to include an involvement in discrete stages of tumor initiation and development. Gliomas are the most aggressive and also the most common brain malignancies. Current treatment modalities have only a modest effect on patient outcomes. Resistance to apoptosis, a hallmark of most cancers, has driven the search for novel targets in cancer therapy. The autophagy lysosomal pathway is one such target that is being explored in multiple cancers including gliomas and is a promising avenue for further therapeutic development. This review summarizes our current understanding of the autophagic process and its potential utility as a target for glioma therapy. (Source: Brain ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488436 Sat, 10 Dec 2011 14:02:02 +0100 5488436 http://www.medworm.com/index.php?rid=5488435&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00543.x AbstractLysosomal myopathies are hereditary myopathies characterized morphologically by the presence of autophagic vacuoles. In mammals, autophagy plays an important role for the turnover of cellular components, particularly in response to starvation or glucagons. In normal muscle, autolysosomes or autophagosomes are typically inconspicuous. In distinct neuromuscular disorders, however, lysosomes become structurally abnormal and functionally impaired, leading to the accumulation of autophagic vacuoles in myofibers. In some instances, the accumulation of autophagic vacuoles can be a prominent feature, implicating autophagy as a contributor to disease pathomechanism and/or progression. At present, there are two disorders in the muscle that are associated with a primary defect in lysosomal pr... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488435 Sat, 10 Dec 2011 14:01:59 +0100 5488435 http://www.medworm.com/index.php?rid=5488434&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00547.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5488434 Sat, 10 Dec 2011 14:01:57 +0100 5488434 http://www.medworm.com/index.php?rid=5526917&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00552.x AbstractMeningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well‐defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high‐power fields, vasculo‐nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5526917 Tue, 15 Nov 2011 05:00:00 +0100 5526917 http://www.medworm.com/index.php?rid=5410345&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00551.x AbstractCentral nervous system (CNS) tumors in Von Hippel‐Lindau syndrome (VHL) include hemangioblastomas and metastatic clear cell renal cell carcinomas (Met CCRCC). While these tumors often show similar histologic features, differentiating them is of significant importance as Met CCRCC are higher‐grade tumors with worse prognosis. No single current immunohistochemical marker unequivocally differentiates between these two entities. MicroRNAs (miRNA) are non‐coding cellular small RNA molecules that play an important role in cancer. We hypothesized that hemangioblastomas and Met CCRCC display distinct miRNA signatures enabling their histologic differentiation. MiRNAs were profiled in 10 cases each of hemangioblastomas, Met CCRCC and primary CCRCC. Ten miRNAs had greater abundance (inc... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5410345 Tue, 15 Nov 2011 05:00:00 +0100 5410345 http://www.medworm.com/index.php?rid=5459475&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00557.x In this study we investigate ECM organization in primary sensory, secondary and associative areas of the temporal and occipital lobe. By detecting all major PN components we show that the distribution, structure and molecular properties of PNs remain unchanged in AD. Intact PNs occurred in close proximity to amyloid plaques and were even located within their territory. Counting of PNs revealed no significant alteration in AD. Moreover, neurofibrillary tangles never occurred in neurons associated with PNs. ACs were only lost in the core of amyloid plaques in parallel with the loss of synaptic profiles. In contrast, hyaluronan was enriched in the majority of plaques. We conclude that the loss of brevican is associated with the loss of synapses, while PNs and related matrix components resist ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5459475 Tue, 01 Nov 2011 04:00:00 +0100 5459475 http://www.medworm.com/index.php?rid=5410344&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00552.x AbstractMeningeal Solitary Fibrous Tumors and haemangiopericytomas (HPC) are distinct entities in the WHO classification of CNS tumors while they belong to the same spectrum of tumors in other locations. Well‐defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per ten high‐power fields, vasculo‐nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features b... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5410344 Tue, 01 Nov 2011 04:00:00 +0100 5410344 http://www.medworm.com/index.php?rid=5401646&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00550.x AbstractNumerous inflammatory conditions are associated with elevated YKL‐40 expression by infiltrating macrophages. Thus we were surprised to observe minimal macrophage and abundant astrocyte expression of YKL‐40 in neuroinflammatory conditions. The aims of the current study were to better delineate this discrapancy, characterize the factors that regulate YKL‐40 expression in macrophages and astrocytes and study whether YKL‐40 expression correlates with cell morphology and/or activation state. In vitro, macrophages expressed high levels of YKL‐40 that was induced by classical activation and inhibited by alternative activation. Cytokines released from macrophages induced YKL‐40 transcription in astrocytes that was accompanied by morphological changes and altered astrocytic moti... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5401646 Tue, 01 Nov 2011 04:00:00 +0100 5401646 http://www.medworm.com/index.php?rid=5389801&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00548.x In conclusion, by using this transgenic reporter mouse in experimental models of perinatal complications, we could assess NF‐κB activity in vivo and subsequently determine the cellular origin in the tissues. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5389801 Tue, 01 Nov 2011 04:00:00 +0100 5389801 http://www.medworm.com/index.php?rid=5316816&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00533.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316816 Sat, 15 Oct 2011 15:14:32 +0100 5316816 http://www.medworm.com/index.php?rid=5316815&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00527.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316815 Sat, 15 Oct 2011 15:14:30 +0100 5316815 http://www.medworm.com/index.php?rid=5316814&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00529.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316814 Sat, 15 Oct 2011 15:14:28 +0100 5316814 http://www.medworm.com/index.php?rid=5316813&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00528.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316813 Sat, 15 Oct 2011 15:14:26 +0100 5316813 http://www.medworm.com/index.php?rid=5316812&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00536.x AbstractEpigenetic regulation of gene expression by DNA methylation and histone modification is frequently altered in human cancers including gliomas, the most common primary brain tumors. In diffuse astrocytic and oligodendroglial gliomas, epigenetic changes often present as aberrant hypermethylation of 5′‐cytosine‐guanine (CpG)‐rich regulatory sequences in a large variety of genes, a phenomenon referred to as glioma CpG island methylator phenotype (G‐CIMP). G‐CIMP is particularly common but not restricted to gliomas with isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) mutation. Recent studies provided a mechanistic link between these genetic mutations and the associated widespread epigenetic modifications. Specifically, 2‐hydroxyglutarate, the oncometabolite produced by mutan... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316812 Sat, 15 Oct 2011 15:14:10 +0100 5316812 http://www.medworm.com/index.php?rid=5316811&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00534.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316811 Sat, 15 Oct 2011 15:14:08 +0100 5316811 http://www.medworm.com/index.php?rid=5316809&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00542.x ABSTRACTQuantifying antigens in formalin‐fixed tissue is challenging and limits investigation in population‐based studies of brain aging. To address this major limitation, we have developed a new technique that we call “Histelide”: immunohistochemistry (HIST‐) and ELISA (‐EL‐) performed on a glass slide (‐IDE). We validated Histelide in sections of prefrontal cortex from 20 selected cases: 12 subjects with clinically and neuropathologically diagnosed Alzheimer's disease (AD), either autosomal dominant or late‐onset forms, and 8 clinical and neuropathologic Controls. AD cases had significantly increased amyloid beta (Aβ) peptide and paired helical filament– (PHF‐) tau per area of neocortex that was proteinase K‐sensitive, and significantly decreased amount of synapt... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316809 Sat, 15 Oct 2011 15:13:19 +0100 5316809 http://www.medworm.com/index.php?rid=5305861&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00540.x AbstractThe locus ceruleus is among the earliest affected brain regions in Parkinson's disease (PD) showing Lewy body pathology and neuronal loss. To improve our understanding of the pathogenesis of PD, we performed the first proteomic analysis ever of post‐mortem locus ceruleus tissue of six pathologically confirmed PD patients, and six age‐ and gender‐matched non‐neurological controls. In total 2495 proteins were identified, of which 87 proteins were differentially expressed in the locus ceruleus of PD patients compared to controls. The majority of these differentially expressed proteins are known to be involved in processes that have been implicated in the pathogenesis of PD previously, including mitochondrial dysfunction, oxidative stress, protein misfolding, cytoskeleton dysre... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5305861 Tue, 11 Oct 2011 04:00:00 +0100 5305861 http://www.medworm.com/index.php?rid=5365294&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00539.x AbstractBeta‐amyloid (Aβ) plaques and local inflammation are central to the pathogenesis of Alzheimer's disease. Although an association between circulating pentameric C‐reactive protein (pCRP) and Alzheimer's disease has been reported no pathomechanistic link has been established. We hypothesized that Aβ plaques induce the dissociation of pCRP to individual monomers (mCRP), which possess strong pro‐inflammatory properties not shared with pCRP and localizing inflammation to Alzheimer's plaques. pCRP was incubated with Aβ plaques generated in vitro and with non‐aggregated Aβ42 peptide. pCRP dissociation to mCRP was found only when co‐incubated with Aβ plaques. Furthermore, sections of frontal cortex from brains of patients with and without Alzheimer's disease were stained wit... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5365294 Thu, 22 Sep 2011 04:00:00 +0100 5365294 http://www.medworm.com/index.php?rid=5252052&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00538.x AbstractProgressive multifocal leukoencephalopathy (PML) and JCV granular cell neuronopathy occur secondary to JCV polyomavirus (JCV) infection of oligodendrocytes and cerebellar granular cell neurons (CGNs) during immunosuppression. Pure populations of astrocytes, oligodendrocytes, CGNs and microglia from frontal cortex and cerebellum of 17 non‐PML patients (9 immunocompetent; 8 immunosuppressed) were isolated by laser capture microdissection (LCM). JCV large T antigen (LT) DNA was detected by triple nested PCR. Sequence analysis was performed to assess LT gene variation.JCV DNA was detected in oligodendrocytes, astrocytes and CGNs of non‐PML brains. The most common site for viral latency was cortical oligodendrocytes (65% of samples analysed). Immunosuppressed patients were significa... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5252052 Thu, 22 Sep 2011 04:00:00 +0100 5252052 http://www.medworm.com/index.php?rid=5252051&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00537.x AbstractIt is well known that cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). We have analyzed the function of CD300f immunoreceptor in a model of excitotoxic rat brain damage. First, to explore the presence of endogenous ligand(s) for this receptor we used a human CD300f‐Ig soluble protein and confocal microscopy, showing specific staining mainly in CNS white matter and on the surface of oligodendrocytes and certain astrocytes. Next, we demonstrated in a model of in vivo rat brain excitotoxic damage that the overexpression of human CD300f induced a significant reduction in the lesion volume. To validate these results, we cloned the rat ortholog of CD300f protein (rCD300f). The overexpression of rCD30... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5252051 Thu, 22 Sep 2011 04:00:00 +0100 5252051 http://www.medworm.com/index.php?rid=5365295&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00531.x AbstractRelease of interleukin (IL)‐1β from immunocompetent cells requires formation of the NACHT, LLR and PYD domains‐containing protein 3 (NLRP3) inflammasome and caspase 1 activation. Adenosine 5′‐triphosphate (ATP), acting on the P2X7 receptor, is one factor that stimulates inflammasome assembly. We show that a novel specific P2X7 receptor antagonist, GSK1370319A, inhibits ATP‐induced increase in IL‐1β release and caspase 1 activation in lipopolysaccharide (LPS)‐primed mixed glia by blocking assembly of the inflammasome in a pannexin 1‐dependent manner. GSK1370319A also inhibits ATP‐induced subregion‐specific neuronal loss in hippocampal organotypic slice cultures, which is dependent on its ability to prevent inflammasome assembly in glia. Significantly, GSK137031... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5365295 Tue, 20 Sep 2011 04:00:00 +0100 5365295 http://www.medworm.com/index.php?rid=5239867&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00531.x ABSTRACTRelease of IL‐1β from immunocompetent cells requires formation of the NLRP3 inflammasome and caspase‐1 activation. Adenosine 5’‐triphosphate (ATP), acting on the P2X7 receptor, is one factor that stimulates inflammasome assembly. We show that a novel specific P2X7 receptor antagonist, GSK1370319A, inhibits ATP‐induced increase in interleukin‐1β (IL‐1β) release and caspase‐1 activation in lipopolysaccharide (LPS)‐primed mixed glia by blocking assembly of the inflammasome in a pannexin 1‐dependent manner. GSK1370319A also inhibits ATP‐induced subregion specific neuronal loss in hippocampal organotypic slice cultures which is dependent on its ability to prevent inflammasome assembly in glia. Significantly GSK1370319A attenuates age‐related deficits in long t... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5239867 Tue, 20 Sep 2011 04:00:00 +0100 5239867 http://www.medworm.com/index.php?rid=5389802&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00530.x Abstractα‐Synuclein (α‐Syn) is a neuronal protein that accumulates progressively in Parkinson's disease (PD) and related synucleinopathies. Attempting to identify cellular factors that affect α‐Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α‐Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA), a 22:6 PUFA, affects α‐Syn oligomerization by activating retinoic X receptor (RXR) and peroxisome proliferator‐activated receptor γ2 (PPARγ2). In addition, we show that dietary changes in brain DHA levels affect α‐Syn cytopathology in mice transgenic for the PD‐causing A53T mutation in human α‐Syn. A diet enriched in DHA, an activating ligand of RXR, increased the accumulation of ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5389802 Mon, 19 Sep 2011 04:00:00 +0100 5389802 http://www.medworm.com/index.php?rid=5239869&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00532.x In this study, the prognostic relevance of IDH1/2 mutations in 74 GCs (43 type 1 and 31 type 2) was evaluated. We detected 33 (44.6%) IDH1 mutations, including R132H and R132S, by bidirectional Sanger sequencing. No mutations were detected in IDH2. The percentage of two‐year overall survival for wild‐type IDH1 patients was 46% versus 72% for patients with IDH1‐mutated tumors. Mutations of IDH1 were strongly correlated with both increased overall survival (OS) and progression‐free survival (PFS) in patients with type 2 GCs, and IDH1 mutations were also an independent prognostic factor predicting increased OS and PFS in type 2 GC patients in multivariate analysis. However, IDH1 mutations did not correlate with survival outcomes in patients with type 1 GCs. Finally, the subgroup of GC... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5239869 Mon, 19 Sep 2011 04:00:00 +0100 5239869 http://www.medworm.com/index.php?rid=5239868&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00530.x Abstractα‐synuclein (α‐Syn) is a neuronal protein that accumulates progressively in Parkinson's disease and related synucleinopathies. Attempting to identify cellular factors that affect α‐Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α‐Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA) a 22:6 PUFA affects α‐Syn oligomerization by activating retinoic X receptor (RXR) and peroxisome proliferator‐activated receptor γ2 (PPARγ2). In addition, we show that dietary changes in brain DHA levels affect α‐Syn cytopathology in mice transgenic for the Parkinson's disease‐causing A53T mutation in human α‐Syn. A diet enriched in docosahexaenoic acid, an activating ligand of RXR, inc... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5239868 Mon, 19 Sep 2011 04:00:00 +0100 5239868 http://www.medworm.com/index.php?rid=5316810&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00526.x AbstractTwo cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK‐1 and UK‐2, were investigated further by transmissions to wild‐type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrPSc immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild‐type mice; Pr... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5316810 Thu, 15 Sep 2011 04:00:00 +0100 5316810 http://www.medworm.com/index.php?rid=5228025&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00525.x AbstractPathological processing of tau protein during the formation and maturation of neurofibrillary tangles (NFTs) includes abnormal phosphorylation, conformational changes, and truncation of the C‐terminus at aspartic‐acid421 (apoptotic product) and glutamic‐acid391 residues. Abnormal phosphorylation and misfolding may serve as recognition signals for ubiquitin‐targeting and proteosomal processing. For this reason, we sought to determine whether ubiquitin‐targeting of tau is associated with particular tau modifications that herald specific stages of NFTs maturation in the hippocampus of Alzheimer's disease cases. Using multiple tau antibodies, we found that 30% of the total load of NFTs is ubiquitin‐associated. As reported previously ubiquitin immunoreactivity was associated... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228025 Thu, 15 Sep 2011 04:00:00 +0100 5228025 http://www.medworm.com/index.php?rid=5305860&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00541.x AbstractMultiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized by myelin and axonal pathology. In a viral model of MS, we tested whether axonopathy initiation and development are based on an impaired transport of neurofilaments.Spinal cords of Theiler's murine encephalomyelitis virus (TMEV)‐infected and mock‐infected mice and TMEV infected neuroblastoma N1E‐115 cells were analyzed by microarray analysis, light microscopy and electron and laser confocal microscopy. In vivo axonal accumulation of non‐phosphorylated neurofilaments after TMEV infection revealed a temporal development due to impairments of the axonal traffic consisting of the down‐regulation of kinesin family member 5A, dynein cytoplasmic heavy chain 1, tau‐1 and β‐tubulin III expr... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5305860 Thu, 01 Sep 2011 04:00:00 +0100 5305860 http://www.medworm.com/index.php?rid=5252050&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00539.x AbstractBeta‐amyloid plaques and local inflammation are central to the pathogenesis of Alzheimer's disease. Although an association between circulating pentameric CRP (pCRP) and Alzheimer's disease has been reported no pathomechanistic link has been established. We hypothesized that beta‐amyloid plaques induce the dissociation of pCRP to individual monomers (mCRP), which possess strong pro‐inflammatory properties not shared with pCRP and localizing inflammation to Alzheimer's plaques.pCRP was incubated with beta‐amyloid (Aβ) plaques generated in vitro and with non‐aggregated Aβ42 peptide. pCRP dissociation to mCRP was found only when co‐incubated with beta‐amyloid plaques. Furthermore, sections of frontal cortex from brains of patients with and without Alzheimer's disease w... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5252050 Thu, 01 Sep 2011 04:00:00 +0100 5252050 http://www.medworm.com/index.php?rid=5239866&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00536.x AbstractEpigenetic regulation of gene expression by DNA methylation and histone modification is frequently altered in human cancers including gliomas, the most common primary brain tumors. In diffuse astrocytic and oligodendroglial gliomas, epigenetic changes often present as aberrant hypermethylation of 5’‐CpG‐rich regulatory sequences in a large variety of genes, a phenomenon referred to as glioma CpG island methylator phenotype (G‐CIMP). G‐CIMP is particularly common but not restricted to gliomas with IDH1 or IDH2 mutation. Recent studies provided a mechanistic link between these genetic mutations and the associated widespread epigenetic modifications. Specifically, 2‐hydroxyglutarate, the oncometabolite produced by mutant IDH1 and IDH2 proteins, has been shown to function a... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5239866 Thu, 01 Sep 2011 04:00:00 +0100 5239866 http://www.medworm.com/index.php?rid=5228024&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00526.x AbstractTwo cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK‐1 and UK‐2, were investigated further by transmissions to wild type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and sub‐passage, incubation period (IP) of disease, PrPSc immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterise the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild type mice; PrPSc deposition ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228024 Thu, 01 Sep 2011 04:00:00 +0100 5228024 http://www.medworm.com/index.php?rid=5147614&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00524.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5147614 Wed, 24 Aug 2011 13:53:10 +0100 5147614 http://www.medworm.com/index.php?rid=5147613&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00522.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5147613 Wed, 24 Aug 2011 13:53:08 +0100 5147613 http://www.medworm.com/index.php?rid=5147612&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00521.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5147612 Wed, 24 Aug 2011 13:53:06 +0100 5147612 http://www.medworm.com/index.php?rid=5147611&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00516.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5147611 Wed, 24 Aug 2011 13:52:50 +0100 5147611 http://www.medworm.com/index.php?rid=5228028&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00515.x In this study, we show that GBM cells with stem cell characteristics are resistant to lysis mediated by resting natural killer (NK) cells because of the expression of MHC class I molecules. However, GSCs are killed by lectin‐activated NK cells. Furthermore, in experiments using the therapeutic antibody CetuximAb, we show that GSCs are sensitive to antibody‐mediated cytotoxicity. We confirm the sensitivity of GSC to cytotoxicity carried out by IL2‐activated NK cells and tumor‐specific T cells. More importantly, we show that GSCs are more sensitive to NK and T cell‐mediated lysis relatively to their corresponding serum‐cultured GBM cells obtained from the same initial tumor specimen. Altogether, these results demonstrate the sensitivity of GSC to immune cell cytotoxicity and, the... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228028 Tue, 26 Jul 2011 04:00:00 +0100 5228028 http://www.medworm.com/index.php?rid=5228026&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00520.x AbstractThe neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques made of Aβ peptide, neurofibrillary tangles containing hyperphosphorylated tau protein and neuronal loss. The pro‐apoptotic kinase PKR can be activated by Aβ and can phosphorylate tau protein via GSK3β kinase activation. The activated form of PKR (pPKR) accumulates in affected neurons and could participate in neuronal degeneration in AD. The mechanism of abnormal PKR activation in AD is not elucidated but could be linked to the PKR activator PACT. PACT stainings, and levels were assessed in the brains of AD patients and in APP/PS1 knock‐in transgenic mice and in cell cultures exposed to stresses. We showed that PACT and pPKR colocalizations are enhanced in AD brains. Their levels are increased... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228026 Mon, 25 Jul 2011 04:00:00 +0100 5228026 http://www.medworm.com/index.php?rid=5064861&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00520.x ABSTRACTThe neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques made of Aβ peptide, neurofibrillary tangles containing hyperphosphorylated tau protein and neuronal loss. The pro‐apoptotic kinase PKR can be activated by Aβ and can phosphorylate tau protein via GSK3β kinase activation. The activated form of PKR (pPKR) accumulates in affected neurons and could participate in neuronal degeneration in AD. The mechanism of abnormal PKR activation in AD is not elucidated but could be linked to the PKR activator PACT. PACT stainings and levels were assessed in the brains of AD patients and in APP/PS1 knock‐in transgenic mice and in cell cultures exposed to stresses. We showed that PACT and pPKR co‐localisation are enhanced in AD brains. Their levels are enhanced... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5064861 Sun, 24 Jul 2011 23:00:00 +0100 5064861 http://www.medworm.com/index.php?rid=5228027&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00517.x AbstractThe blood–brain barrier (BBB) consists of dense contacts between endothelial cells, the tight junctions, which are complemented by membrane‐bound transporters belonging to the ATP‐binding cassette (ABC) transporter family. Liver X receptors (LXR) have previously been shown to stabilize the integrity of atherosclerotic noncerebral arteries. Their effects on ischemic cerebral vessels are still unknown. By delivering LXR agonists, T0901317 and GW3965, to mice submitted to 30 minutes intraluminal middle cerebral artery occlusion, we show that LXR activation reduces brain swelling and decreases BBB permeability by upregulating LXR's target calpastatin that deactivates calpain‐1/2, stabilizing p120 catenin. p120 catenin specifically interacts with RhoA and Cdc42, inactivating the... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228027 Mon, 18 Jul 2011 04:00:00 +0100 5228027 http://www.medworm.com/index.php?rid=5041665&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00517.x AbstractThe blood‐brain barrier consists of dense contacts between endothelial cells, the tight junctions, which are complemented by membrane‐bound transporters belonging to the ATP‐binding cassette (ABC) transporter family. Liver X receptors (LXR) have previously been shown to stabilize the integrity of atherosclerotic non‐cerebral arteries. Their effects on ischemic cerebral vessels was still unknown. By delivering LXR agonists, T0901317 and GW3965, to mice submitted to 30 min intraluminal middle cerebral artery occlusion, we show that LXR activation reduces brain swelling and decreases BBB permeability by upregulating LXR's target calpastatin that deactivates calpain‐1/2, stabilizing p120 catenin. p120 catenin specifically interacts with RhoA and Cdc42, inactivating the former... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5041665 Sun, 17 Jul 2011 23:00:00 +0100 5041665 http://www.medworm.com/index.php?rid=5041664&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00518.x ABSTRACTAccumulation of extracellular matrix (ECM) and glial scar formation are considered important factors for the failure of regeneration in CNS injury and multiple sclerosis. Theiler's murine encephalomyelitis (TME) as a model of multiple sclerosis served to evaluate the spatio‐temporal course of ECM alterations in demyelinating conditions. Microarray analysis revealed only mildly up‐regulated gene expression of ECM molecules, their biosynthesis pathways, and pro‐fibrotic factors, while up‐regulation of matrix remodeling enzymes was more prominent. Immunohistochemistry demonstrated progressive accumulation of chondroitin sulfate proteoglycans, glycoproteins and collagens within demyelinated TME lesions, paralleling the development of astrogliosis. Deposition of collagen IV, l... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5041664 Sun, 17 Jul 2011 23:00:00 +0100 5041664 http://www.medworm.com/index.php?rid=5071876&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00523.x AbstractMicroRNAs (miRNAs) regulate a variety of cellular processes via the regulation of multiple target genes. We screened 48 medulloblastomas for mutation, deletion, and amplification of nine miRNA genes which were selected on the basis of the presence of potential target sequences within the 3’‐untranslated region of the MYCC mRNA. Differential PCR revealed deletions in miR‐186 (15%), miR‐135a‐1 (33%), miR‐548d‐1 (42%), miR‐548d‐2 (21%) and miR‐512‐2 (33%) genes, whereas deletion or amplification was detected in miR‐135b (23%) and miR‐135a‐2 (15%). In miR‐33b, deletion, amplification or a mutation at the precursor miRNA were detected in 10% of medulloblastomas. Overall, 35/48 (73%) medulloblastomas had at least one alteration. Real‐time RT‐PCR revealed... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5071876 Thu, 30 Jun 2011 23:00:00 +0100 5071876 http://www.medworm.com/index.php?rid=5064860&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00515.x In this study, we show that GBM cells with stem‐cell characteristics are resistant to lysis mediated by resting NK cells due to the expression of MHC class I molecules. However, GSC are killed by lectin‐activated NK cells. Furthermore, in experiments using the therapeutic antibody CetuximAb, we show that GSC are sensitive to antibody‐mediated cytotoxicity. We confirm the sensitivity of GSC to cytotoxicity carried out by IL2‐activated NK cells and tumour‐specific T cells. More importantly, we show that GSC are more sensitive to NK and T cell‐mediated lysis relatively to their corresponding serum‐cultured GBM cells obtained from the same initial tumour specimen. Altogether, these results demonstrate the sensitivity of GSC to immune cell cytotoxicity and, therefore, strongly sug... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5064860 Thu, 30 Jun 2011 23:00:00 +0100 5064860 http://www.medworm.com/index.php?rid=5041663&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00519.x AbstractCortical tubers are malformations of cortical development in patients with tuberous sclerosis complex (TSC), and highly associated with pediatric intractable epilepsy. Recent evidence has shown that signaling mediated through vascular endothelial growth factor‐C (VEGF‐C) and its receptors, VEGFR‐2 and VEGFR‐3, has direct effects on both neurons and glial cells. To understand the potential role of VEGF‐C system in the pathogenesis of cortical tubers, we investigated the expression patterns of VEGF‐C signaling in cortical tubers compared to age‐matched normal control cortex (CTX). We found that VEGF‐C, VEGFR‐2 and VEGFR‐3 were clearly upregulated in tubers at both the mRNA and protein levels, compared to CTX. The in situ hybridization and immunostaining results de... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5041663 Thu, 30 Jun 2011 23:00:00 +0100 5041663 http://www.medworm.com/index.php?rid=4978647&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00514.x AbstractAvian influenza A virus H5N1 has the proven capacity to infect humans through cross‐species transmission, but to date efficient human‐to‐human transmission is limited. In natural avian hosts, animal models, and sporadic human outbreaks, H5N1 infection has been associated with neurological disease. We infected BALB/c mice intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune response during acute encephalitis. Using immunohistochemistry and in situ hybridization, we compared the time course of viral infection with activation of immunity. By 5 days post infection (DPI), mice had lost substantial body weight and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early as 1 DPI, while infected neurons were not observed until 4 DPI. H5N1 in... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4978647 Wed, 29 Jun 2011 19:52:36 +0100 4978647 http://www.medworm.com/index.php?rid=4978648&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00513.x AbstractWhilst a history of single traumatic brain injury (TBI) is associated with the later development of syndromes of cognitive impairment, such as Alzheimer's disease (AD), the long‐term pathology evolving after single TBI is poorly understood. However, a progressive tauopathy, chronic traumatic encephalopathy, is described in selected cohorts with a history of repetitive concussive / mild head injury. Here, post‐mortem brains from long‐term survivors of just a single TBI (1 to 47 years survival; n = 39) versus uninjured, age‐matched controls (n = 47) were examined for neurofibrillary tangles (NFTs) and amyloid‐β (Aβ) plaques using immunohistochemistry and thioflavin‐S staining. Detailed maps of findings permitted classification of pathology using semi‐quantitative scor... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4978648 Tue, 28 Jun 2011 23:00:00 +0100 4978648 http://www.medworm.com/index.php?rid=4971572&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00512.x In this study, we determined the levels MMP‐2 and MMP‐9 in plasma and their brain expression in CAA‐associated hemorrhagic stroke. Although MMP‐2 and MMP‐9 plasma levels did not differ among patients and controls, their brain expression was increased in perihematoma areas of CAA‐related hemorrhagic strokes compared to contralateral areas and non‐hemorrhagic brains. In addition, MMP‐2 reactivity was found in Aβ‐damaged vessels located far from the acute ICH and in chronic microbleeds. MMP‐2 expression was associated to endothelial cells, histocytes and reactive astrocytes, whereas MMP‐9 expression was restricted to inflammatory cells. In summary, MMP‐2 expression within and around Aβ‐compromised vessels might contribute to the vasculature fatal fate, triggering a... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4971572 Mon, 27 Jun 2011 22:40:17 +0100 4971572 http://www.medworm.com/index.php?rid=5228029&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00511.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5228029 Fri, 24 Jun 2011 04:00:00 +0100 5228029 http://www.medworm.com/index.php?rid=4971573&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00511.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4971573 Thu, 23 Jun 2011 23:00:00 +0100 4971573 http://www.medworm.com/index.php?rid=4939696&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00510.x In this study we aimed to identify selective molecules that are present at this site. Myofibers of 4 biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled, and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected 9 extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of 9 proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine‐rich repeat proteins PRELP and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM an... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4939696 Sat, 18 Jun 2011 19:47:40 +0100 4939696 http://www.medworm.com/index.php?rid=4924575&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00503.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4924575 Mon, 13 Jun 2011 23:33:11 +0100 4924575 http://www.medworm.com/index.php?rid=4924573&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00502.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4924573 Mon, 13 Jun 2011 23:33:10 +0100 4924573 http://www.medworm.com/index.php?rid=4924572&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00497.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4924572 Mon, 13 Jun 2011 23:33:09 +0100 4924572 http://www.medworm.com/index.php?rid=4924571&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00496.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4924571 Mon, 13 Jun 2011 23:33:09 +0100 4924571 http://www.medworm.com/index.php?rid=4924570&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00498.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4924570 Mon, 13 Jun 2011 23:33:04 +0100 4924570 http://www.medworm.com/index.php?rid=5133647&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00510.x In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine‐rich repeat proteins proline arginine‐rich end leucine‐rich repeat protein (PRELP) and biglycan were deposited precisely at myofi... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5133647 Mon, 13 Jun 2011 23:00:00 +0100 5133647 http://www.medworm.com/index.php?rid=4939697&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00509.x AbstractProgressive aggregation of α‐synuclein (αS) from pale bodies (PBs) and extension from Lewy neurites (LNs) are candidate mechanisms for Lewy body (LB) formation. To identify how aggregation of αS is related to its extension along neurites, 60‐µm‐thick brainstem sections of Parkinson disease (PD) patients were prepared for three‐dimensional (3D) reconstruction of αS‐positive neurites with neurofilament (NF) and thiazin red (TR), a fluorochrome with an affinity to solid aggregates. This demonstrated 3D layering of αS surrounded by NF with the aggregates probed by TR in the center, corresponding to the eosinophilic core of mature LBs. This eosinophilic/TR‐positive profile, characteristically absent in PBs, premature counterpart of LBs, was similarly absent in some LNs... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4939697 Mon, 13 Jun 2011 23:00:00 +0100 4939697 http://www.medworm.com/index.php?rid=5064862&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00508.x AbstractGerstmann–Sträussler–Scheinker (GSS) P102L disease is a familial form of a transmissible spongiform encephalopathy (TSE) that can present with or without vacuolation of neuropil. Inefficient disease transmission into 101LL transgenic mice was previously observed from GSS P102L without vacuolation. However, several aged, healthy mice had large plaques composed of abnormal prion protein (PrPd). Here we perform the ultrastructural characterization of such plaques and compare them with PrPd aggregates found in TSE caused by an infectious mechanism. PrPd plaques in 101LL mice varied in maturity, with some being composed of deposits without visible amyloid fibrils. PrPd was present on cell membranes in the vicinity of all types of plaques. In contrast to the unicentric plaques seen ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5064862 Thu, 02 Jun 2011 23:00:00 +0100 5064862 http://www.medworm.com/index.php?rid=5133648&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00506.x AbstractMutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes occur frequently in diffuse astrocytoma and oligodendroglioma. The consecutive amino acid substitutions in the mutant proteins result in a gain of the function to catalyze the reduction of alpha‐ketoglutarate to 2‐hydroxyglutarate (2HG). So far, all investigated IDH mutations share this gain of function. We here describe a method to detect 2HG levels in archival formalin‐fixed paraffin‐embedded tumor specimens by stable isotope dilution using gas chromatography followed by mass spectrometry (GC/MS). While 2HG levels are notably decreased during the routine embedding process, preserved amounts are still sufficient to indicate a mutation. Detection of 2HG in archival specimens could make routinely processed tissue ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5133648 Wed, 01 Jun 2011 23:00:00 +0100 5133648 http://www.medworm.com/index.php?rid=4886891&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00506.x AbstractMutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes occur frequently in diffuse astrocytoma and oligodendroglioma. The consecutive amino acid substitutions in the mutant proteins result in a gain of the function to catalyze the reduction of alpha‐ketoglutarate to 2‐hydroxyglutarate (2HG). So far, all investigated IDH mutations share this gain of function. We here describe a method to detect 2HG levels in archival formalin‐fixed paraffin‐embedded tumor specimens by stable isotope dilution using gas‐chromatography followed by mass‐spectrometry (GC/MS). While 2HG levels are notably decreased during the routine embedding process, preserved amounts are still sufficient to indicate a mutation. Detection of 2HG in archival specimens could make routinely processed tis... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4886891 Wed, 01 Jun 2011 23:00:00 +0100 4886891 http://www.medworm.com/index.php?rid=4866399&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00504.x AbstractPerinatal brain injury including white matter damage (WMD) is highly related to sensory, motor or cognitive impairments in humans born prematurely. Our aim was to examine the neuroanatomical, functional and behavioral changes in adult rats that experienced prenatal ischemia (PI), thereby inducing WMD. PI was induced by unilateral uterine artery ligation at E17 in pregnant rats. We assessed performances in gait on treadmill, cognitive abilities, topographical organization of maps and numerical density of neurons and glial cells in both primary motor and somatosensory cortices, neuronal and glial density in the hippocampus and prefrontal cortex, as well as axonal degeneration and astrogliosis in white matter tracts. We found WMD in the corpus callosum and brainstem, and associated wi... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4866399 Wed, 25 May 2011 23:00:00 +0100 4866399 http://www.medworm.com/index.php?rid=5133650&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00500.x This study sought to determine the role of pathogenic DNA variants in the HCN1–4 genes in a large SUDEP cohort collected from 1993 to 2009. Post‐mortem DNA samples were amplified and analyzed for each HCN exon. Genetic analysis in 48 SUDEP cases (age range 12–82 years) identified six novel and three previously reported nonsynonymous (amino acid changing) variants in HCN1 (n = 1), HCN2 (n = 2), HCN3 (n = 2) and HCN4 (n = 4). The Phe738Cys and Pro802Ser variants in HCN2, and Gly973Arg in HCN4 were absent in control alleles and affecting highly conserved residues in the carboxyl‐cytoplasmic tail region. Our results support a pathogenic link between the heart and brain in SUDEP, mediated by the HCN neuro‐cardiac ion channel genes. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5133650 Tue, 24 May 2011 23:00:00 +0100 5133650 http://www.medworm.com/index.php?rid=4856262&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00500.x This study sought to determine the role of pathogenic DNA variants in the HCN1‐4 genes in a large SUDEP cohort collected from 1993‐2009. Post‐mortem DNA samples were amplified and analysed for each HCN exon. Genetic analysis in 48 SUDEP cases (age range 12‐82 years) identified 6 novel and 3 previously reported non‐synonymous (amino acid changing) variants in HCN1 (n = 1), HCN2 (n = 2), HCN3 (n = 2) and HCN4 (n = 4). The Phe738Cys and Pro802Ser variants in HCN2 and Gly973Arg in HCN4 were absent in control alleles and affecting highly conserved residues in the carboxyl‐cytoplasmic tail region. Our results support a pathogenic link between the heart and brain in SUDEP, mediated by the HCN neuro‐cardiac ion channel genes. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4856262 Tue, 24 May 2011 23:00:00 +0100 4856262 http://www.medworm.com/index.php?rid=4896726&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00508.x AbstractGerstmann‐Sträussler‐Scheinker (GSS) P102L disease is a familial form of a transmissible spongiform encephalopathy (TSE) that can present with or without vacuolation of neuropil. Inefficient disease transmission into 101LL transgenic mice was previously observed from GSS P102L without vacuolation. However several aged, healthy mice had large plaques composed of abnormal prion protein (PrPd). Here we perform the ultrastructural characterisation of such plaques and compare them with PrPd aggregates found in TSE caused by an infectious mechanism. PrPd plaques in 101LL mice varied in maturity with some being composed of deposits without visible amyloid fibrils. PrPd was present on cell membranes in the vicinity of all types of plaques. In contrast to the unicentric plaques seen in... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4896726 Sat, 30 Apr 2011 23:00:00 +0100 4896726 http://www.medworm.com/index.php?rid=4886890&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00507.x AbstractRRP22 (Ras‐related protein on chromosome 22) has been suggested as a candidate tumor suppressor in human cancers. Investigating a panel of 70 human gliomas we found a frequent decrease in the RRP22 mRNA expression levels (67%), preferentially in high‐grade gliomas (WHO grades III and IV) as compared to low‐grade gliomas (WHO grade II). Moreover, reduced RRP22 mRNA expression was associated with shorter overall survival in 180 glioblastoma patients included in the NIH REMBRANDT database. Decreased RRP22 expression levels were in part explained by 5’‐CpG island hypermethylation and increased by the treatment with the demethylating agent 5‐aza‐2’‐deoxycytidine in glioblastoma cell lines. In addition, the in vitro treatment with the histone deacetylase inhibitor trich... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4886890 Sat, 30 Apr 2011 23:00:00 +0100 4886890 http://www.medworm.com/index.php?rid=4866398&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00505.x AbstractComplex signaling cross‐talks between different growth factor cascades orchestrate the primary brain cancer development. Among the frequent deregulated oncogenic pathways, the ligand activated wild‐type EGFR, constitutively activated EGFRvIII mutant and sonic hedgehog pathways have attracted much attention due to their pivotal roles in pediatric medulloblastomas and adult glioblastoma multiformes (GBMs). The enhanced expression levels and activation of EGFR, EGFRvIII mutant and hedgehog signaling elements can provide key roles for the sustained growth, migration and local invasion of brain tumor‐initiating cells (BTICs) and their progenies, resistance to current therapies and disease relapse. These tumorigenic cascades also can cooperate with Wnt/β‐catenin, Notch, platelet... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4866398 Sat, 30 Apr 2011 23:00:00 +0100 4866398 http://www.medworm.com/index.php?rid=4856261&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00501.x We report here that ceramide accumulates in reactive astrocytes in active lesions of multiple sclerosis and periventricular leukomalacia, as well as in animal models of demyelination. Serine palmitoyltransferase, the rate‐limiting enzyme for ceramide de novo biosynthesis, was consistently upregulated in reactive astrocytes in the cuprizone mouse model of demyelination. Mass spectrometry confirmed the upregulation of specific ceramides during demyelination and revealed a concomitant increase of sphingosine as well as a suppression of sphingosine‐1‐phosphate, a potent signaling molecule with key roles in cell survival and mitogenesis. Importantly, this altered sphingolipid metabolism during demyelination was restored upon active remyelination. In culture, ceramide acted synergistically... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4856261 Sat, 30 Apr 2011 23:00:00 +0100 4856261 http://www.medworm.com/index.php?rid=4737341&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00495.x ABSTRACTMultiple Sclerosis (MS) is a demyelinating/inflammatory disease of the central nervous system. Relapsing‐remitting MS is characterised by a relapsing phase with clinical symptoms and the production of inflammatory cell infiltrates, and a period of remission during which patients recover partially. Myeloid‐derived suppressor cells (MDSCs) are immature cells capable of suppressing the inflammatory response through Arginase‐I (Arg‐I) activity, among other mechanisms. Here we have identified Arg‐I+‐MDSCs in the spinal cord during experimental autoimmune encephalomyelitis (EAE), cells that were largely restricted to the demyelinating plaque and that always exhibited the characteristic MDSC surface markers Arg‐I/CD11b/Gr‐1/M‐CSF1R. The presence and density of Arg‐I+�... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4737341 Fri, 22 Apr 2011 19:15:58 +0100 4737341 http://www.medworm.com/index.php?rid=4915439&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00494.x AbstractThe second International Workshop for Glycosylation Defects in Muscular Dystrophies took place on November 11 and 12, 2010 in Charlotte, North Carolina, USA. The meeting was hosted by the Carolinas Medical Center with financial support from the Carolinas Muscular Dystrophy Research Endowment at the Carolinas HealthCare Foundation, the Muscular Dystrophy Association and funds raised by the “Jeans, Genes & Geniuses” event organized by Jane and Luther Lockwood. Since conducting the first workshop in May 2008, significant progress has been made in a subset of muscular dystrophies associated with defects in alpha‐dystroglycan (α‐DG) glycosylation. New findings on α‐DG glycosylation and creation of novel animal models have expanded our understanding of the disease mechani... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4915439 Tue, 19 Apr 2011 23:00:00 +0100 4915439 http://www.medworm.com/index.php?rid=4737342&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00494.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4737342 Tue, 19 Apr 2011 23:00:00 +0100 4737342 http://www.medworm.com/index.php?rid=4711187&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00479.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4711187 Thu, 14 Apr 2011 20:58:51 +0100 4711187 http://www.medworm.com/index.php?rid=4711186&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2008.00487.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4711186 Thu, 14 Apr 2011 20:58:50 +0100 4711186 http://www.medworm.com/index.php?rid=4711185&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00483.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4711185 Thu, 14 Apr 2011 20:58:49 +0100 4711185 http://www.medworm.com/index.php?rid=4711184&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00482.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4711184 Thu, 14 Apr 2011 20:58:48 +0100 4711184 http://www.medworm.com/index.php?rid=4711183&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00484.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4711183 Thu, 14 Apr 2011 20:58:42 +0100 4711183 http://www.medworm.com/index.php?rid=4688045&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00492.x AbstractWe recently reported that the vast majority (>90%) of low‐grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one of the following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% of cases were triple‐negative (i.e. lacking any of these alterations). In the present study, array CGH in 15 triple‐negative WHO grade II gliomas (8 diffuse astrocytomas and 7 oligodendrogliomas) showed loss at 9p21 (p14ARF, p15INK4b, p16INK4a loci) and 13q14–13q32 (containing the RB1 locus) in 3 cases and 2 cases, respectively. Further analyses in 31 triple‐negative cases as well as a total of 160 non‐triple‐negative cases revealed that alterations in the RB1 pathway (homozygous deletion and promoter methylation of... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4688045 Tue, 05 Apr 2011 23:00:00 +0100 4688045 http://www.medworm.com/index.php?rid=4646096&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00489.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4646096 Sun, 27 Mar 2011 23:00:00 +0100 4646096 http://www.medworm.com/index.php?rid=5064863&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00491.x The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 5... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=5064863 Thu, 24 Mar 2011 00:00:00 +0100 5064863 http://www.medworm.com/index.php?rid=4856263&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00490.x In conclusion, this study supports the concept that PTX promotes EAE, at least in part, by inducing vascular changes necessary for the recruitment of patrolling leukocytes. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4856263 Tue, 22 Mar 2011 00:00:00 +0100 4856263 http://www.medworm.com/index.php?rid=4617801&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00488.x AbstractInflammatory resolution is an active, highly regulated process already encoded at the onset of inflammation and required to prevent the transition into chronic inflammation associated with spreading of tissue injury and exacerbated scarring. We introduce objective, quantitative measurements (resolution indices [Ri] and resolution plateau [RP]) to characterize inflammatory resolution and to determine the persistence (‘dwell time’) of differential leukocyte subpopulations at the lesion site after acute experimental spinal cord injury (SCI). The cell type‐specific resolution interval Ri (time between maximum cell numbers and the point when they are reduced to 50%) ranges from 1.2 days for neutrophils, 1.5 days for T‐lymphocytes, to 55 days for microglia/macrophages. Since the ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4617801 Tue, 22 Mar 2011 00:00:00 +0100 4617801 http://www.medworm.com/index.php?rid=4672504&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00485.x AbstractNumerous epidemiological studies have proposed a link between herpes simplex virus (HSV) infection and several common chronic neuropsychiatric and neurodegenerative diseases. Experimental HSV infection of mice can lead to chronic behavioral and neurological deficits and chronic pain. While neuron injury and loss are well‐documented consequences of the acute phase of infection, the pathologic consequences of latent HSV infection are poorly understood. To determine whether latent HSV infection can cause neuronal injury in mice, trigeminal ganglia (TG) derived from adult BALB/c mice 1, 12 and 31 weeks after corneal HSV type 1 (HSV‐1) inoculation were analyzed for evidence of productive or latent HSV‐1 infection, inflammation and changes in neuron size, density and number. We fou... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4672504 Fri, 04 Mar 2011 00:00:00 +0100 4672504 http://www.medworm.com/index.php?rid=4688044&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00493.x AbstractPrimary papillary tumors of the central nervous system and particularly the pineal region are rare. Papillary tumor of the pineal region (PTPR) is a recently described neoplasm that has been formally recognized in the 2007 World Health Organization Classification of Tumors of the Nervous System. Due to their rarity, further pheno‐ and genotypical observations as well as therapeutic experience are necessary to differentiate PTPR from other primary or secondary papillary tumors of this region. We herein present three cases of PTPR characterized by local recurrence in two of them. Primary and recurrent tumors were analyzed by immunohistochemistry and comparative genomic hybridization (CGH). From our results clonal chromosomal aberrations can be postulated which seems to be a feasibl... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4688044 Tue, 01 Mar 2011 00:00:00 +0100 4688044 http://www.medworm.com/index.php?rid=4628323&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00491.x The objectives are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to harmonize the healthcare of patients affected by PCNST. Over 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma 48.9%, all other neuroepithelial tumors 5%, meningioma 28.8%, nerve sheath tumor 8.4%, lymphoma 3.2% and others 5.7%. Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78%, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors are detailed for each histology, for example, out of 6053 glioblastomas [MA 63 years, male 59.4%, R 62%, 1611 were cryoprese... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4628323 Tue, 01 Mar 2011 00:00:00 +0100 4628323 http://www.medworm.com/index.php?rid=4617800&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00490.x In conclusion, this study supports the concept that PTX promotes EAE, at least in part, by inducing vascular changes necessary for the recruitment of patrolling leukocytes. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4617800 Tue, 01 Mar 2011 00:00:00 +0100 4617800 http://www.medworm.com/index.php?rid=4556048&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00486.x AbstractNeprilysin (NEP), which degrades Aβ, is expressed by neurons and cerebrovascular smooth muscle cells (CVSMCs). NEP immunolabeling is reduced within cerebral blood vessels of Alzheimer's disease (AD) patients with cerebral amyloid angiopathy (CAA). We have now measured NEP enzyme activity in leptomeningeal and purified cerebral cortical blood vessel preparations from control and AD patients with and without CAA. Measurements were adjusted for smooth muscle actin (SMA) to control for variations in CVSMC content. NEP activity was reduced in CAA, in both controls and AD. In leptomeningeal vessels, NEP activity was related to APOE genotype, being highest in ε2‐positive and lowest in ε4‐positive brains. To assess the role of NEP in protecting CVSMCs from Aβ toxicity, we measured ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4556048 Tue, 01 Mar 2011 00:00:00 +0100 4556048 http://www.medworm.com/index.php?rid=4546297&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00485.x AbstractNumerous epidemiological studies have proposed a link between herpes simplex virus (HSV) infection and several common chronic neuropsychiatric and neurodegenerative diseases. Experimental HSV infection of mice can lead to chronic behavioral and neurological deficits and chronic pain. While neuron injury and loss are well documented consequences of the acute phase of infection, the pathologic consequences of latent HSV infection are poorly understood. To determine whether latent HSV infection can cause neuronal injury in mice, trigeminal ganglia (TG) derived from adult BALB/c mice 1, 12, and 31 weeks after corneal herpes simplex virus type 1 (HSV‐1) inoculation were analyzed for evidence of productive or latent HSV‐1 infection, inflammation, and changes in neuron size, density, ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4546297 Tue, 01 Mar 2011 00:00:00 +0100 4546297 http://www.medworm.com/index.php?rid=4503598&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00481.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4503598 Tue, 22 Feb 2011 18:41:54 +0100 4503598 http://www.medworm.com/index.php?rid=4474018&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00480.x AbstractRecent work has identified novel point mutations in isocitrate dehydrogenase 1 (IDH1) in the majority of WHO grade II and III infiltrative gliomas and secondary grade IV glioblastomas. Gangliogliomas consist of neoplastic ganglion and glial cells and, in contrast to infiltrative gliomas, are generally indolent. Yet distinguishing between a ganglioglioma and an infiltrative glioma with admixed grey matter can be difficult, perhaps accounting for some “gangliogliomas” that ultimately show aggressive behavior. In this multi‐institutional study, 98 cases originally diagnosed as ganglioglioma were analyzed for IDH1 mutations, 86 of which had follow‐up data available. Eight cases (8.2%) were positive for R132H IDH1 mutations; six had silent IDH2 mutations, and two had nonsense ID... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4474018 Mon, 14 Feb 2011 21:38:27 +0100 4474018 http://www.medworm.com/index.php?rid=4401918&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00473.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4401918 Thu, 27 Jan 2011 17:22:56 +0100 4401918 http://www.medworm.com/index.php?rid=4401917&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00472.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4401917 Thu, 27 Jan 2011 17:22:55 +0100 4401917 http://www.medworm.com/index.php?rid=4401916&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00471.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4401916 Thu, 27 Jan 2011 17:22:55 +0100 4401916 http://www.medworm.com/index.php?rid=4401915&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00470.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4401915 Thu, 27 Jan 2011 17:22:50 +0100 4401915 http://www.medworm.com/index.php?rid=4514227&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00476.x This study focused on one subtype of pituitary tumor, the prolactin (PRL) pituitary tumors, to identify molecular events associated with the aggressive and malignant phenotypes. We combined a comparative genomic hybridization and transcriptomic analysis of 13 PRL tumors classified as nonaggressive or aggressive. Allelic loss within the p arm region of chromosome 11 was detected in five of the aggressive tumors. Allelic loss in the 11q arm was observed in three of these five tumors, all three of which were considered as malignant based on the occurrence of metastases. Comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. Data filtering allowed us to highlight five deregulated genes (DGKZ, CD44, TSG101, ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4514227 Wed, 19 Jan 2011 00:00:00 +0100 4514227 http://www.medworm.com/index.php?rid=4508808&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00477.x We examined expression of the major cannabinoid receptors [(CBRs) cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)] and a key enzyme involved in synthesis of the endocannabinoid anandamide [N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD)] in autopsy brain samples from patients with MS. CB1 was expressed in neurons, injured axons, oligodendrocytes, macrophages/microglia, some astrocytes, endothelial cells, smooth muscle cells and pericytes. CB2 and NAPE‐PLD were localized to cerebral endothelial cells, pericytes, smooth muscle cells, astrocytes and macrophages/microglia. NAPE‐PLD immunoreactivity was also seen in neurons. Endothelial CB2 expression was greatest in chronic inactive plaques, and in areas was seen in segments of endothelium where the endothelial... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4508808 Wed, 19 Jan 2011 00:00:00 +0100 4508808 http://www.medworm.com/index.php?rid=4374094&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00476.x This study focused on one subtype of pituitary tumour, the prolactin pituitary tumours, to identify molecular events associated with the aggressive and malignant phenotypes. We combined a comparative genomic hybridization and transcriptomic analysis of 13 prolactin tumours classified as non‐aggressive or aggressive. Allelic loss within the p arm region of chromosome 11 was detected in five of the aggressive tumours. Allelic loss in the 11q arm was observed in three of these five tumours, all three of which were considered as malignant based on the occurrence of metastases. Comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. Data filtering allowed us to highlight five deregulated genes (DGKZ, CD44, ... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4374094 Wed, 19 Jan 2011 00:00:00 +0100 4374094 http://www.medworm.com/index.php?rid=4461478&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00474.x This study supports the hypothesis that expression of viral capsid proteins as self influences the extent of axonal pathology following Theiler's virus–induced demyelination. The findings provide insight into the role of axonal injury in the development of functional deficits that may have relevance to human demyelinating disease. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4461478 Tue, 11 Jan 2011 00:00:00 +0100 4461478 http://www.medworm.com/index.php?rid=4395830&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00478.x In conclusion, claudin‐6 immunohistochemistry is of limited sensitivity and specificity for the diagnosis of AT/RT and does not correlate with clinical behaviour. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4395830 Sat, 01 Jan 2011 00:00:00 +0100 4395830 http://www.medworm.com/index.php?rid=4374093&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00477.x We examined expression of the major cannabinoid receptors (CB1 and CB2) and a key enzyme involved in synthesis of the endocannabinoid anandamide (N‐acyl phosphatidylethanolamine phospholipase D, NAPE‐PLD) in autopsy brain samples from patients with multiple sclerosis. CB1 was expressed in neurons, injured axons, oligodendrocytes, macrophages/microglia, some astrocytes, endothelial cells, smooth muscle cells and pericytes. CB2 and NAPE‐PLD were localized to cerebral endothelial cells, pericytes, smooth muscle cells, astrocytes and macrophages/microglia. NAPE‐PLD immunoreactivity was also seen in neurons. Endothelial CB2 expression was greatest in chronic inactive plaques, and in areas was seen in segments of endothelium where the endothelial expression of adhesion molecules (VCAM‐... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4374093 Sat, 01 Jan 2011 00:00:00 +0100 4374093 http://www.medworm.com/index.php?rid=4357263&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00475.x AbstractSelective aquaporin‐4 (AQP4) loss and vasculocentric complement and immunoglobulin deposition are characteristic of neuromyelitis optica (NMO). We recently reported extensive AQP4 loss in demyelinated and myelinated layers of Baló's lesions without perivascular immunoglobulin and complement deposition. We aimed to reappraise AQP4 expression patterns in NMO and multiple sclerosis (MS). We evaluated AQP4 expression relative to glial fibrillary acidic protein, extent of demyelination, lesion staging (CD68 staining for macrophages), and perivascular deposition of complement and immunoglobulin in 11 cases with NMO and NMO spectrum disorders (NMOSD), five with MS, and 30 with other neurological diseases. The lesions were classified as actively demyelinating (n= 66), chronic active (n=... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4357263 Sat, 01 Jan 2011 00:00:00 +0100 4357263 http://www.medworm.com/index.php?rid=4333381&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2011.00474.x This study supports the hypothesis that expression of viral capsid proteins as self influences the extent of axonal pathology following Theiler's virus‐induced demyelination. The findings provide insight into the role of axonal injury in the development of functional deficits that may have relevance to human demyelinating disease. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4333381 Sat, 01 Jan 2011 00:00:00 +0100 4333381 http://www.medworm.com/index.php?rid=4261147&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00469.x AbstractEarly‐onset familial Alzheimer's disease caused by presenilin‐1 mutation E280A (PS1‐E280A) presents wide clinical and neuropathological variability. We characterised clinically and neuropathologically PS1‐E280A focusing in cerebellar involvement and compared it with early‐onset sporadic Alzheimer's disease (EOSAD). Twelve E280A brains and 12 matched EOSAD brains were analysed for beta‐amyloid and hyperphosphorylated tau (pTau) morphology, beta‐amyloid subspecies 1‐40, 1‐42 levels, pTau levels, and expression of stress kinases in frontal cortex and cerebellum. The data were correlated to clinical and genetic findings. We observed higher beta‐amyloid load, beta‐amyloid 1‐42 and pTau concentrations in frontal cortex of PS1‐E280A compared with EOSAD. High beta... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4261147 Wed, 15 Dec 2010 21:02:07 +0100 4261147 http://www.medworm.com/index.php?rid=4261148&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00468.x AbstractDiffuse intrinsic pontine glioma (DIPG) is a fatal malignancy due to its diffuse infiltrative growth pattern. Translational research suffers from the lack of a representative DIPG animal model. Hence, human E98 glioma cells were stereotactically injected into the pons of nude mice. The E98 DIPG tumors presented a strikingly similar histhopathology to autopsy material of a DIPG patient, including diffuse and perivascular growth, brainstem‐ and supratentorial invasiveness and leptomeningeal growth. MRI was effectively employed to image the E98 DIPG tumor. [18F]FLT PET imaging was applied to assess the subcutaneous (s.c.) E98 tumor proliferation status but no orthotopic DIPG activity could be visualized. Next, E98 cells were cultured in vitro and engineered to express firefly lucife... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4261148 Wed, 15 Dec 2010 00:00:00 +0100 4261148 http://www.medworm.com/index.php?rid=4227090&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00448.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227090 Sat, 04 Dec 2010 04:39:41 +0100 4227090 http://www.medworm.com/index.php?rid=4227089&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00462.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227089 Sat, 04 Dec 2010 04:39:40 +0100 4227089 http://www.medworm.com/index.php?rid=4227088&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00451.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227088 Sat, 04 Dec 2010 04:39:39 +0100 4227088 http://www.medworm.com/index.php?rid=4227087&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00450.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227087 Sat, 04 Dec 2010 04:39:39 +0100 4227087 http://www.medworm.com/index.php?rid=4227086&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00455.x AbstractEmbryonal brain tumors are a heterogeneous group of neoplasms united by the presence of poorly differentiated stem‐like cells. Molecular details are increasingly being used to separate them into biologically and clinically meaningful groups. For medulloblastoma, integrated mRNA expression profiling and DNA analysis by a number of research groups defines 4–6 distinctive molecular variants. A subset with prominent Wnt activity is associated with good clinical outcomes and classic histology. Medulloblastomas showing a Hedgehog gene expression signature are frequently of the desmoplastic/nodular subtype. Interestingly, Hedgehog activity is found in tumors arising either in infants or older teenagers and adults. The association of clinically aggressive medulloblastoma with MYC expre... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227086 Sat, 04 Dec 2010 04:39:37 +0100 4227086 http://www.medworm.com/index.php?rid=4227085&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00456.x AbstractThe diffuse gliomas are a heterogeneous group of malignancies with highly variable outcomes and diagnosis is largely based on the histological appearance of the tumors. Tumor classification according to cello type and grade provides some prognostic information. However, the diversity of gliomas, within tumor type and grade categories, has made prognostic determinations based purely on clinicopathologic variables difficult. There is an increasing body of data suggesting a significant amount of molecular diversity accounts for the heterogeneity of clinical observations, such as response to treatment and time to progression. The last decade has witnessed an explosive advance in our knowledge of the molecular genetics of brain tumors, due in large part to the availability of high‐thr... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227085 Sat, 04 Dec 2010 04:39:36 +0100 4227085 http://www.medworm.com/index.php?rid=4227084&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00454.x AbstractFor some, glioma biomarkers have been expected to solve common diagnostic problems in routine neuropathology service caused by insufficient material, technical shortcomings or lack of experience. Further, biomarkers should predict patient outcome and direct optimal therapy for the individual patient. Unfortunately, current biomarkers still fall somewhat short of these grand expectations. While there has been some progress, it has generally been slow and in small steps. In this review, the newest set of glioma biomarkers: O6‐methylguanine‐DNA methyltransferase (MGMT) methylation, BRAF fusion and IDH1 mutation are discussed. MGMT methylation is well established as a prognostic/predictive marker for glioblastoma; however, technical questions regarding testing remain, it is not cur... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227084 Sat, 04 Dec 2010 04:39:35 +0100 4227084 http://www.medworm.com/index.php?rid=4227083&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00453.x AbstractFluorescence in situ hybridization (FISH) is a powerful, morphology‐based technique to assess targeted copy number alterations or gene rearrangements in formalin‐fixed, paraffin‐embedded tissues. It has a wide range of applications in routine clinical contexts to identify cytogenetic biomarkers for more accurate diagnosis and prognostic stratification. This review and update addresses practical uses of FISH as a molecular diagnostic tool in the setting of brain tumors, including gliomas, embryonal neoplasms, ependymomas and meningiomas, focusing on key genetic biomarkers, such as 1p19q codeletion, epidermal growth factor receptor (EGFR) gene amplification, BRAF rearrangement and many others. Also discussed are lessons learned over the past decade, including common technical i... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227083 Sat, 04 Dec 2010 04:39:34 +0100 4227083 http://www.medworm.com/index.php?rid=4227082&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00452.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227082 Sat, 04 Dec 2010 04:39:34 +0100 4227082 http://www.medworm.com/index.php?rid=4227081&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00458.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4227081 Sat, 04 Dec 2010 04:39:31 +0100 4227081 http://www.medworm.com/index.php?rid=4209760&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00466.x AbstractNeuroaxonal damage and loss are increasingly recognized as disability determining features in multiple sclerosis (MS) pathology. However, little is known about the long term sequelae of inflammatory demyelination on neurons and axons.Spinal cord tissue of 31 MS patients was compared to 3 amyotrophic lateral sclerosis (ALS) and 10 control subjects. MS lesions were staged according to the density of KiM‐1P+ macrophages and microglia and presence of MBP+ phagocytes. T cells were quantified in the parenchyma and meninges. Neuroaxonal changes were studied by immunoreactivity (IR) for APP and variably phosphorylated neurofilaments (SMI312, SMI31, SMI32).Little T cell infiltration was still evident in chronic inactive lesions. The loss of SMI32 IR in ventral horn neurons correlated with... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4209760 Mon, 29 Nov 2010 00:00:00 +0100 4209760 http://www.medworm.com/index.php?rid=4216451&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00460.x AbstractGlioblastoma (GBM) prognosis remains dismal, with most patients succumbing to disease within 1 or 2 years of diagnosis. Recent studies have suggested that many solid tumors, including GBM, are maintained by a subset of cells termed cancer stem cells (CSCs). It has been shown that these cells are inherently radio‐ and chemotherapy resistant, and may be maintained in vivo in a niche characterized by reduced oxygen tension (hypoxia). This review examines the recently described effects of hypoxia on CSC in GBM, and the potential promise in targeting the hypoxic pathway therapeutically. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4216451 Fri, 05 Nov 2010 00:00:00 +0100 4216451 http://www.medworm.com/index.php?rid=4136497&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00461.x In this study, we use ultrastructural analysis, in situ transcription assay and molecular markers for DNA damage, nucleoli and CB components to demonstrate that PC degeneration involves the progressive accumulation of nuclear DNA damage associated with disruption of nucleoli and CBs, disassembly of polyribosomes into monoribosomes, ribophagy and shut down of nucleolar and extranucleolar transcription. Microarray analysis reveals that four genes encoding repressors of nucleolar rRNA synthesis (p53, Rb, PTEN and SNF2) are upregulated in the cerebellum of pcd mice. Collectively, these data support that nucleolar and CB alterations are hallmarks of DNA damage‐induced neurodegeneration. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4136497 Wed, 03 Nov 2010 00:00:00 +0100 4136497 http://www.medworm.com/index.php?rid=4209759&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00467.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4209759 Mon, 01 Nov 2010 00:00:00 +0100 4209759 http://www.medworm.com/index.php?rid=4201449&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00465.x AbstractTo evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, which may contribute to a number of debilitating signs and symptoms, we assessed the mRNA levels of histidine decarboxylase (HDC) and the volume and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed mRNA levels of histamine N‐methyltransferase (HMT) and of histamine receptors (H1R, H2R and H3R) in the inferior frontal gyrus (IFG) (HD n = 9, controls n = 9) and the caudate nucleus (CN) (HD n = 6, controls n = 6) by real‐time PCR. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). However, the levels of HDC mRNA (P = 0.046) and IFG HMT (P < 0.001), H1R (P < 0.001) and H3R mRN... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4201449 Mon, 01 Nov 2010 00:00:00 +0100 4201449 http://www.medworm.com/index.php?rid=4193234&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00464.x AbstractDEP‐1/PTPRJ is a transmembrane protein‐tyrosine phosphatase which has been proposed as a suppressor of epithelial tumors. We have found LOH of the PTPRJ gene and loss of DEP‐1 protein expression in a subset of human meningiomas. RNAi‐mediated suppression of DEP‐1 in DEP‐1 positive meningioma cell lines caused enhanced motility and colony formation in semi‐solid media. Cells devoid of DEP‐1 exhibited enhanced signaling of endogenous platelet‐derived growth factor (PDGF) receptors, and reduced paxillin phosphorylation upon seeding. Moreover, DEP‐1 loss caused diminished adhesion to different matrices, and impaired cell spreading. DEP‐1 deficient meningioma cells exhibited invasive growth in an orthotopic xenotransplantation model in nude mice, indicating that el... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4193234 Mon, 01 Nov 2010 00:00:00 +0100 4193234 http://www.medworm.com/index.php?rid=4173302&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00463.x In this report, we provide evidence that IbeA and its receptor, vimentin, play a key role in E. coli‐induced PMN transmigration across BMEC. In vitro and in vivo studies indicated that the ibeA‐deletion mutant ZD1 was significantly less active in stimulating PMN transmigration than the parent strain E44. ZD1 was fully complemented by the ibeA gene and its product. E. coli‐induced PMN transmigration was markedly inhibited by withaferin A, a dual inhibitor of vimentin and proteasome. These cellular effects were significantly stimulated and blocked by overexpression of vimentin and its head domain deletion mutant in human BMEC, respectively. Our studies further demonstrated that IbeA‐induced PMN migration was blocked by bortezomib, a proteasomal inhibitor, and correlated with up‐reg... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4173302 Mon, 01 Nov 2010 00:00:00 +0100 4173302 http://www.medworm.com/index.php?rid=4136496&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00460.x AbstractGlioblastoma (GBM) prognosis remains dismal, with most patients succumbing to disease within one or two years of diagnosis. Recent studies have suggested that many solid tumors, including GBM, are maintained by a subset of cells termed cancer stem cells (CSC). It has been shown that these cells are inherently radio‐ and chemo‐therapy resistant, and may be maintained in vivo in a niche characterized by reduced oxygen tension (hypoxia). This review examines the recently described effects of hypoxia on CSC in GBM, and the potential promise in targeting the hypoxic pathway therapeutically. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4136496 Mon, 01 Nov 2010 00:00:00 +0100 4136496 http://www.medworm.com/index.php?rid=4111779&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00459.x ABSTRACT (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4111779 Fri, 29 Oct 2010 19:26:20 +0100 4111779 http://www.medworm.com/index.php?rid=4102326&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00457.x Abstract (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4102326 Tue, 26 Oct 2010 03:17:14 +0100 4102326 http://www.medworm.com/index.php?rid=4243220&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00457.x AbstractPrenatal systemic inflammation has been implicated in neurological diseases, but optimal animal models have not been developed. We investigated whether a partial genetic deletion of glial cell line‐derived neurotrophic factor (Gdnf+/−) increased vulnerability of dopamine (DA) neurons to prenatal lipopolysaccharide (LPS). LPS [0.01 mg/kg intraperitoneal (i.p.)] or saline was administered to wild‐type (WT) or Gdnf+/− pregnant mice on gestational day 9.5. Male offspring were examined at 3 weeks, 3 and 12 months of age. There was a progressive degeneration of tyrosine hydroxylase (TH)‐positive neurons in the substantia nigra (SN) with age in Gdnf+/− but not in WT mice, with no observed effects on locus coeruleus (LC) noradrenergic neurons or DA neurons of the ventral tegm... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4243220 Mon, 25 Oct 2010 00:00:00 +0100 4243220 http://www.medworm.com/index.php?rid=4033610&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00436.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033610 Wed, 06 Oct 2010 15:39:36 +0100 4033610 http://www.medworm.com/index.php?rid=4033609&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00424.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033609 Wed, 06 Oct 2010 15:39:35 +0100 4033609 http://www.medworm.com/index.php?rid=4033608&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00442.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033608 Wed, 06 Oct 2010 15:39:35 +0100 4033608 http://www.medworm.com/index.php?rid=4033607&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00435.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033607 Wed, 06 Oct 2010 15:39:34 +0100 4033607 http://www.medworm.com/index.php?rid=4033606&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00434.x (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033606 Wed, 06 Oct 2010 15:39:34 +0100 4033606 http://www.medworm.com/index.php?rid=4033605&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00449.x Abstract (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4033605 Wed, 06 Oct 2010 15:39:21 +0100 4033605 http://www.medworm.com/index.php?rid=4156735&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00449.x AbstractSeveral lines of evidence support protective as well as deleterious effects of oleic acid (OA) on Alzheimer's disease (AD) and other neurological disorders; however, the bases of these effects are unclear. Our investigation demonstrates that amyloid precursor protein (APP) 695 transfected Cos‐7 cells supplemented with OA have reduced secreted amyloid‐beta (Aβ) levels. An early‐onset AD transgenic mouse model expressing the double‐mutant form of human APP, Swedish (K670N/M671L) and Indiana (V717F), corroborated our in vitro findings when they were fed a high‐protein, low‐fat (18% reduction), cholesterol‐free diet enriched with OA. These mice exhibited an increase in Aβ40/Aβ42 ratio, reduced levels of beta‐site APP cleaving enzyme (BACE) and reduced presenilin leve... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4156735 Tue, 05 Oct 2010 00:00:00 +0100 4156735 http://www.medworm.com/index.php?rid=4128508&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00447.x In conclusion, identification of molecular malignancy as proposed will aid in establishing a risk profile for individual patients and thereby in therapeutic decision making. (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4128508 Thu, 30 Sep 2010 00:00:00 +0100 4128508 http://www.medworm.com/index.php?rid=4128507&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00443.x AbstractThe expression of hypoxia‐inducible factor‐1‐alpha (HIF‐1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF‐1α was observed during 1–12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2‐methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre‐silencing HIF‐1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip‐like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF‐1α with siRNA 12 h after oxygen–glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor... Brain Pathology journals http://www.medworm.com/rss/comments.php?id=4128507 Thu, 30 Sep 2010 00:00:00 +0100 4128507 http://www.medworm.com/index.php?rid=3937335&cid=s_32229_25_f&fid=32229&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1750-3639.2010.00433.x Abstract (Source: Brain Pathology) Brain Pathology journals http://www.medworm.com/rss/comments.php?id=3937335 Tue, 07 Sep 2010 06:36:28 +0100 3937335