Abstract:
:In the central nervous system, tuberous sclerosis complex (TSC) is characterized by a range of lesions including cortical tubers, white matter heterotopias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). Recent studies have implicated an important role for the TSC genes TSC1 and TSC2, in a signaling pathway involving the mammalian target of rapamycin (mTOR) kinase. We performed immunohistochemical and genetic analyses on SEGAs from 7 TSC patients, 4 with mutations in TSC1, and 3 with mutations in TSC2. SEGA cells show high levels of phospho-S6K, phospho-S6, and phospho-Stat3, all proteins downstream of and indicative of mTOR activation. Such expression is not seen in histologically normal control tissue. Five of 6 SEGAs also showed evidence of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex. We conclude that TSC SEGAs likely arise through a two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of the mTOR kinase.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Chan JA,Zhang H,Roberts PS,Jozwiak S,Wieslawa G,Lewin-Kowalik J,Kotulska K,Kwiatkowski DJdoi
10.1093/jnen/63.12.1236subject
Has Abstractpub_date
2004-12-01 00:00:00pages
1236-42issue
12eissn
0022-3069issn
1554-6578journal_volume
63pub_type
杂志文章abstract::The endoneurial lead and water content was serially evaluated in the nerves of rats fed lead carbonate and related to the onset and severity of segmental demyelination and remyelination. Lead began to accumulate significantly in the endoneurium by 5 days, reached a maximum level (71 microgram/g dry weight) by 34 days,...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198011000-00008
更新日期:1980-11-01 00:00:00
abstract::Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleuk...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318187a279
更新日期:2008-10-01 00:00:00
abstract::Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.3.218
更新日期:2000-03-01 00:00:00
abstract::The most common histologic feature in patients with frontotemporal lobar degeneration (FTLD) is intracellular brain inclusions of yet uncharacterized proteins that react with antiubiquitin (Ub) antibodies, but not with tau or synuclein (FTLD-U). We identified a four-generation Belgian FTLD family in which 8 patients h...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000205147.39210.c7
更新日期:2006-03-01 00:00:00
abstract::Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurod...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.8.759
更新日期:2001-08-01 00:00:00
abstract::Precise temporal and spatial coordination of expression of the myogenic regulatory factors (MRF) plays a critical role in the development of skeletal muscle. Whether this pattern is recapitulated postnatally during regeneration of mature muscle after injury is not known. The aim of this study was to determine the cell...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199605000-00002
更新日期:1996-05-01 00:00:00
abstract::Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encodi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa034
更新日期:2020-06-01 00:00:00
abstract::Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181654386
更新日期:2008-03-01 00:00:00
abstract::Canine smooth muscle cells (SMCs), cultured from amyloid-affected brain blood vessels accumulate Alzheimer amyloid-beta peptide (Abeta) intracellularly, either spontaneously or after treatment with apolipoprotein E (apoE). ApoE is codeposited with Abeta, which suggests that apoE participates in Abeta accumulation. We ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199903000-00008
更新日期:1999-03-01 00:00:00
abstract::A single oral dose of clofibrate (30 mg/100 gm body weight) given to 250-300 gm male rats produced myotonic discharges from both the gastrocnemius and soleus muscles 2 hours after feeding. Rats fed the same dosage for 14 consecutive days exhibited electromyographic discharges consistent with profound myotonia. Fibers ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197911000-00004
更新日期:1979-11-01 00:00:00
abstract::Early inflammatory events may inhibit functional recovery after injury in both the peripheral and central nervous systems. We investigated the role of the inflammatory tumor necrosis factor/nuclear factor-kappaB (NF-kappaB) axis on events subsequent to sciatic nerve crush injury in adult rats. Electrophoretic mobility...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181a7c14e
更新日期:2009-06-01 00:00:00
abstract::In attempting to control the pain of disseminated carcinoma, a variety of agents has been injected intrathecally. This report deals with the neuropathologic changes in spinal roots and spinal cord of four patients into whose lumbar sacs 100 to 285 ml of distilled water was infused. Survival following the procedure ra...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197509000-00002
更新日期:1975-09-01 00:00:00
abstract::Lewy bodies and Lewy neurites are the hallmark neuropathologic findings in Parkinson disease, Parkinson disease with dementia, dementia with Lewy bodies, and other alpha-synucleinopathies. They have also been described in the brains of normal older individuals and referred to as incidental Lewy body disease. The purpo...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181ac10a7
更新日期:2009-07-01 00:00:00
abstract::Truncations of tau protein at aspartic acid421 (D421) and glutamic acid391 (E391) residues are associated with neurofibrillary tangles (NFTs) in the brains of Alzheimer disease (AD) patients. Using immunohistochemistry with antibodies to D421- and E391-truncated tau (Tau-C3 and MN423, respectively), we correlated the ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31817275c7
更新日期:2008-05-01 00:00:00
abstract::Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular S...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199511000-00004
更新日期:1995-11-01 00:00:00
abstract::Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previous...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlw105
更新日期:2017-01-01 00:00:00
abstract::Multiple system atrophy (MSA) is a neurodegenerative disorder that predominantly affects motor-related neuroanatomic structures. The role of microglia in MSA is unknown. To address this issue, we conducted quantitative image studies on the brains from 13 cases of MSA, comprising 8 cerebellar and 5 parkinsonian variant...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.1.43
更新日期:2004-01-01 00:00:00
abstract::Peptidylarginine deiminase (PAD) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of PAD2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. We performed subcellular fractionation and electron microscop...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318207559e
更新日期:2011-02-01 00:00:00
abstract::Abnormalities were detected by two-dimensional gel electrophoresis in the protein composition of both the dorsal and ventral roots of three of six patients who succumbed to amyotrophic lateral sclerosis (ALS). The abnormalities consisted of a cascade of acidic protein spots on silver-stained gels which were shown by i...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198411000-00005
更新日期:1984-11-01 00:00:00
abstract::The aim of this study was to clarify pathological and anatomical relationships between adamantinomatous craniopharyngiomas (ACP) and their surrounding structures. We previously established a QST classification scheme based on the apparent anatomic origin of the tumors. According to this classification, 13 type Q tumor...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nly083
更新日期:2018-11-01 00:00:00
abstract::Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuol...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197603000-00003
更新日期:1976-03-01 00:00:00
abstract::Brain arteriovenous malformations (bAVMs) are congenital anomalies of blood vessels that cause intracranial hemorrhage in children and young adults. Chromosomal rearrangements and fusion genes play an important role in tumor pathogenesis, though the role of fusion genes in bAVM pathophysiological processes is unclear....
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa126
更新日期:2021-01-01 00:00:00
abstract::Studies dealing with transport of proteins from the oligodendrocyte cell body to the myelin sheath reveal the presence of different transport pathways. Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.1.12
更新日期:2002-01-01 00:00:00
abstract::How to assess the substantial neuronal loss in a neurodegenerative disease such as Alzheimer disease is still being debated. Recently, stereological procedures have been proposed that claim improved accuracy and statistical power, but the results of some of these investigations have been controversial. In this study w...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199711000-00004
更新日期:1997-11-01 00:00:00
abstract::After the finding that anti-prion antibodies stain sensory and sympathetic ganglia in variant Creutzfeldt-Jakob disease (vCJD), it was suggested that this localization supported the oral route of entry. However, prion accumulation subsequently also appeared in the peripheral nervous system (PNS) in sporadic cases. Thi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000175330.66715.08
更新日期:2005-08-01 00:00:00
abstract::An effective method was sought to immunize rats against the growth of intracerebrally (IC) injected T9 tumor, a gliosarcoma cell line. Rats which were immunized with either 10(6) T9 cells mixed with 0.14 mg C. parvum, or 10(7) irradiated T9 cells showed tumor immunity to intradermal (ID) transplantation. However, to o...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198303000-00002
更新日期:1983-03-01 00:00:00
abstract::PROX1 is a prospero-related transcription factor that plays a critical role in the development of various organs including the mammalian lymphatic and central nervous systems; it controls cell proliferation and differentiation through different transcription pathwaysand has both oncogenic and tumor-suppressive functio...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181ca4767
更新日期:2010-02-01 00:00:00
abstract::We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age....
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.9.911
更新日期:2004-09-01 00:00:00
abstract::Smooth muscle cells cultured from leptomeningeal vessels from old dogs with amyloid-angiopathy accumulate intracellular deposits that are immunoreactive for amyloid-beta peptide (A beta). We used this cellular model in the present study to examine the influence of sera and cerebrospinal fluid on intracellular accumula...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199703000-00005
更新日期:1997-03-01 00:00:00
abstract::In a recent study we estimated the number and frequency distribution of the diameters of the cytons of all of the combined motoneuron columns of L3, L4 and L5 ventral horn of the spinal cord of man. In the present study we have estimated the number and frequency distribution of the diameter of motoneuron cytons in the...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197711000-00007
更新日期:1977-11-01 00:00:00