Abstract:
:Fibrosis is the main cause of irreversible nerve damage in leprosy. Phenotypic changes in Mycobacterium leprae (ML)-infected Schwann cells (SCs) have been suggested to mediate this process. We found that SC line cultures stimulated with ML upregulated transforming growth factor-β1 (TGF-β1), and that TGF-β1 or ML induced increased numbers of α-smooth muscle actin (α-SMA)-positive cells with characteristic stress fibers. Mycobacterium leprae and TGF-β1 also induced increased type I collagen and fibronectin mRNA and secretion and augmented mRNA levels of SOX9 and ZEB1, which are involved in the epithelial-mesenchymal transition. These effects could be inhibited by the TGF-β1 type I receptor (ALK5) inhibitor, SB-431542. In nerve biopsies from leprosy-infected patients with varying grades of fibrosis (n = 11), type I and III collagen and fibronectin were found in the endoneurium and perineurium, α-SMA-positive cells filled the fibrotic perineurium but not the endoneurium, and CD34-positive fibroblasts predominated in the endoneurium. Results of transcriptional studies of 3 leprosy nerves and 5 controls were consistent with these data, but α-SMA and other mRNA levels were not different from those in the control samples. Our findings suggest that TGF-β1 may orchestrate events, including reprogramming of the SC phenotype, leading to transdifferentiation, connective tissue cell expansion, and fibrogenesis in the evolution of leprosy nerve lesions during some evolutionary stages.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Petito RB,Amadeu TP,Pascarelli BM,Jardim MR,Vital RT,Antunes SL,Sarno ENdoi
10.1097/NEN.0b013e31828bfc60subject
Has Abstractpub_date
2013-04-01 00:00:00pages
351-66issue
4eissn
0022-3069issn
1554-6578journal_volume
72pub_type
杂志文章abstract::Brain parenchymal involvement of mycosis fungoides (MF) is very rare. This study reports a patient with known cutaneous MF (under treatment) who presented with a CNS syndrome and multiple brain lesions. Brain biopsy demonstrated massive eosinophilic infiltrates but no MF cells. Despite treatment, new lesions developed...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000245
更新日期:2015-10-01 00:00:00
abstract::Nijmegen breakage syndrome caused by NBS1 germline mutations is a rare autosomal recessive disease with clinical features that include microcephaly, increased radiosensitivity, and predisposition to cancer. NBS1 plays a key role in DNA double-strand break repair and the maintenance of genomic stability. We screened 87...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31819724c2
更新日期:2009-02-01 00:00:00
abstract::The role of axonal transport in the pathogenesis of the axonal swellings which develop at the severed ends of transected axons was studied by electron microscopic (EM) autoradiography. Proteins carried by fast anterograde transport in rat sciatic nerves were labeled with [3H]-leucine or [3H]-fucose; [3H]-leucine, [3H]...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197703000-00002
更新日期:1977-03-01 00:00:00
abstract::Tuberous sclerosis (TSC) is a multi-system disorder characterized by hamartomatous tumors and abnormal brain development, with multiple foci of disrupted neuronal migration and giant dysmorphic neurons within cortical tubers. TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.7.711
更新日期:2001-07-01 00:00:00
abstract::Two basic proteins, P1 of molecular weight 14,200 and P2 of molecular weight 12,300, purified from bovine peripheral nerve, were assayed for biological activity. The P1 protein is an exclusively neuritogenic agent, capable of producing clinical signs of experimental allergic neuritis (EAN) and histological abnormaliti...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197501000-00004
更新日期:1975-01-01 00:00:00
abstract::The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or mac...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.9.798
更新日期:2000-09-01 00:00:00
abstract::Gliomas with hybrid oligodendroglial/astrocytic features are diagnostically problematic, and our ability to predict tumor behavior is limited. Some likely represent intermingled mixed oligoastrocytomas (MOAs), though precise diagnostic criteria and specific markers for this lesion are lacking. From the files at Washin...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.11.1118
更新日期:2003-11-01 00:00:00
abstract::We describe the clinical, pathological, ultrastructural and biochemical features in the case of a 15-year-old boy with multiple sulfatase deficiency. Clinical abnormalities included hypotonia, retarded psychomotor development, hepatosplenomegaly, pigmentary degeneration of the retina, myoclonic seizures, aortic insuff...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1097/00005072-199007000-00005
更新日期:1990-07-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e318093f40d
更新日期:2007-07-01 00:00:00
abstract::We have encountered a series of 8 third ventricular neoplasms with a distinctive chordoid appearance that appear to represent a clinicopathologic entity. The tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In all cases, imaging studies showed a large well-circumscribed third ventricular ma...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199803000-00009
更新日期:1998-03-01 00:00:00
abstract::Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.4.350
更新日期:2001-04-01 00:00:00
abstract::The microtubule-associated phosphoprotein, tau, is an integral component of paired helical filaments in Alzheimer neurofibrillary tangles (NFT). The mechanism of NFT formation is unknown but aberrant phosphorylation of tau may be contributory. Calcium/calmodulin-dependent protein kinase type II (CaM kinase II), the mo...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199001000-00006
更新日期:1990-01-01 00:00:00
abstract::Glial cytoplasmic inclusions (GCIs) are a pathologic hallmark of multiple system atrophy (MSA), but their pathogenetic roles need to be clarified. To determine possible roles of GCIs in individual cells, serial optical sections obtained by confocal microscopy were reconstructed to yield 3-dimensional (3D) images of th...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181b67678
更新日期:2009-10-01 00:00:00
abstract::A series of 43 human gliomas, consisting of 30 glioblastomas, 7 anaplastic astrocytomas, 3 low grade astrocytomas, 2 ependymomas, and 1 oligodendroglioma, was studied for amplification of the epidermal growth factor receptor (EGFR) and mouse double minute 2 (MDM2) genes. DNA extracted from formalin-fixed, paraffin-emb...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199501000-00007
更新日期:1995-01-01 00:00:00
abstract::The evolving neuropathology of primarily undamaged cortical regions adjacent to the injured site has been studied in 36 infants who survived a variety of perinatally acquired encephalopathies (microgyrias, ulegyrias, multicystic encephalopathies, porencephalies, and hydranencephalies) and later died of unrelated cause...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199905000-00001
更新日期:1999-05-01 00:00:00
abstract::Experimental autoimmune neuritis (EAN) is a demyelinating disease of the peripheral nervous system (PNS). This acute inflammatory disease is mediated by CD4+ T cells and bears significant similarities to the Guillain-Barré syndrome of humans. In the present study, we investigated the function of IL-18 in T cell-mediat...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.7.614
更新日期:2002-07-01 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::Nemaline myopathy is the most common congenital myopathy and is caused by mutations in various genes such as ACTA1 (encoding skeletal α-actin). It is associated with limb and respiratory muscle weakness. Despite increasing clinical and scientific interest, the molecular and cellular events leading to such weakness rem...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318293b1cc
更新日期:2013-06-01 00:00:00
abstract::Cytologic evaluation of cerebrospinal fluid (CSF) is an effective means for diagnosing many disorders involving the central nervous system (CNS). Interpretation of these samples requires an understanding of the spectrum of neurologic diseases which involves the subarachnoid space, either primarily or secondarily, as w...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1097/00005072-199205000-00001
更新日期:1992-05-01 00:00:00
abstract::Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.12.1181
更新日期:2001-12-01 00:00:00
abstract::Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder reported worldwide in kindreds with a G654A or G654T gelsolin gene mutation. The clinically characteristic peripheral nerve involvement has been poorly characterized morphologically, and its pathogenesis remains unknown. We studied peripheral ne...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.6.565
更新日期:2002-06-01 00:00:00
abstract::The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurof...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000190067.20935.42
更新日期:2005-12-01 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::Neuropathologists use anti-glial fibrillary acidic protein (GFAP) antibodies as specific markers for glial cells, and neurobiologists use GFAP for targeting transgenes to glial cells. Since GFAP has also been detected in non-glial cells, we systematically analyzed GFAP expression in human and murine non-CNS tissues us...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.5.449
更新日期:2001-05-01 00:00:00
abstract::Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in autonomic ganglia, which innervate and control the activity of most visceral organs. By combining ultrastructural, immunocytochemical, and pharmacological analyses, we characterized the nAChR subtypes in the rat superior cervical ganglion...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.2.138
更新日期:2004-02-01 00:00:00
abstract::Tissue microarrays (TMAs), also known as "tissue chips," are a recently developed method that allows small cores or discs of tissue from dozens or hundreds of (usually paraffin-embedded) specimens to be re-embedded in a tissue block, which can then be further sectioned. The tissue cores can subsequently be studied usi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/61.8.653
更新日期:2002-08-01 00:00:00
abstract::The triplication of the DYRK1A gene encoding proline-directed serine/threonine kinase and located in the critical region of Down syndrome (DS) has been implicated in cognitive deficits and intellectual disability of individuals with DS. We investigated the effect of abnormal levels of this kinase on the cytoskeleton i...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31827733c8
更新日期:2012-12-01 00:00:00
abstract::Rates of remyelination decline with age and this has been attributed to slower recruitment of oligodendrocyte progenitor cells (OPCs) into areas of demyelination and slower differentiation of OPCs into remyelinating oligodendrocytes. When considering causes for reduced recruitment rates, intrinsic causes (alterations ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.9.908
更新日期:2003-09-01 00:00:00
abstract::Experimental cerebral ischemia was produced in gerbils by occlusion of the right common carotid artery in the neck. The evolution of the ischemic lesions was followed from five minutes to six hours by using the immunohistochemical techniques for tubulin and creatine kinase BB-isoenzyme. The earliest lesion was found i...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198503000-00009
更新日期:1985-03-01 00:00:00
abstract::Much of the morbidity after traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. It is unknown, howev...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e31829d8d9d
更新日期:2013-08-01 00:00:00