The emergence of superoxide anion radicals (O2-) in the guinea pig inner ear following acoustic trauma was investigated by histochemical methods. Five minutes after exposure to sound at 120-125 dB SPL for 3 h, an O2- reaction product was detected in the cochlea along the luminal membrane of the marginal cells of the stria vascularis. This reaction product could not be found at 30 min, but reappeared at 2 h. The first appearance of O2- is not explainable by our studies, but the second appearance may be related to recirculation of strial blood flow after blood flow stasis. The present observations raise the possibility that free radicals are produced in the inner ear after acoustic trauma and lead to inner ear damage.
Edited by Ulrike KutayKeywords: S1-1 RBM10 RBM5 Alternative splicing Fas, Bcl-x a b s t r a c t RBM10, originally called S1-1, is a nuclear RNA-binding protein with domains characteristic of RNA processing proteins. It has been reported that RBM10 constitutes spliceosome complexes and that RBM5, a close homologue of RBM10, regulates alternative splicing of apoptosis-related genes, Fas and cFLIP. In this study, we examined whether RBM10 has a regulatory function in splicing similar to RBM5, and determined that it indeed regulates alternative splicing of Fas and Bcl-x genes. RBM10 promotes exon skipping of Fas pre-mRNA as well as selection of an internal 5 0 -splice site in Bcl-x premRNA. We propose a consensus RBM10-binding sequence at 5 0 -splice sites of target exons and a mechanistic model of RBM10 action in the alternative splicing.
S1-1 constitutes hundreds of nuclear domains, which dynamically change their structures in a reversible manner. Upon globally reducing RNA polymerase II transcription, S1-1 nuclear bodies enlarge and decrease in number. They are novel domains different from paraspeckles or IGAZs, despite their similar occurrence adjacent to nuclear speckles. We discuss S1-1 granules in terms of their association with gene expression. In addition, this is the first report of a TIDR-localized protein.
To clarify mechanisms of inner ear cell death induced by aminoglycosides, we used an in situ nick-end labelling method to examine guinea pig vestibular epithelia after chronic systemic treatments with gentamicin to produce apoptosis. Such changes occurred in damaged hair cells, suggesting that this process may be crucial for subsequent repair and cell regeneration.
Although aminoglycosides have been investigated for their cochleotoxicity, it has still not been determined whether apoptosis or necrosis results in cochlear hair cell death following aminoglycoside treatment. To study possible mechanisms of cell death, we used in situ DNA break-labeling to examine guinea pig cochleae affected by Kanamycin ototoxicity. Chronic kanamycin treatment induced DNA fragmentation that was detectable in both outer and inner hair cells, suggesting the occurrence of apoptosis. These findings suggest that apoptosis achieves deletion of affected hair cells without disrupting tissue architecture in the organ of Corti.
ConclusionSignificant reduced visualization of the reuniting duct (ductus reuniens; RD), saccular duct (SD) and endolymphatic sinus (ES) in Meniere's disease (MD) compared with normal control ears on three-dimensional (3D) CT imaging suggests the blockage of endolymphatic flow there with radiodense substances, which may be explained by dislodged otoconia from the saccule. These structures could be involved in the pathogenesis of MD.ObjectiveThis study was designed to visualize and assess the RD, SD and ES in patients with MD using 3D CT.MethodsSixty-two patients with a definite diagnose of unilateral MD, based on criteria proposed by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), were compared with contralateral ears and normal controls (26 ears) using 3D CT. The RD, SD and ES were scrutinized for patency on 3D CT images.ResultsMD ears showed loss of continuity of the RD, SD and ES based on evaluation of 3D CT images, and differed significantly from normal healthy control ears (p < 0.01).
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