ATP8B1 is essential for maintaining normal hearing.

ATP8B1 deficiency is caused by autosomal recessive mutations in ATP8B1, which encodes the putative phospatidylserine flippase ATP8B1 (formerly called FIC1). ATP8B1 deficiency is primarily characterized by cholestasis, but extrahepatic symptoms are also found. Because patients sometimes report reduced hearing capability, we investigated the role of ATP8B1 in auditory function. Here we show that ATP8B1/Atp8b1 deficiency, both in patients and in Atp8b1(G308V/G308V) mutant mice, causes hearing loss, associated with progressive degeneration of cochlear hair cells. Atp8b1 is specifically localized in the stereocilia of these hair cells. This indicates that the mechanosensory function and integrity of the cochlear hair cells is critically dependent on ATP8B1 activity, possibly through maintaining lipid asymmetry in the cellular membranes of stereocilia.

Detection of bacteria in healthy middle ears during cochlear implantation.

OBJECTIVE: To assess whether free-living and/or biofilm bacteria are present in the putative sterile middle ear cavity before insertion of the electrode array during cochlear implantation. DESIGN: Prospective study. SETTING: Tertiary academic hospital. PATIENTS: The study included 45 healthy children (with or without a history of otitis media) undergoing cochlear implantation. INTERVENTIONS: Transmission electron microscopy or scanning electron microscopy was used to detect the presence of bacteria. MAIN OUTCOME MEASURE: Presence of both free-living bacteria and biofilm bacteria on the epithelial surface of biopsy specimens of middle ear mucosa. RESULTS: A majority of all mucosal specimens from clinically healthy tympanic cavities displayed inflammatory areas as well as dispersed, nonmatrix-enclosed bacteria. Also, rarely, fragments of biofilms were found. CONCLUSIONS: The presence of bacteria in the tympanic cavity, which is generally assumed to be sterile in healthy individuals, may provide an explanation for infectious complications after cochlear implantation. However, the possibility that the electrode array of a cochlear implant will actually become contaminated during insertion is unlikely because of the small amounts and dispersed presence of bacteria, which may account for the relatively low incidence of infectious complications after cochlear implantation.

Involvement of glycosaminoglycans in the attachment of pneumococci to nasopharyngeal epithelial cells.

Streptococcus pneumoniae is a major bacterial pathogen involved in the development of otitis media. The pathogenic mechanisms of this middle ear disease, including the bacterial adherence mechanisms to the mucosal epithelial cells of the host, are poorly understood. In this study, the role of glycosaminoglycans in the adhesion of pneumococci to mucosal epithelial cells is examined. Both nasopharyngeal epithelium from rats and an oral epithelial cell line were used for pneumococcal adherence experiments. Preincubation of pneumococci with heparin, heparan sulfate (HS) and to a lesser extent, chondroitin 4-sulfate (C-4S), was found to inhibit attachment of S. pneumoniae to oral epithelial cells, while dermatan sulfate and hyaluronate did not interfere with pneumococcal binding. Enzymatic removal of HS moieties by heparinase III from nasopharyngeal epithelial cells abolished the attachment of pneumococci to nasopharyngeal epithelium. This study demonstrates that heparin, HS and C-4S are involved in pneumococcal binding to mucosal epithelial cells. This knowledge may contribute to the development of a new prophylactic strategy for otitis media.

Genetic relatedness between pneumococcal populations originating from the nasopharynx, adenoid, and tympanic cavity of children with otitis media.

Previous studies have shown that Streptococcus pneumoniae exists in both middle ear effusions and the upper respiratory region from children with otitis media with effusion (OME), but it remains unclear whether these strains represent genetically identical clones. Therefore, it cannot be determined whether these bacteria originate from a common source. To determine the presence of pneumococci at different anatomical locations of OME patients, conventional culture and PCR techniques were used. To analyze the possible genetic relatedness between pneumococci from different anatomical sites, molecular typing by amplified fragment length polymorphism was utilized. The percentage of middle ear effusions of OME patients that are positive for pneumococci after PCR analysis (13%) was higher than after conventional culture (5%). Molecular fingerprints from pneumococci derived from two different anatomic sites within patients were very similar in 80% of OME patients and in 90% of acute otitis medium patients, indicating their genetic relatedness. Biofilm formation or pneumococcal L-forms probably play a role in OME, since culture-negative effusions prove to contain pneumococcal DNA. Bacteria involved in this process most likely originate from the nasopharynx since they show a close genetic relatedness with their nasopharyngeal counterparts.

Differences in endolymphatic sac mitochondria-rich cells indicate specific functions.

OBJECTIVE/HYPOTHESIS: The purpose of the study was to examine the specific involvement of endolymphatic sac mitochondria-rich cells in endolymph homeostasis. STUDY DESIGN: Transmission electron microscopy and immunohistochemistry were performed on the endolymphatic sac of young adult rats, and two important developmental stages were also investigated. METHODS: Ultrastructural characteristics of endolymphatic sac mitochondria-rich cells were studied more concisely and compared with renal mitochondria-rich cells (i.e., the intercalated cells). In addition, expression of cytokeratins 7 and 19 was determined. RESULTS: Until birth, only one type of mitochondria-rich cell is observed in the rat endolymphatic sac. In young adult animals, distinct differences in mitochondria-rich cell ultrastructure in the endolymphatic sac enables classification into subtypes or configurations. Comparison of endolymphatic sac mitochondria-rich cells with renal intercalated cells reveals striking similarities and provides additional information on their specific function in endolymph homeostasis. Furthermore, differences in cytokeratin expression are determined in endolymphatic sac mitochondria-rich cells. CONCLUSIONS: Differences in morphology of endolymphatic sac mitochondria-rich cells develop after birth and may reflect a distinct functional or physiological state of the cell. In analogy to renal intercalated cells, the distribution patterns of H+-adenosine triphosphatase and Cl-/HCO3- exchanger may differ between subtypes. We propose that subtype A mitochondria-rich cells, from which protruding A mitochondria-rich cells are the activated state, are involved in proton secretion (apical H+-adenosine triphosphatase) and thus are potential candidates for hearing loss accompanying renal tubular acidosis. Subtype B mitochondria-rich cells are the most likely candidates to be affected in Pendred syndrome because of the assumed function of pendrin as apical Cl-/HCO3- exchanger.