Yukihide Maeda

Language development of a multiply handicapped child after cochlear implantation

The presence of additional handicaps in hearing-impaired children makes the prediction of language ability after cochlear implantation unreliable. Only limited follow-up data on developmental improvement after implantation among multiply handicapped children is available. The present study reports the course of development (audiological and linguistic) after cochlear implantation in one subject with moderate mental retardation. Preoperatively, his language development showed 34 months delay when compared to chronological age. The difference had shortened to 23 months by 2 years post-surgery. The subjects cognitive delay had not changed upon 2-year follow-up. The cochlear implant can be credited to his improvement in language development.

Ménière's disease in childhood

We report 3 rare cases of Ménières disease in children. In Case 1 and 3, vertigo, hearing loss and tinnitus recovered soon after medical therapy. In Case 2, however, vertigo recurred and the hearing level on the right side markedly deteriorated. The equal-loudness contours on three-dimensional audiogram showed that right-sided aggravated hearing loss fluctuated for 4 years at middle-and low-frequencies despite medication. Finally intratympanic injection of gentamicin sulfate was performed. The patient has had no definitive spell of vertigo after gentamicin therapy. At our department, the incidence of Ménières disease in pediatric patients with vertigo was 2.9%.

Time Courses of Changes in Phospho- and Total- MAP Kinases in the Cochlea after Intense Noise Exposure

Mitogen-activated protein kinases (MAP kinases) are intracellular signaling kinases activated by phosphorylation in response to a variety of extracellular stimuli. Mammalian MAP kinase pathways are composed of three major pathways: MEK1 (mitogen-activated protein kinase kinase 1)/ERK 1/2 (extracellular signal-regulated kinases 1/2)/p90 RSK (p90 ribosomal S6 kinase), JNK (c-Jun amino (N)-terminal kinase)/c-Jun, and p38 MAPK pathways. These pathways coordinately mediate physiological processes such as cell survival, protein synthesis, cell proliferation, growth, migration, and apoptosis. The involvement of MAP kinase in noise-induced hearing loss (NIHL) has been implicated in the cochlea; however, it is unknown how expression levels of MAP kinase change after the onset of NIHL and whether they are regulated by transient phosphorylation or protein synthesis. CBA/J mice were exposed to 120-dB octave band noise for 2 h. Auditory brainstem response confirmed a component of temporary threshold shift within 0–24 h and significant permanent threshold shift at 14 days after noise exposure. Levels and localizations of phospho- and total- MEK1/ERK1/2/p90 RSK, JNK/c-Jun, and p38 MAPK were comprehensively analyzed by the Bio-Plex® Suspension Array System and immunohistochemistry at 0, 3, 6, 12, 24 and 48 h after noise exposure. The phospho-MEK1/ERK1/2/p90 RSK signaling pathway was activated in the spiral ligament and the sensory and supporting cells of the organ of Corti, with peaks at 3–6 h and independently of regulations of total-MEK1/ERK1/2/p90 RSK. The expression of phospho-JNK and p38 MAPK showed late upregulation in spiral neurons at 48 h, in addition to early upregulations with peaks at 3 h after noise trauma. Phospho-p38 MAPK activation was dependent on upregulation of total-p38 MAPK. At present, comprehensive data on MAP kinase expression provide significant insight into understanding the molecular mechanism of NIHL, and for developing therapeutic models for acute sensorineural hearing loss.

Quantification of TECTA and DFNA5 expression in the developing mouse cochlea.

TECTA and DFNA5 are the mouse orthologues of the human deafness-associated genes TECTA and DFNA5. To determine how expression of these genes is regulated during development, relative mRNA abundance was examined in mice by non-radioactive RT-PCR. TECTA mRNA was detected on embryonic day 15 (E15), increased to its highest level on postnatal day 3 (P3) and then dramatically decreased by P15. Low levels persisted (adulthood, P45 to 67) with mean mRNA abundance after P15 less than 25% of P3 levels. DFNA5 mRNA expression was constant throughout these time points. These results imply that TECTA is transcribed at a particularly high level during tectorial membrane morphogenesis. In contrast, DFNA5 is present in both the developing and mature cochlea.

Deletion mapping of split hand/split foot malformation with hearing impairment: a case report

Split hand/split foot malformation (SHFM), which typically appears as lobster-like limb malformation, is a rare clinical condition caused by a partial deletion of chromosome 7q. Hearing impairment sometimes accompanies syndromic SHFM cases; a case of inner and middle ear malformation with SHFM is described in this report. We conducted a genetic evaluation of this patient and found a deleted region that overlaps a previously reported locus of SHFM as well as a DFNB14 locus that can cause nonsyndromic hearing impairment by autosomal recessive inheritance.

Microarray analysis of the effect of dexamethasone on murine cochlear explants

Abstract Conclusions: The microarray analysis identified 39 genes up- or down-regulated by dexamethasone in the cultured tissue of mice cochlea. Of the eight genes most highly affected, several are suggested to have protective effects in the traumatized inner ear (Fkbp5, Glucocorticoid-induced leucine zipper (Gilz), glutathione peroxidase 3) and for others, a plausible mechanism of action can be offered (claudin 10, glutamate-ammonia ligase). The present data may support the use of dexamethasone to treat acute sensorineural hearing loss. It is warrantable to test these results in the in vivo cochlea. Objectives: To identify genes whose expression is markedly up- or down-regulated by dexamethasone in the cochlear tissue. Methods: Murine cochlear tissue was cultured with or without dexamethasone for 48 h in vitro. The gene expression profiles were compared between the dexamethasone-treated and untreated cochlear tissue using a microarray that covers 33 696 transcripts (24 878 genes) of mice and quantitative real-time RT-PCR. Results: The microarray analysis identified 39 genes that are up- or down-regulated by more than twofold in the presence of dexamethasone in the cochlear culture. Genes up- or down-regulated by at least threefold include Fkbp5, Gilz, glutathione peroxidase 3, claudin 10, glutamate-ammonia ligase, proteoglycan 1, integrin beta-like 1, and alpha subunit of glycoprotein hormone.

Role of macrophage migration inhibitory factor in age-related hearing loss

Hearing loss related to aging is the most common sensory disorder among elderly individuals. Macrophage migration inhibitory factor (MIF) is a multi-functional molecule. The aim of this study was to identify the role of MIF in the inner ear. MIF-deficient mice (MIF(-/-) mice) of BALB/c background and wild-type BALB/c mice were used in this study. Expression of MIF protein in the inner ear was examined by immunohistochemistry in wild-type mice (WT). The hearing function was assessed by the click-evoked auditory brainstem response in both MIF(-/-) mice and WT at 1, 3, 6, 9, 12, and 18months of age. Morphological examination of the cochlea was also performed using scanning electron microscopy and light microscopy. MIF was observed in the spiral ligament, stria vascularis, Reissners membrane, spiral ganglion cells (SGCs), saccular macula, and membranous labyrinth. The MIF(-/-) mice had a significant hearing loss as compared with the WT at 9, 12, and 18months of age. In the MIF(-/-) mice, scanning electron microscopy showed that the outer cochlear hair cells were affected, but that the inner cochlear hair cells were relatively well preserved. The number of SGCs was lower in the MIF(-/-) mice. MIF was strongly expressed in the mouse inner ear. Older MIF(-/-) mice showed accelerated age-related hearing loss and morphological inner ear abnormalities. These findings suggest that MIF plays an important role in the inner ear of mice.

Expression of Notch1 and Hes5 in the developing olfactory epithelium

Conclusion. Notch signaling pathway may play an important role in the development of the olfactory epithelium (OE). Objectives. To elucidate whether the Notch signaling pathway mediates the developmental processes in the developing OE. Materials and methods. The expression of Notch1 and Hes5 in the developing OE of mice with ages ranging from embryonic day (E) 11 to postnatal day (PN) 14 was examined. Results. As detected by in situ hybridization, Notch1 was expressed in scattered cells located in the basal portion of the embryonic OE and later in the cell layer adjacent to the basal lamina from E11 to PN14. Hes5 was expressed in scattered cells located in the basal portion of the embryonic OE from E11. However, at the late embryonic stage, the number of Hes5-positive cells decreased and after birth distinct Hes5-positive cells were not observed in the OE.

Monosyllable speech perception of Japanese hearing aid users with prelingual hearing loss: implications for surgical indication of cochlear implant.

OBJECTIVE The monosyllable speech perception ability after years of educational intervention was compared between prelingually deafened pediatric hearing aid users and their cochlear implant counterparts. DESIGN An open-set monosyllabic speech perception test was conducted on all subjects. The test required subjects to indicate a corresponding Japanese character to that spoken by the examiner. Fifty-two subjects with prelingual hearing impairment (47 hearing aid users and 5 cochlear implant users) were examined. RESULTS Hearing aid users with average pure-tone thresholds less than 90 dB HL demonstrated generally better monosyllable perception than 70%, which was equivalent or better performance than that of the cochlear implant group. Widely dispersed speech perception was observed within the 90-99 dB HL hearing-aid user group with most subjects demonstrating less than 50% speech perception. In the cluster of >100 dB HL, few cases demonstrated more than 50% in speech perception. The perception ability of the vowel part of each mora within the cochlear implant group was 100% and corresponding to that of hearing aid users with moderate and severe hearing loss. CONCLUSION Hearing ability among cochlear implant users can be comparable with that of hearing aid users with average unaided pure-tone thresholds of 90 dB HL, after monosyllabic speech perception testing was performed.

Macrophage Migration Inhibitory Factor Deficiency Causes Prolonged Hearing Loss After Acoustic Overstimulation.

Hypothesis Macrophage migration inhibitory factor plays an important role in noise-induced hearing loss. Background Macrophage migration inhibitory factor is an essential factor in axis formation and neural development. Macrophage migration inhibitory factor is expressed in the inner ear, but its function remains to be elucidated. Methods Macrophage migration inhibitory factor-deficient mice (MIF−/− mice) were used in this study. Wild-type and MIF−/− mice received noise exposure composed of octave band noise. Auditory brainstem response thresholds were examined before (control) and at 0, 12, and 24 hours and 2 weeks after the intense noise exposure. Morphological findings of cochlear hair cells were investigated using scanning electron microscopy. Histopathological examination with hematoxylin and eosin staining and TUNEL assay were also performed. Results In both the wild-type and MIF−/− mice, acoustic overstimulation induced significant hearing loss compared with the control level. Two weeks after the intense noise exposure, the MIF−/− mice had an increased hearing threshold compared with the wild-type mice. Scanning electron microscopy demonstrated that the outer hair cells in the MIF−/− mice were affected 2 weeks after noise exposure compared with the wild-type mice. TUNEL-positive cells were identified in the organ of Corti of the MIF−/− mice. Conclusion The MIF−/− mice had prolonged hearing loss and significant loss of cochlear hair cells after intense noise exposure. Macrophage migration inhibitory factor may play an important role in recovery from acoustic trauma. Management of macrophage migration inhibitory factor may be a novel therapeutic option for noise-induced hearing loss.