Animal Models of Middle Ear Cholesteatoma

Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma

<ORIGINAL REPORT>IMMUNOHISTOCHEMICAL STUDIES ON LACTATE DEHYDROGENASE SUBUNITS IN LUNG CANCER CELLS

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました。Immunohistochemical distribution of lactate dehydrogenase (LDH) subunits in human lung cancer cells were studied using fluorescent antibody technique. Both in cytological and histological specimen, specific fluorescence of LDH-H and LDH-M were seen in the cytoplasm of cancer cells, and in most cases no remarkable difference could be demonstrated between the distribution of H and M subunit. But in some cases specific fluorescence of M-subunit was stronger than that of H-subunit. The fluorescence of M-subunit was demonstrated as fine granules diffusely in the cytoplasm. On the other hand the fluorescence of H-subunit was rather localized and demonstrated as rather coarse granules. And this observation was discussed

Cold Rolling and Annealing Texture of 1% Carbon Steel

1% carbon steel was cold-rolled to 50～98.4% reduction by adhering ductile materials to the sheet edges. Globular cementite particles (Fe_3C) were formed on annealing the cold-rolled sheet below A_1 point. The effect of these particles on the annealing process and texture was studied. The results obtained are summarized as follows : (1) The cold rolling texture consists of three preferred orientations, (001) [110], (112) [110] and (111) [211], as in the case of iron and low carbon steels, but with increasing reduction. (111) [211] component disappears, while (001) [110] and (112) [110] components become dominant. (2) The mean inter-spacing of Fe_3C particles is smaller than the critical size of the recrystallization nuclei at the annealing 700℃×10 hr and becomes nearly equal to at 700℃×hr, that is, the nucleation of recrystallization is remarkably retarded by Fe_3C particles. (3) Even after a prolonged annealing (700℃×100 hr), the annealing textures are similar to the rolling texture, but at 98.4% reduction the (112) [110] component which has a higher growing rate of its subgrains than that of (001) [110] component becomes very dominant. From these results the recrystallization mechanisms are discussed

Bilateral Cochlear Implantation for Children in Nagasaki, Japan

Objectives: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. Methods: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. Results: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. Conclusion: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere

What Factors Are Associated with Good Performance in Children with Cochlear Implants? From the Outcome of Various Language Development Tests, Research on Sensory and Communicative Disorders Project in Japan: Nagasaki Experience

ObjectivesWe conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss.MethodsWe evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests.ResultsOverall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school.ConclusionIn this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss

Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity.

To investigate the cell-biological effect of topically applied 5-fluorouracil (5-FU) on middle ear cholesteatoma, 12 attic cholesteatomas were treated with topical application of 5-FU cream, two to five times with an interval of 2 weeks (5-FU group). The control group comprised 65 cholesteatoma that were not treated with 5-FU. All lesions were later excised surgically and processed for immunohistochemical analyses of Ki-67, keratinocyte growth factor (KGF) and its receptor (KGFR). 5-FU significantly reduced the expression of KGF, did not change KGFR expression, and significantly reduced the Ki-67 labeling index, relative to the control group. The effect of 5-FU on cholesteatoma seems to be mediated, at least in part, through downregulation of KGF in stromal cells and reduction of the proliferative activity of epithelial cells

A Novel Function of Noc2 in Agonist-Induced Intracellular Ca2+ Increase during Zymogen-Granule Exocytosis in Pancreatic Acinar Cells

Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell imaging, we investigated its role in Ca2+-dependent zymogen granule (ZG) exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO) mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of progress of ZG exocytosis did not differ significantly between the two strains. ZG exocytosis from KO acinar cells was seldom observed at physiological concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash photolysis of a caged calcium compound confirmed the integrity of the fusion step of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at physiological concentrations of agonists raised the possibility of impaired elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells by a high agonist concentration: (a) they always started at the apical portion and traveled to the basal portion, and (b) calcium oscillations over the 10 µM level were observed, as in WT acinar cells. At physiological concentrations of agonists, however, sufficient calcium spikes were not observed, suggesting an impaired [Ca2+]i-increase mechanism in KO acinar cells. We propose that in pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG per se, but instead performs a novel function favoring agonist-induced physiological [Ca2+]i increases

Epidemiological survey of acute low-tone sensorineural hearing loss

Objectives: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically.Methods: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student’s t-test, χ2 test and logistic regression.Results: Female gender (p < .013), younger age (p < .001), low-grade hearing loss (p < .001), and shorter interval between onset and initial visit (p < .004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p < .007).Conclusions: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL

The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss : a nationwide survey in Japan

Objective: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies.Methods: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups.Results: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids.Conclusion: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss

Relationships among drinking and smoking habits, history of diseases, body mass index and idiopathic sudden sensorineural hearing loss in Japanese patients

Objectives: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan.Materials and methods: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index.Results: The proportion of current smokers was significantly higher among men aged 50–59, 60–69 and 70+ and among women aged 30–39, 40–49 and 60–69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50–59, 60–69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60–69 showed lower proportions of current drinking; and female SSNHL subjects aged 60–69 showed higher proportions of overweight (BMI ≥25 kg/m2).Conclusions: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls