Minako Sato

A Gene for Fluctuating, Progressive Autosomal Dominant Nonsyndromic Hearing Loss, DFNA16, Maps to Chromosome 2q23-24.3

The sixteenth gene to cause autosomal dominant nonsyndromic hearing loss (ADNSHL), DFNA16, maps to chromosome 2q23-24.3 and is tightly linked to markers in the D2S2380-D2S335 interval. DFNA16 is unique in that it results in the only form of ADNSHL in which the phenotype includes rapidly progressing and fluctuating hearing loss that appears to respond to steroid therapy. This observation suggests that it may be possible to stabilize hearing through medical intervention, once the biophysiology of deafness due to DFNA16 is clarified. Especially intriguing is the localization of several voltage-gated sodium-channel genes to the DFNA16 interval. These cationic channels are excellent positional and functional DFNA16 candidate genes.

Evaluation of cigarette smoke-induced emphysema in mice using quantitative micro-computed tomography

Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few studies evaluated the dynamic structural changes in a CS-induced emphysema mouse model. A novel micro-CT technique with respiratory and cardiac gating has resulted in high-quality images that enable processing for further quantitative and qualitative analyses. Adult female C57BL/6J mice were repeatedly exposed to mainstream CS, and micro-CT scans were performed at 0, 4, 12, and 20 wk. Emphysema was also histologically quantified at each time point. Air-exposed mice and mice treated with intratracheal elastase served as controls and comparisons, respectively. End-expiratory lung volume, corresponding to functional residual volume, was defined as the calculated volume at the phase of end-expiration, and it evaluated air trapping. The end-expiratory lung volumes of CS-exposed mice were significantly larger than those of air controls at 12 and 20 wk, which was in line with alveolar enlargement and destruction by histological quantification. However, CS exposure neither increased low attenuation volume nor decreased the average lung CT value at any time point, unlike the elastase-instilled emphysema model. CS-exposed mice had rather higher average lung CT values at 4 and 12 wk. This is the first study characterizing a CS-induced emphysema model on micro-CT over time in mice. Moreover, these findings extend our understanding of the distinct pathophysiology of CS-induced emphysema in mice.

Electrocochleography during experimental cochlear ischemia of the guinea pig

It has been postulated that impairment of cochlear blood flow (CoBF) is one of the most important causes of hearing loss occurring during acoustic neuroma (AN) surgery. However, it remains unclear how the degree of cochlear ischemia influences the evoked responses in electrocochleography. (ECochG) which has been used for monitoring cochlear functions. In the present study, we investigated alterations in ECochG during cochlear ischemia of varying degree in the guinea pig. In order to induce cochlear ischemia, the anterior inferior cerebellar artery (AICA) was mechanically compressed via the transclival approach. The compression of AICA resulted in the reduction of CoBF in 55 out of 70 guinea pigs. A constant reduction of CoBF was maintained during the compression of AICA in 44 (63%) guinea pigs. CoBF abruptly decreased upon compressing AICA, and promptly recovered after releasing the compression. N1 and N2 in ECochG were also altered by compression. During 3-min ischemia, N1 and N2 disappeared in 36% and 41% of the cases, respectively. The residual CoBF in cases whose N1 and N2 disappeared was significantly lower than that in other cases whose N1 and N2 were sustained during 3-min ischemia. In addition, there was a tendency that the lower the residual CoBF was, the shorter the survival time of N1 and N2. In cases whose N1 and N2 did not disappear, the prolongation of N1 and N2 latencies after 3-min ischemia was positively correlated to the residual CoBF. On the basis of these results, we discuss the mechanisms underlying the changes in CoBF and ECochG during cochlear ischemia, and conclude that the degree of cochlear ischemia during AN surgery can be estimated with ECochG.

Pneumococcal Infection Aggravates Elastase-Induced Emphysema via Matrix Metalloproteinase 12 Overexpression

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (COPD)--typically caused by bacterial or viral infection--is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. METHODS We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. RESULTS In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, an increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly owing to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and emphysema progression. CONCLUSIONS These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD.

Effects of neuropeptide Y on cochlear blood flow in guinea pigs

The aim of this study was to clarify the effects of neuropeptide Y (NPY) on cochlear blood flow (CBF) in pigmented guinea pigs. NPY was administered with or without noradrenaline (NA) by systemic perfusion or perilymphatic local perfusion, and CBF was measured using a laser Doppler flowmeter. The systemic and perilymphatic administrations of NPY with NA induced greater prolongation of the increase in and recovery of CBF than the administration of NA or NPY alone. Continuous reduction in CBF induced by NPY may play an important role in the pathogenesis of stress-induced sensorineural hearing losses, such as sudden deafness.The aim of this study was to clarify the effects of neuropeptide Y (NPY) on cochlear blood flow (CBF) in pigmented guinea pigs. NPY was administered with or without noradrenaline (NA) by systemic perfusion or perilymphatic local perfusion, and CBF was measured using a laser Doppler flowmeter. The systemic and perilymphatic administrations of NPY with NA induced greater prolongation of the increase in and recovery of CBF than the administration of NA or NPY alone. Continuous reduction in CBF induced by NPY may play an important role in the pathogenesis of stress-induced sensorineural hearing losses, such as sudden deafness.

Impact of cataract on health-related quality of life in a longitudinal Japanese chronic obstructive pulmonary cohort:

Cigarette smoking increases the risk of developing both cataract and chronic obstructive pulmonary disease (COPD). The prevalence of cataract and the clinical characteristics of COPD patients with cataract were retrospectively investigated in a 2-year observational COPD cohort. We analyzed 395 patients with complete data on ophthalmologic evaluation (319 subjects with COPD and 76 subjects at risk of COPD). There was no difference in the prevalence of cataract between COPD patients and those at risk (47.0% vs. 42.1%, p = 0.44). Age ≥ 75 years, low body mass index, and hypertension were independently associated with cataract as a comorbidity in COPD. The incidence of exacerbation within 2 years was significantly higher in COPD patients with cataract than those without cataract (36.6% vs. 18.3%, p = 0.0019). COPD patients with cataract exhibited significantly higher COPD assessment test score compared to those without cataract (13.7 ± 8.9 vs. 11.5 ± 7.2, p = 0.0240). Overall St George’s Respiratory Questionnaire score and each component were significantly worse in COPD patients with cataract compared to those without cataract. COPD patients with cataract exhibited poor health-related quality of life and frequent exacerbations. The association between cataract and exacerbations of COPD deserves further attention.

Predictors of readmission after successful electroconvulsive therapy for depression: a chart review study

Abstract Objective: The study aimed to identify the predictors for readmission after a successful electroconvulsive therapy (ECT) course. Methods: Medical charts of patients who received ECT for major depressive episodes were reviewed. Patients’ demographic characteristics and treatment parameters, such as ECT charge, seizure duration, the number of ECT sessions and pharmacotherapy, were extracted. We compared differences between those who were readmitted after successful ECT within 6 and 12 months, versus those not readmitted. We also conducted a multivariate logistic regression analysis to identify the predictors for readmission. Results: Out of 51 patients who were discharged after ECT, 27 patients met the inclusion criteria and were included in the analysis. Eight patients were readmitted within 6 months after discharge, and four more patients were readmitted during the next 6-month follow up. Comparing patients who were and were not readmitted, we found no significant differences between groups, including ECT parameters such as the number of ECT sessions, average charge and final charge. No predictors for readmission were found through multivariate analysis. Conclusions: Although patients who require higher ECT charge and more sessions seem to be prone to readmission, our dataset suggested that none of these types of ECT parameters were risk factors for readmission.