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Sun G.-W.,Sensory Medical | Fujii M.,Sensory Medical | Matsunaga T.,Sensory Medical
Journal of Neuroscience Research | Year: 2012

Spiral ligament fibrocytes (SLFs) play an important role in normal hearing as well as in several types of sensorineural hearing loss attributable to inner ear homeostasis disorders. Our previous study showed that transplantation of mesenchymal stem cells (MSCs) into the inner ear of rats with damaged SLFs significantly accelerates hearing recovery compared with rats without MSC transplantation. To elucidate this mechanism of SLF repair and to determine the contribution of transplanted MSCs in this model, we investigated the mutual effects on differentiation and proliferation between MSCs and SLFs in a coculture system. Factors secreted by SLFs had the ability to promote the transdifferentiation of MSCs into SLF-like cells, and the factors secreted by MSCs had a stimulatory effect on the proliferation of SLFs. Cytokine antibody array analysis revealed the involvement of transforming growth factor-β (TGF-β) in SLF proliferation induced by MSCs. In addition, a TGF-β inhibitor reduced SLF proliferation induced by MSC stimulation. Our results suggest that there are two mechanisms of hearing recovery following transplantation of MSCs into the inner ear: 1) MSCs transdifferentiate into SLF-like cells that compensate for lost SLFs, and 2) transplanted MSCs stimulate the regeneration of host SLFs. Both mechanisms contribute to the functional recovery of the damaged SLF network. © 2012 Wiley Periodicals, Inc.


Kleinbongard P.,University of Duisburg - Essen | Gedik N.,University of Duisburg - Essen | Witting P.,University of Sydney | Freedman B.,Concord Repatriation General Hospital | And 2 more authors.
British Journal of Pharmacology | Year: 2015

Background and Purpose In pigs, ivabradine reduces infarct size even when given only at reperfusion and in the absence of heart rate reduction. The mechanism of this non-heart rate-related cardioprotection is unknown. Hence, in the present study we assessed the pleiotropic action of ivabradine in more detail. Experimental Approach Anaesthetized mice were pretreated with ivabradine (1.7mg·kg-1 i.v.) or placebo (control) before a cycle of coronary occlusion/reperfusion (30/120min ± left atrial pacing). Infarct size was determined. Isolated ventricular cardiomyocytes were exposed to simulated ischaemia/reperfusion (60/5min) in the absence and presence of ivabradine, viability was then quantified and intra- and extracellular reactive oxygen species (ROS) formation was detected. Mitochondria were isolated from mouse hearts and exposed to simulated ischaemia/reperfusion (6/3min) in glutamate/malate- and ADP-containing buffer in the absence and presence of ivabradine respectively. Mitochondrial respiration, extramitochondrial ROS, mitochondrial ATP production and calcium retention capacity (CRC) were assessed. Key Results Ivabradine decreased infarct size even with atrial pacing. Cardiomyocyte viability after simulated ischaemia/reperfusion was better preserved with ivabradin, the accumulation of intra- and extracellular ROS decreased in parallel. Mitochondrial complex I respiration was not different without/with ivabradine, but ivabradine significantly inhibited the accumulation of extramitochondrial ROS, increased mitochondrial ATP production and increased CRC. Conclusion and Implications Ivabradine reduces infarct size independently of a reduction in heart rate and improves ventricular cardiomyocyte viability, possibly by reducing mitochondrial ROS formation, increasing ATP production and CRC. © 2015 The British Pharmacological Society.


Kaga K.,Sensory Medical
Brain and nerve = Shinkei kenkyu no shinpo | Year: 2017

The 20, 21, and 22 areas in the temporal lobe as classified by Brodmann are almost identical with Economo and Koskinas's TA, TE1, and TE2, and, generally, with the gyrus, middle temporal gyrus, and inferior temporal gyrus according to brain anatomy. Before Brodmann's classification, Flechsig published his book "Soul and Brain" in 1897, in which primary, secondary, and association areas in the brain were classified. More recently, results from research using magnetic resonance imaging (MRI) and fMRI support the parcellation of the cerebral cortex proposed by Flechsig, Brodmann, and Economo more than one century ago.


Saka S.K.,Sensory Medical | Saka S.K.,International Max Planck Research | Honigmann A.,Max Planck Institute for Biophysical Chemistry | Eggeling C.,Weatherall Institute of Molecular Medicine | And 3 more authors.
Nature Communications | Year: 2014

Most proteins have uneven distributions in the plasma membrane. Broadly speaking, this may be caused by mechanisms specific to each protein, or may be a consequence of a general pattern that affects the distribution of all membrane proteins. The latter hypothesis has been difficult to test in the past. Here, we introduce several approaches based on click chemistry, through which we study the distribution of membrane proteins in living cells, as well as in membrane sheets. We found that the plasma membrane proteins form multi-protein assemblies that are long lived (minutes), and in which protein diffusion is restricted. The formation of the assemblies is dependent on cholesterol. They are separated and anchored by the actin cytoskeleton. Specific proteins are preferentially located in different regions of the assemblies, from their cores to their edges. We conclude that the assemblies constitute a basic mesoscale feature of the membrane, which affects the patterning of most membrane proteins, and possibly also their activity. © 2014 Macmillan Publishers Limited.


Masuda S.,National Mie Hospital | Usui S.,National Mie Hospital | Matsunaga T.,Sensory Medical
International Journal of Pediatric Otorhinolaryngology | Year: 2013

Objective: Radiological and genetic examination has recently advanced for diagnosis of congenital hearing loss. The aim of this study was to elucidate the prevalence of inner-ear and/or internal auditory canal malformations in children with unilateral sensorineural hearing loss (USNHL) for better management of hearing loss and genetic and lifestyle counseling. Methods: We conducted a retrospective study of charts and temporal bone computed tomography (CT) findings of 69 consecutive patients 0-15 years old with USNHL. In two cases, genetic examination was conducted. Results: Of these patients, 66.7% had inner-ear and/or internal auditory canal malformations. The prevalence of malformations in infants (age <1 year) was 84.6%, which was significantly higher than that in children 1-15 years old (55.8%; p<0.01). Almost half of the patients (32; 46.4%) had cochlear nerve canal stenosis; 13 of them had cochlear nerve canal stenosis alone, and in 19 it accompanied other malformations. Internal auditory canal malformations were observed in 22 subjects (31.8%), 14 (20.3%) had cochlear malformations, and 5 (7.2%) had vestibular/semicircular canal malformations. These anomalies were seen only in the affected ear, except in two of five patients with vestibular and/or semicircular canal malformations. Two patients (2.9%) had bilateral enlarged vestibular aqueducts. Mutations were found in SLC26A4 in one of the two patients with bilateral large vestibular aqueducts. The prevalence of a narrow internal auditory canal was significantly higher in subjects with cochlear nerve canal stenosis (50.0%) than in subjects with normal cochlear nerve canals (11.1%; p<0.01). There were no correlations between the type and number of malformations and hearing level. Conclusions: The prevalence of inner-ear and/or internal auditory canal malformations detected by high-resolution temporal bone CT in children with USNHL was very high. Radiological and genetic examination provided important information to consider the pathogenesis and management of hearing loss. Temporal bone CT should be recommended to children with USNHL early in life. SLC26A4 mutation also should be examined in cases with bilateral enlarged vestibular aqueduct. © 2012 Elsevier Ireland Ltd.


Tsunoda M.,Tsunoda Clinic | Tsunoda K.,Sensory Medical
Annals of Family Medicine | Year: 2014

Various methods are used to treat ingrown or pincer-like toenails. We developed a novel taping method to prevent topical interruption of the circulation and resulting skin conditions and evaluated it over 14.5 years. We instructed 541 patients or their guardians in the use of the technique. Ingrown toenail symptoms and abnormal nail growth were resolved and no additional therapy was required in 276 patients. The novel taping method was significantly more effective than treatments our patients had received previously. Patient-controlled taping is the first-line treatment for every ingrown or curved toenail seen in our clinic.


Hatou S.,Sensory Medical | Hatou S.,Keio University
Cornea | Year: 2011

Na-and K-dependent ATPase (Na +,K +-ATPase) in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in these cells. Mouse corneal endothelial cells were exposed to dexamethasone or insulin. ATPase activity was evaluated by spectrophotometric measurement, and pump function was measured using an Ussing chamber. Western blotting and immunocytochemistry were performed to measure the expression of the Na,K-ATPase ±1-subunit. Dexamethasone increased Na,K-ATPase activity and the pump function of endothelial cells. Western blot analysis indicated that dexamethasone increased the expression of the Na,K-ATPase ±1-subunit but decreased the ratio of active to inactive Na,K-ATPase ±1-subunit. Insulin increased Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were transient and blocked by protein kinase C inhibitors and inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A). Western blot analysis indicated that insulin decreased the amount of inactive Na,K-ATPase ±1-subunit, but the expression of total Na,K-ATPase ±1-subunit was unchanged. Immunocytochemistry showed that insulin increased cell surface expression of the Na,K-ATPase ±1-subunit. Our results suggest that dexamethasone and insulin stimulate Na +,K +-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells was mediated by Na,K-ATPase synthesis and an increased enzymatic activity because of dephosphorylation of Na,K-ATPase ±1-subunits. The effect of insulin is mediated by the protein kinase C, PP1, and/or PP2A pathways. © 2011 by Lippincott Williams & Wilkins.


For the past 10 years, number of evidence has shown that activation of complement cascade has been associated with age-related macular degeneration (AMD). The genome wide association study in American population with dominantly dry-type AMD has revealed strong association with single nucleotide polymorphism (SNP) of complement genes. Protein composition of drusen, a deposit observed in sub-retinal space between Bruch's membrane and retinal pigment epithelial (RPE), contains active complement molecules in human and monkey. These evidences have leaded us to consider the possibility of suppressing complement cascade in the retina to delay or reverse the onset of AMD. To test is hypothesis we used the C3 inhibitor Compstatin on primate model with early-onset macular degeneration which develop drusen in less than 2 years after birth. Our preliminary result showed drusen disappearance after 6 months of intravitreal injection. © Springer Science+Business Media, LLC 2010.


Wen S.,Sensory Medical | Schroeter A.,Sensory Medical | Klocker N.,Sensory Medical
Archives of Biochemistry and Biophysics | Year: 2013

Hepatic encephalopathy (HE)1 is a common neuropsychiatric complication of both acute and chronic liver disease. Clinical symptoms may include motor disturbances and cognitive dysfunction. Available animal models of HE mimic the deficits in cognitive performance including the impaired ability to learn and memorize information. This review explores the question how HE might affect cognitive functions at molecular levels. Both acute and chronic models of HE constrain the plasticity of glutamatergic neurotransmission. Thus, long-lasting activity-dependent changes in synaptic efficiency, known as long-term potentiation (LTP) and long-term depression (LTD) are significantly impeded. We discuss molecules and signal transduction pathways of LTP and LTD that are targeted by experimental HE, with a focus on ionotropic glutamate receptors of the AMPA-subtype. Finally, a novel strategy of functional proteomic analysis is presented, which, if applied differentially, may provide molecular insight into disease-related dysfunction of membrane protein complexes, i.e. disturbed ionotropic glutamate receptor signaling in HE. © 2013 Elsevier Inc. All rights reserved.


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