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Full-Text Articles in Medicine and Health Sciences

A Deafness Mechanism Of Digenic Cx26 (Gjb2) And Cx30 (Gjb6) Mutations: Reduction Of Endocochlear Potential By Impairment Of Heterogeneous Gap Junctional Function In The Cochlear Lateral Wall, Ling Mei, Jin Chen, Liang Zong, Yan Zhu, Chun Liang, Raleigh O. Jones, Hong-Bo Zhao Dec 2017

A Deafness Mechanism Of Digenic Cx26 (Gjb2) And Cx30 (Gjb6) Mutations: Reduction Of Endocochlear Potential By Impairment Of Heterogeneous Gap Junctional Function In The Cochlear Lateral Wall, Ling Mei, Jin Chen, Liang Zong, Yan Zhu, Chun Liang, Raleigh O. Jones, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26+/−/Cx30+/−) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26+/−/Cx30+/− heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26−/−) mice, the cochlea in Cx26 …


P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao Nov 2017

P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma …


Progressive Age-Dependence And Frequency Difference In The Effect Of Gap Junctions On Active Cochlear Amplification And Hearing, Liang Zong, Jin Chen, Yan Zhu, Hong-Bo Zhao Jul 2017

Progressive Age-Dependence And Frequency Difference In The Effect Of Gap Junctions On Active Cochlear Amplification And Hearing, Liang Zong, Jin Chen, Yan Zhu, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low …


Hypothesis Of K+-Recycling Defect Is Not A Primary Deafness Mechanism For Cx26 (Gjb2) Deficiency, Hong-Bo Zhao May 2017

Hypothesis Of K+-Recycling Defect Is Not A Primary Deafness Mechanism For Cx26 (Gjb2) Deficiency, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

K+-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K+ ions after hair cell excitation, causing accumulation of K+-ions in the extracellular space around hair cells producing K+-toxicity, which eventually induces hair cell degeneration and hearing loss. However, this hypothesis has never been directly evidenced, even though it has been widely referred …


Correlation Of Positron Emission Tomography/Computed Tomography Scan With Smoking, Tumor Size, Stage And Differentiation In Head And Neck Cancer Patients, Jordan L. Pleitz, Partha Sinha, Emily V. Dressler, Rony K. Aouad Jan 2017

Correlation Of Positron Emission Tomography/Computed Tomography Scan With Smoking, Tumor Size, Stage And Differentiation In Head And Neck Cancer Patients, Jordan L. Pleitz, Partha Sinha, Emily V. Dressler, Rony K. Aouad

Otolaryngology--Head & Neck Surgery Faculty Publications

The goal of this study was to identify associations between positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) in patients presenting with head and neck squamous cell carcinoma (SCC) with tumor site, size, histologic differentiation, smoking, and diabetes. Charts of patients with oropharyngeal and laryngeal SCC who underwent 18F-fluorodeoxyglucose PET/CT scans were reviewed between May 2007 and August 2013. Statistical analyses included modeling log-transformed SUVmax values by tumor site, size, histologic differentiation, smoking status, and diabetes using unadjusted linear regressions. Differences were considered statistically significant for P< 0.05. A total of 111 patients (54 with oropharynx and 57 with larynx cancers) were included, 83 men and 28 women with an average age of 57.5 years old. There was a significantly higher pack-year smoking history (P = 0.005) in the larynx cancer group. While tumor …