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Li H.-P.,Chang Gung University | Huang H.-Y.,Chang Gung University | Lai Y.-R.,Chang Gung University | Huang J.-X.,Chang Gung University | And 3 more authors.
Oncotarget | Year: 2014

MicroRNAs (miRNAs) play a pivotal role in carcinogenesis by suppressing oncogenes or tumor suppressor genes. Various studies have identified numerous miRNAs and their diverse targets; however, the consequences of dysregulated miRNAs in nasopharyngeal carcinoma (NPC) remain unclear. For this study, we found that miR-148a is downregulated through hypermethylation in NPC biopsies and NPC cell lines compared with adjacent normal and NP cells respectively. Promoter assays demonstrated that upstream stimulatory factor 1 (USF1) is a crucial transcription factor that activates miR-148a promoter activity. EMSA assays confirmed that purified USF1 binds better toward the unmethylated than the methylated CG-containing USF1 consensus probe. The ectopic expression of miR-148a inhibits cell migration in NPC cells through the suppression of integrin-mediated signaling by targeting VAV2, WASL and ROCK1. Biochemical and functional assays provided supporting evidence that these 3 genes are the downstream targets of miR-148a in NPC cells. Furthermore, immunohistochemical staining and Western blotting analysis revealed that the 3 oncogenic targets of miR-148a were overexpressed in NPC biopsies, suggesting that the inactivation of miR-148a caused by DNA methylation promotes NPC progression. Overall, our findings revealed that miR-148a can act as tumor suppressor miRNA and serve as a biomarker as well as a therapeutic target for NPC.

Kelleher J.E.,Purdue University | Zhang K.,Purdue University | Siegmund T.,Purdue University | Chan R.W.,Otolaryngology Head and Neck Surgery
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2010

The vocal ligament is known to have nonlinear variation in geometry, yet this is rarely considered in empirical or computational studies. This paper investigates the effects of a nonlinear variation of the anterior-to-posterior geometry and the corresponding spatial variation in elastic modulus on the fundamental frequency of vibration for the vocal ligament. Uniaxial tensile tests were performed on a vocal ligament specimen dissected from an excised 60-year-old male larynx. Digital image correlation (DIC) was used to obtain the spatial deformation field for the entire ligament specimen. DIC results revealed that the tensile deformation was very heterogeneous, with the least amount of deformation occurring in the region of smallest cross-sectional area. The elastic modulus was calculated locally and was found to be approximately 10 times higher at the midpoint of the vocal ligament than in the anterior and posterior macula flavae regions. Based on the spatially varying material properties obtained, finite element models (isotropic and transversely isotropic) were created to investigate how the effects of varying cross-section, heterogeneous stiffness, and anisotropy could affect the fundamental frequency of vibration. It was found that the spatial cross-section variation and the spatially varying anisotropy (i.e. modulus ratio) are significant to predictions of the vibration characteristics. Fundamental frequencies predicted with a finite element model are discussed in view of rotatory inertia and contribution of transverse shear deformation. © 2010 Elsevier Ltd.

Minami K.,Otolaryngology Head and Neck Surgery
Otolaryngology - Head and Neck Surgery (Japan) | Year: 2012

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism, accounting for approximately 1-2% of these patients. It sometimes causes severe clinical symptoms such as marked hypercalcemia and acute pancreatitis. Since the initial operation offers the best chance for cure, preoperative suspicion and intra-opera-tive recognition of the parathyroid cancer are essential. The initial operation should be en bloc resection of the tumor, avoiding rupture of the tumor capsule and the spillage of tumor cells. We described two cases of parathyroid carcinoma with no recurrence or metastasis. The clinical features and treatment approach for parathyroid carcinoma were discussed.

Buss E.,Otolaryngology Head and Neck Surgery
Proceedings of Meetings on Acoustics | Year: 2013

Auditory frequency discrimination is a basic ability that may limit the maturation of speech and language skills in some listeners. Despite its importance, the factors affecting frequency discrimination in school-aged children are poorly understood. The goal of the present study was to evaluate effects related to memory for pitch, musical training, and the utilization of temporal fine-structure cues. Listeners were normal-hearing children, 5.1 to 13.6 years old, and adults. One subgroup of children had musical training (>150 hours) and the other did not. The standard stimulus was either a 500- or a 5000-Hz pure tone, and the target stimulus was either a tone of higher frequency or a frequency-modulated tone (2- or 20-Hz rate) centered on the standard frequency. As commonly observed, mean frequency discrimination thresholds tended to be elevated in younger listeners. This developmental effect was smaller for FM detection than for pure-tone frequency discrimination, consistent with an effect of memory for pitch. The child/adult difference tended to be smaller for musically trained than untrained children. Children were not particularly poor at 2-Hz FM detection for the 500-Hz standard, a condition thought to rely on temporal fine-structure cues. © 2013 Acoustical Society of America.

Sequeira S.M.,Otolaryngology Head and Neck Surgery | Whiting B.R.,Mallinckrodt Institute of Radiology | Shimony J.S.,Mallinckrodt Institute of Radiology | Vo K.D.,Mallinckrodt Institute of Radiology | And 2 more authors.
Otology and Neurotology | Year: 2011

Hypothesis: High-resolution temporal bone computed tomography (CT) may erroneously demonstrate a superior semicircular canal dehiscence (SSCD) where none exists and inaccurately display the size of a dehiscence. Background: CT is an integral component of the diagnosis of SSCD. The prevalence of dehiscence as measured on computed tomographic scan is approximately eightfold higher than that on histologic studies, suggesting that CT may have a relatively low specificity for identifying canal dehiscence. This, in turn, can lead to an inappropriate diagnosis and treatment plan. Methods: We quantified the accuracy of CT in identifying a dehiscence of the superior semicircular canal in a cadaver model using microCT as a gold standard. The superior canals of 11 cadaver heads were blue lined. Twelve of the 22 ears were further drilled to create fenestrations of varying sizes. Heads were imaged using medical CT, followed by microCT scans of the temporal bones at 18-μm resolution. Diagnosis of dehiscence and measurements of dehiscence size were performed on clinical CT and compared with that of microCT. Results: Clinical CT identified 7 of 8 intact canals as dehiscent and tended to overestimate the size of smaller fenestrations, particularly those surrounded by thin bone. Conclusion: These findings confirm that medical CT cannot be used as the exclusive gold standard for SSCD and that, particularly for small dehiscences on CT, clinical symptoms must be clearly indicative of a dehiscence before surgical treatment is undertaken. Preoperative counseling for small dehiscences may need to include the possibility that no dehiscence may be found despite radiologic evidence for it. © 2011, Otology & Neurotology, Inc.

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