Sea-Yuong Jeon

Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition

RATIONALE Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES To determine if hypoxia drives nasal polyposis by epithelial-to-mesenchymal transition (EMT). METHODS Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1α inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS E-cadherin and α-smooth muscle actin (α-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (α-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and β-catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1α and decreased in normoxia by expressing HIF-1α. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to α-SMA induction. In CRS sinonasal specimens, HIF-1α expression was found to correlate with E-cadherin loss and α-SMA expression. Finally, HIF-1α inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.

Staphylococcus aureus enterotoxin B contributes to induction of nasal polypoid lesions in an allergic rhinosinusitis murine model.

Background Studies on the pathophysiology of nasal polyps in human subjects have been limited; thus an animal model is needed. There is increasing evidence supporting the role of Staphylococcus aureus enterotoxin B (SEB) in the pathogenesis of nasal polyposis. The aim of this study was to investigate the histological and immunologic effects of SEB on the formation of nasal polypoid lesions in an allergic rhinosinusitis murine model. Methods After induction of an ovalbumin (OVA)-induced allergic rhinosinusitis, OVA with SEB (5 or 500 ng) was instilled into the nasal cavity of mice for 8 weeks. Control mice did not receive SEB or OVA instillation. Histopathological changes were observed using hematoxylin and eosin, Sirius red, Giemsa, Massons trichrome, and Alcian blue stains. The levels of interleukin (IL)-4, IL-5, IL-8, IL-13, eotaxin, interferon gamma, total IgE, and OVA-specific IgE from serum or nasal lavage fluid were measured using enzyme-linked immunosorbent assay. Results The group treated with OVA plus 5 ng of SEB had significantly more mucosal lesions with epithelial disruption and nasal polypoid lesions than mice treated with OVA only, showing a significant increase in the infiltration of total inflammatory cells, eosinophils, and lymphocytes than the other groups. Levels of IL-5, eotaxin, and OVA-specific IgE in nasal lavage fluid were increased in the group treated with OVA plus 5 ng of SEB than in the other groups. A higher number of secretory cells in the groups treated with OVA plus SEB was observed than in other groups. Conclusion Low-dose SEB induced nasal polypoid lesions with an increased eosinophilic infiltration in an allergic rhinosinusitis murine model.

Clinical characteristics and treatment of benign paroxysmal positional vertigo after traumatic brain injury.

BACKGROUND Traumatic brain injury (TBI) has been reported to be a common cause of benign paroxysmal positional vertigo (BPPV). However, only a few studies have investigated BPPV after TBI. The aim of this study was to identify the clinical characteristics of BPPV after TBI and to determine whether there are clinical differences between BPPV after TBI and idiopathic BPPV. METHODS The authors reviewed the medical records of 192 consecutive patients with positional vertigo after head injury during the period 2003 to 2009 and investigated 112 patients with idiopathic BPPV treated over the same period. The clinical characteristics of BPPV after TBI and the clinical differences between the traumatic BPPV and idiopathic BPPV groups were investigated. RESULTS A total of 32 patients with BPPV after TBI fulfilled the inclusion criteria. Twenty-four patients in the traumatic BPPV group had posterior semicircular canal-BPPV and 11 patients lateral semicircular canal-BPPV. A total of 58 repositioning maneuver sessions were performed in these 32 patients. Members of the traumatic BPPV group required more treatment sessions than members of the idiopathic group (p<0.05), but no tendency to recur was observed in the traumatic group (p>0.05). Recurrence rates in the traumatic and idiopathic BPPV groups were 15.6% and 18.8%, respectively (p>0.05). CONCLUSIONS It is likely that BPPV after TBI is more difficult to treat than idiopathic BPPV, but no tendency to recur was observed in patients who developed BPPV after TBI compared with idiopathic BPPV. Further prospective clinical meta-analytic studies are needed to investigate the outcome of BPPV after TBI.

Microsurgical Intranasal Reconstruction of Isolated Blowout Fractures of the Medial Orbital Wall

The middle meatus is opened using a long Killian speculum. The uncinate process is resected with a knife, and the bulla and ethmoidal air cells are resected using forceps. Fractured bones of the lamina papyracea and herniated orbital contents are identified behind the resected air cells. Fractured lamina papyracea is removed. Orbital contents are separated from air cell mucosa and pushed back laterally with the long blade of a Killian speculum.

The status of the olfactory cleft may predict postoperative olfactory function in chronic rhinosinusitis with nasal polyposis.

Background Preoperative inflammation of the olfactory cleft may cause not only the obstruction of this area, but also damage of the olfactory neuroepithelium, resulting in anosmia. Therefore, the evaluation of the affected olfactory cleft by computed tomography (CT) might help predict postoperative olfaction. Methods Fifty-two patients who underwent functional endoscopic sinus surgery for chronic rhinosinusitis (CRS) with nasal polyps were examined preoperatively and at 6 months after surgery. OMU CT was obtained preoperatively and olfactory function tests such as the butanol threshold test, the cross-cultural smell identification test, and questionnaires were performed at the initial preoperative visit and at 6 months after surgery. The correlation between the status of the olfactory cleft on CT and the postoperative olfactory results were investigated. Results The findings of olfactory cleft opacification and the CT scores had a negative correlation with preoperative olfactory results (p < 0.05). The olfactory cleft opacification showed a stronger correlation with the preoperative olfactory results than the CT score. The total olfactory cleft opacification score and anterior olfactory cleft opacification score (AOCS) were more significantly correlated with the postoperative olfactory results than the other parameters (p < 0.05). Among the CT findings, the AOCS was a significant prognostic factor of olfactory results after surgery; these findings were significant on multiple regression analysis (p < 0.05). The postoperative olfactory scores and the improvement of olfactory scores after surgery were increased more in the mild AOCS group than in the moderate and severe AOCS groups (p < 0.05). Recovery and normosmia rates were much better in the mild AOCS group in this study (p < 0.05). Conclusion Preoperative CT findings, especially the anterior portion of the olfactory cleft, had a statistically significant association with the postoperative olfactory results in patients with CRS with nasal polyps.

Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model

Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model.

Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

PURPOSE Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). METHODS AND MATERIALS To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. RESULTS Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. CONCLUSION The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma.

Effects of β‐Toxin of Staphylococcus aureus on Ciliary Activity of Nasal Epithelial Cells

Objectives To investigate the in vitro effects of staphylococcal β‐to‐in on ciliary activity and the in vivo effects on sinusitis induction.

Periostin may play a protective role in the development of eosinophilic chronic rhinosinusitis with nasal polyps in a mouse model.

Several genes have been reported to be upregulated in human nasal polyps in previous genetic analyses. Among these genes, periostin is known to be overexpressed in nasal polyps obtained from aspirin‐sensitive patients. Using periostin‐null mice, we investigated the role of periostin in a murine model of eosinophilic rhinosinusitis with nasal polyps.

Clinical and histologic studies of olfactory outcomes after nasoseptal flap harvesting.

Since the introduction of an endonasal endoscopic approach in transsphenoidal pituitary surgery, reports of perioperative olfactory changes have presented conflicting results. We examined the incidence of olfactory loss in cases of endoscopic transsphenoidal pituitary surgery with skull base repair using the nasoseptal flap (NSF) and the effects of monopolar electrocautery commonly used in designing the NSF.