Ju Wan Kang

Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase‐3‐dependent apoptosis in oral cavity cancer cells

EGb 761, extracted from Ginkgo biloba leaves, has been proven to induce caspase‐3‐dependent apoptosis in oral cavity cancer cells. Since EGb 761 is a composition of various components, it is important to identify which components are responsible for its anticancer effects to reduce the total dosage and to avoid toxicity. Therefore, the study aimed to determine the effective compounds of EGb 761 that induce apoptosis in oral cavity cancer cells and to identify whether caspase‐3 was involved in apoptosis of oral cancer cells by EGb 761 components. The results of cell proliferation assays on oral cavity cancer cells showed that kaempferol and quercetin significantly inhibited cellular proliferation at a concentration of 40 µM. Flow cytometry showed that the antiproliferative effects of each component were due to increased apoptosis. Kaempferol and quercetin induced apoptosis in various oral cancer cell lines (SCC‐1483, SCC‐25 and SCC‐QLL1) and showed cleavage of poly (ADP‐ribose) polymerase (PARP). Caspase‐3 activity assay revealed that induction of apoptosis by kaempferol and quercetin was caspase‐3‐dependent. In conclusion, the results suggest that kaempferol and quercetin, two components of EGb 761, effectively induce caspase‐3‐dependent apoptosis of oral cavity cancer cells and can be considered as possible anti‐oral cavity cancer agents. Copyright

Effects of a Low Concentration Hypochlorous Acid Nasal Irrigation Solution on Bacteria, Fungi, and Virus†

Objectives/Hypothesis: Saline irrigation would be more effective for chronic sinusitis patients if it had bactericidal effects. Low concentrations of hypochlorous acid may be used as a nasal irrigation solution. First, we developed a 0.85% NaCl solution by adding NaCl to tap water (pH 7.0 and 8.4) and measuring the concentration of free chlorine and hypochlorous acid after giving the solution a short electrical impulse of 20 seconds. Then we investigated whether the derived hypochlorous acid had a toxic effect on human primary nasal epithelial cells, if and what effect it had on the expression of mucin genes, and, finally, if it had bactericidal, fungicidal, or virucidal effects.

Activation of c‐Myb transcription factor is critical for PMA‐induced lysozyme expression in airway epithelial cells

Lysozyme is a major component of airway epithelial secretions, acts as cationic anti‐microbial protein for innate immunity. Although lysozyme plays an important role in airway defense and is a key component of airway secretions under inflammatory conditions, little is understood about the regulation of its expression and the associated signaling pathway. We wanted to examine whether Phorbol 12‐myristate 13‐acetate (PMA), one of PKC activators, treatment of the airway epithelial cell line NCI‐H292 increases lysozyme gene expression. In this study, we sought to determine which signal molecules are involved in PMA‐induced lysozyme gene expression. We found that PKC and mitogen‐activating protein/ERK2 kinase are essential for PMA‐induced lysozyme expression and also mediate the PMA‐induced activation of c‐Myb protein. We identified a proximal region of the lysozyme promoter essential for promoter activity containing c‐Myb transcription factor binding site. Additionally, by site‐directed promoter mutagenesis, we identified that c‐Myb preferred the CAA motif of the −85/−73 region of the lysozyme promoter. Finally, we showed that overexpression of c‐Myb without PMA treatment increased the lysozyme promoter activity and protein expression. From these results, we conclude that PMA induces overexpression of lysozyme via ERK1/2 MAP kinase—c‐Myb signaling pathways in NCI‐H292 cells. J. Cell. Biochem. 111: 476–487, 2010.

Association of serum 25-hydroxyvitamin D with serum IgE levels in Korean adults

OBJECTIVE Studies about the association between vitamin D and allergic disease and the immune-modulatory function of vitamin D have increased in the recent years. However, not enough studies have been conducted for concrete conclusion about the association vitamin D and allergy. We investigate the association between serum immunoglobulin E (IgE) and serum 25-hydroxyvitamin D (25(OH)D) levels in Korean adults. METHODS We used data of 1969 subjects from the 2010 Korean National Health and Nutrition Examination Survey. Total IgE, Dermatophagoides farinae (Df)-specific IgE, and serum 25(OH)D levels were analyzed. Other variables included sex, age, body mass index, smoking history, and economic status. Adjusted regression analysis was used to examine the independent association of 25(OH)D with serum IgE levels. RESULTS When we divided all subjects into four groups according to the serum 25(OH)D level: Q1 (lowest), Q2, Q3, and Q4 (highest), the median TIgE level increased with higher quartiles in the Kruskal-Wallis test (p<0.001). Also, the prevalence of Df sensitization was highest in Q4. Serum vitamin D was positively associated with logarithmic transformed total IgE with base of 10 (LogTIgE) (coefficient (B), 0.011; 95% confidence interval, 0.001-0.021). Furthermore, a positive association between 25(OH)D and LogTIgE was found only in men with Df sensitization, but not in men without Df sensitization and women with/without Df sensitization. However, the mean serum 25(OH)D level was significantly lower in participants who were clinically diagnosed with asthma or atopic dermatitis than participants without a history of asthma or atopic dermatitis, respectively. CONCLUSION Serum 25(OH)D levels were positively associated with total IgE levels. Furthermore, the association between serum 25(OH)D and total IgE levels could vary depending on sex or allergic sensitization. But, the mean serum 25(OH)D level was lower in participants with asthma or atopic dermatitis history than participants without history of asthma or atopic dermatitis. Prospective further studies will be required to verify this discrepancy.

Robotic nasopharyngectomy via combined endonasal and transantral port: A preliminary cadaveric study

The objective of this study was to determine the potential role of a surgical robotic system in nasopharyngeal surgery using bilateral transantral or combined endonasal/transantral port.

Histamine skin reactivity increases with body mass index in Korean children

OBJECTIVE Histamine skin prick testing is most commonly used to diagnose immunoglobulin E (IgE)-mediated allergic diseases, and histamine reactivity is used as a standardized positive control in the interpretation of a skin prick test. However, reactivity to histamine differs among individuals for reasons that are poorly understood. The present study aimed to evaluate the potential association between body mass index (BMI) and histamine skin reactivity in children. METHODS A total of 451 children (246 boys, 205 girls) aged 7-8 years were enrolled in this study. The skin prick test was performed with 26 aeroallergens commonly found in Korea. Other information was collected, including sex, age, BMI, parental allergy history, and parental smoking status. Multivariate analysis was used to confirm the association between histamine skin reactivity and BMI. RESULTS The histamine wheal size was revealed to be associated with BMI (Spearmans Rho 0.161, p<0.001). This association was confirmed by multivariate analysis, after adjusting for sex, age, parental allergy history, parental smoking status, and allergic sensitization (coefficient B 0.071, 95% confidence interval 0.030-0.112). CONCLUSIONS Skin responses to histamine were primarily correlated with increased BMI. Further studies are needed to understand the clinical implication of BMI when interpreting the results of skin prick test.

The association between serum vitamin D level and immunoglobulin E in Korean adolescents

OBJECTIVE Vitamin D has immune modulatory functions, and thus its relationship with allergic disease has been evaluated in a number of studies. However, no concrete link between serum IgE level and vitamin D has been established. Thus, the purpose of study was to confirm the association of serum vitamin D level with the serum IgE (total and Dematophagoides farinae specific IgE) in Korean adolescents. METHODS A total of 365 subjects between 10 and 18 years of age were enrolled through the Korea National Health and Nutrition Examination Survey (KNHANES). Serum levels of vitamin D, total IgE, and Dermatophagoides farinae (Df) specific IgE were measured, and data for potential confounding variables were collected. Multivariate regression analyses were used to determine the independent effects of these variables. RESULTS Levels of both total and Df specific IgE were positively correlated with serum concentration of vitamin D (Spearmans rho (R)=0.126, p=0.016; R=0.152, p=0.004, respectively). These results were confirmed by multivariate linear regression analysis after adjusting for sex, age, and body mass index (coefficient (B): 10.45 95% confidence interval (CI): 0.59-20.31; B: 1.06, 95% CI: 0.31-1.80, respectively). And, the association between serum vitamin D and IgE showed the different results depending on the presence or absence of Df sensitization. CONCLUSIONS Serum concentration of vitamin D was positively associated with levels of both total IgE and Df-specific IgE in Korean adolescents.

Intranasal mycetoma-induced Splendore-Hoeppli phenomenon

The Splendore-Hoeppli phenomenon represents eosinophilic radiate structures surrounded by inflammatory cells, such as eosinophils and lymphocytes, and has been reported in infectious and noninfectious (inflammatory reactions to silk suture material) processes. This reaction can occur at various regions, such as the skin, subcutaneous tissue, and conjunctiva. To our knowledge, a case of intranasal Splendore-Hoeppli phenomenon has not been reported to date. This study was approved by the institutional review board of Severance Hospital. A 54-year-old man with a history of nasal obstruction of several months duration was seen. He did not have any special history. Nasal examination showed a polypoid mass that completely filled the right nasal cavity. Paranasal computed tomography (CT) showed that the expansile mass was heterogeneously enhanced. This mass lesion extended to the ipsilateral maxillary sinus, ethmoid sinus, and frontal sinus. The right middle turbinate was partially destroyed. The perpendicular plate of the ethmoid bone was remodeled. The mass did not extend to the intracranial or intraorbital areas (Fig 1). Suspected diagnoses were inverted papilloma, nasal polyposis, or chronic granulomatous disease. An incisional biopsy was performed, and histologic examination showed nonspecific chronic inflammation. Endoscopic sinus surgery was performed. A bluish mass that bled easily on gentle probing filled the nasal cavity. The stalk of the mass was cut and the mass was removed. Histologic examination (hematoxylin and eosin) showed eosinophilic material surrounding the fungal ball (Fig 2), and Gomori methenamine silver staining slide revealed numerous fungal hyphae and was highly suspicious for Aspergillus. Ziehl-Neelsen stain was performed, revealing acid-fast bacilli, and the results were negative, which was consistent with the SplendoreHoeppli phenomenon. The patient was discharged after three days without any problems. He was well 10 months after surgery. Discussion Eosinophilic radiate structures that form around fungi, helminth ova, and certain bacteria have been variously termed “asteroid bodies” and “rosette-like clubs” and are indicative of the Splendore-Hoeppli phenomenon. The SplendoreHoeppli phenomenon has been sporadically described since the early 20th century, mainly in the veterinary fields. The first report of the phenomenon was by Splendore in 1908. He described an amorphous eosinophilic material surrounded by granulomatous inflammation with an abundance of eosinophils. In 1932, Heoppli reported a similar phenomenon associated with fungal infection. There are numerous causative agents, such as fungi (Candida and Aspergillus species), bacteria (Nocardia and Actinomyces), and noninfectious conditions in allergic conjunctival granuloma asso-

Relationship between various anthropometric measures and apnea-hypopnea index in Korean men

OBJECTIVE Body mass index (BMI) has been shown to be strongly correlated with severity of OSA. However, BMI has not been shown to be correlated with sleep apnea in all patients studied. The purpose of this study was to evaluate the relationship between various anthropometric measures and severity of OSA according to BMI in men. METHODS We conducted a retrospective analysis of the medical records of patients who visited for evaluation of OSA. Polysomnography results, height, weight, neck circumference, waist circumference, and hip circumference were obtained in all subjects. BMI, body adiposity index, waist to hip ratio, and waist to height ratio were also calculated. RESULTS A total of 195 male participants were included in the final analysis. BMI showed the strongest correlation with AHI in all subjects. In 125 participants with a BMI of 25 or more, BMI was most strongly correlated with high AHI compared to other measurements. However, waist to hip ratio showed the strongest correlation with AHI in 70 participants with a BMI of less than 25 and, in this group, BMI did not show significant correlation with AHI. CONCLUSION Considerations about anthropometric measurements in OSA patients should differ according to degree of obesity or BMI.

Hypoxia Modulates Epithelial Permeability via Regulation of Vascular Endothelial Growth Factor in Airway Epithelia

Abstract Hypoxia resulting from occlusion of the sinus ostium is known to be one of the major pathogenic mechanisms of sinusitis. Hypoxia‐inducible factor (HIF)‐1 is a widely known transcription factor that induces the cellular response to hypoxic conditions and activates the transcription of several genes, including vascular endothelial growth factor (VEGF). We hypothesized that induced permeability caused by hypoxia is a major pathophysiologic mechanism of upper airway diseases, such as sinusitis. The aim of this study was to investigate the mechanism of hypoxia‐induced hyperpermeability, which mediates increased paracellular permeability and enhanced microbial invasiveness in the airway epithelium. We show that expression of VEGF mRNA and protein and HIF‐1&agr; protein increased as a function of time under hypoxia in normal human nasal epithelial cells. Our results also indicate that VEGF expression was induced by transfection with a mammalian expression vector encoding HIF‐1 but down‐regulated by transfection with small interfering RNA specific for HIF‐1&agr; under hypoxic conditions. Results of a transepithelial permeability assay measuring transepithelial electrical resistance indicated that permeability was increased as a function of time under hypoxia and was rescued by anti‐VEGF monoclonal antibody (bevacizumab) and small interfering RNA specific for HIF‐1&agr;. We detected up‐regulated HIF‐1&agr; and VEGF expression in mucosal epithelium samples from patients with sinusitis compared with normal mucosal epithelium using Western blotting and immunohistochemical staining. In conclusion, we suggest that the hypoxia‐HIF‐1&agr;‐VEGF axis plays an important role in hyperpermeability of airway epithelial cells, implying a role in the pathophysiology of upper respiratory tract diseases, such as sinusitis.