Effect of Retinoic Acid on the Differentiation and Lysozyme Expression in Human Airway Epithelial Cells

BACKGROUND AND OBJECTIVES: Retinoic acid (RA)-deprived cultures of normal human tracheobronchial epithelial (NHTBE) cells became squamous metaplastic, failed to produce mucin and instead secreted or released large amounts of lysozyme (LZ). The purpose of this study was to elucidate the relationship between RA-deficiency induced squamous metaplasia and increased LZ as a function of time. MATERIALS AND METHOD: The change of lysozyme protein and lysozyme mRNA was investigated over time in cultures using passage-2 normal human tracheobronchial epithelial (NHTBE) cells and passage-2 normal human keratinocytes (NHK). The amount of lysozyme and mucin was measured with dot blot, message of lysozyme with RT-PCR, and cornifin mRNA with Northern blot. RESULTS: Lysozyme message levels were consistently higher in RA-sufficient than RA-deficient cultures. Intracellular and extracellular LZ increased to a peak on the day 16 and thereafter decreased in the RA-deficient cultures. LZ gene expression in the RA-deficient cultures was barely detectable on the day 7 but was clearly expressed between days 10 and 14, but thereafter message levels decreased markedly. On day 12, large numbers of cells began to exfoliate in the RA-deficient cultures. Extracellular LZ appeared simultaneously at the apical surface, presumably released from the exfoliated cells, which contained high concentrations of LZ. Intracellular LZ levels were more than 11 fold less in NHK cells compared to NHTBE cells. CONCLUSION: This study suggests that cellular accumulation of lysozyme protein is a unique feature of metaplastic squamous differentiation. Further studies are needed to find out what mechanisms are involved.ope

Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling

The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADHope

Can drug-induced sleep endoscopy improve the success rates of tongue base surgery?

BACKGROUND: The purpose of this study was to determine the therapeutic value of drug-induced sleep endoscopy (DISE) by comparing the outcomes of tongue base surgery based on Muller's maneuver (MM) and those based on DISE in obstructive sleep apnea (OSA) patients. METHODS: Ninety-five patients who underwent the tongue base surgery in combination with palatal surgery for OSA at a tertiary referral hospital between March 2012 and March 2019 were enrolled in this retrospective comparative study. Forty-seven patients underwent MM for surgical decision and 48 patients underwent DISE in addition to MM for surgical decision. Surgical success was defined according to the Sher criteria (postoperative apnea-hypopnea index [AHI] < 20/h and ≥ 50% reduction in preoperative AHI), and AHI improvement (%) was defined as (preoperative AHI-postoperative AHI) × 100/preoperative AHI. For comparison between the MM and DISE groups, p-values were calculated using independent or paired t-tests for continuous variables and using chi-square test for categorical variables. RESULTS: By comparing the results of MM and DISE, consensus on the tongue base level showed insignificant concordance (kappa = 0.017, p = 0.865), whereas that on the oropharynx level showed fair agreement (kappa =0.241, p = 0.005). AHI, supine AHI, rapid eyeball movement (REM) AHI, non-REM AHI, and nadir oxygen saturation were all significantly improved after the tongue base surgery in both groups. The MM group showed a significant improvement in the Epworth sleepiness scale after the tongue base surgery (p = 0.014), whereas the DISE group did not (p = 0.165). However, there was no significant difference in the AHI improvement (MM group = 47.0 ± 32.0, DISE group = 48.3 ± 35.4, p = 0.852) and surgical success (MM group = 42.6%, DISE group = 45.8%, p = 0.748) between the groups. Tonsil grade (p < 0.05) and occlusion at the oropharynx lateral wall (p = 0.031) were significantly related to surgical success in the MM group. CONCLUSIONS: In the judgment of the tongue base surgery, MM and DISE findings showed poor agreement. DISE might affect the surgical decision on the tongue base surgery in OSA patients; however, there was a lack of evidence regarding the superiority of DISE over MM with respect to the surgical outcomes.ope

Epidemiological Study for Allergic Disease of School Aged Children and Adolescence in Rural Area of Korea

Background and Objectives：Basic epidemiologic investigations are important given the need for prevention and proper treatment of the patient with allergic disease. However, basic epidemiologic data of allergic disease in Korea are rarely found. Especially, data about school children in the rural areas of Korea are not found in the review of literature. We attempted to obtain epidemiological data of allergic diseases, such as prevalence rate, skin test results and family history, in school children living in the rural area of Korea. Materials and Methods：We performed statistical analysis of 13,160 students who responded to the questionnaire concerning several allergic symptoms and family history. Of these 13,160 students, 171 students were given skin tests, and their results were also statistically analyzed. Results and Summary：The percentage of students who had ever suffered from allergic diseases were as follows：atopic dermatitis (11.2%), urticaria (31.3%), asthma (11.1%), and allergic rhinitis (28.5%). The prevalence rate of allergic disease at the point of study performed were as follows：atopic dermatitis (1.5%), urticaria (4.7%), asthma (2.2%), and allergic rhinitis (5.3%). Students with allergic symptoms showed positive skin test results (64.7%). The most common allergen causing the allergic symptoms were Dermatophagoides pteronyssinus and Dermatophagoides farinae. Seasonal predominance was prominent in the winter (33.8%) for students who have allergic rhinitis.ope

An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response

Purpose: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs. Methods: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization. Results: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment. Conclusions: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs.ope

Expression of Sialic Acids according to the Differentiation of Cultured Human Nasal Epithelial Cells

BACKGROUND: Sialic acid residues are known to play a key role in the normal function of the glycoconjugates. Recently, with the development of specific sialic acid binding lectins such as Maackia seed agglutinin(MAA) and Sambucus nigra agglutinin(SNA), it has made easier to localize the sialic acid residues by the histochemical staining methods. OBJECTIVES: We were to observe the expression of sialic acids according to the differentiation of cultured human nasal epithelial cells by the immunohistochemistry method using Wheat germ agglutinin(WGA), MAA, and SNA. MATERIALS AND METHODS: Human nasal epithelial cell culture was done as floating method for the induction of differentiation. The cultured cells were fixed with 2.5% glutaraldehyde and the epon 812 was used as embedding material. The immunohistochemistry was done as Lim's method. RESULTS: The WGA and MAA positive reactions were noted from the floating zero day through the fourteenth day. The reactions were positive to the squamous-like cells and differentiating cells(ciliated and secretory epithelial cells). The WGA binding patterns were homogeneous but MAA binding patterns were inhomogeneous. The SNA positive reaction was noted only in the fourteenth day and the reaction was inhomogeneous. These results meant that N-acetyl glucosamine and N-acetyl neuraminic acid(alpha 2,3) galactose were expressed from the floating zero day and N-acetyl neuraminic acid(alpha 2,6) galactose was expressed from the floating fourteenth day. CONCLUSION: N-acetyl neuraminic acid(alpha 2,3) galactose may be more important to the primary defence of human nasal epithelial cell. Due to the inhomogeneity of the reaction, the further study using Lowicryl K4M will be needed.ope

The Role of p38 MAP Kinase Signal Transduction in the Induction of MUC 8 Gene Expression in Normal Human Nasal Epithelial Cells

ABSTRACT BACKGROUND AND OBJECTIVES: In cystic fibrosis, chronic bronchitis, and asthma, the mucociliary mechanism is impaired when mucin is produced excessively. The mRNA encoding MUC8 has been shown to be the major up-regulated mucin under inflammatory condition and is likely to contribute to the airway mucus plugging characteristic of these diseases. The aim of this study is to determine the intracellular signaling pathway directly involved in the MUC8 regulation following inflammatory mediator treatments. MATERIALS AND METHOD: Passage-2 normal human airway epithelial cells were used in all experiments. Inflammatory signal-induced MAP kinase activity was measured by Western blot analysis using phosphospecific anti-active MAP kinase antibodies. Inflammatory signal-induced MUC8 expression was measured in the absence or presence of SB203580 by the semi-quantative RT-PCR. RESULTS: Inflammatory stimuli such as LPS, TNF-alpha, and IL-lbeta activated the p38 MAP kinase and subsequently up-regulated the MUC8 expression. Interestingly, the TNF-alpha or IL-lbeta-inducibility of the MUC8 gene expression was greatly enhanced by specific inhibition of the p38 MAP kinase by using SB 203580 CONCLUSION: These results suggest that the intracellular p38 MAP kinase activity is a negative regulator for the MUC8 up-regulation in human nasal epithelial cells following infiammatory stimuli.ope

Retropharyngeal Lymph Node Metastasis from Olfactory Neuroblastoma : A Report of 2 Cases

Olfactory neuroblastoma is a rare, malignant neoplasm arising from the olfactory epithelium. It has an aggressive biological behavior that is characterized by local recurrence, atypical distant metastasis, and poor long-term prognosis. The incidence of cervical lymph node metastasis in olfactory neuroblastoma is variable, and treatment modalities are controversial. Moreover, few reports have been published concerning retropharyngeal lymph node metastasis from olfactory neuroblastoma. We present two cases of olfactory neuroblastoma with retropharyngeal lymph node metastasis. In addition, we provided a review of the current literature regarding olfactory neuroblastoma and retropharyngeal lymph node metastasis from olfactory neuroblastoma.ope

Treatment Outcomes of Olfactory Neuroblastoma: A Report of 5 Cases.

Background and Objectives：Several strategies have been reported for the treatment of olfactory neuroblastoma such as radiation therapy, chemotherapy, craniofacial resection, or their combination. However, a consensus regarding the optimal management has not been obtained. In this study, we examined the outcomes of different treatment modalities in five patients with olfactory neuroblastoma. Material and Method：Five patients diagnosed as olfactory neuroblastoma during the past 10 years were retrospectively analyzed. Results：Five patients were categorized by the modified Kadish's staging system. Three patients underwent surgery. Radiotherapy was given concurrently with chemotherapy for two patients. Distant metastases were observed in two cases, one in the heart and the other in the cervical lymph node. After a median follow-up of 34 (12-87) months, two patients who underwent craniofacial resection only and another two patients who received combined radiotherapy and chemotherapy are still alive. One patient who underwent Denker's operation with postoperative radiotherapy had died of heart failure as a result of cardiac metastasis. Conclusion：We suggest a complete surgical resection as a primary treatment modality, however, a multi-drug chemotherapy with radiotherapy could be the choice of treatment in cases of children or one with distant metastasis.ope

Mucin and Lysozyme Expression in the Epithelium of Normal Human Nasal Inferior Turbinate and Polyps

Background and Objectives：In chronic bronchitis, rhinitis or cystic fibrosis, the number of goblet cells increases along with hypertrophy of mucous cells in submucosal gland, resulting ineffective mucociliary clearance. But, it is still not fully understood what role each gene plays in producing airway secretions. This study aimed to figure out which mucin gene is expressed in the epithelium of normal human nasal mucosa and nasal polyps, and to verify whether the epithelium of nasal polyp itself contributes to the increased nasal secretion as in chronic sinusitis with nasal polyp. Materials and Methods： Normal nasal epithelial cells were obtained from the inferior turbinates of ten normal healthy volunteers, and nasal polyps from six patients who underwent sinus surgery. The epithelial cells were enzymatically isolated, and intracellular levels of mucin and lysozyme were measured from cell lysates using immunoblot assay. And, RT-PCR was used for the detection of mucin mRNA and lysozyme mRNA. Results：The level of intracellular mucin was 2.9 times higher in the epithelium of nasal polyp, and this was statistically significant. Among seven mucin genes (MUC1, 2, 4, 5AC, 5B, 7, 8) expressed in the epithelium of normal inferior turbinate and polyps, MUC2 and MUC8 were more strongly expressed in the epithelium of nasal polyp than those of normal inferior turbinate. Conclusion：This results suggest that the polyp epithelium itself is contributing to increased secretion in chronic sinusitis, and MUC2 and MUC8 are thought to be responsible for this change. However, further study is required to uncover the full sequence of MUC8 mRNA and its exact function. (Korean J Otolaryngol 2000;43:377-82)ope