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손명현,홍정연,배종환,이경은,김미나,김민희,강현정,박은혜,유경숙,정세규,김경원,김규언 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.6
Purpose: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. Materials and Methods: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effectiveinhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1atm1Knt Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. Results: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ releasein a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. Conclusion: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeuticpathway in IgE/FcεRI-mediated diseases.
손명현,Yeo Hoon Park,Kyung Won Kim,Bong Seok Choi,지혜미,Kyu-Earn Kim 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.1
Purpose: We tested the hypothesis that cesarean section might increase the risk for allergic diseases compared to vaginal delivery, by depriving the newborn of exposure to maternal microflora. Methods: We evaluated the prevalence of allergic diseases, allergic inflammation, and allergic sensitization according to mode of delivery for 279 Korean children aged ≤16 years. Data were extracted from medical records and a questionnaire filled out by parents. Logistic regression was used to determine the association between cesarean section and the outcomes of interest. Results:Of the 279 children, 179 (62.6%) were delivered vaginally and 100 (37.4%) by cesarean section. There were no differences in the prevalence of allergic diseases, allergic inflammation, or allergic sensitization according to mode of delivery. Children born by cesarean section had no higher risk of allergic disease than those delivered vaginally, regardless of a parental history for allergic disease. Adjusted odds ratios (95% confidence intervals)for cesarean section compared to vaginal delivery were not statistically significant for any outcome considered: asthma, 0.76 (0.37-1.57), allergic rhinitis,1.14 (0.61-2.10), atopic dermatitis, 1.01 (0.59-1.71). Conclusions: Delivery by cesarean section may not be associated with the subsequent development of asthma, allergic rhinitis, or atopic dermatitis in Korean children.
Chitinase, Chitinase-like Protein과 알레르기 염증
손명현 대한 소아알레르기 호흡기학회 2009 Allergy Asthma & Respiratory Disease Vol.19 No.4
Chitin, the second most abundant polysaccharide in nature after cellulose, consist exoskeleton of lower organisms such as fungi, crustaceans and insects except mammals. Mammalian chitinase and chitinase-like proteins (CLPs) are a family of mediators increasingly associated with infection, T cell-mediated inflammation, wound healing, allergy and asthma. Although our current knowledge of the function of mammalian chitinases and CLPs is very limited, important information can be deduced from research carried out in lower organisms, and in different immunopathological conditions. It is most striking that both chitinases and CLPs are up- regulated in T-helper type 2 (Th2)-driven conditions, and the first evidence is now emerging that these proteins may accentuate Th2 reactivity, and possibly contribute to the repair process that follows inflammation. In addition, regulatory SNPs in CHI3L1 were associated with asthma, atopy, and immunemediated diseases. In this review, recent findings on the role of chitinase and CLPs in allergic inflammation will be highlighted and the genetic studies in the genes encoding CHI3L1 will be discussed.
The Cockroach and Allergic Diseases
손명현,김규언 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.5
The cockroach represents one of the most common sources of indoor allergens worldwide, and 40%-60% of patients with asthma in urban and inner-city areas possess IgE antibodies to cockroach allergens. In Korean homes, four cockroach species have been found, of which the most commonly encountered is the German cockroach. The pathogenic mechanism underlying the association between cockroach allergens and allergic diseases has not been fully elucidated. Allergenicity is associated with the cockroach allergens themselves, enzymatic protease activity, and ligands for pattern recognition receptors. Although allergen-specific adaptive immune responses orchestrate the cockroach allergic response, recent data suggest that the innate immune system is also a critical contributor to pathogenesis. We review the current evidence for the demographics of cockroach exposure and sensitization, characteristics of cockroach allergens, and inflammatory responses to cockroach allergens initiated through protease-dependent pathways.