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      • KCI등재

        소규모 경시적 마이크로어레이 실험의 통계적 분석

        이근영,양상화,김병수,Lee, Keun-Young,Yang, Sang-Hwa,Kim, Byung-Soo 한국통계학회 2008 응용통계연구 Vol.21 No.1

        소규모 경시적 마이크로어레이 실험이란 시점의 개수가 적은 경시적 마이크로어레이 실험으로서 현재까지 보고된 경시적 마이크로어레이 실험의 약 80%를 차지한다. 최근 들어 소규모 경시적 마이크로어레이 실험을 대상으로 하는 통계적 분석 방법이 몇 가지 제안되었다. 최근에 제안된 세 가지 방법들을 실제 소규모 경시적 마이크로어레이 실험자료에 적용하여 분석하고 모의실험 자료를 생성하여 각 방법들의 검정력과 위양성율을 비교해 보았다. 그 결과 낮은 위양성율을 보이는 STEM방법이 다른 방법에 비해서 우위에 있음이 드러났다. Small scale time-course microarray experiments are those which have a small number of time points. They comprise about 80 percent of all time-course microarray experiments conducted up to 2005. Several statistical methods for the small scale time-course microarray experiments have been proposed. In this paper we applied three methods, namely, QR method, maSigPro method and STEM, to a real time-course microarray experiment which had six time points. We compared the performance of these three methods based on a simulation study and concluded that STEM outperformed, in general, in terms of power when the FDR was set to be 5%.

      • KCI등재

        House Dust Mite-Derived Chitin Enhances Th2 Cell Response to Inhaled Allergens, Mainly via a TNF-α-Dependent Pathway

        최준표,이상민,최현일,김민혜,전성규,장명호,지영구,양상화,조영주,김윤근 대한천식알레르기학회 2016 Allergy, Asthma & Immunology Research Vol.8 No.4

        Purpose: Chitin is a potent adjuvant in the development of immune response to inhaled allergens in the airways. According to other studies, chitin is known as multi-faced adjuvants which can induce Th2 responses. Recently, we found that TNF-α is a key mediator in the development of Th2 cell response to inhaled allergens. Here, we evaluated the immunologic mechanisms in the development of airway hypersensitivity to inhaled allergens, enhanced by house dust mite (HDM)-derived chitin. Methods: The role of TNF-α and TLRs was evaluated in an airway hypersensitivity mouse model induced by a sensitization with an allergen (ovalbumin, OVA) and HDM-derived chitin using mice with the null mutation of target genes. Results: The present study showed that airway sensitization with HDM-derived chitin plus OVA enhanced OVA-induced airway inflammation v. OVA alone. This phenotype was associated with the increased expression of Th1, Th2, and Th17 cytokines and also with the enhanced production of OVA-specific IgE, IgG1, and IgG2a. As for T cell responses, OVA-specific Th2 cell response, enhanced by chitin, was abolished by the treatment of chitinase, whereas Th1 and Th17 cell responses enhanced by this treatment. Moreover, the null mutation of the TNF-α gene revealed similar effects as the chitinase treatment. In contrast, all the OVA-specific T cell responses, enhanced by chitin, were blocked by the absence of TLR2, but not of TLR1, TLR4, or TLR6. Conclusions: In conclusion, these data suggest that HDM-derived chitin may enhance airway hypersensitivity to inhaled allergens, via the TLR2-dependent pathway, and that chitin-induced TNF-α can be a key mediator in the development of Th2 cell response to inhaled allergens.

      • KCI등재

        Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced by Staphylococcus aureus-derived Extracellular Vesicles

        김민혜,최성진,최현지,최준표,박한기,김은경,김민정,문병석,민택기,노미나,조영주,양상화,김윤근,김유영,편복양 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

        Purpose: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition. Methods: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively. Results: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level. Conclusions: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

      • KCI등재

        A Metagenomic Analysis Provides a Culture-Independent Pathogen Detection for Atopic Dermatitis

        김민혜,노미나,최준표,최현일,박한기,송우정,민택기,조상헌,조영주,김윤근,양상화,편복양 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.5

        Purpose: Atopic dermatitis (AD) is an inflammatory skin disease, significantly affecting the quality of life. Using AD as a model system, we tested a successive identification of AD-associated microbes, followed by a culture-independent serum detection of the identified microbe. Methods: A total of 43 genomic DNA preparations from washing fluid of the cubital fossa of 6 healthy controls, skin lesions of 27 AD patients, 10 of which later received treatment (post-treatment), were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform. Results: Microbial diversity was decreased in AD, and was restored following treatment. AD was characterized by the domination of Staphylococcus, Pseudomonas, and Streptococcus, whereas Alcaligenaceae (f), Sediminibacterium, and Lactococcus were characteristic of healthy skin. An enzyme-linked immunosorbent assay (ELISA) showed that serum could be used as a source for the detection of Staphylococcus aureus extracellular vesicles (EVs). S. aureus EV-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) were quantified in the serum. Conclusions: A metagenomic analysis together with a serum detection of pathogen-specific EVs provides a model for successive identification and diagnosis of pathogens of AD.

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