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        A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

        Palikhe, Sailesh,Uuganbayar, Udval,Trinh, Hoang Kim Tu,Ban, Ga-Young,Yang, Eun-Mi,Park, Hae-Sim,Kim, Seung-Hyun Carfax 2017 MEDIATORS OF INFLAMMATION Vol.2017 No.-

        <P>The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between <I>ABCC4</I> gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (−1508A>G and −642C>G) in the <I>ABCC4</I> promoter were genotyped. The functional variability of the promoter polymorphisms was analyzed by luciferase reporter assay. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Serum and urinary eicosanoid metabolites, sphingosine-1-phosphate, were evaluated by quadrupole time-of-flight mass spectrometry. Asthma patients carrying the G allele at −1508A>G had significantly higher serum levels of periostin, myeloperoxidase, and urinary levels of 15-hydroxyeicosatetraenoic acid and sphingosine-1-phosphate (<I>P</I> = 0.016, <I>P</I> = 0.027, <I>P</I> = 0.032, and <I>P</I> = 0.010, resp.) compared with noncarrier asthma patients. Luciferase activity was significantly enhanced in human epithelial A549 cells harboring a construct containing the −1508G allele (<I>P</I> < 0.01 for each) compared with a construct containing the −1508A allele. A functional polymorphism in the <I>ABCC4</I> promoter, −1508A>G, may increase extracellular 15-hydroxyeicosatetraenoic acid, sphingosine-1-phosphate, and periostin levels, contributing to airway inflammation in asthmatics.</P>

      • KCI등재

        Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal Superantigens in Chronic Urticaria

        Sailesh Palikhe,김승현,Le Duy Pham,예영민,박해심 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.3

        Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP®. Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis.

      • KCI등재

        Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma

        김승현,배수진,Sailesh Palikhe,예영민,박해심 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-

        Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (−554 G4C, − 431A4C and − 225 G4C) in the MBL2 promoter were genotyped, and serum MBL levels were determined by enzyme-linked immunosorbent assay. Functional variabilities in the promoter polymorphisms were analyzed by a luciferase reporter assay and electrophoretic mobility shift assay (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA carrying ht2 [CAG] had significantly lower PC20 methacholine levels (Po0.001) than the non-carriers. The serum MBL levels were significantly higher in the DI-exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028). Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2 [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a − 554G probe produced a specific shifted band compared with the − 554C probe. These findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2 gene may increase susceptibility to the development of DI-OA in DI-exposed individuals.

      • Increased basophil activation in adult patients with anaphylaxis

        ( Ji-hye Kim ),( Seung-hyun Kim ),( Sailesh Palikhe ),( Eun-mi Yang ),( Young-min Ye ),( Hae-sim Park ) 대한내과학회 2015 대한내과학회 추계학술대회 Vol.2015 No.1

        Introduction: Anaphylaxis is a life-threatening allergic reaction mediated by IgE antibodies that interact with basophils and mast cells to release vasoactive and proinflammatory mediators. We evaluated basophil activation status using CD203c and CD63 expressions in adult patients with anaphylaxis. Methods: 41 patients with asthma/rhinitis, chronic urticaria and anaphylaxis and 23 normal controls were recruited and divided into three groups; anaphylaxis (n=13), non-anaphylaxis (n=28) and normal control groups. Basophil CD203c and CD63 expressions were measured by flow cytometry. The whole blood samples were collected and red blood cells (RBCs) were lysed with a RBC lysis buffer. Basophils wereincubated with anti-IgE antibody or calcium ionophore. The resuspended cells were stained with anti-human CD203c or CD63, anti-human CD123, and anti-human human leukocyte antigen- DR, or isotype-matched controls on ice in the dark. Results: Baseline expression levels of CD203c and CD63 were higher in the anaphylaxis group than NC group (30.28±23.10 vs 13.76±14.60, p=0.036; 17.67±20.48 vs 3.31±3.73, p=0.028, respectively) and tended to be higher in anaphylaxis group than in non-anaphylaxis group (p=0.320, p=0.922, respectively). The positive BAT rates tended to be higher in anaphylaxis group than in non-anaphylaxis group (38.46% vs 17.85%, p=0.20), while no differences were noted in CD63 expression levels. Conclusions: These findings suggest that increased basal activation status of basophils may contribute to the development of anaphylaxis in adult patients.

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