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      • SCIESCOPUSKCI등재

        Flavonoids Inhibit Histamine Release and Expression of Proinflammatory Cytokines in Mast Cells

        Park, Hyo-Hyun,Lee, So-Young,Son, Hee-Young,Park, Seung-Bin,Kim, Mi-Sun,Choi, Eun-Ju,Singh, Thoudam S.K.,Ha, Jeoung-Hee,Lee, Maan-Gee,Kim, Jung-Eun,Hyun, Myung-Chul,Kwon, Taeg-Kyu,Kim, Yeo-Hyang,Kim, 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

        Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin (IL)-$1{\beta}$, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-$\alpha$ and IL-6 but not (IL)-$1{\beta}$ and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-${\kappa}B$ indicated by inhibition of nuclear translocation of NF-${\kappa}B$, NF-${\kappa}B$/DNA binding, and NF-${\kappa}B$-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

      • SCOPUSKCI등재

        Crystalline podocytopathy and tubulopathy without overt glomerular proteinuria in a patient with multiple myeloma

        ( Eun Jeong Lee ),( Su Yeon Lee ),( So Young Park ),( Yonjin Kim ),( Jae Shin Choi ),( Mi Jeoung Kim ),( Ji Hyeon Park ),( Jung Eun Lee ),( Ghee Young Kwon ),( Yoon-goo Kim ) 대한신장학회 2016 Kidney Research and Clinical Practice Vol.35 No.4

        Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain-secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury. Copyright ⓒ 2016. The Korean Society of Nephrology. Published by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

      • 소아메밀알레르기의 진단 및 임상적 특성에 관한 연구

        이기영(Ki Young Lee),김현영(Hyun Young Kim),이현희(Hyun Hee Lee),정병주(Byung Ju Jeoung),김규언(Kyu Earn Kim),박경화(Kyung Hwa Park),박소미(So Mi Park) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1998 소아알레르기 및 호흡기학회지 Vol.8 No.1

        목적 : 메밀은 우리나라에서 흔하게 발견되는 중요한 식품항원이며 그 증상이 단순한 두드러기에서부터 심한 경우에는 아나필락시?脊沮?다양하다. 식품알레르기의 진단은 문진, 알레르기피부시험 및 경구유발시험 등이 있는데 가장 정확한 검사는 경구유발시험이다. 그런데 경구유발시험을 일반 외래에서 일률적으로 실시하기에는 여러 어려움이 따른다. 이에 저자들은 손쉽게 시행할 수 있는 병력청취와 알레르기피부시험의 진단적 가치를 평가하고 메밀알레르기의 임상양상과 특성을 알아보기 위해서 본 연구를 실시하였다. 대상 및 방법 : 연세대학교 의과대학 세브란스병원 소아알레르기크리닉에 내원하여 피부시험을 실시하여 메밀항원에 양성 반응을 보였거나 메밀을 먹은 후 알레르기 증상을 보인 과거력이 있었던 환아들 중 경구유발시험이 가능했던 55명을 대상으로 하여 임상양상 및 특성을 분석하였다. 경구유발시험은 소량부터(가루를 입주위에 바르는 방법) 시작해서 증상이 안나타나면 점차 양을 늘려서 먹이는 방법으로 시행하였다. 결과 1) 경구유발시험을 실시했던 총 55례중 양성 반응을 보여서 메밀알레르기로 진단할 수 있었던 경 우는 40례로 72.7%였다. 2) 이중 남아 32명(80%), 여아 8명(20%)으로 남아가 여아에 비하여 4배가 많았고, 호발연령은 5세이하가 25명(62.5%)으로 가장 많았다. 3) 피부시험과 과거력 모두에서 양성이었던 환아중 경구유발시험과 일치했던 환아는 31례(86.1%)로 매우 높은 예측도를 보였다. 4) 메밀을 섭취한 후 기관지천식이나 아나필락시?瘠?같은 위중한 증상을 보였던 경우가 약 60%나 되었다. 5) 증상을 유발시켰던 메밀의 양은 1-100gm 사이가 27례(67.5%)로 가장 많았고 11례(27.5%)에서는 소량으로 냄새를 맡거나 맛을 보는 것만으로도 증상이 유발되었다. 결론 :식품알레르기의 진단은 원인으로 생각되는 음식을 금식시킨후 증상이없을 때 유발시험을 실시하는 것이 가장 좋은 방법이다. 그러나 메밀은 심한 경우에는 아나필락시?脊沮?도 유발할 정도로 항원성이 강한 식품이며 알레르기피부시험과 과거력이 모두 양성인 경우 에는 그 예민도가 매우 높음으로 모든 환자들에게 일괄적으로 유발시험을 실시하기 전에 우 선 철저한 제한식을 권고하여 심한 알fp르기 증상을 예방하는 것이 좋을 것으로 사료된다. Purpose : Buckwheat is one of the most common allergen in food allergy, the pathomechanism is IgE-mediated, type I immune reaction. Antigenicity of Buckwheat is extremely strong, and hypersensitivity symptoms included asthmatic attacks, urticaria eruption, gastrointestinal disorders even anaphylactic shock. The purpose of this study is to evaluate diagnostic significance of allergy skin test and allergy history and analyze clinical features of buckwheat allergy confirmed by oral provocation test. Methods : We carried out the retrospective study on 55 patients who had been performed oral buckwheat provocation test at Yonsei university children`s allergic clinic. Results = 1) 40 out of 55 cases(72.7%) showed positive buckwheat oral provocation test. 2) The most common clinical finding after oral provocation test was urticaria. 60% showed severe allergic reactions such as asthma attack or anaphylactic shock. 3) The rate which past history and positive skin test corresponded to oral provocation test was very high(86.1 0). Conclusions : The most valuable diagnosis of food allergy is oral provocation test. However, predictive value of allergy skin test and past history was very high in buckwheat allergy. Our study suggest that the troblesome oral provocation test may be not needed in all cases of suspicious buckwheat allergy patients.

      • SCISCIESCOPUS

        Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist

        Park, Sang Eun,Song, Ji Hoon,Hong, Chansik,Kim, Dong Eun,Sul, Jee-Won,Kim, Tae-Youn,Seo, Bo-Ra,So, Insuk,Kim, Sang-Yeob,Bae, Dong-Jun,Park, Mi-Ha,Lim, Hye Min,Baek, In-Jeoung,Riccio, Antonio,Lee, Joo- Springer US 2019 Molecular Neurobiology Vol.56 No.4

        <P>Oxidative stress is a key mediator of neuronal death in acute brain injuries, such as epilepsy, trauma, and stroke. Although it is accompanied by diverse cellular changes, increases in levels of intracellular zinc ion (Zn<SUP>2+</SUP>) and calcium ion (Ca<SUP>2+</SUP>) may play a critical causative role in oxidative neuronal death. However, the mechanistic link between Zn<SUP>2+</SUP> and Ca<SUP>2+</SUP> dyshomeostasis in neurons during oxidative stress is not well-understood. Here, we show that the exposure of cortical neurons to H<SUB>2</SUB>O<SUB>2</SUB> led to a zinc-triggered calcium influx, which resulted in neuronal death. The cyclin-dependent kinase inhibitor, NU6027, inhibited H<SUB>2</SUB>O<SUB>2</SUB>-induced Ca<SUP>2+</SUP> increases and subsequent cell death in cortical neurons, without affecting the early increase in Zn<SUP>2+</SUP>. Therefore, we attempted to identify the zinc-regulated Ca<SUP>2+</SUP> pathway that was inhibited by NU6027. The expression profile in cortical neurons identified transient receptor potential cation channel 5 (TRPC5) as a candidate that is known to involve in the generation of epileptiform burst firing and epileptic neuronal death (Phelan KD et al. 2012a; Phelan KD et al. 2013b). NU6027 inhibited basal and zinc-augmented TRPC5 currents in TRPC5-overexpressing HEK293 cells. Consistently, cortical neurons from TRPC5 knockout mice were highly resistant to H<SUB>2</SUB>O<SUB>2</SUB>-induced death. Moreover, NU6027 is neuroprotective in kainate-treated epileptic rats. Our results demonstrate that TRPC5 is a novel therapeutic target against oxidative neuronal injury in prolonged seizures and that NU6027 is a potent inhibitor of TRPC5.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1007/s12035-018-1258-7) contains supplementary material, which is available to authorized users.</P>

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