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      • Role of Reactive Oxygen Species in Transforming Growth Factor Beta1-Induced Alpha Smooth-Muscle Actin and Collagen Production in Nasal Polyp-Derived Fibroblasts

        Park, Il-Ho,Park, Se-Jin,Cho, Jung-Sun,Moon, You-Mi,Kim, Tae Hoon,Lee, Sang Hag,Lee, Heung-Man S. Karger AG 2012 International archives of allergy and immunology Vol.159 No.3

        <P>Abstract</P><P><B><I>Background:</I></B> Myofibroblasts are detected in nasal polyps and are involved in nasal polyp formation by inducing extracellular matrix accumulation. Reactive oxygen species (ROS) are released during the differentiation of fibroblasts to myofibroblasts. The purpose of this study was to investigate ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) expression in nasal polyp-derived fibroblasts (NPDFs) and to evaluate whether ROS from NOX mediates transforming growth factor (TGF)-β1-induced production of alpha smooth-muscle actin (α-SMA) and collagen production. <B><I>Methods:</I></B> NPDFs were incubated and treated with TGF-β1. The mRNA expression of <I>NOXs, </I>α<I>-SMA,</I> and <I>collagen type I </I>and<I> IV</I> was determined by reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the SirCol assay. The ROS generation of cells was investigated using the 2′,7′-dichlorfluorescein-diacetate. The fluorescence was captured by fluorescent microscope and measured using a fluorometer. <B><I>Results:</I></B> Stimulation with TGF-β1 increased ROS production by NPDFs compared with NPDFs not treated with TGF-β1. Stimulation with TGF-β1 increased the expression of <I>NOX4</I> mRNA most potently among various Nox enzymes. <I>siNOX4</I> was able to decrease the level of ROS production. Myofibroblast differentiation and the production of collagen in NPDFs were prevented by inhibition of ROS generation with diphenyliodonium, N-acetylcysteine, ebselen, and <I>siNox4</I>. <B><I>Conclusions:</I></B> This study showed that NOX4 and ROS have a role in myofibroblast differentiation and collagen production of TGF-β1-induced NPDFs and that these processes are inhibited by the elimination of ROS.</P><P>Copyright © 2012 S. Karger AG, Basel</P>

      • SCISCIESCOPUS

        Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population

        Park, Heung-Woo,Lee, Jong-Eun,Shin, Eun-Soon,Lee, Jae-Young,Bahn, Joon-Woo,Oh, Heung-Bum,Oh, Sun-Young,Cho, Sang-Heon,Moon, Hee-Bum,Min, Kyung-Up,Elias, Jack A.,Kim, You-Young,Kim, Yoon-Keun Elsevier 2006 The journal of allergy and clinical immunology Vol.117 No.4

        <P><B>Background</B></P><P>Vascular endothelial growth factor (VEGF) has been suggested to be a key mediator in the development of atopy and T<SUB>H</SUB>2 inflammation.</P><P><B>Objective</B></P><P>We sought to evaluate the effects of variations in the gene coding VEGF receptor (VEGFR) 2 on intermediate phenotypes of asthma in the Korean population.</P><P><B>Methods</B></P><P>A cohort of 2055 children and adolescents responded to a questionnaire concerning asthma symptoms and risk factors and underwent methacholine bronchial challenge and skin tests. The <I>VEGFR2</I> gene, including the promoter area, was sequenced on 24 healthy subjects to discover informative single nucleotide polymorphisms (SNPs; minor allele frequency >2%). After haplotype reconstruction, 4 tagging SNPs (IVS6+54A>G, +889G>A, +1416T>A, and IVS25-92G>A) were scored. These SNPs were also scored in 480 adult asthmatic patients to verify the above genetic association study.</P><P><B>Results</B></P><P>The prevalence of atopy was associated with a single SNP (+889G>A) of VEGFR2 with borderline significance (<I>P</I> = .048; relative risk, 1.13; 95% CI, 1.00-1.28). However, haplotype analysis showed that the atopy prevalence was strongly associated with a haplotype (AGAG) of VEGFR2 (<I>P</I> = .002; relative risk, 1.25; 95% CI, 1.09-1.42). As for airway hyperresponsiveness, neither individual SNPs nor haplotypes were found to be associated. Interestingly, the significant association was also found between atopy and the AGAG haplotype among adult asthmatic patients (<I>P</I> = .008; odds ratio, 1.66; 95% CI, 1.14-2.44).</P><P><B>Conclusions</B></P><P>The present study demonstrated that genetic variations of VEGFR2 are significantly associated with atopy in the Korean population.</P>

      • SCIESCOPUSKCI등재

        Development of an automatic system for cultivating the bioluminescent heterotrophic dinoflagellate Noctiluca scintillans on a 100-liter scale

        You, Ji Hyun,Jeong, Hae Jin,Park, Sang Ah,Ok, Jin Hee,Kang, Hee Chang,Eom, Se Hee,Lim, An Suk The Korean Society of Phycology 2022 ALGAE Vol.37 No.2

        Noctiluca scintillans is a heterotrophic dinoflagellate that causes red-colored oceans during the day (red tides) and glowing oceans at night (bioluminescence). This species feeds on diverse prey, including phytoplankton, heterotrophic protists, and eggs of metazoans. Thus, many scientists have conducted studies on the ecophysiology of this species. It is easy to cultivate N. scintillans at a scale of <1 L, but it is difficult to cultivate them at a scale of >100 L because N. scintillans cells usually stay near the surface, while prey cells stay below the surface in large water tanks. To obtain mass-cultured N. scintillans cells, we developed an automatic system for cultivating N. scintillans on a scale of 100 L. The system consisted of four tanks containing fresh nutrients, the chlorophyte Dunaliella salina as prey, N. scintillans for growth, and N. scintillans for storage, respectively. The light intensities supporting the high growth rates of D. salina and N. scintillans were 300 and 20 µmol photons m<sup>-2</sup> s<sup>-1</sup>, respectively. Twenty liters of D. salina culture from the prey culture tank were transferred to the predator culture tank, and subsequently 20 L of nutrients from the nutrient tank were transferred to the prey culture tank every 2 d. When the volume of N. scintillans in the predator culture tank reached 90 L 6 d later, 70 L of the culture were transferred to the predator storage tank. To prevent N. scintillans cells from being separated from D. salina cells in the predator culture tank, the culture was mixed using an air pump, a sparger, and a stirrer. The highest abundance of N. scintillans in the predator culture tank was 45 cells mL<sup>-1</sup>, which was more than twice the highest abundance when this dinoflagellate was cultivated manually. This automatic system supplies 100 L of N. scintillans pure culture with a high density every 10 d for diverse experiments on N. scintillans.

      • Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats

        You, Jae-Sung,Park, Mi-Na,Song, Wook,Lee, Yeon-Sook Canadian Science Publishing 2010 APPLIED PHYSIOLOGY NUTRITION AND METABOLISM Vol.35 No.3

        <P> Reduced muscle activity leads to impaired insulin signaling, which leads to loss of contractile proteins and muscle mass via the Akt pathway. Dietary fish oil rich in long chain n-3 polyunsaturated fatty acids has been shown to prevent insulin signaling resistance in skeletal muscle. This study was conducted to elucidate the protective effect of dietary fish oil on disuse-induced perturbations in insulin signaling and soleus muscle atrophy. To accomplish this, rats were fed a corn-oil- (control) or fish-oil-based diet for 2 weeks, and then subjected to hindlimb immobilization while still receiving the same diets. After 10 days of immobilization, the soleus muscle mass and myosin heavy chain level had markedly decreased; however, these losses were significantly suppressed in rats fed dietary fish oil, compared with the control group. Dietary fish oil nearly completely attenuated the disturbances in activation of the Akt and p70 S6 kinase proteins, as well as the gene expression of muscle-specific E3 ubiquitin ligases (muscle atrophy F-box and muscle RING finger 1). However, insulin receptor substrate 1 associated with the p85 subunit of phosphoinositide 3-kinase was not altered during immobilization. Dietary fish oil also inhibited alterations in the gene expression of cyclooxygenase-2 and inducible nitric oxide synthase, with no additional observation of oxidative stress. Collectively, these findings indicate that dietary fish oil prior to and during immobilization may alleviate the immobilization-induced soleus muscle atrophy, at least in part, via the Akt pathway through E3 ubiquitin ligases and p70s6k. </P>

      • SCIESCOPUSKCI등재
      • SCIEKCI등재

        The Korean Severe Asthma Registry (KoSAR): real world research in severe asthma

        ( Sang-heon Kim ),( Hyun Lee ),( So-young Park ),( So Young Park ),( Woo-jung Song ),( Joo-hee Kim ),( Heung-woo Park ),( You Sook Cho ),( Ho Joo Yoon ) 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.2

        Severe asthma constitutes a serious health burden with significant morbidity and socioeconomic costs. The development and introduction of new biologics targeting type 2 inflammation changed the paradigm for management of severe asthma and initiated a biological era. These changes impose a challenge to clinicians in managing difficult-to-treat and severe asthma. To understand the characteristics and heterogeneity of severe asthma and to develop a better strategy to manage it, the Korean Academy of Asthma, Allergy and Clinical Immunology, Working Group on Severe Asthma, has organized the Korean Severe Asthma Registry (KoSAR). In this review, we describe the challenges of severe asthma management regarding diagnosis, disease burden, heterogeneity, guidelines, and organization of severe asthma clinics. This review also examines the current global activities of national and regional registries and study groups. In addition, we present the KoSAR vision and organization and describe the findings of KoSAR in comparison with those of other countries.

      • KCI등재

        Co-transplantation of Human Mesenchymal Stem Cells Promotes Human CD34+ Cells Engraftment in a Dose-dependent Fashion in NOD/SCID Mice

        Park, Seong-Kyu,Won, Jong-Ho,Kim, Hyun-Jung,Bae, Sang-Byung,Kim, Chan-Kyu,Lee, Kyu-Taeg,Lee, Nam-Su,Lee, You Kyoung,Jeong, Dae-Chul,Chung, Nak-Gyun,Kim, Hyun-Soo,Hong, Dae-Sik,Park, Hee-Sook The Korean Academy of Medical Sciences 2007 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.22 No.3

        <P>Mesenchymal stem cells (MSCs) have recently been identified and characterized in humans. Moreover, MSC secrete cytokines that can support hematopoietic progenitor growth. In the present study, we evaluated whether the efficacy of hematopoietic stem cell transplantation is improved by their co-transplantation with MSC, and whether this is positively correlated with the dose of infused MSCs. Accordingly, irradiated NOD/SCID mice were transplanted with 1×10<SUP>5</SUP> human CD34+ cells in the presence or absence of culture expanded MSCs (1×10<SUP>6</SUP> or 5×10<SUP>6</SUP>). We evaluated human hematopoietic cell engraftment by flow cytometry and assessed MSC tissue distributions by fluorescence in situ hybridization. We found that CD45+ and CD34+ cell levels were significantly elevated in a dose-dependent manner in cotransplanted mice 4 weeks after transplantation. The engraftments of CD33+ and CD19+ cells also increased dose-dependently. However, the engraftment of CD3+ cells did not increase after co-transplantation with MSCs. Human Y chromosome+ cells were observed in multiple tissues and were more frequently observed in mice co-transplanted with 5×10<SUP>6</SUP> rather than 1×10<SUP>6</SUP> MSCs. These results suggest that MSCs are capable of enhancing hematopoietic cell engraftment and distribution in multiple organs in a dose-dependent fashion.</P>

      • Conductive deafness with normal eardrum: absence of the long process of the incus

        Park, Keehyun,Choung, Yun-Hoon,Shin, You Ree,Hong, Sung Pyo Scandinavian University Press 2007 Acta oto-laryngologica Vol.127 No.8

        <P> Conclusions. The most likely cause of lesions with an absence of the long process of the incus was congenital origin because many cases were associated with the stapedial anomaly. However, the possibility of a potential inflammation of this lesion could not be completely excluded, especially in cases with only an absence of the long process of the incus. Objective. To clarify whether the absence of the long process of the incus is caused by congenital anomaly or a potential inflammation. Subjects and methods. A total of 21 patients (5 bilateral cases, 16 unilateral cases) with absence of the long process of the incus were reviewed. Operative and histopathological findings of the removed incus were analyzed. Results. The 21 cases with absence of the long process of the incus were classified into 6 types. Thirteen cases showed the absence of the long process associated with the stapedial anomaly, which were all unilateral. Eight cases showed no association with the stapedial anomaly, among which five cases were bilateral. Three of eight cases not associated with the stapedial anomaly showed evidence of resorption in the incus body such as fibrosis and Haversian canal widening.</P>

      • Poster Session : PS 0875 ; Lower GI Tract : The Clinical Characteristics of Crohn`s Disease Patients with Free Perforation in Korea: Results from the Connect Study

        ( You Sun Kim ),( Young Seok Doh ),( Young Il Park ),( Jong Pil Im ),( Jae Hee Cheon ),( Byong Duk Ye ),( Ji Won Kim ),( Sung Noh Hong ),( Young Ho Kim ),( Joo Sung Kim ),( Dong Soo Han ),( Won Ho Kim 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Among the complications of CD, free perforation is the most debilitating complication. A higher incidence of perforation has been reported in Japan than in western countries. However, no large-scale studies concerning perforations in Korean CD patients have been conducted. Methods: The CrOhn`s disease cliNical NEtwork and CohorT (CONNECT) study was conducted in Korea; CD patients who were diagnosed between 1982 and 2008 were included in retrospective cohort. We investigated perforation sites, clinical features, and operation records. We analyzed the association between clinical features and perforation. Results: 1,382 patients were enrolled from the 32-center retrospective CD cohort and 88 patients (6.4%) with perforation were identified. The mean age of the patients with perforation was 31.8±13.0 years, which is significantly higher than the others (27.5±12.1 years)(p=0.04). Free perforation was the presenting sign of CD in 47 patients (53%) and developed after diagnosis in 41 patients (47%). Of 94 perforations from the 88 patients, 81 involved the ileum, 6 the jejunum, and 7 the colon, and 5 patients had perforations at multiple sites. By multivariate analysis, free perforation had a significant association with age over 30 years at diagnosis (OR 1.974, p = 0.008) and bowel stricture (OR 2.235, p = 0.001), but did not show any significant association with steroids, azathioprine, and infliximab. The mortality of patients with free perforation was higher (4.6%; RR = 7.72, p = 0.001) than that of patients without perforation (0.6%). Conclusions: The incidence of free perforation in Korean patients with CD was 6.4% and it was higher than that in western countries. Old age at diagnosis and bowel stricture are significant risk factors for free perforation. Early diagnosis of CD is therefore important in reducing free perforation.

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