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      • KCI등재

        페르시아어 ra 연구 : 격 표지와 주제화 표지로서의 역할을 중심으로

        곽새라 ( Sae Ra Kwak ) 한국외국어대학교 중동연구소 2010 중동연구 Vol.29 No.2

        This paper is to show how Persian "ra" functions in sentences both in grammatical Level and pragmatical level. In Persian traditional grammar, and even in the recent grammar books, "ra" has been introduced as a direct object marker, later as a definite direct object marker. However, several linguistic data show that this element can go with Persian indefinite marker "ye(k)" and "-i", which is the counter example of a definite direct object marker. We witness that Persian "ra" follows nouns or pronouns which are specific. All nouns which are definite are specific. Moreover, for indefinite nouns, if the nouns are only familiar to speakers, not to hearers, the nouns are specific. In sum, ra" can occur following specific direct objects. Another function of "ra" is its pragmatical function, which is topicalization marker. Topicalization is the strategy which expresses given information. Again, this topicalization also implies specificity. However, I argue that even though both functions imply one coommon characteristic, we cannot see "ra" in both cases as a functional marker, which is a specific marker. The facts that "ra" cannot follow subject position and this element is not a necessary condition for topicalization proves the argument. To sum up, Persian "ra" has two functions - one as a specific object marker, and the other as a topicalization marker, and thess two functions cannot be considered as one marker, such as specificity marker.

      • KCI등재

        Retinoic acid induces expression of Ig germ line α transcript, an IgA isotype switching indicative, through retinoic acid receptor

        Mi-Hee,Park,박석래,Mi-Ra,Lee,Young-Ha,Kim,Pyeung-Hyeun,Kim 한국유전학회 2011 Genes & Genomics Vol.33 No.1

        Retinoic acid (RA) is considered to possess an activity of IgA isotype switching. Thus far, TGF-β1 is known to be the most powerful IgA isotype switch factor. To elucidate the molecular mechanisms underlying the Ig germ line (GL) α transcriptional regulation by RA, we constructed three different sizes of mouse GLα promoter reporters; short-GLα(-130/+14), middle-GLα(-448/+72) and long-GLα(-3028/+72). Based on luciferase assay, RA increased the activity of all three GLα promoter reporters by approximately 2-fold and the effect was further enhanced by TGF-β1. Overexpression of Smad3/4 increased TGF-β1-induced GLα promoter activities but had no effect on RA-induced GLα promoter activities. In order to analyze the characteristics of the RA-inducible GLα promoter region,we also constructed two mutant reporters: Smad3 binding elements (SBEs)-substituted short-GLα (short-GLα mSBE)and Runx3 binding elements (RBEs)-substituted short-GLα(short-GLα mRBE) promoter reporters. Promoter activities of the two mutant reporters to RA were comparable to that of wild type reporter, while those of the two mutant reporters to TGF-β1 were markedly diminished as compared to that of WT short-GLα. Finally, RA-induced GLα transcription was virtually disappeared by LE540, an antagonist of RA receptor (RAR). Taken together, these results suggest that RA induces GLα transcription mainly through RAR pathway, where neither Smad3/4 nor Runx3 is involved.

      • SCIESCOPUSKCI등재

        IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future.

        Kim,,Go,Woon,Lee,,Na,Ra,Pi,,Ryo,Han,Lim,,Yee,Seul,Lee,,Yu,Mi,Lee,,Jong,Min,Jeong,,Hye,Seung,Chung,,Sung,Hyun Pharmaceutical Society of Korea 2015 Archives of Pharmacal Research Vol.38 No.5

        <P>Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis. Numerous agents with varying mechanisms are used in the treatment of RA, including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and some biological agents. Studies to uncover the cause of RA have recently ended up scrutinizing the importance of pro-inflammatory cytokine such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the pathogenesis of RA. TNF-α inhibitors are increasingly used to treat RA patients who are non-responsive to conventional anti-arthritis drugs. Despite its effectiveness in a large patient population, up to two thirds of RA patients are found to be partially responsive to anti-TNF therapy. Therefore, agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment. In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers including sarilumab, ALX-0061, sirukumab, MEDI5117, clazakizumab, and olokizumab, and their future perspectives in the treatment of RA.</P>

      • KCI등재

        류마티스관절염 환자의 인슐린 저항성 결정인자

        이정욱 ( Joung Wook Lee ), 박영은 ( Young Eun Park ), 조미라 ( Mi Ra Cho ), 백승훈 ( Seung Hoon Baek ), 김근태 ( Geun Tae Kim ), 이준희 ( Jun Hee Lee ), 김성일 ( Sung Il Kim ) 대한류마티스학회 2009 대한류마티스학회지 Vol.16 No.2

        Objective: Rheumatoid arthritis (RA) is associated with an increased cardiovascular events. These may be related to insulin resistance (IR). We evaluated status of IR and analyzed the relationship between IR and clinical and laboratory characteristics in patients with RA. Methods: We examined 52 RA patients (43 females) and 52 age and sex matched healthy controls. We measured Homeostasis model assessment (HOMA) IR, calculated according to fasting serum glucose and insulin. Results: In patients, age was 50.8±10.2 years old, disease duration was 42.1±30.9 months. In controls, HOMA IR was 0.62±0.30 and in patients, it was 1.28±0.50. This difference was highly significant (p<0.001). Patients with early RA (disease duration is less than 36 months) were 28, and established RA (more than 36 months) were 24. HOMA IR was significantly higher in patients with established RA (1.42±0.45) than those with early RA (1.16±0.45) (p=0.03), and significantly correlated with disease duration (r=0.36, p=0.01), BMI (r=0.36, p<0.001), total cumulative prednisolon dose (r=0.34, p=0.01). Disease duration and BMI were independent predictors for HOMA IR (p<0.01, p=0.03). Conclusion: In patients with RA, IR measured by HOMA IR was more significantly increased than that of healthy control and significantly correlated with disease duration, BMI, and total cumulative prednisolon dose; however, the determinants of HOMA IR in RA patients were disease duration and BMI.

      • KCI등재

        Retinoic Acid 가 Bromodeoyuridine 표지 Hep G2 간암 세포주의 세포 주기 역동성에 미치는 효과

        안득수,김대곤,안중기,장동석,이수택,김이엽,이세라 대한내과학회 1993 대한내과학회지 Vol.45 No.5

        Objectives: Measuring the total cellular DNA and BrdU content simultaneously by using the monoclonal antibody to BrdU and propidium iodide (PI) has been possible. So it has been advanced that the making a correct diagnosis and the predicting a prognosis in cancer as well as the evaluation of the responses of anti-cancer therapy, We intended to exam new anticancer chemotherapeutic agent, retinoic acid (RA) which has been reported to show antiproliferative effect and also differentiation-inducing effect on tumor cells, for the treatment of the hepatocarcinoma prevailed in our country. This study was designed to probe beneficial effects of RA for preventing tumor recurrence and secondary metastasis through the application of it to recently wide spreaded chemoembolization therapy in heaptomas. Methods: A semi-logarithmic plot of the proliferation was made in Hep G2 cells, and the changes of the proliferative activities from adding RA to the medium were evaluated in according to various concentrations of it. After staining the Hep G2 cells with fluoroscence conjugated anti-BrdU and PI, the tumor cell kinetics was analyzed and the effects of RA on the changes of the kinetics were also evaluated in the univariate and bivariate distribution of flowcytometric measurement of DNA content/BrdU incorporation. Results: Hep G2 cells stained with FITC conjugated anti-BrdU and with propidium iodide (PI), were anal- yzed in the distribution of bivariate BrdU/DNA content or univariate DNA content to investigate the tumor kinetics. Data from this expreiments showed that actual doubling time (Td) is 51 hrs, potential doubling tiem (Tpot) is 29 hrs, the mean DNA synthesis time (Ts) is 9. 3 hrs, the labelling index is 27.6%. From the evaluation of the effects of RA, known to enhance the differentiation and inhibit the growth of tumor cells on Hep G2 cells, RA inhibited the proliferation of Hep G2 cells significantly and the inhibition lasted for 10 days. To understand the growth inhibition of RA on Hep G2 cells in terms of tumor cell kinetics, bivariate BrdU/DNA content distributions were analyzed. Early stage of culture (day 1) showed increase in S phase percentage of cells and decrease in Go/G1 phase. But late stage of culture (day 4) show decrease in S phase percentage of cell to minimum and increase in Go/G1 phase at either 1 μM or 0.1 μM concentration of RA as compared with those of control. The influences on cell cycle and the antiproliferative effect were more pronounced at 1 μM than at 0.1 μM concentration. Conclusion: These results demonstrated that RA inhibits the proliferation of Hep G2 cells and the anti-proliferative effect is suggested to be driven from arresting cell cycle progression from Go/G1 to S-phase in tumor cell kinetics.

      • Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression

        Lee,,Jeong-Min,Jang,,Young-Saeng,Jin,,Bo-Ra,Kim,,Sun-Jin,Kim,,Hyeon-Jin,Kwon,,Bo-Eun,Ko,,Hyun-Jeong,Yoon,,Sung-il,Lee,,Geun-Shik,Kim,,Woan-Sub,Seo,,Goo-Young,Kim,,Pyeung-Hyeun CHINESE SOCIETY OF IMMUNOLOGY 2016 CELLULAR AND MOLECULAR IMMUNOLOGY Vol.13 No.6

        <P>Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, T beta RIII) and activation of canonical TGF-beta signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line alpha (GL alpha) transcription and GLa promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced T beta RIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and alpha 4 beta 7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9(+)IgA(+) plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.</P>

      • SCIESCOPUSKCI등재

        Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β<SUB>25-35</SUB> induced impairment of cognition and memory function

        Ah,Young,Lee,Bo,Ra,Hwang,Myoung,Hee,Lee,Sanghyun,Lee,Eun,Ju,Cho 대한지역사회영양학회 2016 Nutrition Research and Practice Vol.10 No.3

        BACKGROUND/OBJECTIVES: The accumulation of amyloid-β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an Aβ25-35-injected mouse model. MATERIALS/METHODS: Male ICR mice were intracerebroventricularly injected with aggregated Aβ25-35 to induce AD. Aβ25-35-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test. RESULTS: Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by Aβ25-35, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the Aβ25-35-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the Aβ25-35-injected mouse brain. CONCLUSIONS: These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by Aβ.

      • SCIESCOPUSKCI등재

        Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β<sub>25-35</sub> induced impairment of cognition and memory function

        Lee,,Ah,Young,Hwang,,Bo,Ra,Lee,,Myoung,Hee,Lee,,Sanghyun,Cho,,Eun,Ju The Korean Nutrition Society 2016 Nutrition Research and Practice Vol.10 No.3

        BACKGROUND/OBJECTIVES: The accumulation of amyloid-${\beta}$ ($A{\beta}$) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an $A{\beta}_{25-35}$-injected mouse model. MATERIALS/METHODS: Male ICR mice were intracerebroventricularly injected with aggregated $A{\beta}_{25-35}$ to induce AD. $A{\beta}_{25-35}$-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test. RESULTS: Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by $A{\beta}_{25-35}$, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the $A{\beta}_{25-35}$-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the $A{\beta}_{25-35}$-injected mouse brain. CONCLUSIONS: These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by $A{\beta}$.

      • S-481 : Digital ulceration due to the change of hand microvasculature induced by rheumatoid arthritis

        ( Yu Ra Sim ), ( Yea Jin Lee ), ( Sung Jae Choi ), ( Young Ho Seo ), ( Gwan Gyu Song ) 대한내과학회 2015 대한내과학회 추계학술대회 Vol.2015 No.1

        Background: Severe Raynaud's phenomenon enough to make digital necrosis is a rare manifestation of rheumatoid arthritis(RA) without other evidences of overlapped systemic sclerosis. Here we report a case of a severe Raynaud's phenomenon with finger tip ulceration and gangrene in uncontrolled RA patient. Case Report: A 54-year-old male with 8-year history of taking weekly methotrexate 7.5 mg for RA visitedour cardiovascular surgery department complaining of 2-week history of ulceration of left third fingertip with Raynaud's phenomenon. Physical examination revealed tenderness, swelling, and limitation of movement in bilateral wrist, 2nd & 3rd MCP and PIP joints. The ulcerative lesion in left 3rd fingertip was combined with bluish color change. He had normal bilateral radial and ulnar pulses. Left forearm arteriography revealed localized hypervascularity of RA affected joints and multiple occlusions at interosseous arteries and digital arteries, especially most severe in third finger. We increased the dosage of methotrexate to 12.5 mg/week, additionaly preiscribed methylprednisolone 4 mg/day and tadalafil. We strongly recommended quitting of smoking. After 2 months, the ulcerated lesion in fingertip was improved and arthritic joint pain was resolved. Conclusions: In uncontrolled RA activity, deprivation of distal blood flow induced by the shunt like filling of the veins through hypervascularized region in severely affected arthiritic joints, can result in Raynaud's phenomenon and digital gangrene.

      • KCI우수등재

        엉겅퀴 뿌리 물 추출물의 류마티스 관절염 동물 모델에 대한 개선 효과

        노종현(Jong Hyun Nho), 이현주(Hyeun Joo Lee), 이에나(E Na Lee), 우경완(Kyeong Wan Woo), 장지훈(Ji Hun Jang), 김선라(Sun Ra Kim), 조현우(Hyun Woo Cho), 노세응(Se Eung Noh), 정호경(Ho Kyung Jung) 한국약용작물학회 2020 韓國藥用作物學會誌 Vol.28 No.6

        Background: The roots of Cirsium japonicum var. ussuriense (RCJ) have been used as traditional medicine in Korea for hematuria and hematemesis. These extracts exert anti-oxidative and anti-inflammatory effects by scavenging for free radical and regulating the inflammatory response. However, the effect of RCJ on rheumatoid arthritis (RA) has not been elucidated. Thus, we evaluated the water extract of RCJ (WRCJ) using type II collagen-induced RA models. Methods and Results: RA was induced by immunization with type II collagen. All experimental materials were orally administered daily for three weeks. The positive control group was administered with 0.2 ㎎/㎏ methotrexate (n = 7), while the experimental group was administered with WRCJ (100 or 500 ㎎/㎏, n = 7). Serum levels of TNF-alpha, Interleukin 6 (IL-6), and type II collagen IgG (CII) were measured using ELISA. Administration of 500 ㎎/㎏ WRCJ decreased the levels of TNF-alpha, IL-6, and CII. Moreover, WRCJ treatment diminished swelling of hind legs and infiltration of inflammatory cells in RA models' synovial membrane. Conclusions: These results indicate that WRCJ could improve RA, reduce inflammatory indicators and synovial inflammation. However, further experiments are required to determine how WRCJ can influence the signal transduction pathway in RA.

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