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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.
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.
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.
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>
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.
만성 호산구성 폐렴은 드물지만 류마티스관절염에서 동반 될 수 있는 질환이며 호산구성 흉막삼출이 동반되는 경우는 두 질환 모두에서 드문 경우이다. 저자들은 류마티스 관절염과 만성 호산구성 폐렴에 호산구성 흉막삼출이 동반된 환자를 진단하였으며, 스테로이드와 항류마티스 약제의 사용으로 효과가 있었던 예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. We describe a 48-year-old man with family history of rheumatoid arthritis (RA) affected by chronic eosinophilic pneumonia (CEP) with severe peripheral eosinophilia. CEP might develop as a complication of longstanding active RA. The patient with 5 months history of seropositive RA and chronic respiratory symptoms, alveolar and blood eosinophilia, peripheral pulmonary infiltrates and pleural effusion on chest imaging. The lung may be involved as an extraarticular manifestation of RA. However, CEP is not recognized as a typical lung manifestation of RA, and the two diseases rarely coexist. The effusion was an eosinophil predominant exudates and was characterized by low pH, and glucose level and high lactic dehydrogenase. The patient responded rapidly to combination of steroids and disease modifying anti-rheumatic drugs.
Poster Session : PS 0691 ; Rheumatology ; A Randomized, Double-Blind, Phase 3 Equivalence Trial Comparing the Etanercept Biosimilar, Hd203, to Reference Etanercept, in Combination with Methotrexate (MTX) in Korean Patients with Rheumatoid Arthritis (RA)
Background: Etanercept is a recombinant fusion protein that blocks TNF. HD203 is a biosimilar of etanercept with demonstrated comparability across pharmacokinetics, safety and tolerability. The objectives of this study were to evaluate equivalence in effi cacy and compare safety of HD203 with reference etanercept, in combination with MTX in patients with RA. (ClinicalTrials. gov NCT01270997). Methods: Korean patients (male or female aged =20 years) with active RA were randomized (1:1) to 25 mg HD203 or reference etanercept, administered subcutaneously twice weekly with MTX for 48 weeks. The primary endpoint was the proportion of patients achieving ACR20 at week 24. Secondary endpoints included ACRn, DAS28, andEULAR response at week 24 and 48, safety and immunogenicity. Results: In total, 294 patients were randomized: HD203, n=147; reference etanercept, n=147. The proportion of patients achieving ACR20 at week 24 was not signifi cantly different between HD203 and reference etanercept. Equivalent effi cacy was demonstrated within predefined margins. There were no significant differences between proportions achieving ACR20 at week 12 and 48. ACR50 and ACR70 displayed similar trends. There were no signifi cant differences between groups for ACRn, DAS28, and EULAR response. Safety set analysis (HD203, n=147; reference etanercept, n=146) revealed no signifi cant difference for treatment-emergent (all-causality) adverse events (AEs): HD203 76. 87% vs. reference etanercept 78. 08% (p=0. 8040). No significant differences between HD203 and reference etanercept were observed for adverse drug reactions, serious AEs, or discontinuations due to AEs. Few patients tested positive for anti-drug antibodies. Conclusions: The study met the primary endpoint of demonstrating equivalent effi cacy of HD203 compared to reference etanercept. HD203 was well tolerated, with a safety profi le comparable to reference etanercept in this population of patients with RA.
Objective. We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis. Methods. We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin. Results. In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA. Conclusion. Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.
Kang, Li‐,Jung,Kwon, Eun‐,Soo,Lee, Kwang Min,Cho, Chanmi,Lee, Jae‐,In,Ryu, Young Bae,Youm, Tae Hyun,Jeon, Jimin,Cho, Mi Ra,Jeong, Seon‐,Yong,Lee, Sang‐,Rae,Kim, Wook,Yang John Wiley and Sons Inc. 2018 British journal of pharmacology Vol.175 No.23
<P><B>Background and Purpose</B></P><P>3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in <I>in vitro</I> and <I>in vivo</I> models.</P><P><B>Experimental Approach</B></P><P>The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes <I>in vitro</I> and an <I>in vivo</I> mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects <I>in vitro</I>. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining.</P><P><B>Key Results</B></P><P>3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis <I>via</I> NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models.</P><P><B>Conclusions and Implications</B></P><P>3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated <I>via</I> blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.</P>
The mass media promote the standardization of the languages they use, because in this way they are able to make communication with their readers and audiences more efficient. The mass media have, in addition, gone beyond national frontiers. Spanish is no exception, since it is spoken in more than 20 countries and regions, including North America. In the U.S.A a large number of programs are produced in Spanish and many TV productions are dubbed for subsequent distribution in Latin America and Spain. However, in international programs the oral media -television and radio- introduce variants, especially regarding the phonological and lexical components of the language. The selection of these variants would seem to correspond to the demographic volume of the audiences and to their distribution in the different countries of the Spanish-speaking world. This panorama offers important contradictions in different areas. Internationally, Spanish competes with English; nationally, it would appear to impose itself on minority languages, especially in Spanish America. Finally, within the Spanish community there are also conflicts between the different variants that are heard in the mass media. This paper offers a discussion of these problems and suggest possible ways of taking decisions, especially regarding variants in the Spanish language on the international level.