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      • 방송 프로그램 제목에 나타난 국어, 외래어 사용 실태와 그에 대한 방송현업인의 태도 연구

        손세희 서강대학교 언론대학원 2001 국내석사

        RANK : 247631

        This study analyzed the borrowed words used in Broadcasting according to sociolinguistic views and different opinions between producers and evaluation committee about Broadcasting language. English has not been used as the first language or an official language. Educated people, however, can communicate with others by speaking English, and most people has been accustomed to mix Korean with English together. We also have used a word written in Chinese characters for a long time, and it became hard to communicate without using a word written in Chinese characters. Moreover when we want to speak fairly and politely, we used a word written in Chinese characters. We think that it is good manners by using a word written in Chinese characters when we speak or write. The language used in Broadcasting has reflected this appearance. In this study, I interpreted the fact of Broadcasting language have been related to multilingualism or diglossia. Because the example of 'code-mixing' occurred in diglossia could be easily found in Broadcasting language. It is of long standing, especially, the number of case of mixing Korean with English in Broadcasting language has been increased. To understand the current situations of Broadcasting language, the title of current Broadcasting programs of four different channels was analyzed as basic data for this paper. The attitude of both producers and evaluation committee was also analyzed and compared by using questionnaires about their views of Broadcasting language. According to the investigation, the percent of used language that mixed Korean, a word written in Chinese characters and a borrowed word was 53.5 in broadcasting language. These titles can be translated and expressed by using only Korean. The fact has shown that the mixed language was not only used as in communication with others but also other meaning of 'code-mixing'. According to the result of questionnaire, both producers and evaluation committees agree with the power of Broadcasting language, but they usually do not have the critical mind of using the mixed language in broadcasting. However, in case of evaluation committee, over 50% of them agreed that it might be bad effect to people, as the number of case of using the mixed language in Broadcasting has been increased. This opinion was different with the producers. Finally, the value of this research was described as follows. First, the problem of mixed language used in broadcasting language was analyzed in the view of sociolinguistic. Second, I discussed the basis of common views between two groups have different standpoint about broadcasting language. On the other hand, it was hard to define a borrowed language. In this research, a word written in Chinese characters and foreign language which have been used as Korean was also included in the group of a borrowed language because of the importance and characteristics of Korean. However, according to the results, we should only include and define as a borrowed language with the hard Chinese characters and foreign language without translated language.

      • 개화기 선교사들의 교육사업의 성격 : The Korean repository와 The Korea review를 중심으로

        손세희 광주교육대학교 교육대학원 2009 국내석사

        RANK : 247631

        Protestant missionaries started to come into Korea for evangelism since 1884. They began to work mainly in the field of educational and medical services after noticing governmental attitude and policy, which was not at all favorable to the Christianity. This study investigates the strategies and activities of the educational projects by the missionaries and their outcomes in detail by analysing the missionaries’ articles appeared in their monthly periodicals, The Korean Repository and The Korea Review. It also tries to evaluate their effects on Korean education at that time and afterwards. The missionaries diagnosed the educational situations of Korea at that time as follows. First, due to the inequity in opportunity of education, only the ruling class(so called Yangban) could enjoy the opportunity of education; however they have become a reactionary social group rather than the engine of national development. Second, low social recognition toward teachers(particularly Seodang teachers) and accordingly the poor salaries lowered teachers’ morale and the quality of their educational performances. Third, the contents of education lacked modern and useful knowledges, the teaching/learning methods mainly revolved around simple reproduction and memorization. As a result, education functioned only to maintain one’s social status without any relevance with the real life in the modern world. Fourth, the educational system and facilities were unstructured and poor, mainly due to the lack of support from the government. After making diagnoses described above, the missionaries set the goals of their educational projects, first, to realize equity in educational opportunities, second, to reinforce liberal education, and third, to educate Korean students with Christian beliefs. To realize such goals, first, they founded modern schools open to all kinds of people. Second, they adopted several branches of modern knowledge, and tried various new methods of education. Third, they emphasized language education including Hangul (Korean alphabet) and other foreign languages to facilitate the fast and effective dissemination of knowledge. Fourth, textbooks, newspapers, and magazines were published to be utilized in education and to enhance the general interests in education. However, the Korean people did not responded as expected by the missionaries. The Korean government and the elites who supported open-door policy were interested mainly in using modern education provided by the missionaries only as a means of enhancing national prosperity and defense. Theoretically their position was based on the doctrine of Dongdo-Seogi(which means allowing the adoption of Western technologies on the basis of Eastern moral codes). Ordinary people also found in modern education good opportunities to obtain a job in governmental ranks and to get a higher salary. Although the missionaries worried about Korean's attitude which regarded education merely as a means, but they could not entirely reject such an attitude. Despite their original purpose of enlightening the Korean people through the modern forms of schooling, it was very hard for Korean people, who were brought up in totally different tradition, to understand and accept Western values. They only paid attention to and accepted the instrumental values of Western culture, neglecting the intrinsic values cherished by the missionaries. Although the modern education in Korea was initiated and led by the missionaries partially at the least, Korean people did not accept it just passively; rather they actively accepted only the aspects of the new education according to their actual needs. The missionaries brought visible models of modern education into the Korean educational system and before the eyes of Korean people. However, because of the differences in perspectives between them and the Korean people, they could not fully achieve their original educational goals. In this sense, it was a half success and a half failure. 기독교 선교사들은 1884년부터 선교 목적을 갖고 조선에 입국하기 시작했다. 그들은 기독교에 대해 호의적이지 않은 조선 정부를 의식하여 교육과 의료 부문에서 먼저 활동을 개시했다. 본 연구는 The Korean Repository와 The Korea Review라는 당시 선교사들의 월간잡지에 나타난 그들의 의견을 분석하여 선교사들이 설정한 조선 교육 사업의 전략과 활동, 교육 사업의 성공 여부를 구체적으로 알아보고, 더 나아가 개화기 선교사들의 교육 사업이 우리나라 근대 교육에 끼친 영향을 재조명해 보는 데 목적이 있다. 선교사들이 진단한 당시 조선 교육의 문제점은 다음과 같다. 첫째, 교육 기회의 편중으로 양반 계층만이 교육을 받을 수 있었으나 그들은 더 이상 조선 사회에 기여하지 못하고 오히려 발전을 저해하는 걸림돌이었다. 둘째, 교사들 특히 서당 훈장들에 대한 낮은 사회적 인식과 대우는 교육의 질을 매우 낮게 만드는 요인으로 작용하고 있었다. 셋째, 교육 내용은 유용한 근대적 지식들을 결여하고 있었고, 교수/학습 방법은 단순한 재생산과 암기 위주였다. 그 결과 교육은 근대화된 세계에서의 실생활과의 관련성을 잃고 그저 신분 유지의 수단으로 사용되고 있었을 뿐이었다. 넷째, 교육 제도·시설·지원 등은 정부에서 관심을 기울이지 않아 비체계적이고 열악했다. 선교사들은 이와 같이 조선 교육의 문제점을 진단하고 교육 사업의 전략과 목적을 교육의 기회 균등 실현, 자유 교육 실시, 기독교 신앙을 가진 한국인 양성으로 설정했다. 구체적 교육 활동으로는 첫째, 누구나 입학하여 공부할 수 있는 신식 학교를 설립하여 교육의 대중화를 꾀했다. 둘째, 교육 내용과 방법 등에 변화를 주어 실생활에 유용한 지식을 전달하고 여러 가지 교육 방법을 구사했다. 셋째, 한글 교육과 외국어 교육을 통해 대중에게 많은 지식을 빨리 전달하고 습득할 수 있도록 했다. 넷째, 교과서·신문·잡지 등을 출판하여 교육 활동에 이용하였으며 교육에 대한 관심을 고취시켰다. 그러나 조선인들의 반응은 선교사들이 의도와 거리가 있는 것이었다. 정부와 개화 추진 세력들은 선교사들이 제공한 신교육을 동도서기론에 입각한 부국강병이나 사회 통제 수단으로 활용하고자 하였다. 그리고 조선 민중들은 신교육을 관직에 나아가고 높은 자리와 급료를 얻기 위한 수단으로 이용하려고 하였다. 선교사들은 이처럼 교육을 수단으로 이용하려는 태도에 대해 우려를 나타냈지만 그러한 경향이 워낙 강하여 어쩔 수 없이 거기에 동조하며 협력하게 된다. 조선을 개화시키고자 서구식 학교를 세우고 교육의 기회 균등, 자유교육 등의 목적을 실현해 나가고자 한 선교사들의 의도와는 달리 오랜 교육 전통을 지닌 뿌리 깊은 유교 국가였던 조선에서 서양 선교사들이 서구식 자유 교육이 추구하는 내재적 가치를 조선인들이 단기간에 이해·수용하도록 만들기는 매우 어려웠다. 결국, 조선인들은 선교사들이 추구했던 내재적 가치는 도외시한 채 외재적 가치만을 주목하고 받아들인 셈이었다. 이와 같이 미션스쿨을 통한 근대 교육은 선교사의 주도로 실시되었지만, 조선인들이 그것을 단지 수동적으로 받아들인 것은 아니다. 조선인들은 선교사들이 제공한 교육 중 필요한 부분만 수단적으로 받아들였다. 선교사들의 교육 사업은 조선 교육의 근대화에 외적인 성장과 교육 방법의 근본적인 변화를 가져오긴 했지만 그 교육을 대하는 조선인들의 요구와 태도로 인해 선교사들이 원하는 교육 목적을 온전히 달성할 수는 없었다. 그것은 이를테면 절반의 성공과 절반의 실패였다.

      • LED Cube조형물의 콘텐츠 구현에 관한 연구

        손세희 경북대학교 대학원 2010 국내석사

        RANK : 247631

        This thesis is about a process of implementing a LED Cube (8x8x8) in more theoretical approach than practical one. First of all, creating LED cube gives a possibility to create cubic contents inside, and it has lots of potential to apply for many artistic works. Also the artistic meaning can be found from the 'Grid' that are used to array LED chips. 'Grid' is very important method when designers and artists measure the shape and compose the objects. In this study grid has been the base structure to the frame and the contents. After considering theoretical meaning, practical side was mentioned in phrase. 512 LED chips are soldered on the wire as positive current and on electric lines as negative current. Starting with lightening up the whole cube, the current of each light element was disconnected selectively to make the shape of a sphere in the cube. Actually the shape appears to be a diamond-like. Consequently, even though the elements of the cube have been controlled by changing the electrical current by now, in future Micro-controller system will be connected to the each light element that will show the contents image to animate and interact with serial data. This thesis is the first step of the whole project to create interactive cubic lightening system with various contents animation possible.

      • 한국 노동자의 반세계화 운동

        손세희 고려대학교 2005 국내석사

        RANK : 247631

        Abstract The labor movement in Korea sine the 1997 financial crisis clearly reveals different characteristics compared to pre-1997 labor movement. First, it has been increasing in its frequency. The labor strikes had constantly decreased since 1987, but it started to increase again since 1997. Second, the issue shows a clear distinction between pre-1997 labor strikes and post-1997 labor strikes. Whereas the wage was the most important issue in pre-1997 labor strikes, the collective agreement became the most important issue in post-1997 labor strikes. Lastly, the union density shows a constant decrease since 1989. However, the reason of decrease seems different between pre-1997 and post-1997. The radical increase in non-regular workers after the financial crisis seems to be one of the critical reasons that affected the decrease in union density since 1997. Paying attention to this change in labor movements in Korea since 1997, this thesis aims to reveal what affected the emergence of such new form of labor movements, naming them labor’s anti-globalization movement. First in chapter 2, it seeks what changes the neo-liberal globalization brought that deteriorated the socio-economic status of labor. To begin with, how deindustrialization phenomenon and merger and acquisition due to domestic companies’ foreign investment and opening of capital market affected the labor was revealed. Next, the non-regular worker issue that is seriously threatening the labor was studied as the impact of globalization. All these factors generated by globalization have highly influenced Korean labor and deteriorated their livings. In chapter 4, how the agency affected the emergence of labor’s anti-globalization movement is revealed. Especially, this thesis focused on the leader’s role in collective identity reframing and mobilization. First, to show the leadership effectiveness in collective identity reframing, the Korean Confederation of Trade Unions (KCTU)’s activities to educate union members was studied. The cadre of KCTU educated their union members to realize how badly they were influenced by globalization so that they could share the collective identity as the same victim of globalization. Also, how the union member’s collective identity was reframed was shown through the change in their interests and enemy. Lastly, the leaders’ role in stimulating and increasing the mobilization of union members was studied. First, the KCTU leader determined strategy, repertoire of action, and tactics for general strike to increase mobilization. Second, they tried to fortify inter and intra-networking, because solid network facilitates the mobilization of union members in a collective action. As in collective identity reframing, the use of propaganda was also effective to increase mobilization of union members. The strong and impressive images and expressions could effectively stimulate the union members’ participation. Lastly, the KCTU leaders visited individual companies to appeal to union members to participate into general strike, and they also temporarily reorganized the KCTU into the strikers’ headquarters. Abstract The labor movement in Korea sine the 1997 financial crisis clearly reveals different characteristics compared to pre-1997 labor movement. First, it has been increasing in its frequency. The labor strikes had constantly decreased since 1987, but it started to increase again since 1997. Second, the issue shows a clear distinction between pre-1997 labor strikes and post-1997 labor strikes. Whereas the wage was the most important issue in pre-1997 labor strikes, the collective agreement became the most important issue in post-1997 labor strikes. Lastly, the union density shows a constant decrease since 1989. However, the reason of decrease seems different between pre-1997 and post-1997. The radical increase in non-regular workers after the financial crisis seems to be one of the critical reasons that affected the decrease in union density since 1997. Paying attention to this change in labor movements in Korea since 1997, this thesis aims to reveal what affected the emergence of such new form of labor movements, naming them labor’s anti-globalization movement. First in chapter 2, it seeks what changes the neo-liberal globalization brought that deteriorated the socio-economic status of labor. To begin with, how deindustrialization phenomenon and merger and acquisition due to domestic companies’ foreign investment and opening of capital market affected the labor was revealed. Next, the non-regular worker issue that is seriously threatening the labor was studied as the impact of globalization. All these factors generated by globalization have highly influenced Korean labor and deteriorated their livings. In chapter 4, how the agency affected the emergence of labor’s anti-globalization movement is revealed. Especially, this thesis focused on the leader’s role in collective identity reframing and mobilization. First, to show the leadership effectiveness in collective identity reframing, the Korean Confederation of Trade Unions (KCTU)’s activities to educate union members was studied. The cadre of KCTU educated their union members to realize how badly they were influenced by globalization so that they could share the collective identity as the same victim of globalization. Also, how the union member’s collective identity was reframed was shown through the change in their interests and enemy. Lastly, the leaders’ role in stimulating and increasing the mobilization of union members was studied. First, the KCTU leader determined strategy, repertoire of action, and tactics for general strike to increase mobilization. Second, they tried to fortify inter and intra-networking, because solid network facilitates the mobilization of union members in a collective action. As in collective identity reframing, the use of propaganda was also effective to increase mobilization of union members. The strong and impressive images and expressions could effectively stimulate the union members’ participation. Lastly, the KCTU leaders visited individual companies to appeal to union members to participate into general strike, and they also temporarily reorganized the KCTU into the strikers’ headquarters.

      • 폐암세포주에서 방사선치료 효과의 극대화를 위한 β-lapachone의 병용과 세포사멸 기전 연구

        손세희 울산대학교 일반대학원 2008 국내박사

        RANK : 247631

        Non-small cell lung cancer (NSCLC) accounts for 70~80% of all lung carcinoma. Due to NSCLC resistance to current treatment regimens, the survival rate is less than 10% after diagnosis within recent 5 years. Therefore, alternative therapeutic efficacy for NSCLC are essentially required. Recent reports show that cancer patients has been improved by concomitant treatment of irradiation and anticancer drugs. β-lapachone is a natural compound presented in the bark of the South American Lapacho tree. β-lapachone is reduced by 2-electron reductase NQO1, and induces through occurring DNA alkylation. β-lapachone also elevates efficacy of taxol by combination with it. Although β-lapachone is a novel anticancer agent, mechanisms of β-lapachone-induced cell death and radiosensitization by cotreatment with irradiation have not been clear. Here, this study elucidates anticancer effect of β-lapachone and mechanism of β-lapachone-induced cell death when β-lapachone is treated simultaneously with irradiation in NSCLC. To demonstrate the relationship between β-lapachone-induced cytotoxicity and NQO1, as well as their mechanism, we examined cytotoxicity by MTT or MTS analysis in NQO1-rich NCI-H460, A549 and NQO1-deficient NCI-H596. In result, β-lapachone significantly increased cytotoxicity in NQO1 overexpressing A549 and NCI-H460 in comparison with NQO1 lacking NCI-H596. To answer whether β-lapachone can induce DNA damage, we examined DNA damage marker, γ-H2AX expression by Western blot. In consequence, γ-H2AX expression was remarkably increased in NCI-H460 by 5 μM β-lapachone. On the other hand, NQO1-deficient NCI-H596 didn’t show the induction of γ-H2AX protein after treatment of 5 μM β-lapachone. We also found that phosphorylation of Chk2 (Thr68) was induced by β-lapachone treatment, implying ATM kinase, upstream modulator of Chk2 and γ-H2AX might involve in cytotoxicity by β-lapachone in NCI-H460. Therefore, we tested the effect of ATM kinase specific inhibitor, KU-55933 on β-lapachone-induced cytotoxicity. Ku-55933 was treated before 1 hour and then β-lapachone 5 μM for 4 hour in NCI-H460. The treatment of KU-55933 resulted in significant decrease of phospho-Chk2 and γ-H2AX proteins, which suggests that ATM pathway is involved in β-lapachone-induced cytotoxicity. In addition, to investigate the effect of β-lapachone as a radiosensitizer that evokes synergistic effect on irradiation-induced DNA damage and cell death, we treated NSCLC with β-lapachone and/or irradiation, and examined the DNA damage and cell death in NSCLC. Co-administration of irradiation caused PARP cleavage and notable increase of γ-H2AX expression in NQO1 overexpressing NCI-H460 cells. β-Lapachone enhanced irradiation-induced DNA damage response and cytotoxicity in NQO1-overexpressing cells, but not in NQO1-deficient cells, which indicates that NQO1 might play a important role for the radiosensitization mediated by β-lapachone. Therefore, this study demonstrates that β-lapachone is a promising anticancer drug or a radiosensitizer for human cancer therapy, which potentially enhances effectiveness of therapy in radioresistant cancer cells. Since NQO1 is overexpressed up to 50 fold in many tumors compared to normal tissue, β-lapachone can be developed as a specific targeting agent for cancer therapy. 전체 폐암 (lung carcinoma)의 70~80%를 차지하는 비소세포암 (non-small cell lung cancer)은 현재 치료법에 대한 저항성 때문에 5년 이상 생존율이 10% 이하로 매우 낮아서 NSCLC를 위한 새로운 치료전략이 요구되고 있다. 최근 보고에 의하면 방사선치료와 항암제 치료를 병용함으로써 고형암 환자들의 치료효과가 크게 증가되었다. Lapacho 나무에서 추출된 천연물인 β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtol[1,2-b]pyran-5,6-dione)은 2-전자환원효소 (electron reductase)인 NQO1 (NAD(P)H:quinine oxidoreductase)에 의해 환원됨으로써 DNA를 알킬화 (alkylation) 시켜 세포사망을 일으키며 taxol과 병용시 taxol 효과를 증진시키는 것으로 알려져 있다. 이러한 특징 때문에 β-lapachone은 유용한 차세대 항암제로써 각광받고 있다. 그럼에도 불구하고 β-lapachone이 암세포를 사망시키는 기전은 아직 명확하지 않으며 방사선과의 병용에 있어서의 자세한 작용기전은 규명되지 않았다. 따라서 본 연구에서는 β-lapachone의 암세포에 대한 항암 효과와 방사선과의 병용시에 나타나는 항암효과의 기전을 규명하고자 하였다. β-lapachone의 항암효과와 NQO1의 관련성을 규명하고 그에 따른 작용기전을 명확히 이해하고자 NQO1의 발현이 매우 높은 A549, NCI-H460세포주와 NQO1의 발현이 거의 없는 NCI-H596 폐암세포주를 이용하여 β-lapachone에 대한 세포 독성을 비교하는 실험을 수행하였다. 그 결과 NQO1의 발현이 현저하게 높은 A549와 NCI-H460 세포주에서 β-lapachone에 대한 세포독성이 NQO1 발현이 거의 없는 NCI-H596세포주에 비해 현저하게 증가함을 볼 수 있었다. 암세포에 대한 세포독성을 나타내는 β-lapachone 이 DNA 손상이나 DNA double-strand break (DSB)를 유발하는지 밝히기 위해 β-lapachone 처리 후 DNA 손상 표지자 (marker)인 γ-H2AX 단백질 발현을 western blot 방법으로 확인한 결과 β-lapachone 5 μM 처리 후 γ-H2AX 가 점진적으로 증가하다가 8시간에 크게 증가함을 보였다. 반면에 NQO1 의 발현이 거의 없는 NCI-H596에서는 γ-H2AX 가 거의 발현되지 않았다. 또한 Western blot을 통해 인산화된 Chk2단백질 발현의 증가를 확인한 바, β-lapachone 이 나타내는 세포독성은 인산화된 Chk2와 γ-H2AX 단백질의 활성화를 상위단계에서 조절하는 ATM kinase가 작용할 수 있음을 확인하였다. 따라서 이를 명확히 하기 위해 ATM kinase 저해제인 KU-55933을 β-lapachone 처리 1시간 전에 처치하였을 때 인산화된 Chk2 와 γ-H2AX 의 발현이 현저하게 감소함으로써 β-lapachone 에 의한 세포 사망에 ATM이 관여할 수 있다는 것을 확인할 수 있었다. 한편, 방사선 민감제로써 방사선과의 병용시 방사선 효과를 극대화하여 DNA 손상과 암세포 사망에 있어 상승작용을 나타내는지 확인하기 위해 2.5 μM β-lapachone을 전처리하여 24 시간 후에 4 Gy 방사선 조사하거나 조사하지 않은 채로 4시간 또는 8시간 배양하여 MTT 분석방법을 통해 세포독성 조사를 시행하였고, 유세포분석을 통해 세포주기와 세포 사망 정도를, western blot 방법을 통해 β-lapachone 단독 또는 방사선과의 병용시 여러 단백질의 발현 정도를 비교 조사하여 세포사망시 작용하는 기전에 대해 알아보고자 하였다. 그 결과 NQO1의 발현이 높은NCI-H460 세포주에서 PARP cleavage와 γ-H2AX 의 단백질의 현저한 증가를 확인하였다. 특히 β-lapachone과 방사선 조사를 병합하여 8시간을 배양한 세포들에서 β-lapachone과 방사선의 병합처리에서 PARP cleavage와 γ-H2AX 의 극명한 증가를 보여주었는데, 이것은 방사선 조사에 의하여 작동되는 DNA repair system과의 시간적 상관관계가 있을 것으로 짐작된다. 지금까지의 결과들을 종합해 보면 폐암세포주에 있어서 β-lapachone은 세포고사를 유발하며 DNA 손상을 유발하였다. 또한 방사선과의 병용 처리를 통해 암세포 사멸에 대한 상승작용이 나타나는 것으로 확인되었으며, 여기에 NQO1 발현의 차이가 관여 할 수 있음을 확인하였다. 따라서 방사선에 저항성을 보이는 암세포에 β-lapachone을 병용한다면 방사선 치료 효과를 증진시킬 수 있을 것이며, β-lapachone에 의한 방사선 민감도 증진 기전을 밝힘으로써 암치료의 효능을 증가시키는 방법을 개발할 수 있을 것이다.

      • Effects of CKD-M808, a novel histone deacetylase 6 inhibitor, on fibroblast-like synoviocytes and regulatory T cells in rheumatoid arthritis

        손세희 서울대학교 대학원 2018 국내석사

        RANK : 247631

        Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose hallmark is joint destruction caused by synovial proliferation and leukocyte infiltration in synovial membrane. Histone deacetylase (HDAC) inhibitor was suggested as a promising therapeutic agent in cancer and autoimmune diseases. Recently, the toxicity of pan-HDAC inhibitor (pan-HDACi) has been reported in clinical trials. HDAC6 is a member of HDAC family, mainly targeting non-histone proteins. We examined the therapeutic effect of selective inhibitor of HDAC6 in RA. Objective: We investigated anti-inflammatory effects of a novel HDAC6 inhibitor, CKD-M808 (M808), on fibroblast-like synoviocytes (FLS), peripheral blood mononuclear cells (PBMCs) and regulatory T cells (Treg) in RA as well as adjuvant-induced arthritis (AIA) rat model. Methods: Cell viability was analyzed by cell-counting kit 8 (CCK-8). RA FLS were incubated with HDAC6 inhibitor, M808 and tubastatin A as a positive control, and then stimulated with IL-1β. The levels of metalloproteinase (MMP) -1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 were measured in culture supernatants of FLS by Magnetic Luminex Screening Assay multiplex kit (Luminex assay) or enzyme-linked immunosorbent assay (ELISA). Expression of HDAC6, α-tubulin, acetylated tubulin, cortactin, acetylated cortactin, ICAM-1, VCAM-1, and GAPDH in FLS were assessed by western blot. Wound healing assay and cell adhesion assay in FLS were performed. RA PBMCs were incubated with HDAC6 inhibitors, tubastatin A or M808, and then stimulated with LPS. TNF-α, IL-1β, IL-6, and IL-10 were measured in culture supernatants of PBMCs by Luminex assay and ELISA. CD4+CD25- T cells were isolated from RA PBMCs and induced to regulatory T cells. The markers of induced Treg (iTreg) were analyzed by flow cytometry. CD4+CD25- T cells (effector T cells, Teff) from healthy donor or murine splenocytes were stained with carboxyfluorescein succinimidyl ester (CFSE) or eFluor®670 and cocultured with iTreg from RA patients or Treg from murine splenocytes respectively. The proliferation of healthy Teff was analyzed by flow cytometry. Adjuvant-induced arthritis (AIA) was developed in Lewis rat. Clinical score of arthritis was measured after M808 treatment. Result: M808 decreased the production of MMP-1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 in RA FLS. M808 increased the acetylation of tubulin and cortactin and inhibited the expression of ICAM-1 and VCAM-1 in RA FLS. The migration of RA FLS and adhesion of U937 cells or Jurkat cells on RA FLS were declined with the treatment of M808. M808 reduced TNF-α and increased IL-10 production, but had negligible effects on IL-1β and IL-6 in RA PBMCs. The function of iTreg induced from RA cells under the presence of M808 significantly improved by suppressing the proliferation of Teff. M808 had enhanced suppressive function of Treg and improves the clinical score of arthritis in AIA rat model. Conclusion: A novel HDAC6 inhibitor, M808 exhibits the suppressive effects on inflammation by reducing the production of MMPs, pro-inflammatory cytokines, and chemokines, decreasing cell migration and adhesion of RA FLS, and improving the suppressive function of Treg derived from RA patients. M808 improved clinical score of arthritis in AIA animal model. M808 could be a potential therapeutic agent in RA.

      • 미세형태학적 형질에 근거한 Rumiceae Dum.족(마디풀과)의 계통분류학적 연구 :

        손세희 경희대학교 대학원 1999 국내석사

        RANK : 247631

        To assess the systematic values of four micromorphologicalcharacters(e.g. pollen, inner tepal cells, leaf surfaces and anter endothecial thickening) among the tribe Rumiceae Dum. (4 genera, 61 species, 9 subspecies; 94 specimens in total), a detailed light microscopy (LM) and canning electron microscopy (SEM) including the cryomicrotomy-method with SEM studies were carrie out, and are presented. On the basis of the present data including some additional data from the previous literatures, the cladistic approach is employed in examining gereric interrelationships. The pollen grains of investigated taxa are monad, 3(-4-9) clporate, perforate surface sculpturing(less than1㎛) with scattered microspinules; sizes are variable (23.9×16.4-55.4×43.3㎛). The exine thickness of the genera Rheum and Emex (ca. 2-3 ㎛) is somewhat thicker than that of Oxyria and Rumex(1-2㎛), which shows slight correlation between pollination vector and exine thickness. The inner tepal surfaces have revealed some differences among the taxa studied. Four main patterns of sculpturing and cell shape can be recognized. Type I: straight or slightly undulate anticlinal walls; Type II: undulate anticlinal wall with small wart-like outgrowth (i.e., verruculous); Type III: undulate anticlinal wall with well developed cuticles ; Type Ⅳ: undulate anticlinal wall with smooth surface. The well developed epidermis cuticles of tepal in Rheum is probably well-adapted entomophily, while the smooth surface of tepal in most of Rumex groups can be related to the anemophily. Epidermal cell type of leaf was variable (e.g., rectangular/arched, undulate, straight with scattered small wart-like outgrowth, etc.). The leaf is amphistomatic, and anisocytic and anomocytic(rarely paracytic) stomata are the most frequent types. Three endothecial thickening types of anther are found: helical, annuli, psudoannuli, rarely baseplate. Cladistic analysis produced four equally parsimonious trees, 36 tree length with a consistence index (CI) = 0.714 and a retention index (RI) = 0.843. The present study group is monophyletic, but weakly supported by only one synapomorphic character(articulate pedicel). Oxyria and Emex are well distinguished independently by having several autoapomorphic characters. Rumex sect. Platypodium and Emex are apperaed as a sister group, thus the generic status of Emex is also briefly discussed. In conlusion, most of the studied micromorphological characters, except the endotecial thickening of anther, can be useful for improving the classification of the tribe Rumiceae in some degrees.

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