美軍政期 日本 財閥(Zaibatsu) 解體에 관한 硏究

학위논문(석사)--서울대학교 대학원 :외교학과,2001.Maste

Roles of IKKβ and TLR3 in Inflammation and Axon Regeneration after Spinal Cord Injury

학위논문 (박사)-- 서울대학교 대학원 : 협동과정 유전공학전공, 2013. 2. 이성중.Traumatic spinal cord injury (SCI) is accompanied by widespread neuronal cell death, consecutive inflammation processes and glial scar formation. Damage in an injured spinal cord is modulated by the progressive functions of microglia, neutrophils, macrophages and astrocytes. Many studies have reported that neutrophils and macrophages have an effect on the damage and recovery of the injured spinal cord. However, it is still controversial whether these cells play a beneficial or harmful role in the spinal cord injury. In the first chapter, to address the in vivo role of these immune cells in SCI, I utilized myeloid cell-specific IκB kinase (IKK)-β conditional knockout (ikkβΔmye) mice, in which ikkβ gene is specifically deleted from myeloid cells including neutrophils and macrophages. IkkβΔmye mice showed significantly reduced inflammatory responses of neutrophils and macrophages in SCI compared to ikkβ+/+ controls: SCI-induced expression of proinflammatory mediators and a potent neutrophil-attractant, C-X-C motif (CXC) ligand 1, were reduced in ikkβΔmye mice. In addition, neuronal loss, axonal damage, and behavioral deficits in motor activity were attenuated. These results demonstrate that IKK-β-dependent neutrophil and macrophage activation potentiates neuroinflammation and increases neuronal damage after SCI. In the second chapter, I characterized the in vivo role of TLR3 in SCI using TLR3 knockout mice to test whether TLR3 signaling is involved in the inflammatory responses observed in the injured spinal cord. TLR3 plays important roles in innate immune cell activation in response to tissue damage. However, it is not clear whether TLR3 functions beneficial or detrimental in SCI. At 5 days post-injury (dpi), axon demyelination and vestibulospinal tract (VST) axon did not differ in the wild-type and TLR3 knockout mice. However, in TLR3 knockout mice, behavioral recovery was improved at 14 dpi, and the axon demyelination and lesion volume were attenuated at 35 dpi compared to the wild-type mice. In addition, more axons in the corticospinal tract (CST) and VST were detected in the TLR3 knockout mice at 24 dpi or 35 dpi, respectively. Upon SCI, TLR3 expression increased mainly in astrocytes and oligodendrocytes. Furthermore, astrocytes were vigorously activated in SCI-induced wild-type mice, which were relatively attenuated in TLR3 knockout mice. In addition, there was less chondroitin sulfate proteoglycans (CSPGs) deposited in the TLR3 knockout mice compared to the wild-type mice. Interestingly, expression and activation of matrix metalloproteinase-2 (MMP-2), a protease involved in CSPG degradation, increased more in the TLR3 knockout mice compared to the wild-type mice after SCI. MMP-2 expression was detected mostly in astrocytes in the injured spinal cord. In the in vitro assays, recombinant CSPG was degraded by MMP-2. The expression level of MMP-2 was higher in astrocytes from the TLR3 knockout mice than from the wild-type mice. Furthermore, TLR3 stimulation inhibited TGF-β-induced MMP-2 expression in wild-type astrocytes. These data suggest that the TLR3 signaling inhibits MMP-2 expression in astrocytes in the spinal cord during SCI. Taken together, my data show that TLR3 has a detrimental role in SCI at least by partly inhibiting astrocytic MMP-2 expression, which results in the accumulation of CSPG and the impairment of axon regeneration and functional recovery after SCI. In this study, I conclusively found that IKK-dependent macrophage and neutrophil activation exacerbates SCI and that TLR3-mediated inhibition of MMP-2 expression in astrocytes impedes recovery from SCI.CONTENTS ABSTRACT ------------- i CONTENTS ------------- iv LIST OF FIGURES ----- ix LIST OF TABLES ------ xi GENERAL INTRODUCTION AND PURPOSE GENERAL INTRODUCTION ------------- 2 1. Introduction of the Spinal Cord ---- 2 1.1. Spinal Cord ----------------------- 2 1.2. Spinal Tracts --------------------- 2 1.2.1. Ascending Tracts ------------- 3 1.2.2. Descending Tracts ------------ 4 2. Spinal Cord Injury ------------------- 5 2.1. Pathophysiology of SCI --------- 6 2.2. Immune Response of SCI ------- 7 2.3. Axon Regeneration of SCI ------ 9 2.3.1. Glial Scar and CSPG ---------- 9 2.3.2. Matrix Metalloprotease -------- 10 3. Toll-like Receptors ----------------- 11 3.1. TLRs in CNS --------------------- 12 3.2. TLRs in the Spinal Cord -------- 14 3.2.1. TLRs in SCI -------------------- 14 3.2.2. TLRs in Regeneration --------- 15 PURPOSE ------------------------------ 28 CHAPTER 1. IKK-β-mediated myeloid cell activation exacerbates inflammation and inhibits recovery after spinal cord injury INTRODUCTION ---------------------------- 30 MATERIALS AND METHODS--------------- 32 Mice and spinal cord injuries ------------ 32 Immunohistochemistry ------------------- 33 Luxol Fast Blue (LFB) staining and lesion volume measurement --- 34 Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining --- 34 Real-time RT-PCR ------------------------ 35 Behavioral tests -------------------------- 35 Neutrophil and monocyte isolations ---- 36 Migration assay -------------------------- 36 In situ zymography ----------------------- 37 Fluorescence activated cell sorting (FACS) assay --- 37 CXCL1 ELISA ------------------------------ 38 Statistical Analysis ---------------------- 38 RESULTS ---------------------------------- 39 Attenuated myeloid cell infiltration in ikkβΔmye mice after SCI --- 39 SCI-induced neutrophil chemoattractants are reduced in ikkβΔmye mice --- 40 Compromise of SCI-induced neuronal cell death and behavioral deficit in ikkβΔmye mice ---- 42 Reduced ROS and reactive nitrogen species (RNS) production after SCI in ikkβΔmye mice -- 44 DISCUSSION ----------------------- 69 CHAPTER 2. Toll-like receptor 3 signaling inhibits astrocyte MMP-2 activation and recovery from spinal cord injury INTRODUCTION --------------------- 74 MATERIALS AND METHODS -------- 76 Mice and spinal cord injury ------- 76 Behavioral tests -------------------- 76 Cresyl violet staining/Luxol Fast Blue (LFB) staining and volume measurement ---- 77 Immunohistochemistry ------------- 77 Biotinylated dextran amine injection and tissue processing --- 78 Primary astrocyte cell cultures ----- 79 Real-time PCR ----------------------- 80 Gelatin gel zymography ------------- 80 In vitro MMP assay ------------------ 81 Fluorescence activated cell sorting (FACS) assay --- 82 Statistical analysis ------------------ 82 RESULTS ----------------------------- 84 Functional recovery is enhanced in TLR3 knockout mice after SCI ---- 84 Neuronal axon regeneration is enhanced in TLR3 knockout mice after SCI --- 85 TLR3 is expressed in astrocytes and oligodendrocytes after SCI ---- 86 Astrocyte activation and CSPGs production due to SCI are reduced in TLR3 knockout mice -- 87 SCI-mediated MMP-2 expression and activation were increased in TLR3 knockout mice --- 88 CSPGs are degraded by MMP-2 in astrocytes --- 89 TLR3 signaling inhibits MMP-2 expression in astrocytes ---- 90 DISCUSSION ------------ 110 SUMMARY --------------- 114 REFERENCES ------------ 116 ABSTRACT IN KOREAN -- 136Docto

(A) comparative study of stress and the coping methods used by manual workers and clerical workers

보건간호학과/석사[한글] 본 연구는 생산직과 사무직 근로자의 직무에 따른 스트레스 정도와 스트레스에 적응하 는 방법을 파악·비교하고자 한 서술적 조사연구이다. 구로공단 소재 8개 제조업체 남녀 생산직·사무직 근로자 320명을 대상으로 Ilfeld에 의하여 제작된 정신건강지수(Psychiatria Symptom Index)와 Bell이 고안한 스트레스법 사 용 척도(Stress Coping methods Scale)를 이용하여 스트레스 증상별 정도와 스트레스에 대처하는 적응방법을 측정하였다. 자료수집은 1989년 4월 5일부터 4월 10일까지 본 연구자가 8개 제조업체를 방문하여 설 문지법을 이용하여 조사하였다. 수집된 자료는 SPSS(Statistical Package for the Social Science)를 이용하여 전산처 리 하였으며 본 연구는 산업장 근로자의 정신건강관리를 위한 방안모색을 위하여 기초자 료로 제공되어질 것이다. 연구의 결과는 다음과 같다. 1) 생산직은 사무직에 비하여 육체적·정신적 스트레스 증상을 많이 느꼈으며 특히 불 안증상·우울증상·인지장애증상에서 사무직보다 높은 스트레스 점수를 보였다. 2) 사회·인구학적 특성별로 보면 여성이 남성보다 스트레스가 높았고, 연령이 적을수 록 불안증상이 높았으며, 고졸이하군이 대졸군에 비하여 불안·분노증상을 높게 호소하였 다. 3) 남자군에서는 생산직이 사무직에 비해 전체 스트레스 정도가 높았으며, 여자군에서 는 생산직이 사무직에 비해 인지장애 증상이 높았다. 두 군 모두 연령이 적을수록 불안증상이 높았으며(r= -.13 P<.05), 고졸이하군에서는 생산직이 사무직에 비해 전체 스트레스 정도가 높았다. 4) 생산직이 사무직에 비해 단기적응 방법을 많이 사용하였으며, 사무직이 생산직에 비 해 장기적응방법을 많이 사용하였다. 5) 스트레스가 높은군은 낮은군에 비해 단기적응방법 사용 점수가 높고 장기적응방법 사용 점수는 낮았으나 통계적으로 유의한 차이는 없었다. 결론적으로 생산직이 사무직에 비하여 스트레스 정도가 높고 단기적응방법을 많이 사용 하였는데 산업장 근로자의 건강관리를 담당하는 간호사는 스트레스로 인하여 경험하는 신 체적·정신적 스트레스 증상을 감소시켜주기 위한 건강관리 계획시 이 연구를 기초자료로 활용하여 건강상담 및 정신 건강관리에 임해주길 바라며 스트레스 상황에서 장기적응방 법을 사용하도록 유도하는 한편 건강기록부를 이용한 체계적인 정신 건강관리가 이루어져 야 할 것이다. 특히 스트레스 증상중에서 연령이 적을수록 불안이 높았는데 앞으로 연소 근로자에 대 하여 불안증상을 감소시켜주기 위한 구체적인 정신 건강관리방안과 대처방법에 대한 연구 가 시도되었으면 한다. [영문] This study was conducted on stress and the coping methods used by manual workers and clerical workers between April 5 and April 10, 1989. The study population consisted of 165 manual workers and 155 clerical workers of the 8th Industrial factory of the Guu-Ro Industrial Base in Seoul, Korea. This study purposed to identify the difference in stress symptoms and severity of stress, and the difference in coping methods used by each of the manual worker group and the clerical worker group. Two instruments were used in this study. Stress symptom were measured by Ilfeld's (1977) PSI (Psychiatric Symptom Index) which consists of 29 item. J.M. Bell's (1977) 34 item instrument was used to identify coping methods. Twenty-six of these items are concerned with short term coping methods and eighttems items are concerted with long-term methods. The materials were analyzed by SPSS (Statitical Package for the Social Science) program. These results can be used by public Health Nurses in Psychiatric health management of Korean industrial workers. The result of analysis is as follows: 1) The scores of psysical and psychological complains were much higher in manual work ers than in clerical workers, especially anxiety, depression and cognitive disturbances. 2) Mean score of psychiatric symptoms for broth workers was higher in females, youth, and low educated workers. 3) Mean score of psychiatric symptom in man workers was higher in manual worriers than in clerical workers. Mean score of cognitive disturbance symptoms in female workers were higher in manual workers than in clerical workers. Mean score of psychiatric symptom in low educated workers was higher in manual workers than in clerical workers. The yonger age group has the more complaints of psychiatric symptoms(r=-.13 p<.05). 4) Manual workers used more Short-term coping methods than clerical workers and clerical workers used more Long-term coping methods than manual workers. 5) The mean score of Short-term coping methods was higher in high stressed group than in the low stressed group, but there was no statistical significant difference between the two groups. The mean score of Long-term coping methods was higher in the low stressed group than in the high stressed group, but there was no significant difference between the two groups.prohibitio

(The) effect of a social support program on burden and well-being in caregivers of elderly people with dementia living in the

간호학과/박사[한글] 급격한 노인인구의 증가추세와 함께 대표적 노인성 질환인 치매는 높은 유병율을 보이며 의료적, 사회적 측면에서 큰 사회문제로 떠오르고 있다. “치매”는 장기적이고 퇴행적 특성을 지니며 24시간 동안 전적으로 돌보는 사람이 옆에 있지 않으면 안되는 상황이기 때문에 치매노인의 돌봄이는 여러 가지 어려움과 정신적, 신체적 부담감이 증가하게 된다. 치매노인을 간호하는 것은 커다란 희생을 요구하는 것으로 신체적, 정신적 스트레스 및 사회적 관계의 악화, 시간과 자유의 제한, 경제적 고통 등을 수반한다. 그러나 전통적으로 치매노인 문제는 가정 내 문제로 국한하여 가정에서 돌보는 것이 당연한 것으로 간주되어 왔으며 이들 돌봄이를 위한 사회적 지지는 매우 부족한 실정이다. 본 연구의 목적은 보건소에 등록된 치매노인의 돌봄이에게 사회적지지 중재를 하여 효과가 있는지 보기 위한 비동등성 전후 유사실험 설계이다. 연구의 독립변수는 사회적지지 프로그램이고 종속변수는 돌봄이의 부담감과 안녕으로서 안녕감은 삶의 질, 삶의 만족도, 건강증상으로 측정하였다. 사회적지지 프로그램의 내용은 정저적, 정보적, 물질적&#8228;도구적 지지와 휴식간호 로 구성되어 있으며 점진적 근육이완요법을 이용한 스트레스 관리기술을 포함한 중재는 10주간 실시하였으며 주 1회 모임에 90분이 소요되었다. 연구장소는 경기도 A 보건소 회의실이었으며 연구기간은 2003년 5월부터 7월까지였고, 편의추출에 의하여 18명의 실험군에 19명은 대조군으로 연구에 참여하였다. 자료수집은 설문지를 이용하였으며 실험군은 프로그램 실시 전 사전조사, 5주 후에 중간조사, 10주 후에 사후조사 하였고, 대조군은 프로그램 실시 없이 사전조사, 중간조사, 사후조사 하였다. 연구도구는 사회적지지 프로그램을 독립변인으로 하였다. 종속변인은 서미혜와 오가실(1993)의 부담감 측정도구, 건강증상 조사서, 삶의 질 측정도구를 사용하였고 서경희(1988)의 삶의 만족도 측정도구를 사용하였다. 자료 분석은 SPSS분석을 사용하였으며 통계방법으로 Fisher''s Exact test, Mann-Whiteney U test, Repeated Measured ANOVA, Spearman''s Correlation을 이용하였다. 연구결과는 다음과 같다. 사회적지지 프로그램에 참여한 실험군은 대조군에 비하여 부담감이 낮을 것이라는 가설에서 실험군은 대조군에 비해 측정시기별로 부감감이 유의하게 감소하여 중간조사에 비해 사후조사에 유의한 부담감의 감소를 보였으며 대조군은 중간조사, 사후조사 모두 유의하게 증가하였다. 사회적지지 프로그램에 참여한 실험군은 대조군에 비하여 삶의 질이 높을 것이라는 가설에서 실험군은 대조군에 비해 측정시기별로 삶의 질이 유의하게 증가하여 중간조사와 사후조사에서 삶의 질이 유의하게 증가하였으며 대조군은 중간조사, 사후조사 모두 유의한 감소를 보였다. 사회적지지 프로그램에 참여한 실험군은 대조군에 비하여 삶의 만족도가 높을 것이라는 가설에서 실험군은 대조군에 비하여 측정시기별로 삶의 만족도가 증가하여 중간조사에 비해 사후조사에 삶의 만족도가 통계적으로 유의하게 증가하였으며 대조군은 중간조사, 사후조사 모두 유의한 감소를 보였다. 사회적지지 프로그램에 참여한 실험군은 대조군에 비하여 건강증상이 감소할 것이라는 가설에서 실험군은 대조군에 비하여 건강증상이 감소하였으며 특히 사후조사에서 건강증상이 통계적으로 유의하게 감소하였다. 대조군은 중간조사, 사후조사 모두 유의하게 건강증상이 많아졌다. 결론적으로 사회적지지 프로그램은 치매노인 돌봄이의 부담감을 감소시키고 삶의 질, 삶의 만족도를 증가시키며 건강증상을 감소시키는 효과적인 중재방법이었다. 추후 사회적지지 모임이 보건소를 비롯한 지역사회 치매 돌봄이 프로그램으로 되어 활용될 수 있으리라 기대한다. [영문]As the number of elderly people in the population is rapidly increasing, the prevalence rate for dementia is also increasing and becoming an issue with medical and social aspects. ''Dementia'' is characterized as a chronic and degenerative disease and elderly patients with dementia depend on their caregivers for 24 hour a day care. Therefore the burden placed on the caregivers accumulates and they experience various hardships and discomfort. Providing care is often done at great personal sacrifice for caregivers who experience physical, emotional and social stress, restrictions on time and freedom, and economic hardships. Traditionally, it has been taken for granted that caregives will provide care at home by themselves without any government social support programs. Social support programs are known to mediate burden and increase the state of well-being. The purpose of this study was to develop a social support program for caregivers of elderly people with dementia and to examine the effects of the social support program on reduction of burden and increase in well-being in the caregivers. The research used a quasi-experimental pre-and post-test design. The participants in the study were 37 caregivers of elderly people with dementia who were registered at the Dementia Counselling Center of four public health centers. Eighteen were assigned to the intervention group and 19 to the control group. The independent variable was the social support program and the dependent variables were burden and well-being. Well-being was conceptualized as including quality of life, life satisfaction and health status and operationalized as the scores for quality of life, life satisfaction and physical symptoms. The program for the intervention group consisted of 10 sessions, once a week for one and a half hours, over a period of 10 weeks. Emotional, informational and material support, and respite care were provided. Data were collected from both groups before the program began, at the mid point (5 weeks), and after completion of the program (10 weeks). A questionnaire was used and data collection was done from May to July, 2003. The data were processed using the Statistical Package for Social Sciences (SPSS) program and analyzed with Fisher''s exact test, Mann-Whiteney U test, repeated measured ANOVA, and Spearman''s correlation. The results are as follows : Hypothesis 1, that there would be a decrease in burden for the intervention group which received the social support program compared to the control group which did not, was accepted. Burden for the intervention group decreased significantly at the end of the 10 week program. Burden for the control group increased significantly at both the mid point (5 weeks) and at the end of the study (10 weeks). Hypothesis 2, that there would be an increase in quality of life for the intervention group which received the social support program compared to the control group which did not, was accepted. Quality of Life for the intervention group increased significantly at both the mid point (5 weeks) and the at the end of the 10 week program. Quality of Life for the control group decreased significantly at both the mid point (5 weeks) and at the end of the study (10 weeks). Hypothesis 3, that there would be increase in life satisfaction for the intervention group which received the social support program compared to the control group which did not, was accepted. Life satisfaction for the intervention group increased significantly at the end of the 10 week program. Life Satisfaction for the control group decreased significantly at both the mid point (5 weeks) and at the end of the study (10 weeks). Hypothesis 4, that there would be an decrease in physical symptoms for the intervention group which received the social support program compared to the control group which did not, was accepted. Physical symptoms for the intervention group decreased significantly at the end of the 10 week program. Physical symptoms for the control group decreased significantly at both the mid point (5 weeks) and at the end of the study (10 weeks). There was no significant correlation between the caregiver burden and problem behavior in the elderly people with dementia, nor between caregiver burden and family hardiness. There were negative correlations between the caregiver burden and well-being, quality of life, life satisfaction and the health status of the caregivers. In conclusion, the social support program for caregivers of elderly people with dementia was shown to be an effective intervention to reduce burden, improve quality of life, life satisfaction, and health status. It is hoped that nurses will use the program developed in this study when caring for caregivers of patients with various chronic illness and thus add to the comprehensiveness of nursing.ope