Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis.

BACKGROUND: This study was aimed to investigate the diagnostic value of fiberoptic bronchoscopy (FOB) with chest high-resolution computed tomography (HRCT) for the rapid diagnosis of active pulmonary tuberculosis (PTB) in patients suspected of PTB but found to have a negative sputum acid-fast bacilli (AFB) smear. METHODS: We evaluated the diagnostic accuracy of results from FOB and HRCT in 126 patients at Gangnam Severance Hospital (Seoul, Korea) who were suspected of having PTB. RESULTS: Of 126 patients who had negative sputum AFB smears but were suspected of having PTB, 54 patients were confirmed as having active PTB. Hemoptysis was negatively correlated with active PTB. Tree-in-bud appearance on HRCT was significantly associated with active PTB. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FOB alone was 75.9%, 97.2%, 95.3%, and 84.3%, respectively, for the rapid diagnosis of active PTB. The combination of FOB and HRCT improved the sensitivity to 96.3% and the NPV to 96.2%. CONCLUSIONS: FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB.ope

Whole Blood Interferon-γ Release Assay Is Insufficient for the Diagnosis of Sputum Smear Negative Pulmonary Tuberculosis

PURPOSE: We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. MATERIALS AND METHODS: We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. RESULTS: Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. CONCLUSION: Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.ope

Stress Related Cardiomyopathy during Flexible Bronchoscopy

Flexible bronchoscopy is a safe medical procedure, but the incidence rate of major complications is 0.08-0.3%. Here, we report 2 cases of stress induced cardiomyopathy, which developed immediately after flexible bronchoscopy. Stress related cardiomyopathy was confirmed by EKG, echocardiography, and coronary angiogram. The cardiac functions of these patients were fully recovered with conservative treatment. Although, the pathogenesis of stress related cardiomyopathy is not well understood, post-bronchoscopy tachycardia or arrhythmia is thought to be associated with hypoxemia or catecholamine excess. Because the clinical presentation is quite similar to acute myocardial infarction, discrete evaluations are required for appropriate treatment.ope

Clinical outcomes of tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii infection

PURPOSE: Acinetobacter baumannii (A. baumannii) has emerged as a major cause of nosocomial pneumonia and sepsis in seriously ill patients. Multidrug-resistant A. baumannii (MDRAB) is increasing in frequency, and the management of it's infections is consequently difficult. Therefore, tigecycline is considered to be the drug of choice for MDRAB treatment. The aim of our study was to evaluate the microbiological eradication and clinical effectiveness of tigecycline against MDRAB in seriously ill patients, including patients with ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: We conducted a retrospective study including patients with A. baumannii infections who were treated with tigecycline between April 1, 2009 and March 31, 2010. We treated 27 patients with tigecycline for MDRAB infections. RESULTS: The mean age of patients was 66.2 years, and 20 (74.1%) patients were male. The median length of stay at hospital was 74.6 days. MDRAB was eradicated from the site of infection in 23 cases (85.2%), however, only 17 cases (63.0%) showed positive clinical responses. Overall, an in-hospital mortality rate of 51.9% was observed, and 4 cases of death were attributable to sepsis. The combination therapy showed better clinical and microbial success rates than the monotherapy without significant difference. CONCLUSION: We observed the relatively low clinical success rate although the microbial eradication rate was high, probably due to superinfections in VAP and bacteremia. We suggest that clinicians should limit tigecycline monotherapy for MDRAB infection in critically ill patients, until large controlled clinical trials should be conducted.ope

The Clinical and Pathologic Features according to Expression of Acyl Protein Thioesterase-1 (APT1) in Stage I Non-small Cell Lung Cancer

BACKGROUND: Acyl protein thioesterase-1 (APT1) is a cytosolic protein that may function in the depalmitoylation of numerous proteins, including the Ras family. However, the clinical role of depalmitoyl thioesterase in human cancer is not known. We evaluated the APT1 expression in lung cancer tissue and its clinicopathological findings according APT1 expression pattern. METHODS: APT1 expression was examined by immunohistochemistry in the tumor tissue from 79 patients, who had undergone curative surgical removal of the primary lesion; all patients had been diagnosed with stage I non-small cell lung cancer between 1993 and 2004, at Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. RESULTS: The APT1 expression was seen in 50 out of 79 (63.3%) cases. The positive APT1 expression was significantly related with histologic subtype and T stage, but was not influenced by differentiation. The positive APT1 expression was not significantly related to patient age, gender, or smoking history. The median follow-up duration was 10.0 years; the 5-year survival rate was 71.0%. The positive APT1 expression group showed significantly worse overall survival and worse disease-free survival without statistical significance. CONCLUSION: We conclude that positive APT1 expression in stage I lung cancer after surgery is closely associated with overall survival. To evaluate APT1 as a prognostic marker in lung cancer, comprehensive studies on advanced stage cases are needed.ope

Late respiratory infection after lung transplantation

Background : Aiming to improve outcome of lung transplantation (LTx) patients, we reviewed risk factors and treatment practices for the LTx recipients who experienced respiratory infection in the late post-LTx period (＞1 month after LTx). Materials and Methods : We analyzed the clinical data of 48 recipients and donors from 61 LTx, who experienced late respiratory infections. Late respiratory infections were classified according to the etiology, time of occurrence, and frequency of donor-to-host transmission or colonization of the recipient prior to transplantation. Results : During the period of observation, 42 episodes of respiratory infections occurred. The organisms most frequently involved were gram (−) bacteria: Acinetobacter baumannii (n=13, 31.0%), Pseudomonas aeruginosa (n=7, 16.7%), and Klebsiella pneumoniae (n=4, 10.0%). Among the 42 episodes recorded, 14 occurred in the late post-LTx period. These were bacterial (n=6, 42.9%), fungal (n=2, 14.3%), viral (n=4, 28.5%), and mycobacterial (n=2, 14.3%) infections. Of 6 bacterial infections, 2 were from multidrug-resistant (MDR) A. baumannii and one from each of MDR P. aeruginosa, extended spectrum β-lactamase (＋) K. pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Infection-related death occurred in 6 of the 14 episodes (43%). Conclusion : Although the frequency of respiratory infection decreased sharply in the late post-LTx period, respiratory infection was still a major cause of mortality. Gram (−) MDR bacteria were the agents most commonly identified in these infections.ope

SMALL SAMPLE BEHAVIOR OF A BIOEQUIVALENCE TESTING PROCEDURE UTILIZING t-BASED CONFIDENCE INTERVALS

일반적인 경우에 가설 검정을 하려고 하면 귀무가설 H(o) : ?(1) = ?(2) 과 대립가설 H(1) : ?(1) ≠ ?(2) 을 놓고 새롭게 보이고자 하는 것을 대립가설로 설정하여 추출된 표본을 바탕으로 하여 판정을 내린다. 만약 귀무가설을 기각하는데 실패하면 H(1) : ?(1) ≠ ?(2) 을 기각하게 되고 통계학적으로 ?(1) 과 ?(2)가 같지 않다는 결론을 얻지 못하게 된다. 그러나 이것이 곧 귀무가설이 옳다는 것을 확증해 주지는 못한다. 기존의 통계학 이론에서는 ?(1) = ?(2) 을 증명 할 방법이 없다. 또한 표본 크기가 증가하게 되면 검정에 있어서 검정력이 커지게 된다. 따라서 본 논문에서는 최근에 발표된 신뢰구간을 통한 동등성 검정을 통해 PR 곡선의 움직임을 관찰하였다. 특히 소표본에서의 PR 곡선을 구하고 동등성을 기각할 확률이 표본 크기에 따라 어느정도나 변화하는지 확인해 보았다.TABLE OF CONTENTS = 0 CHAPTER 1 INTRODUCTION = 1 CHAPTER 2 SIMULATION OF PR CURVES = 6 CHAPTER 3 BEHAVIOR OF PR CURVE = 10 CHAPTER 4 CONCLUDING REMARKS = 22 BIBLIOGRAPHY = 23 APPENDIX = 25 논문 초록 = 2

출생 초기의 섬광자극 노출이 망막 신경세포의 발달에 미치는 영향

Background : The nature and intensity of visual stimuli has changed in recent years due to addition of television and other dynamic light sources. Although light stimuli accompanied by contrast and strength changes are thought to have an influence on visual system development, little information is available on the effects of dynamic light stimuli such as a strobe light on visual system development. The purpose of this study was to examine the effect of dynamic light stimuli on retinal development in the guinea pig and rat model. Methods : This study used 42 litters of albino Hartley guinea pigs and 80 litters of Sprague-Dawley rats. From eye opening (postnatal (P) day 0 in guinea pig and postnatal day 14 in rat), animals were randomly divided into control and experimental group. Half of the litters were maintained on a daily 12-h light/dark cycle (control group) and the remaining animals were raised under a 12-h strobe light (2 Hz)/dark cycle (strobe light-reared group). Immunohistochemistry and ERG were performed at P1, 2, and 4 weeks in guinea pig model, and immunohistochemistry, western blot analysis, real-time PCR and ERG were performed at P3, 4, 6, 8, and 10 weeks in rat models. Results : In guinea pig model, the thickness of the ONL decreased by 14.8% in the strobe-reared animals compared to the control group at P4 weeks. The thickness of the ONL did not change at P1 and 2 weeks. The Müller cells and rod bipolar cells showed abnormal morphology. In strobe-reared animals, the branches of Müller cells were stouter and axon-like processes emerged from the rod bipolar cell bodies . In rat model, there was no differences in retinal thickness and the ONL morphology. However, TH-IR cells (dopaminergic amacrine cells) showed marked plastic changes in the INL. The number of type I TH-IR cells decreased and the soma size increased in strobe reared animals at P6, 8, and 10 weeks. In contrast, the number of type II TH-IR cells increased in strobe reared animals at P6 weeks. Functional assesment by scotopic ERG revealed that the a-wave and b-wave amplitudes increased at P6 and 8 weeks in strobe reared animals. Conclusion : These findings demonstrate that strobe-light stimuli cause morphological and functional changes in retinal neurons, which may lead to the disturbance of normal visual processing during development.;연구배경 : 최근 다양한 전자기기의 발달로 인해 우리 눈은 여러 종류의 빛자극에 노출되고 있다. 이렇듯 강도와 대비의 다양한 변화를 동반하는 빛 자극에 노출되고 있음에도 불구하고 이러한 자극이 시각 계통의 발달에 미치는 영향에 대한 연구는 많지 않다. 이에 본 연구에서는 시각 계통이 발생이 진행되는 동안 섬광자극에 노출된 경우 망막에 어떠한 변화를 초래하는지 알아보고자 하였다. 실험방법 : 실험동물로는 42마리의 신생 기니피그와 80마리의 신생 흰쥐를 사용하였다. 기니피그는 출생 직후부터, 흰쥐는 출생 2주 후부터 무작위로 대조군과 실험군으로 분류하여 대조군은 하루 12시간 지속적인 빛/ 12시간 어둠의 환경에서 사육하였으며 실험군은 하루 12시간 정상 빛을 대신하여 초당 2회의 섬광자극을 가하였다. 이 후 기니피그 모델에서는 각각 생후 1, 2, 4주에, 흰쥐 모델에서는 생후 3, 4, 6, 8, 10주에 형태학적, 기능적 변화를 관찰하였다. 실험결과 : 섬광자극에 의한 망막의 변화는 두 모델에서 각각 다르게 관찰되었다. 기니피그 모델에서는 생후 2주령부터 형태학적 변화가 관찰되었다. 바깥핵층의 두께가 생후 1, 2 주령에는 차이가 없었으나 4 주령 실험군에서 대조군에 비하여 14.8% 감소하였으며 실험군의 뮐러세포에서 2, 4 주령에 비대해진 가지가 관찰되었다. 또한 일부 막대두극세포 (rod bipolar cell)에서 나온 축삭돌기와 유사한 돌기가 바깥얼기층으로 향하는 모양 이상이 생후 2, 4주령에서 관찰되었다. 쥐 모델에서 tyrosine hydroxylase에 면역염색되는 도파민무축삭세포 (dopaminergic amacrine cell)가 생후 6주령부터 수적 변화 및 세포체 크기의 차이를 보였다. 생후 6, 8, 10 주령의 실험군 망막에서 I 형 도파민무축삭세포의 수가 줄고 세포체의 크기는 증가하였으며 II 형 도파민무축삭세포의 수는 증가하였다. 또한 6, 8 주령 실험군의 암망막전도(scotopic electroretinogram)에서 a 파형과 b 파형의 진폭이 유의하게 증가하였다. 결론 : 본 연구에서 출생초기 섬광자극 노출이 망막 세포의 발달 과정에서 형태학적 변화를 일으키는 것을 확인하였으며, 이러한 형태학적 변화는 시각계통의 기능에도 영향을 미친다는 것을 암시하고 있다.I. Introduction 1 II. Materials and Methods 4 A. Animals 4 B. Tissue preparation 5 C. General histology 5 D. Immunohistochemistry 6 E. Analysis of TH-IR cell number and morphology 10 F. Western blot analysis 13 G. Real-time PCR 14 H. ERG 16 III. Results 18 A. Morphological analysis 18 1. General histology 18 a. Guinea pig 18 b. Rat 22 2. Immunohistochemistry 24 a. Guinea pig 24 (1) Caspase 3 expression 24 (2) Changes in Mller cells 26 (3) Changes in rod bipolar cells 28 b. Rat 34 (1) Immonolabel with various antibodies 34 (2) Changes in TH-IR cells 37 B. Quantitative analysis 42 1. Western blot analysis 42 2. Real-time PCR 45 C. Functional analysis 47 IV. Discussion 49 References 56 국문초록 6

A Study on the Appropriation of Postmodern Art : Focused on Parody and Pastiche

본 논문의 목적은 포스트모더니즘 미술이 차용의 방식 중에서도 패러디와 패스티쉬의 방법이 작품제작에 있어서 새로운 창작의 가능성을 지니는 점을 밝히는데에 있다. 이를 위해 패러디와 패스티쉬에 대한 프레드릭 제임슨과 린다허천의 상반된 입장을 비교하면서, 허천의 입장을 바탕으로 패러디와 패스티쉬가 포스트모더니즘 미술에 있어 어떠한 긍정적 측면을 드러낼 수 있는지에 관하여 논의해볼 것이다. 이른바 모더니즘 시대의 작가들은 예술의 독창성에 위배된다는 생각 아래 차용의 전략을 감추거나 차용을 자신의 독자적인 양식의 개발을 위한 수단으로 이용해왔던 반면, 포스트모더니즘 시대에 와서 작가들은 차용 그 자체를 작품 제작의 목적으로 취해서 관객이 그 의도를 파악하도록 한다. 이는 매스미디어에 의해 다수의 이미지들이 대량 생산되고 계속 복제되는 현대 사회의 상황 속에서 더 이상 온전히 새로운 양식은 있을 수 없다는 것을 보여주기 위한 하나의 전략이다. 이 전략은 작품의 독창성 및 고유성을 추구한 모더니즘의 창조 신화를 극복하기 위해 작품의 원본성을 정면에서 공격하는 것이다. 또한 포스트모더니즘 미술에서의 차용은 매체 간의 혼합과 확산을 가져온다는 점에서 모더니즘이 추구했던 매체의 순수성에 대한 강력한 도전이기도 하다. 주지하듯 패러디와 패스티쉬는 대중들에게 익숙한 기존의 것을 재해석하여 거기에 새로운 가치를 부여하는 포스트모더니즘 미술의 대표적 차용 방식으로서 변화된 예술 창작의 양상을 보여준다. 이 두 방식은 그 목적에 따라 구분되는데, 먼저 패러디는 유명한 원작의 일부를 차용하여 풍자 또는 익살의 효과를 노리는 것이며, 이 때 어떤 목적의식을 가지고 작가가 원작의 권위를 비판하는 방식으로 원작과의 차이를 통해 그 의도를 드러낸다. 한편, 패스티쉬는 기존의 이미지를 활용하지만 그것들을 거의 변형 없이 차용하거나 혼합하여 원래의 의미를 박탈하고 새로운 맥락에서 의미를 발생시키는 방식으로 형식의 유사성을 통해 기존작품의 독창성과 원본성을 파괴하는 것을 목적으로 한다. 다시 말해 패스티쉬도 어떤 비판적 내용을 드러내지만 그것이 원작에 대한 비판이 아니라 이미지들의 조합을 통해서 우연히 발생하는 새로운 의미를 나타내려 하는 것이다. 린다 허천은 패스티쉬를 기존의 텍스트를 기반으로 하여 새로운 텍스트를 창조하는 패러디의 기본적인 본질을 바탕으로 하되, 포스트모더니즘 이라는 시대적 환경의 영향 아래 그 특성들을 반영하고, 방법이 혼성모방적이라는 점에서 포스트모던 패러디로 본다. 그런데 패러디와 패스티쉬는 모두 다른 작품에 의지하는 방식이라는 점에서 혁신적이지 않고, 독창성이 결여된 것이라는 비판을 받기도 한다. 하지만 허천에 따르면 패러디와 패스티쉬는 기존의 작품이나 이미지를 새로운 맥락에 놓여지게 함으로써 과거를 새로운 관점에서 다시 보게 한다는 점에서 긍정적이다. 그렇게 함으로써 과거의 문화와 현재의 문화가 모두 활성화된다. 뿐만 아니라 패러디와 패스티쉬는 하나의 작품에 다양한 장르를 접목할 수 있고, 기존의 이미지를 다양한 관점에서 보게 하므로 관객의 미적 경험의 영역을 확장시킨다. 특히 패스티쉬의 경우 여러 가지 이미지 또는 여러 가지 장르를 혼합하여 제시함으로써 관객에게 형식적 새로움을 경험하게 한다. 또한 이것은 원작을 이용하여 원작 밖의 현실을 비판하는 경향을 보이는데, 이는 기존의 이미지가 지니는 하나의 의미에서 벗어나 다양한 사회 문화적 맥락과의 관련성 속에서 해석되게 하므로 관객으로 하여금 좀 더 능동적인 참여의 태도를 취하도록 한다. 이는 결과적으로 예술과 삶, 작품과 관객의 거리를 좁히는 것이다. 요컨대 패러디와 패스티쉬는 모더니즘 미술의 독창성의 개념을 파괴하고자 다양한 작품이나 이미지들을 새로운 작품 생산을 위한 도전과 실험의 대상으로 삼고 있다는 점에서 오히려 과거의 어느 때보다도 미술 주제의 범위를 확대시키고, 때문에 오히려 독창성의 범위를 확대되는 현상을 가져올 수 있다. 뿐만 아니라 형식적 측면에 있어서도 패러디와 패스티쉬는 하나의 이미지가 기존의 한계를 탈피하여 무한히 다양한 방식으로 변모될 수 있음을 드러낸다는 점에서 형식적 새로움의 개발 가능성을 연다.;The purpose of this thesis is to discuss how post-modernism art possesses the possibility to create infinitely various pieces of art through approriation such as parody and pastiche. For this purpose, the difference in approriation in post-modernism compared to that of its earlier era will be examined based on the general characteristics of post-modernism art and its connection to approriation. Further, based on Linda Hutcheon’s view, the positive aspects of parody and pastiche on post-modernism art will be discussed. The artists of the so-called modernism era have either been discrete of their borrowing strategies or have merely used such as a method in developing their unique styles, based on the idea that such strategies are in violation of the originality of art. However, artists in the post-modernism era have come to use such methods of borrowing itself as the aim of creating art, thereby allowing the spectator to understand their intentions through this method. This is a strategy to show the absence of new and original form in a modern society where multiple images are produced on a large scale and constantly reproduced through the mass media. This strategy directly attacks the originality of artwork in order to overcome the myth of modernism that pursued originality and character of art. As we are well aware, parody and pastiche are typical approriation in post-modernism art that re-interprets familiarity among the mass and bestows new value, which shows a changed form of art creation. These two types of methods can be differentiated based on their methodology. First, parody aims at satire or humor through borrowing a fragment of a famous original art, and the artist would reveal its intentions through the differences with the original artwork by criticizing its authority. On the other hand, while pastiche also applies pre-existing images, it borrows or commingles without modification. It aims to destroy the originality and uniqueness of the pre-existing artwork through similarity of form by destroying its original meaning and creating a new meaning. In other words, while pastiche also criticizes, it is not directed towards the original work but strives to create coincidental new meaning through a combination of images. Linda Hutcheon is considered as post-modernism parody in that pastiche is based on the fundamental essence of parody that creates new text on pre-existing texts, but also reflects the characteristics of a post-modernism era and uses a mixture of imitation. Meanwhile, parody and pastiche are both criticized as lacking originality and innovativeness in that they both rely on other works of art. However, according to Hutcheon, parody and pastiche are positive in that they allow us to see the past in new light by placing the pre-existing art or image in a new context. This allows for both the past and present cultures to be revitalized. In addition, parody and pastiche not only combines various genres in a single work of art, but it also expands the scope of artistic experience for the spectator by allowing various viewpoints of a pre-existing image. Especially in the case of pastiche, it allows for the spectators to experience a novel formality by presenting several images or genres. Further, they tend to criticize the outside world by using the original work, and because the pre-existing images are taken out of their original meaning and interpreted in relation to the various societal and cultural contexts, it allows for the spectators to take a more proactive participatory attitude. This, in effect, brings closer together art, life, artwork and spectators. In summary, parody and pastiche places various arts or images as objects of challenge and experiment to destruct the concept of uniqueness, and this in turn, may expand themes of art and thereby bring expansion to the scope of uniqueness. In addition, parody and pastiche opens the doors to a possibility of development is new formalities in that one image can overcome its existing limits and reveal infinite potentials.논문개요 = v I. 서론 = 1 II. 포스트모더니즘 미술의 특성 = 4 A. 포스트모더니즘의 개념 및 사회적 배경 = 4 B. 포스트모더니즘 미술의 특성 = 9 1. 고급문화와 대중문화간 경계의 와해 = 13 2. 상호텍스트성- 저자의 죽음 = 16 3. 알레고리적 성격 - 차용, 장소성, 절충주의 = 19 III. 포스트모더니즘 미술에서 차용의 전략 = 27 A. 포스트모더니즘 이전의 차용의 역사 = 28 B. 포스트모더니즘에서의 차용 = 34 IV. 차용의 방식으로서의 패러디와 패스티쉬 = 45 A. 패러디의 개념 및 사례들 = 45 1. 패러디의 개념 = 45 2. 패러디 미술의 사례들 = 50 B. 패스티쉬의 개념 및 사례들 = 53 1. 패스티쉬의 개념 및 패러디와의 차이점 = 53 2. 패스티쉬 미술의 사례들 = 60 C. 포스트모더니즘 미술의 방법적 새로움 제시 = 72 IV. 결론 = 78 참고문헌 = 81 도판 = 87 Abstract = 9

폐손상에서 Romo1에 의하여 유발되는 미토콘드리아 활성산소의 역할 규명

Dept. of Medicine/박사Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the outer membrane of mitochondria and increases mitochondrial ROS production through complex III mitochondrial electron transport chain. However, the role of Romo1-mediated mitochondrial ROS production in lung epithelial cell apoptosis and lung injury has not been identified yet. In this study, we investigated the role of Romo1 as a mediator in mitochondrial ROS production and apoptotic cell death induced by oxidative stress in lung epithelial cells.H2O2 treatment increased cellular ROS levels and Romo1 expression. Romo1 knockdown blocked H2O2-induced ROS production. H2O2 treatment induced death of BEAS-2B cells in a time- and a dose-dependent manner, and it was inhibited by Romo1 knockdown. The terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)-stained apoptotic bodies were significantly less in the BEAS-2B cells transfected with Romo1 siRNA compared with control siRNA transfected cells. The Romo1 knockdown inhibited expression of cleaved PARP and γH2AX, which were induced by H2O2 treatment. These findings suggest that Romo1 is an important mediator of apoptotic cell death induced by H2O2 treatment. The TUNEL-positive alveolar epithelial cells were detected in most idiopathic pulmonary fibrosis (IPF) tissues, whereas not observed in normal appearing lung tissues. Also, Romo1 overexpression of alveolar epithelial cells were detected in most IPF tissue, but not observed in normal controls. In conclusion, Romo1 knockdown suppressed the cellular ROS levels increased by exogenous H2O2 in lung epithelial cells. We observed that decreased ROS levels by Romo1 knockdown inhibited cell death by oxidative stress with exogenous H2O2. These results suggest that Romo1-induced ROS play an important role in cell death mechanism in lung epithelial cells.restrictio