면역조직화학염색을 통해 분류한 근육침윤성 방광 요로상피암 소집단간의 분자유전학적 발현 비교 분석

학위논문(박사) -- 서울대학교대학원 : 의과대학 의학과, 2021.8. 문경철.Introduction: A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. Material and methods: In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. In addition, IHC staining for CK5/6, CK20, CK14, CD44, GATA3, FOXA1 and programmed cell death-ligand 1 (PD-L1) was performed on 189 muscle-invasive urinary bladder urothelial carcinoma (MIBC) using tissue microarray. Results: The results of gene ontology terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, IL6-JAK-STAT3 signaling pathway and tumor necrosis factor-α signaling via nuclear factor-κB signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. We evaluated PD-L1 expression by the SP142, SP263 and 22C3 assays, and classified the cases “positive” or “negative” according to the manufacturer’s recommendations. The high positivity in the SP142, SP263 and 22C3 assay were significantly correlated with positive CK5/6, CK14 and CD44 expression, negative CK20, GATA3 and FOXA1 expression. The CK5/6 SP subgroup showed high positivity in the SP142, SP263 and 22C3 assay. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival (p = 0.008). Conclusions: These results suggests that the IHC-defined subgroups may be important to apply the PD-1/PD-L1 blockades in MIBC. And our study indicates that the CK5/6-positive group exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.서론: 다양한 mRNA기반 요로상피암 분류법들이 보고되고 있다. 각 분자아형마다 치료반응, 예후적 특징이 이질적이라고 알려져 있다. 방법: 본 연구에서는 CK5/6, CK20에 대한 면역조직화학염색 결과에 따라 근육침윤성 방광 요로상피암을 구분하였다. CK5/6 단일 양성 소그룹, CK20 단일 양성 소그룹, 이중 양성 소그룹, 이중 음성 소그룹으로 분류하였고 각 소그룹별로 구분하여 유전자 발현을 확인하였다. 그리고 189명의 근육침윤성 방광 요로상피암 환자 조직 마이크로어레이에 CK5/6, CK20, CK14, CD44, GATA3, FOXA1 그리고 PD-L1 (SP142, SP263 and 22C3) 면역조직화학염색을 시행하였다. 결과: 차별 발현유전자를 이용한 유전자 온톨로지 분석과 기능분석 결과, 세포 이동, 면역반응 활성화, IL6-JAK-STAT3 신호전달, NF- κB를 통한 tumor necrosis factor-α 신호전달 관여 유전자들은 CK5/6 단일 양성 및 이중 양성 소그룹에 더 관여되는 것으로 나타났다. 그리고 다른 소그룹들과 비교했을 때, 이중 음성 소그룹은 세포운동, 세포이동과 세포 활성화 관련 유전자가 저해되어 있었다. PD-L1 발현을 다음 세 가지 항체를 (SP142, SP263 그리고 22C3) 이용하여 분석하였다. PD-L1 세 항체 모두 높은 양성율은 CK5/6 양성, CK14 양성, CD44 양성, CK20 음성, GATA3 음성 그리고 FOXA1 음성소견과 밀접한 연관성을 보였다. 면역조직화학염색 기반 분류 소그룹별로 비교했을 때, CK5/6 단일 양성 소그룹이 가장 높은 PD-L1 양성율을 보였다. 그리고 카플란-마이어 생존분석을 통해 CK5/6 단일 양성 소그룹이 더 짧은 무진행 생존기간을(p = 0.008) 가진다는 사실을 밝혔다. 결론: 본 연구를 통해 면역조직화학염색 기반 분류가 근육침윤성 방광 요로상피암 환자에서 PD-1/PD-L1 억제 면역항암제 적용하는 데 있어 중요한 역할을 할 가능성을 제시하였다. 그리고 CK5/6 양성 그룹이 종양 악성화와 관련된 유전자를 높게 발현하며, 불량한 예후를 보이는 사실을 밝혔다.Introduction 1 Materials and Methods 4 Results 10 Discussion 43 Bibliography 52 Abstract in Korean 59박

창과 관현악의 상호관계를 중심으로

학위논문(박사) -- 서울대학교대학원 : 음악대학 음악과, 2023. 2. 김승근.This dissertation examines the stylistic development of pansori concertos with a particular focus on the diachronic changes in the relationship between chang, the pansori singer, and the supporting orchestra, hoping to evaluate the further establishment of the genre. To do so, I have analyzed the structural development and the stylistic language of pansori concertos created between 1971 and 2021, arriving at the following findings. First, the overall density of the supportive instrumental parts has undergone a textural transformation to emphasize dramatic effects. Instrumentation has expanded to accompany both chang, a song, and aniri, a narrative recitation, in contrast to the past trend of the latter being solo. Also, concluding drumming patterns are now accompanied by combinations of orchestral parts, allowing artistic freedom lacked when mostly played as orchestra tutti. Moreover, the usage of suseonggarak, an instrumental melody played with a pansori vocal part, has broadened, no longer following the vocal melody. Instead, it interdependently acts as a counterpoint to the vocal melody, giving more artistic freedom to the orchestral part. Also, the rhythm-oriented orchestration is more actualized and emphasized. For example, when a rhythmic section occurs to guide its singer, it tunes to the singers breath and acts as the second percussion. Along with other western-classical ideas, harmony has been accepted gradually and utilized functionally, but today its functional significance is less-prominent. The texture and density of counterpoint parts have become intricate and elaborate: an indicator that each part is characteristically appreciated and independently regarded. Second, introducing a short instrumental prelude, especially to prepare the pansori vocal, has been widely practiced throughout different eras. These methods include playing the first note for the singer and using the first phrase of the vocal melody as the introduction. There are, however, subtle attempts to emphasize the tonic note, to approach chromatically, to allude to the new scale, and to deviate from the expected pitch. I further confirmed new attempts to align tonic notes vertically with vocal tones. Third, a study of word painting methods, such as creating contextual mood, reveals that the horizontal sustention of instrumental parts is first constructed and then followed by the vertical expansion of orchestral parts and techniques, experimenting with its programmatic nature. Originally, expressing the singers emotional state mostly involved a reiteration of the vocal melody and ornamentation, whereas today, composers incorporate various techniques, such as introducing thematic motifs or deliberate dissonances to denote the protagonist's inner conflicts. Sudden descending melodies for accompanying onomatopoeias and mimetic words progress chromatically and are faster and longer for more dramatic effects. These different techniques are first fused tightly before expanding. These stylistic changes in pansori concertos prove that the form is constantly evolving. Accordingly, we must delve into a deeper discussion about various aspects concerning the future of pansori concerto: diversifying subject materials, annotating Chinese characters, organizing the cadential structure with doseop (a pansori technique of dramatic slowing down), examining the musical potential of aniri, exploring the aspects of program music, establishing the standard key structure, standardizing the notation system for gayageum byeongchang, etc. My only wish is that further vigorous and passionate endeavours from composers and scholars will continue to thrive and contribute to the musical evolution of pansori concerto.본 논문은 판소리 협주곡의 양식 변화를 통시적으로 고찰한 연구이다. 특히 협연 주체인 창과 이를 보조하는 관현악 사이의 상호관계가 시대의 흐름에 따라 어떻게 달라졌는지 알아보고 앞으로의 방향성을 논하는 것이 그 목적이다. 이를 위하여 1971년부터 2021년 사이에 창작된 판소리 협주곡의 전개 및 관현악 어법의 분석을 통해 시대에 따른 변화 양상을 파악하였고, 다음과 같은 결론을 얻었다. 첫째, 창을 보조하기 위한 관현악의 밀도는 반주 질감의 총체적 변화에 따라 극적인 효과가 강화되었다. 창에 대한 보조적 역할은 아니리도 수용하게 되었으며, 소리북의 맺는 가락을 총주(Tutti)로 구현하던 양상은 성부의 수직적 확대로 인하여 여러 악기에 걸쳐 분포 및 변화되었다. 창 선율에 의존적이던 수성가락은 표현 범위가 확장되어 가사나 성부 사이에서 밀접한 상호작용을 하며 관현악의 어법을 다채롭게 하였다. 관현악의 리듬 보조 역할은 구체화 및 강화되었는데, 예를 들어 창자의 박자인지를 돕는 역할에서 나아가 함께 호흡하고, 타악기처럼 리듬 보조에 집중하기도 하였다. 화성은 서양음악 어법과 함께 점진적으로 수용된 이후 기능적으로 쓰였고, 점차 그 용법을 탈피하게 되었다. 대위의 텍스쳐는 매우 촘촘하고 정교해졌는데, 이는 관현악 각 성부의 개성과 독립성이 존중되었음을 의미한다. 둘째, 관현악은 창 음정을 예비하기 위하여 창의 첫 음을 직접 제시하거나 창의 첫 소절을 전주에 활용하는 직접적 방식을 모든 시대에 걸쳐 통상적으로 활용하였다. 간접적으로는 본청 강조, 반음계적인 도입, 새로운 조의 정체성 제시 및 창 음정으로부터 의도적으로 이탈하는 방식도 보였다. 또한 창의 음정과 본청을 수직적으로 결합하는 직·간접적 방식도 새롭게 확인할 수 있었다. 셋째, 음화기법 중 배경 및 분위기를 표현하는 방식은 악기의 결을 활용한 수평적 지속에서 시작하여 수직적 확대를 거쳐, 관현악의 여러 요소를 결합하며 표현의 폭을 넓히게 되었다. 화자의 어조 및 내적 정서를 표현함에 있어서는 특정 가사의 선율과 시김새를 모방하던 방식에서 나아가 화자 내면의 정서를 대변하는 관현악 주제를 등장시키거나 창 음정과의 의도된 불협화를 사용하기도 하였다. 의성어·의태어 표현을 위하여 활용되던 방식 중 급격한 하행은 반음계적으로 더욱 빠르고 길게 변화하며 강한 자극을 주었고, 여러 요소가 촘촘한 붙임새로 결합한 뒤에 확장되었다. 위와 같이 판소리 협주곡의 양식은 시대의 흐름에 따라 변화해왔다. 한편 판소리 협주곡이 나아가야 할 방향에 있어 소재의 다양화, 한자어 사설의 풀이, 도섭을 활용한 카덴차 형식의 확립, 아니리의 가능성 탐구, 극(劇) 기능의 강화, 표준 청(Key)의 합의, 가야금병창 기보 방식의 합리적 기준 마련 등의 추가적인 논의가 필요하다. 앞으로 이 분야의 창작과 연구가 더욱 활발해져서 판소리 협주곡의 발전에 기여하기를 바란다.Ⅰ. 서론 1 1. 문제제기 및 연구목적 1 2. 선행연구 검토 6 3. 연구범위 13 4. 연구방법 16 Ⅱ. 판소리 협주곡의 전개 21 1. 초기 판소리 협주곡(1971~1989) 21 2. 1990년대 판소리 협주곡(1990~1994) 25 3. 2000년대 판소리 협주곡(2000~2008) 29 4. 2010년대 이후 판소리 협주곡(2010~2021) 33 5. 소결 41 Ⅲ. 창과 관현악의 상호관계와 음악적 특징 44 1. 김희조 편곡, 창과 관현악을 위한 심청가 중 (1972) 45 2. 김희조 편곡, 가야금병창과 관현악을 위한 춘향가 중 (1991) 83 3. 김대성 편곡, 창과 관현악을 위한 (2005) 124 4. 황호준 작곡, (2013) 174 5. 최지혜 작·편곡, 창과 국악관현악을 위한 (2021) 229 Ⅳ. 창과 관현악의 상호관계에 활용된 주요 관현악 기법의 시대별 변화 양상 288 1. 주요 관현악 기법 288 2. 주요 관현악 기법의 시대별 변화 양상 295 3. 동일 원곡 의 비교 300 4. 판소리 협주곡의 남은 과제와 방향성 303 Ⅴ. 결론 306 참고문헌 310 부록 - 판소리 협주곡 작품목록 및 초연 정보 316 Abstract 324박

Sural Artery Flap

Purpose: Our clinical experiences in distally based sural artery island flap is presented to show the usefulness and the reliability as an alternative to flaps currently used for defect in lower extremity. Materials and Methods: From February 1998 to September 2001, nine cases of soft tissue defects in the lower leg, the foot, and around the ankle were treated with distally based sural artery island flap. The cause of the wound was trauma in 6cases, and osteomyelitis in 3 cases. Defects were located at the lower leg in 2 cases, at the foot in 3 cases and around the ankle in 4 cases. The results were retrospectively analyzed. Results: The defect size ranged from 3×3 ㎝ to 20×3 ㎝. Among 9 cases, 7 cases survived and 2 cases were failed. Flap failure was due to not including the deep fascia in one case and due to extensive soft tissue damage in the other case. Both failed cases were reoperated with the split thickness skin graft. Conclusion: The advantages of distally based sural artery island flap follows : (1) reliable blood supply, (2) ease of flap elevation, (3) preservation of the major arteries, (4) less donor site morbidity. Owing to the advantages of this flap, we think it is useful for the soft tissue coverage of the lower leg, the foot and around the ankle. Also we believe it will continue to gain acceptance and use in the majority of lower leg reconstruction.ope

Comparison of Treating Tibial Nonunion with Bone & Soft Tissue Defect: Ilizarov Only Versus Free Flap and Ilizarov

Purpose : To statistically analyze the advantages of distraction osteogenesis in combination with free flap in the treatment of tibial open fracture with bone and soft tissue defect. Materials and Methods : Twenty patients with tibial open fracture with bone and soft tissue defect were treated by distraction osteogenesis with or without flap. Patients were followed up for a minimum of 12 months and retrospectively analyzed, for the admission period, the out patient follow-up period, and the intravenous antibiotic period, and distraction consolidation indices were determined. Results : Those treated with free flap showed statistically significance shorter antibiotic period, admission period, and distraction consolidation indices. Conclusion : Free flap and distraction osteogenesis with an Ilizarov external fixator has many advantages for treating tibial open fracture with bone and soft tissue defect.ope

Serial plasma levels of angiogenic factors in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND AND OBJECTIVES: Patients with acute myocardial infarction show varying degrees of collateral development. However, the relationships between angiogenic factors and degree of collaterals are not well known. SUBJECTS AND METHODS: Fifty-nine patients (mean age, 59±10 years) with ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Patients were divided into one of 2 groups: group I (Rentrop collateral grade 0/1, n=34) or group II (grade 2/3, n=25). Plasma levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sFlt-1), angiopoietin (Ang)-2, and soluble Tie-2 at baseline, 24 and 48 hours after PCI were measured. RESULTS: There were fewer diabetic patients and higher incidence of previous angina and multi-vessel disease in group II. Group II had a lower left ventricular ejection fraction and a trend toward longer pain-to-balloon time. Plasma levels of Ang-2, sFlt-1 were elevated prior to primary PCI and decreased after PCI, whereas plasma level of VEGF was relatively low initially, however rose after PCI. sTie-2 levels showed no significant interval change in group I, but decreased over time in group II. VEGF, sFlt-1, and Tie-2 levels did not differ between the groups at each time point. However, plasma levels of Ang-2 were higher in group I than in group II at baseline and at 48 hours. CONCLUSION: Presence of collaterals in STEMI patients undergoing primary PCI was associated with lesser rise in Ang-2 plasma level. VEGF showed a delayed response to acute ischemia compared to Ang-2. Clinical implications of our findings need to be investigated in further studies.ope

Correlations between coronary plaque tissue composition assessed by virtual histology and blood levels of biomarkers for coronary artery disease

PURPOSE: We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98±0.09 vs. 1.10±0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core. CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.ope

세포주 실험과 동물 실험에서 커피 페놀 성분의 항 염증 및 항 전이 효과

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(A) study on the composers ideology in their musical works : focused on Kang Jun-ils concerto for traditional orchestra <Be a Hana>

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Guggulsterone이 간성상세포의 활성화와 생존에 미치는 영향

학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2011.2. 윤정환.Docto

Valuing American Options with Kernel-Based Monte Carlo Simulation

Maste