바흐친의 라블레론에 나타난 민중의 타자성

학위논문(석사)--서울대학교 대학원 :노어노문학과 노문학전공,2002.Maste

혈관 비틀림이 백서 천층하복부동맥의 초미세문합에 미치는 영향

학위논문 (석사)-- 서울대학교 대학원 : 치의과학과, 2011.8. 김성민.Maste

펜톡시필린의 대식세포에서 단백질 발현 양상과 백서 방사선골괴사증 모델에서 골 치유에 대한 효과

학위논문 (박사)-- 서울대학교 대학원 : 치의학대학원 치의과학과, 2019. 2. 김성민.연구 배경 및 연구 목적 방사선 치료는 두경부 암의 치료에 있어, 오랫동안 확립되어 온 치료 방법이다. 악골의 방사선 골괴사증 (osteoradionecrosis, ORN)은 방사선 치료의 심각한 부작용 중의 하나이다. 최근에, 방사선 유발 섬유화 이론이 악골의 방사선 골괴사증에 적용됨에 따라, 펜톡시필린 (pentoxifylline, PTX)이 방사선 골괴사증의 치료 및 예방에 사용됨이 보고된 바 있다. 이 연구의 목적은, 마우스 대식 세포 계열인 RAW 264.7 세포에서 펜톡시필린의 효과를 면역 침전 고성능 액체 크로마토그래피 (immunoprecipitation-high performance liquid chromatography, IP-HPLC)를 사용하여 분석하고, 방사선 골괴사증 백서 동물 모델에 펜톡시필린을 적용하여 그 효과에 대해서 알아보는 것이다. 연구 방법 1. PTX를 처리한 대식 세포의 단백질 발현 양상에 대한 연구 펜톡시필린의 세포에 대한 효과를 알아보기 위하여, RAW 264.7 세포에 펜톡시필린을 10 μg/ml을 12시간, 24시간, 48시간 처리한 후 단백질 발현 양상을 IP-HPLC를 통하여 분석하였다. 2. PTX의 백서 방사선 골괴사증 모델에서 골 치유에 미치는 효과 총 48마리의 Spraque-Dawley 백서를 실험에 사용하였다. 40 마리는 하악의 좌측에 35 Gy로 방사선을 조사하였다. 8마리는 방사선 조사를 하지 않고 대조군으로 설정하였다. 백서는 실험군에 따라 펜톡시필린 (T1, C1), 토코페롤 (T2, C2), 펜톡시필린과 토코페롤의 병용 (T3, C3), 생리 식염수 (T4, C4)를 방사선 조사 다음날부터 투여하였다. 방사선 조사 3주 후, 하악 좌측의 대구치 2개를 발거하였고, 약제는 실험 종료일까지 투여하였다. 백서는 발치 4주 후 (방사선 조사 7주 후) 희생하였다. 매주 체중, 피부 변화 등의 임상적 평가를 시행하였으며, 방사선 조사 전, 3주 후, 7주 후에 일반 혈액 검사 (complete blood cell count, CBC)와 C 반응성 단백 (C-reactive protein, CRP)을 측정하였다. 희생 후 micro CT, 헤마톡실린-에오신 (hematoxylin and eosin, H&E)과 Massons trichrome 염색을 사용한 조직학적 분석, 면역화학 분석, quantitative reverse transcription PCR (RT-qPCR) 분석을 시행하였다. 연구 결과 1. PTX를 처리한 대식 세포의 단백질 발현 양상에 대한 연구 펜톡시필린은 면역 관련, 골형성과 연관된 단백질은 증가시켰으며, 반면에 세포 증식, 염증, 세포 자멸사 연관된 단백질은 감소시켰다. 펜톡시필린은 RAW 264.7 세포에서 세포 증식, 면역, 항염증, 세포 자멸사, 골형성과 관련된 단백질의 전반적인 발현에 영향을 미치는 것으로 볼 수 있다. 2. PTX의 백서 방사선 골괴사증 모델에서 골 치유에 미치는 효과 체중, 피부 탈모, 희생 시 골 노출 정도는 실험군에 따른 차이는 관찰되지 않았다(p >0.05). 혈액 검사에서는 CRP는 방사선 조사에 따른 차이가 관찰되지 않았고, 방사선 조사 7주 후의 CBC에서실험군에 따른 차이가 있었다. 백혈구 수, 중성구 수, 림프구 수, 단핵구 후, 중성구 림프구 비율 (neutrophil to lymphocyte ratio, NLR)은 약제 복용에 따라, 통계학적으로 유의미한 차이가 있었다. 헤모글로빈 수치는 대조군인 T4에서 다른 실험군에 비하여 낮은 수치를 보였다 (p <0.05). Micro CT 분석에서 bone volume/tissue volume, 골 소주 수, 골 소주 공간, 골밀도 (bone mineral density, BMD)에서 실험군에 따른 차이가 관찰되었다 (p <0.05). 조직학적 분석에서 펜톡시필린과 토코페롤을 병용한 실험군 (T3)에서 골의 재형성이 가장 증가하여 나타났으며, 살아 있는 골세포 (osteocyte)의 수가 다른 실험군에 비하여 유의미하게 높게 나타났다 (p <0.05). 면역 화학 분석에서는 TNF-α의 발현이 펜톡시필린과 토코페롤을 함께 사용한 실험군 (T3)에서 대조군 (T4)과 토코페롤 복용군 (T2)에 비하여 낮게 나타났다. RT-qPCR에서는 PECAM, VEGF-A, osteocalcin의 mRNA 발현이 펜톡시필린과 토코페롤을 함께 복용시킨 그룹 (T3)에서 증가하였다. 결론 세포 실험에서 펜톡시필린은 항염증 효과, 세포 자멸사 억제 효과, 골형성 촉진 효과를 나타내었다. 동물 실험에서 펜톡시필린은 토코페롤과 함께 사용될 때 방사선 조사를 받은 발치와 결손부에서 골 형성을 촉진시키는 효과가 있었다. 따라서, 펜톡시필린은 토코페롤과 함께 사용할 때, 악골 방사선골괴사증의 치료에 유용하게 사용될 수 있으며, 추가적인 전향적 임상 연구가 진행되어야 할 것으로 사료된다.Background and purpose Radiation therapy has long been an established treatment modality for the head and neck cancer. Osteoradionecrosis (ORN) of the jaws is one of the serious complications of radiotherapy. Since the radiation-induced fibrosis theory was introduced, pentoxifylline (PTX) have been used to treat or prevent of ORN. The purpose of this study was to investigate the effects of PTX through both in vivo animal experiment using rat ORN model and in vitro experiment using RAW 264. 7 cells.   Materials and methods 1. Protein expression profiles in macrophage treated with PTX To understand the cellular effects of PTX, protein expression in PTX-treated RAW 264.7 cells was analyzed by using immunoprecipitation high performance liquid chromatography (IP-HPLC). 2. Animal study: the effects of PTX on the bone healing in a rat ORN model A total of 48 Sprague-Dawley rats were used in this experimental animal study: 40 received a single irradiation dose of 35 Gy on the left mandible, and eight were used as the nonirradiated control group. The rats were treated with pentoxifylline (T1, C1), tocopherol (T2, C2), a combination of pentoxifylline and tocopherol (T3, C3), or normal saline (T4, C4). Three weeks after irradiation, the mandibular posterior teeth were extracted. The drugs were administered daily from the irradiation to the end of study. The rats were sacrificed at 4 weeks after extraction, and were evaluated clinically, and using micro-CT, histology, immunohistochemistry, and quantitative reverse transcription PCR (RT-qPCR). Statistical analyses were performed using SPSS 25.0® (SPSS Inc., Chicago, IL, USA). The Kruskal-Wallis test was performed, and the Mann-Whitney U test was used for post-hoc testing. p < 0.05 was considered to indicate statistical significance. Results 1. Protein expression profiles in macrophage treated with PTX RAW 264.7 cells treated with PTX for 12, 24, 48 hours showed gradual increases in the expressions of immunity-, and osteogenesis-related proteins and concurrent decreases in the expressions of proliferation-, matrix inflammation-, cellular apoptosis-related proteins. 2. Animal study: the effects of PTX on the bone healing in a rat ORN model The areas of skin alopecia and intraoral bony exposure and the changes in body weight showed no statistically significant differences among the experimental groups. In the laboratory analysis, statistically significant differences were observed seven weeks after irradiation: WBC, neutrophil count, lymphocyte count, monocyte count, and the neutrophil to lymphocyte ratio differed significantly between test groups. The T4 control group had lower hemoglobin values than the other groups (p < 0.05). In the micro-CT analysis, significant differences between experimental groups occurred in the bone volume/tissue volume ratio, trabecular number, trabecular spaces, and bone mineral density (p < 0.05). In the histological observation, T3 group which received both PTX and tocopherol showed the most prominent bone remodeling and viable osteocytes in significantly higher number than the other groups (p < 0.05). In the immunohistochemical staining, the expression of TNF-α was lower in the T3 group (PTX and tocopherol) than in the control (T4) and tocopherol alone (T2) groups. In the RT-qPCR, mRNA expressions of PECAM, VEGF-A, osteocalcin were increased in the group treated with PTX and tocopherol (T3). Conclusions IP-HPLC results indicate that PTX plays wound healing roles by regulating cellular proliferation-, immunity-, anti-inflammation-, apoptosis-, and osteogenesis-related proteins in RAW 264.7 cells. In animal studies, PTX has been shown to promote bone healing when combined with tocopherol. These data suggest that PTX is effective in the treatment of ORN when combined with tocopherol.I. Introduction II. Review of literature II-1. Osteoradionecrosis (ORN) II-2. Pentoxifylline (PTX) II-3. Tocopherol II-4. Immunoprecipitation-high performance liquid chromatography (IP-HPLC) III. Materials and methods III-1. Protein expression profiles in macrophage treated with PTX III-2. Animal study: the effects of PTX on the bone healing in a rat ORN model IV. Results IV-1. Protein expression profiles in macrophage treated with PTX IV-2. Animal study: the effects of PTX on the bone healing in a rat ORN model V. Discussion VI. Conclusion References Tables Figure legends and Figures Supplement Abstract in KoreanDocto

Development of Prediction Models for Thyroid Peroxidase Inhibitors Using Ensemble Machine Learning Methods and Their Application to Synthetic Flavors

학위논문 (석사) -- 서울대학교 대학원 : 생활과학대학 식품영양학과, 2021. 2. 권훈정.자연계에 존재하는 양파, 순무, 콜리플라워 등의 많은 식용식물 및 홍차나 커피와 같은 음료류에서 갑상샘 과산화효소(thyroid peroxidase, TPO)를 저해하는 물질들이 발견되어왔다. TPO는 갑상샘 호르몬 합성에 중요한 역할을 하는 효소이기 때문에 식품 원료의 개발 시 TPO 저해 물질을 파악하는 것이 매우 중요하다. 한편, 최근 3R(Reduction, Refinement, Replacement)원칙의 중요성이 다시 한 번 조명되면서 머신 러닝을 기반으로 한 정량적 구조-활성 관계(QSAR)가 약물 개발 및 독성 예측 등 다양한 분야에서 대체시험방법으로서 폭 넓게 적용되고 있다. 따라서 본 연구에서는 다양한 머신 러닝 기법을 이용하여 TPO 저해 물질을 예측하는 모델을 설계함으로써 식품 내 존재하는 위해물질을 신속하게 파악할 수 있는 대체시험방법을 개발하였다. 2장에서 예측 모델의 개발을 위해서 총 587개 화합물의 TPO 저해 데이터를 수집하였고 수집된 데이터는 최대 저해 정도와 IC50에 따라 두 개, 세 개 또는 네 개의 독성 등급으로 분류되었다. 모델 설명 변수로는 분자 핑거프린트(FP)와 표현자를 사용하였고, 특성 추출 방법인 주성분분석(PCA) 또는 선형판별분석(LDA)을 사용하여 데이터의 차원을 축소하였으며 각 특성 추출 방법을 사용한 모델의 예측 성능을 비교하여 보았다. 모델 학습 방법으로는 간단한 학습 방법과 복잡한 앙상블 학습 방법을 사용하여 앙상블 학습 방법이 예측 성능을 증가시키는지 비교하였고, 하드 투표 분류기에서 뚜렷한 예측 성능의 향상이 관찰되었다. 모델의 평가는 정밀도와 재현율의 조화평균으로 계산되는 지표인 F1 점수를 이용하여 실시하였으며 테스트 점수를 바탕으로 각 그룹핑 방법별 최적의 예측 모델을 선정하였다. 3장에서는 모델의 개발과 함께 모델 학습에 사용된 물질들 중 TPO 저해 효과가 강한 물질에서 빈번하게 나타나는 substructure인 활성 구조를 분석하였다. Quaternary 분류를 기준으로 독성이 가장 강한 그룹에서의 빈도가 독성이 없는 그룹에 비해 1.2 이상인 것을 활성 구조로 정의하였고, 분석 결과 primary aromatic amine, enol, enolether, phenol, vinylogous carbonyl, heterocyclic S, N 등이 활성 구조로 나타났다. 또한 4장에서는 2장에서 개발 및 선택된 최적 모델들을 국내에서 사용되는 향료 중 1774종에 대하여 적용하였으며, 모델의 예측 결과 1774종 중 22종이 강한 TPO 저해 작용을 할 것으로 나타났다. 이 22종의 향료들은 물질의 경구독성 평가 체계 중 하나인 Cramer class와 비교함으로써 예측 결과를 평가하였다. 본 연구에서 개발된 예측 모델과 이들의 적용 결과 데이터는 향후 식품 원료 중 존재하는 위해 물질을 신속하게 파악할 수 있는 대체시험방법의 개발에 활용될 수 있을 거라 생각된다.There are many edible plants containing thyroid peroxidase (TPO) inhibitors such as onions, turnips, cauliflowers, and beverages like tea and coffee in nature. As TPO is a crucial enzyme in thyroid hormone synthesis, TPO inhibitors should be detected during food ingredient development process. Meanwhile, an importance of 3R (Reduction, Refinement, Replacement) principle has been emerging nowadays, machine-learning-based quantitative structure-activity relationship(QSAR) is being widely applied in various fields such as drug developments and toxicity predictions. In this study, therefore, the prediction models for TPO inhibitors using various machine-learning methods were designed. To construct prediction models in Chapter 2, the TPO inhibition assay data of 587 chemicals were collected from Environmental Protection Agency(EPA) Chemistry Dashboard database and existing articles and categorized into two, three, or four groups, based on their max inhibition(%) and IC50 values. Topological and key-based fingerprints(FPs), and descriptors were calculated for each compound to be used as model features. Either principal component analysis(PCA) or linear discriminant analysis(LDA) was introduced as feature extraction methods and their performances were compared. Various machine-learning strategies were employed, from simple methods to complicated ensemble methods to investigate if ensemble methods could improve the prediction performances, and as a result, hard-voting classifier remarkably improved the model performances in all grouping methods. The model performances were evaluated using F1 score, the harmonic mean of precision and recall. The best-performing models for each grouping method were selected based on their test scores. Along with the model development, typical substructures dominantly occurred in the most highly active compounds were analyzed using substructure frequency analysis method in Chapter 3. Substructures that occurred 1.2 times more frequently in class A1 than in class C were defined as active substructures. These active substructures included primary aromatic amine, enol, enolether, phenol, vinylogous carbonyls, heterocyclic sulfur, heterocyclic nitrogen and so on. Furthermore, in Chapter 4, the best-predicting models selected in Chapter 2 were applied to synthetic flavors and 22 out of 1774 agents appeared to have a strong inhibition potential towards TPO activities. Afterward, in order to assess the results of model application on synthetic flavors, these 22 agents were compared with their Cramer classes, a method to assess oral toxicity of chemical substances. The prediction models designed in this study and their application results could be utilized to develop alternative testing methods to rapidly detect hazardous substances in food components in the future.목 차 제1장 서론 1 제2장 갑상샘 과산화효소 저해제 예측모델의 개발 및 평가 7 2.1. 서론 7 2.2. 연구 방법 22 2.2.1 데이터 수집 및 전처리 22 2.2.2 특성의 선택 및 계산 24 2.2.3 모델 학습 및 평가 26 2.3. 결과 및 고찰 30 제3장 TPO 저해제의 활성 구조 분석 36 3.1. 서론 36 3.2. 연구 방법 37 3.3. 결과 및 고찰 38 제4장 개발된 예측 모델을 이용한 합성향료 스크리닝 44 4.1. 서론 44 4.2. 연구 방법 47 4.3. 결과 및 고찰 48 제5장 요약 및 결론 53 참고문헌 57 Abstract 66Maste

Anatomical Review of Rectus Abdominis Muscle Free Flap for the Oral and Maxillofacial Reconstruction

Midfacial reconstruction following resection of extensive malignant oral cavity tumors constitutes a challenging problems for reconstructive surgeons. Rectus abdominis muscle free flap (RAMFF) can be considered as the optimal reconstructive option in this case, because this flap has some advantages including consistent deep inferior epigastric artery anatomy, easy to dissect with well defined skin boundaries, acceptable donor site morbidity and the ability to perform simultaneous flap harvest with oral cancer ablation surgery. The rectus abdominis muscle forms an important part of the anterior abdominal wall and flexes the vertebral column, which is a long strap-like muscle divided transversely by three tendinous intersections, fibrous bands which are adherent to the anterior rectus sheath, which is thickly enclosed by the rectus sheath, except for the posterior part below the arcuate line that is usually located midway between the umbilicus and symphysis pubis. Below the arcuate line, this muscle lies in direct contact with the transversalis fascia and parietal peritoneum. For the better understanding of RAMFF as a routine reconstructive procedure in oral and maxillofacial surgery, the constant anatomical findings muse be learned and memorized by the young doctors in the course of the special curriculum periods for the Korean national board of oral and maxillofacial surgery. This review article will discuss the anatomical basis of RAMFF with Korean language.N

Surgical Anatomy of Sural Nerve for the Peripheral Nerve Regeneration in the Oral and Maxillofacial Field

Peripheral nerve injuries in the oral and maxillofacial regions require nerve repairs for the recovery of sensory and/or motor functions. Primary indications for the peripheral nerve grafts are injuries or continuity defects due to trauma, pathologic conditions,ablation surgery, or other diseases, that cannot regain normal functions without surgical interventions, including microneurosurgery. For the autogenous nerve graft, sural nerve and greater auricular nerve are the most common donor nerves in the oral and maxillofacial regions. The sural nerve has been widely used for this purpose, due to the ease of harvest, available nerve graft up to 30 to 40 cm in length, high fascicular density, a width of 1.5 to 3.0 mm, which is similar to that of the trigeminal nerve, and minimal branching and donor sity morbidity. Many different surgical techniques have been designed for the sural nerve harvesting, such as a single longitudinal incision, multiple stair-step incisions, use of nerve extractor or tendon stripper, and endoscopic approach. For a better understanding of the sural nerve graft and in avoiding of uneventful complications during these procedures as an oral and maxillofacial surgeon, the related surgical anatomies with their harvesting tips are summarized in this review article.N

Review of Current Facial Allotransplantation and Future Aspects

Advances in immunosuppressive treatments and microsurgical techniques have rendered composite tissues allotransplantation (CTA), such as heteregeneous or non-organ tissues, possible in humans. CTA has evolved dramatically since the first successful rat hind limb allotransplantation. Numerous clinical applications including face, hand, trachea, larynx, and vascularized joint have been performed. Although composite tissue allografts are still in their infancy, they have opened a new era in the field of transplantation surgery and pathology, so that maxillofacial reconstructive surgeons may occasionally be faced with the challenge of diagnosing skin refection of a composite tissue allograft. Facial allotransplantation (FAT) is a new surgical technique that could be considered as a new paradigm in facial reconstruction. Since the first human FAT had been achieved in 2005, 17 cases have been reported in the world up to date. However, many problems such as life-long immunosuppression,immune rejection, ethical problems and psychological problems are remained, so facial CTA is new reconstructive option with no general acceptance. The authors reviewed the indications, the results of 17 cases and their complications, and additional consideration factors in this article, and intended to raise the awareness of oral and maxillofacial surgeons in this type of facial transplantation.N

Developmental Field Repair for the Facial Tissue Engineering Regeneration

In growing child, corrective surgery for congenital malformation can cause complication and problems, such as repetitive relapse and growth disturbance over time. These are because the biologic rationale of the procedure is incorrect, and the anatomic pattern of relapse points an accusatory finger at the pathology. Recent updates in surgical approach for the clefting are focused on facial development and origin of clefting. Successful treatment of congenital craniofacial defect can be acquired by understanding of developmental processes. The developmental field repair (DFR) is based on the neuromeric model, which propose facial tissues are originated from embryonic nervous system. This concept consider the identification and reassignment specific developemental field. Goals of DFR surgery are 1) resolution of all pathologic processes of clefting, 2) dissection following the embryonic separation plane, 3) preservation of vascular supply for alveolar mucoperiosteum, 4) primary unification of alveolus, 5) reassignment of all developmental field to correct relation. Therefore, understanding of developmental field theory must be proceeded surgical approach. This concepts are based on reconstruction of deformed tissues following embryonic origin, which are able to be functional and anatomical repair. Therefore, in this article the author reviewed the developmental neuromeric theory, and the developmental field repair concept based on this neuromeric model.N

Twisting Effect on Supermicroanastomosis of the Superficial Inferior Epigastric Artery in a Rat Model

Purpose: The advent of microsurgical technique and instruments, particularly in the field of perforator flap and supermicrosurgery,which have expanded the scope of microsurgery. However, supermicroanastomosis without any compression,tension, or distortions must be achieved to reach successful outcomes. Small-caliber vessels, such as those with an internal diameter less than 0.2 mm, are susceptible to inadvertent twisting of the anastomosis. In this study, using the superficial inferior epigastric artery (SIEA)-based flap model in Sprague-Dawley (SD) rats, we evaluated the acceptable limits of twisting effects on supermicroanastomotic sites. Methods: A total of 20 supermicroanastomoses were performed using the SIEA-based flap model in 10 male SD rats,10-weeks-of-age, weighing 300∼350 g. Rats were divided into five groups of two with four flaps as follows: 1) sham, 2)control group with end to end SIEA arterial supermicroanastomosis, 3) experimental I (EA1) with 90o twisting, 4) experimental II (EA2) with 180o twisting, and 5) experimental III (EA3) with 270o twisting of the supermicroanastomosis. Each SIEA was anastomosed using six 11-0 Ethilon? (Ethicon Inc. Co., NJ, USA) stitches except in the sham group where the SIEA was only clamped with Supermicro vascular clamps? (S&amp;T, Neuhausen, Switzerland) for 20 minutes. Results: The anastomosed arterial patency showed no remarkable changes according to doppler waveforms measured with a Smardop 45 Doppler System (Hadeco Inc., Kawasaki, Japan). The pulsatility index (PI) was increased at postoperative day 10 in the EA2 and EA3 groups, and the resistance index (RI) showed no statistically significant difference between preoperative and postoperative values at 10 days. Histologic specimens from the EA3 group showed increased tunica media necrosis,convolution of the internal elastic lamina, densely packed platelets, fibrin, and erythrocytes. Flap viability and anastomosed vessel patency were not significantly affected by the degree of arterial twisting in this study, other than in the EA3 group where minor effects on arterial patency of the microanastomoses were encountered. Conclusion: It appears that minor twisting on small caliber arteries, used in supermicroanastomoses, can be tolerated. However,twisting should be avoided as much as possible, and more than 180o twisting must be prevented in clinical practice.N

Differential Diagnosis of Oral Lesions for the Initial Diagnosis of Acute Lymphoblastic Leukemia

Careful examination of the oral cavity may reveal findings indicative of an underlying systemic condition, and allow for early diagnosis and treatment. Examination should include evaluation for mucosal changes, periodontal inflammation and bleeding,and general condition of the teeth. A 12-year-old man visited for molar pain during 3 months. He was diagnosed with having a possibility of hematopoietic malignancy, showing the loss of lamina dura, destruction of bony crypt, and high attenuation in the bone marrow. He was referred to department of pediatrics, additional study, including peripheral cell morphology and bone marrow exam, were performed, and diagnosed as acute lymphoblastic anemia. Despite chemotherapy to cure leukemia,he was expired 8 months after initial diagnosis. The purpose of this report is to promote and evoke the awareness regarding an initial examination of the dentist to make an effort to acquire accurate knowledge and information about life-threatening disease in usual dental practice.N