청소년에서 프탈레이트의 노출 바이오마커와 이른 초경과의 관련성

학위논문(석사) -- 서울대학교대학원 : 보건대학원 환경보건학과, 2021.8. 백도명.프탈레이트는 플라스틱 제품, 장난감, 식품 포장 용기 등 여러 용도에 사용되는 화학 물질로서, 일상 생활에서 꾸준한 환경적 노출이 일어난다. 프탈레이트는 시상하부-뇌하수체-생식선 축의 여러 호르몬계에 교란을 일으켜 사춘기 및 2차 성징 시기에 영향을 줄 수 있다. 한편 전세계적으로 초경 연령은 지속적으로 감소해왔으며, 한국에서도 같은 추세를 보인다. 여러 실험 연구에서 프탈레이트와 같은 내분비계 교란 물질이 사춘기 시기에 영향을 줄 수 있음이 밝혀졌지만, 사람 대상 역학 연구에서 프탈레이트 노출과 초경 연령 사이 관계는 일정하지 못한 결과를 보여주고 있다. 이에 제 2장에서는 체계적 문헌 고찰(systematic review)을 통해 산전 및 사춘기 무렵 프탈레이트 노출과 초경 연령 사이의 관련성을 알아보았다. PubMed, EMBASE, Web of Science 데이터베이스에서 프탈레이트와 초경에 대한 논문들을 검색하였고, 총 13개 연구가 문헌 고찰에 포함되었다. 가장 자주 관련성을 보였던 프탈레이트 대사산물은 MEP, 그리고 DEHP의 대사산물이었으나, 연구에 따라 초경 연령이 빨라지는 결과와 늦어지는 결과가 공존하고 있었다. 이는 연구 시기, 그리고 연구가 이루어진 국가들 사이에 프탈레이트 사용 및 노출의 분포가 달랐기 때문인 것으로 추정할 수 있다. 또한 프탈레이트와 초경 사이 관련성에 영향을 줄 수 있는 공변수들로는 연령, 인종, 어머니의 초경 연령, 체지방, 빈곤 또는 가계 수입, 보호자의 교육 수준이 조사되었다. 이들 중 인종, 가계 소득, 보호자 교육 수준, 비스페놀 A의 노출은 교란 변수로서 작용할 수 있는 반면 BMI와 같은 체지방 관련 변수들은 프탈레이트 노출에서 초경 사이 경로에서 부분적인 매개자로서 작용할 가능성이 있다. 제 3장에서는 제 3기 국민환경보건기초조사 (2015-2017) 자료를 이용하여 한국 중학생 여아에서 프탈레이트와 이른 초경 사이의 관계를 연구하였다. 우선 선형 회귀 분석을 통해 체내 프탈레이트 대사산물 농도와 초경 연령 사이 관계성이 있는지를 분석하였다. 또한 로지스틱 회귀 분석을 시행하여 프탈레이트의 삼분위 농도 수준에 따라 이른 초경의 비율에 차이가 있는지를 분석하였다. 선형 회귀 분석에서는 특별히 유의한 관련성이 나타난 대사산물은 없었다. 그러나 로지스틱 회귀 분석에서는 MnBP에서 가장 낮은 삼분위에 비해 가장 높은 삼분위에서, 가계 수입, 보호자 교육 수준 및 BMI를 보정하였을 때 이른 초경의 위험이 유의하게 증가하였다 (Adjusted OR: 2.12; 95% CI: 1.04, 4.30). 또한 프탈레이트 대사산물의 총합 (total phthalates)에서도 마찬가지로 가장 높은 삼분위에서 이른 초경의 위험이 증가함을 보였다 (Adjusted OR: 2.10; 95% CI: 1.03, 4.31). 본 연구의 결과는 한국에서 MnBP 및 전체 프탈레이트 수준이 이른 초경과 관계가 있을 수 있음을 제시하고 있다. 본 연구에서는 체계적 문헌 고찰을 통해 MEP, DEHP 대사산물 등에서 프탈레이트 노출과 초경 연령 사이 다양한 크기와 방향의 관련성이 있음을 확인할 수 있었다. 지역별 프탈레이트 노출의 분포와 함께 인종, 체지방, 가계 소득, 보호자 교육 수준, 비스페놀 A에 대한 노출과 같은 변수들이 초경과의 관련성에 영향을 줄 수 있었다. 또한 본 연구를 통해서 한국 청소년 여아에서 프탈레이트 노출과 이른 초경 연령 사이 관련성의 존재를 확인할 수 있었다.Phthalates are a group of chemicals to which people have constant environmental exposure while using plastics, toys, food packaging, and personal care products. Phthalates can influence pubertal timing through disruption of multiple systems of hypothalamus-pituitary-gonadal axis. Average age at menarche has been declining through the years worldwide as well as in Korea. Although experimental studies partly held exposure to endocrine-disrupting chemicals responsible for the change in pubertal onset, human epidemiologic evidence on relationship between phthalates and menarche is still inconsistent. In Chapter II, we conducted a systematic review to examine the association of prenatal and peripubertal exposure to phthalates with age at menarche. We searched relevant papers in databases of PubMed, EMBASE, and Web of Science, and included 13 studies in our review. Types of phthalates that repeatedly presented association with menarche were mono-ethyl phthalate (MEP) and metabolites of di-(2-ethylhexyl) phthalate (DEHP), although the direction of association varied. Inconsistency of the results from the included studies might be related to the period of exposure and distinct levels and distributions of phthalates in study regions. We reviewed covariates for the relationship between phthalate exposure and menarche, and identified age, race/ethnicity, maternal age at menarche, body fat status, poverty index, caregiver education, and co-exposure to bisphenol A. Race/ethnicity, family poverty, caregiver education, and co-exposure to bisphenol A can have confounding effect, while body fat status might also work as a partial mediator in the biological pathway. In Chapter III, we investigated the association between exposure to phthalates and early menarche in Korean middle-school girls, using data from Korean National Environmental Health Survey 2015–2017. Using linear regression analysis, we probed for possible linear association of eight phthalate metabolites with age at menarche. We also performed multiple logistic regression analysis to evaluate association between levels of phthalate metabolites and early onset of menarche. As a result, no significant association was found for any phthalate metabolites in linear regression. In logistic regression analysis, however, odds ratios (ORs) of early menarche were significantly increased for mono-n-butyl phthalate (MnBP) and for sum of all phthalates. When compared to group with the lowest level, high concentration group for MnBP presented significantly increased risk of early menarche (OR: 2.12; 95% confidence interval [CI]: 1.04, 4.30) after adjusting for household income, caregiver education, and body mass index. Furthermore, high concentrations of sum of all phthalates were associated with significant increase of risk for early menarche (OR: 2.10; 95% CI: 1.03, 4.31) after adjustment, compared to the lowest concentration group. Our results suggest that higher levels of MnBP and total phthalates might have association with early menarche in Korea. In this thesis, we conducted a systematic review and found that association between phthalate exposure and menarche existed with varying degrees and directions, especially for MEP and metabolites of DEHP. Distribution of phthalate exposure, along with covariates such as race/ethnicity, body fat status, family poverty, caregiver education, and co-exposure to bisphenol A might have affected the association. Furthermore, we discovered that exposure to certain phthalate metabolites might be associated with early menarche in Korean population.Chapter I. Introduction 1 I-1. Background 2 I-2. Objectives 6 Chapter II. Systematic review of association between exposure to phthalates and age at menarche 7 II-1. Introduction 8 II-2. Methods 9 II-3. Results 13 II-4. Discussion 24 II-5. Conclusion 29 Chapter III. Association of phthalates and early menarche in Korean adolescent girls from Korean National Environmental Health Survey (KoNEHS) 2015–2017 30 III-1. Introduction 31 III-2. Methods 32 III-3. Results 38 III-4. Discussion 47 III-5. Conclusion 52 Chapter IV. Summary and conclusion 53 REFERENCES 56 APPENDICES 67 ABBREVIATIONS 69 국문 초록 71석

Conventional endoscopic features are not sufficient to differentiate small, early colorectal cancer

AIM: To evaluate the depth of invasion of small, early colorectal cancers (ECCs) using conventional endoscopic features. METHODS: From January 2005 to September 2011, colonoscopy cohort showed that a total of 72 patients with small colorectal cancers with the size less than 20 mm underwent colonoscopy at the Yonsei University College of Medicine, Seoul, South Korea. Among them, 8 patients were excluded due to incomplete medical records. Finally, a total of 64 ECCs with submucosa (SM) invasion and size less than 20 mm were included. One hundred fifty-two adenomas with size less than 20 mm were included as controls. Nine endoscopic features, including seven morphological findings (i.e., loss of lobulation, excavation, demarcated and depressed areas, stalk swelling, fullness, fold convergence, and bleeding ulcers), pit patterns, and non-lifting signs, were evaluated retrospectively. All endoscopic features were evaluated by two experienced endoscopists who have each performed over 1000 colonoscopies annually for more than five years without knowledge of the histology. RESULTS: Among the morphological findings, the size of deep submucosal cancers was bigger than that of superficial lesions (16.9 mm vs 12.3 mm, P < 0.001). Also, demarcated depressed areas, stalk swelling, and fullness were more common in deep SM cancers than in superficial tumors (demarcated depressed areas: 52.0% vs 15.7%, P < 0.001; stalk swelling: 100% vs 4.2%, P < 0.001; fullness: 25.0% vs 0%, P = 0.001). Among deep SM cancers, 96% of polyps showed invasive pit patterns, whereas 19.4% of superficial tumors showed invasive pit patterns (P < 0.001). A positive non-lifting sign was more common in deep SM cancers (85.0% vs 28.6%, P < 0.001). Diagnostic accuracy of invasive morphology, invasive pit patterns, and non-lifting signs for deep SM cancers were 71%, 82%, and 75%, respectively. CONCLUSION: Conventional endoscopic findings were insufficient to discriminate small, deep SM cancers from superficial SM cancers by white light, standard colonoscopy.ope

Impact of tumor location on clinical outcomes of gastric endoscopic submucosal dissection

AIM: To determine whether there is a correlation between the location of the lesion and endoscopic submucosal dissection (ESD) outcome. METHODS: From January 2008 to December 2010, ESD of 1443 gastric tumors was performed. En bloc resection rate, complete resection rate, procedure time and complication rate were analyzed according to the tumor location. RESULTS: The rates of en bloc resection and complete resection were 91% (1318/1443) and 89% (1287/1443), respectively. The post-ESD bleeding rate was 4.3%, and perforation rate was 2.7%. Tumors located in the upper third of the stomach were associated with a longer procedure time and significantly higher rates of incomplete resection, piecemeal resection, and perforation than tumors below the upper third of the stomach. Posterior wall lesions had significantly longer procedure times and higher rates of incomplete resection and piecemeal resection than lesions in other locations. In multivariate analysis, posterior wall lesions and upper third lesions were significantly associated with incomplete resection and perforation, respectively. In post-ESD bleeding analysis, location was not a significant related factor. CONCLUSION: More advanced endoscopic techniques are required during ESD for lesions located in the upper third or posterior wall of the stomach to decrease complications and improve therapeutic outcomes.ope

중국의 식량안보 : 중국의 곡물 수급 현황과 그것이 세계에 미치는 영향

Thesis(masters) --서울대학교 국제대학원 :국제학과(국제지역학전공),2010.2.Maste

시간분해능 비접촉 원자힘 현미경을 이용한 나노크기 물기둥의 파열과정에 관한 연구

학위논문(박사)--서울대학교 대학원 :자연과학대학 물리·천문학부,2015. 2. 제원호.The nanometric water bridge is formed by capillary condensation between two close bodies in ambient condition, and is a commonplace phenomenon in nature. The water bridge plays an important role in the dynamic processes such as friction, adhesion and solvation, and is widely used in nanotechnology including dip-pen lithography, atomic force microscopy (AFM) and micro-electro-mechanical systems. Recently, it has been well known that the water bridge is essential in understanding the biological mechanisms of the ion-channel and protein folding. Therefore, it is important to have better and broader understanding of the mechanics, dynamics as well as kinetics of the capillary-condensed water bridge in ambient condition, from its formation to rupture. There have been extensive studies on the formation of the capillary water nanobridges over the last several decades. In most previous theoretical studies, the Kelvin-Laplace equation has been used to determine the size and shape of the water bridge, which forms at the nanoscopic contacts of solid surfaces. In particular, if the water bridge is formed in thermodynamic equilibrium, the radius of curvature of the bridge is equal to the Kelvin radius, and thus the bridge should break up or rupture at the distance equal to twice the Kelvin radius. However, the applicability of this approach to the capillary bridge at the nanoscale is still in debate. Based on the experimental observation and theoretical model of the water bridge, Riedo et al. have found that the volume of the stretched water bridge is proportional to the rupture distance. Because the curvature radius of the water bridge changed during the tip retraction, the state of the water bridge is not in thermodynamic equilibrium. From the results, they found that the stretched water bridge breaks up a distance that is much larger than twice of the Kelvin radius. In thermodynamic nonequilibrium, the rupture process of the water bridge is associated with the chemical potential gradients that may result in material transfer and trigger the irreversible bridge rupture. Thus, the Kelvin equation is not applicable in thermodynamic nonequilibrium. Men et al. applied the density functional theory, which is based on the energy barrier, in order to study the rupture process of the water bridge. Their work demonstrated the origin of the hysteresis behavior in the formation and rupture of the water bridge, and the rupture started by overcoming the energy barrier, which is so called the thermal activation process. Despite the established theoretical results, however, experimental works on the kinetics of the nanoscale rupture process in terms of thermal activation still lack, unlike the well studied capillary formation. In this Letter, we directly measure the activation time needed for the water bridge to be ruptured by using the quartz-tuning-fork (QTF) based AFM in ambient condition. We find that the activation time obtained at the various rupture distance exhibits random distribution and shows the characteristic exponential decay, which indicates that the rupture process follows the Poisson statistics, which is typical of the thermal activation processes. We also have measured the dependence of the rupture rate on the tip-sample distance as well as the temperature, from which we can estimate the values of the activation energy.Abstract i List of Figures vii Chapter 1 Introduction 1 1.1 Rupture kinetics of capillary-condensed water nanobridge . . . . 1 1.2 Time-resolved dynamic force microscopy by QTF based AFM . 3 1.3 Outline of this thesis . . . . . . . . . . . . . . . . . . . . . . . . 5 Chapter 2 Quartz Tuning-Fork for Force Measurement 9 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.2 Electrical Driven Quartz Tuning-Fork . . . . . . . . . . . . . . . 10 2.3 Mechanical Oscillation Amplitude of QTF . . . . . . . . . . . . 14 2.4 Electrical modulation QTF as a Force Sensor . . . . . . . . . . 15 2.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Chapter 3 Mechanical study of water nanobridge using QTF- AFM 20 iv3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.2 Quartz Tuning-Fork based Atomic Force Microscopy . . . . . . 21 3.3 Measurement of Mechanical Properties of water nanobridge . . 25 3.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Chapter 4 Rupture Process of water nanobridge 31 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 4.2 Activation Process associated with Rupture of water nanobridge 32 4.2.1 Time-Resolved Dynamic Force Microscopy . . . . . . . 32 4.2.2 Rupture rate of water nanobridge . . . . . . . . . . . . 34 4.3 Thermal Enhancement of Rupture Rate . . . . . . . . . . . . . 44 4.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Chapter 5 Chapter 5 59 5.1 Summary and Perspective . . . . . . . . . . . . . . . . . . . . . 59 Appendix A 62 A.1 Phase behavior of rupture process for water nanobridge . . . . 62 Appendix B 64 B.1 Actual and Apparent Probability . . . . . . . . . . . . . . . . 64 Appendix C 67 C.1 Spectral fl uctuations on excitonic transitions of InGaAs SQDs 67 C.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 67 vC.1.2 Optical Fiber Probes for Low-Temperature Near-fi eld Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . 69 C.1.3 Spectral Random Fluctuation of InGaAs SQDs . . . . 71 초록 ........82Docto

The Debate on Military Use of Colonial Koreans in the Japanese Army Before and After the March First Movement

이 글은 2018년도 도쿄대학(東京大学) 제출 박사학위논문 제3·6장의 내용을 수정·보완하여, 『일본비평』 제21호 특집의 취지에 맞도록 새로이 집필한 것이다The First World War (1914~18) and the March First Movement (1919) shook the ruling order of Japanese imperialism. With these events as the momentum, Imperial Japan, as well as Japanese Army, sought the reorganization of imperial ruling order. The Japanese Korean Army (Chosen-gun) was optimistic about the possibility of assimilating colonial Koreans and using them in the military. Therefore, to promote the assimilation of Koreans, the Army insisted that Military Academy should be open to Koreans and Korean volunteer units should be organized. Also, the reinforcement of deployed forces in Korea was requested, partly to accept Koreans into the Army. These stances remained firm in spite of the shock from the March First Movement. On the other hand, the Ministry of War (Rikugunsho) focused on political, economic, and military legitimacy. For them, the military use of colonial Koreans was the final goal to be realized after assimilating Koreans enough for the conscription law to be enforced in Korea. Also, the March First Movement weakened their optimism about the possibility of such assimilation. As a result, the Ministry of War remained negative to the military use of Koreans until the mid-1930s.1914~1918년의 제1차 세계대전 및 1919년의 3.1운동의 발발은 일본의 제국 지배 질서를 동요시켰다. 이를 계기로 일본은 기존의 제국 지배 질서의 재편을 모색하게 되었으며 이는 육군도 마찬가지였다. 그중 아카시 모토지로, 이구치 쇼고, 우쓰노미야 다로 등 조선헌병대 혹은 조선군에서 활동한 이 들은 영국·프랑스 등 구미 제국의 식민지 군대의 선례를 중시하였고, 또 병합 직후부터 식민지 조선 인의 동화 및 그 군사적 이용 가능성을 낙관하였다. 따라서 조선에서 징병을 실시할 수 있을 만큼의 동화를 촉진한다는 조선 지배 정책의 측면에서 조선인에게 육사의 문호를 개방하거나 조선인 지원 병 부대를 편성하는 등 군이 앞장서서 조선인을 군사적으로 이용할 것, 그리고 이를 전제로 하여 조선 주둔 병력을 증강할 것을 주장하였다. 이러한 주장은3 .1운동의 충격 속에서 더욱 절실해졌다. 반면 주로 육군 중앙에서 활동한 다나카 기이치는 러일전쟁 이후 대러시아 작전·군비라는 당면 의 목표, 이를 실현하기 위한 국가 예산과 국내 정치적 환경이라는 정치·경제·군사적 합리성을 중 시하였다. 그에게 조선인의 군사적 이용은 조선에서 징병을 실시할 수 있을 만큼의 동화가 이루어진 다음에야 실행할 수 있는 최종적인 목표에 불과했으며, 또 조선인을 일본 군대에 받아들이기 위해 조 선군을 증강한다는 발상도 가지고 있지 않았다. 그뿐만 아니라 3.1운동의 발발은 조선인의 동화 가 능성에 대한 기존의 낙관적 인식을 약화시켰다. 따라서 그는 조선인 장교의 재생산, 조선인 부대 편성 및 이를 전제로 한 조선군 증강에는 소극적이었다. 이와 같은 조선인의 군사적 이용에 관한 조선군과 육군 중앙의 대립은 1930년대 중반까지 이어지게 되는 것이다.이 논문은 2019년 서울대학교 일본연구소 일본학연구지원사업의 지원을 받아 수행되었

바이오 센싱을 위한 유기-무기 혼성 나노 물질 개발

학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2016.8 ,[ix, 114 p. :]In recent years, an intense interest has grown in the synthesis of functional hybrid organic-inorganic nanostructured materials. Several research groups have reported different hybrid organic-inorganic nanomaterials by employing organic materials (such as proteins, amino acids, and organic acids) and inorganic materials (such as metal ion and metal nanoparticles). Based on the aforementioned unique combinations of organic-inorganic hybrid nanomaterials, we have developed a novel nanostrucuted materials employed in sensing different biomolecules such $H_2O_2$, glucose, choline, and acetyl choline. In chapter 2, we developed a simple but efficient method to synthesize protein-inorganic hybrid nanostructures with a flower-like shape (nanoflowers), which relies on sonication to facilitate the synthesis of the nanoflowers. With this technique, we synthesized nanoflowers containing laccase as a model enzyme and copper phosphate within 5 minutes at room temperature. The resulting laccase nanoflowers yielded greatly enhanced activity, stability, and reusability, and their usefulness was successfully demonstrated by applying them in the colorimetric detection of epinephrine. In chapter 3, we reported sonicated bovine serum albumin (BSA)-incorporated $Cu_3(PO_4)_2.3H_2O$ nanoflowers (SBSA-NFs) possess an intrinsic peroxidase-mimicking activity and also demonstrate that glucose oxidase (GOx) incorporated in nanoflowers showed enhanced activity compared with free GOx for the detection of target glucose in the cascade reaction, due to the synergistic effect arises from improved spatial coupling between enzymes and peroxidase-mimicking copper(II). In chapter 4, we synthesized different amine grafted MIL-100(Fe) metal organic frameworks (MOFs) and found that N,N,N&amp;apos;,N&amp;apos; Tetramethyl- 1, 4- butanediamine (TMBDA)-MIL-100(Fe) showed excellent peroxidase-mimicking activity. Further, we developed detection strategy by employing TMBDA-MIL-100(Fe) for the detection of biomolecules and obtained excellent limit of detection for $H_2O_2$, choline, and acetylcholine with $0.329 \mu M$ , $0.027 \mu M$, and $0.036 \mu M$ respectively. The diagnostic capability of this method is also demonstrated by detecting choline and acetyl choline in serum, showing its great potential in practical application.한국과학기술원 :생명화학공학과

Metabolic syndrome is an independent risk factor for synchronous colorectal neoplasm in patients with gastric neoplasm

BACKGROUND AND AIM: There are no data on how metabolic syndrome (MetS) affects the prevalence of synchronous colorectal neoplasm (CRN) in gastric neoplasm (GN) patients. The aim of this study was to investigate a model for risk stratification for colorectal screening by evaluating the clinical characteristics of synchronous CRN in GN patients classified according to the presence of MetS. METHODS: A cross-sectional, case-control study of 492 patients (368 males and 124 females) with GN, and 492 age-matched healthy controls undergoing simultaneous upper endoscopy and colonoscopy, was conducted. RESULTS: The GN group involved 446 patients without MetS, and 46 patients with MetS. In total, 177 (39.7%) and 28 (60.9%) synchronous CRN were detected in GN patients without MetS and with MetS, respectively (P=0.006). A total of 143 (34.7%) synchronous colorectal adenomas were detected in GN patients without MetS, whereas 17 (48.6%) were detected in GN patients with MetS (P=0.101), as well as more synchronous colorectal cancers (11.2% vs 37.9%, P<0.001). A multivariate logistic regression analysis revealed that the presence of GN (OR=1.54, 95% CI: 1.18-2.00, P=0.001) and the presence of MetS (odds ratio=1.82, 95% confidence interval: 1.19-2.78, P=0.006) were significant independent risk factors associated with the prevalence of CRN. The frequency of synchronous CRN in GN patients with MetS was 1.96 times greater than that in the GN group without MetS. CONCLUSION: The risk of synchronous CRN is significantly increased by the presence of GN, especially in MetS patients. Screening for synchronous CRN is highly recommended for GN patients with MetS.ope