한국인 사망과 관련된 건강 행태요인의 복합위험도에 관한 코호트 연구

학위논문 (석사)-- 서울대학교 대학원 : 의학과 예방의학 전공, 2013. 2. 유근영.Objectives Lifestyle factors such as obesity, smoking habit and alcohol drinking habit are known to be associated with increased risk of all-cause mortality in Korea. However, little has examined the association of combined life-style factors with the risk of mortality. Methods The study population of 15,740 participants over 20 years old was selected from the Korean Multi-center Cancer Cohort (KMCC) study. Information on lifestyle factors was obtained through structured questionnaire interview. The total number of persons who completed the follow-up through the Death Certificate database of the National Statistical Office was 145,218.4 person-years by the end of December 31, 2008. The total number of death during the study period was 1,094 persons, and 474 deaths were due to cancer and 229 persons were due to cardio-vascular diseases. Each risk factor was dichotomized based on the previous study as followsbody mass index (BMI) under 22.6 or over 27.5 kg/m2 versus 22.6~27.5 kg/m2current or past smokers versus non-smokersnon-drinkers or drinkers with alcohol amount of 90 gram per week or more versus drinkers less than 90 grams per week. Combined effect of three risk factors was estimated in two different waysaccording to the number of risk factors qualitatively, and to the combined risk scores ranged from 0 to 14 quantitatively. The hazard ratios (HRs) and 95% confidence intervals (CI) for mortality were estimated by Coxs proportional hazard regression model adjusting for age, sex, locality, education, marriage, and the past history of chronic diseases. Results The risk of dying was 1.47 times (95% CI = 1.27~1.69) in BMI, 1.50 times (95% CI=1.25~1.79) in smoking habit, and 1.36 times (95% CI=1.08~1.72) higher in alcohol drinking habit than the baseline hazard. The HRs for cancer death was 1.35 (95% CI=1.10~1.66) in BMI, and 1.75 (95% CI=1.32~2.33) in smoking habit, but not statistically significant in alcohol drinking habit. The HRs for both all-causes mortality and cancer mortality showed linearly increasing pattern with statistical significant according to the number of risk factor (p<0.001). Overall, the combined effect of lifestyle factors was more prominent in female. Particularly noteworthy was that the risk of dying increases according to the combined risk score increasing (p<0.001). Subjects with highest score (1`0~14) had significantly at the greatest risk of deaths (HR=3.46, 95% CI=1.89-6.32). The risk of dying was more prominent in female and participants under age<60. Conclusions This study confirms abnormal BMI, smoking habit and alcohol drinking habit are major risk factor of premature deaths, as well as cancer death in Korea. Combined effect of lifestyle factors would additively be associated with marked increased risks of both all-causes and cancer-specific death in Korea.Abstract ⅰ Contents iv List of tables v List of figures viii List of abbreviation ix Introduction 1 Materials and Methods 5 Study population and follow-up for outcomes 5 Measurement of lifestyle factors 7 Classification of risk lifestyle factors 8 Estimation of the combined effect 9 Statistical analysis 11 Results 14 Discussion 20 References 66 Abstract in Korean 71Maste

Timing of Admission to the Surgical Intensive Care Unit is Associated with in-Hospital Mortality

Purpose The relationship between the timing of admission (work-hours or after-hours) to the intensive care unit (ICU) and mortality among surgical ICU (SICU) patients is unclear. This study aimed to investigate whether admission to SICU during after-hours was associated with in-hospital mortality. Methods This retrospective cohort study was conducted in a tertiary academic hospital. The data of 571 patients who were admitted to the SICU and whose complete medical records were available were analyzed. Work-hours were defined as 07:00 to 19:00 Monday to Friday, during which the ICU was staffed with intensivists. After-hours were defined as any other time during which the SICU was not staffed with intensivists. The primary outcome measure was in-hospital mortality according to the time of admission (work-hours or after-hours) to the SICU. Results A total of 333 patients, were admitted to the SICU during work-hours, and 238 patients after-hours. Unplanned admissions (47.1% vs. 33.3%, p < 0.001), acute physiology and chronic health evaluation II score ≥ 25 (23.9% vs. 11.1%, p < 0.001), the need for ventilator support (34.0% vs. 17.4%, p < 0.001), and the use of vasopressors (50.0% vs. 33.3%, p < 0.001) were significantly higher in the after-hours group compared with the work-hours group. Multivariate analyses revealed that the timing of SICU admission was an independent predictor of in-hospital mortality (odds ratio, 2.526; 95% confidence interval, 1.010-6.320; p = 0.048). Conclusion This study showed that admission to the SICU during after-hours was associated with increased in-hospital mortality.ope

Isolated Splenic Metastasis from Colorectal Carcinoma

Most splenic metastasis occurs in patients with the widespread visceral metastasis. However, isolated splenic metastasis is very rare. Here we report an isolated splenic metastasis in a patient with colon cancer without any other metastasis and a review of the literature are presented. A 57-year female underwent right hemicolectomy for adenocarcinoma of ascending colon on February, 2004 and the stage of carcinoma was T3N2M0. On August 2004, she hospitalized due to isolated splenic metastasis. The serum carcinoembryonic antigen level was 1.69 ng/ml. An abdominal CT scan revealed a 1 cm sized metastatic mass at the hilum of the spleen. The same finding was shown on MRI and PET. There was no other recurrence or metastatic evidence in radiologic study. Splenectomy was performed and pathologic result of the splenic tumor was metastatic adenocarcinoma from colon cancer. After operation, she was treated with adjuvant chemotherapy. It may be necessary to attend the splenic metatasis in patients who underwent curative resection for colorectal cancer even though splenic metastasis is very rare.ope

Effect of Yogurt Enriched Water-soluble Fiber on Functional Constipation

Purpose Although a diet that is rich in fiber is widely recommended to prevent and treat constipation, the efficacy of fiber supplements with yogurt has not been studied sufficiently. The aim of this study was to evaluate the effect of a yogurt enriched water-soluble fiber on the various symptoms of constipation in female adults with functional constipation. Methods We did a double-blind and case-controlled study between two groups (placebo vs. fiber group), which were randomly allocated out of 42 subjects with functional constipation by using Rome II criteria. Bowel habits, daily nutritional intakes and physical activities were determined by using a questionnaire, and the segmental colonic transit time was evaluated three times: before treatment, after 4 weeks of treatment, and at the end of the study (2 weeks after treatment). Results After 4 weeks of treatment, all defecation symptoms tested, except manual evacuation, showed significant improvements in the fiber group; fiber-enriched yogurt increased the number of bowel movements (P=0.002), reduced the presence of hard stools (P=0.001), improved the frequency of straining (P=0.048), the sense of incomplete evacuation (P=0.013), and the sense of anorectal obstruction (P=0.032). The total colonic transit time was shortened after intake of fiber-enriched yogurt (P=0.023). Satisfactory relief was significantly higher in the fiber group (P=0.011). Conclusions Functional constipation may be improved with water-soluble fiber supplements in yogurt without serious side effects.ope

Prognostic Factors and Survival Rate of Ampulla of Vater Cancer after Curative Surgery

Purpose: Ampulla of Vater cancer has a more favorable prognosis than other malignant tumors of the periampullary region, but prognostic factors have not been identified. The aim of this study was to evaluate the prognostic factors of ampulla of Vater cancer from a single hospital experience. Methods: The medical records of the 102 patients with ampulla of Vater cancer which underwent curative surgery between 1992 and 2002, were reviewed. All specimens were critically reviewed by an expert pathologist. The relationships between survival and the clinicopathological variables were assessed. Results: In 120 patients that presented with ampulla of Vater cancer, 102 (85%) were resected. The 5 year survival rate was 69.1%. A univariate analysis showed the survival was closely related to gender, the tumor gross morphology, invasion depth and lymph node metastasis. A multivariate analysis identified two significant factors; the depth of invasion and gender. Twenty nine of the 102 patients suffered a recurrence. Conclusion: The depth of invasion and gender were independent significant prognostic factors of resectable ampulla of Vater cancer. Careful observation is essential for liver metastasis after surgery, especially in patients that have these factors.ope

학습부진 진단을 위한 연산유창성 검사 개발 및 타당화

학위논문(석사)--서울대학교 대학원 :협동과정 특수교육전공,2004.학위논문(석사)-

인체간암세포에서 고추의 매운 성분인 capsaicin에 의해 유도되는 Nrf2 활성화 및 항산화 효과를 가진 heme oxygenase-1의 발현 기전

학위논문(석사) --서울대학교 대학원 :약학과,2007.Maste

Inhibitory Effect of coptisine on Epithelial-to-Mesenchymal Transition

학위논문 (석사)-- 서울대학교 대학원 : 약학과, 2014. 8. 이상국.Epithelial-to-mesenchymal transition (EMT)은 상피세포 (epithelial cell)가 고유의 특성과 cell-cell junction을 잃고 간엽세포 (mesenchymal cell)의 형태와 성질을 획득하는 과정으로 암의 침윤, 전이의 중요한 특징이다. 본 연구에서는 사람 폐암 세포주인 A549를 이용하여 황련 (Coptis japonica)에서 분리된 isoquinoline alkaloid계 물질인 coptisine의 EMT 억제 효능을 확인하고 그 작용기전을 연구하였다. A549세포에 대한 세포 증식 억제 효능을 평가한 결과, coptisine에 의해 세포의 증식이 시간 및 농도 의존적으로 억제됨을 확인하였다 (IC5042.7 μM (24h), 15.9 μM (48h), 8.4 μM (72h)). EMT와 관련한 작용기전을 알아본 결과, coptisine은 암의 진행을 억제하고 세포간 연결을 유지하여 이동성을 감소시키는 E-cadherin의 유전자와 단백질의 발현을 모두 증가시켰다. 또한 E-cadherin의 내인성 억제제로 작용하는 Snail에도 영향을 미쳐 유전자와 단백질의 발현을 억제하였다. 그 외에 EMT에서 특이적으로 변화하는 matrix metalloproteinase-2 (MMP-2), vimentin, N-cadherin 등에 영향을 미치는 것을 확인하였다. 또한 wound healing assay, colony dispersion assay, invasion assay 등을 통해 coptisine이 A549 세포의 이동성, 침윤성을 저해함을 밝혔다. 더욱 구체적인 EMT 저해 기전을 알아보기 위해 transforming growth factorβ1 (TGFβ1)를 처리한 A549 세포에서 coptisine의 효과를 살펴본 결과 Extracellular signal-regulated kinases (ERK)1/2, Akt, glycogen synthase kinase3β (GSK3β) 의 인산화를 억제하였으며 Smad 신호전달체계도 억제하였다. 이로인해 coptisine이 Snail의 상위 신호전달체계에 영향을 미쳐 Snail의 발현을 저해하는 것을 알 수 있으며, 이러한 coptisine의 Snail 억제와 E-cadherin 증가 작용을 통해 EMT가 효과적으로 저해되는 것으로 여겨진다. 따라서 coptisine은 암 전이 치료의 천연 후보 물질이 될 수 있을 것으로 사료된다. 골 항상성 (bone homeostasis)은 파골세포 (osteoblast)의 골 흡수 (bone resorption)와 조골세포 (osteoblast)의 골 형성 (bone formation)에 의해 유지되며 항상성이 파괴될 경우 골다공증과 같은 골 관련 질환이 발생한다. 조골세포는 Wnt 신호전달체계에 의해 분화가 촉진되어 extracellular matrix (ECM) 단백질의 발현과 무기질화 (mineralization)가 일어나며 이러한 이유로 Wnt 신호전달체계의 활성화는 골다공증 치료제의 새로운 표적으로 여겨지고 있다. 본 연구에서는 천연물 중 바디나물 (Angelica decursiva)에서 분리한 furano-coumarin계열의 nodakenetin이 Wnt 신호전달체계를 활성화시켜 조골세포의 분화에 영향을 미치는지 살펴보았다. Nodakenetin은 인간 신장 배아 세포주인 HEK293 세포와 쥐 전조골세포주인 CM3T3-E1 세포에서 T-cell factor/Lymphoid-enhancing factor (TCF/Lef)의 전사활성을 크게 증가시켰다. Wnt 신호전달체계의 저해자인 Dickkopf1 (DKK1)을 감소시키고 반대로 β-catenin은 크게 증가시켰다. Wnt 신호전달체계의 표적 유전자의 발현을 증가 시켰으며 그 중 조골세포 분화와 관련된 runt-related transcription factor2 (Runx2)의 유전자와 bone morphogenetic protein (BMP)의 발현을 증가시켰다. MC3T3-E1 세포에서 Alizarin red S staining과 alkaline phosphatase (ALP) activity를 수행한바, 무기질화가 증가하고, ALP가 활성화되어 조골세포의 분화를 촉진하는 것을 확인하였다. 결과적으로 nodakenetin은 조골세포의 분화를 촉진하는 골다공증의 치료에 유효한 선도물질로 사료된다.Coptisine, an isoquinoline alkaloid, is a component of Coptis japonica Makino (Ranunculaceae). C. japonica has been used as a traditional medicine for the treatment of fungal infection and inflammation. The present study was designed to investigate the inhibitory effect of coptisne on epithelial-to-mesenchymal transition (EMT) in cancer cells. EMT is a differentiation switch in which polarized epithelial cells differentiate into contractile and motile mesenchymal cells. Coptisine showed a potential growth inhibitory activity in human lung cancer A549 cells (IC50= 8.4 μM for 72 h). Coptisine increased E-cadherin promoter activity and the expressions of E-cadherin protein and mRNA level. In addition, coptisine down regulated the EMT-related protein expressions including Snail, MMP-2, vimentin, and N-cadherin. Coptisine also suppressed the expressions of phosphorylated ERK1, Akt and GSK3β in TGFβ-treated or untreated A549 cells. These results indicated that coptisine inhibited upstream signaling of Snail. Further study revealed that coptisine inhibited cell migration in the wound healing and colony dispersion assays. Cell invasion was also mediated by coptisine in the matrigel invasion assay. Coptisine might have a potential anti-metastatic activity, and thus will be a lead candidate as an anti-cancer agent. Nodakenetin, a furanocoumarin compound, is a component of Angelica decursiva (Umbelliferae). A. decursiva is used as a traditional medicine to relive the symptoms associated with allergy and skin whitening. In the present study, the effect of nodakenetin anti-osteoporosis activity was evaluated. The Wnt signaling pathway is an evolutionarily conserved pathway involved in various biological events, including stem cell differentiation, cell motility, and cell proliferation. Activation of the Wnt signaling is known to contribute to differentiation in osteoblast. Nodakenetin was found to have an activation effect β-catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells. The activation sequentially stimulated of Wnt signaling target genes and β-catenin in both HEK293 cells and MC3T3-E1 cells. In addition, nodakenetin surppressed the expression of DKK1, a Wnt inhibitor. Nodakenetin is considered a potent Wnt activator. Nodakenetin markedly increased alkaline phosphatase (ALP) activity and extracellular matrix (ECM) calcium deposits in osteoblast cells. These data demonstrated that nodakenetin activated the Wnt signaling, which increased BMPs and Runx2 expressions, and stimulated osteoblast differentiation. Therefore, the activation of Wnt signaling by nodakenetin is considered to be associated with the anti-osteoporotic activity.초 록 i 목 차 iv 그 림 목 차 vii 표 목 차 x Part 1. 천연물 유래 Alkaloid계 Coptisne의 Epithelial-to- Mesenchymal Transition 억제 연구 1 I. 서 론 2 II. 실험 재료 및 방법 6 A. 실험 재료 6 1. 시약 6 2. 시험물질 7 3. 세포 배양 7 B. 실험 방법 9 1. 세포 독성 실험 (SRB assay) 9 2. Transfection and luciferase reporter gene assay 10 3. Western blot analysis 10 4. Reverse transcription real-time PCR 11 5. Wound healing assay 13 6. Colony dispersion assay 13 7. Invasion assay 13 III. 실험 결과 16 1. Coptisine의 사람 폐암 세포에 대한 증식 억제 효과 16 2. E-cadherin promoter에 미치는 효과 18 3. EMT관련 단백질과 mRNA의 발현에 미치는 효과 20 4. 세포의 이동성에 미치는 효과 23 5. 세포의 침윤성에 미치는 효과 26 6. ERK와 Akt의 인산화에 미치는 효과 28 7. TGFβ를 처리한 A549에서 ERK와 Akt의 인산화, E-cadherin과 Snail의 발현에 미치는 효과 30 8. TGFβ관련 단백질인 Smad에 미치는 효과 32 IV. 고 찰 34 Part 2. 천연물 유래 Coumarin계 Nodakenetin의 조골세포 분화 연구 36 I. 서 론 37 II. 실험 재료 및 방법 41 A. 실험 재료 41 1. 시약 41 2. 시험물질 42 3. 세포 배양 42 B. 실험 방법 44 1. 세포 독성 실험 (MTT assay) 44 2. Transfection and luciferase reporter gene assay 44 3. Western blot analysis 45 4. Reverse transcription real-time PCR 46 5. Measurement of Alkaline phosphatase (ALP) activity 47 6. Measurement of extracellular matrix (ECM) calcium deposits 47 III. 실험 결과 50 1. Nodakenetin의 β-catenin/T-cell factor (TCF) transcriptional activity에 미치는 효과 50 2. Wnt signaling pathway에 관련된 단백질에 미치는 효과 53 3. 조골세포에서 Wnt signaling pathway에 관련된 단백질에 미치는 효과 56 4. 조골세포 분화에 미치는 효과 59 5. BMPs와 Runx2에 미치는 효과 62 IV. 고 찰 64 참 고 문 헌 66 Abstract 70Maste

A Study on Pintings of Eight Royal Tombs and Historic Sites in Hamgyong Province in Joseon Dynasty

함경도는 북방 변경지대이며 태조 이성계와 그 선조들의 유적이 있는 豊沛之鄕으로 지칭되었다. 조선은 건국 직후부터 세종조에 걸쳐 수차례 두만강 일대를 공략하여 여진족을 몰아내고 6진을 세워 강역을 확보하였다 이후 함경도 국방을 위해 徙民政策과 동시에 이 지역의 유력한 세력을 회유하고 행정체계에 편입시키는 士官制를 시행하였다. 15세기 중엽 이후는 국경이 확보되고 사회가 안정되면서 함경도에 대한 관심은 점차 줄었다. 그러나 1712년 (숙종 38) 조선과 청 사이의 白頭山定界는 함경도를 비롯한 북방 지역의 인식을 새롭게 하는 계기가 되었다. 영조대에는 국왕중심의 정치체제를 중시하면서 왕실의 권위를 높이려는 정책의 일환으로 왕실사적 현창사업이 추진되면서 함경도 왕실사적의 정비가 본격화된다. 1736년(영조 12) 흑석리에 태조 탄생 기적비를 세우자는 영흥 유생들의 발의를 시작으로 1747년 함흥출신 위창조가 함경도 왕실 사적을 모아 『북로능전지』를 편찬하였고, 1758년 국가 차원의 『북도능전지』 편찬 사업이 진행되었다. 이러한 사업은 정조대에도 그대로 계승되어 흑석리·독서당·치마대 등에 기적비를 세우고, 1795년 『成興本宮儀式 · 『永興本宮儀式』을 간행하여 함흥과 영흥의 본궁의식을 정비하였다. 또한 1797년 桓祖의 八回寶甲(480주년)을 맞아 편찬한 『豊沛賓興錄』은 함흥과 영흥본궁에서 제향을 지내고 취재한 科文을 모아 엮은 것으로, 국왕 정조의 주도로 조선 건국 위업과 왕조의 위상을 높이려는 의지를 잘 보여주는 사례이다. 홍양호가 1799년 정조에게 함경도 왕실사적에 대해 기록한 『興王肇乘』을 올린 것도 이러한 당시 분위기를 반영한 것이었다. > 역시 함경도의 함흥 · 영흥 · 안변 · 문천 등에 소재한 태조 四代祖 및 그 妃에 대한 陵·殿宮의 위치와 그 구조를 그린 일종의 圖形이다. 규장각에는 北道陵殿圖形, 장서각과 문화재청에는 北道各陵殿圖形이란 이름으로 각각 한 부씩 소장되어 총 3부가 전한다. 이 자료는 태조 즉위 이후 왕으로 추존된 태조의 4대 조상들의 능묘, 사적 및 옛터 등을 정리하여 조선 왕조의 정통성 확립에 활용되었으며, 이후 조선왕실 능묘 조성에도 지속적인 영향을 미쳤던 점에서 연구 가치가 높다. >에 대한 제작시기는 선생 연구마다 다소 차이를 보인다. 제1설은 규장각본의 세주를 근거로 1755년경에서 제작된 것으로 추정하였고, 나머지 2본은 적어도 1776년 이전 영조연간 그려진 것으로 추정하였다. 제 2설은 >과 동일한 내용으로 제작된 낱장의 함흥본궁과 경흥전을 촬영한 유리건판 사진 2점의 우측 하단 기록을 근거로 1759년 9월 洪象漢(1701~1769)이 북도 순찰 후 올린 도형과 관계있을 것으로 추정하였다. 제3설은> 중 제12폭 에 보이는 1716년(숙종 42) 독서당 기적비를 1797년 반룡산 치마대 옛터에 정조의 어제를 새긴 사적비로 간주하고, 그 비각을 세운 1808년을 제작 연도의 상한으로 보았다. 제3설 이후 미술사학계에서는 19세기 제작설이 일반화되고 있다. 따라서 필자는 >에 모사된 사적에 대한 사료를 상세히 검토하기 위해 1747년(영조 23) 필사된 『北路陵殿志』와 이를 1758년(영조 34) 수정·보완하여 목판본으로 간행한 『北道陵殿誌』의 내용과 비교·고찰을 선행할 것이며, 이를 토대로 각 능전의 사적 연혁을 밝혀 구체적인 제작 시기를 유추하려 한다. 또한 > 화면 위의 注記와 화풍을 비교·분석하여 양식적 특징을 살펴봄으로써, 조선후기 왕실 산릉도의 典型을 유추하는 데도 의미 있는 작업이 될 것이다. 이를 위해 19세기 그려진 규장각 소장 함경도 소재 8릉 관련 도형과 비교하여 상호 연관성은 물론, 화풍 상의 차이를 살펴볼 것이다. This study is aimed at reviewing the paintings of eight royal tombs and historic sites in Hamgyong Province in Joseon Dynasty. Bukdo Neungjeon-dohyeong (北道陵殿圖形) painted the eight royal tombs and historic sites in Hamgyong Province are three Albums at Gyujang-gak, Jangseo-gak and Cultural Heritage Administration. After come to throne, the first king of the Joseon Dynasty, Yi Seong-gye launched to honor his eight forebears as kings and queens and to worship at national level. So the eight tombs and historic sites of Yis ancestors in Hangyong Province were regarded as a royal sanctuary. Bukdo Neungjeon-ji (北路陵殿志) is documentary of eight royal tombs and historic sites in Hamgyong Province in Joseon Dynasty. According to the book, King Yeongjo(r. 1724-1776) had Jo Yeong-guk (1698-1760) to paint royal historic sites in Hamgayong Province to commemorate the first King Taejos 420th birthday in 1755. Bukdo Neungjeon-dohyeong of the album at Gyujang-gak included an explanation in 1755 King Yeongjos reign on Heukseok-ri(birth town of Taejo). Two albums of Jangseo-gak and Cultural Heritage Administration copied the album of Gyujang-gak and they have delicate difference in style each other. Two albums of Jangseo-gak and Cultural Heritage Administration correspond closely in style and contents. There is not the memorial stone with inscription written by king Jeongjo(r. 1776-1800) in 1787 on Gyeongheung-jeon(a former residence of Teajo) of two albums, therefore they were painted in at least 1787. Bukdo Neungjeon-dohyeong and Bukdo Neungjeon-ji are valuable as a historical materials to secure Joseon Dynastys legitimacy and reference of another royal tombs