한국 내 다이빙으로 인한 척수 손상 환자에서 재활 결과

학위논문 (석사) -- 서울대학교 대학원 : 의과대학 임상의과학과, 2021. 2. 방문석.Background: As economy of South Korea grows, interest in leisure activity and sports has been increasing, and diving is no longer a rare cause of traumatic spinal cord injury (SCI). To prevent SCI due to diving accident, general information and risk factors are necessary, but there has been a paucity of studies about SCI due to diving accident in South Korea. Objectives: The purpose of this study is to describe the demographics and neurological outcomes in people with diving injuries of the cervical spine. We also investigated circumstances at the time of diving injury in order to identify the risk factors, and general rehabilitation outcomes after SCI. Methods: People with SCI due to diving accident who went to Seoul National University Hospital from 2000 to 2019 and National Traffic Injury Rehabilitation Hospital from 2014 to 2019 were investigated. The electronic medical records were reviewed for medical and neurologic information. Then, telephone interviews were performed with questionnaire regarding specific circumstances at the time of injury and social status. Results: A total of 33 people with SCI due to diving accident were analysed and 27 persons responded to telephone interviews. 32 (97%) participants were male and 27 (81.8%) were younger than 40 years at the time of injury. American Spinal Injury Association A grade was the most common with 16 (48.5%) participants, and C4 was the most common neurologic level of the injury (n=13, 39.4%). SCI due to diving accident most commonly occurred in swimming pool in holiday lodge (n=12, 36.4%). 5 out of 13 married couples with motor complete deficit were divorced or separated after injury. 8 out of 33 persons started their job or study again after injury, with mean (SD) return time 33 (24.4) months. Conclusions: SCI resulting from diving accident causes not only functional severe impairment but also changes of marital and employment status. Our study can be used as basic source of education and publicity needed to prevent further SCI due to diving accident.배경: 한국의 경제가 발전하면서, 레저 및 스포츠 활동에 대한 관심은 늘어나고 있으며, 한국에서 다이빙은 더 이상 외상성 척수 손상의 드문 원인이 아니다. 다이빙으로 인한 척수 손상의 예방을 위해 환자들의 기본적인 정보와 위험 요소에 대한 정보가 필수적이나, 현재까지 한국 내 다이빙으로 인한 척수 손상에 대한 연구는 거의 이루어지지 않았다. 목적: 본 연구는 다이빙으로 인한 척수 손상 환자들의 인구학적 및 신경학적 결과를 기술하는데 목적이 있으며, 사고 당시 상황을 조사함으로써 다이빙으로 인한 척수 손상의 위험 요소를 파악하고자 하였다. 더불어, 사고 전후 결혼 및 직장 변화를 비롯한 재활 결과를 알아보고자 하였다. 방법: 2000년부터 2019년 사이 서울대학교병원 및 2014년부터 2019년 사이 국립교통재활병원에 내원한 다이빙으로 인한 척수 손상 환자들을 대상으로 분석하였다. 전자 의무기록 후향적 분석을 통하여 의학적 및 신경학적 소견을 추출하였고, 설문지를 이용한 전화 인터뷰를 통하여 사고 당시 구체적인 상황 및 사고 전후 사회적인 상태 변화에 대한 정보를 얻었다. 결과: 총 33명의 다이빙으로 인한 척수 손상 환자들이 분석되었으며, 그 중 27명이 전화 인터뷰에 응답하였다. 연구 대상자 중 32명(97%) 은 남성이었으며, 27명 (81.8%)는 사고 당시 40세 이하였다. American Spinal Injury Association A 등급이 16명(48.5%) 으로 가장 흔하였으며, C4가 13명으로 가장 흔한 신경학적 손상 수준이었다. 가장 많이 다이빙 사고가 발생한 곳은 펜션에 있는 수영장으로, 12건(36.4%) 이었다. 사고 당시 결혼 상태였던 완전 마비 13명 중 5명은 사고 이후 이혼 또는 별거하였다. 연구 대상자 33명 중 8명은 사고 발생 평균 33개월 (표준편차 24.4개월) 이후 직장 또는 학업에 복귀하였다. 결론: 다이빙으로 인한 척수 손상은 심각한 기능적 저하뿐 아니라 결혼 및 직업에도 많은 영향을 미친다. 본 연구는 다이빙으로 인한 척수 손상의 예방을 위한 교육 및 홍보를 위한 기본 자료로 활용될 수 있다.Abstract ..........................................................................................................i Table of contents........................................................................................ iii List of tables and figures........................................................................... iv Introduction ..................................................................................................1 Materials and methods.................................................................................4 Results............................................................................................................6 Discussion ....................................................................................................21 Conclusion...................................................................................................27 References....................................................................................................28 Appendix .....................................................................................................31 요약 (국문초록)..........................................................................................39Maste

Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress

ZNF509 is unique among POK family proteins in that four isoforms are generated by alternative splicing. Short ZNF509 (ZNF509S1, -S2 and -S3) isoforms contain one or two out of the seven zinc-fingers contained in long ZNF509 (ZNF509L). Here, we investigated the functions of ZNF509 isoforms in response to DNA damage, showing isoforms to be induced by p53. Intriguingly, to inhibit proliferation of HCT116 and HEK293 cells, we found that ZNF509L activates p21/CDKN1A transcription, while ZNF509S1 induces RB. ZNF509L binds to the p21/CDKN1A promoter either alone or by interacting with MIZ-1 to recruit the co-activator p300 to activate p21/CDKN1A transcription. In contrast, ZNF509S1 binds to the distal RB promoter to interact and interfere with the MIZF repressor, resulting in derepression and transcription of RB. Immunohistochemical analysis revealed that ZNF509 is highly expressed in normal epithelial cells, but was completely repressed in tumor tissues of the colon, lung and skin, indicating a possible role as a tumor suppressorope

Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter

Kr-pok (kidney cancer-related POZ domain and Krüppel-like protein) is a new proto-oncogenic POZ-domain transcription factor. Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes fatty acids in cancer cells. Sp1 and SREBP-1c are the two major transcription activators of FASN. We investigated whether Kr-pok modulates transcription of the FASN. FASN expression is significantly decreased in Kr-pok knockout murine embryonic fibroblasts. Coimmunoprecipitation, GST fusion protein pull-down, and immunocytochemistry assays show that the zinc-finger domain of Kr-pok interacts directly with the bZIP DNA binding domain of SREBP-1. Electrophoretic mobility shift assay, oligonucleotide pull-down, and chromatin immunoprecipitation assays showed that Kr-pok changes the transcription factor binding dynamics of Sp1 and SREBP-1c to the SRE/E-box elements of the proximal promoter. We found that Kr-pok expression increased during 3T3-L1 preadipocyte differentiation and that FASN expression is decreased by the knockdown of Kr-pok. Kr-pok facilitates the SREBP-1c-mediated preadipocyte differentiation and/or fatty acid synthesis. Kr-pok may act as an important regulator of fatty acid synthesis and may induce rapid cancer cell proliferation by increasing palmitate synthesis.ope

The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation

The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG–binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex– and the NuRD complex–associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation.ope

종양억제인자 HKR3의 p300과의 상호작용, 발암인자 FBI-1의 작용억제를 통한 종양억제인자 ARF의 발현 활성

Dept. of Medical Science/석사Relatively uncharacterized POK family transcription factor HKR3 (Human Krüppel-related 3) has a POZ-domain in the N-terminus and 11 zinc-finger domain in the c-terminus half. The mapped HKR3 gene region is commonly rearranged (leiomyoma, leukemias) or deleted (neuroblastoma, melanoma, Merkel cell carcinomas, pheochromocytoma and breast and colon carcinomas). Correlation of deletion or rearrangement and HKR3 in human cancer suggested the role of HKR3 as a potential tumor suppressor. I investigated whether the HKR3 has a regulatory effect on cell cycle by controlling gene expression of the p53 pathway (ARF-MDM2-TP53-CDKN1A). HKR3 is an activator of the p53 pathway through activating transcription of ARF, p53, and CKDN1A genes. In particular, HKR3 potently activated transcription of tumor suppressor gene ARF by acting on the proximal promoter region (bp, -149 ~ +53) containing Sp1 and FBI-1 binding elements (FREs). HKR3 interacted with co-activator p300 to activate ARF, which increased the acetylation of histone H3 and H4 around the proximal promoter. Oligoucleotide pull-down assays and ChIP assays revealed that HKR3 interferes with FBI-1 binding to the proximal FREs and thereby lifted transcription repression by FBI-1, a proto-oncoprotein known to repress transcription of ARF. HKR3 inhibited cell proliferation, but did not induce apoptosis, suggesting that HKR3 is potentially a tumour suppressor.prohibitio

Kr-pok의 G6pc, Pck1 유전자 전사활성화를 통한 포도당 신생합성 조절

Dept. of Medical Science/박사Gluconeogenesis is essential for maintenance of blood glucose level during fasting. Gluconeogenesis is tightly regulated by the key enzymes, including glucose-6-phophatase (G6pc) and phosphoenolpyruvate carboxykinase (PEPCK). Transcription of the genes encoding the two enzymes is tightly regulated under fasting condition. Kr-pok knockout mice showed a decrease in blood glucose level. Differential gene expression analysis of Kr-pok wild type and knockout mice liver showed that mRNA of G6pc and Pck1 are decreased. I investigated the role of Kr-pok in the regulation of gluconeogenesis. I found that Kr-pok is induced in the liver of fasted mice. Also, forskolin treatment increased Kr-pok expression in mice primary hepatocytes and knockout of Kr-pok decreased transcription of G6pc and Pck1. These results showed that, under fasting condition, Kr-pok can increase expression of G6pc and Pck1genes. I investigated how Kr-pok can increase transcription of G6pc and Pck1 genes. Transient transcription assays of the reporter plasmid showed that Kr-pok increases transcription by acting on the IRSs of the G6pc and Pck1 promoters. ChIP assays revealed that Kr-pok reduces acetylation of FoxO1 and thereby increases FoxO1 binding to the IRS elements of the promoters to activate transcription of G6pc and Pck1. Kr-pok increased the interaction between FoxO1 and HDAC3 and deacetylated FoxO1. Also, I found that protein stability of Kr-pok is increased by treatment of forskolin. These results suggested that Kr-pok might be a metabolic regulator controlling expression of the two key gluconeogenic enzymes, G6pc and PEPCK.ope

Yun Jaehyun

학위논문(석사)--아주대학교 일반대학원 :금융공학과,2017. 21 Introduction 1 2 Structured Notes 3 2.1 Introduction 3 2.2 Pricing of Structured Notes 5 2.2.1 Hull-White model 5 2.2.2 Least-Squares Monte-Carlo method 13 3 Interpolation Methods for Yield Curve 14 3.1 Introduction 14 3.2 Interpolation Methods 15 3.2.1 Piecewise linear interpolation 15 3.2.2 Cubic spline interpolation 16 3.2.3 Monotone convex method 16 3.3 Comparison of Interpolation Results 20 4 Numerical Results 23 5 Conclusion 31 References 33MasterThis study aims to find the interpolation methods to construct a yield curve. In this paper, first, we construct the yield curve using three methods: the piecewise linear interpolation, cubic spline interpolation, and the monotone convex method. Second, we evaluate the structured notes, which contain the Bermudan call option, through the Hull-White model and the least square Monte-Carlo method. According to the simulation results, the hedge performance is contingent on how a yield curve is interpolated. This study, thus, suggests that one needs to choose an interpolation method carefully by comparing the methods in different settings to find the one, which can improve the hedge performance

Method for promoting production of biogas using pancreatin in an anaerobic digestion process

본 발명은 혐기소화공정에서 판크레아틴을 이용한 바이오가스 생산 촉진을 위한 방법에 관한 것으로서, 판크레아틴(pancreatin)을 유효성분으로 포함하는 가수분해 효율 증진용 또는 바이오가스 생산 촉진용 조성물 및 이를 이용한 유기성 축산분뇨에서 바이오가스의 생산을 촉진(또는 증대)시키는 방법에 관한 것이다. 본 발명의 판크레아틴(pancreatin)을 유효성분으로 함유하는 조성물은 유기성 폐기물 처리를 위한 혐기소화공정에 있어서 가수분해 효율을 증진시키고 바이오가스 생산을 촉진시키는 효과를 가지므로, 이를 유효성분으로 포함하는 본 발명의 조성물은 혐기소화공정을 이용한 유기성 폐기물 처리과정에 유용하게 사용될 수 있다. 특히 본 발명의 유효성분인 판크레아틴(pancreatin)은 pH 7.0 내지 8.0에서 최적의 활성을 가지므로 유기물을 하나의 소화조에서 넣어 혐기소화시키는 단상식 시스템에서 사용하는 경우, 메탄발효를 위한 최적의 pH인 7.0~8.0과 일치함에 따라 단상식 시스템에서 더욱 효과적으로 사용될 수 있다

Promyelocytic Leukemia Zinc Finger-Retinoic Acid Receptor α (PLZF-RARα), an Oncogenic Transcriptional Repressor of Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) and Tumor Protein p53 (TP53) Genes

Promyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) is an oncogene transcriptional repressor that is generated by a chromosomal translocation between the PLZF and RARα genes in acute promyelocytic leukemia (APL-type) patients. The molecular interaction between PLZF-RARα and the histone deacetylase corepressor was proposed to be important in leukemogenesis. We found that PLZF-RARα can repress transcription of the p21WAF/CDKN1A gene, which encodes the negative cell cycle regulator p21 by binding to its proximal promoter Sp1-binding GC-boxes 3, 4, 5/6, a retinoic acid response element (RARE), and distal p53-responsive elements (p53REs). PLZF-RARα also acts as a competitive transcriptional repressor of p53, RARα, and Sp1. PLZF-RARα interacts with co-repressors such as mSin3A, NCoR, and SMRT, thereby deacetylating histones Ac-H3 and Ac-H4 at the CDKN1A promoter. PLZF-RARα also interacts with the MBD3-NuRD complex, leading to epigenetic silencing of CDKN1A through DNA methylation. Furthermore, PLZF-RARα represses TP53 and increases p53 protein degradation by ubiquitination, further repressing p21 expression. Resultantly, PLZF-RARα promotes cell proliferation and significantly increases the number of cells in S-phase.ope

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding

The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box#3 (bp, -55 to -63) and the MIZ-1-binding elements, MRE-A (bp, -90 to -64) and MRE-B (bp, -27 to -17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp, -95 to -100) and #3 (bp, -55 to -63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.ope