Development of a noninvasive KIM-1-based live-imaging technique in the context of a drug-induced kidney-injury mouse model

Tae-Jun Kwon,Da-Sol Lee,Md. Enamul Haque,Rang-Woon Park,Byungheon Lee,Dongkyu Kim,Yong-Hyun Jeon,Kil-Soo Kim,Sang Kyoon Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

The development of reliable methods to diagnose acute kidney injury is essential to allow the adoption of early therapeutic interventions and evaluate their effectiveness. Based on the fact that kidney injury molecule-1 (KIM-1) expression levels in kidneys are markedly upregulated early after a damage event, here we developed a noninvasive KIM- 1-based molecular imaging technique to detect kidney injury. First, we took advantage of a phage-display platform to select small peptides demonstrating a specific high binding affinity to KIM-1. The promising candidate was conjugated with fluorescent probes, and its imaging potential was validated in vitro and in vivo. This peptide, with the sequence CNRRRA, not only showed a high imaging potential in vitro, allowing a strong detection of KIM-1 expressing cells by microscopy and flow cytometry but also generated a strong kidney-specific signal in live-imaging in vivo experiments in the context of a drug-induced kidney-injury mouse model. Our data overall suggest that the CNRRRA peptide is a promising probe to use in the context of in vivo imaging for the detection of KIM-1 overexpression in damaged kidneys.

일반논문 1 : 김종익의 유언과 경성여자의학전문학교 설립과정

백운기 ( Woon Ki Paik ),김상덕 ( Sang Duk Kim ) 연세대학교 의과대학 의사학과 의학사연구소 2011 연세의사학 Vol.14 No.1

Dr. Rosetta Hall, an American missionary physician, and Dr. Jeong-hee Gil, a young Korean physician, founded the Joseon (Keijo) Women`s Training Institute in 1928. Between 1933 and 1937, Dr. Gil and her husband, Dr. Kim Tak-won, maintained and financed the medical institute. Supporting the institute placed a heavy burden on the young doctors who were just establishing their private medical practice. Despite this burden, they undertook the work necessary to elevate the institute to a full medical college. In order to generate the substantial funds needed to establish the medical college, they created a foundation for the “creation of a women`s medical college” in 1934 and solicited funding. In 1937, a philanthropist interested in furthering education, Mr. Kim Jong-ik, agreed to donate the funding necessary to elevate the institute to a medical college. Mr. Kim, however, unexpectedly contracted dysentery and died. In his will, Mr. Kim bequeathed a portion of his estate to upgrading the institute to a medical college. The executor, contrary to Mr. Kim`s intent as set forth in his will, however, did not use the funds to elevate the institute, but rather established a completely new women`s medial college. The executor`s actions were a clear violation of Drs. Kim`s and Gil`s legal rights as beneficiaries under the will. They, nonetheless, accepted the outcome, because challenging the executor`s actions under Japanese rule would have been futile as Dr. Kim was a noted anti-Japanese patriot well known to the Japanese. Moreover, Sato Gozo had been Dr. Kim`s teacher at the Keijo Medical College. Most importantly, their dream of establishing a women`s medical college in Korea had been realized regardless of how. Regardless of whether the institute had been elevated to a medical college or not, Drs. Kim Tak-won and Gil Jeong-hee made great sacrifices to further the education of women medical doctors in Korea and should be recognized for their great contributions to the creation of Korea Women`s Medical College.

정상과 갑상선 종양조직에서 사람 IGF-I 유전자의 발현

김성운,장현하,박상미,김덕윤,우정택,양인명,김진우,김영설,김광원,고석환,홍성화,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

Many of the growth-promoting properties of growth hormone(GH) are mediated by insulin-like growth factor-I(IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In thyroid tissue, thyroid stimulating hormone(TSH) and IGF-I are the most possible candidates for follicular cell proliferation and hypertrophy. Actually IGF-I had autocrine and paracrine effect for tissue growing. We prepared thyroid tumor tissue mRNAs using single step method for detecting IGF-I levels according to different tissues, i.e., thyroid adenoma or papillary thyroid carcinoma. We used Northern blot analysis for IGF-I mRNA and RNase protection assay (RPA) for IGF-I transcription start sites. For Northern blot, we used whole human IGF-I cDNA as a DNA probe and for RPA, we used IGF-I exon 1 containing noncoding promoter 1 as a riboprobe. We got good RNA bands from Northern blot analysis around 1 kb (IGF-IA) and 7.5 kb (IGF-IB) region. To clarify the amount of both IGF-IA and IB mRNAs, we measured autoradiographied signal of IGF-I mRNAs bands using densitometer. In IGF-IA signals, there's no change among liver and thyroid tissues, but in case of IGF-IB mRNA bands, the signal was markedly increased in thyroid carcinoma tissues than that of normal thyroid tissue (85% vs 14%). In the study of RPA, all thyroid tissues used the same transcription start sites as those of liver's. We concluded that that this different regulation of IGF-I mRNA was originated from tissue specificity. That meant some tissue specific transcription factor/s were related to tissue IGF-I expression.

배양된 쥐 인슐린종 세포에서 성장인자들에 대한 인슐린 유전자의 발현

김성운,양인명,김진우,김영설,김광원,최영길 경희대학교 유전공학연구소 1989 遺傳工學論文集 Vol.1 No.-

인슐린 유전자 발현의 실험실적 모델로서 쥐 인슐린종 세포(RINm5F cell;rat insulinorraceil)를 이용하여 몇 개의 성장인자에 대한 반응을 조사하고 인슐린 유전자의 활성에 관여하는 상황을 이해하고자 인슐린 유전자의 mRNA를 조사하였다. RINm5F 세포는 glucose 와 EGF 등의 성장인자에 대해 세포분화 및 성장에 자극을 받으며 인슐린, IGF-Ⅰ IGF-Ⅱ등에는 영향을 받지 않았다. 따라서 RINm5F TPVHSMS 생체내 췌도 베타세포의 기능을 대변하기는 어려웠으나 각종 성장인자의 세포내 활성양상을 간접적으로 알 수 있었다. Insulin secretion of RINm5F cells can be stimulated by some of the growth factors, however, not in the same manner compared to pancreatic islet beta cells. We observed that insulin superfamily (insulin IGF-Ⅰ, IGF-Ⅱ) were not affected to insulin mRNA of RINm5F cells, but EGF (50ng/㎖) increased insulin mRNA levels, and dexamethasone (300ng/㎖) decreased insulin mRNA levels in RIAm5F cells. So some of growth factors regulated insulin gene at transcription level in RINm5F cells line.

Streptozotocin-당뇨병 백서에서 당뇨병 이환기간에 따른 대동맥의 이완능 저하 및 Oxygen-Free Radical에 의한 이완능의 손상정도

김정국,김신우,김수동,서예경,하승우,김보완,백운이,권삼,강승완 경북대학교 병원 1997 경북대학교병원의학연구소논문집 Vol.1 No.1

목적: 당뇨병의 이환기간이 혈관의 내피세포 의존성 및 비의존성 이완능의 저하에 미치는 영향과 이환기간에 따라 oxygen-free radical(OFR)에 의한 동맥이완능의 손상정도에 차이가 있는지를 알아보고자 하였다. 방법: Streptozotocin(STZ)으로 당뇨병이 유도된 3 주 및 10주째의 백서군과 연령이 비슷한 정상 대조백서군의 적출 대동맥환을 norepinephrine으로 수축시킨 상태에서 내피세포 의존성 이완제인 acetylcholine(ACh) 및 비의존성 이완제인 nitroglycerine(NTG)에 대한 이완능을 즉정하여 비교 관찬하였다. 또한 xanthine과 xanthine oxidase의 혼합으로 생성된 H₂O₂에 대동맥환을 노출시킨뒤 역시 ACh과 NTG에 대한 이완능의 손상정도를 비교하였다. 결과: 3주및 10주째 당뇨병 백서의 대동맥환은 모두 대조군 백서의 대동맥환에 비해 ACh에 대한 이완능이 유의하게 감소하였으며 10주째 당뇨병 백서군에서의 ACh에대한 이완능의 저하는 3 주째 당뇨병 백서군에 비해 유의하게 심하였다.H₂O₂에 노출시킨 뒤 ACh에대한 이완능은 3주 및 10주 째 당뇨병 백서군에서 모두 대조군에 비해 유의하게 심한 손상을 보였으나 3주와 10주째 당뇨병 백서군 사이의 손상정도의 차이가 통계학적으로 유의하지는 않았다. 한편 3주 및 10주째 당뇨병 백서군 모두 NTH에 대한 대동맥환의 이완능은 대조 백서군과 별다른 차이가 없었으며 또 H₂O₂에 노출시킨 뒤에도 NTG에 대한 이완능의 손상은 관찰되지 않았다. 결론: STZ-당뇨병백서에서 대동맥의 이완능은 당뇨병에 이환된지 3 주째에 이미 ACh에 대한 내피세포 의존성 이완능이 선택적으로 저하되며 당뇨병의 이환기간이 길수록 이완능의 저하가 심하였고, OFR에 의한 동맥 이완능의 손상도 내피세포 의존성 이완능에만 선택적으로 나타나나 이환기간에 따라 OFR에 의한 이완능 손상정도에는 뚜렷한 차이가 없음을 시사하고 있다. Objectives: Diabetes mellitus produces histological evidence of endothelial as well as changes in vascular function in experimental animal. Oxygen free radicals interfere with of destroy endothelium-dependent relaxation in normal and diabetic blood vessels. The present study was investigated whether the duration of diabetic state can affect the severity of impairment in endothelium-dependent and/or independent relaxation and the sensitivity to oxygen free fadical (OFR)-induced damage in diabetic rat vasculature. Methods: The relaxative responses of aortic ring precontracted with norepinephrine in vitro to cumulative concentrations of acetylcholine (ACh) and nitroglycerine (NTG) were conducted in 3- and 10- week streptozotocin (STZ)-diabetic rats and agematched controls. After exposure to H₂O₂generated by mixing xanthine and xanthine oxidase, the degree of impairment in relaxative responses to ACh and NTG were also compared between 3- and 10-week diabetic rats. Results: The relaxative responses of aortic rings produced by cumulative concentrations of ACh were significantly lower in both 3- and 10-week diabetic rats than in the age-matched controls. The impairments of relaxative responses to ACh in 10-week diabetic rats were significantly greater than those in 3-week ones. After H₂O₂ exposure, the impairments of relaxative responses to ACh in 3- and 10-week diabetic aortas was also significantly greater than those in the control in the control ones. However, the severity of H₂O₂-induced damage in 10-week diabetic aortas was not significantly different than that in 3-week ones. In contrast, aortic rings of 3- and 10-week diabetic rats could still be fully relaxed by NTG, even after exposure to H₂O₂. Conclusion: These findings suggest that in SRZ-diabetic rat aortas selective impairment of endothelium-dependent relaxation to Ach can be found early even over a 3-week period after the induction of diabetes and the impairment may be greater in those with the longer duration of the diabetic state and that the impairment of the vascular relaxation by OFR is also selective to endothelium-dependent response but the sensitivity of OFR-induced damage may not be related to the duration of the diabetic state.

Impact of Interferon-Based Treatment on Quality of Life and Work Related Productivity from the Korean Cohort in the MOSAIC Study

( Sang Hoon Ahn ),( Won Hyeok Choe ),( Yoon Jun Kim ),( Jeong Heo ),( Dorota Latarska-smuga ),( Jiho Kang ),( Seung Woon Paik ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Chronic Hepatitis C Virus (HCV) infection increases the risk for progressive liver disease, hepatocellular carcinoma and negatively impacts the patient’s quality of life. HCV treatment is evolving with direct acting antivirals but IFN based therapy has been the standard of care for many years and remains available in some countries. The MOSAIC study aims to characterize patients with chronic HCV infection and assess the impact of IFN-containing treatment on health-related quality of life, work related productivity and health care utilization. Methods: MOSAIC is an international prospective multicenter observational study that has been conducted in 20 countries. Consecutive patients with chronic HCV infection were enrolled and those who initiated an IFN based regimen were prospectively followed for 48 weeks. We report results from the Korean cohort Results: 100 patients were enrolled: 86 were treatment naïve and 14 were treatment experienced. 33 patients initiated an IFN based regimen: 6 patients started IFN + RBV, 26 patients started Peg-IFN + RBV, none started Peg-IFN + RBV + DAA and 1 patient received other treatment. Among the treated cohort, demographic and disease characteristics were the following: the mean age was 54.5 years; 14 patients were male. 14 had minimal or no fibrosis, 2 portal fibrosis, 3 bridging fibrosis and 6 patients suffered from cirrhosis. HCV Genotype distribution was as follows: genotype 1: 11; genotype 2: 19 and genotype 3: 3. Table 1 describes the results at baseline and changes over 4, 12 and 48 weeks and end-of-treatment (EOT) for the quality of life and work productivity outcome measures (EQ-5D-5L, HCV-PRO and WPAI). Conclusions: Results from the Korean cohort of the MOSAIC study show a moderate trend for deterioration of health-related quality of life and work productivity associated with IFN based treatment for patients with chronic HCV infection during treatment period. Acknowledgements: The design, study conduct, analysis, and financial support of MOSAIC study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the content of the abstract. All authors had access to all relevant data and participated in writing, review, and approval of this abstract. Medical writing support was provided by Olivier Van de Steen of Medeor-consulting, funded by AbbVie. Disclosures: Sang Hoon Ahn: served as an advisor and lecturer for Bristol-Myers Squibb, Gilead Sciences, F.Hoffmann-La Roche, Merck, AbbVie, and has received unrestricted grants from Bristol-Myers Squibb, Gilead Sciences, and F. Hoffmann-La Roche for investigator- initiated trials Won Hyeok Choe: Nothing to disclosure Yoon Jun Kim: Nothing to disclosure Jeong Heo: received a grant from GSK; Research support from BMS, and Roche; Advisor for Abbvie, BMS, Gilead Sciences, Pharma Essentia, SillaJen, and Johnson & Johnson. Dorota Latarska-Smuga, Jiho Kang: are employees of AbbVie, Inc. and may hold stock or stock options. Seung Woon Paik: received grant and research support from AbbVie, BMS, Gilead, GSK, Merck, Novartis, and Roche

C 의과대학에서 문제강의에 대한 학생들의 직접평가가 강의개선에 미친 영향

김석용, 이상진, 최재운, 김승렬, 김용대, 배성은, 김영규 충북대학교 의과대학 충북대학교 의학연구소 2012 忠北醫大學術誌 Vol.22 No.1

연구목적: 팀티칭에 근거한 통합강의는 최근 대부분의 의과대학에서 시행되는 강의형태이다. 그러나 기 존에 사용되고 있는 온라인 강의평가 방식은 이러한 강의 특성에서 나타나는 문제점을 파악하기 힘든 점이 있다. 본 대학에서는 팀티칭에 의한 통합강의에서 문제강의를 직접적으로 파악하는 ‘문제강의 직 접평가지’를 개발하였다. 본 연구의 목적은 새로이 개발된 문제강의 직접평가지가 강의개선에 끼친 영 향력을 알아보고자 하는 것이었다. 연구방법: 2007년 2학기부터 2009년 2학기까지 충북대학교 의과대학 1, 2학년을 대상으로 문제강의 직접평가지에 의한 강의평가를 실시하였다. 평가지 질문 중에서 두 가지 객관식 질문에 대한 답변을 분 석대상으로 선택하였다. 질문은 첫째, ‘가장 유익하고 도움이 많이 되었던 강의들은 무엇입니까?’와 둘 째, ‘가장 어렵거나 이해하기 힘들었던 강의들은 무엇입니까?’였다. 강의평가를 실시한 강좌들 중에서 2 년 이상 연속적으로 강좌구조와 평가지의 객관식 질문 형식이 변하지 않은 14개의 강좌를 분석대상으로 하였다. 각각 연도의 평균 긍정비율을 다른 연도의 것과 카이제곱 검정 방법을 사용하여 비교하였다. 결과: 14개의 강좌 중에서 시작연도와 마침 연도 간에 긍정비율이 증가된 경우는 13개 강좌였다. 그 러나 통계적으로 의미가 있는 경우는 5개 강좌에서 나타났다. 결론: 문제강의 직접평가지에 의한 문제강의를 판별해 내는 방법은 단기간에 통합강좌의 개선에 효과 적이다.

T형 합성보의 구조거동에 대한 실험적 연구

이지운,김성배,김상모,이창남,김상섭 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.2(구조계)

Composite action can be achieved by providing shear connectors between steel top flange and concrete topping. Composite sections have larger stiffness than the summation of the individual stiffness of slab and beam, therefore, can carry larger load or similar loads with appreciably smaller deflection and are less prone to transient vibration. T-type Steel Composite beam(TSC-beam) is developed and tested. The test results of TSC beam are compared with the theoretical results based on composite actions.

TSC 합성보의 제작방법에 따른 구조적 거동에 관한 실험적 연구

이지운,김도훈,김성배,이창남,김상섭,김규석 대한건축학회 2004 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.24 No.1(구조계)

Composite action can be achieved by providing shear connectors between steel top flange and concrete topping. Composite sections have larger stiffness than the summation of the individual stiffness of slab and beam, therefore, can carry larger load or similar loads with appreciably smaller deflection and are less prone to transient vibration. T-type Steel Composite beam(TSC-beam) is developed and tested. To make the part of steel beam, we used the way of welding two steel plates as well as the way of folding one steel plate.

당뇨병 백서의 간세포에서 Glucokinase 활성도 및 유전자 발현에 대한 인슐린의 영향

강성이,팽정령,서광식,안규정,우정택,김성운,양인명,김진우,김영설,김광원,최영길 경희대학교 유전공학연구소 1993 遺傳工學論文集 Vol.5 No.-

목적 당대사의 조절 상태에 따른 생체 변화를 분자 수준에서 이해하고자 식이 조건을 달리한 정상 백서와 화학적으로 유도된 당뇨병 백서의 간조직에서 혈당수준과 인슐린치료 정도에 따라 나타나는 글루코키나제 활성도 및 유전자 발현을 분석하였다. 방법 스트렙토조토신 정맥투여 후 당뇨병의 유발을 확인하고, 인슐린을 1일 3회 3일간 복강내로 투여하여 상태를 안정시킨 후, 인슐린 투여군은 인슐린 투여 6시간이내에 그리고 인슐린 비투여군은 24시간 후 단두하여 채혈하고 복강을 열어 간조직을 채취하였다. 채취한 간조직에서 글루코키나제 활성도는 인산화된 포도당에서 NADH의 형성을 형광분광계로 측정하였으며, 글루코키나제 유전자 mRNA발현은 Northern 분석법을 이용하였다. 성적 정상 백서에서 공복상태와 식이를 섭취한 경우에 간조직의 글루코키나제 효소의 활성은 차이가 없었으나, 글루코키나제 유전자 mRNA 발현은 증가되었다. 당뇨병이 유발된 백서의 간조직에서 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA 발현은 정상 백서에 비하여 낮았다. 인슐린 투쳐 후 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA 발현이 증가되었고, 특히 혈당이 정상화된 경우에서 글루코키나제 유전자의 mRNA 발현이 증가도었다. 결론 인슐린에 의한 간조직에서 글루코키나제 효소의 활성 및 글루코키나제 유전자의 mRNA을 증가를 볼수 있었다. 당뇨병 백서에서 인슐린 투여 후에 혈당조절이 안된 경우 간조직의 글루코키나제 유전자의 mRNA 발현이 증가가 없는 것으로 보아 글루코키나제 mRNA의 발현에는 인슐린 이외의 다른 요소가 관여할 것으로 생각된다. The liver-specific hexokinase isoenzyme, referred to as glucokinase, is thought to play a key reglulatory role in hepatic glucose metabolism. The glucokinase gene is, therefore, of interest both because of its tissue-specific expression and because of the several regulatory processes that can be analyzed. The level of hepatic glucokinase activity appears to be determined essentially by regulation of the rate of enzyme synthesis, with insulin playing a leading role as an inducer. We investigated the role of insulin for the induction of glucokinase in the liver of diabetic rats. Experimental diabetes was induced by injection of streptozotocin 7 days before the experiment. Regular insulin was given by three days intraperitoneal injection at 8-h interval. The glucokinase mRNA in the liver was estimated by Nothern blot assay, as well as by fluorometric enzyme activity assay. Glucokinase activity was not reduced in the liver of normal fasting rats as compared to normal fed rats. And glucokinase activity was reduced in the liver of diabetic rats as compared to normal rats. In diabetic rats treated with insulin, glucokinase enzyme activity were increased. But glucokinase mRNA expression was only increased in normoglycemic diabetic rat with treated with insulin as compared to hyperglycemic rat. These data indicate that insulin stimulates hepatic glucokinase enzyme activity and mRNA expression. But other hormonal or metabolic factors may be contribute to regulation of glucokinase mRNA expression.