In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

Lee, Sunghun,Lee, Dong Hun,Park, Bong-Woo,Kim, Riyoun,Hoang, Anh Duc,Woo, Sang-Keun,Xiong, Wenjun,Lee, Yong Jin,Ban, Kiwon,Park, Hun-Jun Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.2

<▼1><P>Vascular regeneration in ischemic hearts has been considered a target for new therapeutic strategies. It has been reported that ETV2 is essential for vascular development, injury-induced neovascularization and direct cell reprogramming of non-endothelial cells into endothelial cells. Thus, the objective of this study was to explore the therapeutic potential of ETV2 in murine models of myocardial infarction in vivo. Direct myocardial delivery of lentiviral ETV2 into rodents undergoing myocardial infarction dramatically upregulated the expression of markers for angiogenesis as well as anti-fibrosis and anti-inflammatory factors in vivo. Consistent with these findings, echocardiography showed significantly improved cardiac function in hearts with induced myocardial infarction upon ETV2 injection compared to that in the control virus-injected group as determined by enhanced ejection fraction and fractional shortening. In addition, ETV2-injected hearts were protected against massive fibrosis with a remarkable increase in capillary density. Interestingly, major fractions of capillaries were stained positive for ETV2. In addition, ECs infected with ETV2 showed enhanced proliferation, suggesting a direct role of ETV2 in vascular regeneration in diseased hearts. Furthermore, culture media from ETV2-overexpressing cardiac fibroblasts promoted endothelial cell migration based on scratch assay. Importantly, intramyocardial injection of the adeno-associated virus form of ETV2 into rat hearts with induced myocardial infarction designed for clinical applicability consistently resulted in significant augmentation of cardiac function. We provide compelling evidence that ETV2 has a robust effect on vascular regeneration and enhanced cardiac repair after myocardial infarction, highlighting a potential therapeutic function of ETV2 as an efficient means to treat failing hearts.</P></▼1><▼2><P><B>Cardiovascular disease: New hope for healing the heart</B></P><P>A gene therapy strategy that stimulates cardiovascular repair could improve recovery for heart attack patients. Heart attacks inflict severe damage on the heart and blood vessels, tissues with limited capacity for self-repair. Researchers led by Kiwon Ban of the City University of Hong Kong and Hun-Jun Park of the Catholic University of Korea, Seoul, have now demonstrated that a gene responsible for cardiovascular development can also efficiently stimulate heart repair. They used viruses to deliver the gene into a mouse model of heart attack, and showed that treated heart tissues exhibited strong recovery relative to untreated controls. The treatment reduced scar tissue formation and promoted proliferation of the cells lining blood vessels and blood vessel formation, measurably improving heart function. This approach could lay the groundwork for treating a common potentially fatal event.</P></▼2>

Studies on the Effects of Biomedicinal Agents on Serum Concentration of Ca2+ , P and ALP Activity in Osteoporosis-Induced Rats

Sang-keun Kim,Myung-hun Lee,Man-hee Rhee 대한수의학회 2003 Journal of Veterinary Science Vol.4 No.2

on the Effects of Biomedicinal Agents on Serum Concentration of Ca2+, P andALP Activity in Osteoporosis-Induced RatsSang-keun Kim, Myung-hun Lee1 and Man-hee Rhee2College of Veterinary Medicine, Chungnam National University, 220 Gungdong, Yusong-Gu, Daejeon 305-764, Korea1National Veterinary Research and Quarantine Service, Anyang 430-824, Korea2College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, KoreaReceived April 3, 2003 / Accepted July 9, 2003J. Vet. Sci. (2003), 4(2), 151-154JOURNAL OFVeterinaryScience*Corresponding author: Sang-keun Kim Dept. of Vet. Med., Chungnam National University, Daejeon 305764, Korea Tel: +82-42-821-6754, Fax: +82-42-821-6754 E.-mail: kskkim@cnu.ac.kr

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

건강한 성인에서 발병한 칸디다와 연관된 위궤양 1례

박지훈,이상혁,김희,이재호,박성재,지삼룡,양성연,박은택,이연재,설상영,정정명,강미선 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Fungus such as Candida albicans is a normal flora that is frequently found in the oral cavity, gastrointestinal tract, genitourinary tract, vaginal mucosa in a normal person. However, candida can cause opportunistic infection in an immune compromised host. Candidiasis has broad spectrum of disease from mucocutaneous infection to invasive or disseminated infection. But, it is rarely reported that candida is associaed with gastrointestinal tract disease in a healthy adult. The case of gastric ulcer associated with candida particularly in a health adult is reported with relevant literature.

Novel Methylation Biomarker for Non-invasive Diagnostics in Lung Cancer

오태정,( Chang Hun Lee2 ),( Min Ki Lee ),( Yeul Hong Kim ),( Sang Yull Lee ),( Hyo Sung Jeon ),( Shin Yup Lee ),( Seung Soo Yoo ),( Jae Yong Park ),( Sung Whan An ) 대한결핵 및 호흡기학회 2012 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.114 No.-

To identify aberrantly hypermethylated DNA in lung cancer cells we established a genome-wide analysis for hypermethylation sites, namely Methyl DNA Isolation and Amplification (MeDIA) coupled-CpG microarray analysis. In the comprehensive methyaltion profiling analysis between human lung cancer, A549 cells and normal NHBE cells, we observed that several clusters of genes show a significant level of aberrancy in CpG island methylation pattern in cancer cells compared to normal cells. We further identified PCDHGA12 gene as a new marker of non-invasive diagnostics for lung cancer based on followings. 1) Transcription of PCDHGA12 gene is reactivated after treatment of A549 cells with demethylating agent. 2) Bisulfide clonal-sequencing reveals that CpG island of PCDHGA12 shows a distinctive differential methylation between two cell lines. 3) Pyrosequencing-based quantitative methylation assay for such region in tumor and non-tumorous tissues from lung cancer patients shows aberrant hypermethylation in 37 (92%) of the 40 tumor tissues. In clinical validation by pyrosequencingin induced-sputum of lung cancer patients (n=87) and healthy controls (n=51), we observed aberrant hypermethylation incident at significantly elevated level in samples derived from lung cancer patients. According to the optimal threshold calculated by ROC curve analysis, sensitivity and specificity of PCDHGA12 was 86.2% and 82.4%, respectively. PCDHGA12 methylation status could be a potential methylation biomarker alone or combined with others for the screen and the detection of relapse of lung cancer.

비외상성 두개내 출혈 환자에서 심근손상의 발생과 예후에 미치는 영향

강구현,황성호,이강현,조준휘,김성환,문중범,박해상,이서영,이성수,김헌주 대한응급의학회 2000 대한응급의학회지 Vol.11 No.4

Objective: The aim of this study was to investigate the clinical significance of myocardial injuries in patients with nontraumatic intracranial hemorrhage by identifying the occurrence of myocardial injury and defining its correlation with subsequent cardiovascular events. Subjects and methods: One hundred twenty-four patients with nontraumatic intracraninal hemorrhage presented to the emergency department within six hours from onset of symptoms were enrolled. Brain CT, serial electrocardiography, and echocardiography were done at the emergency center. Blood samples for troponin I and creatine kinase(CK)-MB were drawn immediately and eight hours after admission, Troponin I and CK-MB were measured using a chemiluminescent immunoassay, respectively. Results: Electrocardiographic and echocardiography abnormalities were found in 65 cases(52.4%) and 21 cases(17%), respectively. Serum troponin I and creative kinase-MB were increased in 35 cases (28.2%) and in 58 cases(46.8%), respectively. Abnormal findings of echocardiography and ECG, as well as elevated levels of serum troponin I and creative kinase-MB, were associated with an increased risk of cardiovascular event and survival. Logistic regression analysis revealed that an abnormal echcocardiographic finding and elevation of serum troponin I were factors associated with the occurrence an adverse cardiovascular event and that electrocardiographic abnormalities and initial mental status were factors associated with poor prognosis. Conclusion: This study reveals that actual myocardial injury develops in a significant proportion of patients with nontraumatic intracranial hemorrhage and that the development of the myocardial injury is associated with an adverse cardiovascular event that occurs during admission.

고빌리루빈혈증을 동반한 자가면역성 간염 1례

서영범,김성욱,장재식,강혁주,이중현,윤병구,김욱년,이광헌,이구,유석동,양창헌,이정호,이영현,이창우,서정일 동국대학교 의학연구소 2000 東國醫學 Vol.7 No.-

자가면역성 간염은 대개 만성 경과를 가지며, 혈중 자가면역항체와 혈청 글로불린치의 상승, 그리고 조직학적으로 괴사 염증성 변화를 특징으로 하는 질환으로 아직 정확한 병인이 밝혀져 있지 않은 상태이다. 발병연령은 대개 젊은 영자(15-25세)에서 호발한다. 이 질환은 급성 간염의 임상경과를 보일 수 있으나, 심한 급성 간염이나 전격성 간염으로도 나타날 수 있는데, 이 경우 아주 나쁜 예후를 보인다고 한다. 치료는 자가면역성 간염 임상 경과의 다양성이나 병인, 병리기전의 불확실성에도 불구하고 대개 steroid 치료에 반응하는 것으로 알려져 있으며 대개 80%의 관해율을 나타내며 궁극적으로 간경변으로의 진행을 막을 수 있는 것으로 보인다. 저자들은 58세 남자에서 발생한 급성의 경과를 가지고 심한 황달을 동반한 자가면역성 간염을 경험하였기에 문헌고찰과 함께 보고하는 바이다. Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disorder of unknown cause associated with circulating autoantibodies and a high serum globulin level. The age of onset of AIH show a peak between the age of 15 and 25 years. AIH can develop and be manifested as acute hepatitis, but severe form of acute hepatitis or fulminant hepatic failure has a poor prognosis. Although AIH is likely to progress from chronic active hepatitis to cirrhosis, steroid therapy can control the disease activity, prolong survival, improve the quality of life , and defer liver transplantation. In the present report we describe a 58-year-old man who admitted because of progressive jaundice and fatigue. He was diagnosed with AIH from laboratory test result showing positivity for antinuclear antibodies, anti-smooth muscle antibodies, and negativity for hepatitis viral markers and from liver biopsy. Steroid therapy, oral administration of prednisolone, was effective in improving the liver function test. Following liver biopsy 6 months after onset shows markedly improved necroinflammatory activity.

수입각증후군에 의한 급성 복증 1례

정은욱,지삼룡,이영태,박지훈,김동기,제인수,채두근,박성재,박은택,이연재,이상혁,설상영,정정명 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Afferent loop syndrome is an uncommon complication of a gastrectomy and Billroth Ⅱ reconstruction. It may cause symtoms at any time from the first postoperative day to many years after the gastrectomy. Afferent loop syndrome is characterized by abdominal pain, vomiting and elevation of serum amylase. Thus, it is difficult to differentiate afferent loop syndrome from other cause of acute pancreatitis. However, the history of gastrectomy can be an important clue for diagnosing afferent loop syndrome. We experienced one case of chronic afferent loop syndrome with acute pancreatitis. After appropriate management, the abdominal pain disappeared and serum amylase level decreased. We report this case with a review of relevant literatures.

마우스 대장암 모델 구축 및 항암제 활성 평가를 위한 예비 연구

김예솔,강봉석,이상은,이은주,이경록,정상헌,박정숙 충남대학교 약학대학 의약품개발연구소 2014 藥學論文集 Vol.29 No.-

Abstract – Aberrant crypt foci (ACF) are early imorphological changes observed in rodents after administration of colon-specific carcinogen such as azoxymethane (AOM). ACF are considered to be putative preneoplastic lesions and are widely used as a surrogate biomarker to rapidly evaluate chemopreventive potential of compounds. The size of colorectal cancer was evaluated after administration of three anticancer drugs, 1 parent drug and 2 prodrugs. The body weights of mice were measured daily and considered as a surrogate for evaluation of general wellbeing. Colons were removed, cut along the longitudinal axis and flushed with phosphate-buffered saline. Each colon was cut into three equal lengths and fixed flat between filter papers. The fixed colon sections were stained with methylene blue. The number of ACF per colon, the number of aberrant crypts observed in each focus and the location of each focus were recorded. After single administration of AOM and multiple doses of anticancer drugs, no significant changes in the body weights of the mice was observed which was recorded for 52 days. However, an expected ACF was not observed in any treated groups. These findings suggest the induction of ACF in mice requires the promotion by dextran sulfate sodium as well as the initiation by AOM.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.