Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

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.

Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

Lip Bumper를 이용한 치료의 성공과 실패

김용기,김종수,김종빈,맹명호 大韓小兒齒科學會 1999 大韓小兒齒科學會誌 Vol.26 No.3

혼합치열기의 소아환자의 경미한 하악 전치부의 총생을 해결하는 문제와 하악 제 2 유구치의 조기 상실로 인한 하악 제 1 대구치의 근심경사 그리고 이에 따른 제 2 소구치의 맹출 공간 부족등을 해소하기 위한 여러가지의 방법들이 시도되어왔지만 저마다 그 술식의 적용범위나 방법 등에는 많은 어려움 들이 있어왔다. 이 연구의 목적은 이런 선택이 어려움을 가만하여 실제 임상에서 보다 간편하고 환자의 불편감을 줄여줄 수 있는 한 방법으로 Lip bumper를 이용한 술식을 소개하고 그 적용례를 통하여 성공과 실패 사례들을 소개함으로써 임상가들에게 보다 유익한 정보를 주기 위함이다. In the mixed dentition,many chidren have mild crowing of anterior dentition on the mandibular arch and mesial of mandibular molar.Lip bumper have been used to gain arch length for the alignment of mild to moderate crowded dental arches.As such,they may provide an alternative to extraction therapy.The claimed therapeutic effect of the lip bumper is bodily forward incisor movement,flaring of the low incisors,and distal tipping of the molar.The dental changes can be attributed to removal of lip pressure on the lower anterior dentition and the distal forces exerted at the molar at the abutment.The purpose of this study is to show more easily method of treatment for mild anterior crowding of mandible.

기종성 방광염을 동반한 기종성 신우신염 1예

김선두,김순제,이길도,김정수,김지훈,윤호상,송종오,문언수 대한노인병학회 2000 Annals of geriatric medicine and research Vol.4 No.3

목형의 엔드 밀링시 절삭조건에 따른 가공 특성에 관한 연구

김성일,김종택,김민호,신형곤,김태영 한국공작기계학회 2006 한국공작기계학회 추계학술대회논문집 Vol.2006 No.-

The cutting tests of wood patterns are carried out using CNC milling machine. The cutting forces and surface characteristics of machined surface are investigated at various cutting conditions such as spindle speed, feed speed, cutting direction of wood pattern and wood material. In the CNC end-milling, the surface roughness increases as feed speed increases and decreases as spindle speed increases. However, the cutting force and surface roughness are different along the cutting direction and material of wood pattern.

단기간의 저용량 Cytosine arabinoside 치료에 반응하였던 Down 증후군에 병발한 급성골수성백혈병 1례

김현수,이정호,이정찬,강정현,곽상혁,김철희,배광봉,김종숙,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

The incidence of hematologic disorders in patients with Down's syndrome is significantly increased, about 14∼30 - fold higher than in general population and includes neonatal transient abnormal myelopoieis and acute leukemias. The age of onset of leukemia in Down's syndrome is peaking first in the newborn period and then under 4 years of age. Down's syndrome with acute leukemia above the age of 20 is very rare and it's treatment oucome is unclear. The treatment of Down's syndrome with leukemia has been controversial because of toxicity and associated congenital cardiac and other abnormalities. But if treated adequately, children with Down's syndrome show a favorable response to anti-leukemia therapy. A 24-year-old man with Down's syndrome was first seen for the evaluation of anemia and thrombocytopenia. The peripheral blood morphology and bone marrow study revealed acute myelogenous leukemia, cytogenetic study of bone marrow showed trisomy 21. Beacuse of his sicioeconomic condition and medical abnormalities including deafness, visual loss, he was treated with low dose subcutaneous cytosine arabinoside(Ara-C) for 11 days. Complete remission was obtained after 37 days. The complete remission lasted for 5 months. He subsequently relapsed, and died 6 months later.

정전위 SSRT법에 의한 해양구조물용 Cu함유 고장력저합금강의 수소취성한계전위 규명에 관한 연구

김성종,박태원,심인옥,김종호,김영식,문경만 한국해양대학교 해양과학기술연구소 2001 硏究論文集 Vol.10 No.1

A marine structural material was well known to have high tensile strength, good weldability and proper corrosion resistance . Cu-containing high strength low alloy (HSLA) steel was recently developed for their purposes mentioned above, And the steel is free about preheating for welding, therefore it is reported that shipbuilding cost by using it can be saved more or less. However the marine structural materials like Cu-containing HSLA steel are being generally adopted with cathodic protection method in severe corrosive environment like natural sea water but the high strength steel may give rise to Hydrogen Embrittlement due to over protection at high cathodic current density for cathodic protection. In this study, Cu-containing HSLA steel using well for marine atructure was investigated about the susceptibility of Hydrogen Embrittlement as functions of tensile strength, strain ratio, fracture time, and fracture mode, etc. and an optimum cathodic protection potential by slow strain rate test(SSRT) method as well as corrosion properties in natural sea water. And its corrosion resistance was superior to SS400 steel , but Hydrogen Embrittlement susceptibility of Cu-containing HSLA steel was hider than that of SS400 steel. However Hydrogen Embrittlement of its steel by SSRT method was showed with pheonomena such as decreasing of fracture time. strain ratio and fracture mode of QC (quasi-cleavage) Eventually it is suggested that an optimum cathodic protection potential not presenting Hydrogen Embrittlement of Cu-containing of HSLA steel by SSRT method was from-770mV(SCE) to - 900mV(SCE) under natural sea water. (Received September 21, 2000)

당뇨병성 합병증을 가진 환자에서 혈증 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 조선의대 1998 The Medical Journal of Chosun University Vol.23 No.1