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.

부산지역 소방공무원의 폐기능과 호흡기증상

김성훈,김정원,,김종은,손병철,김정호,이창희,장상환,이채관 大韓産業醫學會 2006 대한직업환경의학회지 Vol.18 No.2

목적: 본 연구에서는 소방관 집단의 호흡기 증상과 폐기능을 조사하여 호흡기 질환의 유병 정도를 비교 분석함으로써 소방관의 호흡기 질환과 화재 노출과의 관련성을 규명하고자 하였다. 방법: 2004년 11월 13일부터 동년 12월 15일까지 부산 소재 4개 소방서와 부속 파출소의 남성 소방공무원 699명을 대상으로 폐기능 검사와 호흡기 설문조사를 실시하였다. 호흡기 증상 설문은 BMRC에서 개발한 설문조사표를 이용하였다. FVC, FEV_(1), MMEF 예측치는 Morris의 폐기능 예측식을 사용하여 계산하였고, 폐기능 검사 이상을 판정하기 위하여 미국 NHNES 기준에 따라 정하였다. 폐기능 측정치와 호흡기 증상은 노출유무와 흡연여부로 집단을 나누어 각각 비교분석하였다. 유의수준은 p<0.05로 정하였다. 결과: 폐기능 비교에서 화재노출군이 FVC, FVC%, FEV_(1), FEV_(1)%, FEF_(25%)는 비노출군에 비해 통계학적으로 유의하게 저하되어 있었고, 이를 흡연여부에 따라 층화하였을 때, FVC 와 FEV_(1)은 흡연여부와 관계없이 노출 여부에 따른 차이를 보이나 FVC%, FEV_(1)%, PEFR은 흡연군에서만 차이를 보였다. 폐기능 검사 이상을 비교하면 전체적으로 화재노출군이 비노출군보다 폐기능 이상자의 수가 많았고 흡연군에서 FEV_(1) 이상자의 차이는 통계적으로 유의하였다. FVC, FEV_(1), MMEF를 종속변수로 하여 다중회귀분석을 시행하였을 때, FVC와 FEV_(1)은 부분적으로 화재노출유무와 관련성이 있었다. 호흡기 증상 조사에서 화재노출군은 비노출군에 비해 코막힘, 목아픔, 흉부압박감의 증상의 호소율이 통계학적으로 유의하게 높았으나, 이를 흡연여부에 따라 층화하면 이들 증상들은 경계역의 차이를 보였다. 결론: 이러한 결과들을 종합하면 소방관은 화재진압과정에서 노출되는 많은 호흡기 유독물질로 인해 급성 폐기능 저하와 높은 호흡기 증상 호소율을 보이며, 이는 화재노출 외에 흡연의 부가적 효과가 영향을 미친다고 생각된다. 따라서 폐기능이 저하된 경방군에서 주기적인 폐기능 검사가 실시되어야 하며, 금연과 호흡기 보호구의 철저한 착용이 권장되어야 하겠다. Objective: The purpose of this study was to evaluate the relationship between respiratory disorders and fire exposure by investigating and analyzing the lung function and respiratory symptoms of firefighters. Methods: The health effects of firefighting on respiratory function were investigated in 699 male fire officers in 4 fire departments in Busan by recording respiratory symptoms and measuring lung function. The data were analysed according to fire exposure and smoking habits. Results: Mean spirometric data showed significantly decreased levels in the fire-exposed group (FVC, -0.20 L; FVC%, -4.2%; FEV_(1) -0.21 L; FEV_(1)%, -5.1%; FEF25%, -0.13 L/SEE p<0.05). After stratification by smoking habits, FVC and FEV1 showed a significant difference between groups. The prevalence of spirometric abnormality was greater for the fire-exposed group than for the non-exposed group. Significantly higher prevalences of nasal stiffness (16.7% vs. 10.9%), sore throat (17.7% vs. 14.2%) and chest tightness (6.5% vs. 2.5%) were recorded in fire fighters compared to controls (p<0.05). However, after stratification by smoking habits, the 3 symptoms were showed only marginal differences in the smoking group. Conclusions: This study demonstrated that fire-exposed firefighters generally suffer a decline of lung function and a higher prevalence of respiratory symptoms. These results suggest that the exposure to routine firefighting activity is associated with adverse health effects to the respiratory system.

고효율 충전탑에서 유해가스처리

김장호,김형호,김종수 동아대학교 환경문제연구소 2001 硏究報告 Vol.24 No.2

In control technology of green house gas CO₂ exhausted, CO₂recovery by chemical absorption technology is recommended. In application to a power station and industrial field with using the absorbent MEA and AMF for carbon dioxide removal. we used packing tower(D=0.l5m, H=1.05m) for experimental apparatus on the chemical absorbtion being used extensively as recovery technique of CO₂. The pressure drop of structured packing Mellapak N. 250Y and random packing 25mm Pall nng was 5.2, 8.5 [mm H₂O/m in the gas capacity factor [kg^(1/2) m^(-1/2) s^(-1)]. Metallic Ralu-Pack 250YC, however, structured packing. has recently being used in petrochemical production plant in general. The decision of tower height depends on the number of transfer unit(NTU) and HTU influence on liquid distribute. If liquid flow is not good material separation, it is bad and usually occurs in the foolding point. In the normal condition, new systematic understanding is given on metal Ralu-Pack 250 YC.

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.

콘크리트의 급속염화물침투시험에 의한 염화물이온 확산계수 평가에 관한 실험적 연구

김갑수,조봉석,장종호,김재환,김용로,김무한 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.1(구조계)

Chloride ions are considered to be the major cause of steel corrosion in concrete structures exposed to seashore environments and also permeation of chloride is controlled by chloride diffusion. Therefore, the study on chloride diffusion of concrete have been done so far by many researchers. In this study, several factors such as capacity of voltage, time of an electric current, concentration of NaCl solution, water-cement ratio, and temperature of the solution were examined to grasp what influence they were on the chloride ion diffusion properties using the Rapid Chloride Penetration Test(RCPT) by electrophoresis. Also standing on the basis of the such result application possibility of Rapid Chloride Penetration Test(RCPT) used in this study will be evaluated and the basic data on the durability design for the chloride attack will be suggested.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1994)

김재홍,안진균,정성재,김영태,김중환,김시영,이석종,이홍렬,서호석,김경훈,권혁진,정우권,고우석,이용석,안필수,오준규,오용섭 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.1

Background : In recent years gonorrhoea has been panendemic and remains one of the most common Sexually Transmitted Diseases in the world, especially in developing countries. Objective & Method : For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria Gonorrhoeae(PPNG), Ive have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results : In 1994, 168 strains of N. gonorrhoeae were isolated, among which 109 (64,9% ) were PPNG. Conclustion : Our results suggests that the prevalence of PPNG in Seoul is still increasing.

알데히드탈수소효소 2(ALDH2) 및 CYP2E1 유전자 다형성에 따른 요중 뮤콘산 농도와 요중 8-hydroxydeoxyguanosine과의 관련성

김용대,강종원,엄상용,장연위,김성훈,김은영,이철호,문재동,김헌 대한산업의학회 2007 대한직업환경의학회지 Vol.19 No.2