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.

소에서 盲腸擴張을 동반한 第4胃食滯 手術 1例

김명철,김덕환,신상태,임준호,김남중,김종만 충남대학교 수의과대학 동물의과학연구소 1998 動物醫科學硏究誌 Vol.6 No.-

Abomasal impaction with cecal dilatation was diagnosed in a 3 years old holstein cow. The clinical signs were loss of appetite, scant feces and moderate distension of the abdomen. Ping sound was revealed in the right 11th intercostal space by auscultation. Cecal dilatation and abomasal impaction were ascertained by right flank laparotomy and abdominal exploration, and intestinal content and gas were removed from the cecal apex incised. One day later, 2.5㎏ of sand was removed by ventral paramedian abomasotomy.

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.

PVA-ECC를 활용한 Half PC 복합체의 역학적 특성에 관한 실험적 연구

김재환,김영덕,김갑수,조봉석,장종호,김무한 대한건축학회 2003 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.23 No.2

ECC represents one particular class of HPFRCC, which are defined by an ultimate strength higher than their first cracking strength and the formation of multiple cracking during the inelastic deformation process. This study is to provide the fundamental data for the development of hybrid construction method such as the half PC(Precast concrete) reinforced by PVA-ECC, the mechanical properties of half PC according to the alteration of properties of PVA-ECC in terms of the type of fiber, Vr, S/M, placing height of PVA-ECC, are experimentally investigated. As the results. it is found that the half PCs of PVA-ECC have very higher mechanical performance in terms of yield load, strain capacity beyond yield point and maximum flexural load than that of mortar. Also, flexural crack in the half PCs of PVA-ECC are not localized at first crack and are growed to many micro crack, especially multiple cracking in specimen of P(12)-30-0.1ㆍ3 occurred.

A Study on Crisis Management and Negotiation Strategies for the Denuclearization of the Korean Peninsula

Ho Jung Kim,Jong-ha Kim 위기관리 이론과 실천 2018 Crisisonomy Vol.14 No.8

The purpose of this article is to examine what types of crisis management and negotiation strategies the Korean government should pursue in the denuclearization process of the Korean peninsula. The findings are as follows. First, it is necessary to make political and diplomatic commitments to the North Korean leader Kim Jong-un for the security of his regime. Second, North Korea sanctions should remain in place until complete denuclearization. Third, the US-South Korea military cooperation must be reinforced to put pressure on North Kore. Fourth, a ‘win-win’ cooperative negotiation strategy should be used, even if North Korea abandons its nuclear program. The implications of these findings include that South Korea needs to boost strategic and tactical responsiveness in the debates on the dismantlement of North Korea’s nuclear weapons and prepare for crisis management and negotiation strategies to ensure and maximize national interests. 본 논문의 목적은 한반도 비핵화를 추진해 나가는 과정에서 한국정부가 어떤 위기관리 및 협상전략을 추구해 나가야 하는지를 고찰하는데 있다. 연구결과는 다음과 같다. 첫째, 북한의 김정은 위원장에게 체제보장에 대한 정치적 ·외교적 공약을 제시하는 것이다. 둘째, 북한에 대한 경제측면에서 봉쇄적 제재를 비핵화가 완성될 때까지 지속하는 것이다. 셋째, 한미 간의 군사 협력과 안보협력 강화를 통한 대북 군사적 압박을 하는 것이다. 넷째, 북한이 핵을 포기하더라도 상호 윈-윈(Win-Win)할 수 있도록 협력적 협상이 되도록 하는 것이다. 이런 연구결과의 시사점은 북핵 폐기를 위한 남북 및 북미 실무회담에서 전략적, 전술적 대응력을 강화하고, 최대의 국익을 보장하기 위한 위기관리 및 협상 전략을 마련할 필요가 있다는 것이다. 따라서 한국은 철저히 준비된 위기관리전략과 협상전략으로 북핵 폐기를 완성해야 할 필요가 있을 것이다.

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