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.

하악골에 발생한 골막 골육종

김태우,김승범,권혁찬,문선재,윤정훈,김형준,차인호,육종인,김진 대한악안면성형재건외과학회 2002 Maxillofacial Plastic Reconstructive Surgery Vol.24 No.1

Periosteal osteosarcoma is a distinct entity of malignant bone tumor with characteristic clinical, morphological, and histological features within the group of juxtacortical osteosarcoma. Periosteal osteosarcoma is predominantly located in the tubular long bones, and extremely rarely involving the jaws. A case of periosteal osteosarcoma of the right mandible is presented. A 27-year-old woman complained of the gingival swelling and bleeding tendency of the right posterior mandible. Clinical examination revealed a reddish brown strawberry-like swelling on the affected mucosa, which measured 1.5㎝×1.5㎝. The tumor was located on the lingual cortex of the mandible and extended into the surrounding soft tissues. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. A minimal bone marrow involvement was noted and the adjacent cortex was free of tumor. These findings suggested that the tumor originated from the periosteal cambium layer, which lies between the periosteal fibrous layer and the cortex of mandible.

당뇨병성 합병증을 가진 환자에서 혈중 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 朝鮮大學校 附設 醫學硏究所 1998 The Medical Journal of Chosun University Vol.23 No.1

연구 배경 : 고혈당성에 의한 산화환원반응 이상(가저산소증)이 조절 되지않는 당뇨병의 특징으로 혈관과 신경 기능에 대한 진성 저산소증의 효과와 유사하며, 당뇨 합병증의 병태생리에 중요한 역할을 한다. 고혈당이 있는 인슐린 비의존형 당뇨병 환자에서 인슐린 수준이 정상이듯이, 빈혈이 있는 당뇨병 환자에서 EPO의 농도는 실제 혈색소 농도의 감소비율과 차이가 있을 것이라 추측된다. Friedman 등은 당뇨병성 합병증 원인 인자로 가저산소증(pseudohypoxia) 또는 저산소증(hypoxia)을 제기하였고 이런 인자들이 EPO의 상대적 또는 절대적 결핍에 의한 것임을 보고하였다. 방법 : EPO-Trac^(TM 125)I RIA kit을 이용하여 방사면역측정법으로 EPO 수준을 검사하였다. 전혈 3㎖을 5-10㎖ 시험관에 정맥 채혈하였으며, 용혈과 장기간의 보존을 위하여 원심분리를 즉시 시행하여 혈청을 영하 200C에서 냉동 보관 후 일괄적으로 검사 결과를 얻었다. 결과 : 1996년 9월부터 1997년 2월까지 조선대학교 부속병원 내과에 입원한 2형 당뇨병 환자 63례를 대상으로 하여 다음과 같은 결과를 얻었다. 1) 당뇨병성 합병증이 없는 군과 있는 군간의 혈색소, 혈중 EPO농도의 차이는 유의한 차이가 있었으며 혈색소의 감소율보다 혈중 EPO의 감소율이 더 높았다. 2) 당뇨병성 망막증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으나 혈중 EPO농도는 유의한 차이가 있었다. 증식성군에서만 혈중 EPO의 감소비율이 혈색소에 비해 높았다. 3) 당뇨병성 신증의 유무에 따른 혈색소, 혈중 EPO농도는 유의한 차이가 있었고 혈색소 감소율에 비해 EPO농도의 감소율이 높았다. 신증의 중증도에 따른 혈색소, EPO의 차이는 미세알부민뇨군을 제외하고는 유의한 차이를 보였고 혈색소 감소율에 비해 EPO의 감소율이 더높았다. 4) 당뇨병성 신경병증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으며 EPO농도는 유의한 차이를 보였다. 혈색소와 EPO의 감소비율은 비슷하였다. 신경병증의 중등도에 따른 혈색소와 EPO농도의 변화는 유의한 차이가 없었으나 stage 3에서는 혈색소감소율보다 EPO감소율이 더높았다. 결론 : 당뇨병성 합병증을 가진 환자에서 빈혈의 정도는 대부분 혈청 EPO치의 절대적 감소에 의함을 간접적으로 밝혀낼 수 있었으며 차후 더 많은 대상으로 비교 분석이 필요하리라 사료된다. Background: Hyperglycemic-induced redox(pseudohypoxia) imbalance is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural functions and plays an important role on the pathogenesis of diabetic complications. As is true for apparently "normal" insulin levels typically found in NIDDM even in the presence of hyperglycemia, a "normal" erythropoietin level in an anemic diabetic subject may be disproportionally low for the actual red cell mass. Therefore, Friedman et al suggested that pseudohypoxia or hypoxia as an etiological factor of diabetic complications are due to absolute or relative erythropoietin deficiency Method: EPO-TracTM 125I RIA kit was used for the quantitative determination of erythropoietin(EPO) in serum by radioimmunoassay. An adequate sample of blood (3ml whole blood) was collected aseptically by venipuncture in a 5~10ml glass tube to yield a minimum of 400 L of serum per assay. The serum was promptly removed from the clot by centrifugation in order to avoid hemolysis. Then to increase its storage time it was frozen at -200C in a nonself defrosting freezer. Finally, tests were undertaken simultaneously Results We studied 63 cases with diabetes mellitus, who were admitted to Chosun University Hospital from September, 1996 to February, 1997 at the Department of Internal Medicine. We defined the control group, as diabetic patients who did not have anemia(<13mg/dl), diabetic complications(retinopathy, nephropathy, neuropathy) and the remainders were defined as the experimental group(we excluded anemic patients, who had secondary causes of anemia and diabetic patients with end stage renal disease)Data were as follow 1) The relationship of Hb and the 24hr urine protein between diabetic patients with and without complications significantly differed(p=0.02, < 0.001 respectively), but the Hb level was poorly related between diabetic patients with and without retinopathy(except in preproliferative, proliferative subgroups) and neuropathy. 2) Subgroups of patients with diabetic complications had higher 24hr urine protein than patients without diabetic complications, except stage I diabetic neuropathy 3) The EPO level was significantly different between diabetic patients with and without complications. 4) The correlation between EPO and Hb was significantly different, especially in diabetic patients with retinopathy and nephropathy according to severity of diabetic complications, compared with patients who did not have diabetic complications such as retinopathy and nephropathy. Conclusion: We know that anemia induced by diabetic complications is due to relative EPO deficiency than absolute EPO deficiency, and further evaluation and studies are needed on many cases in the future

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

Rifampicin에 의한 것으로 추정되는 위막성 대장염1예

김수현,이은우,정종혁,문승현,김동한,양혁승,오영상,김호동,김도현,박혁,박정환,박경옥,이영직 朝鮮大學校 附設 醫學硏究所 2006 The Medical Journal of Chosun University Vol.31 No.2

Pseudomembranous colitis, caused by altering the normal colonic flora and allowing the multiplication of Clostridium difficile, is an deleterious adverse effect of antibiotics. But it is rarely reported by rifampicin. Rifampicin is one of the first line drug in the treatment of tuberculosis and many patients are exposed to its potential adverse effects. We experienced a patient that had abdominal discomfort and hematochezia due to pseudomembranous colitis after receiving antituberculous medication, and which was probably caused by rifampicin. A 82 years old man was admitted with abdominal discomfort and hematochezia for one week. On the past history he had been diagnosed as endobronchial tuberculosis about 4 months ago. Colonoscopy revealed multiple discrete whitish mucosal lesion on rectosigmoid colon, and histologic findings were consistent with pseudomembranous colitis. The antituberculous agents were discontinued and vancomycin was administered. The patient's symptoms were resolved within several days. There was no recurrence after reinstitution of the antituberculous agents excluding rifampicin. We report here on a case of pseudomembranous colitis probably due to rifampicin.

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.

Azithromycin으로 치료한 임신 중 쓰쓰가무시병 1예

김광석,최진욱,서호종,김기훈,박성호,서광섭,고성만,김순혜,김호정 대한감염학회 2001 감염 Vol.33 No.5

We report a case of tsutsugamushi disease in a 26 year-old pregnant woman who was treated with azithromycin. Her gestation period was 27 weeks and she admitted with fever, rash, and eschar on the right shoulder. Currently recommended medications for the treatment of scrub typhus are doxycycline or chloramphenicol. But, these drugs are class D drugs according to the U.S. Food and Drug Administration (FDA) Fetal Risk Summary, so they couldn't be used to treat pregnant women. Recently, a few case reports suggested that azithromycin, a relatively new macrolide antibiotic, was effective and safe for the treatment of scrub typhus in pregnant women. And, there is no evidence that azithromycin causes harmful effects to the developing fetus or to children. On the basis of current in vivo test that confirms the effectiveness of azithromycin, it may be the drug of choice for the treatment of scrub typhus in pregnant women and children. (Korean J Infect Dis 33:380-382, 2001)