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>

신규 방사성 항암제 DW-166HC 의 소핵시험

문은이(Eun Yi Moon),이진(Jin Lee),이원용(Won Yong Lee),최청하(Chung Ha Choi),이덕근(Dug Keun Lee),유제만(Jei Man Ryu),정용호(Yong Ho Chung),윤성준(Sung June Yoon),박경배(Kyung Bae Park) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

DW-166HC (^(166)Holmium (^(166)Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumorigenic spectrum, especially against human hepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous arid intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I (^(165)Ho-Chitosan complex : cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC (^(166)Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr arid 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative controi group but there was significant difference of this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

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.

항암제 AG60이 흰생쥐 위점막 상피세포의 DNA합성에 미치는 영향 : 자기방사법적연구

박경호,안의태,고정식,하상선,한영복,정영신,홍은경,유보림,김상건,이경영,강종구 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.1

모듈화된 계층의 구조를 갖는 시뮬레이션 모델에서의 모델간 연결 방법론과 그 적용 예

하경재,정민수,조대호 慶南大學校 附設 基礎科學硏究所 1995 硏究論文集 Vol.7 No.-

대량의 지식베이스를 처리하는 시스템의 모델링을 하기 위해서는 큰 규모의 데이터베이스에 저장되어 있는 정보를 효과적으로 접근할 수 있어야 한다. 본 논문에서는 데이터가 계층의 구조를 갖고 모듈화 되어 있는 능동적인 기억소자(Processor/memory pair)에 저장되어 있는 시스템의 모델링에 사용할 수 있는 단계적접근(level access)방법론을 어떻게 유사추론 시스템(analogical reasoning system)에 적용 할 수 있는가를 보여준다.

부신적출 토끼신의 Li^(+)처리에 미치는 코티존의 영향

하혜경,장환일,성호경,한홍우 경희대학교 1989 慶熙醫學 Vol.5 No.3

독립협회의 성립과 의회설립운동

하봉규,김경호 釜慶大學校 2000 釜慶大學校 論文集 Vol.5 No.-

The Dong Nip Hyup Hoe was a political and social association, which was organized for the purpose of modernizing Korea through self-independence of Lee dynasty and independent social reform. They contributed remarkably to the modern political history of korea by adapting western political thoughts widely into the traditional political thoughts which had been based on Confucianism. They asserted that sovereignty lies in people because people are the origin of a nation and the government exists for the benefit of people. They insisted that the Eui Whai Won, a kind of parliament, be established as a political system which would realize the korean people's franchise. They tried to realize their political ideals of the government of the people, by the people and for the people by turning an absolute monarchy into constitutional monarchy with the foundation of the Eui Whai Won Now, we can see that they had political thoughts which were very close to those of democracy. They regarded the people at that time as the objects of enlargement, shoeing their skeptical responses as to the people's ability to get the political power.

흰쥐 샘뇌하수체의 면역전자현미경적 연구 : 젖샘자극호르몬 분비세포와 성장자극호르몬 분비세포

하상선,박경호,양남길,안의태,고정식 순천향의학연구소 1995 Journal of Soonchunhyang Medical Science Vol.1 No.2

본 실험은 흰쥐 샘뇌하수체의 세포형태를 밝히기 위하여 이중면역금입자표지법을 이용하였다. 체중 200-250g의 Sprague Dewley계 숫흰쥐를 실험동물로 사용하였다. ether로 마취된 후 뇌하수체전엽을 적출하여 1% glutaraldehyde- 1% paraformaldehyde액으로 일차고정하였으며, 2% osmium tetroxide액에 이차고정하였다. 고정이 끝난 조직은 alcohol과 propylene oxide로 탈수한 후 araldite혼합액에 포매하였다. 포매된 조직은 LKB-V ultratome으로 60-70cm두께의 얇은 절편을 작성하여 300 mesh nickel grid에 붙인 다음 면역염색 및 이중면역금입자표지법을 시행하였다. 젖샘자극호르몬에 대한 면역염색은 sodium m-periodate로 45분간 처리한 다음, 비특이적 면역반응을 제거하기 위해서 bovine serum albumin(BSA, Sigma) 1% 용액을 사용하였으며, 완충용액으로는 Tris buffered saline, pH 8.2(TBS; 20mM Tris buffered + 20mM NaCl + 0.01% sodium azide)을 사용하였다. 일차항체는 rabbit anti ovine prolactin(ICN Chemicals)을 1 : 3,000으로 희석하여 사용하였으며, 이차항체는 biotin이 표시된 goat anti rabbit Ig G(희석비율 1 : 500, Amersham)을 사용하였고, 금입자표지는 streptavidin gold(희석비율 1 : 100, 10nm, Amersham)을 사용하였다. 성장자극호르몬에 대한 면역염색은 sodium m-periodate로 45분간 처리한 다음, 완충용액으로는 phosphate buffered saline, pH 7.4(0.01M)을 사용하였다. 비특이적 반응을 줄이기 위하여 100mM ammonium chloride로 처리한 후 rabbit anti human growth hormone(BioGenex)을 1 : 40으로 희석하여 면역 반응을 시킨후, protein A-gold(희석비율 1 : 50, 5 nm, BioCell)로 금입자표지를 하였다. 이중면역염색은 Bendayan(1982)의 방법을 변형하여 시행하였는데, grid의 한쪽 면은 젖샘분비자극호르몬의 항체, 다른 쪽 면은 성장자극호르몬의 항체로 반응시켰다. 면역염색이 끝난 절편은 uranyl acetate와 lead citrate로 염색한 후 JEM 100 CX-Ⅱ 전자현미경으로 관찰하여 다음과 같은 결과를 얻었다. 흰쥐 샘뇌하수체를 이중면역금입자표지법을 이용하여 젖샘자극호르몬분비세포는 3종류, 성장자극호르몬세포는 2종류로 구분할 수 있었다. 1. 젖샘자극호르몬분비세포는 불규칙한 모양을 한 큰 분비과립(300-700 nm)을 가진 성숙세포, 크기가 다양한 둥근 분비과립(150-200 nm)을 가진 중간 세포와 크기가 작은 둥근 분비과립(100-150 nm)을 가진 미성숙세포로 나눌 수 있었다. 2. 성장자극호르몬분비세포는 크고 둥근 분비과립(200-500 nm)을 가진 제 1 형 세포와 상대적으로 작고 둥근 분비과립 (150-200 nm)을 가진 제 Ⅱ형 세포로 나눌 수 있었다. 3. 젖샘자극호르몬과 성장자극호르몬이 한 세포내에 함께 존재하는 경우는 관찰 할 수 없었다. This experiment was aimed at clarifying immunocytochemical characteristics of growth hormone cells and prolactin cells in male rat adenohypophysis, using double immunogold method. Under ether anestehesia, male rats weighing 200-250 gm were decapitated. Adenohypophysis were fixed in the 1% glutaraldehyde - 1% paraformaldehyde solution. followed by refixation in the 2%osmium tetroxide solution. Dehydrated blocks were embedded in araldite mixture. The sections were cut on a LKB V ultrotome, and ultrathin sections were placed on nickel rid(300 mesh). The section-bearing grids were floated upside down on th esolutions in a moisture chamber at room temperature. Sections were etched with a saturated solution of sodium m-periodate for 45 min. Aftr etching. sections were pretreated with 0.02M Tris buffered saline(TBS), pH 8.4, with 1% bovine serum albumin(BSA, Sigma) for 60 min, then treated with rabbit anti-sheep prolactin(ICN incubated 60 min in biotinylated goat anti-rabbit IgG(Amersham) diluted 1:100 in TBS with 0.1% BSA. Then sections were incubated on streptavidin gold rinsed with TBS with 0.1% BSA. After each step, the grids were briefly rinsed with TBS with 0.1% BSA. After the streptavidin gold step, the sections were jet washed with distilled water. According to Bendayan(1982) method, the opposite side of the grid was etched with saturated solutin of sodium m-periodate for 45 min. Aftr etching, sections were treated with 0.01M phosphate buffered saline(PBS), pH 7.4, with 0.1% BSA and 0.1M ammonium chloride for 60 min, then treated with rabbit anti-human growth hormone(BioGenex) diluted 1:40 in PBS with 0.1% BSA for overnight. Grids were incubated 60 min in protein A-gold(5 nm, BioCell) diluted 1:50 in PBS with 0.1% BSA. The sections were jet washed with distilled water. The ultrathin sections stained with uranyl acetate and lead citrate were observed with JEM 100CX II electron microscope. The results were as follow: Three types of prolactin cells and two types of growth hormone cells of the rat adenohypophysis were recognized by double immunogold electron microscopy. 1. Matrue prolactin cells are characterized by irregulary shaped large secretory granules (300-700 nm): intermediate type cells contain round granules of varying sizes(150-200 nm): and immature type cells have small round secretory granules(100-150 nm). 2. Type I growth hormone cells are characterized by large round secretory granules(200-500 nm): type II growth hormone cells are characterized by large round secretory granules(150-200 nm). 3. In the male rat adenohypophysis double immunogold labeled with 10 nm gold particles for prolactin and with 5 nm gold particles for growth hormone proved that growth hormone and prolactin were not contained in the same cell at the same time.

실시간 렌더링을 위한 다각형 감소 기법 연구

하정호,윤경현 중앙대학교 기술과학연구소 1997 기술과학연구소 논문집 Vol.27 No.-

현재 컴퓨터 그래픽스 기술을 이용하여 물체를 표현하기 위한 작업들은 물체의 복잡도에 따라 많은 시간을 요구한다. 따라서, 실시간 렌더링을 요구하는 응용분야에서는 다른 기술을 요구한다. 이러한 요구에 따라 본 연구에서는 실시간 렌더링을 지원하기 위해서 물체의 원형을 유지하면서 단순화시키는 다각형 감소 기술을 다루고 있다. 다각형 감소를 위해서 물체의 지형정보 분석, 면합성, 재삼각형화 같은 기술들이 필요하다. 본 연구를 통하여 기대되는 효과는 현재 많이 연구되고 있는 가상현실 공간에서나 지형저보시스템등에서 더욱 빠른 시간내에 현실감있는 영상을 만들 수 있을 것으로 기대된다. In present, the jobs which express objects with computer graphics need execution time as much as object complexity. So, real-time application needs other techniques. In this research, we studied the polygon reduction technique which maintain the object frame and reduce the object. This technique require the geometric analysis of object, face merge and re-triangulation. In this research, the applied region which we hope are VR(Virtual Reality) and GIS(Geographical Information System).

동국대학경주병원에서 분리된 각종 병원성 세균 및 항생제 감수성 양상

하경임,고은하,전창호,정병욱,안우섭,김우택,배정수,어경윤 동국대학교 경주대학 1993 東國論集 Vol.12 No.-

We investigated characteristics of bacterial infection and antimicrobial suscerptibility patterns of clinical specimens in Dong Guk University Kyong Ju Hospital from october 1991 to december 1992. The types of clinical specimens requested for culture were as follows ; pus(34.2%), urine(29.6%), sputum(25.2%), blood(9.2%), etc. The most frequently isolated organisms were E. coli(17.6%), Pseudomonas(12.7%), S. aureus(12.2%), and CNS(11.2%), orderly. Predominant organisms from pus, urine and sputum were S.aureus, E. coli and Pseudomonas. Blood culture was requested 1,244 samples from 614 patients, 91 pathogeni organisms were isolated(14.8% from patient and 7.3% from requested clinical samples). E. coli was most frequently isolated(29.7%) and Salmonella typhi was noted 8.8% from the requested samples. The patterns of isolated organisms according to departments were as follows ; E.coli and Klebsiella were frequently isolated in internal medicine and general surgery, E.coli and Pseudomas in Neurosurgery, S. aureus and Pseudomonas in orthopedic surgery. In ICU, Pseudomonas was predominatly isolated and the rate of mixed infection was also high(16.4%). Most of gram-negative bacilli revealed relatively high susceptibility to Chlorampenicol, Amikacin, Tobramycin and Carbenicillin, but Acinetobacter were only susceptible to Carbenicillin and Tetrecyclin, and Serratia were to Carbenicillin and Amikacin while Salmonella were susceptible to all tested first drugs. The proportions of multi-drug resistant bacteria were 34.9% of Acinetobacter, 21.1% of Serratia, 20.0% of Pseudomonas and 15.4% of Citrobacter but Aztreonam was highly susceptible(84∼100%) except Acinetobacter. S. aureus and CNS were susceptible to Chlorampenicol, Oxacillin, Cephalothin and Vancomycin, especially, 100% susceptible to Vancomycin. But Methicillin reistant Staphylococcus aureus were very high(49%) inspite of new constructed hospital. Pneumococcus and Streptococcus species were relatively high susceptible to all tested drugs.