Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we 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 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression

Yun-Jeong Choe,고경원,Hyein Lee,이선영,Byung-Chul Kim,Ho-Shik Kim,Ho-Shik Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4

Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</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.

Stain improvement in the white button mushroom ‘Seolgang’ and its varietal characteristics in Agaricus bisporus

Byung-Joo Lee,Mi-Ae Lee,Yong-Gyun Kim,Kwang-Won Lee,Yong-Pyo Lim,Byung-Eui Lee,Ho-Yeon Song 한국버섯학회 2012 한국버섯학회지 Vol.10 No.4

The button mushroom (Agaricus bisporus) is one of the most widely cultivated important edible mushroom species. In the breeding of new button mushroom, ‘Seolgang’ was developed by crossing two monokaryons ‘CM020913-27’ and ‘SSU423-31’. Because of the secondarily homothallism, only a small percentage of the basidia produce 3 or 4 spores, which are mostly haploid (n) and do not fruit. Single spore cultures derived from these types of spores produce a vegetative mycelium that also contain a variable number of genetically identical nuclei per cell called monokaryon. The lack of clamp connections between monokaryon and dikaryon required a series of mycelial culture and fruiting test. After crossing, hybrids were cultivated on a small scale and on a commercial scale at a farm. For this, the spawn was made by a commercial spawn producer and the spawned compost by a commercial compost producer. Mycelial growth of ‘Seolgang’ on CDA was better at 20℃ and 25℃ when it was compared with that of ‘505 Ho’. The mature cap shape of new strain ‘Seolgang’ is oblate spheroid and the immature cap shape is round to oblate spheroid. The cap diameter was 41.2 mm on average. In comparison with white strain ‘505 Ho’, the strain had a yield that was 9% higher. It produced fruiting bodies which had a higher weight on average per fruiting body and were 19% firmer with a good shelf life. Days of fruiting body were 3-4 days later than those of ‘505 Ho’. The physical characteristics such as elasticity, chewiness, adhesiveness were better than that of ‘505 Ho’. Genetic analysis of the new strain ‘Seolgang’ showed different profiles compared to ‘505 Ho’, CM02913-27, SSU413-31, when RAPD primers A02 and O04 were used.

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.

紫胡淸肝湯이 CCI₄ 中毒白鼠의 肝損傷에 미치는 影響에 ?하여

金德鎬,金定濟,金秉蕓,禹弘楨 慶熙大學校韓醫科大學韓醫學硏究所 1980 慶熙韓醫大論文集 Vol.3 No.-

노인 환자에서 경피적 관동맥 중재술 후 조영제 유발 신부전의 발생률, 위험인자와 임상적 의의

김광일,배장환,강현재,채인호,김효수,손대원,김철호,오병희,이명묵,박영배,최윤식 대한노인병학회 2004 대한노인병학회지 Vol.8 No.1

질소산화물의 급성 노출로 인한 폐 손상 1례

김정호,김대환,손병철,이창희,김정원,문덕환,이채언,김주인 대한산업의학회 2000 대한직업환경의학회지 Vol.12 No.2

Objectives : Lung injuries due to exposure to nitrogen oxides can occur in various process in industry. We experienced a case of chemical pneumonitis induced by accidental inhalation of nitrogen oxides emitted from the bath in an acid dipping operation. Case : Dyspnea, cough and blood-tinged sputum production, cyanosis, and tachypnea occurred after exposure to oxides of nitrogen. There were bilateral diffuse ground glass opacities in simple chest radiography and high resolutional computed tomography, hypoxemia in arterial blood gas analysis, mixed ventilation defect and reduced diffusion capacity in spirometry. As an oxygen and supportive therapy, after hospitalization, was given, the patient recovered completely from the lung injury on the 8th day after admission. There was no evidence of delayed onset of bronchiolitis obliterance or pulmonary edema in a follow-up for about 6 months. Conclusions : Acid dip operation require more efficient hooding and exhausting system for the prevention of lung injuries caused by inhalation of nitrogen oxides. Also health education for worker need.