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.

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.

혈관질환 정보관리 시스템

김동익,김덕경,허세호,이병붕,김용신,김은숙,문지영,도영수,신성욱,김동수,김만태,진재욱,김용신 대한혈관외과학회 2002 Vascular Specialist International Vol.18 No.1

As medical technology progresses rapidly, there is a rise in the average age along with the Korean dietary lifestyle becoming more westernized, which leads to an increase in the number of vascular disease patients in Korea. Thus, we need to manage the medical information of a disease systematically in order to diagnose and treat constructively. However, since there has been no standardized method of man agement to date, a great deal of information could not be properly utilized nor studied. Therefore, the departments of Cardiology, Radiology and Neurology of Samsung Seoul Hospital recently got together to develop an information management system called the Vascular Data System. This program was developed to be run on win98 O/S, upper Pentium Ⅲ, and upper 128 MB Memory, and its source code is Dephi 4.0. It was configured for the user to set the configurations as well as do a variety of search and analysis. If this program were to be updated continuously, it may be used extensively as well as in various parts of clinical research activities.

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.

전통누룩 진균류를 이용한 입국의 제조 및 입국곰팡이의 동정

김재호 ( Jae Ho Kim ),권영희 ( Young Hee Kwon ),이애란 ( Ae Ran Lee ),김혜련 ( Hye Ryun Kim ),안병학 ( Byung Hak Ahn ) 한국균학회 2012 韓國菌學會誌 Vol.40 No.4

다양한 향미를 가진 막걸리의 개발을 위해 전통누룩으로부터 분리한 곰팡이로 입국을 제조한 후 품질특성을 분석하여 입국의 규격에 적합하며 이취가 없고 관능이 우수한 9균주를 입국 제조용 우수균주로 최종 선발하였다. 선발된 균주는 Aspergillus oryzae(C1-5-2-2, C20-7-3, CN1.3.1-4, CN16.19.1-1, N152-1, N220-1), Mycocladus corymbiferus (N162-2), Rhizopus oryzae(N20), Lichtheimia corymbifera (N21)로 동정되었으며, 제조한 입국의 산도는 5.0~6.8, 당화력은 128~241sp이었다. Various koji were prepared by fungi isolated from traditional nuruk and their quality characteristics were investigated. Acidity and saccharification power of their koji were ranged in 5.0~6.8 and 128sp~241sp. Nine fungi which were showed good quality and sensory evaluation were identified by analysis of their nucleotide sequences with PCR-amplified 18S rDNA internal transcribed spacer-1(ITS-1) and ITS-4 genes. Among them, six strains were identified as Aspergillus oryzae and the other strains were identified as Mycocladus corymbiferus, Rhizopus oryzae, Lichtheimia corymbifera.

수면량과 집중력의 상관관계

김병우,류지근,박우진,박계원,김미정,임지은,백대현,최재덕,최윤호,이가현,이관,김덕수 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.1

수면, 기억 그리고 학습의 연관성은 실제 매우 복잡하다. 많은 연구에도 불구하고 명확한 연구결과는 아직 없다. 우리는 이 연구에서 평소와는 달리 시험 전날 수면 변화 양상이 집중력에 어느 정도 영향력을 미치는지 알아보고자 하였고, 이를 이용해 효율적인 수면 관리를 할 수 있는 기초자료로 삼고자 하였다. 동국대 의대 본과 1학년생 중 지원자 30명과 본과 2학년생 10명을 대상으로 평상시 상태와 시험 직후 수면이 부족한 상태에서 각각 K-PES TEST를 실시하여 총 8항목에 걸쳐 암기력, 판단력, 단순반응의 변화정도를 검사하였다. 또 설문조사를 병행하여 결과에 영향을 미칠 수 있는 다른 인자들도 파악하였다. 수면량에 대한 부호 숫자 짝짓기(순간 판단력)을 검사한 결과, 인간의 최대 생리학적 기능은 꼭 수면부족에 의해 좌우되는 것은 아니다. 그러나, 수면감소는 피로를 증가시키고, 동기부여를 감소시키나 단, 새로운 사실을 학습하는 데에는 큰 영향을 끼치지 않는다. 즉, 수면부족으로 장시간 깨어있는 것은 정확성과 반응성을 떨어뜨린다. 흡연에 대한 부호 숫자 짝짓기(순간 판단력)을 검사한 결과, 니코틴의 수면에 대한 상호관계는 알려지지 않았고, 인간의 감정이나 의식, 인식에 영향을 주는 것으로 알고있지만, 장기적은 측면에서 흡연이나 알코올은 인식능력과 무관한 것 같다. 카페인에 대한 숫자 외우기(암기력)검사 결과, 카페인은 spacial selective attention에는 특별한 영향을 주지 않지만 지각과정이나 주의 집중에 큰 효과를 주며, 인간의 의식 수행에 긍정적인 효과를 준다. 즉 카페인은 활력, 혼란, 피로상태를 변화시키고 visual analog scales에서 휴식상태에 가까운 양상을 나타낸다. 또 48시간 동안 수면을 취하지 않은 사람에게 카페인은 집중력과 장시간의 좋은 기분을 유지하게 하였다. 그러나 규칙적, 비규칙적으로 먹는 사람간에는 인지수행력의 차이를 보이지 않으며 상용자에서는 상당한 내성이 보인다. 수면패턴에 대한 숫자 더하기(순간 판단력)검사 결과, 집중력은 수면패턴에 의해서도 영향을 받고, 수면패턴이 바뀌게 되면 순간판단력을 저하시킨다. This study was performed to evaluate relationship of sleep and attention, and to control sleep effectively. We conducted a K-PES test of 40 medical students. K-PES contains eight elements, for example, simple response, selective response, color pairing, OddEven discrimination, number addition, number-symbol matching, memory, right-tapping, left tapping. Through these, we tested changes of memory, judgement, simple response. And we conducted a questionnaire survey to exclude bias. Results are as follows. As a results of number-symbol matching test, we know that sleeplessness is not complete responsible for physiologic function for humans. But, decreased sleep increases fatigue and decreases motivation, but no influence on learning new materials. So, long term sleeplessness decreases precision and responsibility. As a results of number-symbol matching test on smoking, a relationship of nicotine and sleep is not certain. A point of view in long term period, smoking and drinking is not related cognition, even if we know that those influence mood, consciousness and cognition. As a results of memory work test on caffeine, caffeine does not influence spacial selective attention, but mainly does perception, attention and consiousness process. Namely caffeine changes energetic activities, chaos, fatigue states and shows resting state in visual analog scales In sleeplessness for 48 hours, caffeine produced attention and good mood for a long time. But, in case of cognitive process no significance shows in regular or irregular diet. Regular diet shows high resistance. As a results of number addition test on sleep patterns, seep patterns influence attention, changes of sleep patterns decrease a moment judgement.

경막내 척수외 종양의 수술적 치료

신병준,이재철,윤태경,정호원,한성우,김동원,김경제,김연일 대한척추외과학회 2002 대한척추외과학회지 Vol.9 No.3