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>

사과 추출물과 phloretin에 의한 항염증 활성

김근호(Geun-Ho Kim),이은주(Eun-Joo Lee),류승민(Seung-Min Ryu),손호용(Ho-Yong Sohn),김종식(Jong-Sik Kim) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

본 연구에서는 풋사과의 열수추출물(GAHW)과 에탄올추출물(GAE), 그리고 애사과 열수추출물(UAHW)을 제조하고 LPS로 활성화된 RAW264.7세포주를 이용하여 이들의 항염증 활성을 연구하였다. 모든 추출물이 세포생존율에는 영향을 미치지 않고 nitric oxide (NO) 생산을 저해하였으며, iNOS의 발현도 감소시켰다. 반면, UAHW만이 COX-2의 발현을 저해하였다. 또한 모든 추출물이 모든 MAPKs의 인산화를 감소시켰다. 모든 추출물이 ROS의 생산을 농도의존적으로 감소시켰으며, GAHW와 GAE에 의해 HO-1의 발현이 증가됨을 확인하였다. 또한, 사과 flavonoid인 phloretin과 phloridzin의 항염증 활성을 연구하였다. Phloretin은 농도의존적으로 NO의 생산을 저해하였으나, phloridzin은 NO 생산에 아무 영향이 없었다. 또한, phloretin은 iNOS와 COX-2 단백질의 발현을 감소시킨 반면, phloridzin은 두 단백질 발현에 영향을 주지 못하였다. 따라서, 이러한 연구결과는 사과 추출물은 MAPK 경로와 HO-1 경로를 조절함으로써 항염증 활성을 가지며, phloretin이 사과의 항염증 활성을 담당하는 파이토케미칼의 하나가 될 수 있음을 제시한다. In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

Mg₂SiO₄ : La, Ho 열형광선량계에서 활성제 농도가 글로우 커브에 미치는 영향 La, Ho TLD on Activation Concentration

김영국,손인호,채건식,노경석,오재근,이은숙 경남대학교 신소재연구소 1996 論文集 Vol.6 No.-

본 연구에서는 Mg₂SiO₄에 활성화 물질로 La, Ho를 첨가하여 열형광체를 제작하였고 불순물의 농도를 1wt.% ∼5 wt.%까지 변화시키면서 열평광강도의 glow curve를 측정하였다. 도한 열형광체의 glow curve를 peak shape법으로 분석해서 TL특성에 대한 포획 매개변수와 활성화 에너지, 발광차수, 선량의존성등을 조사하였으며, 그 물리적 특성을 조사하고 선량계로서 타당성과 실용성을 확인하였다. The Mg₂SiO₄: La, Ho thermoluminescent phospher has been prepared by sintring Mg₂SiO₄after doping the transition elements La and Ho. The heating rate is 10℃/sec at this thermoluminescent phospher are heated. The maximum peaks are found in the measured Mg₂SiO₄: La and Ho. TL glow curve at 229℃ and 345 C when the 1 wt.%-5 wt.%. The glow curve of TLD increased TL intensity and temperature of peak appears to the high temperature when the heating rate is l0℃/sec-25℃/sec. The activation energy of the main peak has been estimated by the peak shape method. The estimated activation energies are 1.77 eV. 1.52 eV respectively. The thermoluminescence process in Mg₂SiO₄: La and Ho are found to the 2nd order when the main peak of the glow curve is analyzed by peak shape method. The dose responses of Mg₂SiO₄: La and Ho TLD are linear up to intensity of X-ray.

사회보장법 총론의 가능성

이호근(Lee, Ho?Geun) 한국사회보장법학회 2012 사회보장법학 Vol.1 No.1

본 논문은 우리나라 사회보장기본법 관련 그 연원, 체제, 구성 및 주요 내용과 쟁점 사항을 분석한다. 논문은 헌법상 사회권과 사회보장의 법적 성격과 관련 판례 및 그 주요 쟁점사항들을 살펴본다. 특히, 논문은 최근 개정되어 2013년 1월에 그 시행을 앞둔 개정 사회보장기본법의 체제와 그 세부적인 내용을 검토하고 개정 법의 방향과 그 쟁점들을 분석 ? 평가한다. 논문은 개정 사회보장기본법이 한편에서 ‘새로운 사회적 위험’을 재정의하고 그리고 다른 한편에서, 기존 사회보장의 대상과 수급권보장 방법에 대한 효율화를 전제로 제 사회보장의 문제에 대한 대응을 개선하고자 하는 목적에서 그 개정논의가 진행되어 왔다고 평가하면서 그 내용과 체제에 대한 현황 분석과 함께 한계와 문제점들을 지적하고 있다. 즉 개정 법은 먼저, 우리나라 법체계상 사회권과 사회보장 기본권이 실현되는 헌법?사회보장기본법-사회보장관련 개별법간의 구조에서 사회보장기본법의 법적성격의 근본적인 변화나 사회보장의 규범력을 제고시켜주는 방향으로의 근본적인 변화는 크지 않다고 평가한다. 둘째, 반면 기존의 ‘사회복지 관련 서비스’를 대신하여 새롭게 제시된 ‘사회서비스’는 그 개념의 포괄성에도 불구하고 실제로는 법적구속력이 없거나 약하며 재량행위로 여겨질 수 있는 정책사항이 대부분으로 사실상 미래의 사회보장권은 그 천명된 방향성에도 불구하고 그 권리의 성격이 제고되었다고 말하기 힘들다고 평가한다. 셋째, 논문은 사회보장관련 통합전산망의 강화 등 효율화에 대한 강화조처는 징벌적 제재에 의해 수급권의 범위가 오히려 축소되는 현상이 나타나고 있음을 지적하고 있다. 다시 말해 개정법은 미래의 위험에 대해서는 ‘현금’대신 재량행위나 정책사항으로 보장성이 약한 ‘어음’을 지급하고 현실의 위험에 대해서는 오히려 예외여야 할 사회보장수급권의 오ㆍ남용이 사회보장의 중심 사안인 것처럼 그 법적 제재나 규제가 강화되어 오히려 사회보장 수급권은 전체적으로 약화되는 결과가 될 우려를 지적하고 있다. 넷째, 법적체제의 중복과 불완전성으로 중앙과 지역차원의 통일적인 사회보장ㆍ사회복지체제의 연계의 문제와 통합의 강화 주장에도 불구하고 여전히 중앙과 지역간 법체계의 중복과 법적권한의 불분명성 등 법체계와 재정분담 재조정 문제 등 정비되어야 할 과제를 안고 있다고 지적한다. 마지막으로, 논문은 사회보장의 사각지대에 있는 영세자영업자 포괄의 문제, 정규직 사회보장 중심으로 되어있는 현행 체제의 문제점 등에 대해 개정법안은 여전히 해법을 제시하지 못하고 있다고 지적한다. 또 장기적인 과제로 궁극적으로 사회보장수급권을 담지하고 이행하기 위한 ‘통합사회법’ 제정의 필요성과 독립적인 ‘사회보장청’ 신설문제와 같은 점을 향후 사회보장기본법의 또 다른 과제로 지적하고 있다. This article is trying to analyze the historical development, content, system and structure as well as some controversial issues of the (revised) Social Security Basic Act in Korea. The article is first focusing on the legal character of social rights and social security envisaged in the Constitution and Social Security Basic Act and its related jurisdiction and the central issues. Especially, the article is intensively analyzing the newly revised Social Security Basic Act, which would be implemented from the January in 2013 on, and the important trend and orientation for the future welfare policy. The revised Social Security Basic Act is being to be spoken as the preparatory trial for the future welfare reform, in which one is redefining the new Social Risks at one side, and one is trying to get more trans parency and efficiency in welfare distribution at the other side. However, there are yet some controversial issues and points in this new Act. First, it is not to see, that even though there are redefinition of the new Social Risks and some kind of emphases on them, one can recognize either any significant change in the basic status of the social rights or its improved legal character. Secondly, in spite of introducing new concept of ‘Social Service’ to the old social welfare and related services, there are not any binding legal ‘rights’, while they remain at best in the beneficiary and voluntary meature. Thirdly, there are several intensified measures (penalty and sanction of the social security entitlements) to make the welfare delivery system more transparent and efficient through the introduction of Electronically Integrated Information Service System to control the unlawful beneficiaries. While this Electronically Integrated Information Service System can be serving to limit the entitlements against the misuse and mal practices of welfare distribution, it is on the brink of falling in the risk to exclude the existence rights of some needy social groups. Fourthly, the revised Social Security Basic Act is lacking in the any improvement of legal rights, while the control function and mechanism in the name of efficiency and transparency have been intensified. At the same time, there should be some institutional improvement for the better coordination between the central social policy and regionally specified social requirements, including the financial burden-sharing. Finally, it is to request that the future welfare policy and law should find out the way to integrate the precarious self-employers and the non-standard workers in the welfare system. And for the better efficiency and transparency of the Social Service Delivery, one should consider the introduction of the Integrated Social Security Act as well as the establishment of the Social Security Office in the long term.

다중흐름모형에서 정책기업가의 역할 시론적 연구 : 공무원 범죄에 관한 몰수 특례법(전두환 추징금 사례 1997~2013)의 개정 논의를 중심으로

Dong Kyu Lee,Dong Geun Yum,Jun Ho Lee,Kyoung Rok Kim 위기관리 이론과 실천 2014 Crisisonomy Vol.10 No.11

This study examines the preceding researches on the policy entrepreneurs at home and abroad and after discussing the policy entrepreneurs, analyzes the flow of the revision process of the partial revised bill(hereinafter referred to as Chun Doo-hwan Collection Law) of the confiscation special law about public official crime by administration using the multiple streams framework model, and this researcher attempts to analyze the activities of how the policy entrepreneur among diverse policy actors who plays an important role in opening policy window influenced the revision process in the process of enacting the partial revised bill of the confiscation special law about public official crime. And how the policy window of the partial revised bill of the confiscation special law about public official crime that was not opened in the previous administrations came to be opened in the Park Geun-hye administration is analyzed. The results of this study confirmed that in the previous administrations the policy entrepreneur to open the policy window did not appear but in the Park Geun-hye administration President Park Geun-hye played the role of the policy entrepreneur, producing Chun Doo-hwan 본 연구는 정책기업가 대한 국내외 선행연구를 검토하고, 정책 기업가에 대한 심도있는 논의를 하고자 하였다. 또한 공무원 범죄에 관한 몰수 특례법 일부 개정안(이하 전두환 추징법)의 정책과정을 다중흐름모형을 이용하여 각 정권별로 흐름을 분석하였다. 공무원 범죄에 관한 몰수 특례법 일부 개정안의 정책결정 과정에서, 정책기업가 (policy entrepreneur)가 어떻게 중요한 영향을 미칠 수 있는 활동을 할 수 있었는지에 대한 분석을 시도하고자 한다. 그리고 이전 정권에서는 열리지 않던 ‘공무원 범죄에 관한 몰수 특례법’ 일부 개정안에 대한 정책의 창이 현재 박근혜 정부에 와서는 어떻게 열리게 되었는지에 대한 분석을 한다. 연구결과, 이전의 정권들에서는 정책의 창을 여는 정책기업가가 나타나지 않았고, 박근혜 정부에서는 박근혜 대통령이 정책기업가의 역할을 하여 전두환 추징법이 산출되었다는 것을 확인하였다.

복어중독에 의한 가사 상태에서 소생한 1예

송승찬,신진호,강석우,박경남,최호순,박근태,문희식,기춘석,이성희,윤병철,노우균,조균석,이민호 大韓應急醫學會 1998 대한응급의학회지 Vol.9 No.3

Tetrodotoxin is a neurotoxin produced by about 90 species of puffer fish and causes paralysis of central nervous system and peripheral nerves by blocking the movement of all monovalent cation. Ingestion of tetrodotoxin produces clinical manifestations such as paresthesias(within 10-45 min), vomiting, lightheadedness, salivation, muscle twitching, dysphagia, difficulty in speaking, convulsion and death that expressed by cardiopulmonary arrest with loss of brain stem reflex sometimes. Tetrodotoxin prevents or delays ischemia induced neuronal death by way of following 3 mechanisms. Firstly, it reduces the energy demand of the brain tissues. Secondly, it delays or even prevents anoxic depolarization. Finally, it deminishes ischemia induced cell swelling and cerebral edema. We report a case of puffer fish poisoning which presented with cardiopulmonary arrest and loss of brain stem reflex, but completely recovered by aggressive cardiopulmonary resuscitation.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae-Kyeong,Kang, Mi-Sun,Lee, Ho-Youn,Seo, Moo-Sang,Kim, Si-Geun,Kim, Chi-Dae,Lee, Won-Suk The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

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.

항공레이저 측량 자료의 해상도에 따른 DEM 오차 비교평가 연구

이근상,고덕구,채효석,신영호 한국지리정보학회 2003 한국지리정보학회지 Vol.6 No.3

최근 높은 수직정확도를 갖는 항공레이저측량 기술이 개발됨에 따라 이를 이용한 DEM(digital elevation model) 생성, 건물추출, 홍수위험지도 제작, 3차원 도시모델 구축 등의 다양한 연구가 활발하게 수행되고 있다. 본 연구에서는 항공레이저측량으로부터 취득한 원시자료로부터 생성한 해상도별 DEM의 표준편차를 계산하기 위해 점비교법, 등고선비교법 그리고 1/5,000 수치지형도를 활용하였다. 비교결과 점비교법이 등고선비교법보다 낮은 DEM 표준오차를 나타냈으며, 이것은 등고선비교법이 점비교법에 비해 조밀한 격자 연산이 이루어지지 않은 것이 원인으로 파악되었다. 또한 1/5,000 수치지형도는 평균수평거리인 25.4m 이하에서는 점비교법과 등고선비교법에 비해 높은 오차를 보였으며, 25.4m 이상에서는 등고선비교법과 유사한 결과를 나타냄을 알 수 있었다. As airborne laser scanning technique is developed with high vertical accuracy recently, there come many studies on DEM(digital elevation model creation, building extraction, flood risk mapping and 3D virtual city modeling. This study applied point comparative method, contour comparative method and digital map with scale 1/5,000 to calculate RMSE of DEM in according to resolution that was constructed using rawdata being acquired by airborne laser scanning. As a result, point comparative method showed lower DEM standard error than contour comparative method, it is a reason that contour comparative method was not carried out detailed grid calculation for point comparative method. Also, digital map with scale 1/5,000 showed higher DEM standard error than point comparative method and contour method in below 25.4m that is average horizontal distance among contour line, and showed similar result with contour comparative method in over 25.4m.