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>

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

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.

조구등(釣鉤藤)의 4-VO로 유발한 흰쥐뇌허혈에 대한 신경방어효과

李仁煥,林康鉉,李鍾錫,石庚浩,安德均,朴虎君,김頀哲 대한본초학회 1999 大韓本草學會誌 Vol.14 No.2

Uncariae Ramulus et Uncus(UR, ???) has sweet in flavour and slightly cold in property, acting on the liver and pericardium channels. This drug was described in a medical classic as having the ability to remove "heat", check hyperfunction of the liver and relieve dizziness, tremors, and convulsion, and subdue "endogenous wind". So this study was planned to check the neuroprotective effect of UR on the global ischemia induced by 4-vessel occlusion in Wistar rats. and UR extract was lyophilized after extraction with 70% methanol. We induced 4-vessel occlusion for 10 minutes and reperfused again. The number of CA1 pyramidal neurons were counted after 7 days of reperfusion under the cresyl violet staining. In 4-VO ischemia model, UR showed significantly neuroprotective effects(1,000 and 500 ㎎/㎏ of UR extracts, p<0.05) compared with control group. Each neuroprotective ratio was about 23.0%, 19.0% respectively. Consequently, Uncariae Ramulus et Uncus has neuroprotective effects on the global ischermia induced by 4-vessel occlusion in Wistar rats. So we expect that Uncariae Ramulus et Uncus can be used as a drug for neurodegenerative disease.

Adult Patients with Congenital Muscular Torticollis Treated with Bipolar Release : Report of 31 Cases

Lee, Gun Sang,Lee, Myung Ki,Kim, Woo Jae,Kim, Ho Sang,Kim, Jeong Ho,Kim, Yun-Suk The Korean Neurosurgical Society 2017 Journal of Korean neurosurgical society Vol.60 No.1

Objective : We assessed the surgical results of bipolar release in 31 adult patients with uncorrected congenital muscular torticollis (CMT) and more than 12 months of follow-up. Methods : Thirty-one patients underwent a bipolar release of the sternocleidomastoid muscle (SCM) and were retrospectively analyzed. The mean follow-up period was 14.9 months (range, 12-30). The mean age at time of surgery was 30.3 years (range, 20-54). Patients were evaluated with a modified Lee's scoring system, cervicomandibular angle (CMA) measurement, and a global satisfaction rating scale using patient self-reporting. Results : The modified Lee's scoring system indicated excellent results in 4 (12.9%) patients, good in 18 (58.1%), and fair in 9 (29.0%) at the last follow-up after surgery. The improvements in neck movement and head tilt were statistically significant (p<0.05). The preoperative mean CMA was $15.4^{\circ}$ (range, 5.4-29.0), which was reduced to a mean of CMA of $6.3^{\circ}$ (range, 0-25) after surgery (p<0.05). The global satisfaction rating scale was 93.7% (range, 90-100). A transient sensory deficit on the ipsilateral lower ear lobe was noted in three cases. No significant permanent complications occurred. Conclusion : Bipolar release of the SCM is a safe and reliable technique for the treatment of CMT in adults.

콩의 식품적 의의 및 생산수급과 식용콩의 자급 향상

이홍석,이영호,이석하 대한민국 학술원 2011 학술원논문집 : 자연과학편 Vol.50 No.2

콩은 단백질 공급을 비롯하여 영양가가 높아 예로부터 우리의 중요 식품으로 널리 다양하게 이용하여 왔을 뿐 아니라 지속적인 밭작물 재배를 가능케 하는 중요한 역할을 하여 왔으며, 최근에는 건강식품으로 또 친환경 농업 작물로 주목을 받고 있다. 콩은 세계적으로 99,501천ha에서 223,185천톤(2,243kg/ha)이 생산되고 그의 35.5% (35,130백만불)가 수출되고 그 중 43%는 미국 콩이, 96.5%는 미대륙 생산 콩이 수출되고 있으며, 수입의 반 정도는 중국이, 37.6% 정도는 유럽의 선진국과 일본 등 10여 개국에서 각각 수입하고 있고, 우리나라도 10번째의 수입국이며 세계적 소비수요는 계속 증가되고 있다. 우리나라는 1968년의 313,501ha의 재배에서 계속 감소하여 현재는 75,242ha에서 132,674톤이 생산되고 1,261천톤이 수입되었으며, 전체 자급률은 수요량 1,333천톤의 8.6%, 식용 및 기타는 수요량 387천톤의 29.5%에 불과하다. 콩, 특히 식용콩의 증산에 의한 자급율 향상은 경지정리 및 주산단지 조성을 통한 생력기계화 재배를 전제로 첫째, 밭의 작부체계 개선 둘째, 논의 밭 전환재배 셋째, 북한의 동해안 지대의 밭을 장기임대하여 재배하고 그 대가를 쌀 지원으로 하는 것이며 넷째는 인접국에서 밭을 매입 또는 장기 임대하여 생산 공급하는 방법 등을 생각할 수 있을 것이다.

난치성 만성정신분열증 환자의 생활의 질에 미치는 정신사회치료 프로그램의 효과에 대한 예비연구

송동호,배민진,이종호,이홍식,김선경,서호석,김찬형,전지용 大韓神經精神醫學會 1995 신경정신의학 Vol.34 No.4

Objects : Recent studies of psychosocial adjustment after hospitalization have found that the combination of maintenance antipsychotic drug treatment and psychosocial treatment including psychoeducational program are highly predictive of social rehabilitation and reduction of subsequent relapse. Two groups of patients with refractory chronic schizophrenia were preliminarily compared to determine the effect of a psychosocial treatment program on the quality of life in refractory chronic schizophrenics in an open comparative trial. Methods : One group(N=11) was assigned to approximately six months of the psychosocial treatment program(including psychoeducation program and activity program such as interpersonal relationship program, social skill training, self management program, outings, etc), in a group format, twice a week and a fixed maintenance dosage of clozapine ; while scale(QLS) was used to provide an objective measure of changes in patient's psychosocial functioning and a general assessment of psychopathology was made using the Brief Psychiatric Rating Scale(BPRS). Results : Both BPRS total positive score and the QLS total score, especially in the intrapsychic foundation factor of the scale showed a statistically significant improvement in the psychosocial treatment group. But there was no significant change in both BPRS and QLS scores over a 6-month period in the non-psychosocial treatment group. A significant negative correlation was found between the negative symptom and changes of QLS total, instrumental role and common object and activities scores respectively after receiving a 6-month of the psychosocial treatment program. Conclusion : These results suggest that a psychosocial treatment program including the integration of psychoeducation and a skill training oriented activity program serve as an outpatient treatment modality to improve the quality of the life in refractory chronic schizophrenia. To further clarify the effect of psychosocial treatment in chronic schizophrenia, a randomized trial should be done.

Toluene, Xylene, Trichloroethylene 투여가 흰쥐의 시상하부와 뇌하수체의 GnRH, GnRH Receptor, Pit-1 유전자 발현에 미치는 영향

기노석,이종태,강대성,김대환,이채관,이헌,전진호,김정호,이채언 大韓産業醫學會 1998 대한직업환경의학회지 Vol.10 No.2

The workplace exposure of chemicals has steadily increased, therefore the concern for subsequent effect on reproductive outcome has been an important issue in occupational medicine. In previous studies, higher rates of spontaneous abortion, reduced fertility and menstrual disorder among women, and an impairement of sperm quantity and quality among men have been associated with a wide variety of chemical agents. This study was conducted to evaluate the effects of toluene, xylene and trichloroethylene(TCE) injection on the mRNA levels of GnRH, GnRH receptor and Pit-1 genes in male rats hypothalamus and pituitary and the effects on the plasma levels of FSH, LH, prolactin and testosterone. Sprague-Dawley male rats were divided into five groups of five each according to concentration of toluene, xylene and TCE. The rats were injected subcutaneously to 0, 50, 100, 200, 400 mg/kg body weight/day of toluene, xylene and TCE, respectively for 6 days. Rat brains were excised and hypothalamus and pituitary were separated. Reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay(RPA) were used to evaluate the GnRH, GnRH receptor and Pit-1 mRNA levels. Plasma concentrations of FSH, LH, prolactin and testosterone were assayed by radioimmunoassay(RIA). The results were as follows; 1. GnRH, GnRH receptor and Pit-1 mRNA levels in toluene and xylene injected groups, and GnRH receptor mRNA levels in TCE injected group were lowered dose-dependently. Especially, GnRH receptor and Pit-1 mRNA levels in 200mg/kg of toluene injected group, and GnRH, GnRH receptor and Pit-1 mRNA levels in 400mg/kg of toluene injected group were significantly lower than control group (p<0.05). GnRH receptor and Pit-1 mRNA levels in 400mg/kg of xylene injected group, and GnRH receptor mRNA levels in 400mg/kg of TCE injected group were significantly lower than control group(p<0.05). 2. The plasma levels of prolactin and testosterone in 400mg/kg of toluene injected group, and LH in 100, 200 and 400mg/kg of xylene injected group, and testosterone in 400 mg/kg of TCE injected group were significantly lower than control group(p<0.05). In conclusion, we speculated that toluene and xylene affected reproductive system secondarily through hypothalamus-pituitary axis, and TCE affected directly through steroidogenesis. And we recommended that further study for assessment of the reproductive toxicity of mixed organic solvent exposures should be conducted.

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-kB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

( Jae Ho Choi ),( Sun Woo Jin ),( Eun Hee Han ),( Bong Hwan Park ),( Hyung Gyun Kim ),( Tilak Khanal ),( Yong Pil Hwang ),( Minh Truong Do ),( Hyun Sun Lee ),( Young Chul Chung ),( Hee Suk Kim ),( Tae 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. Methods: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. Results: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. Conclusion: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.ⓒ2014 Elsevler Gmbh. All rights reserved.

Safety Critical 시스템의 센서 결함 허용을 위한 Kalman Hybrid Redundancy 개발

김만호(Man Ho Kim),이석(Suk Lee),이경창(Kyung Chang Lee) 제어로봇시스템학회 2008 제어·로봇·시스템학회 논문지 Vol.14 No.11

As many systems depend on electronics, concern for fault tolerance is growing rapidly in the safety critical system such as intelligent vehicle. Tn order to make system fault tolerant, there has been a body of research mainly from aerospace field including predictive hybrid redundancy by Lee. Although the predictive hybrid redundancy has the fault tolerant mechanism to satisfy the fault tolerant requirement of safety crucial system such as x-by-wire system, it suffers form the variability of prediction performance according to the input feature of system. As an alternative to the prediction method of predictive hybrid redundancy for robust fault tolerant, Kalman prediction has attracted some attention because of its well-known and often-used with its structure called Kalman hybrid redundancy. In addition, several numerical simulation results are given where the Kalman hybrid redundancy outperforms with predictive smoothing voter.