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중증 허혈성 지체질환 환자에서 시행된 vascular endothelial growth factor의 혈관신생 유전자치료 1예
김현중,장신이,김종묵,김선영,김병문,김원배 대한내과학회 2003 대한내과학회지 Vol.65 No.1
저자 등은 기존의 치료에 반응하지 않는 중증 허혈성 지체질환 환자를 대상으로 하여 vascular endothelial growth factor를 이용한 혈관신생 유전자 치료를 시행하 였다. 치료 후 환자의 허혈에 의한 하지 통증이 현격하 게 감소하고 상처의 진행이 멈추었으며 추적 하지혈관 조영술상에서 하지의 측부혈관이 많이 증가됨이 관찰되 어 이에 문헌고찰과 함께 보고하는 바이다. 감사의 글 본 유전자 치료는 동아제약 연구소, ㈜바이로메드와 의 공동연구로서 삼성서울병원의 윤리위원회, 생물학적 안정성위원회, 식품의약품안전청의 유전자 제조품목 허 가 및 임상시험 인허가를 획득한 연구입니다. Cardiac and Vascular Center, Samsung Medical Center, Seoul, Korea; ViroMed Co. Ltd. Seoul, Korea*; Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea†; Research Laboratories, Dong-A Pharm Co, Ltd, Kyunggi-do, Korea‡ We report VEGF-induced angiogenic gene therapy in a patient with critical limb ischemia, who did not respond to conventional treatment. This patient was the first case in a dose-escalating series of phase I clinical trial. The patient had severe resting pain, gangrene and diffuse ulcer in his left foot. Total 1,000 μg of naked DNA encoding human VEGF165 was administered intramuscularly to 8 sites of the left lower extremity. Four weeks after the first 1,000 μg injection, a second 1,000 μg was administered to the same sites (total dose: 2,000 μg). After gene therapy, resting pain gradually reduced and the amount of analgesics taken by the patient decreased. The ischemic wound of lower extremity slightly improved. However, there was no complete wound healing at 12 weeks of treatment. Digital subtraction angiography at 12 weeks after gene therapy showed an increase in collateral vessels at the mid-tibial, ankle and foot arch levels. Immediately and up to 12 weeks, there was no complication related to gene therapy. These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA of VEGF165 may induce therapeutic angiogenesis in a patient with critical limb ischemia. Further clinical evaluation of VEGF-induced gene therapy is needed to evaluate the safety and efficiency of this treatment.(Korean J Med 64:85-90, 2003)
중증 허혈성 지체질환 환자에서 시행된 vascular endothelial growth factor의 혈관신생 유전자치료 1예
김현중,장신이,김종묵,김선영,김병문,김원배,김덕경 대한내과학회 2003 대한내과학회지 Vol.64 No.1
저자 등은 기존의 치료에 반응하지 않은 중증 허혈성 지체질환 환자를 대상으로 하여 vascular endothelial growth factor를 이용한 혈관신생 유전자 치료를 시행하였다. 치료 후 환자의 허혈에 의한 하지 통증이 현격하게 감소하고 상처의 진행이 측부혈관이 많이 증가됨이 관찰되어 이에 문헌고찰과 함께 보고하는 바이다. We report VEGF-induced angiogenic gene therapy in a patient with critical limb ischemia, who did not respond to conventional treatment. This patient was the first case in a dose-escalating series of phase I clinical trial. The patient had severe resting pain, gangrene and diffuse ulcer in his left foot. Total 1,000㎍ of naked DNA encoding human VEGF165 was administered intramuscularly to 8 sites of the loft lower extremity. Four weeks after the first 1,000㎛ was administered to the same sites (total dose: 2,000㎛). After gene therapy, resting pain gradually reduced and the amount of analgesics taken by the patient decreased. The ischemic wound of lower extremity slightly improved. However, there was no complete wound healing at 12 weeks of treatment. Digital subtraction angiography at 12 weeks after gene therapy showed an increase in collateral vessels at the mid-tibial, ankle and foot arch levels. Immediately and up to 12 weeks, there was no complication related to gene therapy. These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA of VEGF_165 may induce therapeutic angiogencsis in a patient with critical limb ischemia. Further clinical evaluation of VEGF-induced gene therapy is needed to evaluate the safety and efficiency of this treatment.(Korean J Med 64:85-90, 2003)
Differential effects of quercetin glycosides on GABAC receptor channel activity
김현중,나승열,최선혜,정석원,김현수,이준희,황성희,표미경,김형춘,이병환 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.1
Quercetin, a representative flavonoid, is acompound of low molecular weight found in various coloredplants and vegetables. Quercetin shows a wide rangeof neuropharmacological activities. In fact, quercetin naturallyexists as monomer-(quercetin-3-O-rhamnoside)(Rham1), dimer-(Rutin), or trimer-glycosides [quercetin-3-(2G-rhamnosylrutinoside)] (Rham2) at carbon-3 in fruitsand vegetables. The carbohydrate components are removedafter ingestion into gastrointestinal systems. The role of theglycosides attached to quercetin in the regulation of caminobutyricacid class C (GABAC) receptor channelactivity has not been determined. In the present study, we examined the effects of quercetin glycosides on GABACreceptor channel activity by expressing human GABACalone in Xenopus oocytes using a two-electrode voltageclamp technique and also compared the effects of quercetinglycosides with quercetin. We found that GABA-inducedinward current (IGABA) was inhibited by quercetin orquercetin glycosides. The inhibitory effects of quercetinand its glycosides on IGABA were concentration-dependentand reversible in the order of Rutin & quercetin & Rham1[Rham 2. The inhibitory effects of quercetin and itsglycosides on IGABA were noncompetitive and membranevoltage-insensitive. These results indicate that quercetinand its glycosides regulate GABAC receptor channelactivity through interaction with a different site from thatof GABA, and that the number of carbohydrate attached toquercetin might play an important role in the regulation ofGABAC receptor channel activity.
A weight-adjusted voting algorithm for ensembles of classifiers
김현중,김혁,Hojin Moon,Hongshik Ahn 한국통계학회 2011 Journal of the Korean Statistical Society Vol.40 No.4
We present a new weighted voting classification ensemble method, called WAVE, that uses two weight vectors: a weight vector of classifiers and a weight vector of instances. The instance weight vector assigns higher weights to observations that are hard to classify. The weight vector of classifiers puts larger weights on classifiers that perform better on hardto-classify instances. One weight vector is designed to be calculated in conjunction with the other through an iterative procedure. That is, the instances of higher weights play a more important role in determining the weights of classifiers, and vice versa. We proved that the iterated weight vectors converge to the optimal weights which can be directly calculated from the performance matrix of classifiers in an ensemble. The final prediction of the ensemble is obtained by voting using the optimal weight vector of classifiers. To compare the performance between a simple majority voting and the proposed weighted voting, we applied both of the voting methods to bootstrap aggregation and investigated the performance on 28 datasets. The result shows that the proposed weighted voting performs significantly better than the simple majority voting in general.
김현중,신은주,이병환,최선혜,정석원,조익현,황성희,김준용,한정수,정지혜,장춘곤,임혜원,김형춘,나승열 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.9
Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer’s disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced [Ca2+]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca2+]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin- enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-β protein (Aβ)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltran-