• Archives of Plastic Surgery
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• 제49권2호
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• pp.253-257
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• 2022

The free fibula flap (FFF) is based on the peroneal artery (PA) system, and it is well known that several anatomical variations of the lower limb vascular system exist, including peronea arteria magna (PAM). PAM is a rare congenital variation in which both anterior tibial artery and posterior tibial artery are either aplastic or hypoplastic, and as a result, PA will be the dominant blood supply to the foot. This variation was described as type III-C in Kim-Lippert's Classification of the Infra-Popliteal Arterial Branching Variations. The awareness of its existence is crucial as it often precludes FFF from being harvested due to the risk of significant limb ischemia and limb loss. Despite some literature reporting donor site complications and impending limb loss following FFF harvest in PAM, preoperative vascular mapping before FFF transfer remains controversial among the microsurgeons. We present a case with an incidental intraoperative finding of PAM that had a successful FFF harvest by luck, without preoperative vascular mapping.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.123-134
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• 1993

연구배경 : 조직형플라스미노겐활성체는 생리적인 플라스미노겐활성체이므로 혈전의 섬유소에 결합된 플라스미노겐만을 활성화시키는 특이성이 있어 효과적이고 안전한 혈전용해제로 사용될 수 있다고 기대된다. 그러나 조직형플라스미노겐활성체의 투여방법에 대해서는 장시간동안 계속 주입해야한다는 주장과 투여시간을 1시간이내로 해도 혈전용해효과는 지속적으로 나타나고 부작용을 유발하는 정도도 미미하므로 투여시간을 짧게 하자는 주장이 양립하고 있는 실정이다. 본 연구에서는 폐혈전색전증에서 조직형플라스미노겐활성체의 투여방법에 따라 혈전용해효과가 어떻게 달라지고 폐색전증으로 인한 심폐기능장애가 약제의 투여방법에 따라 어떠한 영향을 받는지를 알아보고자 하였다. 방법 : 실험견에 방사성동위원소로 표지된 자가혈병으로 대량의 폐색전종을 유발시켜서 대조군은 특이치료를 하지 않고 제 1 치료군은 15분동안, 제 2 치료군은 3시간에 걸쳐서 재조합형의 조직형플라스미노겐활성체를 체중당 1mg씩 정맥주입하였다. 그리고 실험과정중 4시간동안 혈전색전에서 방출되는 감마선량과 각종 혈역학적 지표를 감시하고 주기적으로 동맥혈 및 혼합정맥혈의 가스분석을 시행하여 어떠한 약제투여방법이 더 효율적인가를 분석하였다. 결과: 1) 혈전용해효과는 제 1 치료군이 $36.2{\pm}3.3%$, 제 2 치료군이 $39.6{\pm}2.3%$로 유의한 차이가 없었으며, 혈전용해속도는 제 1 치료군이 $81.4{\pm}16.8%/hr$, 제 2 치료군이 $37.3{\pm}2.4%/hr$로 제 1 치료군에서 급속한 혈전용해효과를 보였다 (p<0.05). 2) 약제의 작용시간은 제 1 치료군이 $63.3{\pm}22.2$분, 제 2 치료군이 $148.5{\pm}14.0$분으로 (p<0.05), 제 1 치료군에서는 약제투여후에도 지속적인 혈전용해효과를 보이지만 제 2 치료군에서는 약제투여중에 혈전용해효과가 정지되었다. 3) 폐색전증으로 인한 혈역학적 장애와 가스교환의 장애는 제 1 치료군 및 제 2 치료군에서 비슷한 정도로 개선되었으나, 제 1 치료군에서 보다 신속하게 개선되었다(p<0.05). 결론 : 폐색전증에서 치료목적으로 동량의 조직형플라스미노겐활성체를 투여할때 약제의 투여시간이 15분인 경우와 180분인 경우를 비교해보면, 혈전색전의 용해정도는 비슷하지만 혈전의 용해속도 및 폐색전증으로 인한 심폐기능장애의 개선효과는 약제의 투여시간이 15분일 때 더 우수하였다. 따라서 약제의 투여시간을 짧게하여 혈전의 용해속도를 촉진함으로써 폐색전증으로 인한 심폐기능장애를 신속히 개선할 수 있겠다.

• BMB Reports
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• 제46권10호
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• pp.484-489
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• 2013

Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit anti-hyperlipidemic, antiplatelet and anti-melanogenic activities. Here, the anticoagulant activities of PL were examined by monitoring activated-partial-thromboplastin-time (aPTT), prothrombin-time (PT), and the activities of thrombin and activated factor X (FXa). The effects of PL on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) activated HUVECs. The results showed that PL prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. PL inhibited the generation of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, PL prolonged in vivo bleeding time and inhibited TNF-${\alpha}$ induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by PL. Collectively, our results suggest that PL possesses antithrombotic activities and that the current study could provide bases for the development of new anticoagulant agents.

• BMB Reports
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• 제48권10호
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• pp.577-582
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• 2015

Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. Here, the anticoagulant effects of scolymoside, an active compound in C. subternata, were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). The effects of scolymoside on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) expression were evaluated in tumor necrosis factor (TNF)-α-activated human endothelial cells. Treatment with scolymoside resulted in prolonged aPTT and PT and the inhibition of thrombin and FXa activities and production. In addition, scolymoside inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Scolymoside also elicited anticoagulant effects in mice, including a significant reduction in the PAI-1 to t-PA ratio. Collectively, these findings indicate that scolymoside possesses anticoagulant activities and could be developed as a novel anticoagulant.

• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.516-524
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• 1997

목 적 : 악성 종양에 있어서 단백질 분해 효소에 의한 세포외기질의 분해는 종양 침습 및 전이에 있어서 중요한 역할을 한다. Urokinase-type plasminogen activator(u-PA)는 이러한 단백질 분해효소 중 하나이며, u-PA의 길항제인 plasminogen activator inhibitor(PAI-1, PAI-2)도 u-PA에 의한 종양조직 자체의 분해를 방어하여 종양의 성장, 침습 및 혈관신생을 촉진하는 역할을 한다. u-PA와 PAI-1은 폐암 등의 종양 조직내의 양이 증가하며, 침습도 및 예후 둥과 유의하게 상관되는 것으로 보고되고 있다. 저자 등은 폐암환자의 혈장 u-PA와 PAI-1의 농도를 측정하여 조직형 및 병기와의 관련성을 조사해 보고자 한다. 방 법 : 폐암 환자 37예, 여러 가지 양성 폐질환 환자 21예 및 유사연령의 정상 대조군 24예에서 혈장 u-PA 및 PAI-1 항원의 농도를 ELISA법으로 측정하였다. 결 과 : 혈장 u-PA 항원 농도는 정상 대조군에서 $1.0{\pm}0.3ng/mL$, 양성 폐질환군에서 $1.0{\pm}0.3ng/mL$, 폐암환자군에서 $0.9{\pm}0.3ng/mL$로 유의한 차이가 없었다. 혈장 PAI-1 항원 농도는 정상 대조군에서 $14.2{\pm}6.7ng/mL$, 양성 폐질환군에서 $14.9{\pm}6.3ng/mL$, 폐암 환자군에서 $22.1{\pm}9.8ng/mL$로 폐암 환자에서 정상 대조군 및 양성 폐질환군에 비하여 유의하게 높았다. 혈장 u-PA 항원 농도는 편평상피암에서 $0.7{\pm}0.4ng/mL$, 선암에서 $0.8{\pm}0.3ng/mL$, 대세포암에서 0.9ng/mL, 소세포암에서 $1.1{\pm}0.7ng/mL$로 유의한 차이가 없었다. 혈장 PAI-1 항원 농도는 편평상피암에서 $22.3{\pm}7.2ng/mL$, 선암에서 $22.6{\pm}9.9ng/mL$, 대세포암에서 42ng/mL, 소세포암에서 $16.0{\pm}14.2ng/mL$로 유의한 차이가 없었다. u-PA 항원 농도는 stage I에서 0.74ng/mL, stage II에서 $1.2{\pm}0.6ng/mL$, stage IIIA에서 $0.7{\pm}0.4ng/mL$, stage IIIB에서 $0.7{\pm}0.4ng/mL$, stage IV에서 $0.7{\pm}0.3ng/mL$였고, 혈장 PAI-1 항원 농도는 stage I에서 21.8ng/mL, stage II에서 $22.7{\pm}8.7ng/mL$, stage IIIA에서 $18.4{\pm}4.9ng/mL$, stage IIIB에서 $25.3{\pm}9.0ng/mL$, stage IV에서 $21.5{\pm}10.8ng/mL$로 유의한 차이가 없었다. 폐암 환자에서 T기를 T1-3 와 T4로 나누어서 비교를 한 결과, 혈장 u-PA 항원 농도는 T1-3에서 $0.8{\pm}0.4ng/mL$였고 T4에서 $0.7{\pm}0.4ng/mL$로 차이가 없었으나, 혈장 PAI-1 항원 농도는 T1-3에서 $17.9{\pm}5.6ng/mL$였고 T4에서 $26.1{\pm}9.1ng/mL$로 T4에서 유의하게 높았다. 혈장 u-PA 항원 농도는 M0에서 $0.8{\pm}0.4ng/mL$, M1에서 $0.7{\pm}0.3ng/mL$였고, 혈장 PAI-1 항원 농도는 M0에서 $23.6{\pm}8.3ng/mL$, M1에서 $21.5{\pm}10.8ng/mL$로 유의한 차이가 없었다. 결 론 : 이상의 결과에서 폐암 환자에서 혈장 PAI-1은 정상대조군 및 양성 폐질환에 비하여 특이적으로 증가하였고, 또한 폐암의 국소적 침습 정도와의 관련성을 보여 주었다.

• Journal of Korean Neurosurgical Society
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• 제63권4호
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• pp.427-432
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• 2020

Three randomized control trials (RCTs), published in 2013, investigated efficacy of mechanical thrombectomy in large vessel occlusions and did not show better results compared to intravenous (IV) recombinant tissue-type plasminogen activator (tPA) alone. However, most clinicians treating stroke consider mechanical thrombectomy as the standard treatment rather than using IV tPA alone. This paradigm shift was based on five RCTs investigating efficacy of mechanical thrombectomy in acute ischemic stroke conducted from 2010 to 2015. They demonstrated that mechanical thrombectomy was effective and safe in acute ischemic stroke with anterior circulation occlusion when performed within 6 hours of stroke onset. There are four reasons underlying the different results observed between the trials conducted in 2013 and 2015. First, the three RCTs of 2013 used low-efficiency thrombectomy devices. Second, the three RCTs used insufficient image selection criteria. Third, following the initial presentation at the hospital, reperfusion treatment required a long time. Fourth, the three RCTs showed a low rate of successful recanalization. Time is the most important factor in the treatment of acute ischemic stroke. However, current trends utilize advanced imaging techniques, such as diffusion-weighted imaging and multi-channel computer tomographic perfusion, to facilitate the detection of core infarction, penumbra, and collateral flows. These efforts demonstrate that patient selection may overcome the barriers of time in specific cases.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.261-264
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• 2002

CHO (Chinese hamster ovary) cells were transfected with plasmids containing both cis-acting HRE (hypoxia response element) and CMV-promoter that controls tissue-type plasminogen activator (t-PA). CHO cells with HRE produced 16.2 fold higher t-PA concentration than CHO cells without HRE. It was noted that hypoxia strongly induced CHO cell apoptosis. which resulted in decrease of cell viability and protein production. In this study. by introducing Bcl-2, anti-apoptotic gene, we tried to recover cell viability and increase the protein production. When batch culture of both control cells without transfection of Bcl-2 and cells transfected with Bcl-2 were performed in the absence of CoCl ι hypoxia mimic condition. the cells with Bcl-2 were effected specific cell growth rates, maximum cell density. Immunoblotting assay showed Bcl-2 was recombinant with HRE dependent t- P A expression cassette, and their expression level was depended on hypoxia. By introducing Bcl-2, both cell viability and maximum cell density could be increased.

• Reproductive and Developmental Biology
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• 제33권2호
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• pp.107-111
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• 2009

The transfection efficiency of a transgene into pig and goat fetal fibroblast cells (PFF and GFF, respectively) was tested using co-transfection of a human tissue-type plasminogen activator (tPA) transgene and neomycin-resistant ($Neo^r$) gene, followed by G418 selection. To initially test G418 resistance, GFF and PFF were incubated in culture medium containing different concentration of G418 for 2 weeks, and cell survival was monitored over time. Based on the obtained results, the concentrations chosen for G418 selection were 800 ug/ml and 200 ug/ml for GFF and PFF, respectively. For co-transfection experiments, the pBC1/tPA and $Neo^r$ vectors were co-transfected into GFF and PFF ($1{\times}10^6$ cells in each case) using the FuGENE6 transfection reagent, and resistant colonies were obtained following 14 days of G418 selection. We obtained 96 and 93 drug-resistant colonies of GFF and PFF, respectively, only 54 and 39 of which, respectively, continued proliferating after drug selection. PCR-based screening revealed that 23 out of 54 analyzed GFF colonies and 5 out of 39 analyzed PFF colonies contained insertion of the tPA gene. Thus, the experimentally determined transfection efficiencies for tPA gene co-transfection with the $Neo^r$ gene were 42.6% for GFF and 12.8% for PFF. These findings suggest that co-transfection of a transgene with the $Neo^r$ gene can aid in the successful integration of the transgene into fetal fibroblast cells.

• 한국발생생물학회지:발생과생식
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• 제2권2호
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• pp.135-140
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• 1998

Protease nexin-1 (PN-1)은 활성화 자리에 serine기를 갖는 단백질 분해 효소 즉, 트롬빈, 트립신, 플라스미노겐 활성화 효소 등의 작용을 억제한다. 본 연구에서는 흰쥐의 Sprague-Dawley계통을 이용하여 조직별 mRNA발현여부 및 정도를 조사하였다. PN-1의 발현이 나타난 조직은 뇌 (전뇌, 후뇌), 심장, 간, 폐, 난소, 난관 등이다. 이들 중 유전자 발현이 가장 높은 조직은 암컷의 전뇌(forebrain) 였다. 특히, 생식기관들 중에서는 암컷의 난소와 난관에서만 발현이 관찰되는 등 PN-1 유전자는 성별에 따라 서로 다르게 발현됨이 확인되었다 이러한 결과들로 미루어 PN-1은 여포 형성과정과 초기배 형성과정 등의 생식 및 발생작용과 관련이 있을 것으로 생각된다.

• Journal of Ginseng Research
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• 제22권3호
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• pp.216-221
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• 1998

We examined the anti-invasive activity of ginsenosides Rhl, Rha on the highly metastatic HT1080 human fibrosarcoma cell line. In vitro invasion assay showed ginsenoside Rhr reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber more than ginsenoside Rh1. Significant down-regulation of matrix metalloproteinase-9 (MMP-9) by ginsenosides Rh, and Rh2 was detected by Northern blot analysis. However, the expression of MMP-2 was not affected by Rh, and Rhr. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by Rhl after 0.5, 1 or 3 day-treatment but reduced after 6 day-treatment. However, the expression of TIMP-2 was not changed by treatment with Rh2. Plasminogen activator inhibitor (PAI) and urokinase-type plasmlnogen activator (uPA) were not changed by treatment with Rh1 and Rh2 for 3 and 6 days. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but MMP-2 after treatments with ginsenosides Rhl and Rha. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of ginsenosides Rhl and Rhr in the HT1080 cells.