• 제목/요약/키워드: plasminogen activator

검색결과 201건 처리시간 0.026초

A Recombinant Human ${\alpha}_1$-Antitrypsin Variant, $M_{malton}$, Undergoes a Spontaneous Conformational Conversion into a Latent Form

  • Jung, Chan-Hun;Im, Hana
    • Journal of Microbiology
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    • 제41권4호
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    • pp.335-339
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    • 2003
  • Many genetic variants of ${\alpha}_1$-antitrypsin have been associated with early onset emphysema and liver cirrhosis. However, the detailed structural basis of pathogenic ${\alpha}_1$-antitrypsin molecules is rarely known. Here we found that a recombinant $M_{malton}$ variant (Phe52-deleted) lost inhibitory activity by spontaneous conformational conversion into a more stable, inactive form under physiological conditions. Biochemical and spectroscopic data suggested that the variant converts into a reactive center loop-inserted conformation, resembling the latent form of plasminogen activator inhibitor-1.

Function of hepatocyte growth factor in gastric cancer proliferation and invasion

  • Koh, Sung Ae;Lee, Kyung Hee
    • Journal of Yeungnam Medical Science
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    • 제37권2호
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    • pp.73-78
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    • 2020
  • Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

Primary thrombolysis for free flap surgery in head and neck reconstruction: a case report and review

  • Zhang, Steven Liben;Ng, Hui Wen
    • Archives of Plastic Surgery
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    • 제48권5호
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    • pp.511-517
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    • 2021
  • The use of free flaps is an essential and reliable method of reconstruction in complex head and neck defects. Flap failure remains the most feared complication, the most common cause being pedicle thrombosis. Among other measures, thrombolysis is useful when manual thrombectomy has failed to restore flap perfusion, in the setting of late or established thrombosis, or in arterial thrombosis with distal clot propagation. We report a case of pedicle arterial thrombosis with distal clot propagation which occurred during reconstruction of a maxillectomy defect, and was successfully treated with thrombolysis using recombinant tissue plasminogen activator. We also review the literature regarding the use of thrombolysis in free flap surgery, and propose an algorithm for the salvage of free flaps in head and neck reconstruction.

Urokinase Conjugated with Water-Soluble Dextran

  • 김남득;김현표;변시명;김성완
    • Bulletin of the Korean Chemical Society
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    • 제6권4호
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    • pp.210-214
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    • 1985
  • Urokinase, a plasminogen activator, was conjugated with dextran by the cyanogen bromide activation-coupling method. The resulting water-soluble conjugate was purified by gel permeation chromatography on Sephadex G-200. The maximal activity was obtained when the ratio of urokinase/dextran was 1/20 for the coupling. The final preparation showed 5 CTA units/mg conjugate, 300 CTA units/mg protein, 8.4 % activity retention, and 47 % protein retention. The urokinase-dextran conjugate had good thermal, pH and storage stabilities. In addition, it showed greater resistance to the inhibitory effect of human plasma than native urokinase. Also in vitro biological half-life of urokinase increased 40 times by this conjugation. In view of activity, excellent stability and increased half-life, the conjugate can be a potential fibrinolytic agent in an injectable form.

Current Opinion on Endovascular Therapy for Emergent Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Stenosis

  • Dong-Hun Kang;Woong Yoon
    • Korean Journal of Radiology
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    • 제20권5호
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    • pp.739-748
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    • 2019
  • For recanalization of emergent large vessel occlusions (ELVOs), endovascular therapy (EVT) using newer devices, such as a stent retriever and large-bore catheter, has shown better patient outcomes compared with intravenous recombinant tissue plasminogen activator only. Intracranial atherosclerotic stenosis (ICAS) is a major cause of acute ischemic stroke, the incidence of which is rising worldwide. Thus, it is not rare to encounter underlying ICAS during EVT procedures, particularly in Asian countries. ELVO due to underlying ICAS is often related to EVT procedure failure or complications, which can lead to poor functional recovery. However, information regarding EVT for this type of stroke is lacking because large clinical trials have been largely based on Western populations. In this review, we discuss the unique pathologic basis of ELVO with underlying ICAS, which may complicate EVT procedures. Moreover, we review EVT data for patients with ELVO due to underlying ICAS and suggest an optimal endovascular recanalization strategy based on the existing literature. Finally, we present future perspectives on this subject.

The Effect of Glutamine on Production of Tissue-type Plasminogen Activator from Recombinant Human Melanoma Cells in Glutamine-limited Fed-batch Cultivation

  • Kim, Hyun-Goo;Kim, Tae-Ho;Kim, Dae-Seok;Park, Kyung-Yu;Park, jin-seo;Ahn, Chol;Lee, Jin-Ha;Lee, Hyeon-Yong
    • Journal of Microbiology and Biotechnology
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    • 제6권4호
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    • pp.295-298
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    • 1996
  • Under glutamine-limited condition, $2\times10^6$ (viable cells/ml) of maximum cell density and 13.5 ($\mu g$/ml) of tissue-type Plasminogen Activators (tPA) production were maintained by spike feeding fresh medium in fed-batch cultivation of human recombinant melanoma cells. It showed that tPA production was much seriously affected than cell growth according to initial glutamine concentrations. Above 3.4 (mmol/I) of glutamine concentration both cell growth and tPA production were not much affected by increasing initial glutamine concentration. Glutamine depleted situation was occurred at latter periods of batch and fed-batch cultivations below 5.4 (mmole/I) of initial glutamine concentration. It also showed that maximum glutamine consumption and ammonia evolution rates were closely related to initial glutamine concentrations. Maximum specific tPA production rate was estimated as $8.1\times19^{-6}$ ($\mu g$/cells/h) at 3.4(mmol/I) of glutamine concentration, which is higher than that from other batch and fed-batch processes.

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Antiangiogenic and Antitumor Activities of the Cryptic Fragments with Kringle Architecture

  • Joe, Young-Ae;Kim, Myung-Rae;Shim, Byoung-Shik;Oh, Dae-Shik;Hong, Sung-Hee;Hong, Yong-Kil
    • Biomolecules & Therapeutics
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    • 제11권4호
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    • pp.205-213
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    • 2003
  • Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

The Effect of Locally Administered Fibrinolytic Drugs Following Aneurysmal Subarachnoid Hemorrhage : A Meta-Analysis with Eight Randomized Controlled Studies

  • Jang, Kyoung Min;Choi, Hyun Ho;Nam, Taek Kyun;Park, Yong Sook;Kwon, Jeong Taik;Byun, Jun Soo;Hwang, Doyeon
    • Journal of Korean Neurosurgical Society
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    • 제64권2호
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    • pp.207-216
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    • 2021
  • Objective : Rapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. Methods : From PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. Results : Data from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32-0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32-0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34-0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37-0.80). Conclusion : This meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.

만성폐쇄성폐질환에서 우심실 기능 부전에 따른 혈액응고 및 섬유소용해계 변화 (Alteration of Coagulation and Fibrinolysis System According to Right Ventricular Dysfunction in Chronic Obstructive Pulmonary Disease)

  • 김영;장윤수;김형중;김세규;장준;안철민;김성규;곽진영;최진화
    • Tuberculosis and Respiratory Diseases
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    • 제60권6호
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    • pp.625-630
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    • 2006
  • 배 경: COPD 환자에서 흡연은 폐혈관에 직접 작용하여 혈관 수축, 확장 및 혈관세포 증식을 조절하는 매개물질을 분비하여 혈관의 부적절한 개형 및 생리 현상을 초래하여 폐성고혈압을 유발한다. COPD 환자에서는 종종 급성 및 만성 폐혈전증이 일어나고 혈장내 응고전구물질 및 섬유소용해계의 표지자들이 증가되어 있다. 그러나 COPD 환자에서 혈액 응고계 및 섬유소용해계가 우심실 기능 장애에 어떤 기여를 하는지는 잘 알려져 있지 않다. 본 연구에서는 진행된 COPD 환자에서 multidetector CT scan (MDCT)을 이용하여 측정한 우심실 기능에 따른 혈액내 응고계 및 섬유소용해 계의 변화를 알아보고자 하였다. 방 법: GOLD 지침에 따라 COPD로 진단한 26명에서 심장 MDCT scan을 이용하여 우심실 박출계수를 구하였다. 혈액내 thrombin antithrombin (TAT) 및 plasminogen activator inhibitor (PAI)-1은 enzyme linked immunoassay 방법으로 측정하였다. 결 과: COPD 환자의 혈중 TAT는 $10.5{\pm}19.8{\mu}g/L$으로 정상인의 혈중 TAT $3.4{\pm}2.5{\mu}g/L$보다 의미 있게 증가되었으나 (p<0.01) COPD 환자의 혈중 PAI-1는 $29.6{\pm}20.7ng/mL$으로 정상인의 혈중 PAI-1 $25.9{\pm}17.9ng/mL$와 비교하여 의미 있는 변화가 없었다. COPD 환자에서 혈중 TAT는 MDCT scan으로 측정한 우심실 박출계수와 의미 있는 역 상관관계를 보였으나 (r=-0.645, p<0.01) 혈중 PAI-1은 우심실 박출계수와 상관관계를 보이지 않았다 (r=0.022, p=0.92). 결 론: COPD 환자에서 혈중내 응고계는 활성화되어 있으며 혈중 TAT는 우심실 기능 장애의 의미있는 표지자로 사료된다.