성인에서의 연령에 따른 내생적 플라스미노겐 활성제에 관한 연구

송인욱,하정호,정두신,어경윤 東國大學校醫學硏究所 2005 東國醫學 Vol.12 No.1

유로키나제형 플라스미노겐 활성제(Urokinase type plasminogen activator, u-PA)와 조직형 플라스미노겐 활성제(Tissue type plasminogen activator, 1-PA)는 현재 까지 알려져 있는 내생적 플라스미노겐 활성제로써 혈전용해력 뿐 만 아니라 세포이주, 조직파괴, 철관형성, 조직재건 등의 다양한 역할을 한다. 이런 내생적 플라스미노겐 활성제는 플라스미노겐 활성 억제제(Plasminogen activator inhibitor-1, PAI-1)에 의해서 강력하게 조절되고 있으나 사람에 있어서 이들 내생적 플라스비노겐 활성제들의 활성 정도가 연령에 의해 어떠한 영향을 주고 있는지는 아직 잘 알려져 있지 않다. 내생적 플라스비노겐 활성제의 연령에 따른 영향을 평가하기 위하여 전에 뇌경색의 과거력이 없는 성인 40명을 대상으로 chromogenic assay에 의해 u-PA, t-PA 그리고 PAI-1의 활성도를 측정하였다. t-PA 활성도는 40대에서는 100%, 50대에서는 90%, 60대에서는 30%, 70대에서는 30%였으며, u-PA의 활성도는 40대에서는 60%, 50대에서는 40%, 60대에서는 40%, 70대에서는 30%에서 나타났다. PAI-1 활성도는 40대에서는 10%, 50대에서는 30%, 60대에서는 40%, 70대에서는 70%에서 나타났다. 내생적 t-PA의 낮은 활성도와 PAI-1의 높은 활성도를 가진 고령에 있어서는 뇌에 만약 허혈 손상이 온다면 뇌의 섬유소 용해력이 떨어짐에 따라 결과적으로 크고 심한 뇌경색의 소인이 될 가능성이 충분히 있다고 하겠다. Urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) play important roles in fibrinolysis, cell migration, tissue destruction, angiogenesis and tissue remodeling. u-PA and t-PA activity in tissue are tightly regulated by plasminogen activator inhibitor-1 (PAI-1). However, little is known of the effect of age on expression of endogenous plasminogen activators in human. To evaluate effect of age on endogenous plasminogen activators in normal human, we measured u-PA, t-PA and PAI-1 activity by chromogenic assay in 40 humans without previous ischemic stroke history. t-PA activity was present in 100% in 5th decade, 90% in 6th decade, 30% in 7th decade, and 30% in 8th decade health human. PAI-1 activity was present more increasing activity in 7th and 8th decade than 5th and 6th decade. Whereas, u-PA activity was not present significant difference. It is possible that lower t-PA activity and higher PAI-1 activity in older human may compromise brain fibrinolysis, predisposing to larger and more disabling cerebral infarction.

Lumbricus Rubellus 가 인체의 섬유소 용해력에 미치는 영향

홍세용(S . Y . Hong),양동호(D . H . Yang),오도연(D . Y . Oh),박선양(S . Y . Park) 대한내과학회 1991 대한내과학회지 Vol.40 No.1

N/A To evaluate the lumbrikinase effect on plasmin (ogen) related physiologic fibrinolytic activity, we measured euglobulin fibrinolytic activity, t-PA activity and t-PA antigen during lumbrikinase therapy and the results were compared with the data of control day of before and after lumbrikinase ingestion. Serial dilution of lumbrikinase showed the fibrinolytic activity on fibrin plate by dose dependent pattern between 375㎍/ml and 1㎍/ml concentration. In regard to the fibrinolytic area, 300㎍ of lunbrikinase equivalent to 25 unit of t-PA and 75㎍ of lumbrikinase equivalent to 5 unit of t-PA. Euglobulin fibrinolytic activity increased in all cases by two or three days after lumbrikinase ingestion but decreased to basal level 36 hours after discontinuation of lunbrikinase. The lumbrikinase added to plasma did not influence to the euglobulin fibrinolytic activity. t-PA ag was increased in 5 out of 6 cases and t-PA activity was increased all of the cases after lumbrikinase ingestion. There was direct correlation between euglobulin fibrinolytic activity and t-PA activity. This finding suggest that the increased fibrinolytic activity of euglobulin after lumbrikinase ingestion is due to increased t-PA rather than direct effect of lumbrikinase itself.

급성기 허혈성 뇌졸중에서 정맥내 t-PA 혈전용해치료법의 안전성 및 효과 : 지역기반 일개 대학병원 연구

오은진 대한뇌졸중학회 2005 Journal of stroke Vol.7 No.1

Department of Neurology, Inje University, Ilsan Paik HospitalB a c k g ro u n d: Clinical trials demonstrated that intravenous tissue plasminogen activator (t-PA) was safe and effective in hyperacute ischemic stroke. Our objective was to determine whether t-PA therapy could be used safely and effectively in a community-based university hospital. Methods: From April 2000 to July 2004, retrospective and prospective data of intravenous t-PA therapy were collected in Ilsan Paik Hospital. Efficacy was assessed by the improvement of National Institutes of Health Stroke Scale (NIHSS) by 4 or more points, the marked improvement (NIHSS decreased ≥10 points or a decrease to an NIHSS score of ≤3), and modified Rankin scale (mRS) at discharge. Safety was assessed by symptomatic intracranial hemorrhage and mortality. R e s u l t: Sixty-eight patients were treated with intravenous t-PA (mean age; 67±13, median NIHSS; 18). Only three (4%) patients were small-vessel occlusion. Time interval from onset to treatment was 151±40 minutes. Improvement of NIHSS by 4 or more points at discharge occurred in thirty-three patients (48%). Twenty-three patients (34%) showed marked improvement. According to mRS, 13% (9/68) of patients had no or minimal symptoms (mRS 0-1) and19% (13/68) had mild to moderate disability (mRS 2-3), while 50% (34/68) remained dependent and 17% (12/68) died. Five patients (7.3%) had symptomatic intracranial hemorrhage. Three deaths were attributed to symptomatic intracranial hemorrhage. Conclusions: Intravenous t-PA therapy was safe in the setting of a community-based university hospital in spite of inferior efficacy compared to those of previous clinical trials. However, considerable number of patients showed marked improvement with t-PA therapy.

당뇨 환자에서 활차 운동 후 혈중 t-PA 및 PAI-1 의 변화

최정혜(Jung Hye Choi),김순길(Sun Gil Kim),이응수(Woong Soo Lee),김태화(Tae Wha Kim),김태영(Tae Young Kim),신진호(Jin Ho Shin),이재웅(Jae Ung Lee),김경수(Kyung Soo Kim),김정현(Jeong Hyun Kim),임헌길(Heon Kim Lim),이방헌(Bang Hun Lee) 대한내과학회 1999 대한내과학회지 Vol.56 No.5

N/A Objectives : Plasma fibrinolytic activity is determined by the balance between plasmonogen activators and their inhibitors. The aim of this study was to compare the fibrinolytic activity before and after exercise of the type 2 diabetic patients with control group. Methods : We measured plasma tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen before and after standardized treadmill exercise in 21 type 2 diabetic patients (14 men, 11 women, ages 46.2±5.6 years) and 21 sex and age- matched control group (10 men, 11 women, ages 48.6±5.4 years). Results : 1) Post exercise t-PA antigen increased in both diabetic group (from 7.36±3.89 to 10.62±4.81 ng/ml, p<0.05) and control group (from 8.30±3.99 to 10.99±5.52 ng/ml, p<0.05). But the rise in t-PA antigen with exercise was similar in both group. 2) Both base line and post exercise PAI-1 antigen levels were similar between the diabetic group (from 29.46±10.35 to 31.48±12.94 ng/ml, p>0.05) and control group (from 30.04±10.40 ng/ml to 31.06±10.88 ng/ml, p>0.05). 3) In diabetic group, significant correlations between base line PAI-1 antigen levels and serum triglyceride levels were observed. And post exercise PAI-1 antigen levels were correlated with systolic blood pressure. Conclusion : The results show that plasma t-PA antigen level is increased after vigorous exercise in patients with type 2 diabetes mellitus and plasma PAI-1 antigen level is not changed. The increment of plasma t-PA level is not different with healthy subjects.

A novel variant of t-PA resistant to plasminogen activator inhibitor-1; expression in CHO cells based on In Silico experiments

( Fatemeh Davami ),( Soroush Sardari ),( Keivan Majidzadeh A ),( Mahdi Hemayatkar ),( Farzaneh Barkhordari ),( Somayeh Enayati ),( Ahmad Adeli ),( Fereidoun Mahboudi ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.1

Resistance to PAI-1 is a factor which confers clinical benefits in thrombolytic therapy. The only US FDA approved PAI-1 resistant drug is Tenecteplase(R). Deletion variants of t-PA have the advantage of fewer disulfide bonds in addition to higher plasma half lives. A new variant was developed by deletion of the first three domains in t-PA in addition to substitution of KHRR 128-131 amino acids with AAAA in truncated t-PA. The specific activity of this new variant, 570 IU/μg, was found to be similar to those found in full length t-PA (Alteplase(R)), 580 IU/μg. A 65% and 85% residual activity after inhibition by rPAI-1 was observed for full length and truncated-mutant form, respectively. This new variant as the first PAI-1 resistant truncated t-PA may offer more advantages in clinical conditions in which high PAI-1 levels makes the thrombolytic system prone to re-occlusion. [BMB reports 2011; 44(1): 34-39]

활차 운동이 인체의 섬유소 용해능에 미치는 영향

김순길,신승호,양동호,김선주,홍세용 대한내과학회 1992 대한내과학회지 Vol.42 No.2

저자들은 섬유소 용해능 자극 검사로서 활차운동의 유용성을 조사하기 위하여 일차적으로 활차운동 후 혈액의 섬유소 용해능의 변화를 조사하였다. 15세에서 68세 사이의 건강한 남자 16명의 활차운동 전후의 euglobulin 섬유소 용해능 및 tissue-type plasminogen activator 와 urokinase-type plasminogen activator의 antigen 농도를 측정하여 다음과 같은 결과를 얻었기에 보고하는 바이다. 1) Euglobulin 섬유소 용해능은 활차운동 전 98.4±9.5 BAU (Blood Activator Unit)에서 운동 후 116.4±17.4 BAU로 증가하였다(p<0.0005). 2) t-PA antigen 농도는 활차운동전 3.2±2.3ng/㎖에서 운동후 4.9±2.6ng/㎖로 증가하였다(p<0.0001). 3) u-PA antigen 농도는 활차운동전 1.7±0.3ng/㎖에서 운동후 1.7±0.4ng/㎖로 의미있는 변화는 없었다. 결론적으로 활차운동 후 혈장 섬유소 용해능과 t-PA antigen 농도는 현저히 증가하였으며, 전신적인 섬유소 용해능을 자극하는 임상적인 방법으로서 활차운동은 비교적 안전하고 유용한 검사하고 사료된다. The systemic fibrinolytic potential could not be deter-mined by simple measurement of plasma fibrinolytic activity or plasma plasminogen activators, and stimulation test is essential to determine systemic fibrinolytic potential. In general plasma fibrinolytic activity is increased by emotional stress, physical exercise, venous occlusion, and DDAVP (desamino-d-arginine vasopressin) infusion. But until recently standardized test to stimulate systemic fibrinolysis is not established in clinical field. The treadmill exercise is one of the method to stimulate systemic fibrinolysis and is relatively safe in every clinical situations> Moreover standardization of exercise test as clinical standardized stimulation test of systemic fibrinolysis. On the first step, we measured plasma fibrinolytic activities before and after standardized treadmill exdrcise in normal individuals to testify its reliability. Sixteen healthy men (age from 15 to 68) performed more than 85% of maximal exercise determined by heart rate for their age group on treadmill. Before and after exercise we measured euglobulin fibrin lysis area, and antigen levels of t-PA and u-PA by ELISA method. After exercise euglobulin fibrin plate lysis area was increased from 98.4±9.5 BAU (Blood Activator Unit) to 116.4±17.4 (p<0.0005) (Normal pooled plasma: 100 BAU). And t-PA antigen level was also increased from 3.2±2.3ng/㎖ (before exercise) to 4.9±2.6ng/㎖ (after exercise) (p<0.0001). The antigen level of u-PA was not changed after exercise: from 1.7±0.3ng/㎖ pre-exercise to 1.7±0.4ng/㎖ post-exercise. In conclusion we found that systemic fibrinolytic activity and antigen level of t-PA were enhanced after exercise. And we consider that standardized treadmill exercise is safe and reliable method to stimulate systemic fibrinolysis.

운동생리학 : 유산소 트레이닝이 비만남성의 Acute Inflammatory Markers, t-PA 및 Cholesterol 농도에 미치는 영향

류호상(HoSangYoo),박승한(SungHanPark),변재철(JaeChulByun) 한국체육학회 2005 한국체육학회지 Vol.44 No.4

C-reactive protein (CRP), fibrinogen, albumin, and white blood cell (WBC) counts were used as the markers for acute systemic inflammation. CRP was significantly associated with obesity, high CRP level associated with increased cardiovascular disease risk. And generally, increased serum t-PA (tissue plasminogen activator) level is believed to reduce the risk of cardiovascular disease. Moreover, t-PA level may show to increase significantly after chronic exercise.The purpose of this study was to examine the effects of blood cholesterol and inflammatory markers and enhancement of systemic fibrinolytic activity after 8 weeks of aerobic exercise training. A total of 16 healthy males (n=8, control group) and obese males (n=8, experiment group) were served as subjects. Aged between 20-27 years. Subjects were assigned to a supervisor and given an exercise program 3 days a week. All subjects participated in an aerobic exercise training for 30 minutes, then did additional treadmill exercise for 30 minutes at which they were instructed to maintain a continuous 55% to 70% of the peak heart rate according to an initial exercise training.The present study showed that WBC count and serum Albumin level were no changes between groups. There were significantly different on plasma fibrinogen and serum CRP and t-PA levels between groups. Also, fibrinogen and CRP levels after aerobic exercise training were lower than pre exercise training in two groups, although serum t-PA level was increased after 8 weeks. There were significant differences on TC level between pre and post exercise training in two groups, and HDL-C and LDL-C levels were shown to decreased.Aerobic exercise training may lowered CRP level, and there was enhanced t-PA level. In conclusion, regular physical activity may decrease the risk of cardiovascular diseases in both normal and obese men.

제2시와 제3시 설법의 관계에 대한 원측(圓測) 인식의 특징-『해심밀경소』 티벳어역 속 신발굴자료에 대한 소개를 겸해

장규언(JANG, Gyu-eon) 불교학연구회 2014 불교학연구 Vol.40 No.-

이 논문은『 해심밀경(解深密經)』의 이른바‘삼시교판(三時敎判)’에 등장하는 제2시『반야경(般若經)』과 제3시『해심밀경(解深密經)』간의 관계에 대한 원측(圓測, 613-696) 인식의 특징에 대한 연구이다. 이를 위해 필자는 근래에『해심밀경소(解深密經疏)』｢서품(序品)｣ 교체론의 티벳어역(대응하는 한문이 생략된 부분) 속에서 새로 발굴한 자료들과 원측 저작 속에 산재하는 관련 자료들을 근거로 하여 원측 교판론(敎判論)의 해석학적 전제, 료의(了義)와 불료의(不了義) 판단의 기준, 그 이면의 불교사에 대한 인식 등을 차례대로 살펴보고자 한다. 첫째 주제와 관련하여, 󰡔해심밀경󰡕의 주석가 원측은 ｢무자성상품｣의 삼시 교판의 해석학적 전제에 따라 (1)무상과 료의는 공이라는 설법 주제를 공유하지만, (2)상이한 청중의 수행적 지향에 따라 각기 다른 방식으로 설해진 가르침이며, 또 (3)논쟁과 야기와 종식이라는 관점에서 양자 간에는 ‘결과적으로’ 우열이 존재하는 것으로 인식했음을 밝혔다. 둘째 주제와 관련하여, 원측에게 있어 제2시 불료의와 제3시 료의의 차이는 ‘설법 주제[所詮]’ 자체의 차이가 아니며 설법 주체 측면의 중생의 근기에 따른 설법 방식의 차이와 함께 설법 수용 측면의 ‘설법 효과의 차이’(=부정적 유산의 유무)를 의미함을 지적하였다. 셋째 주제와 관련하여, 신발굴자료를 중심으로 양자의 차이와 동일성에 대한 앞선 원측 인식이 기반하고 있는 교리적 또는 불교사관적 근거를 조명하여 원측이 스스로 공(空)을 진정으로 이해하고 있다고 자부하는 유식(唯識)의 료의의 입장에 서서 제2시 ‘무상(無相)’을 제3시 ‘삼성(三性)’과의 관계 속에서 ‘료의’로 재해석함으로써 양자를 통합적으로 인식하려 했음을 지적하였다. 또 위의 연장선상에서 제2시 ‘『반야경』이 삼성을 설하고 있기 때문에 료의’라는 원측의 일면 파격적인 주장도 ‘궁극적 진리[勝義]의 관점’에서 무상은 삼성을 설하는 것으로 인식될 수 있다는 의미로 해석 가능함을 밝혔다. 이상 양자의 관계에 대한 원측 인식은 제3시의 관점에서 제2시를 포괄함으로써 양자 간의 연속성과 궁극적 동일성을 강조하려는 경향이 우선 두드러진다. 하지만 동시에 원측의 마음속에는 제3시 료의가 제1시 설법이 유발하게 되는 유집의 극단과 제2시 설법이 쉽게 빠질 수 있는 무집의 극단을 모두 변증법적으로 지양(止揚)했다는 점에서 제2시 무상보다 더 높은 가르침이라는 우열 의식이 여전히 존재하는 듯하다. 이것은 어쩌면 논쟁의 종식이라는 관점에서 완전한 가르침으로 인식된『해심밀경』을 최고 권위로 인정하는 ‘유가행(瑜伽行) 사상가’ 원측의 운명에 기인한 것인지도 모르겠다. In this paper, I illuminate some characteristics of Woncheuk's view on the relationship between the Second and Third Buddhacakras presented in Sa.dhinirmocana-s.tra. For this, based on some newly identified materials (parts of the section Discourse on Essence of Buddha's Teaching (教體論) of "Seo pum" (序品; Ch. Xu pin, Introductory Chapter); omitted in classical Chinese) in Ḥphags pa dgoṅs pa zab mo ṅes par ḥgrel paḥi mdo rgya cher ḥgrel pa, the Tibetan version of Haesimmilgyeong so (解深密經疏; Ch. Jieshenmijing shu, Commentary on Saṃdhinirmocana-sūtra), written by Woncheuk (圓測 613-696; Ch. Yuance), and related materials in his works, I present some hermeneutical premises of his view on the Three Buddha-cakras, his interpretation of the criteria of discrimination between nītārtha and neyārtha, and his views on the development of Buddhist thought. First, as a commentator on Saṃdhinirmocana-sūtra, Woncheuk, according to the hermerneutical premises of Three Buddha-cakras, presents that (1) the common theme of both the Second and Third Buddha-cakras are Emptiness (空), so there is neither superiority nor inferiority between them, but (2) from the viewpoint of either ending or creating disputes, the Third is actually superior to the Second Budda-cakra. Second, he further interprets that the criteria of discrimination between nītārtha and neyārtha is not the theme of Buddha-cakra itself, but both the differences of the speaker's preaching style according to the hearer's abilities, and the effects of preaching on the part of the hearer. Third, with special reference to the newly identified materials mentioned above, I illuminate that Woncheuk, from the standpoint of a Yogacāra thinker who thinks that only his school really understands Emptiness, reinterprets Emptiness as nītārtha based on his own hermeneutical horizon that Emptiness itself, in fact, penetrates through Three Characters (三性), therefore integrating both the Second and Third Buddha-cakras as one. Futhermore, extending the line of thought above, I reveal that his sensational opinion that the Second Buddha-cakra, Prajñā-pāramitā literatures are also nītārtha is understandable in that from the viewpoint of Ultimate Truth (勝義諦), Emptiness is conceived to be Three Characters. In conclusion, Woncheuk's view, first of all, is characterized by the emphasis on the continuity and ultimate sameness between the two Buddha-cakras in terms of including the Second from the standpoint of the Third Buddha-cakra. But at the same time, the status of the Third Buddha-cakra is actually higher in his mind than the Second since the former is a perfect teaching that overcomes the negative extremes of the latter. I believe that this derives from his fate as a Yogacāra commentator who regarded Saṃdhinirmocana-sūtra as one of the supreme canonical authorities.

신경차단이 정맥압박에 의한 t - PA 분비에 미치는 영향

홍세용(Sae Yong Hong),양동호(Dong Ho Yang),신현길(Hyun Kil Shin),김순길(Sun Kil Kim),김난숙(Nam Suk Kim),김형미(Hyung Mi Kim),신정순(Jung Sunn Shin) 대한내과학회 1992 대한내과학회지 Vol.43 No.2

N/A Background: Fibrinoiytic response to venous occlusion of the limbs had been regarded as a sensitive and reliable method for assessing the individual fibrinolytic capacity, but the exact mechanism of the increased fibrinolytic activity after venous occlusion is not clear. Methods: In order to investigate the influence of neurotransmitter on t-PA release by venous occlusion, we compared the increase in t-PA and fibrinolytic activity in the euglobulin fraction initiated by cubital venous occlusion (100mmHg for 10mins), in pre-neural block and post-neural block states, in seven cases. In all patients, the supra-clavicular approach was used to obtain a brachial plexus block and venous occlusion was achieved at the cubital levels on the ipsilateral arm. Results: The euglobulin fibrinolytic activity before venous occlusion was 100.9±27,5 BAU in the pre nerve block state and 102.7±29.4 BAU in the post nerve block state (p>0.5). The t-FA antigen level before venous occlusion was 3.5±1.2ng/ml in the pre nerve block state and 4.0±1.0ng/ml in the post nerve block state (p>0.5). The increase in the euglobulin fibrinolytic activity after venous occlusion was 18.0±16.7 BAU in the pre nerve block state, and 18.3±15.6 BAU in the post nerve block state (p>0.5). The increase in the t-PA antigen levels after venous occlusion was 3.0±2.0ng/ ml in the pre nerve block state and 3.0±2.1ng/ml in the post nerve block state (p>0.5). Conelwion: These findings suggest that the peripheral nervous system does not exert any influence on t-PA release during venous occlusion.

유전자치료 효율향상을 위한 세포특이적 Vector의 개발

김계영,남명진,유천권,진동훈,백묘아,박만석,심수경,이혜경,이병철,박미연 국립보건연구원 2000 국립보건원보 Vol.37 No.-