• 제목/요약/키워드: PAI-1

검색결과 795건 처리시간 0.041초

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

  • Davami, Fatemeh;Sardari, Soroush;Majidzadeh-A, Keivan;Hemayatkar, Mahdi;Barkhordari, Farzaneh;Enayati, Somayeh;Adeli, Ahmad;Mahboudi, Fereidoun
    • BMB Reports
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    • 제44권1호
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    • pp.34-39
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    • 2011
  • 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, $570\;IU/{\mu}g$, was found to be similar to those found in full length t-PA (Alteplase$^{(R)}$), $580\;IU/{\mu}g$. 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.

Nutritional Regulation of Plasminogen Activator Inhibitor-1, Leptin and Resistin Gene Expression in Obese Mouse

  • Lee, Hyun-Jung;Yang, Jeong-Lye;Kim, Young-Hwa;Kim, Yangha
    • Nutritional Sciences
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    • 제6권2호
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    • pp.73-77
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    • 2003
  • PAI-1 (plasminogen activator inhibitor-1), leptin, and resistin are synthesized and secreted by Int cells of rodents and have recently been postulated to be an important link to obesity. This study was conducted to identify the nutritional regulation of PAI-1, leptin, and resistin gene expression in 0b/ob mice. The mice were divided into four groups according to nutritional status: control, 48 hour fasting, 48 hour-fasting/12 hour-refeeding, and 48 hour-fasting/24 hour-refeeding. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. In visceral fat tissue, the level of PAI-1 mRNA increased markedly when 48h-fasted animals were refed with a high carbohydrate-low fat diet. However, lasting/refeeding did not appreciably change PAI-1 mRNA levels in subcutaneous fat tissue. Similar results were obtained for resistin mRNA levels in both types of fat tissues. These findings suggest that visceral adipose tissue might be more sensitively involved in the nutritional regulation of PAI-1 and resistin gene expression compared to subcutaneous fat tissue. The level of leptin mRNA decreased markedly in the 48h-fasted animals, and increased markedly when 48h-fasted animals were refed with a high carbohydrate-low fat diet. The nutritional regulation of leptin mRNA showed similar patterns in both types of fat tissues. In conclusion, the nutritional regulation of gene expression encoding PAI-1, resistin, and leptin from adipocytes may vary according to the type of adipose tissue.

한국인의 허혈성 뇌경색 발생과 플라스미노겐 활성 억제인자-1(PAI-1) 유전자 다형성과의 관계 (The Association of the -675 4G/5G and A-844G Polymorphisms of the Plasminogen Activator Inhibitor-1 Gene with a Risk of Ischemic Stroke in Korean Population)

  • 이병철;변상혁;김순일;강기훈;안세영;두호경;서정철;임강현;조성호;;안영민
    • 대한한방내과학회지
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    • 제25권4호
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    • pp.18-24
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    • 2004
  • 연구배경 : 플라스미노겐 활성 억제인자-1 (plasminogen activator inhibitor-1; PAI-1)은 허혈성 뇌경색의 발생의 원인이 되는 섬유소 용해작용의 저하를 매개하는 인자로서, PAI-1의 작용이 촉진되면 섬유소 용해기능이 저하되어 관상동맥 및 뇌혈관질환의 발생을 증가시키게 된다. PAI-1 유전자의 촉진자(promoter) 영역에는 -675 4G/5G (4G/5G)와A -844G (A/G)의 두 개의 유전자 다형성이 존재하며, 이는 PAI-1의 유전자 전사과정에 영향을 미쳐 혈청 PAI-1의 농도를 증가시키고 결과적으로 허혈성 뇌경색의 발생확률을 높이는 작용을 하게 된다. 연구방법 : 허혈성 뇌경색으로 진단 받은 167명의 환자와 173명의 건강인의 말초혈액에서 DNA를 분리한 후 PAI-1의 4G/5G와 A/G 유전자 다형성에 대한 연쇄중합반응 및 제한효소 절편길이 다형성 (polymerase chain reaction-restriction fragment length polymorphism; PCR-RFLP) 방법을 이용하여 허혈성 뇌경색 발생과 유전자 다형성과의 관계를 비교 분석하였다. 결과 : 허혈성 뇌경색 환자에서의 4G/4G의 유전자형의 빈도는 15.0%으로 정상 대조군의 33.5%에 비해 현저하게 낮게 나타났다 (P < 0.0001). 각각의 유전자형과 허혈성 뇌경색의 발생 위험도 (odd ratio ; OR)와의 관계를 분석했을 때 4G/4G 유전자형을 가질 경우 위험도는 0.35배로 현저하게 낮아졌으며, (P < 0.0001), 5G/5G 유전자형을 가질 경우 위험도는 4.49배 로 현저하게 높아졌다 (P < 0.0001). 그러나, A/G 유전자 다형성과 허혈성 뇌경색의 발생과는 유의한 연관성을 발견하지 못하였다. 결론 : 이상의 결과로 볼 때 PAI-1 유전자의 4G/4G 유전자형은 허혈성 뇌경색의 발생 비율을 감소시키는 작용을 하는 것으로 여겨진다.

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가속된 열적 스트레스에 의한 PAI / Nano Silica 하이브리드 코일의 절연수명 추정 (Estimation of Insulation Life of PAI/Nano Silica Hybrid Coil by Accelerated Thermal Stress)

  • 박재준
    • 전기학회논문지
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    • 제68권1호
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    • pp.52-60
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    • 2019
  • In this paper, four types of insulation coils were fabricated by adding various kinds of glycols to improve the flexibility and adhesion of insulating coils in varnish dispersed with PAI / Nano Silica_15wt%. The applied voltage and frequency were 1.5 kV / 20 kHz for accelerated life evaluation. Through the 6th temperature stress level, the cause of the insulation breakdown of the coil was ignored and only the breakdown time was measured. The Arrhenius model was chosen based on the theoretical relationship between chemical reaction rate and temperature for estimating the insulation life of the coil due to accelerated thermal stress. Three types of distributions (Weibull, Lognormal, Exponential) were selected as the relationship between thermal stress model and distribution. The average insulation lifetime was estimated under the temperature stress of four types of insulation coils through the relationship between one kind of model and three kinds of distributions.

쑥 (Artemisia princeps P.) 추출물이 고지방식이를 급여한 흰쥐의 대사장애 및 아디포카인 조절에 미치는 영향 (Amelioration of metabolic disturbances and adipokine dysregulation by mugwort (Artemisia princeps P.) extract in high-fat diet-induced obese rats)

  • 김윤혜;박충무;윤군애
    • Journal of Nutrition and Health
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    • 제49권6호
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    • pp.411-419
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    • 2016
  • 본 연구는 고지방식이와 쑥추출물이 흰쥐의 지질대사, 인슐린저항성, 아디포카인 분비에 미치는 효과를 측정하였다. 고지방식이에 의해 부고환지방과 복막후강지방의 축적이 증가되었고, 그 결과 혈장 항염증성 아디포카인은 감소하고 염증성 아디포카인은 증가하여 아디포넥틴/렙틴 및 아디포넥틴/PAI-1 비가 저하되는 불균형을 초래하였다. 내장지방 축적과 관련된 아디포카인의 불균형은 TG, TG/HDL-C, TC/HDL-C를 증가시키고 HOMA-IR의 증가를 유발한 것으로 추정된다. 이에 비해 쑥 에탄올추출물의 첨가는 부고환지방과 복막후강지방의 축적을 완화함으로써 PAI-1과 렙틴을 감소시켜 아디포넥틴/렙틴 및 아디포넥틴/PAI-1 비의 저하를 억제하고 아디포카인의 균형을 상대적으로 유지하였으며, TG, TG/HDL-C, TC/HDL-C 및 HOMA-IR 수치가 감소하였다. 따라서 쑥 에탄올추출물은 내장지방 축적을 억제하고 아디포카인의 분비, 특히 염증성물질인 렙틴과 PAI-1의 분비를 저하시켜 아디포카인의 균형을 조절함으로써 지질대사 및 인슐린저항성을 개선하는 효과가 있는 것으로 나타났다.

두 종류 임계 섞임체 단백질-물의 상전이 온도 근방에서 비선형 광학적 특성 (Nonlinear Optical Behavior of Binary Mixture Protein and Water near the Phase Separation Temperature)

  • 조창호;서영석;김칠민;박종대;이종수
    • 자연과학논문집
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    • 제9권1호
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    • pp.83-88
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    • 1997
  • 임계 혼합물인 Lysozyme 과 물의 임계온도 근처에서 임계현상을 연구하였다. 자기유도 타원편광축회전에 의한 제3차 비선형 광학감수율을 상전이 온도 근처에서 측정하였으며, 불순물인 소금의 양의 증가는 상전이온도를 높이고 글리세롤 양이 증가함으로서 상전이 온도가 감소함을 관측하였다.

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Hormonal Regulation of Leptin, Resistin, and Plasminogen Activator Inhibitor-1 Gene Expression in 3T3-L1 Adipocytes

  • Lee, Hyun-Jung;Kim, Yang-Ha
    • Preventive Nutrition and Food Science
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    • 제9권4호
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    • pp.336-341
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    • 2004
  • Leptin, resisitn and PAI-1 (plasminogen activator inhibitor-1) are synthesized and secreted by rodent fat cells and recently postulated to be an important link to obesity. This study was conducted to characterize the hormonal regulation of leptin, resistin, and PAI-1 gene expression in the 3T3-L1 adipocytes. The cells were treated with 0.5 $\mu$M insulin, 1 $\mu$M dexamethasone (Dex), or 0.05 $\mu$M triiodothyronine (T3) for 72 hours. The mRNA levels of each peptide were measured by semi-quantitative RT-PCR. The mRNA level of the leptin-producing ob gene was significantly increased by insulin, Dex, and T3 by 3.2-, 3.1- and 2.7-fold, respectively, compared to the control (p < 0.05). The level of resistin mRNA was increased by insulin, Dex, and T3 by 2.7-, 2.5- and 2-fold, respectively, compared to the control (p < 0.05). Likewise, the level of PAI-1 mRNA was significantly increased by insulin, Dex, and T3 compared to the control (p < 0.05). Taken together, our results suggest that insulin, Dex, and T3 may regulate the gene expression of leptin, resistin, and PAI-1 in 3T3-L1 adipocytes.

Effect of Winding Coil Diameter on AC Insulation Breakdown Voltage of Polyamideimide/Nanosilica Wire

  • Park, Jae-Jun;Woo, Myung-Ha;Lee, Jae-Young;Han, Se-Won
    • Transactions on Electrical and Electronic Materials
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    • 제17권4호
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    • pp.231-234
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    • 2016
  • The AC insulation breakdown voltage was investigated for seven types of winding coils made of polyamideimide (PAI), flexural PAI (nanosilica 5 wt%) and anti-corona PAI (nanosilica 15 wt%) wires with various winding coil diameters of φ5, φ15 and φ25 mm. The winding coil was made of enameled wire with an enamel thickness of 30~50 μm, and the rectangular copper wire had a thickness of 0.77~ to 0.83 mm and width of 1.17~ to 1.23 mm, respectively. The insulation breakdown voltages of the original PAI coils with diameters of φ5, φ15 and φ25 mm were 7.30, 6.58, and 5.95 kV, respectively, and those values decreased as the winding coil diameter increased, regardless of the wire types.