• Title/Summary/Keyword: vWF

Search Result 36, Processing Time 0.024 seconds

Long-Term Expression of von Willebrand Factor by a VSV-G Pseudotyped Lentivirus Enhances the Functional Activity of Secreted B-Domain-deleted Coagulation Factor VIII

  • Park, Sang Won;Choi, Sang-Yun
    • Molecules and Cells
    • /
    • v.24 no.1
    • /
    • pp.125-131
    • /
    • 2007
  • von Willebrand factor (vWF) is a multimeric glycoprotein which functions within the coagulation system. It colocalizes with factor VIII (FVIII) by non-covalent interaction and alters its intracellular trafficking. vWF is also instrumental in maintaining the stability of secreted FVIII. The principal objective of this study was to generate a lentivirus-based vWF expression vector for gene therapy of hemophilia A. We inserted a vWF of 8.8 Kb into a lentiviral vector thereby producing VSV-G-pseudotyped vEx52. However, its titer was quite low, presumably because the length of vWF gene exceeds the size limit of the lentiviral vector. In order to overcome the low-titer, we concentrated the vEx52 and thus increased the efficiency of transduction approximately 6-fold with $1/100^{th}$ of the volume. However, as concentration requires an additional laborious step, we attempted to enhance the transduction efficiency by deleting exons 24-46 and 29-46 in pRex52 to construct pRex23 and pRex28, and in pvEx52, yielding pvEx23 and pvEx28, respectively. The transfected pRex52 had a profound effect on the activity of secreted FVIII, and this activity declined as domains of vWF were deleted. However, when the domain-deleted vWF-lentiviruses were transduced into K562 cells, the vEx28 increased the activity of the secreted FVIII compared to what was observed with vEx52. This result is probably due to higher efficiencies of transduction and expression while retaining the essential domains required for proper interaction with FVIII.

EXPRESSION OF THE GENES OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VON WILLEBRAND FACTOR IN SALIVARY GLAND TUMORS (타액선 종양에서 혈관내피성장인자와 von Willebrand 인자 유전자 발현에 관한 연구)

  • Chung, Ji-Hun;Kim, Ji-Hyuk;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • v.30 no.1
    • /
    • pp.41-51
    • /
    • 2008
  • Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

ARIMA Based Wind Speed Modeling for Wind Farm Reliability Analysis and Cost Estimation

  • Rajeevan, A.K.;Shouri, P.V;Nair, Usha
    • Journal of Electrical Engineering and Technology
    • /
    • v.11 no.4
    • /
    • pp.869-877
    • /
    • 2016
  • Necessity has compelled man to improve upon the art of tapping wind energy for power generation; an apt reliever of strain exerted on the non-renewable fossil fuel. The power generation in a Wind Farm (WF) depends on site and wind velocity which varies with time and season which in turn determine wind power modeling. It implies, the development of an accurate wind speed model to predict wind power fluctuations at a particular site is significant. In this paper, Box-Jenkins ARIMA (Auto Regressive Integrated Moving Average) time series model for wind speed is developed for a 99MW wind farm in the southern region of India. Because of the uncertainty in wind power developed, the economic viability and reliability of power generation is significant. Life Cycle Costing (LCC) method is used to determine the economic viability of WF generated power. Reliability models of WF are developed with the help of load curve of the utility grid and Capacity Outage Probability Table (COPT). ARIMA wind speed model is used for developing COPT. The values of annual reliability indices and variations of risk index of the WF with system peak load are calculated. Such reliability models of large WF can be used in generation system planning.

Effect of Dietary Fat Sources and L-arginine Supplementation on Endothelial function and Lipid Metabolism in Streptozotocin-Induced Diabetic Rats (식이지방의 종류와 L-arginine 보충이 당뇨쥐의 ENdothelium 기능 및 체내 지질대사에 미치는 영향)

  • 장문정;김연중;김명환
    • Journal of Nutrition and Health
    • /
    • v.35 no.1
    • /
    • pp.5-14
    • /
    • 2002
  • Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

W/TiN 금속 게이트 MOS 소자의 물리.전기적 특성 분석

  • 윤선필;노관종;노용한
    • Proceedings of the Korean Vacuum Society Conference
    • /
    • 2000.02a
    • /
    • pp.123-123
    • /
    • 2000
  • 선폭이 초미세화됨에 따라 게이트 전극에서의 공핍 현상 및 불순물 확산의 물제를 갖는 poly-Si 게이트를 대체할 전극 물질로 텅스텐(W)이 많이 연구되어 왔다. 반도체 소자의 배선물질로 일찍부터 사용되어온 텅스텐은 내화성 금속의 일종으로 용융점이 높고, 저항이 낮다. 그러나, 일반적으로 사용되고 있는 CVD에 의한 텅스텐의 증착은 반응가스(WF6)로부터 오는 불소(F)의 게이트 산화막내로의 확산으로 인해 MOS 소자가 크게 열화될수 있다. 본 연구에서는 W/TiN 이중 게이트 전극 구조를 갖는 MOS 캐패시터를 제작하여 전기적 특성을 살펴보았다. P-Type (100) Si위에 RTP를 이용, 85$0^{\circ}C$에서 110 의 열산화막을 성장 및 POA를 수행한 후, 반응성 스퍼터링법에 의해 상온, 6mTorr, N2/Ar=1/6 sccm, 100W 조건에서 TiN 박막을 150, 300, 500 의 3그룹으로 증착하였다. 그 위에 LPCVD 방법으로 35$0^{\circ}C$, 0.7Torr, WF6/SiH4/H2=5/5~10/500sccm 조건에서 2000~3000 의 텅스텐을 증착하였다. Photolithography 공정 및 습식 에칭을 통해 200$\mu\textrm{m}$$\times$200$\mu\textrm{m}$ 크기의 W/TiN 복층 게이트 MOSC를 제작하였다. W/TiN 복측 게이트 소자와 비교분석하기 위해 같은 조건의 산화막을 이용한 알루미늄(Al) 게이트, 텅스텐 게이트 MOSC를 제작하였다. 35$0^{\circ}C$에서 증착된 텅스텐 박막은 10~11$\Omega$/ 의 면저항을 가졌고 미소한 W(110) peak값을 나타내는 것으로 보아 비정질 상태에 가까웠다. TiN 박막의 경우 120~130$\Omega$/ 의 면저항을 가졌고 TiN (200)의 peak 값이 크게 나타난 반면, TiN(111) peak가 미소하게 나타났다. TiN 박막의 두께와 WF/SiH4의 가스비를 변화시켜가며 제작된 MOS 캐패시터를 HF 및 QS C-V, I-V 그리고 FNT를 통한 전자주입 방법을 이용하여 TiN 박막의 불소에 대한 확산 방지막 역할을 살펴 보았다. W/TiN 게이트 MOS 소자는 모두 순수 텅스텐 게이트보다 우수하였고, Al 게이트와 유사한 전기적 특성을 보여주었다. W/TiN 게이트 MOS 소자는 모두 순수 텅스텐 게이트보다 우수하였고, Al 게이트와 유사한 전기적 특성을 보여주었다. TiN 박막이 300 , 500 이고 WF6/SiH4의 가스비가 5:10인 경우 소자 특성이 우수하였으나, 5:5의 경우에는 FNT 전자주입 특성이 열화되기 시작하였다. 그리고, TiN박막의 두께가 150 으로 얇아질 경우에는 WF6/SiH4의 가스비가 5:10인 경우에서도 소자 특성이 열화되기 시작하였다. W/TiN 복층 게이트 MOS 캐패시터를 제작하여 전기적인 특성 분석결과, 순수 텅스텐 게이트 소자의 큰 저전계 누설 전류 특성을 해결할 수 있었으며, 불소확산에 영향을 주는 조건이 WF6/SiH4의 가스비에 크게 의존됨을 알 수 있었다. TiN 박막의 증착 공정이 최적화 될 경우, 0.1$\mu\textrm{m}$이하의 초미세소자용 게이트 전극으로서 텅스텐의 사용이 가능할 것으로 보여진다.

  • PDF

Bong-Han Corpuscles as Possible Stem Cell Niches on the Organ-Surfaces (줄기세포의 가능한 원천으로서의 장기표면 봉한소체)

  • Kim, Min-Su;Hong, Ju-Young;Hong, Su;Lee, Byung-Cheon;Nam, Chang-Hoon;Woo, Hee-Jong;Kang, Dae-In;Soh, Kwang-Sup
    • Journal of Pharmacopuncture
    • /
    • v.11 no.1
    • /
    • pp.5-12
    • /
    • 2008
  • Objectives : Showing that Bong-Han corpuscles(BHC) are suppliers of the stem cells in adulthood, and the Bong-Han ducts(BHD) are transportation routes of stem cells. Methods : BHC and BHD were obtained from the internal organ-surfaces of rats. The sliced BHC and BHD were immunostained with various stem cell markers. Extracellular matrices were also analyzed by immunohistochemistry. Result : The presence of mesenchymal stem cells was confirmed by the expression of Integrin beta 1, Collagen type 1 and Fibronectin. But CD54 was not expressed. The hematopoietic stem cell marker, Thy 1 was strongly expressed. BHDs showed Collagen type 1, Fibronectin, and vWF expression. Conclusion : Both hematopoietic and mesenchymal stem cell markers were expressed strongly in BHC similarly as in bone marrow. An endothelial cell marker(vWF) demonstrated the possibility of the stem cell transportation routes of BHD.

Comparative Evaluation on Sperm Parameter of Transgenic Pigs with General Pigs (형질전환 돼지의 정자와 일반돼지의 정자성상에 대한 비교평가)

  • Park, Sang Hyoun;Lee, Gunsup;Lee, Joo Yung;Kim, Kyung Woon;Byun, Sung-June;Ock, Sun A;Hwang, Seongsoo;Yang, Hyeon;Woo, Jae-Seok;Oh, Keon Bong
    • Journal of Embryo Transfer
    • /
    • v.32 no.3
    • /
    • pp.227-233
    • /
    • 2017
  • Pig has been known to be one of the most feasible animals as a bioreactor to produce pharmaceuticals in milk and as a mediator in xenotransplantation research. Previously, we generated transgenic pigs for both purposes, which were expressing Factor 8, vWF, hTPA, and hEPO in milk, along with expression of MCP at GalT gene locus ($GalT^{-MCP/-MCP}$) as well as expressing MCP at GalT gene loci with CD73 expression ($GalT^{-MCP/+}/CD73$). In this study, we performed comparative analyses of sperm parameters between wild type male (WT) pig and those transgenic males to examine the effects of transgenes integrated into the pigs on motility, morphology, viability, and acrosome integrity of the spermatozoa. Our results showed that the rates of actively motile spermatozoa of WT, Factor 8, vWF, hTPA, hEPO, $GalT^{-MCP/+}/CD73$, and $GalT^{-MCP/-MCP}$ pigs were 85.0%, 83.3%, 82.5%, 83.3%, 82.5%, 77.5%, and 78.7%, respectively. Whereas, the rates of morphologically normal spermatozoa of WT, Factor 8, vWF, hTPA, hEPO, $GalT^{-MCP/+}/CD73$, and $GalT^{-MCP/-MCP}$ pigs were 90.0%, 80.0%, 80.0%, 83.3%, 85.0%, 91.8%, and 80.8%, respectively. In addition, the viability in spermatozoa of WT, Factor 8, vWF, hTPA, hEPO, $GalT^{-MCP/+}/CD73$, and $GalT^{-MCP/-MCP}$ pigs were 93.9%, 82.4%, 89.9%, 83.9%, 87.4%, 92.8%, and 83.6%, respectively. The rates of spermatozoa with normal acrosome integrity in WT, Factor 8, vWF, hTPA, hEPO, $GalT^{-MCP/+}/CD73$, and $GalT^{-MCP/-MCP}$ pigs were 98.1%, 98.6%, 98.6%, 98.7%, 98.1%, 99.5%, and 95.1%, respectively. There were no significant differences in motility, morphology, viability, and acrosome integrity of the spermatozoa among WT, Factor 8, vWF, hTPA, and hEPO, $GalT^{-MCP/+}/CD73$, and $GalT^{-MCP/-MCP}$ pigs. These mean that neither random integration nor targeted integration of the transgene into chromosome of pig effect on characteristics of spermatozoa. Ultimately, the transgenic male pigs subjected in this study could apply to propagate their progenies for production of human therapeutic proteins and advancing the xenotransplantation research.

Effect of Type I Collagen on Hydroxyapatite and Tricalcium Phosphate Mixtures in Rat Calvarial Bony Defects

  • Kim, Jung-Hwan;Kim, Soung-Min;Kim, Ji-Hyuck;Kwon, Kwang-Jun;Park, Young-Wook
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • v.34 no.1
    • /
    • pp.36-48
    • /
    • 2008
  • To repair bone defects in the oral and maxillofacial field, bone grafts including autografts, allografts, and artificial bone are used in clinical dentistry despite several disadvantages. The purpose of this study was to evaluate new bone formation and healing in rat calvarial bone defects using hydroxyapatite (HA, $Ca_{10}[PO_4]_6[OH]_2,\;Bongros^{(R)}$, Bio@ Co., KOREA) and tricalcium phosphate (${\beta}-TCP,\;Ca_3[PO_4]_2$, Sigma-Aldrich Co., USA) mixed at various ratios. Additionally, this study evaluated the effects of type I collagen (Rat tail, BD Biosciences Co., Sweden) as a basement membrane organic matrix. A total of twenty, 8-week-old, male Sprague-Dawley rats, weighing 250-300g, were divided equally into a control group (n=2) and nine experimental groups (n=2, each). Bilateral, standardized transosseous circular calvarial defects, 5.0 mm in diameter, were created. In each experimental group, the defect was filled with HA and TCP at a ratio of 100:0, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, and 0:100 with or without type I collagen. Rats were sacrificed 4 and 8 weeks post-operation for radiographic (standardized plain film, Kodak Co., USA), histomorphologic (H&E [Hematoxylin and Eosin], MT [Masson Trichrome]), immunohistochemical staining (for BMP-2, -4, VEGF, and vWF), and elementary analysis (Atomic absorption spectrophotometer, Perkin Elmer AAnalyst $100^{(R)}$). As the HA proportion increased, denser radiopacity was seen in most groups at 4 and 8 weeks. In general radiopacity in type I collagen groups was greater than the non-collagen groups, especially in the 100% HA group at 8 weeks. No new bone formation was seen in calvarial defects in any group at 4 weeks. Bridging bone formation from the defect margin was marked at 8 weeks in most type I collagen groups. Although immunohistochemical findings with BMP-2, -4, and VEGF were not significantly different, marked vWF immunoreactivity was present. vWF staining was especially strong in endothelial cells in newly formed bone margins in the 100:0, 80:20, and 70:30 ratio type I collagen groups at 8 weeks. The calcium compositions from the elementary analysis were not statistically significant. Many types of artificial bone have been used as bone graft materials, but most of them can only be applied as an inorganic material. This study confirmed improved bony regeneration by adding organic type I collagen to inorganic HA and TCP mixtures. Therefore, these new artificial bone graft materials, which are under strict storage and distribution systems, will be suggested to be available to clinical dentistry demands.

Control of Platelet Rolling and Adhesion

  • Moskowitz, Samuel E.
    • 제어로봇시스템학회:학술대회논문집
    • /
    • 2002.10a
    • /
    • pp.77.1-77
    • /
    • 2002
  • Platelets arrest bleeding and repair damaged blood vessels. The purpose of this paper is to formulate a mathematical model for the control of platelet adhesion within the vasculature consistent with experimental findings, particularly those of Frenette, Ruggeri , Savage, Yuan, Lawrence and Springer. In addition to providing some, albeit rudimentary, insight into the behavior of platelets, a numerical simulation of this theoretical model may be useful in a systematic study of pathological cases. Glycoprotein receptor complex (GPIb/V/IX), found on the platelet surface membrane, binds to the adhesive protein and ligand von Willebrand factor (vWf), located within the sub-endothelium. The binding...

  • PDF

Type I von Willebrand Disease in a Maltese (한국내 말티즈에서 발생한 제 1형 폰 빌레브란트병 증례)

  • Kim, Seung-Gon;Kang, Min-Hee;Lee, Kyo-Im;Kim, Ha-Jung;Park, Hee-Myung
    • Journal of Veterinary Clinics
    • /
    • v.30 no.5
    • /
    • pp.359-362
    • /
    • 2013
  • A 6-year-old castrated male Maltese weighing 4.16 kg presented with a history of bleeding from the mouth after scaling and dental extraction 2 days prior. The von Willebrand factor antigen (vWf:Ag) level was 54% (reference range, 70-180%), indicating that the dog was homozygous for an inherited von Willebrand disease (vWD). The dog received whole-blood transfusion as initial treatment, consequently showing markedly improved clinical signs, and is currently in good condition. To our knowledge, this is the first reported case of type 1 vWD in a Maltese in Korea.