Abstract：
:Recombinant factor IX (rFIX) is increasingly used to treat patients with hemophilia B. CHO (Chinese Hamster Ovary) cells are commonly used for the production of rFIX but they have a limited capacity for introducing post-translational modifications (PTM) leading to incomplete γ-carboxylation, low phosphorylation and sulfation profiles as compared with plasma-derived preparations. Imperfect PTM might have an impact on the activity of Factor IX molecule. Several studies in animal models as well as clinical trials have previously reported a lower recovery of rFIX compared to plasma-derived FIX concentrates. In the present study, we aimed to produce a rFIX having a profile of PTM similar to plasma-derived FIX, using human hepatoma cell line HuH-7. We showed that rFIX produced by HuH-7 cells followed the classical intracellular pathway before secretion. In addition, improved PTM were associated with fully active molecule compared to plasma-derived and recombinant control FIX molecules. Secreted rFIX presented as a single band at the correct molecular weight. HuH-7 cellular clones were obtained and they secreted a biologically active human FIX. FIX was then purified for a detailed evaluation of PTM. Glycosylation and sialylation profiles were similar to plasma-derived and rFIX and mass spectrometry analysis demonstrated the presence of phosphorylated and sulfated forms of rFIX. These data strongly support that HuH-7 cells may represent an effective cellular system for production of rFIX exhibiting PTM similar to plasma-derived FIX.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Enjolras N,Dargaud Y,Pérot E,Guillaume F,Becchi M,Négrier Cdoi
10.1016/j.thromres.2012.08.313subject
Has Abstractpub_date
2012-11-01 00:00:00pages
e266-73issue
5eissn
0049-3848issn
1879-2472pii
S0049-3848(12)00689-5journal_volume
130pub_type
杂志文章abstract：BACKGROUND:Nuclear factor kappa B (NF-kappa B) activation and tissue factor (TF) expression may contribute to lethality in sepsis. Inappropriate in vivo expression of TF is likely responsible for fibrin deposition in sepsis-associated disseminated intravascular coagulation (DIC). Clinical assessment of TF expression ha...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.thromres.2003.09.017
更新日期：2003-01-01 00:00:00
abstract：:The two objectives of the study were to determine whether a procedure could be developed for measuring cancer procoagulant (CP) activity in human serum and if this procedure provided a method for distinguishing people with cancer from those without cancer. A procedure was developed for processing human serum such that...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90256-9
更新日期：1989-11-01 00:00:00
abstract：:Several sex-related differences in the incidence rate, clinical presentation and outcomes of VTE were recently investigated. Gender-related risk factors, such as the use of oral contraceptives (OC) and pregnancy, in particular in women with a thrombophilic state, are associated with an increased risk of venous thrombo...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/S0049-3848(11)70023-8
更新日期：2011-02-01 00:00:00
abstract：:Radioactivity from I125-labeled human platelets was measured to estimate the extent of binding of platelet surface proteins to immobilized thrombin. 1-3% of the radioactivity was bound with 10-20% of this amount apparently irreversibly bound to the thrombin matrix. Site-specific chemical modification of thrombin with ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(92)90271-b
更新日期：1992-08-15 00:00:00
abstract：:D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample t...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2006.10.020
更新日期：2007-01-01 00:00:00
abstract：BACKGROUND:Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis, which begins during the first trimester, but the exact time of onset is unknown. Thrombin generation, a laboratory marker of thrombosis risk, increases during normal pregnancy but it is unclear exactly how early this...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2017.06.027
更新日期：2017-09-01 00:00:00
abstract：:From kinetic analysis on the initial stage of the fibrinogen-fibrin conversion catalyzed by thrombin, inhibition constants, Kip, of heparin and heparin analogues were obtained by the turbidimetrical method. The inhibitory effect per unit amount in weight of heparin and heparin analogues increased generally with decrea...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90235-x
更新日期：1985-09-01 00:00:00
abstract：:The cerebral vascular supply is constructed to protect the cerebral hemispheres and brainstem from the consequences of blood flow cessation. Reversal of blood flow around local obstructions is a feature of the microvascular beds of the striatum and cerebral cortex. Cerebral capillaries of these beds consist of endothe...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/s0049-3848(00)00218-8
更新日期：2000-05-01 00:00:00
abstract：:A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily accord...
journal_title：Thrombosis research
pub_type： 信件
doi：10.1016/j.thromres.2016.05.020
更新日期：2016-07-01 00:00:00
abstract：:An abnormal prothrombin has been detected in a 26-year-old female, who had no history of excessive bleeding. Prothrombin activity was approximately 10% when measured using either the classical one-stage assay or the assay with Echis carinatus venom, whereas prothrombin antigen level was normal. In keeping with current...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(91)90373-5
更新日期：1991-06-15 00:00:00
abstract：INTRODUCTION:Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to effici...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.05.034
更新日期：2014-08-01 00:00:00
abstract：:The effect of dalteparin, a low molecular weight heparin, on severely antithrombin III (ATIII)-decreased disseminated intravascular coagulation (DIC) model was compared with that of unfractionated heparin (heparin). The DIC model in rabbits was produced by continuous infusion of thrombin in combination with bolus inje...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(95)00191-s
更新日期：1995-12-01 00:00:00
abstract：BACKGROUND:SARS-CoV-2 infection has noted derangements in coagulation markers along with significant thrombotic complications. Post-mortem examinations show severe endothelial injury and widespread thrombotic microangiopathy in the pulmonary vasculature. Early reports describing the use of prophylactic anticoagulation ...
journal_title：Thrombosis research
pub_type： 评论,信件
doi：10.1016/j.thromres.2020.09.030
更新日期：2020-12-01 00:00:00
abstract：PURPOSE:Due to its specific pharmacokinetic profile, tinzaparin, a low-molecular-weight heparin (LMWH), appears not to be associated with anti-factor Xa accumulation. Our meta-analysis aimed at determining whether long-term curative doses of tinzaparin is a valuable alternative to vitamin K antagonists (VKA) for the tr...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析
doi：10.1016/j.thromres.2012.08.290
更新日期：2012-12-01 00:00:00
abstract：:Fractalkine/CX3CR1 pathway is considered a major modulator of atherosclerosis. In the present study, expression of CX3CR1 on PBMCs/monocytes of healthy individuals and coronary artery diseased patients was initially assessed by flow cytometry. Effects of pre-inflammatory cytokines interferon (INF)-gamma and tumor necr...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2007.04.005
更新日期：2007-01-01 00:00:00
abstract：:The efficacy and the safety of a new urokinase dosage regimen (loading dose 250,000 IU, initial maintenance dosage 2,000 IU/kg/h in combination with heparin) was studied in ten cases of deep vein thrombosis with regard to the changes of the blood coagulation and fibrinolytic enzyme system. The coagulation analyses dem...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90210-9
更新日期：1982-01-01 00:00:00
abstract：:The serotonin transporter (SERT) is found in neuron and platelet membranes. Selective serotonin-reuptake inhibitors (SSRIs) are widely prescribed for severe depression. They may at least partly counteract the effects of serotonin on the vascular biology system, can lower agonists-induced platelet activation, aggregati...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2014.02.028
更新日期：2014-07-01 00:00:00
abstract：INTRODUCTION:Antiphospholipid syndrome (APS) is a pro-thrombotic autoimmune disease that affects different vascular beds, with potential risk for recurrence. Systemic lupus erythematosus (SLE), specific autoantibodies profile and atherogenic disorders have been described as risk factors for the occurrence of first thro...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.10.029
更新日期：2015-12-01 00:00:00
abstract：INTRODUCTION:Although recurrent venous thromboembolism is a known risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), the prevalence of CTEPH after recurrent pulmonary embolism (PE) is not clear. MATERIALS AND METHODS:A cohort screening study was performed to clarify the prevalence of echocardiograp...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2011.07.045
更新日期：2011-12-01 00:00:00
abstract：BACKGROUND:There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA). OBJECTIVES:To assess the incidence of DVT with warfarin thromboprophylaxis over time in ...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2008.05.005
更新日期：2008-01-01 00:00:00
abstract：:Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease after coronary artery disease and cerebrovascular disease and is responsible for significant morbidity and mortality in the general population. Full dose anticoagulation is th...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2011.11.003
更新日期：2012-04-01 00:00:00
abstract：:The potency for the inhibition of 5-hydroxytryptamine (5-HT)-induced human platelet aggregation by ketanserin, pipamperone, spiperone, cyproheptadine and BW 501 in vitro decreased as the reaction pH increased progressively from 7.4 to 8.6, the largest shift (X 1125) in IC50 value (pH 7.4: 4 X 10(-9) M; pH 8.6: 4.5 X 1...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90297-x
更新日期：1985-12-01 00:00:00
abstract：BACKGROUND:An association between high red cell distribution width (RDW) and venous thromboembolism (VTE) has been observed. However, it is not known whether this association differs within various manifestations of VTE, nor if there is an interaction between RDW and thrombophilia abnormalities on the risk of VTE. AIM...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.07.020
更新日期：2015-09-01 00:00:00
abstract：:This study evaluates the role of neutrophil granulocytes in mediating acute phase stimulation of fibrinogen synthesis. Turpentine was administered to neutropenic and non-neutropenic rats and fibrinogen synthetic rates measured in an isolated liver perfusion system. Using the (14C) carbonate technique for the measureme...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90032-9
更新日期：1982-10-01 00:00:00
abstract：INTRODUCTION:Inherited thrombophilia has been associated with unexplained recurrent pregnancy loss (RPL) and stillbirth. This thrombotic tendency can manifest as thrombotic lesions in the placenta, and may lead to abortion and stillbirth. The aim of our case-control study was to investigate the prevalence of FVL and FI...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2005.06.005
更新日期：2006-01-01 00:00:00
abstract：OBJECTIVES:Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2004.04.005
更新日期：2004-01-01 00:00:00
abstract：:Endothelial cells in biopsied blood vessels from von Willebrand factor (vWf)-deficient Doberman pinscher dogs contain immunologically detectable vWf. These dogs and normal dogs were treated with DDAVP (0.6 microgram/kg) and epinephrine (0.5 microgram/kg/min for 30 minutes) and were exercised, using 5 different exercis...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(90)90198-l
更新日期：1990-01-01 00:00:00
abstract：:Patients with the nephrotic syndrome are at increased risk of developing venous and arterial thromboembolism, the most common of which is renal vein thrombosis. There are several unanswered or controversial issues relating to the nephrotic syndrome and thromboembolism, which include the mechanism of thromboembolism, a...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2005.03.030
更新日期：2006-01-01 00:00:00
abstract：:The present investigation has used an aggregation-disaggregation-reaggregation model to determine if exposure to potent aggregating agents causing a refractory state in deaggregated platelets results in down-regulation and clearance of GPIb/IX, the receptor for von willebrand factor. Thrombin, the thrombin receptor ac...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(96)00185-5
更新日期：1996-11-15 00:00:00
abstract：:The abnormal Antithrombin-III (AT-III) Toyama has no ability to interact with heparin in the mast cells or heparin-like glycosaminoglycans on the surface of vascular endothelial cells, so that it has low heparin cofactor activity. In the present study, we have measured the binding capacity of 125I-labeled AT-III to cu...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(88)90170-3
更新日期：1988-04-01 00:00:00
