Abstract:
BACKGROUND:The substitution variants K35A,E38A,K74A, E75A,R77A (SakSTAR.M38) and K74A,E75A,R77A,E80A, D82A (SakSTAR.M89) of recombinant staphylokinase (SakSTAR) with reduced antibody reactivity were assayed for thrombolytic potency and antibody induction in animal models and in patients. METHODS AND RESULTS:In a 125I-fibrin-labeled pulmonary embolism model in the hamster, the doses giving 50% clot lysis in 90 minutes were 25 micrograms/kg for SakSTAR, 85 micrograms/kg for SakSTAR.M38, and 90 micrograms/kg for SakSTAR.M89. In rabbits with 125I-fibrin-labeled plasma clots incorporated into extracorporeal arteriovenous loops, lysis within 2 hours was 76 +/- 18% (mean +/- SD, n = 28) with 400 micrograms/kg SakSTAR, 53 +/- 13% (n = 8) with 1000 micrograms/kg SakSTAR.M38, and 39 +/- 13% (n = 6) with 800 micrograms/kg SakSTAR.M89. When groups of eight rabbits were immunized by intravenous administration of 0.2 to 1.0 micrograms/kg compound followed by subcutaneous injection of 0.4 mg in Freund's adjuvant at 2, 3, and 5 weeks, SakSTAR.M38 and SakSTAR.M89 elicited markedly less circulating neutralizing activity, compared with SakSTAR, when determined at 6 weeks (neutralizing 6.1 +/- 3.0 and 4.9 +/- 1.3 micrograms compound/mL plasma, respectively, versus 20 +/- 17 micrograms/mL; P = .02 and P = .01, respectively) and induced significantly less resistance to thrombolysis (residual thrombolytic potency producing 59 +/- 25% and 39 +/- 12% lysis, respectively, versus 8.5 +/- 5.7%; P = .008 and P = .006, respectively). In patients with peripheral arterial occlusion, intra-arterial administration of SakSTAR.M38 (n = 4) or SakSTAR.M89 (n = 4) induced significantly fewer circulating neutralizing antibodies (P = .03) and specific IgG (P = .01) at 2 to 3 weeks than SakSTAR (n = 8). CONCLUSIONS:SakSTAR.M38 and SakSTAR.M89 induce less antibody formation and might constitute preferred agents for thrombolytic therapy in humans.
journal_name
Circulationjournal_title
Circulationauthors
Collen D,Moreau H,Stockx L,Vanderschueren Sdoi
10.1161/01.cir.94.2.207subject
Has Abstractpub_date
1996-07-15 00:00:00pages
207-16issue
2eissn
0009-7322issn
1524-4539journal_volume
94pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:Lead V(1) directly faces the right ventricle and may exhibit ST elevation during an acute inferior myocardial infarction when the right ventricle is also involved. Leads V(1) and V(3) indirectly face the posterolateral left ventricle, and ST depression ("mirror-image" ST elevation) in V(1) through V(3) may r...
journal_title:Circulation
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCULATIONAHA.109.924068
更新日期:2010-08-03 00:00:00
abstract:BACKGROUND:Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS:From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover compari...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1161/01.cir.99.21.2765
更新日期:1999-06-01 00:00:00
abstract::Atherosclerotic coronary artery disease is the major cause of late cardiac transplant failure secondary to silent ischemia and infarction. To increase the longevity of cardiac homografts, we performed percutaneous transluminal coronary angioplasty (PTCA) in five male patients (aged 45 +/- 7 years, mean +/- SEM); 17 le...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND:The clinical significance of minor elevations in creatine kinase-myocardial band isoenzyme (CK-MB) after coronary interventions has not been systematically evaluated. METHODS AND RESULTS:We examined 4484 patients who underwent successful percutaneous transluminal coronary angioplasty or directional coronary...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.7.1528
更新日期:1996-10-01 00:00:00
abstract::The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.81.5.1622
更新日期:1990-05-01 00:00:00
abstract::Twelve patients with medically refractory ventricular tachycardia secondary to ischemic heart disease underwent surgery for cure of their arrhythmia. Preoperatively, the tachycardia could be reproducibly initiated and terminated in each patient by programmed stimulation. In all instances, intraoperative mapping locali...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.60.7.1430
更新日期:1979-12-01 00:00:00
abstract::The anatomy of 58 specimens of aortic outflow tract atresia was studied. All cases had situs solitus and levocardia, 37 had atrioventricular (AV) concordance, two had common inlet to a right ventricle and 19 had mitral atresia. The great arteries were normally interrelated in all cases. Fifty-one cases had an intact v...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.59.1.173
更新日期:1979-01-01 00:00:00
abstract::Fifty-six patients undergoing orthotopic cardiac transplantation were given Minnesota ALG prophylactically or therapeutically for acute cardiac rejection. During a follow-up period of 0-28 months (mean follow-up period, 11.9 months), the actuarial survival for the entire group was 96% and 86% at 30 days and 1 year, re...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND:Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.91.8.2125
更新日期:1995-04-15 00:00:00
abstract:BACKGROUND:The effect of the increasing prevalence of obesity on blood pressure (BP) secular trends is unclear. We analyzed BP and body mass index secular trends between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly developing island state in the African region. METHODS AND RESULTS:School-base...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.796276
更新日期:2009-02-03 00:00:00
abstract:BACKGROUND:It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction. METHODS AND RESULTS:We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitiv...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/hc0202.103311
更新日期:2002-01-15 00:00:00
abstract:BACKGROUND:Spontaneous transient outward potassium currents (STOCs) induce myogenic relaxation in small cerebral vessels. We found STOCs in human coronary artery vascular smooth muscle cells (VSMCs) and studied their regulation. METHODS AND RESULTS:K+ currents were recorded in human coronary VSMCs by current- and volt...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.2.503
更新日期:1997-01-21 00:00:00
abstract::Thirty patients with triple-vessel coronary artery disease proven by angiography, symptomatic angina and a positive ECG stress test were evaluated with thallium-201 (201TI) scintigraphy. Twenty patients also had aortocoronary saphenous vein bypass surgery; 15 of them had repeat noninvasive evaluation. Seventy percent ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.59.4.714
更新日期:1979-04-01 00:00:00
abstract:BACKGROUND:The Ross operation is an alternative to mechanical aortic valve replacement in the young. Early dilatation of the pulmonary autograft root exposed to the systemic circulation has been reported. To define the prevalence of, risk factors for, and consequences of late autograft dilatation, outcome in all consec...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000089183.92233.75
更新日期:2003-09-09 00:00:00
abstract:BACKGROUND:Increased consumption of sugar-sweetened beverages (SSBs) has been associated with an elevated risk of obesity, metabolic syndrome, and type II diabetes mellitus. However, the effects of SSB consumption on blood pressure (BP) are uncertain. The objective of this study was to determine the relationship betwee...
journal_title:Circulation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCULATIONAHA.109.911164
更新日期:2010-06-08 00:00:00
abstract:BACKGROUND:As part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence and long-term case-fatality rates of greater Worcester, Mass, residents hospitalized with confirmed acute myocardial infarction (AMI), we investigated the hypothesis that census tract-level socioe...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.496174
更新日期:2005-06-14 00:00:00
abstract:BACKGROUND:Depressive symptoms have been associated with increased risk of coronary artery disease and poor prognosis among patients with existing coronary artery disease, but whether depressive symptoms specifically influence atherosclerotic progression among such patients is uncertain. METHODS AND RESULTS:The Post-C...
journal_title:Circulation
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCULATIONAHA.107.741058
更新日期:2008-05-06 00:00:00
abstract:BACKGROUND:The signal transduction mechanism linking mitochondrial ATP synthesis with cytosolic ATP utilization in heart changes during postnatal development in vivo. This maturational process occurs in parallel with accumulation of mitochondrial adenine nucleotide translocator (ANT), which provides a possible site for...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.102.11.1323
更新日期:2000-09-12 00:00:00
abstract::Over an 8-year period, 20 patients underwent operative repair of ventricular aneurysms during the first 8 weeks after acute myocardial infarction. All patients with multivessel coronary occlusive disease underwent concomitant coronary artery bypass grafting. There was one hospital death, for an early mortality rate o...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1980-08-01 00:00:00
abstract:BACKGROUND:Previous studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.5.2370
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND:Hypothermic hyperkalemic cardioplegia results in significant myocyte swelling and impaired contractility. These detrimental effects may be eliminated by the addition of an adenosine triphosphate-sensitive potassium (KATP) channel opener. This study evaluated the hypothesis that a KATP channel opener (diazoxi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.523746
更新日期:2005-08-30 00:00:00
abstract::Certain clinical and morphologic observations are described in 27 patients with severe isolated angina pectoris of either the stable (five patients) or the unstable form (22 patients). Twenty-four patients died during or shortly after cardiac operations designed to relieve angina pectoris and three died during cardiac...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.54.3.388
更新日期:1976-09-01 00:00:00
abstract:BACKGROUND:Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. METHODS:In 3281 participants (45-74 years of age), free from cardiovascul...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.116.027034
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein (LDL) receptor (LDLR), and its deficiency in humans results in low plasma LDL cholesterol and protection against coronary heart disease. Recent evidence indicates that PCSK9 also modulates the metabo...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.006720
更新日期:2014-07-29 00:00:00
abstract::The significance of the direction of the ST-segment shifts on the 12-lead electrocardiogram was evaluated in 82 consecutive patients with unstable angina. Eighteen patients with ST-segment elevation (group I) were compared with 64 patients with ST-segment depression (group II). There was no difference between group I ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.51.6.1015
更新日期:1975-06-01 00:00:00
abstract::The movements of the mitral, tricuspid and aortic valves have been recorded echocardiographically and related to the first heart sound (S1) in patients with various hemodynamic and conduction abnormalities. Closure of the mitral and tricuspid valves has been studied with respect to the corresponding atrioventricular p...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.54.6.944
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND:In heart failure, sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling and contractile dysfunction. We have previously shown that increasing SERCA2a expression by gene transfer improves ventricular function in a rat model of heart failure created b...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc3601.095574
更新日期:2001-09-18 00:00:00
abstract:BACKGROUND:Human leukocyte antigen-G (HLA-G) expression in heart transplant patients has been negatively associated with acute cellular rejection and cardiac allograft vasculopathy. We assessed HLA-G expression in vascular human endothelial and smooth muscle cell cultures to determine if future therapeutic agents can b...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.757781
更新日期:2008-09-30 00:00:00
abstract:BACKGROUND:Isoprostanes (iPs) are free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Several iPs exert biological effects in vitro and may contribute to the functional consequences of oxidant stress. For example, iPF(2alpha)-III (8-iso PGF(2alpha)) and iPE(2)-III modulate plate...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.101.24.2833
更新日期:2000-06-20 00:00:00
abstract:BACKGROUND:Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. METHODS AND RESULTS:We used proportional hazards models to analyze first-onset...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.109.886655
更新日期:2010-02-02 00:00:00