Papers by Dana Abendschein
The FASEB Journal, 2015
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Circulation: Cardiovascular Imaging, 2020
January 2020 1 Xingyu Nie, PhD Andrew Elvington, PhD Richard Laforest, PhD Jie Zheng, PhD Thomas ... more January 2020 1 Xingyu Nie, PhD Andrew Elvington, PhD Richard Laforest, PhD Jie Zheng, PhD Thomas F. Voller, MS Mohamed A. Zayed, MD, PhD Dana R. Abendschein, PhD Nilantha Bandara, PhD Jinbin Xu, PhD Ran Li, MS Gwendalyn J. Randolph, PhD Robert J. Gropler, MD Suzanne E. Lapi, PhD Pamela K. Woodard, MD The macrophage-rich core of advanced human atheroma has been shown to be hypoxic, which may have implications for plaque stability.1 Recently, we showed that the hypoxia positron emission tomography (PET) imaging agent 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) could be used for visualizing hypoxic cells in atherosclerosis in animal models.2 In this study, we investigated the feasibility of 64Cu-ATSM Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) for detecting hypoxic cells in human atherosclerotic plaque. The cellular retention mechanism of 64Cu-ATSM is that in vitro Cu-ATSM undergoes bioreductive trapping under hypoxic conditions. Cu-ATSM Cu(II) is a lipophilic molecule, with high membrane permeability and low redox potential, and is reduced only in hypoxic cells. On intracellular reduction, Cu-ATSM becomes trapped irreversibly, and thus the radioactivity accumulates in these cells.3 This prospective human study was approved by the Institutional Review Board at Washington University, and all patients provided informed consent. The data that support the findings of this study are available from the corresponding author on reasonable request. Images of sufficient diagnostic quality for further analysis were obtained in 7 neurologically asymptomatic patients (74.3±6.2 years old) with carotid atherosclerosis and ≥50% diameter stenosis in at least one carotid artery. Dynamic PET imaging was done 0 to 60 minutes after intravenous injection of 740 to 925 MBq 64Cu-ATSM with simultaneously acquired T1-, T2-, proton-density-, and time-of-flightweighted MRI of carotid plaque. Five patients also underwent dynamic contrastenhanced MRI afterwards (20 time points and 12.5-second image interval) with 0.1 mmol/kg gadolinium-based contrast agent injected at 0.5 mL/s. The averaged 30 to 60 minutes 64Cu-ATSM PET acquisition was reconstructed with 1.04×1.04×2.03 mm3 resolution. Volumes-of-interests were drawn on the MRI images of carotid plaques to determine the maximum standard uptake values (SUVmax). As a reference, the activity of the background (SUVbkg) was calculated as the mean SUV of the blood pool within adjacent internal jugular veins. The target-to-background SUV ratios (TBRmax) defined as SUVmax corrected for SUVbkg were calculated. Among these 7 patients, there were 8 carotid arteries with stenosis of ≥50% diameter (one patient with bilateral carotid stenoses). Of these 8 arteries, 3 left arteries displayed 64Cu-ATSM focal uptake (TBRmax is greatly higher than 1.6; Figure [A] through [J]). The TBRmax of the 3 contralateral carotid arteries and all 5 PET-negative carotid plaques as indicated by lack of detection of focal 64Cu-ATSM retention (1.48±0.28 and 1.53±0.17, respectively) were significantly lower (P<0.05 and P<0.001) than those values of the plaques positive for the detection of 64Cu-ATSM hot spots (2.88±0.17). Volume transfer constant (Ktrans) maps determined by describing dynamic contrast-enhanced MRI with the Patlak model was in line with literature © 2020 American Heart Association, Inc. RESEARCH LETTER
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Thrombosis and Haemostasis, 1996
SummaryIncreases in thrombin activity occur in patients treated with streptokinase, but conjuncti... more SummaryIncreases in thrombin activity occur in patients treated with streptokinase, but conjunctive therapy with intravenous heparin does not appear to improve either the rate of early infarct artery patency or survival in patients with acute myocardial infarction. In a recent study we found that concentrations of fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in the first 3 h in patients treated with intravenous heparin (5000 U bolus followed by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U every 12 h, started 4 h after streptokinase, n = 14) administration, but were increased in both groups of patients, consistent with persistent thrombin activity. To determine whether the differential effects of the intensity of heparinization on thrombin formation were reflected in differences in fibrin degradation, we measured cross-linked fibrin degradation products (XL-FDP) before and 1,2,3,8,12, and 24 h after streptokinase in the ...
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Circulation, Nov 22, 2011
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Object recognition supported by user interaction for service robots
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Developments in Cardiovascular Medicine
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The Journal of pharmacology and experimental therapeutics, 2001
Inhibition of factor Xa (FXa) attenuates thrombus progression. This study was designed to determi... more Inhibition of factor Xa (FXa) attenuates thrombus progression. This study was designed to determine whether a novel, synthetic inhibitor of FXa (ZK-807834, molecular mass 527 Da, K(i) = 0.11 nM) administered during and briefly after pharmacologic coronary fibrinolysis increases 24-h patency. Either ZK-807834 (< or = 1.6 mg/kg, n = 10; 6.5 mg/kg, n = 8; or 13 mg/kg, n = 7); a peptide inhibitor of FXa, recombinant tick anticoagulant peptide (rTAP, 13.6 mg/kg, n = 7); heparin (150 U/kg bolus and 50 U/kg/h infusion) and aspirin (5 mg/kg) (n = 7); or saline as a control (n = 13) were administered i.v. over 135 min in conscious dogs after thrombotic occlusion induced by electrical injury to a coronary artery. Fibrinolysis was induced with recombinant human tissue-type plasminogen activator (1.0 mg/kg i.v. over 1 h), and patency was monitored continuously for 24 h with an implanted Doppler probe. Reocclusion occurred in all control and heparin/aspirin-treated dogs within 1 h after fibri...
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The Physiologist, 1982
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The Journal of laboratory and clinical medicine, 1987
This study was undertaken to identify the carboxypeptidase(s) (CPase) in plasma mediating sequent... more This study was undertaken to identify the carboxypeptidase(s) (CPase) in plasma mediating sequential conversion of the tissue isoform of the MM isoenzyme of creatine kinase (MM3 CK) to MM2 and MM1 isoforms and to elucidate relationships between CPase activity measured in plasma and observed rates of isoform conversion in vitro. Purified MM3 was incubated at 37 degrees C in plasma from normal subjects and patients with acute myocardial infarction. Isoforms were quantified by chromatofocusing. Preincubation with antiserum to CPase N prevented conversion of added MM3 to MM2 and MM1. Isoform conversion rates in the absence of antibody were proportional to plasma CPase N activity assayed spectrophotometrically by hydrolysis of furylacryloyl-L-alanyl-L-lysine substrate (r = 0.89, n = 8). Plasma CPase N activity varied by nearly 300% among individuals, but average activity was similar in samples from normal subjects (267 +/- 45 [SD] U/L, n = 18), those from outpatients with angina (289 +/-...
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International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology, 1987
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Medical Imaging 2000: Ultrasonic Imaging and Signal Processing, 2000
ABSTRACT
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Thrombosis Research, 1989
Binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa receptors is essential for normal pl... more Binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa receptors is essential for normal platelet aggregation. We investigated whether inhibition of GP IIb/IIIa receptors with arginine-glycine-aspartate-O-methyltyrosine amide (RGDY), an analog of the receptor recognition sequence found in fibrinogen, is associated with platelet deaggregation. Platelets from five healthy human subjects that were maximally aggregated by addition of adenosine diphosphate to platelet-rich plasma were deaggregated in a dose-dependent manner by subsequent addition of RGDY (86.5 +/- 6.2%, 68.2 +/- 4.3%, 44.9 +/- 6.4%, and 31.6 +/- 4.1% for RGDY concentrations of 400, 200, 133, and 67 microM, respectively vs. 7.8 +/- 2.9% for saline control samples, p less than 0.0001). The extent of deaggregation was decreased as the time of addition of RGDY (400 microM) after maximal aggregation increased (85.6 +/- 6.7%, 58.5 +/- 12.6%, 47.1 +/- 2.7%, and 37.1 +/- 4.2% for 0, 1, 3, and 5 minute intervals, respectively, vs. 8.3 +/- 3.1% in control samples, n = 4, p less than 0.0001) consistent with the occurrence of irreversible aggregation. Thus, RGDY can rapidly and extensively deaggregate human platelets under certain conditions which may enhance its antithrombotic efficacy.
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Magnetic Resonance in Medicine, 2004
Before molecular imaging with MRI can be applied clinically, certain problems, such as the potent... more Before molecular imaging with MRI can be applied clinically, certain problems, such as the potential sparseness of molecular epitopes on targeted cell surfaces, and the relative weakness of conventional targeted MR contrast agents, must be overcome. Accordingly, the conditions for diagnostic conspicuity that apply to any paramagnetic MRI contrast agent with known intrinsic relaxivity were examined in this study. A highly potent paramagnetic liquid perfluorocarbon nanoparticle contrast agent (∼250 nm diameter, >90000 Gd3+/particle) was imaged at 1.5 T and used to successfully predict a range of sparse concentrations in experimental phantoms with the use of standard MR signal models. Additionally, we cultured and targeted the smooth muscle cell (SMC) monolayers that express “tissue factor,” a glycoprotein of crucial significance to hemostasis and response to vascular injury, by conjugating an anti‐tissue factor antibody fragment to the nanoparticles to effect specific binding. Quan...
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Journal of Thrombosis and Haemostasis, 2004
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Journal of Investigative Surgery, 2001
Injury to an artery induces formation of a platelet-rich thrombus, while stasis or trauma to a ve... more Injury to an artery induces formation of a platelet-rich thrombus, while stasis or trauma to a vein induces a fibrin-rich thrombus. We have implemented preparations for evolving both platelet-rich and fibrin-rich thrombi simultaneously in rabbits for use to define the efficacy of novel antithrombotic agents. For platelet-rich thrombosis, a carotid artery and contralateral jugular vein were dissected and an arteriovenous shunt inserted distally to prevent cerebral infarction during thrombus formation. The shunted artery was then instrumented with a proximal Doppler probe for measuring flow velocity and a distal transluminal needle electrode. Electrical injury to the artery was induced by application of 250 microA of anodal current to the indwelling needle electrode. Thrombotic occlusion was consistently observed within 60 min, permitting measurements of the effects on the incidence and time of occlusion of antithrombotic agents administered over 2 h. For fibrin-rich thrombosis, an external jugular vein was dissected, including the distal bifurcation. One of the branches was catheterized and a copper wire with cotton threads attached was advanced through the catheter into the superior vena cava, allowing exposure of the threads to flowing blood. A 25- to 30-mg thrombus was formed within 2 h, permitting reliable measurements of effects on thrombus weight of antithrombotic agents administered during this interval. Implementing both arterial and venous thrombosis simultaneously did not change measurements compared with either method alone. This approach may facilitate recognition of differences in efficacy of selected agents against thrombi of diverse composition.
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Journal of Cardiovascular Magnetic Resonance, 2008
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Journal of Cardiovascular Magnetic Resonance, 2006
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Investigative Radiology, 2005
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Coronary Artery Disease, 1999
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Coronary Artery Disease, 1996
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Papers by Dana Abendschein