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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 297 (1982), S. 691-693 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ABLS 8.1 is a pre-B-cell tumour derived from a BALB/c mouse infected with Abelson virus11. The line was originally classified as B cell because of the presence of surface immuno-globulin12. We can detect neither surface nor cytoplasmic immunoglobulin in these cells, but recently the classification ...
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2013-07-19
    Description: Rationale: Ecto-5'-nucleotidase (CD73) on immune cells is emerging as a critical pathway and therapeutic target in cardiovascular and autoimmune disorders. Objective: Here, we investigated the role of CD73 in postinfarction inflammation, cardiac repair, and remodeling in mice after reperfused myocardial infarction (50-minute ischemia). Methods and Results: We found that compared with control mice (1) cardiac function in CD73 –/– mice more severely declined after infarction (systolic failure with enhanced myocardial edema formation) as determined by MRI and was associated with the persistence of cardiac immune cell subsets, (2) cardiac adenosine release was augmented 7 days after ischemia/reperfusion in control mice but reduced by 90% in CD73 mutants, (3) impaired healing involves M1-driven immune response with increased tumor necrosis factor-α and interleukin-17, as well as decreased transforming growth factor-β and interleukin-10, and (4) CD73 –/– mice displayed infarct expansion accompanied by an immature replacement scar and diffuse ventricular fibrosis. Studies on mice after bone marrow transplantation revealed that CD73 present on immune cells is a major determinant promoting cardiac healing. Conclusions: These results, together with the upregulation of CD73 on immune cells after ischemia/reperfusion, demonstrate the crucial role of purinergic signaling during cardiac healing and provide groundwork for novel anti-inflammatory strategies in treating adverse cardiac remodeling.
    Keywords: Remodeling, Heart failure - basic studies, Imaging, Acute myocardial infarction
    Print ISSN: 0009-7330
    Electronic ISSN: 1524-4571
    Topics: Medicine
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  • 3
    Publication Date: 2017-08-16
    Description: Background— Cardiovascular magnetic resonance with gadolinium-based contrast agents has established as gold standard for tissue characterization after myocardial infarction (MI). Beyond accurate diagnosis, the value of cardiovascular magnetic resonance to predict the outcome after MI has yet to be substantiated. Methods and Results— Recent cardiovascular magnetic resonance approaches were systematically compared for quantification of tissue injury and functional impairment after MI using murine models with permanent left anterior descending coronary artery ligation (n=14) or 50 minutes ischemia/reperfusion (n=13). Cardiovascular magnetic resonance included native/postcontrast T1 maps, T2 maps, and late gadolinium enhancement at days 1 and 21 post-MI. For regional correlation of parametric and functional measures, the left ventricle was analyzed over 200 sectors. For T1 mapping, we used retrospective triggering with variable flip angle analysis. Sectoral analysis of native T1 maps already revealed in the acute phase after MI substantial discrepancies in myocardial tissue texture between the 2 MI models (native T1 day 1: permanent ligation, 1280.0±162.6 ms; ischemia/reperfusion, 1115.0±140.5 ms; P 〈0.001; n=14/13), which were later associated with differential functional outcome (left ventricular ejection fraction day 21: permanent ligation, 24.5±7.0%; ischemia/reperfusion, 33.7±11.6%; P 〈0.05; n=14/13). At this early time, any other parameter was indicative for the subsequent worsening of left ventricular ejection fraction in permanent ligation mice. Linear regression of acute individual measures with contractile function in corresponding areas at day 21 demonstrated for early native T1 values the best correlation with the later functional impairment ( R 2 =0.94). Conclusions— The present T1 mapping approach permits accurate characterization of local tissue injury and holds the potential for sensitive and graduated prognosis of the functional outcome after MI without gadolinium-based contrast agents.
    Keywords: Animal Models of Human Disease, Translational Studies, Myocardial Infarction, Remodeling, Magnetic Resonance Imaging (MRI)
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
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  • 4
    Publication Date: 2012-07-17
    Description: Background— Hypoxic vasodilation is a physiological response to low oxygen tension that increases blood supply to match metabolic demands. Although this response has been characterized for 〉100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin in the heart can reduce nitrite to nitric oxide (NO·) and thereby contribute to cardiomyocyte NO· signaling during ischemia. On the basis of recent observations that myoglobin is expressed in the vasculature of hypoxia-tolerant fish, we hypothesized that endogenous nitrite may contribute to physiological hypoxic vasodilation via reactions with vascular myoglobin to form NO·. Methods and Results— We show in the present study that myoglobin is expressed in vascular smooth muscle and contributes significantly to nitrite-dependent hypoxic vasodilation in vivo and ex vivo. The generation of NO· from nitrite reduction by deoxygenated myoglobin activates canonical soluble guanylate cyclase/cGMP signaling pathways. In vivo and ex vivo vasodilation responses, the reduction of nitrite to NO·, and the subsequent signal transduction mechanisms were all significantly impaired in mice without myoglobin. Hypoxic vasodilation studies in myoglobin and endothelial and inducible NO synthase knockout models suggest that only myoglobin contributes to systemic hypoxic vasodilatory responses in mice. Conclusions— Endogenous nitrite is a physiological effector of hypoxic vasodilation. Its reduction to NO· via the heme globin myoglobin enhances blood flow and matches O 2 supply to increased metabolic demands under hypoxic conditions.
    Keywords: Endothelium/vascular type/nitric oxide
    Electronic ISSN: 1524-4539
    Topics: Medicine
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  • 5
    Publication Date: 2015-04-22
    Description: Background— Noninvasive detection of deep venous thrombi and subsequent pulmonary thromboembolism is a serious medical challenge, since both incidences are difficult to identify by conventional ultrasound techniques. Methods and Results— Here, we report a novel technique for the sensitive and specific identification of developing thrombi using background-free 19 F magnetic resonance imaging, together with α2-antiplasmin peptide (α2 AP )–targeted perfluorocarbon nanoemulsions (PFCs) as contrast agent, which is cross-linked to fibrin by active factor XIII. Ligand functionality was ensured by mild coupling conditions using the sterol-based postinsertion technique. Developing thrombi with a diameter 〈0.8 mm could be visualized unequivocally in the murine inferior vena cava as hot spots in vivo by simultaneous acquisition of anatomic matching 1 H and 19 F magnetic resonance images at 9.4 T with both excellent signal-to-noise and contrast-to-noise ratios (71±22 and 17±5, respectively). Furthermore, α2 AP -PFCs could be successfully applied for the diagnosis of experimentally induced pulmonary thromboembolism. In line with the reported half-life of factor XIIIa, application of α2 AP -PFCs 〉60 minutes after thrombus induction no longer resulted in detectable 19 F magnetic resonance imaging signals. Corresponding results were obtained in ex vivo generated human clots. Thus, α2 AP -PFCs can visualize freshly developed thrombi that might still be susceptible to pharmacological intervention. Conclusions— Our results demonstrate that 1 H/ 19 F magnetic resonance imaging, together with α2 AP -PFCs, is a sensitive, noninvasive technique for the diagnosis of acute deep venous thrombi and pulmonary thromboemboli. Furthermore, ligand coupling by the sterol-based postinsertion technique represents a unique platform for the specific targeting of PFCs for in vivo 19 F magnetic resonance imaging.
    Keywords: Cardiovascular imaging agents/Techniques, Deep vein thrombosis, Fibrinogen/fibrin, CT and MRI
    Electronic ISSN: 1524-4539
    Topics: Medicine
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