5 results on '"Thomas, Mischke"'
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2. Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control of Leishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or Secondary L. major Infection
- Author
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Ulrike Schleicher, Jan Liese, Nicole Justies, Thomas Mischke, Simone Haeberlein, Heidi Sebald, Ulrich Kalinke, Siegfried Weiss, and Christian Bogdan
- Subjects
Leishmania major ,type I interferon ,interferon-alpha/beta ,innate immunity ,cutaneous leishmaniasis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
We previously showed that in mice infected with Leishmania major type I interferons (IFNs) initiate the innate immune response to the parasite at day 1 and 2 of infection. Here, we investigated which type I IFN subtypes are expressed during the first 8 weeks of L. major infection and whether type I IFNs are essential for a protective immune response and clinical cure of the disease. In self-healing C57BL/6 mice infected with a high dose of L. major, IFN-α4, IFN-α5, IFN-α11, IFN-α13, and IFN-β mRNA were most prominently regulated during the course of infection. In C57BL/6 mice deficient for IFN-β or the IFN-α/β-receptor chain 1 (IFNAR1), development of skin lesions and parasite loads in skin, draining lymph node, and spleen was indistinguishable from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-β−/−, IFNAR1−/−, and WT mice exhibited similar mRNA expression levels of IFN-γ, interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1 during the acute and late phase of the infection. Also, myeloid dendritic cells from WT and IFNAR1−/− mice produced comparable amounts of IL-12p40/p70 protein upon exposure to L. major in vitro. In non-healing BALB/c WT mice, the mRNAs of IFN-α subtypes (α2, α4, α5, α6, and α9) were rapidly induced after high-dose L. major infection. However, genetic deletion of IFNAR1 or IFN-β did not alter the progressive course of infection seen in WT BALB/c mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and systemic administration of CpG-ODN 1668 protected WT and IFN-β−/− mice equally well from progressive leishmaniasis. By contrast, the protective effect of CpG-ODN 1668 was lost in BALB/c IFNAR1−/− (despite a sustained suppression of IL-4) and in BALB/c IL-12p35−/− mice. From these data, we conclude that IFN-β and IFNAR1 signaling are dispensable for a curative immune response to L. major in C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12 and IFN-α subtypes are essential for the disease prevention by CpG-ODNs in this mouse strain.
- Published
- 2018
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3. [Cardiac magnetic resonance imaging and the myocardium : Differentiation between vital and nonvital tissue]
- Author
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Mhd Nawar, Alachkar, Thomas, Mischke, and Christian, Mahnkopf
- Subjects
Cicatrix ,Myocardium ,Contrast Media ,Humans ,Magnetic Resonance Imaging, Cine ,Gadolinium ,Heart Atria ,Cardiomyopathies ,Fibrosis ,Magnetic Resonance Imaging - Abstract
Cardiac magnetic resonance (cMR), a well-established imaging tool, is indispensable in the diagnosis and management of cardiovascular disease. Given its high spatial resolution and ability to characterize tissue, cMR represents the gold standard in determining myocardial viability. Gadolinium-based contrast-enhanced cMR can accurately identify myocardial scars and fibrosis in the ventricle and the atria, and differentiate it from normal myocardium. Gadolinium is an extracellular molecule which has been shown to be safe and beneficial in magnetic resonance imaging (MRI). Due to the larger extracellular space in myocardial scars, there is more uptake (wash-in) and slower elimination (wash-out) of gadolinium in those areas as opposed to normal myocardium. When imaged several minutes after intravenous administration of gadolinium, nonviable myocardial areas appear brighter than viable myocardium. The use of late-gadolinium enhancement (LGE) technique in assessing myocardial viability has been shown to highly correlate with histological examinations. Furthermore, this technique is highly reproducible and has very high intra- and interobserver agreement. Extent of LGE after myocardial infarction predicts the occurrence of adverse cardiovascular events. Moreover, LGE is highly accurate in predicting functional recovery of dysfunctional myocardial segments in patients undergoing revascularization and consequently has a key role in guiding revascularization procedures. In addition, use of LGE in the identification of myocardial fibrosis or myocardial damage in inflammatory myocardial disease helps to differentiate the type of cardiomyopathy and to predict sudden cardiac death among patients with heart failure. The role of LGE-MRI in the field of electrophysiology through recognition of different substrate for arrythmias and guiding the ablation therapy is steadily increasing and has fundamentally changed our understanding of atrial myopathy.Die kardiale Magnetresonanztomographie (Kardio-MRT) ist ein etabliertes Verfahren in der Bildgebung des Herzens und stellt eine unverzichtbare Methode in der Diagnose und Behandlung von kardiovaskulären Erkrankungen dar. In Anbetracht ihrer Fähigkeit zur Gewebecharakterisierung stellt die Kardio-MRT den Goldstandard bei der Evaluation der myokardialen Vitalität dar. Die gadoliniumbasierte kontrastverstärkte Kardio-MRT ermöglicht eine genaue Detektion von Myokardnarben und myokardialer Fibrose sowie eine Differenzierung zwischen vitalem und avitalem Myokard im Ventrikel und in den Vorhöfen. Gadolinium ist ein extrazelluläres Molekül, welches in der MRT angewendet wird. Im Gegensatz zu normalem Myokard befindet sich in den Narbenarealen ein größerer Extrazellulärraum, was zu einer stärkeren Aufnahme (Wash-in) und zu einem verzögerten Wash-out des Kontrastmittels führt. Durch höhere verbleibende Konzentration des Kontrastmittels kommt es in diesem Bereich zu einer stärkeren Signalanhebung, daher erscheinen die Narbenareale heller als das normale Myokard. Eine Übereinstimmung der durch das LGE bestimmten Myokardnarben mit der histologisch detektierten myokardialen Nekrose konnte nachgewiesen werden. Das Ausmaß des LGE bietet prognostische Informationen und korreliert mit unerwünschten kardiovaskulären Ereignissen bei Patienten nach akutem Myokardinfarkt. Bei Patienten mit ischämischer Kardiomyopathie und chronisch verschlossenen Gefäßen konnte mittels LGE eine Wiederherstellbarkeit einer regelrechten Kontraktilität der dysfunktionalen myokardialen Abschnitte nach Revaskularisierung vorhergesagt werden. Die Anwendung des LGE zur Erkennung myokardialer Fibrose ermöglicht die Differenzierung verschiedener Kardiomyopathien sowie eine Abschätzung des Risikos eines plötzlichen Herztods bei Patienten mit eingeschränkter Pumpfunktion. Die Rolle des LGE im Bereich der Elektrophysiologie bei der Erkennung der Substrate verschiedener Herzrhythmusstörungen nimmt stetig zu und hat unser Verständnis der atrialen Myopathie grundlegend verändert.
- Published
- 2022
4. Abstract 16648: Covid-19 at the ICU: A Multiorgan Challenge
- Author
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Andreas Markl, Steffen Schnupp, Johannes Brachmann, Thomas Mischke, Christian Mahnkopf, and Georg Breuer
- Subjects
medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Physiology (medical) ,medicine ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Abstract
Introduction: About 5% of all COVID-19 patients require intensive care, mostly because of respiratory failure. Little is known about concomitant multi-organ manifestation under these circumstances. Methods: Retrospective observational study using routine data sets of 13 COVID-19 patients requiring mechanical ventilation in the Regiomed Hospital Coburg, Germany, between March 1 st and June 15 th , 2020. Results: Of 13 patients eligible for this study, all were intubated and ventilated mechanically, with signs of infiltration in chest radiographs. 4 suffered from renal failure and needed dialysis; 3 of these patients died, but none without renal failure. Proteinuria was found in all and microhematuria in all but one patients tested (n=11). All developed metabolic alkalosis (BEmax 9.75±0.99, mean ±SEM), and 6 afterwards polyuria (6.75 ±2.45l per day); both conditions resolved in all surviving patients but 1 spontaneously and were not related to prior renal failure. Liver enzymes were elevated in all patients (γGT 506 ±78U/l), but bilirubin levels only in 4; 2 of these died shortly after. Bacterial superinfection was found in 8 patients, and in all 3 ones finally dying. Rhabdomyolysis affected 12 patients (CKmax 1604±542U/l) and resolved later. All patients had slightly elevated troponin T (0.059 ±0.013ng/ml), and 7 had elevated nt-pro-BNP levels (3566±2359pg/ml), indicating cardiac COVID-19, and elevated d-dimer levels (18.1 ±6.68mg/dl) representing disseminated intravascular coagulation. No thromboembolic was observed. The need of catecholamines was low ( Conclusions: Our data indicate that severe COVID-19 is a multi-organ disease, even though ARDS is the leading problem; renal involvement - together with bacterial superinfection - seems to be a major risk factor for unfavorable disease development. Especially metabolic alkalosis and polyuria without overt renal failure have not been studied yet and require close clinical attention.
- Published
- 2020
5. Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control of
- Author
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Ulrike, Schleicher, Jan, Liese, Nicole, Justies, Thomas, Mischke, Simone, Haeberlein, Heidi, Sebald, Ulrich, Kalinke, Siegfried, Weiss, and Christian, Bogdan
- Subjects
Mice, Knockout ,Mice, Inbred BALB C ,Coinfection ,Gene Expression Profiling ,Immunology ,interferon-alpha/beta ,Leishmaniasis, Cutaneous ,Dendritic Cells ,Receptor, Interferon alpha-beta ,Interleukin-12 ,Immunity, Innate ,Host-Parasite Interactions ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,cutaneous leishmaniasis ,Gene Expression Regulation ,Oligodeoxyribonucleotides ,Interferon Type I ,Animals ,type I interferon ,innate immunity ,Leishmania major ,Signal Transduction ,Original Research - Abstract
We previously showed that in mice infected with Leishmania major type I interferons (IFNs) initiate the innate immune response to the parasite at day 1 and 2 of infection. Here, we investigated which type I IFN subtypes are expressed during the first 8 weeks of L. major infection and whether type I IFNs are essential for a protective immune response and clinical cure of the disease. In self-healing C57BL/6 mice infected with a high dose of L. major, IFN-α4, IFN-α5, IFN-α11, IFN-α13, and IFN-β mRNA were most prominently regulated during the course of infection. In C57BL/6 mice deficient for IFN-β or the IFN-α/β-receptor chain 1 (IFNAR1), development of skin lesions and parasite loads in skin, draining lymph node, and spleen was indistinguishable from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-β−/−, IFNAR1−/−, and WT mice exhibited similar mRNA expression levels of IFN-γ, interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1 during the acute and late phase of the infection. Also, myeloid dendritic cells from WT and IFNAR1−/− mice produced comparable amounts of IL-12p40/p70 protein upon exposure to L. major in vitro. In non-healing BALB/c WT mice, the mRNAs of IFN-α subtypes (α2, α4, α5, α6, and α9) were rapidly induced after high-dose L. major infection. However, genetic deletion of IFNAR1 or IFN-β did not alter the progressive course of infection seen in WT BALB/c mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and systemic administration of CpG-ODN 1668 protected WT and IFN-β−/− mice equally well from progressive leishmaniasis. By contrast, the protective effect of CpG-ODN 1668 was lost in BALB/c IFNAR1−/− (despite a sustained suppression of IL-4) and in BALB/c IL-12p35−/− mice. From these data, we conclude that IFN-β and IFNAR1 signaling are dispensable for a curative immune response to L. major in C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12 and IFN-α subtypes are essential for the disease prevention by CpG-ODNs in this mouse strain.
- Published
- 2017
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