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https://www.readbyqxmd.com/read/28702024/full-length-interleukin-33-aggravates-radiation-induced-skin-reaction
#1
Olga Kurow, Benjamin Frey, Louis Schuster, Verena Schmitt, Susanne Adam, Madelaine Hahn, Derek Gilchrist, Iain B McInnes, Stefan Wirtz, Udo S Gaipl, Gerhard Krönke, Georg Schett, Silke Frey, Axel J Hueber
The interleukin (IL)-1 family member IL-33 has been described as intracellular alarmin with broad roles in wound healing, skin inflammation but also autoimmunity. Its dichotomy between full length (fl) IL-33 and the mature (m) form of IL-33 and its release by necrosis is still not fully understood. Here, we compare functional consequences of both forms in the skin in vivo, and therefore generated two lines of transgenic mice which selectively overexpress mmIL-33 and flmIL-33 in basal keratinocytes. Transgene mRNA was expressed at high level in skin of both lines but not in organs due to the specific K14 promoter...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28643785/dnmt3a-mutant-transcript-levels-persist-in-remission-and-do-not-predict-outcome-in-patients-with-acute-myeloid-leukemia
#2
V I Gaidzik, D Weber, P Paschka, A Kaumanns, S Krieger, A Corbacioglu, J Krönke, S Kapp-Schwoerer, D Krämer, H-A Horst, I Schmidt-Wolf, G Held, A Kündgen, M Ringhoffer, K Götze, T Kindler, W Fiedler, M Wattad, R F Schlenk, L Bullinger, V Teleanu, B Schlegelberger, F Thol, M Heuser, A Ganser, H Döhner, K Döhner
We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3A(mut)). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3A(mut) patients. At the time of diagnosis, DNMT3A(mut) transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3A(mut) transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28566277/enzymatic-lipid-oxidation-by-eosinophils-propagates-coagulation-hemostasis-and-thrombotic-disease
#3
Stefan Uderhardt, Jochen A Ackermann, Tobias Fillep, Victoria J Hammond, Johann Willeit, Peter Santer, Manuel Mayr, Markus Biburger, Meike Miller, Katie R Zellner, Konstantin Stark, Alexander Zarbock, Jan Rossaint, Irene Schubert, Dirk Mielenz, Barbara Dietel, Dorette Raaz-Schrauder, Cihan Ay, Thomas Gremmel, Johannes Thaler, Christian Heim, Martin Herrmann, Peter W Collins, Gernot Schabbauer, Nigel Mackman, David Voehringer, Jerry L Nadler, James J Lee, Steffen Massberg, Manfred Rauh, Stefan Kiechl, Georg Schett, Valerie B O'Donnell, Gerhard Krönke
Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28546330/exploring-new-multimodal-quantitative-imaging-indices-for-the-assessment-of-osseous-tumour-burden-in-prostate-cancer-using-68-ga-psma-pet-ct
#4
Marie Bieth, Markus Krönke, Robert Tauber, Marielena Dahlbender, Margitta Retz, Stephan G Nekolla, Bjoern Menze, Tobias Maurer, Matthias Eiber, Markus Schwaiger
Positron-emission-tomography (PET) combined with computed-tomography (CT) and prostate-specific-membrane-antigen (PSMA) ligands has gained significant interest for staging prostate cancer (PC). In this study, we propose two multimodal quantitative indices as imaging biomarker for the assessment of osseous tumour burden using (68)Ga-PSMA-PET/CT and present preliminary clinical data. We define two Bone-PET-Indices (BPI) that incorporate anatomical information from CT and functional information from (68)Ga-PSMA-PET: BPIVOL is the percental bone volume affected by tumour...
May 25, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28444535/image-analysis-of-immune-cell-patterns-in-the-human-mammary-gland-during-the-menstrual-cycle-refines-lymphocytic-lobulitis
#5
Nadine S Schaadt, Juan Carlos López Alfonso, Ralf Schönmeyer, Anne Grote, Germain Forestier, Cédric Wemmert, Nicole Krönke, Mechthild Stoeckelhuber, Hans H Kreipe, Haralampos Hatzikirou, Friedrich Feuerhake
PURPOSE: To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue. METHODS: Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens...
April 25, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28411187/the-nuclear-receptor-nr4a1-acts-as-a-microglia-rheostat-and-serves-as-a-therapeutic-target-in-autoimmune-driven-central-nervous-system-inflammation
#6
Tobias Rothe, Natacha Ipseiz, Maria Faas, Stefanie Lang, Francesc Perez-Branguli, Daniel Metzger, Hiroshi Ichinose, Beate Winner, Georg Schett, Gerhard Krönke
Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28209912/detection-efficacy-of-hybrid-68-ga-psma-ligand-pet-ct-in-prostate-cancer-patients-with-biochemical-recurrence-after-primary-radiation-therapy-defined-by-phoenix-criteria
#7
Ingo Einspieler, Isabel Rauscher, Charlotte Düwel, Markus Krönke, Christoph Rischpler, Gregor Habl, Sabrina Dewes, Armin Ott, Hans-Jürgen Wester, Markus Schwaiger, Tobias Maurer, Matthias Eiber
The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA ligand) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrent prostate cancer (PC) defined by Phoenix criteria after external beam radiotherapy (EBRT) or brachytherapy as primary treatment. Methods: 118 patients were finally eligible for this retrospective analysis with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range: 2.2-158...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28192515/salmonella-typhimurium-disrupts-sirt1-ampk-checkpoint-control-of-mtor-to-impair-autophagy
#8
Raja Ganesan, Nina Judith Hos, Saray Gutierrez, Julia Fischer, Joanna Magdalena Stepek, Evmorphia Daglidu, Martin Krönke, Nirmal Robinson
During intracellular infections, autophagy significantly contributes to the elimination of pathogens, regulation of pro-inflammatory signaling, secretion of immune mediators and in coordinating the adaptive immune system. Intracellular pathogens such as S. Typhimurium have evolved mechanisms to circumvent autophagy. However, the regulatory mechanisms targeted by S. Typhimurium to modulate autophagy have not been fully resolved. Here we report that cytosolic energy loss during S. Typhimurium infection triggers transient activation of AMPK, an important checkpoint of mTOR activity and autophagy...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28187783/development-of-three-dimensional-prints-of-arthritic-joints-for-supporting-patients-awareness-to-structural-damage
#9
Arnd Kleyer, Laura Beyer, Christoph Simon, Fabian Stemmler, Matthias Englbrecht, Christian Beyer, Jürgen Rech, Bernhard Manger, Gerhard Krönke, Georg Schett, Axel J Hueber
BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) result in severe joint destruction and functional disability if left untreated. We aim to develop tools that help patients with RA and PsA to understand and experience the impact of inflammatory joint disease on the integrity of their (juxta-articular) bone and increase adherence to medical treatment. In this study, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop 3D prototypes of patients' finger joints...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28147522/dynamics-of-local-symmetry-correlators-for-interacting-many-particle-systems
#10
P Schmelcher, S Krönke, F K Diakonos
Recently [P. A. Kalozoumis et al. Phys. Rev. Lett. 113, 050403 (2014)] the concept of local symmetries in one-dimensional stationary wave propagation has been shown to lead to a class of invariant two-point currents that allow to generalize the parity and Bloch theorem. In the present work, we establish the theoretical framework of local symmetries for higher-dimensional interacting many-body systems. Based on the Bogoliubov-Born-Green-Kirkwood-Yvon hierarchy, we derive the equations of motion of local symmetry correlators which are off-diagonal elements of the reduced one-body density matrix at symmetry related positions...
January 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28132835/recent-zika-virus-isolates-induce-premature-differentiation-of-neural-progenitors-in-human-brain-organoids
#11
Elke Gabriel, Anand Ramani, Ulrike Karow, Marco Gottardo, Karthick Natarajan, Li Ming Gooi, Gladiola Goranci-Buzhala, Oleg Krut, Franziska Peters, Milos Nikolic, Suvi Kuivanen, Essi Korhonen, Teemu Smura, Olli Vapalahti, Argyris Papantonis, Jonas Schmidt-Chanasit, Maria Riparbelli, Giuliano Callaini, Martin Krönke, Olaf Utermöhlen, Jay Gopalakrishnan
The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28058455/-bone-specific-therapy-with-radium-223-dichloride-castration-resistant-prostate-cancer-with-symptomatic-bone-metastases
#12
R Tauber, J Gschwend, K Scheidhauer, M Eiber, M Krönke
Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28017969/ikzf1-expression-is-a-prognostic-marker-in-newly-diagnosed-standard-risk-multiple-myeloma-treated-with-lenalidomide-and-intensive-chemotherapy-a-study-of-the-german-myeloma-study-group-dsmm
#13
J Krönke, F Kuchenbauer, M Kull, V Teleanu, L Bullinger, D Bunjes, A Greiner, S Kolmus, S Köpff, M Schreder, L-O Mügge, C Straka, M Engelhardt, H Döhner, H Einsele, F Bassermann, R Bargou, S Knop, C Langer
Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial...
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27914902/ppar%C3%AE-%C3%AE-a-master-regulator-of-mesenchymal-stem-cell-functions
#14
REVIEW
Farida Djouad, Natacha Ipseiz, Patricia Luz-Crawford, Carina Scholtysek, Gerhard Krönke, Christian Jorgensen
Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of physiological and immunological processes. Recently, one of their members PPARβ/δ has been identified as major player in the maintenance of bone homeostasis, by promoting Wnt signalling activity in osteoblast and mesenchymal stem cells (MSC). PPARβ/δ not only controls the fate of MSC but also regulates their immunosuppressive properties by directly modulating their NF-κB activity. In this review, we discuss how the regulation of PPARβ/δ provides an innovative strategy for an optimisation of MSC-based therapy...
May 2017: Biochimie
https://www.readbyqxmd.com/read/27865755/corrigendum-to-fc-gamma-receptors-are-not-involved-in%C3%A2-cartilage%C3%A2-damage-during-experimental-osteoarthritis-osteoarthritis%C3%A2-cartilage%C3%A2-23-2015-1221-1225
#15
M Stock, A Distler, J Distler, C Beyer, G Ruiz-Heiland, N Ipseiz, M Seeling, G Krönke, F Nimmerjahn, G Schett
No abstract text is available yet for this article.
June 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27820809/regulation-of-autoantibody-activity-by-the-il-23-th17-axis-determines-the-onset-of-autoimmune-disease
#16
René Pfeifle, Tobias Rothe, Natacha Ipseiz, Hans U Scherer, Stephan Culemann, Ulrike Harre, Jochen A Ackermann, Martina Seefried, Arnd Kleyer, Stefan Uderhardt, Benjamin Haugg, Axel J Hueber, Patrick Daum, Gordon F Heidkamp, Changrong Ge, Sybille Böhm, Anja Lux, Wolfgang Schuh, Iryna Magorivska, Kutty S Nandakumar, Erik Lönnblom, Christoph Becker, Diana Dudziak, Manfred Wuhrer, Yoann Rombouts, Carolien A Koeleman, René Toes, Thomas H Winkler, Rikard Holmdahl, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27753890/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#17
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27736135/action-versus-state-orientation-moderates-the-impact-of-executive-functioning-on-real-life-self-control
#18
Max Wolff, Klaus-Martin Krönke, John Venz, Anja Kräplin, Gerhard Bühringer, Michael N Smolka, Thomas Goschke
Self-control is commonly assumed to depend on executive functions (EFs). However, it is unclear whether real-life self-control failures result from deficient EF competencies or rather reflect insufficient conflict-induced mobilization of executive control, and whether self-control depends more critically on function-specific EF competencies or general executive functioning (GEF), that is, common competencies that underlie all EFs. Here we investigated whether failure-related action versus state orientation, a personality trait related to the conflict-induced mobilization of cognitive control, moderates the effect of general and function-specific control competencies on self-control...
December 2016: Journal of Experimental Psychology. General
https://www.readbyqxmd.com/read/27643236/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#19
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27492707/the-molecular-mechanism-of-thalidomide-analogs-in-hematologic-malignancies
#20
REVIEW
Stefanie Lindner, Jan Krönke
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells...
December 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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