TY - JOUR A1 - Franke, Werner W. A1 - Berger, S. A1 - Falk, Heinz A1 - Spring, H. A1 - Scheer, Ulrich A1 - Trendelenburg, Michael F. A1 - Schweiger, H. G. A1 - Herth, W. T1 - Morphology of the nucleo-cytoplasmic interactions during the development of Acetabularia cells. I. The vegetative phase N2 - The ultrastructure of th e growin g and ma turing primary nucleus of Acetabularia medite rranea and Acetabularia major has been studied with the use of various fi xation procedures. Particular interest has been focused on the deta ils of the nuclear periphery and the perinuclear region. It is demonstrated that early in nuclear grow th a characteristic perinucl ear structura l complex is formed which is, among the eukaryotic cells, unique to Acetabularia and re lated genera. This perinuclear system consists essentially of a) the nuclear envelope with a very hi gh pore frequency and various pore complex assoc iat ion s w ith granular and/or threadlike structures some of which are continuous with the nucleolus; b) an approx imate ly 100 nm thick intermediate zone densely filled with a filam entOus material and occasional sma ll membraneous structures from which the typical cytOplasmic and nuclear organe lles and particles are excl ud ed ; c) an adjacent Iacunar labyrinthum which is interrupted by many plasmatic junction channels between the intermed iate zone and the free cytOplasm; d) numerous dense perinuclear bodies in the juxtanuclear cytOplasm which a re especia lly frequent at the junction channels and reveal a composition of aggregated fibrillar and granul ar structures; e) very dense exclusively fibrill ar agg regates which occur either in assoc iation with t he perinuclear region of the lacunar labyrinthum or, somewhat further out, in the cytOplasmic strands between the bra nches of the lacun ar labyrinthum in the form of slender, characteristic rods or "sausages". Y1 - 1974 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32363 ER - TY - JOUR A1 - Terpos, Evangelos A1 - Kleber, Martina A1 - Engelhardt, Monika A1 - Zweegman, Sonja A1 - Gay, Francesca A1 - Kastritis, Efstathios A1 - van de Donk, Niels W. C. J. A1 - Bruno, Benedetto A1 - Sezer, Orhan A1 - Broijl, Annemiek A1 - Bringhen, Sara A1 - Beksac, Meral A1 - Larocca, Alessandra A1 - Hajek, Roman A1 - Musto, Pellegrino A1 - Johnsen, Hans Erik A1 - Morabito, Fortunato A1 - Ludwig, Heinz A1 - Cavo, Michele A1 - Einsele, Hermann A1 - Sonneveld, Pieter A1 - Dimopoulos, Meletios A. A1 - Palumbo, Antonio T1 - European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications JF - Haematologica N2 - The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin < 10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A). KW - bone-disease KW - stem-cell transplantation KW - acute kidney injury KW - erythropoiesis-stimulating agents KW - recombinant-human-erythropoietin KW - randomized controlled trial KW - group consensus statement KW - newly-diagnosed myeloma KW - zoledonic acid KW - enal impairment Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141913 VL - 100 IS - 10 SP - 1254 EP - 1266 ER - TY - RPRT A1 - Reinders, Heinz A1 - Gogolin, Ingrid A1 - van Deth, Jan W. A1 - Böhmer, Jule A1 - Bremm, Nina A1 - Gresser, Anne A1 - Schnurr, Simone T1 - Ganztagsschule und Integration von Migranten : Abschlussbericht N2 - Das Projekt hat die Aufgabe zu klären, ob Heranwachsende mit Migrationshintergrund durch den Besuch einer Ganztagsschule im Vergleich zu Migrantenkindern an Halbtagsschulen hinsichtlich ihres Integrationsprozesses besonders unterstützt werden. Diese Leitfrage gliedert sich in spezifische Fragestellungen, die im Rahmen des Projekts empirisch zu beantworten sind. Als Vergleichsmaßstab für die Effekte des Ganztagsschulbesuchs wird der Besuch von Halbtagsschulen herangezogen. Primar-­ und Sekundarstufe werden berücksichtigt, um altersabhängige Möglichkeiten und Bedingungen der Integrationsförderung durch den Ganztagsschulbesuch untersuchen zu können. Das übergeordnete Ziel der Untersuchung ist die Identifikation von Bedingungen, unter denen Ganztagsschulen im Primar- und Sekundarbereich den Integrationsprozess von Kindern und Jugendlichen mit Migrationshintergrund in besonderem Maße fördern können. Das Projekt wurde im Zeitraum vom 01.07.2008 bis 30.06.2010 realisiert. T3 - Schriftenreihe Empirische Bildungsforschung - 15 KW - Ganztagsschule KW - Integration KW - Migration KW - Migrationshintergrund KW - Integrationsprozess Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-54989 SN - 978-3-923959-70-9 ER - TY - JOUR A1 - Vortkamp, A. A1 - Thias, U. A1 - Gessler, Manfred A1 - Rosenkranz, W. A1 - Kroisel, P. M. A1 - Tommerup, N. A1 - Kruger, G. A1 - Gotz, J. A1 - Pelz, L. A1 - Grzeschik, Karl-Heinz T1 - A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p N2 - No abstract available KW - Biochemie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59217 ER - TY - JOUR A1 - Franke, Werner W. A1 - Kartenbeck, Jürgen A1 - Zentgraf, Hanswalter A1 - Scheer, Ulrich A1 - Falk, Heinz T1 - Membrane-to-membrane cross-bridges. A means to orientation and interaction of membrane faces N2 - No abstract available Y1 - 1971 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32122 ER - TY - JOUR A1 - van de Donk, Niels W. C. J. A1 - Palumbo, Antonio A1 - Johnsen, Hans Erik A1 - Engelhardt, Monika A1 - Gay, Francesca A1 - Gregersen, Henrik A1 - Hajek, Roman A1 - Kleber, Martina A1 - Ludwig, Heinz A1 - Morgan, Gareth A1 - Musto, Pellegrino A1 - Plesner, Torben A1 - Sezer, Orhan A1 - Terpos, Evangelos A1 - Waage, Anders A1 - Zweegman, Sonja A1 - Einsele, Hermann A1 - Sonneveld, Pieter A1 - Lokhorst, Henk M. T1 - The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network JF - Haematologica N2 - Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenstrom's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. KW - multiparameter flow-cytometry KW - hematopoietic cell transplantation KW - smoldering multiple-myeloma KW - venous thromboembolic disease KW - bone-mineral density KW - population-based cohort KW - term-follow-up KW - marrow plasma cells KW - significance MGUS KW - malignant transformation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116050 SN - 0390-6078 VL - 99 IS - 6 ER - TY - JOUR A1 - Scheer, Ulrich A1 - Messner, Karin A1 - Hazan, Rachel A1 - Raska, Ivan A1 - Hansmann, Paul A1 - Falk, Heinz A1 - Spiess, Eberhard A1 - Franke, Werner W. T1 - High sensitivity immunolocalization of double and single-stranded DNA by a monoclonal antibody N2 - A monoclonal antibody (AK 30-10) is described which specifically reacts with DNA both in double and single-stranded forms but not with other molecules and structures, including deoxyribonucleotides and RNAs. When used in immunocytochemical experiments on tissue sections and permeabilized cultured cells, this antibody detects DNA-containing structures, even when the DNA is present in very small amounts. Examples of high resolution detection include the DNA present in amplified extrachromosomal nucleoli, chromomeres of lampbrush chromosomes, mitochondria, chloroplasts and mycoplasmal particles. In immunoelectron microscopy using the immunogold technique, the DNA was localized in distinct substructures such as the "fibrillar centers" of nucleoli and certain stromal centers in chloroplasts. The antibody also reacts with DNA of chromatin of living cells, as shown by microinjection into cultured mitotic cells and into nuclei of amphibian oocytes. The potential value and the limitations of immunocytochemical DNA detection are discussed. KW - Cytologie KW - DNA antibodies KW - monoclonal antibodies KW - DNA immunolocalization KW - chromatin KW - mycoplasma tests Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-41063 ER - TY - JOUR A1 - Schmidt-Hieber, M. A1 - Silling, G. A1 - Schalk, E. A1 - Heinz, W. A1 - Panse, J. A1 - Penack, O. A1 - Christopeit, M. A1 - Buchheidt, D. A1 - Meyding-Lamadé, U. A1 - Hähnel, S. A1 - Wolf, H. H. A1 - Ruhnke, M. A1 - Schwartz, S. A1 - Maschmeyer, G. T1 - CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) JF - Annals of Oncology N2 - Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases. KW - Central nervous system KW - Polymerase chain raction KW - Herpes simplex encephalitis KW - Invasive fungal-infections KW - Clinical practice guidelines KW - Liposomal amphotericin-B KW - Immunocompromised patient KW - Progressive multifocal leukoencephalopathy KW - Varicella-zoster-virus KW - Diagnosis KW - Treatment KW - Bone-marrow-transplantation KW - Real-time PCR KW - Guideline KW - Central nervous system infection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188210 VL - 27 IS - 7 ER - TY - JOUR A1 - Boch, Tobias A1 - Spiess, Birgit A1 - Heinz, Werner A1 - Cornely, Oliver A. A1 - Schwerdtfeger, Rainer A1 - Hahn, Joachim A1 - Krause, Stefan W. A1 - Duerken, Matthias A1 - Bertz, Hartmut A1 - Reuter, Stefan A1 - Kiehl, Michael A1 - Claus, Bernd A1 - Deckert, Peter Markus A1 - Hofmann, Wolf‐Karsten A1 - Buchheidt, Dieter A1 - Reinwald, Mark T1 - Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis JF - Mycoses N2 - Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis. KW - antifungal KW - aspergillosis KW - BAL KW - blood KW - cerebrospinal fluid KW - comparison KW - PCR KW - Aspergillus Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214065 VL - 62 IS - 11 SP - 1035 EP - 1042 ER - TY - JOUR A1 - Rieger, C. T. A1 - Liss, B. A1 - Mellinghoff, S. A1 - Buchheidt, D. A1 - Cornely, O. A. A1 - Egerer, G. A1 - Heinz, W. J. A1 - Hentrich, M. A1 - Maschmeyer, G. A1 - Mayer, K. A1 - Sandherr, M. A1 - Silling, G. A1 - Ullmann, A. A1 - Vehreschild, M. J. G. T. A1 - von Lilienfeld-Toal, M. A1 - Wolf, H. H. A1 - Lehners, N. T1 - Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) JF - Annals of Oncology N2 - Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria. KW - infection KW - anti-infective vaccination KW - cancer KW - immunosuppression KW - autologous stem cell transplantation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226196 VL - 29 IS - 6 ER - TY - JOUR A1 - Göbel, Kerstin A1 - Pankratz, Susann A1 - Asaridou, Chloi-Magdalini A1 - Herrmann, Alexander M. A1 - Bittner, Stefan A1 - Merker, Monika A1 - Ruck, Tobias A1 - Glumm, Sarah A1 - Langhauser, Friederike A1 - Kraft, Peter A1 - Krug, Thorsten F. A1 - Breuer, Johanna A1 - Herold, Martin A1 - Gross, Catharina C. A1 - Beckmann, Denise A1 - Korb-Pap, Adelheid A1 - Schuhmann, Michael K. A1 - Kuerten, Stefanie A1 - Mitroulis, Ioannis A1 - Ruppert, Clemens A1 - Nolte, Marc W. A1 - Panousis, Con A1 - Klotz, Luisa A1 - Kehrel, Beate A1 - Korn, Thomas A1 - Langer, Harald F. A1 - Pap, Thomas A1 - Nieswandt, Bernhard A1 - Wiendl, Heinz A1 - Chavakis, Triantafyllos A1 - Kleinschnitz, Christoph A1 - Meuth, Sven G. T1 - Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells JF - Nature Communications N2 - Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. KW - blood coagulation KW - factor XII KW - neuroinflammation KW - dendric cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165503 VL - 7 IS - 11626 ER - TY - JOUR A1 - Roth, Nicolas A1 - Doerfler, Inken A1 - Bässler, Claus A1 - Blaschke, Markus A1 - Bussler, Heinz A1 - Gossner, Martin M. A1 - Heideroth, Antje A1 - Thorn, Simon A1 - Weisser, Wolfgang W. A1 - Müller, Jörg T1 - Decadal effects of landscape-wide enrichment of dead wood on saproxylic organisms in beech forests of different historic management intensity JF - Diversity and Distributions N2 - Aim: European temperate forests have lost dead wood and the associated biodiversity owing to intensive management over centuries. Nowadays, some of these forests are being restored by enrichment with dead wood, but mostly only at stand scales. Here, we investigated effects of a seminal dead-wood enrichment strategy on saproxylic organisms at the landscape scale. Location: Temperate European beech forest in southern Germany. Methods: In a before-after control-impact design, we compared assemblages and gamma diversities of saproxylic organisms in strictly protected old-growth forest areas (reserves) and historically moderately and intensively managed forest areas before and a decade after starting a landscape-wide strategy of dead-wood enrichment. Results: Before enrichment with dead wood, the gamma diversity of saproxylic organisms in historically intensively managed forest stands was significantly lower than in reserves and historically moderately managed forest stands; this difference disappeared after 10 years of dead-wood enrichment. The species composition of beetles in forest stands of the three historical management intensities differed before the enrichment strategy, but a decade thereafter, the species compositions of previously intensively logged and forest reserve plots were similar. However, the differences in fungal species composition between historical management categories before and after 10 years of enrichment persisted. Main conclusions: Our results demonstrate that intentional enrichment of dead wood at the landscape scale is a powerful tool for rapidly restoring saproxylic beetle communities and for restoring wood-inhabiting fungal communities, which need longer than a decade for complete restoration. We propose that a strategy of area-wide active restoration combined with some permanent strict refuges is a promising means of promoting the biodiversity of age-long intensively managed Central European beech forests. KW - dead-wood enrichment KW - integrative management strategy KW - land sharing KW - lowland beech forests KW - saproxylic organisms Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227061 VL - 25 IS - 3 ER - TY - JOUR A1 - Ludwig, Heinz A1 - Delforge, Michel A1 - Facon, Thierry A1 - Einsele, Hermann A1 - Gay, Francesca A1 - Moreau, Philippe A1 - Avet-Loiseau, Hervé A1 - Boccadoro, Mario A1 - Hajek, Roman A1 - Mohty, Mohamad A1 - Cavo, Michele A1 - Dimopoulos, Meletios A A1 - San-Miguel, Jesús F A1 - Terpos, Evangelos A1 - Zweegman, Sonja A1 - Garderet, Laurent A1 - Mateos, María-Victoria A1 - Cook, Gordon A1 - Leleu, Xavier A1 - Goldschmidt, Hartmut A1 - Jackson, Graham A1 - Kaiser, Martin A1 - Weisel, Katja A1 - van de Donk, Niels W. C. J. A1 - Waage, Anders A1 - Beksac, Meral A1 - Mellqvist, Ulf H. A1 - Engelhardt, Monika A1 - Caers, Jo A1 - Driessen, Christoph A1 - Bladé, Joan A1 - Sonneveld, Pieter T1 - Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network JF - Leukemia N2 - During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events. KW - disease prevention KW - myeloma Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237338 VL - 32 ER - TY - JOUR A1 - Went, Molly A1 - Sud, Amit A1 - Speedy, Helen A1 - Sunter, Nicola J. A1 - Försti, Asta A1 - Law, Philip J. A1 - Johnson, David C. A1 - Mirabella, Fabio A1 - Holroyd, Amy A1 - Li, Ni A1 - Orlando, Giulia A1 - Weinhold, Niels A1 - van Duin, Mark A1 - Chen, Bowang A1 - Mitchell, Jonathan S. A1 - Mansouri, Larry A1 - Juliusson, Gunnar A1 - Smedby, Karin E A1 - Jayne, Sandrine A1 - Majid, Aneela A1 - Dearden, Claire A1 - Allsup, David J. A1 - Bailey, James R. A1 - Pratt, Guy A1 - Pepper, Chris A1 - Fegan, Chris A1 - Rosenquist, Richard A1 - Kuiper, Rowan A1 - Stephens, Owen W. A1 - Bertsch, Uta A1 - Broderick, Peter A1 - Einsele, Hermann A1 - Gregory, Walter M. A1 - Hillengass, Jens A1 - Hoffmann, Per A1 - Jackson, Graham H. A1 - Jöckel, Karl-Heinz A1 - Nickel, Jolanta A1 - Nöthen, Markus M. A1 - da Silva Filho, Miguel Inacio A1 - Thomsen, Hauke A1 - Walker, Brian A. A1 - Broyl, Annemiek A1 - Davies, Faith E. A1 - Hansson, Markus A1 - Goldschmidt, Hartmut A1 - Dyer, Martin J. S. A1 - Kaiser, Martin A1 - Sonneveld, Pieter A1 - Morgan, Gareth J. A1 - Hemminki, Kari A1 - Nilsson, Björn A1 - Catovsky, Daniel A1 - Allan, James M. A1 - Houlston, Richard S. T1 - Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology JF - Blood Cancer Journal N2 - The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies. KW - cancer genetics KW - myeloma Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233627 VL - 9 ER - TY - JOUR A1 - Bittner, Stefan A1 - Bobak, Nicole A1 - Feuchtenberger, Martin A1 - Herrmann, Alexander M A1 - Göbel, Kerstin A1 - Kinne, Raimund W A1 - Hansen, Anker J A1 - Budde, Thomas A1 - Kleinschnitz, Christoph A1 - Frey, Oliver A1 - Tony, Hans-Peter A1 - Wiendl, Heinz A1 - Meuth, Sven G T1 - Expression of K\(_2\)\(_P\)5.1 potassium channels on CD4\(^+\)T lymphocytes correlates with disease activity in rheumatoid arthritis patients JF - Arthritis Research & Therapy N2 - Introduction CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Methods Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1. Results K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K2P5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K2P5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Conclusions Disease activity in RA patients correlates strongly with K2P5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K2P5.1 as a potential biomarker for disease activity and differential diagnosis. KW - neurology Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139334 VL - 13 IS - R21 ER -