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  - Pattschull, Grit
A1  - Walz, Susanne
A1  - Gründl, Marco
A1  - Schwab, Melissa
A1  - Rühl, Eva
A1  - Baluapuri, Apoorva
A1  - Cindric-Vranesic, Anita
A1  - Kneitz, Susanne
A1  - Wolf, Elmar
A1  - Ade, Carsten P.
A1  - Rosenwald, Andreas
A1  - von Eyss, Björn
A1  - Gaubatz, Stefan
T1  - The Myb-MuvB complex is required for YAP-dependent transcription of mitotic genes
JF  - Cell Reports
N2  - YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here, we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes coactivated by YAP and B-MYB is associated with poor survival of cancer patients. Our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways.
KW  - YAP
KW  - B-MYB
KW  - Myb-MuvB
KW  - mitotic genes
KW  - enhancer
KW  - transcription
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202039
VL  - 27
IS  - 12
ER  -