TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Davis, Lea K.
A1  - Yu, Dongmei
A1  - Keenan, Clare L.
A1  - Gamazon, Eric R.
A1  - Konkashbaev, Anuar I.
A1  - Derks, Eske M.
A1  - Neale, Benjamin M.
A1  - Yang, Jian
A1  - Lee, S. Hong
A1  - Evans, Patrick
A1  - Barr, Cathy L.
A1  - Bellodi, Laura
A1  - Benarroch, Fortu
A1  - Berrio, Gabriel Bedoya
A1  - Bienvenu, Oscar J.
A1  - Bloch, Michael H.
A1  - Blom, Rianne M.
A1  - Bruun, Ruth D.
A1  - Budman, Cathy L.
A1  - Camarena, Beatriz
A1  - Campbell, Desmond
A1  - Cappi, Carolina
A1  - Cardona Silgado, Julio C.
A1  - Cath, Danielle C.
A1  - Cavallini, Maria C.
A1  - Chavira, Denise A.
A1  - Chouinard, Sylvian
A1  - Conti, David V.
A1  - Cook, Edwin H.
A1  - Coric, Vladimir
A1  - Cullen, Bernadette A.
A1  - Deforce, Dieter
A1  - Delorme, Richard
A1  - Dion, Yves
A1  - Edlund, Christopher K.
A1  - Egberts, Karin
A1  - Falkai, Peter
A1  - Fernandez, Thomas V.
A1  - Gallagher, Patience J.
A1  - Garrido, Helena
A1  - Geller, Daniel
A1  - Girard, Simon L.
A1  - Grabe, Hans J.
A1  - Grados, Marco A.
A1  - Greenberg, Benjamin D.
A1  - Gross-Tsur, Varda
A1  - Haddad, Stephen
A1  - Heiman, Gary A.
A1  - Hemmings, Sian M. J.
A1  - Hounie, Ana G.
A1  - Illmann, Cornelia
A1  - Jankovic, Joseph
A1  - Jenike, Micheal A.
A1  - Kennedy, James L.
A1  - King, Robert A.
A1  - Kremeyer, Barbara
A1  - Kurlan, Roger
A1  - Lanzagorta, Nuria
A1  - Leboyer, Marion
A1  - Leckman, James F.
A1  - Lennertz, Leonhard
A1  - Liu, Chunyu
A1  - Lochner, Christine
A1  - Lowe, Thomas L.
A1  - Macciardi, Fabio
A1  - McCracken, James T.
A1  - McGrath, Lauren M.
A1  - Restrepo, Sandra C. Mesa
A1  - Moessner, Rainald
A1  - Morgan, Jubel
A1  - Muller, Heike
A1  - Murphy, Dennis L.
A1  - Naarden, Allan L.
A1  - Ochoa, William Cornejo
A1  - Ophoff, Roel A.
A1  - Osiecki, Lisa
A1  - Pakstis, Andrew J.
A1  - Pato, Michele T.
A1  - Pato, Carlos N.
A1  - Piacentini, John
A1  - Pittenger, Christopher
A1  - Pollak, Yehunda
A1  - Rauch, Scott L.
A1  - Renner, Tobias J.
A1  - Reus, Victor I.
A1  - Richter, Margaret A.
A1  - Riddle, Mark A.
A1  - Robertson, Mary M.
A1  - Romero, Roxana
A1  - Rosàrio, Maria C.
A1  - Rosenberg, David
A1  - Rouleau, Guy A.
A1  - Ruhrmann, Stephan
A1  - Ruiz-Linares, Andreas
A1  - Sampaio, Aline S.
A1  - Samuels, Jack
A1  - Sandor, Paul
A1  - Sheppard, Broke
A1  - Singer, Harvey S.
A1  - Smit, Jan H.
A1  - Stein, Dan J.
A1  - Strengman, E.
A1  - Tischfield, Jay A.
A1  - Valencia Duarte, Ana V.
A1  - Vallada, Homero
A1  - Van Nieuwerburgh, Flip
A1  - Veenstra-VanderWeele, Jeremy
A1  - Walitza, Susanne
A1  - Wang, Ying
A1  - Wendland, Jens R.
A1  - Westenberg, Herman G. M.
A1  - Shugart, Yin Yao
A1  - Miguel, Euripedes C.
A1  - McMahon, William
A1  - Wagner, Michael
A1  - Nicolini, Humberto
A1  - Posthuma, Danielle
A1  - Hanna, Gregory L.
A1  - Heutink, Peter
A1  - Denys, Damiaan
A1  - Arnold, Paul D.
A1  - Oostra, Ben A.
A1  - Nestadt, Gerald
A1  - Freimer, Nelson B.
A1  - Pauls, David L.
A1  - Wray, Naomi R.
A1  - Stewart, S. Evelyn
A1  - Mathews, Carol A.
A1  - Knowles, James A.
A1  - Cox, Nancy J.
A1  - Scharf, Jeremiah M.
T1  - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
JF  - PLoS Genetics
N2  - The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
KW  - TIC disorders
KW  - missing heritability
KW  - complex diseases
KW  - neuropsychiatric disorders
KW  - common SNPS
KW  - gilles
KW  - family
KW  - brain
KW  - expression
KW  - autism
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127377
SN  - 1553-7390
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Dickneite, G.
A1  - Schorlemmer, H. U.
A1  - Sedlacek, H. H.
A1  - Falk, W.
A1  - Ulrichs, Karin
A1  - Müller-Ruchholtz, W.
T1  - Suppression of macrophage function and prolongation of graft survival by the new guanidinic-like structure, 15-deoxyspergualin
N2  - No abstract available.
KW  - Makrophage
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86991
ER  - 
TY  - JOUR
A1  - Müller, J. G.
A1  - Krenn, V.
A1  - Schindler, C.
A1  - Czub, S.
A1  - Stahl-Henning, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Kneitz, C.
A1  - Kerkau, T.
A1  - Rethwilm, A.
A1  - ter Meulen, V.
A1  - Müller-Hermelink, H. K.
T1  - Alterations of Thymus Cortical Epithelium and Interdigitating Dendritic Cells but No Increase of Thymocyte Cell Death in the Early Course of Simian Immunodeficiency Virus Infection
JF  - American Journal of Pathology
N2  - The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low « 1 in 1 04 T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate andflow cytometry showed a reduction of the immature \(CD4^+/CD8^+\) double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, andfinally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128250
VL  - 143
IS  - 3
ER  - 
TY  - JOUR
A1  - Müller, J.
A1  - Krenn, V.
A1  - Czub, S.
A1  - Schindler, C.
A1  - Kneitz, C.
A1  - Kerkau, T.
A1  - Stahl-Henning, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Rethwilm, Axel
A1  - ter Meulen, Volker
A1  - Müller-Hermelink, H. K.
T1  - The thymus in SIV infection
N2  - no abstract available
KW  - HIV-Infektion
KW  - Tierversuch
KW  - Tiermodell
KW  - Retroviren-Infektion
KW  - Kongress
KW  - Hamburg
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80265
ER  - 
TY  - JOUR
A1  - Müller, J. G.
A1  - Czub, S.
A1  - Rethwilm, Axel
A1  - Müller-Hermelink, H. K.
T1  - Korrelation von Organpathologie und Verteilung virusreplizierenderZellen, nachgewiesen mit der RNA in situ Hybridisierungwährend der SIVmac-Infektion von Macaca mulatta
T1  - Correlation of Organ Pathology and Distribution of SIV detected by in situ Hybridization during SIVmac Infection of Macaca mulatta
N2  - No abstract available
N2  - 22 juvenile rhesus macaques were infected i.v. with SIVmac and killed at defined timepoints after infection. Productively infected cells were detected by RNA in situ hybridization in the paraffin material. Their number was correlated with the pathology of lymph nodes, thymus, extranodallymphatic parenchyma and other organs. In the first weeks alllymphatic tissues and compartiments got infected, as weil as the brain, the bone marrow and other organs. The high virus replication during this first phase dissappeared with the onset of the seroconversion and remained low during all stages of atrophy of the lymphatic parenchyma. The atrophy of the lymphatic parenchyma and its microenvironment was not correlated with virus replication. This may implicate that a virostatic therapy might be more succesfull in the first weeks of infection.
KW  - Virologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47331
ER  - 
TY  - JOUR
A1  - Gattenloehner, Stefan
A1  - Joerissen, H.
A1  - Huhn, M.
A1  - Vincent, A.
A1  - Beeson, D.
A1  - Tzartos, S.
A1  - Mamalaki, A.
A1  - Etschmann, B.
A1  - Muller-Hermelink, H. K.
A1  - Koscielniak, E.
A1  - Barth, S.
A1  - Marx, A.
T1  - A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]
N2  - Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.
KW  - Medizin
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68200
ER  - 
TY  - JOUR
A1  - Merz, H.
A1  - Fliedner, A.
A1  - Lehrnbecher, T.
A1  - Sebald, Walter
A1  - Müller-Hermelink, H. K.
A1  - Feller, A. C.
T1  - Cytokine expression in B-cell non-Hodgkin lymphomas
N2  - No abstract available
KW  - Biochemie
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62539
ER  - 
TY  - JOUR
A1  - Merz, H.
A1  - Fliedner, A.
A1  - Orscheschek, K.
A1  - Binder, T.
A1  - Sebald, Walter
A1  - Müller-Hermelink, H. K.
A1  - Feller, A. C.
T1  - Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth
N2  - No abstract available
KW  - Biochemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62483
ER  - 
TY  - JOUR
A1  - Erhardt, A.
A1  - Akula, N.
A1  - Schumacher, J.
A1  - Czamara, D.
A1  - Karbalai, N.
A1  - Müller-Myhsok, B.
A1  - Mors, O.
A1  - Borglum, A.
A1  - Kristensen, A. S.
A1  - Woldbye, D. P. D.
A1  - Koefoed, P.
A1  - Eriksson, E.
A1  - Maron, E.
A1  - Metspalu, A.
A1  - Nurnberger, J.
A1  - Philibert, R. A.
A1  - Kennedy, J.
A1  - Domschke, K.
A1  - Reif, A.
A1  - Deckert, J.
A1  - Otowa, T.
A1  - Kawamura, Y.
A1  - Kaiya, H.
A1  - Okazaki, Y.
A1  - Tanii, H.
A1  - Tokunaga, K.
A1  - Sasaki, T.
A1  - Ioannidis, J. P. A.
A1  - McMahon, F. J.
A1  - Binder, E. B.
T1  - Replication and meta-analysis of TMEM132D gene variants in panic disorder
JF  - Translational Psychiatry
N2  - A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n = 1670 cases and n 2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n 1038 cases and n 2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P = 1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations.
KW  - candidate gene
KW  - genome-wide association
KW  - Japanese population
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133324
VL  - 2
IS  - e156
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Heiser, A.
A1  - Bosse, M.
A1  - Wacker, H. H.
A1  - Müller-Ruchholtz, W.
T1  - Histologische Untersuchungen des Schweinepankreas zur Verbesserung der Inselausbeute und -integrität nach Kollagenase-Verdauung
N2  - No abstract available.
KW  - Schwein
KW  - Bauchspeicheldrüse
KW  - Histologie
KW  - Kollagenase
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73237
ER  - 
TY  - JOUR
A1  - Gratwohl, A
A1  - Pfirrmann, M
A1  - Zander, A
A1  - Kröger, N
A1  - Beelen, D
A1  - Novotny, J
A1  - Nerl, C
A1  - Scheid, C
A1  - Spiekermann, K
A1  - Mayer, J
A1  - Sayer, HG
A1  - Falge, C
A1  - Bunjes, D
A1  - Döhner, H
A1  - Ganser, A
A1  - Schmidt-Wolf, I
A1  - Schwerdtfeger, R
A1  - Baurmann, H
A1  - Kuse, R
A1  - Schmitz, N
A1  - Wehmeier, A
A1  - Fischer, J Th
A1  - Ho, AD
A1  - Wilhelm, M
A1  - Goebeler, M-E
A1  - Lindemann, HW
A1  - Bormann, M
A1  - Hertenstein, B
A1  - Schlimok, G
A1  - Baerlocher, GM
A1  - Aul, C
A1  - Pfreundschuh, M
A1  - Fabian, M
A1  - Staib, P
A1  - Edinger, M
A1  - Schatz, M
A1  - Fauser, A
A1  - Arnold, R
A1  - Kindler, T
A1  - Wulf, G
A1  - Rosselet, A
A1  - Hellmann, A
A1  - Schäfer, E
A1  - Prümmer, O
A1  - Schenk, M
A1  - Hasford, J
A1  - Heimpel, H
A1  - Hossfeld, DK
A1  - Kolb, H-J
A1  - Büsche, G
A1  - Haferlach, C
A1  - Schnittger, S
A1  - Müller, MC
A1  - Reiter, A
A1  - Berger, U
A1  - Saußele, S
A1  - Hochhaus, A
A1  - Hehlmann, R
T1  - Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment
JF  - Leukemia
N2  - Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
KW  - chronic myeloid leukemia
KW  - stem cell transplantation
KW  - drug treatment
KW  - CML
KW  - tyrosine kinase inhibitors
KW  - allogeneic hematopoietic stem cell transplantation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150368
VL  - 30
ER  - 
TY  - JOUR
A1  - Müller, Stefanie H.
A1  - Girard, Simon L.
A1  - Hopfner, Franziska
A1  - Merner, Nancy D.
A1  - Bourassa, Cynthia V.
A1  - Lorenz, Delia
A1  - Clark, Lorraine N.
A1  - Tittmann, Lukas
A1  - Soto-Ortolaza, Alexandra I.
A1  - Klebe, Stephan
A1  - Hallett, Mark
A1  - Schneider, Susanne A.
A1  - Hodgkinson, Colin A.
A1  - Lieb, Wolfgang
A1  - Wszolek, Zbigniew K.
A1  - Pendziwiat, Manuela
A1  - Lorenzo-Betancor, Oswaldo
A1  - Poewe, Werner
A1  - Ortega-Cubero, Sara
A1  - Seppi, Klaus
A1  - Rajput, Alex
A1  - Hussl, Anna
A1  - Rajput, Ali H.
A1  - Berg, Daniela
A1  - Dion, Patrick A.
A1  - Wurster, Isabel
A1  - Shulman, Joshua M.
A1  - Srulijes, Karin
A1  - Haubenberger, Dietrich
A1  - Pastor, Pau
A1  - Vilariño-Güell, Carles
A1  - Postuma, Ronald B.
A1  - Bernard, Geneviève
A1  - Ladwig, Karl-Heinz
A1  - Dupré, Nicolas
A1  - Jankovic, Joseph
A1  - Strauch, Konstantin
A1  - Panisset, Michel
A1  - Winkelmann, Juliane
A1  - Testa, Claudia M.
A1  - Reischl, Eva
A1  - Zeuner, Kirsten E.
A1  - Ross, Owen A.
A1  - Arzberger, Thomas
A1  - Chouinard, Sylvain
A1  - Deuschl, Günther
A1  - Louis, Elan D.
A1  - Kuhlenbäumer, Gregor
A1  - Rouleau, Guy A.
T1  - Genome-wide association study in essential tremor identifies three new loci
JF  - Brain
N2  - We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.
KW  - quality-control
KW  - disease
KW  - tool
KW  - movement disorders
KW  - genome-wide association study
KW  - tremor
KW  - genetics
KW  - essential tremor
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186541
VL  - 139
ER  - 
TY  - JOUR
A1  - Zeiner, P. S.
A1  - Zinke, J.
A1  - Kowalewski, D. J.
A1  - Bernatz, S.
A1  - Tichy, J.
A1  - Ronellenfitsch, M. W.
A1  - Thorsen, F.
A1  - Berger, A.
A1  - Forster, M. T.
A1  - Muller, A.
A1  - Steinbach, J. P.
A1  - Beschorner, R.
A1  - Wischhusen, J.
A1  - Kvasnicka, H. M.
A1  - Plate, K. H.
A1  - Stefanović, S.
A1  - Weide, B.
A1  - Mittelbronn, M.
A1  - Harter, P. N.
T1  - CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival
JF  - Acta Neuropathologica Communications
N2  - Abstract
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.

We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line.

We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected.

In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.
KW  - CD74
KW  - HLA class II
KW  - brain metastasis
KW  - HLA peptidome
KW  - tumor infiltrating lymphocytes
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233882
VL  - 6
ER  - 
TY  - JOUR
A1  - Gattenlöhner, S.
A1  - Etschmann, B.
A1  - Kunzmann, V.
A1  - Thalheimer, A.
A1  - Hack, M.
A1  - Kleber, G.
A1  - Einsele, H.
A1  - Germer, C.
A1  - Müller-Hermelink, H.-K.
T1  - Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy
N2  - Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.
KW  - Krebs
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68240
ER  - 
TY  - JOUR
A1  - Müller, J. G.
A1  - Stahl-Hennig, Christiane
A1  - Rethwilm, Axel
A1  - Kneitz, C.
A1  - Kerkau, Thomas
A1  - Schmauser, B.
A1  - Schindler, C
A1  - Krenn, V.
A1  - terMeulen, V.
A1  - Müller-Hermelink, H.K.
T1  - Morphologische Untersuchungen von Lymphknoten und Thymusin der Frühphase der SIV-Infektion bei Rhesus-Affen
T1  - Morpholoical alterations of lymph nodes and thymus during the early course of SIV infection of rhesus monkeys
N2  - Rhesus monkeys (M. mulatta) were i. v. infected with SIV mac251. Three phases of lymph node changes were observed. 1: physiological follicular hyperplasia (3 and 6 weeks p.i.). 2: Alterations of germinal centers: loss of follicular mantle zone, fragmentation or sclerosis (12 and 24 weeks p.i.). 3: Partial depletion of T-lymphocytes, accumulation of plasma cells, increased numbers of syncytial giant cells, hemophgocytosis in the sinuses (about 1 year p.i.). The thymus of the juvenile animals showed first changes 12 and 24 weeks after infection with focalloss of immature (and Ki-67 positive) cortical thymocytes, leading to severe accidental involution of the thymuses one year after infection and reduced numbers of Hassalls corpuscles. These investigations show the value of this animal model for the study of morphology and pathogenesis of AIDS.
KW  - Affenimmundefizienzvirus
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47183
ER  - 
TY  - JOUR
A1  - Engemann, R.
A1  - Ulrichs, Karin
A1  - Thiede, A.
A1  - Müller-Ruchholtz, W.
A1  - Hamelmann, H.
T1  - Value of a physiological liver transplant model in rats. Induction of specific graft tolerance in a fully allogeneic strain combination
N2  - No abstract available
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45622
ER  - 
TY  - JOUR
A1  - Koch, R.
A1  - Deger, A.
A1  - Klotz, Karl-Norbert
A1  - Schenzle, D.
A1  - Krämer, H.
A1  - Kelm, S.
A1  - Müller, G.
A1  - Rapp, R.
A1  - Weber, U.
T1  - Characterization of solubilized insulin receptors from rat liver microsomes. Existence of two receptor species with  different binding properties
N2  - Insulin receptors were solubilized from rat liver microsomes by the nonionic detergent Triton X-100. After gel filtration of the extract on Sepharose CL-6B, two insulin-binding species (peak I and peak li) were obtained. The structure and binding properties of both peaks were characterized. Gel filtration yielded Stokes radii of 9.2 nm (peak I) and 8.0 nm (peak Il). Both peaks were glycoproteins. At 4°C peak 1 showed optimal insulin binding at pH 8.0 and high ionic strength. In contrast, peak li bad its binding optimum at pH 7.0 and low ionic strength, where peak I bindingwas minimal. For peak I the change in insulin binding under different conditions of pH and ionic strength was due to a change in receptor affinity only. For peak 11 an additional change in receptor number was found. Both peaks yielded non-linear Scatchard plots under most of the buffer conditions examined. At their binding optima at 4 oc the high affinity dissociation constants were 0.50 nM (peak I) and 0.55 nM (peak II). Sodium dodecyl sulfatejpolyacrylamide gel electrophoresis of peak I revealed five receptor bands with Mr 400000, 365000, 320000, 290000, and 245000 under non-reducing conditions. For peak II two major receptor bands with M\(_r\) 210000 and 115000 were found. The peak II receptor bands were also obtained aftermild reduction of peak I. After complete reduction both peaks showed one major receptor band with M\(_r\) 130000. The reductive generation of the peak II receptor together with molecular mass estimations suggest that the peak I receptor is the disulfide-linked dimer of the peak II receptor. Thus, Triton extracts from rat liver microsomes contain two receptor species, which are related, but differ considerably in their size and insulin-binding properties.
KW  - Toxikologie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60215
ER  - 
TY  - JOUR
A1  - Müller, T.
A1  - Dieckmann, T.
A1  - Sebald, Walter
A1  - Oschkinat, H.
T1  - Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy
N2  - Cytokines are hormones that carry information from ceJI to ceH. This information is read from their surface upon binding to transmembrane receptors and by the subsequent initiation of receptor oligomerization. An inftuence on this process through mutagenesis on the hormone surface is highly desirab)e for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human TL-4 and the medically important IL-4 antagonists YI24D and Y124G are presented. The site a.round YI24 is an important epitope responsible for the a.bility of 11-4 t.o ca.use a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon Iabeiied sa.mples.
KW  - Biochemie
KW  - Interleukin-4
KW  - protein structure
KW  - NMR
KW  - signal transduction
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62444
ER  - 
TY  - JOUR
A1  - Kruse, N.
A1  - Shen, B. J.
A1  - Arnold, S.
A1  - Tony, H. P.
A1  - Müller, T.
A1  - Sebald, Walter
T1  - Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation
N2  - Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.
KW  - Biochemie
KW  - drug design/partial agonists
KW  - receptor signalling
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62451
ER  - 
TY  - JOUR
A1  - Müller, T.
A1  - Sebald, Walter
A1  - Oschkinat, H.
T1  - Antagonist design through forced electrostatic mismatch
N2  - No abstract available
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62408
ER  - 
TY  - JOUR
A1  - Kübler, N.
A1  - Reuther, J.
A1  - Kirchner, T.
A1  - Pfaff, M.
A1  - Müller-Hermelink, H. K.
A1  - Albert, R.
A1  - Sebald, Walter
T1  - IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP)
N2  - Monoclonal hBMP/NCP (human bone morphogenetic protein anrl associaterl noncollagenous proteins) antiborlies of the lgG class were prorlucerl. In vitro, 12 of 19 hBMP/NCP antiborlies showerl functional inhibition of hBMP/ NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of inducerl chondro- and osteogenesis.
KW  - Biochemie
KW  - bone morphogenetic proteins
KW  - neutralizing antibodies
KW  - cartilage induction
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62388
ER  - 
TY  - JOUR
A1  - Christl, Manfred
A1  - Müller, H.
T1  - Induktiver Effekt, negative Hyperkonjugation und Gegenion sind nicht die Ursache der besonderen Eigenschaften des Bicyclo[3.2.1]octa-3,6-dien-2-yl-Anions. - Eine NMR-Studie mit phenylsubstituierten Modellen
T1  - Inductive Effect, Negative Hyperconjugation, and Gegenion do not Cause the Unusual Properties of the Bicyclo[3.2.1]octa-3,6-dien-2-yl Anion. An NMR Study with Phenyl-Substituted Models
N2  - No abstract available
KW  - Organische Chemie
KW  - Tricyclo[3.3.1.0 2
KW  - 4]non-7-en-6-ylpotassium
KW  - 6-phenyl
KW  - Homoaromaticity in carbanions
KW  - Bicyclo[3.2.1]oct-3-en-2-yl anions
KW  - phenyl-substituted
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58655
ER  - 
TY  - JOUR
A1  - Becker, Jürgen C.
A1  - Andersen, Mads H.
A1  - Hofmeister-Müller, Valeska
A1  - Wobser, Marion
A1  - Frey, Lidia
A1  - Sandig, Christiane
A1  - Walter, Steffen
A1  - Singh-Jasuja, Harpreet
A1  - Kämpgen, Eckhart
A1  - Opitz, Andreas
A1  - Zapatka, Marc
A1  - Bröcker, Eva-B.
A1  - thor Straten, Per
A1  - Schrama, David
A1  - Ugurel, Selma
T1  - Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
JF  - Cancer Immunology, Immunotherapy
N2  - Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.

Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).

Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.

Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
KW  - peptide vaccination
KW  - therapy
KW  - survivin T-cell reactivity
KW  - melanoma
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126215
VL  - 61
IS  - 11
ER  - 
TY  - JOUR
A1  - Becker, Jürgen C.
A1  - Andersen, Mads H.
A1  - Hofmeister-Müller, Valeska
A1  - Wobser, Marion
A1  - Frey, Lidia
A1  - Sandig, Christiane
A1  - Walter, Steffen
A1  - Singh-Jasuja, Harpreet
A1  - Kämpgen, Eckhart
A1  - Opitz, Andreas
A1  - Zapatka, Marc
A1  - Bröcker, Eva-B.
A1  - thor Straten, Per
A1  - Schrama, David
A1  - Ugurel, Selma
T1  - Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
JF  - Cancer Immunology, Immunotherapy
N2  - Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.

Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).

Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.

Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
KW  - peptide vaccination
KW  - melanoma
KW  - survivin
KW  - T-cell reactivity
KW  - therapy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124830
VL  - 61
IS  - 11
ER  - 
TY  - JOUR
A1  - Zentgraf, H.
A1  - Müller, U.
A1  - Scheer, Ulrich
A1  - Franke, W. W.
T1  - Evidence for the existence of globular units in the supranucleosomal organization of chromatin
N2  - No abstract available
Y1  - 1981
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-34123
ER  - 
TY  - JOUR
A1  - Koetschan, Christian
A1  - Kittelmann, Sandra
A1  - Lu, Jingli
A1  - Al-Halbouni, Djamila
A1  - Jarvis, Graeme N.
A1  - Müller, Tobias
A1  - Wolf, Matthias
A1  - Janssen, Peter H.
T1  - Internal Transcribed Spacer 1 Secondary Structure Analysis Reveals a Common Core throughout the Anaerobic Fungi (Neocallimastigomycota)
JF  - PLOS ONE
N2  - The internal transcribed spacer (ITS) is a popular barcode marker for fungi and in particular the ITS1 has been widely used for the anaerobic fungi (phylum Neocallimastigomycota). A good number of validated reference sequences of isolates as well as a large number of environmental sequences are available in public databases. Its highly variable nature predisposes the ITS1 for low level phylogenetics; however, it complicates the establishment of reproducible alignments and the reconstruction of stable phylogenetic trees at higher taxonomic levels (genus and above). Here, we overcame these problems by proposing a common core secondary structure of the ITS1 of the anaerobic fungi employing a Hidden Markov Model-based ITS1 sequence annotation and a helix-wise folding approach. We integrated the additional structural information into phylogenetic analyses and present for the first time an automated sequence-structure-based taxonomy of the ITS1 of the anaerobic fungi. The methodology developed is transferable to the ITS1 of other fungal groups, and the robust taxonomy will facilitate and improve high-throughput anaerobic fungal community structure analysis of samples from various environments.
KW  - profile distances
KW  - ITS2
KW  - phylogenetic trees
KW  - RNA sequence
KW  - reconstruction
KW  - diversity
KW  - populations
KW  - tool
KW  - systematics
KW  - herbivores
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117058
VL  - 9
IS  - 3
ER  - 
TY  - CHAP
A1  - Franke, Werner W.
A1  - Scheer, Ulrich
A1  - Zentgraf, Hanswalter
A1  - Trendelenburg, Michael F.
A1  - Müller, U.
A1  - Krohne, G.
A1  - Spring, H.
T1  - Organization of transcribed and nontranscribed chromatin
N2  - No abstract available
KW  - Tumor / Zellteilung
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40656
ER  - 
TY  - JOUR
A1  - Ulrichs, Karin
A1  - Wang, H.
A1  - Müller-Buchholtz, W.
T1  - Down-regulation of xenophile antibodies by 15-deoxyspergualin in an experimental animal model
N2  - No abstract available
KW  - Chirurgie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-44733
ER  - 
TY  - JOUR
A1  - Schüssler, Ulrich
A1  - Okrusch, M.
A1  - Patzak, M.
A1  - Müller, P.
A1  - Kreuzer, H.
T1  - The polyphase thermal history of the Erbendorf-Vohenstrauß (ZEV) and the Erbendorf Greenschist (EGZ) zones of NE Bavaria in the light of Ar-Ar spectra
N2  - no abstract available
KW  - Erbendorf
KW  - Vohenstrauß
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-81862
ER  - 
TY  - JOUR
A1  - Heiser, A.
A1  - Ulrichs, Karin
A1  - Winoto-Morbach, S.
A1  - Vanucchi, A.
A1  - Jäger, H.
A1  - Müller-Ruchholtz, W.
T1  - Erste Kieler Erfahrungen mit 45 Isolierungen von Langerhansinseln aus Schweinepankreas
N2  - No abstract available.
KW  - Langerhans-Inseln
KW  - Bauchspeicheldrüse
KW  - Schwein
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73205
ER  - 
TY  - JOUR
A1  - Karimi, Sohail M.
A1  - Freund, Matthias
A1  - Wager, Brittney M.
A1  - Knoblauch, Michael
A1  - Fromm, Jörg
A1  - M. Mueller, Heike
A1  - Ache, Peter
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - Geilfus, Christoph-Martin
A1  - Alfaran, Ahmed H.
A1  - Hedrich, Rainer
A1  - Deeken, Rosalia
T1  - Under salt stress guard cells rewire ion transport and abscisic acid signaling
JF  - New Phytologist
N2  - Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads.
We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function.
Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations.
Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.
KW  - soil
KW  - stomata
KW  - abscisic acid (ABA)
KW  - glycophyte Arabidopsis
KW  - guard cell
KW  - halophyte Thellungiella/Eutrema
KW  - ion transport
KW  - salt stress
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259635
VL  - 231
IS  - 3
ER  - 
TY  - JOUR
A1  - Matthes, Philipp R.
A1  - Schönfeld, Fabian
A1  - Zottnick, Sven H.
A1  - Müller-Buschbaum, Klaus
T1  - Post-synthetic shaping of porosity and crystal structure of Ln-Bipy-MOFs by thermal treatment
JF  - Molecules
N2  - The reaction of anhydrous lanthanide chlorides together with 4,4'-bipyridine yields the MOFs \(^{2}\)\(_{∞}\)[Ln\(_{2}\)Cl\(_{6}\)(bipy)\(_{3}\)]*2bipy, with Ln = Pr-Yb, bipy = 4,4'-bipyridine, and \(^{3}\)\(_{∞}\)[La\(_{2}\)Cl\(_{6}\)(bipy)\(_{5}\)]*4bipy. Post-synthetic thermal treatment in combination with different vacuum conditions was successfully used to shape the porosity of the MOFs. In addition to the MOFs microporosity, a tuneable mesoporosity can be implemented depending on the treatment conditions as a surface morphological modification. Furthermore, thermal treatment without vacuum results in several identifiable crystalline high-temperature phases. Instead of collapse of the frameworks upon heating, further aggregation under release of bipy is observed. \(^{3}\)\(_{∞}\)[LaCl\(_{3}\)(bipy)] and \(^{2}\)\(_{∞}\)[Ln\(_{3}\)Cl\(_{9}\)(bipy)\(_{3}\)], with Ln = La, Pr, Sm, and \(^{1}\)\(_{∞}\)[Ho\(_{2}\)Cl\(_{6}\)(bipy)\(_{2}\)] were identified and characterized, which can also exhibit luminescence. Besides being released upon heating, the linker 4,4'-bipyridine can undergo activation of C-C bonding in ortho-position leading to the in-situ formation of 4,4':2',2 '':4 '',4'''-quaterpyridine (qtpy). qtpy can thereby function as linker itself, as shown for the formation of the network \(^{2}\)\(_{∞}\)[Gd\(_{2}\)Cl\(_{6}\)(qtpy)\(_{2}\)(bipy)\(_{2}\)]*bipy. Altogether, the manuscript elaborates the influence of thermal treatment beyond the usual activation procedures reported for MOFs.
KW  - energy transfer
KW  - ligand
KW  - Ln-MOFs
KW  - luminescence crystal structure
KW  - metal-organic frameworks
KW  - shaping of porosity
KW  - thermal treatment
KW  - luminescence
KW  - crystal scructure
KW  - coordination polymers
KW  - solid state
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148404
VL  - 20
ER  - 
TY  - JOUR
A1  - Rau, Monika
A1  - Buggisch, Peter
A1  - Mauss, Stefan
A1  - Boeker, Klaus H. W.
A1  - Klinker, Hartwig
A1  - Müller, Tobias
A1  - Stoehr, Albrecht
A1  - Schattenberg, Jörn M.
A1  - Geier, Andreas
T1  - Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry
JF  - PLoS ONE
N2  - Background
Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients.
Methods
The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores.
Results
At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4–24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m\(^{2}\)) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT.
Conclusion
Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors.
KW  - steatosis
KW  - HCV infection
KW  - liver
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300549
VL  - 17
IS  - 6
ER  - 
TY  - JOUR
A1  - Remmele, Christian W.
A1  - Luther, Christian H.
A1  - Balkenhol, Johannes
A1  - Dandekar, Thomas
A1  - Müller, Tobias
A1  - Dittrich, Marcus T.
T1  - Integrated inference and evaluation of host-fungi interaction networks
JF  - Frontiers in Microbiology
N2  - Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi human and fungi mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host fungi transcriptome and proteome data.
KW  - candida genome database
KW  - computational prediction
KW  - potential role
KW  - network inference
KW  - bioinformatics and computational biology
KW  - protein interaction database
KW  - Aspergillus fumigatus
KW  - cell wall
KW  - functional modules
KW  - alzheimers disease
KW  - molecular cloning
KW  - Candida albicans
KW  - pathogen-host interaction (PHI)
KW  - protein-protein interaction
KW  - pathogenicity
KW  - interolog
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148278
VL  - 6
IS  - 764
ER  - 
TY  - JOUR
A1  - Rinaldetti, Sébastien
A1  - Pfirrmann, Markus
A1  - Manz, Kirsi
A1  - Guilhot, Joelle
A1  - Dietz, Christian
A1  - Panagiotidis, Panayiotidis
A1  - Spiess, Birgit
A1  - Seifarth, Wolfgang
A1  - Fabarius, Alice
A1  - Müller, Martin
A1  - Pagoni, Maria
A1  - Dimou, Maria
A1  - Dengler, Jolanta
A1  - Waller, Cornelius F.
A1  - Brümmendorf, Tim H.
A1  - Herbst, Regina
A1  - Burchert, Andreas
A1  - Janßen, Carsten
A1  - Goebeler, Maria Elisabeth
A1  - Jost, Philipp J.
A1  - Hanzel, Stefan
A1  - Schafhausen, Philippe
A1  - Prange-Krex, Gabriele
A1  - Illmer, Thomas
A1  - Janzen, Viktor
A1  - Klausmann, Martine
A1  - Eckert, Robert
A1  - Büschel, Gerd
A1  - Kiani, Alexander
A1  - Hofmann, Wolf-Karsten
A1  - Mahon, François-Xavier
A1  - Saussele, Susanne
T1  - Effect of ABCG2, OCT1, and ABCB1 (MDR1) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial
JF  - Clinical Lymphoma, Myeloma & Leukemia
N2  - Within the EURO-SKI trial, 132 chronic phase CML patients discontinued imatinib treatment. RNA was isolated from peripheral blood in order to analyze the expression of MDR1, ABCG2 and OCT1. ABCG2 was predictive for treatment-free remission in Cox regression analysis. High transcript levels of the ABCG2 efflux transporter (>4.5 parts per thousand) were associated with a twofold higher risk of relapse. Introduction: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. Materials and Methods: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial. Plasmid standards were designed including subgenic inserts of OCT1, ABCG2, and ABCB1 together with GUSB as reference gene. For expression analyses, quantitative real-time polymerase chain reaction was used. Multiple Cox regression analysis was performed. In addition, gene expression cutoffs for patient risk stratification were investigated. Results: The TFR rate of 132 patients, 12 months after TKI discontinuation, was 54% (95% confidence interval [CI], 46%-62%). ABCG2 expression (parts per thousand) was retained as the only significant variable (P=.02; hazard ratio, 1.04; 95% CI, 1.01-1.07) in multiple Cox regression analysis. Only for the ABCG2 efflux transporter, a significant cutoff was found (P=.04). Patients with an ABCG2/GUSB transcript level >4.5 parts per thousand (n=93) showed a 12-month TFR rate of 47% (95% CI, 37%-57%), whereas patients with low ABCG2 expression (<= 4.5 parts per thousand; n=39) had a 12-month TFR rate of 72% (95% CI, 55%-82%). Conclusion: In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation. (C) 2018 The Authors. Published by Elsevier Inc.
KW  - ABCG2
KW  - Biomarker
KW  - CML
KW  - Imatinib
KW  - Prediction
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226281
VL  - 18
IS  - 4
ER  - 
TY  - JOUR
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Kramer, Michael
A1  - Röllig, Christoph
A1  - Krämer, Alwin
A1  - Scholl, Sebastian
A1  - Hochhaus, Andreas
A1  - Crysandt, Martina
A1  - Brümmendorf, Tim H.
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Kunzmann, Volker
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Herbst, Regina
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Baldus, Claudia D.
A1  - Kaufmann, Martin
A1  - Rácil, Zdenek
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Mayer, Jiří
A1  - Serve, Hubert
A1  - Müller-Tidow, Carsten
A1  - Ehninger, Gerhard
A1  - Stölzel, Friedrich
A1  - Kroschinsky, Frank
A1  - Schetelig, Johannes
A1  - Bornhäuser, Martin
A1  - Thiede, Christian
A1  - Middeke, Jan Moritz
T1  - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
JF  - Cancers
N2  - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735
SN  - 2072-6694
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Schumann, S.
A1  - Eberlein, U.
A1  - Lapa, C.
A1  - Müller, J.
A1  - Serfling, S.
A1  - Lassmann, M.
A1  - Scherthan, H.
T1  - α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [\(^{223}\)Ra]RaCl\(_{2}\)-treated prostate cancer patients
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
One therapy option for prostate cancer patients with bone metastases is the use of [\(^{223}\)Ra]RaCl\(_{2}\). The α-emitter \(^{223}\)Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [\(^{223}\)Ra]RaCl\(_{2}\).
Methods
Multiple blood samples from nine prostate cancer patients were collected before and after administration of [\(^{223}\)Ra]RaCl\(_{2}\), up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs.
Results
The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h - 4 weeks after administration), the α-track frequency remained elevated.
Conclusion
The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.
KW  - γ-H2AX
KW  - DNA damage
KW  - nuclear medicine
KW  - dosimetry
KW  - α-Emitter
KW  - biokinetics
KW  - prostate cancer
KW  - [\(^{223}\)Ra]RaCl\(_{2}\)
KW  - 53BP1
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265462
SN  - 1619-7089
VL  - 48
IS  - 9
ER  - 
TY  - JOUR
A1  - Hofrichter, Michaela A. H.
A1  - Mojarad, Majid
A1  - Doll, Julia
A1  - Grimm, Clemens
A1  - Eslahi, Atiye
A1  - Hosseini, Neda Sadat
A1  - Rajati, Mohsen
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - Maroofian, Reza
A1  - Haaf, Thomas
A1  - Vona, Barbara
T1  - The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family
JF  - BMC Medical Genetics
N2  - Background:
Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family.

Methods:
Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed.

Results:
The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change.

Conclusion:
In summary, we report the third overall mutation in S1PR2 and the first report outside the Pakistani population. Furthermore, we describe a novel variant that causes an amino acid exchange (p.Arg108Gln) in the same amino acid residue as one of the previously reported Pakistani families (p.Arg108Pro). This finding emphasizes the importance of the p.Arg108 amino acid in normal hearing and confirms and consolidates the role of S1PR2 in autosomal recessive hearing loss.
KW  - 3D modeling
KW  - autosomal recessive non-synstromic hearing loss
KW  - DFNB68
KW  - mixed hearing loss
KW  - whole exome sequencing
KW  - S1PR2
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175755
VL  - 19
IS  - 81
ER  - 
TY  - JOUR
A1  - Doll, Julia
A1  - Vona, Barbara
A1  - Schnapp, Linda
A1  - Rüschendorf, Franz
A1  - Khan, Imran
A1  - Khan, Saadullah
A1  - Muhammad, Noor
A1  - Alam Khan, Sher
A1  - Nawaz, Hamed
A1  - Khan, Ajmal
A1  - Ahmad, Naseer
A1  - Kolb, Susanne M.
A1  - Kühlewein, Laura
A1  - Labonne, Jonathan D. J.
A1  - Layman, Lawrence C.
A1  - Hofrichter, Michaela A. H.
A1  - Röder, Tabea
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Graves, Tyler D.
A1  - Kong, Il-Keun
A1  - Nanda, Indrajit
A1  - Kim, Hyung-Goo
A1  - Haaf, Thomas
T1  - Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families
JF  - Genes
N2  - The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.
KW  - genetic diagnosis
KW  - consanguinity
KW  - genome-wide linkage analysis
KW  - hearing loss
KW  - Pakistan
KW  - exome sequencing
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219293
SN  - 2073-4425
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Zottnick, Sven H.
A1  - Sprenger, Jan A. P.
A1  - Finze, Maik
A1  - Müller‐Buschbaum, Klaus
T1  - Statistic Replacement of Lanthanide Ions in Bis‐salicylatoborate Coordination Polymers for the Deliberate Control of the Luminescence Chromaticity
JF  - ChemistryOpen
N2  - Based on the strand‐like coordination polymer (CP) type \(^{1}\)\(_{∞}\)[Ln(BSB)\(_{3}\)(py)\(_{2}\)], [BSB]−=bis‐salicylatoborate anion, mixed Eu/Tb‐containing compounds of the constitution \(^{1}\)\(_{∞}\)[Eu\(_{x}\)Tb\(_{1-x}\)(BSB)\(_{3}\)(py)\(_{2}\)] were synthesised ionothermally for a phase width of (x=0.25–0.75) and characterized regarding structure and optical properties. Previously, known only for other lanthanides, the mixed 1D−Eu/Tb‐CPs show excellent options for statistic replacement of the Ln‐cations during synthesis yielding solid solutions. The products are highly luminescent, with the chromaticity being a direct function of the amount of the respective Ln‐ions. Corresponding to an overall addition of emission intensities, the green Tb\(^{3+}\) emission and the red Eu\(^{3+}\) emission allow for a chromaticity control that also includes yellow emission. Control of the luminescence colour renders them suitable examples of the versatility of statistic replacement of metal ions in coordination chemistry. In addition, crystallization of [EMIm]\(_{2}\)[YCl\(_{5}\)(py)] illuminates possible other products of the ionothermal reactions of [EMIm][BSB] with LnCl\(_{3}\) constituted by components not being part of the main CPs.
KW  - borates
KW  - coordination polymers
KW  - ionic liquids
KW  - lanthanides
KW  - luminescence
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239953
VL  - 10
IS  - 2
SP  - 164
EP  - 170
ER  - 
TY  - JOUR
A1  - Müller, Jörg
A1  - Mitesser, Oliver
A1  - Schaefer, H. Martin
A1  - Seibold, Sebastian
A1  - Busse, Annika
A1  - Kriegel, Peter
A1  - Rabl, Dominik
A1  - Gelis, Rudy
A1  - Arteaga, Alejandro
A1  - Freile, Juan
A1  - Leite, Gabriel Augusto
A1  - de Melo, Tomaz Nascimento
A1  - LeBien, Jack
A1  - Campos-Cerqueira, Marconi
A1  - Blüthgen, Nico
A1  - Tremlett, Constance J.
A1  - Böttger, Dennis
A1  - Feldhaar, Heike
A1  - Grella, Nina
A1  - Falconí-López, Ana
A1  - Donoso, David A.
A1  - Moriniere, Jerome
A1  - Buřivalová, Zuzana
T1  - Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests
JF  - Nature Communications
N2  - Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures – an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data.
KW  - animal behaviour
KW  - conservation biology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358130
VL  - 14
ER  - 
TY  - JOUR
A1  - Luther, Christian H.
A1  - Brandt, Philipp
A1  - Vylkova, Slavena
A1  - Dandekar, Thomas
A1  - Müller, Tobias
A1  - Dittrich, Marcus
T1  - Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.
KW  - sky kinases
KW  - kinase signaling
KW  - network analysis
KW  - transcriptome
KW  - transcriptional regulation
KW  - phosphoproteome
KW  - Candida albicans
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311771
SN  - 2235-2988
VL  - 13
ER  - 
TY  - JOUR
A1  - Righesso, L. A. R.
A1  - Terekhov, M.
A1  - Götz, H.
A1  - Ackermann, M.
A1  - Emrich, T.
A1  - Schreiber, L. M.
A1  - Müller, W. E. G.
A1  - Jung, J.
A1  - Rojas, J. P.
A1  - Al-Nawas, B.
T1  - Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration — a randomized in vivo study in rabbits
JF  - Clinical Oral Investigations
N2  - Objectives
Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated.

Materials and methods
Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology.

Results
The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed.

Conclusions
These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.
KW  - animal experimentation
KW  - bone regeneration
KW  - multiparametric magnetic resonance imaging
KW  - neovascularization, physiologic
KW  - tissue engineering
KW  - translational medical research
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307614
SN  - 1432-6981
SN  - 1436-3771
VL  - 25
IS  - 10
ER  - 
TY  - JOUR
A1  - Korth, H.-G.
A1  - Müller, W.
A1  - Sustmann, R.
A1  - Christl, Manfred
T1  - Rearrangement of Free Radicals, XII. ESR Spectroscopic Study of the Ring Opening of the Homobenzvalenyl Radical
N2  - Abstraction of an allylic hydrogen atom in homobenzvalene (4) either in solurion by photolyticaßy generated tert-butoxyl radicals or in an adamantane matrix by X-rays produces the homobcnzvalenyl radical (5). which tbennally rearranps · to tbe tropylium ndical (1). In solution tbe activation cnergy for the rate determined step of the reaction sequence was detennined· to be 13.4 ± O.S kcal/mol.
KW  - Organische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58376
ER  - 
TY  - JOUR
A1  - Müller, S.
A1  - Spriestersbach, F.
A1  - Min, C.-H.
A1  - Fornari, C. I.
A1  - Reinert, F.
T1  - Molecular beam epitaxy of TmTe thin films on SrF\(_{2}\) (111)
JF  - AIP Advances
N2  - The odd parity nature of 4f states characterized by strong spin–orbit coupling and electronic correlations has led to a search for novel topological phases among rare earth compounds, such as Kondo systems, heavy Fermions, and homogeneous mixed-valent materials. Our target system is thulium telluride thin films whose bandgap is expected to be tuned as a function of lattice parameter. We systematically investigate the growth conditions of TmxTey thin films on SrF\(_{2}\) (111) substrates by molecular beam epitaxy. The ratio between Te and Tm supply was precisely tuned, resulting in two different crystalline phases, which were confirmed by x-ray diffraction and x-ray photoemission spectroscopy. By investigating the crystalline quality as a function of the substrate temperature, the optimal growth conditions were identified for the desired Tm1Te1 phase. Additional low energy electron diffraction and reflective high energy electron diffraction measurements confirm the epitaxial growth of TmTe layers. X-ray reflectivity measurements demonstrate that homogeneous samples with sharp interfaces can be obtained for varied thicknesses. Our results provide a reliable guidance to prepare homogeneous high-quality TmTe thin films and thus serve as a basis for further electronic investigations.
KW  - thulium telluride
KW  - molecular beam epitaxy
KW  - thin films
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300876
VL  - 12
IS  - 2
ER  -