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 - 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. 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 - 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 - Müller-Buchholtz, W. A1 - Leyhausen, G. A1 - Peterson, P. A1 - Schubert, G. A1 - Ulrichs, Karin T1 - A simple methodological principle for large scale extraction and purification of collagenase-digested islets N2 - No abstract available KW - Chirurgie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-44770 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 - 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, Thomas A1 - Rethwilm, Axel A1 - terMeulen, Volker 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 N2 - No abstract available Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32583 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 - 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 - Winoto-Morbach, S. A1 - Leyhausen, G. A1 - Schünke, M. A1 - Ulrichs, Karin A1 - Müller-Buchholtz, W. T1 - Magnetic microspheres (MMS) coupled to selective lectins: a new tool for large-scale extraction and purification of human pancreatic islets N2 - No abstract available KW - Chirurgie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-44789 ER - TY - JOUR A1 - Eckstein, V. A1 - Ulrichs, K. A1 - Meincke, G. A1 - Müller-Ruchholtz, W. T1 - Natural xenophile antibodies from sera of type I diabetic patients differ strongly in their reactivity against various porcine pancreatic cells N2 - No abstract available KW - Chirurgie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45277 ER - TY - CHAP A1 - Hedke, K. A1 - Eckstein, V. A1 - May, G. A1 - Kaden, J. A1 - Müller-Ruchholtz, W. A1 - Ulrichs, Karin T1 - Production of Xenophile Antibodies (XA) in Type I Diabetic Patients is Strongly Influenced by Diabetes and/or Dialysis N2 - No abstract available Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45642 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 - Brinkmann, R. A1 - Schwinn, A. A1 - Müller, J. A1 - Stahl-Hennig, C. A1 - Coulibaly, C. A1 - Hunsmann, G. A1 - Czub, S. A1 - Rethwilm, Axel A1 - Dörries, R. A1 - ter Meulen, Volker T1 - In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus N2 - The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue. KW - Virologie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61415 ER - TY - JOUR A1 - Ludwig, K. U. A1 - Sämann, P. A1 - Alexander, M. A1 - Becker, J. A1 - Bruder, J. A1 - Moll, K. A1 - Spieler, D. A1 - Czisch, M. A1 - Warnke, A. A1 - Docherty, S. J. A1 - Davis, O. S. P. A1 - Plomin, R. A1 - Nöthen, M. M. A1 - Landerl, K. A1 - Müller-Myhsok, B. A1 - Hoffmann, P. A1 - Schumacher, J. A1 - Schulte-Körne, G. A1 - Czamara, D. T1 - A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults JF - Translational Psychiatry N2 - The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype. KW - disability KW - sulcal morphology KW - prelevance KW - identification KW - brain KW - cancer KW - association KW - developmental dyscalculia KW - tumor-suppressor gene KW - correlate KW - disorders KW - dyscalculia KW - dyslexia KW - genomic imaging KW - mathematics KW - quantitative trait Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131513 N1 - Supplementary Information accompanies the paper on the Translational Psychiatry website (http://www.nature.com/tp). VL - 3 IS - e229 ER - TY - JOUR A1 - Gentschev, Ivaylo A1 - Müller, Meike A1 - Adelfinger, Marion A1 - Weibel, Stephanie A1 - Grummt, Friedrich A1 - Zimmermann, Martina A1 - Bitzer, Michael A1 - Heisig, Martin A1 - Zhang, Qian A1 - Yu, Yong A. A1 - Chen, Nanhai G. A1 - Stritzker, Jochen A1 - Lauer, Ulrich M. A1 - Szalay, Aladar A. T1 - Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68 JF - PLOS ONE N2 - Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man. KW - Breast-tumors KW - Nude-mice KW - In-vivo KW - Cancer KW - Inhibitor KW - Tissue KW - Agent KW - COX-2 Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135319 VL - 6 IS - 7 ER - TY - JOUR A1 - Semmler, Anna-Lena A1 - Sacconi, Sabrina A1 - Bach, J. Elisa A1 - Liebe, Claus A1 - Bürmann, Jan A1 - Kley, Rudolf A. A1 - Ferbert, Andreas A1 - Anderheiden, Roland A1 - Van den Bergh, Peter A1 - Martin, Jean-Jacques A1 - De Jonghe, Peter A1 - Neuen-Jacob, Eva A1 - Müller, Oliver A1 - Deschauer, Marcus A1 - Bergmann, Markus A1 - Schröder, J. Michael A1 - Vorgerd, Matthias A1 - Schulz, Jörg B. A1 - Weis, Joachim A1 - Kress, Wolfram A1 - Claeys, Kristl G. T1 - Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies JF - Orphanet Journal of Rare Diseases N2 - Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p. Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p. Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim. KW - polyneuropathy KW - MFM KW - next generation sequencing KW - bcl-2 associated athanogene protein 3 KW - protein aggregation KW - hearing impairment KW - early respiratory-failure KW - myopathy KW - muscular-dystrophy KW - skeletal myopathy Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115623 SN - 1750-1172 N1 - Additional files are available here: http://www.ojrd.com/content/9/1/121/additional VL - 9 IS - 121 ER - TY - JOUR A1 - Winoto-Morbach, S. A1 - Leyhausen, G. A1 - Müller-Ruchholtz, W. A1 - Ulrichs, Karin T1 - The Electromagnetic Separation Principle: A Basis for Human Pancreatic Islet Transplantation N2 - No abstract available KW - Allergie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82520 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 -