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  -