Both A.,Hannover Medical School |
Both A.,University of Hamburg |
Krauter J.,Hannover Medical School |
Damm F.,Hannover Medical School |
And 16 more authors.
Annals of Hematology | Year: 2017
Hypomorphic germline variants in TERT, the gene encoding the reverse transcriptase component of the human telomerase complex, occur with a frequency of 3–5% in acute myeloid leukemia. We analyzed the clinical and prognostic impact of the most common TERT A1062T variant in younger patients with acute myeloid leukemia intensively treated within two prospective multicenter trials. Four hundred and twenty patients (age 17–60 years) were analyzed for the TERT A1062T variant by direct sequencing. Fifteen patients (3.6%) carried the TERT A1062T variant. Patients with the TERT A1062T variant had a trend towards less favorable and more intermediate 2/adverse karyotypes/genotypes according to the European Leukemia Net classification. In univariate and multivariate analysis, patients with the TERT A1062T variant had a significantly inferior overall survival compared to wild-type patients (6-year overall survival 20 vs. 41%, p = 0.005). Patients with the TERT A1062T variant showed a high rate of treatment-related mortality: 5/15 (33%) died during induction therapy or in complete remission as compared to 62/405 (15%) of the wild-type patients. In patients with the TERT variant, 14/15 (93%) suffered from non-hematological/non-infectious grade 3/4 adverse events (mostly hepatic and/or mucosal) as compared to 216/405 (53%) wild-type patients (p = 0.006). In multivariate analysis, the TERT A1062T variant was an independent risk factor predicting for adverse events during induction chemotherapy. In conclusion, the TERT A1062T variant is an independent negative prognostic factor in younger patients with acute myeloid leukemia and seems to predispose those patients to treatment-related toxicity. © 2017 Springer-Verlag Berlin Heidelberg
Ritter P.,Max Planck Institute for Human Cognitive and Brain Sciences |
Ritter P.,Bernstein Center for Computational Neuroscience |
Ritter P.,ChariteUniversity Medicine |
Ritter P.,Humboldt University of Berlin |
And 4 more authors.
Brain Connectivity | Year: 2013
Brain function is thought to emerge from the interactions among neuronal populations. Apart from traditional efforts to reproduce brain dynamics from the micro- to macroscopic scales, complementary approaches develop phenomenological models of lower complexity. Such macroscopic models typically generate only a few selected—ideally functionally relevant—aspects of the brain dynamics. Importantly, they often allow an understanding of the underlying mechanisms beyond computational reproduction. Adding detail to these models will widen their ability to reproduce a broader range of dynamic features of the brain. For instance, such models allow for the exploration of consequences of focal and distributed pathological changes in the system, enabling us to identify and develop approaches to counteract those unfavorable processes. Toward this end, The Virtual Brain (TVB), a neuroinformatics platform with a brain simulator that incorporates a range of neuronal models and dynamics at its core, has been developed. This integrated framework allows the model-based simulation, analysis, and inference of neurophysiological mechanisms over several brain scales that underlie the generation of macroscopic neuroimaging signals. In this article, we describe how TVB works, and we present the first proof of concept. © 2013, Mary Ann Liebert, Inc. All rights reserved.
Siepert A.,University of Rostock |
Brosel S.,Charité - Medical University of Berlin |
Vogt K.,Charité - Medical University of Berlin |
Ahrlich S.,Charité - Medical University of Berlin |
And 14 more authors.
American Journal of Transplantation | Year: 2013
To ensure safety tolerance induction protocols are accompanied by conventional immunosuppressive drugs (IS). But IS such as calcineurin inhibitors (CNI), for example, cyclosporin A (CsA), can interfere with tolerance induction. We investigated the effect of an additional transient CsA treatment on anti-CD4mAb-induced tolerance induction upon rat kidney transplantation. Additional CsA treatment induced deteriorated graft function, resulting in chronic rejection characterized by glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular changes. Microarray analysis revealed enhanced intragraft expression of the B cell attracting chemokine CXCL13 early during CsA treatment. Increase in CXCL13 expression is accompanied by enhanced B cell infiltration with local and systemic IgG production and C3d deposition as early as 5 days upon CsA withdrawal. Adding different CNIs to cultures of primary mesangial cells isolated from glomeruli resulted in a concentration-dependent increase in CXCL13 transcription. CsA in synergy with TNF-α can enhance the B cell attracting and activating potential of mesangial cells. Transient B cell depletion or transfer of splenocytes from tolerant recipients 3 weeks after transplantation could rescue tolerance induction and did inhibit intragraft B cell accumulation, alloantibody production and ameliorate chronic rejection. Transient coapplication of cyclosporine A abrogates CD4-specific monoclonal antibody-mediated transplant tolerance by inducing intragraft CXCL13 expression leading to B cell attraction, alloantibody production and complement-mediated tissue destruction. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
Kremer S.,CNRS Computer Science and Engineering Laboratory |
Kremer S.,Hopitaux Universitaires Of Strasbourg |
Renard F.,French National Center for Scientific Research |
Achard S.,French National Center for Scientific Research |
And 52 more authors.
JAMA Neurology | Year: 2015
Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease. Copyright 2015 American Medical Association. All rights reserved.
Benson S.,University of Duisburg - Essen |
Arck P.C.,ChariteUniversity Medicine |
Blois S.,ChariteUniversity Medicine |
Blois S.,University College London |
And 2 more authors.
Stress | Year: 2011
Subclinical depressive symptoms constitute a primary risk factor for major depression as well as for cardiovascular conditions, which may be mediated by endocrine or immune alterations. The aim of this study was to assess the association between the extent of subclinical depressive symptoms and neuroendocrine and immune cell responses to acute psychosocial stress in healthy females. In N 33 healthy premenopausal women, state anxiety, plasma adrenocorticotropic hormone and serum cortisol, and interleukin-6 (IL-6) concentration responses to public speaking stress were assessed. Beck depression inventory (BDI) scores were entered as a covariate in the analyses. The IL-6 response was significantly associated with BDI scores (p < 0.05). Secondary analyses revealed that women with more subclinical depressive symptoms demonstrated a reduced stress-induced increase in circulating IL-6 level (p < 0.05). By contrast, stress-induced neuroendocrine activation was not associated with depressive symptoms. Hence, subclinical depressive symptoms were associated with IL-6 responses to stress in young, healthy women. Unexpectedly, there was a reduced increase of serum IL-6 level in response to stress. Effects of depressive symptoms on the IL-6 response to stress may differ between subclinical and major depression. © 2010 Informa Healthcare USA, Inc.
Schmidt A.F.,Medical School Hamburg |
Babchishin K.M.,University of Ottawa |
Lehmann R.J.B.,ChariteUniversity Medicine
Archives of Sexual Behavior | Year: 2016
Due to unobtrusiveness and ease of implementation, viewing time (VT) measures of sexual interest in children have sparked increasing research interest in forensic contexts over the last two decades. The current study presents two meta-analyses of VT measures adapted to assess pedophilic interest to determine their discrimination between sexual offenders against children (SOC) and non-SOC groups as well as convergent validity (associations with other measures of sexual interest in children). On average, VT measures showed moderate discrimination between criterion groups (fixed-effect d = 0.60, 95 % CI [0.51, 0.68], N = 2705, k = 14) and significant convergent validity with self-reports, penile plethysmography, Implicit Association Tests, and offence behavioral measures ranging from r = .18 to r = .38. VT measures, however, provided better discrimination for adults (fixed-effect d = 0.78, 95 % CI [0.64, 0.92]) than adolescent samples (fixed-effect d = 0.50, 95 % CI [0.40, 0.61]), Qbetween = 9.37, p = .002. Moreover, compared to absolute scores, using pedophilic difference scores within adult samples substantially increased VT measures’ validity (fixed-effect d = 1.03, 95 % CI [0.82, 1.25], N = 414, k = 7). Results are discussed in terms of their theoretical and applied implications for forensic contexts. © 2016 Springer Science+Business Media New York
Seidel C.,University of Hamburg |
Busch J.,ChariteUniversity Medicine |
Weikert S.,Vivantes Humboldt Klinikum |
Steffens S.,Hannover Medical School |
And 2 more authors.
British Journal of Cancer | Year: 2013
Background:The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship.Methods:A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation:-100% to-60%;-59% to-30% and-29% to 0% TS or gain of tumour size from 1% to 19% and ≥20% or occurrence of new lesions (i.e., progressive disease).Results:The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624).Conclusion:The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies. © 2013 Cancer Research UK.
Eggert T.,ChariteUniversity Medicine |
Sauter C.,ChariteUniversity Medicine |
Dorn H.,ChariteUniversity Medicine |
Peter A.,ChariteUniversity Medicine |
And 3 more authors.
Somnologie | Year: 2015
Objective: The purpose of the present analysis was to quantify the magnitude of intersubject and intrasubject variation of sleep spindle characteristics in a sample of healthy young males.Materials and methods: A total of 32 volunteers (age range 20–30 years) participated in a crossover study aimed at investigating possible effects of Terrestrial Trunked Radio (TETRA) signals on cognitive performance and human brain activity during sleep and waking. Sleep was polysomnographically assessed on nine identically organized study nights per individual. The inter- and intraindividual variability of automatically detected stage 2 non-rapid eye movement (NREM) sleep spindle (11–16 Hz) characteristics (number, density, duration, frequency, amplitude) derived from C3-A2 was determined. Stability of individual differences and the underlying variations were quantified using intraclass correlation (ICC) and coefficients of variation (CV), respectively. Note that there was no significant exposure effect on the considered sleep spindle characteristics.Results: All sleep spindle variables showed an ICC coefficient higher than 0.8, indicating almost perfect stability of interindividual differences. Interindividual variability differed strongly between the considered spindle parameters (CV range: 2–53 %). Intraindividual variability was for all parameters less pronounced (mean CV range: 1–24 %), but their ratios underline the high degree of individuality of each of the investigated parameters.Conclusion: The present analysis confirms the strong individual night-to-night stability of sleep spindle characteristics reported by previous studies. The results provide further evidence for treating sleep spindles as a possible trait, an issue which should be considered in studies relying on a parallel-group design. These data can also be used as reference values. © 2015, Springer-Verlag Berlin Heidelberg.