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265 Publications visible to you, out of a total of 265
Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.
LIFE Adult

Abstract (Expand)

Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases … have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 +/- 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 +/- 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity.

Authors: K. Mueller, K. Arelin, H. E. Moller, J. Sacher, J. Kratzsch, T. Luck, S. Riedel-Heller, A. Villringer, M. L. Schroeter

Date Published: 2nd Feb 2016

Publication Type: Not specified

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).
LIFE Adult

Abstract (Expand)

OBJECTIVE: Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, … however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. METHODS: Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. RESULTS: Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. CONCLUSION: Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Authors: S. Roehr, T. Luck, K. Heser, A. Fuchs, A. Ernst, B. Wiese, J. Werle, H. Bickel, C. Brettschneider, A. Koppara, M. Pentzek, C. Lange, J. Prokein, S. Weyerer, E. Mosch, H. H. Konig, W. Maier, M. Scherer, F. Jessen, S. G. Riedel-Heller

Date Published: 15th Jan 2016

Publication Type: Not specified

Human Diseases: dementia

[IT infrastructures in patient-oriented research. Current status and need for action 2015]
LIFE - Leipzig Research Center for Civilization Diseases

Abstract

Not specified

Authors: U.Sax, C. Bauer, T. Ganslandt, T. Kirsten

Date Published: 2016

Publication Type: Not specified

Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma.
LIFE - Leipzig Research Center for Civilization Diseases, Genetical Statistics and Systems Biology

Abstract (Expand)

Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break-through, but levels differences in chemotherapy. … Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo-immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential.

Authors: K. Rosch, M. Scholz, D. Hasenclever

Date Published: 16th Dec 2015

Publication Type: Not specified

Human Diseases: lymphoma

The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.
LIFE HNC - Head and Neck Cancer Group, Genetical Statistics and Systems Biology

Abstract (Expand)

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We … characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.

Authors: G. Wichmann, M. Rosolowski, K. Krohn, M. Kreuz, A. Boehm, A. Reiche, U. Scharrer, D. Halama, J. Bertolini, U. Bauer, D. Holzinger, M. Pawlita, J. Hess, C. Engel, D. Hasenclever, M. Scholz, P. Ahnert, H. Kirsten, A. Hemprich, C. Wittekind, O. Herbarth, F. Horn, A. Dietz, M. Loeffler

Date Published: 15th Dec 2015

Publication Type: Not specified

Human Diseases: head and neck cancer

Incremental value of Veterans Specific Activity Questionnaire and the YMCA-step test for the assessment of cardiorespiratory fitness in population-based studies.
LIFE Heart

Abstract (Expand)

BACKGROUND: Cardiorespiratory fitness is a well-established independent predictor of cardiovascular health. However, the relevance of alternative exercise and non-exercise tests for cardiorespiratory … fitness assessment in large cohorts has not been studied in detail. We aimed to evaluate the YMCA-step test and the Veterans Specific Activity Questionnaire (VSAQ) for the estimation of cardiorespiratory fitness in the general population. METHODS: One hundred and five subjects answered the VSAQ, performed the YMCA-step test and a maximal cardiopulmonary exercise test (CPX) and gave BORG ratings for both exercise tests (BORGSTEP, BORGCPX). Correlations of peak oxygen uptake on a treadmill (VO2_PEAK) with VSAQ, BORGSTEP, one-minute, post-exercise heartbeat count, and peak oxygen uptake during the step test (VO2_STEP) were determined. Moreover, the incremental values of the questionnaire and the step test in addition to other fitness-related parameters were evaluated using block-wise hierarchical regression analysis. RESULTS: Eighty-six subjects completed the step test according to the protocol. For completers, correlations of VO2_PEAK with the age- and gender-adjusted VSAQ, heartbeat count and VO2_STEP were 0.67, 0.63 and 0.49, respectively. However, using hierarchical regression analysis, age, gender and body mass index already explained 68.8% of the variance of VO2_PEAK, while the additional benefit of VSAQ was rather low (3.4%). The inclusion of BORGSTEP, heartbeat count and VO2_STEP increased R(2) by a further 2.2%, 3.3% and 5.6%, respectively, yielding a total R(2) of 83.3%. CONCLUSIONS: Neither VSAQ nor the YMCA-step test contributes sufficiently to the assessment of cardiorespiratory fitness in population-based studies.

Authors: A. Teren, S. Zachariae, F. Beutner, R. Ubrich, M. Sandri, C. Engel, M. Loffler, S. Gielen

Date Published: 15th Dec 2015

Publication Type: Not specified

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

INTRODUCTION Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA …A alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. METHODS We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. RESULTS We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

Authors: Sophie Blein, Claire Bardel, Vincent Danjean, Lesley McGuffog, Sue Healey, Daniel Barrowdale, Andrew Lee, Joe Dennis, Karoline B. Kuchenbaecker, Penny Soucy, Mary Beth Terry, Wendy K. Chung, David E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Laima Tihomirova, Nadine Tung, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Susan L. Neuhausen, Yuan Chun Ding, Anne-Marie Gerdes, Bent Ejlertsen, Finn C. Nielsen, Thomas vO Hansen, Ana Osorio, Javier Benitez, Raquel Andrés Conejero, Ena Segota, Jeffrey N. Weitzel, Margo Thelander, Paolo Peterlongo, Paolo Radice, Valeria Pensotti, Riccardo Dolcetti, Bernardo Bonanni, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Siranoush Manoukian, Liliana Varesco, Gabriele L. Capone, Laura Papi, Laura Ottini, Drakoulis Yannoukakos, Irene Konstantopoulou, Judy Garber, Ute Hamann, Alan Donaldson, Angela Brady, Carole Brewer, Claire Foo, D. Gareth Evans, Debra Frost, Diana Eccles, Fiona Douglas, Jackie Cook, Julian Adlard, Julian Barwell, Lisa Walker, Louise Izatt, Lucy E. Side, M. John Kennedy, Marc Tischkowitz, Mark T. Rogers, Mary E. Porteous, Patrick J. Morrison, Radka Platte, Ros Eeles, Rosemarie Davidson, Shirley Hodgson, Trevor Cole, Andrew K. Godwin, Claudine Isaacs, Kathleen Claes, Kim de Leeneer, Alfons Meindl, Andrea Gehrig, Barbara Wappenschmidt, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Hansjoerg Plendl, Karin Kast, Kerstin Rhiem, Nina Ditsch, Norbert Arnold, Raymonda Varon-Mateeva, Rita K. Schmutzler, Sabine Preisler-Adams, Nadja Bogdanova Markov, Shan Wang-Gohrke, Antoine de Pauw, Cédrick Lefol, Christine Lasset, Dominique Leroux, Etienne Rouleau, Francesca Damiola, Hélène Dreyfus, Laure Barjhoux, Lisa Golmard, Nancy Uhrhammer, Valérie Bonadona, Valérie Sornin, Yves-Jean Bignon, Jonathan Carter, Linda van Le, Marion Piedmonte, Paul A. DiSilvestro, Miguel de La Hoya, Trinidad Caldes, Heli Nevanlinna, Kristiina Aittomäki, Agnes Jager, Ans Mw van den Ouweland, Carolien M. Kets, Cora M. Aalfs, Flora E. van Leeuwen, Frans Bl Hogervorst, Hanne Ej Meijers-Heijboer, Jan C. Oosterwijk, Kees Ep van Roozendaal, Matti A. Rookus, Peter Devilee, Rob B. van der Luijt, Edith Olah, Orland Diez, Alex Teulé, Conxi Lazaro, Ignacio Blanco, Jesús Del Valle, Anna Jakubowska, Grzegorz Sukiennicki, Jacek Gronwald, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Bjarni A. Agnarsson, Christine Maugard, Alberto Amadori, Marco Montagna, Manuel R. Teixeira, Amanda B. Spurdle, William Foulkes, Curtis Olswold, Noralane M. Lindor, Vernon S. Pankratz, Csilla I. Szabo, Anne Lincoln, Lauren Jacobs, Marina Corines, Mark Robson, Joseph Vijai, Andreas Berger, Anneliese Fink-Retter, Christian F. Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng Tea, Mark H. Greene, Phuong L. Mai, Gad Rennert, Evgeny N. Imyanitov, Anna Marie Mulligan, Gord Glendon, Irene L. Andrulis, Sandrine Tchatchou, Amanda Ewart Toland, Inge Sokilde Pedersen, Mads Thomassen, Torben A. Kruse, Uffe Birk Jensen, Maria A. Caligo, Eitan Friedman, Jamal Zidan, Yael Laitman, Annika Lindblom, Beatrice Melin, Brita Arver, Niklas Loman, Richard Rosenquist, Olufunmilayo I. Olopade, Robert L. Nussbaum, Susan J. Ramus, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Banu K. Arun, Gillian Mitchell, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Dominique Stoppa-Lyonnet, Gilles Thomas, Jacques Simard, Fergus J. Couch, Kenneth Offit, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Sylvie Mazoyer, Catherine M. Phelan, Olga M. Sinilnikova, David G. Cox

Date Published: 1st Dec 2015

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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