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960 Publications visible to you, out of a total of 960
Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.
LIFE Adult

Abstract (Expand)

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, … particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.

Authors: S. Teipel, T. Raiser, L. Riedl, I. Riederer, M. L. Schroeter, S. Bisenius, A. Schneider, J. Kornhuber, K. Fliessbach, A. Spottke, M. J. Grothe, J. Prudlo, J. Kassubek, A. Ludolph, B. Landwehrmeyer, S. Straub, M. Otto, A. Danek

Date Published: 11th Aug 2016

Publication Type: Journal article

Human Diseases: aphasia

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body … scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease.

Authors: H. Loffler-Wirth, E. Willscher, P. Ahnert, K. Wirkner, C. Engel, M. Loeffler, H. Binder

Date Published: 29th Jul 2016

Publication Type: Not specified

Human Diseases: obesity

Response to the letter on 'Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses'.
LIFE Adult

Abstract

Not specified

Authors: S. Bisenius, J. Neumann, M. L. Schroeter

Date Published: 20th Jul 2016

Publication Type: Not specified

Human Diseases: dementia, aphasia

Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. …. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. METHODS 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. RESULTS 33/166 (19.9%) patients died during follow-up. Lower values of valine (p\textless0.001), Fischer’s ratio (p\textless0.001) and valine to phenylalanine ratio (p\textless0.001) and higher values of phenylalanine (p\textless0.05) and tyrosine (p\textless0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. CONCLUSIONS Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets.

Authors: Benedict Kinny-Köster, Michael Bartels, Susen Becker, Markus Scholz, Joachim Thiery, Uta Ceglarek, Thorsten Kaiser

Date Published: 13th Jul 2016

Publication Type: Journal article

The Speaking Voice in the General Population: Normative Data and Associations to Sociodemographic and Lifestyle Factors.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Normative data concerning the speaking voice in the general population were gathered with the aim to establish standard values for clinical diagnostics. Associations between the speaking … voice and sociodemographic factors were examined. STUDY DESIGN: This is a prospective cross-sectional population-based study. METHODS: Speaking voice profiles were measured for 2472 (1154 male and 1318 female) participants between the ages of 40 and 79 years, using four speaking voice intensity levels: softest speaking voice (I), conversational voice (II), classroom voice (III), and shouting voice (IV). Smoking status and socioeconomic status were assessed. Data were analyzed using multivariate regression. RESULTS: The mean voice frequencies were 111.8 Hz for male and 161.3 Hz for female participants (I), 111.9 Hz for male and 168.5 Hz for female participants (II), 130.2 Hz for male and 198.0 Hz for female participants (III), and 175.5 Hz for male and 246.2 Hz for female participants (IV). Frequencies increased significantly with age for male but not for female participants. Sound pressure levels rose significantly with age at intensity levels I-III for both sexes, but decreased at intensity level IV. Frequencies and sound pressure levels were similar between nonsmokers and former smokers. Current smokers showed significantly lower frequencies as opposed to non- and former smokers. Speaking voice range and dynamics increased with higher socioeconomic status. CONCLUSIONS: The data are suitable as age-adjusted normative values for clinical measurement of the speaking voice. The mean fundamental speaking voice frequency of female participants was six to seven semitones lower than previously described.

Authors: M. Berg, M. Fuchs, K. Wirkner, M. Loeffler, C. Engel, T. Berger

Date Published: 3rd Jul 2016

Publication Type: Journal article

Novel IGH and MYC Translocation Partners in Diffuse Large B-Cell Lymphomas.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

Chromosomal translocations involving an immunoglobulin (IG) locus and a proto-oncogene play a major role in diffuse large B-cell lymphoma (DLBCL) pathogenesis. Recurrent IG translocation partners in … DLBCL are the BCL6, BCL2, and MYC genes, but other rare translocation partners are also known. We studied 20 DLBCL with fluorescence in situ hybridization-based evidence for IG heavy chain (IGH) locus-associated translocations not involving BCL6, BCL2, MALT1, or MYC by long distance inverse PCR to identify the translocation partners. Moreover, we studied eight DLBCL with MYC translocations not involving IG or known non-IG loci as translocation partner to search for novel MYC translocations. We identified three novel IGH-associated translocations. Chromosomal breakpoints involved the IMMP2L gene in 7q31, the BCAS2 gene in 1p13, and the PVRL2 gene in 19q13. The latter gene, which is recurrently translocated in T-cell lymphomas, is significantly higher expressed in the biopsy with the translocation compared to cases without this genetic aberration, indicating a pathogenetic role of PVRL2 also in DLBCL. In one case with a MYC break we obtained a novel MYC-SOCS1 translocation representing an unusual translocation of a proto-oncogene with a tumor suppressor gene. Indeed, we demonstrate that the oncogene was deregulated and the tumor suppressor gene inactivated. As both genes undergo aberrant somatic hypermutation in the region of the chromosomal breakpoints, this translocation likely happened as a byproduct of the hypermutation process. Overall, our study suggests that chromosomal translocations in DLBCL are more heterogeneous than previously known. (c) 2016 Wiley Periodicals, Inc.

Authors: C. Otto, R. Scholtysik, R. Schmitz, M. Kreuz, C. Becher, M. Hummel, A. Rosenwald, L. Trumper, W. Klapper, R. Siebert, R. Kuppers

Date Published: 30th Jun 2016

Publication Type: Journal article

Human Diseases: diffuse large B-cell lymphoma

USP9X stabilizes XIAP to regulate mitotic cell death and chemoresistance in aggressive B-cell lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions … under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression. We show that high USP9X/XIAP expression is associated with shorter event-free survival in patients treated with spindle poison-containing chemotherapy. Accordingly, aggressive B-cell lymphoma lines with USP9X and associated XIAP overexpression exhibit increased chemoresistance, reversed by specific inhibition of either USP9X or XIAP. Moreover, knockdown of USP9X or XIAP significantly delays lymphoma development and increases sensitivity to spindle poisons in a murine Emu-Myc lymphoma model. Together, we specify the USP9X-XIAP axis as a regulator of the mitotic cell fate decision and propose that USP9X and XIAP are potential prognostic biomarkers and therapeutic targets in aggressive B-cell lymphoma.

Authors: K. Engel, M. Rudelius, J. Slawska, L. Jacobs, B. Ahangarian Abhari, B. Altmann, J. Kurutz, A. Rathakrishnan, V. Fernandez-Saiz, A. Brunner, B. S. Targosz, F. Loewecke, C. J. Gloeckner, M. Ueffing, S. Fulda, M. Pfreundschuh, L. Trumper, W. Klapper, U. Keller, P. J. Jost, A. Rosenwald, C. Peschel, F. Bassermann

Date Published: 19th Jun 2016

Publication Type: Not specified

Human Diseases: B-cell lymphoma

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