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1004 Publications visible to you, out of a total of 1004
Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break … targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Authors: S. M. Aukema, M. Kreuz, C. W. Kohler, M. Rosolowski, D. Hasenclever, M. Hummel, R. Kuppers, D. Lenze, G. Ott, C. Pott, J. Richter, A. Rosenwald, M. Szczepanowski, C. Schwaenen, H. Stein, H. Trautmann, S. Wessendorf, L. Trumper, M. Loeffler, R. Spang, P. M. Kluin, W. Klapper, R. Siebert

Date Published: 2nd Nov 2013

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Analysis of a rare functional truncating mutation rs61757459 in vaspin (SERPINA12) on circulating vaspin levels
Genetical Statistics and Systems Biology

Abstract (Expand)

UNLABELLED\backslashr\backslashnA recent genome-wide association study suggests that genetic variation within the vaspin gene might contribute to the variability in circulating serum visceral adipose … tissue-derived serine protease inhibitor (vaspin) concentrations. Here, we analyzed the functional consequences of the rare variant rs61757459 predicting a premature stop codon and its impact on circulating serum vaspin concentrations. In order to identify genetic variation, we sequenced the vaspin gene in 48 nonrelated Caucasian subjects. Rs61757459 was subsequently genotyped in three metabolically well-characterized German cohorts (N = 4,019). We addressed the impact of rs61757459 on the crystal structure of vaspin and investigated its effects on vaspin expression in vivo as well as in vitro using various cell lines (Escherichia coli, HEK293). Along with previously reported common genetic variants, sequencing of vaspin revealed a rare variant (rs61757459; minor allele frequency: 1 %) which predicts a premature stop codon p.R211X. Heterozygous carriers of this mutation had lower circulating vaspin levels when compared with noncarriers. In silico structure analysis of the truncated vaspin, which was estimated to be 24.5 kDa, suggested misfolding and potential instability due to the absence of core structural domains. Indeed, the truncated protein was detected after recombinant expression in E. coli and in lysate, but not in supernatant of HEK293 cells. We conclude that rs61757459 is a functional mutation that results in a truncated protein whose instability likely results in reduced serum vaspin levels.\backslashr\backslashnKEY MESSAGE\backslashr\backslashnA rare variant (rs61757459) in vaspin coding for the stop codon p.R211X is related to lower circulating vaspin concentrations. Structure analysis suggests misfolding and instability due to the absence of core structural domains. The truncated protein is detectable after recombinant expression in E. coli and in lysate, but not in supernatant of HEK293 cells.

Authors: Jana Breitfeld, John T. Heiker, Yvonne Böttcher, Dorit Schleinitz, Anke Tönjes, Kerstin Weidle, Kerstin Krause, E. Bartholomeus Kuettner, Markus Scholz, Wieland Kiess, Norbert Sträter, Annette G. Beck-Sickinger, Michael Stumvoll, Antje Körner, Matthias Blüher, Peter Kovacs

Date Published: 1st Nov 2013

Publication Type: Journal article

Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVES\backslashr\backslashnThis study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.\backslashr\backslashnBACKGROUND\backslashr\backslashnHigher … circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.\backslashr\backslashnMETHODS\backslashr\backslashnWe conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.\backslashr\backslashnRESULTS\backslashr\backslashnPLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnReducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.

Authors: Michael V. Holmes, Tabassome Simon, Holly J. Exeter, Lasse Folkersen, Folkert W. Asselbergs, Montse Guardiola, Jackie A. Cooper, Jutta Palmen, Jaroslav A. Hubacek, Kathryn F. Carruthers, Benjamin D. Horne, Kimberly D. Brunisholz, Jessica L. Mega, Erik P A van Iperen, Mingyao Li, Maarten Leusink, Stella Trompet, Jeffrey J W Verschuren, G. Kees Hovingh, Abbas Dehghan, Christopher P. Nelson, Salma Kotti, Nicolas Danchin, Markus Scholz, Christiane L. Haase, Dietrich Rothenbacher, Daniel I. Swerdlow, Karoline B. Kuchenbaecker, Eleonora Staines-Urias, Anuj Goel, Ferdinand van ’t Hooft, Karl Gertow, Ulf de Faire, Andrie G. Panayiotou, Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Lesca Miriam Holdt, Frank Beutner, Ron T. Gansevoort, Gerjan J. Navis, Irene Mateo Leach, Lutz P. Breitling, Hermann Brenner, Joachim Thiery, Dhayana Dallmeier, Anders Franco-Cereceda, Jolanda M A Boer, Jeffrey W. Stephens, Marten H. Hofker, Alain Tedgui, Albert Hofman, André G. Uitterlinden, Vera Adamkova, Jan Pitha, N. Charlotte Onland-Moret, Maarten J. Cramer, Hendrik M. Nathoe, Wilko Spiering, Olaf H. Klungel, Meena Kumari, Peter H. Whincup, David A. Morrow, Peter S. Braund, Alistair S. Hall, Anders G. Olsson, Pieter A. Doevendans, Mieke D. Trip, Martin D. Tobin, Anders Hamsten, Hugh Watkins, Wolfgang Koenig, Andrew N. Nicolaides, Daniel Teupser, Ian N M Day, John F. Carlquist, Tom R. Gaunt, Ian Ford, Naveed Sattar, Sotirios Tsimikas, Gregory G. Schwartz, Debbie A. Lawlor, Richard W. Morris, Manjinder S. Sandhu, Rudolf Poledne, Anke H Maitland-van der Zee, Kay-Tee Khaw, Brendan J. Keating, Pim van der Harst, Jackie F. Price, Shamir R. Mehta, Salim Yusuf, Jaqueline C M Witteman, Oscar H. Franco, J. Wouter Jukema, Peter de Knijff, Anne Tybjaerg-Hansen, Daniel J. Rader, Martin Farrall, Nilesh J. Samani, Mika Kivimaki, Keith A A Fox, Steve E. Humphries, Jeffrey L. Anderson, S. Matthijs Boekholdt, Tom M. Palmer, Per Eriksson, Guillaume Paré, Aroon D. Hingorani, Marc S. Sabatine, Ziad Mallat, Juan P. Casas, Philippa J. Talmud

Date Published: 1st Nov 2013

Publication Type: Journal article

Prevalence of minor depression in elderly persons with and without mild cognitive impairment: a systematic review.
LIFE Adult

Abstract (Expand)

BACKGROUND: Minor depression (MinD) and mild cognitive impairment (MCI) are common disorders in late life that often coexist. The aim of the present review is to demonstrate prevalence rates of minor … depression in older patients with and without MCI. METHODS: Electronic database searches were performed through Medline, ISI Web of Knowledge, Psycinfo, and Cochrane library. Two independent reviewers extracted the original studies based on inclusion criteria: representative study population aged 55 and older, diagnostics of MinD according to DSM. Data on prevalence rates, risk factors, comorbidity and health care usage were analyzed. RESULTS: Point prevalence for MinD is higher in medical settings (median 14.4%) than in the community-based settings (median 10.4%) and primary care patients (median 7.7%). Although minor depression is rarely investigated in elderly persons with MCI, nearly 20% of patients with MCI seem to suffer from MinD. No data was found on the prevalence of MCI in patients with MinD. Risk factors associated with MinD include female gender, history of cerebrovascular diseases, generalized anxiety disorder, loneliness, and long-term institutional care. LIMITATIONS: Methodological differences of included studies resulted in a broad range of prevalence rates. No data is shown regarding the prevalence of MCI in MinD group due to insufficient evidence. CONCLUSIONS: Our review indicates that MinD is frequent in elderly population. MCI among those subjects has not been sufficiently investigated. Future studies based on clinical structured interviews should be performed in longitudinal design in order to differentiate late-life depression from progressive MCI or early manifestation of Alzheimer's disease.

Authors: M. Polyakova, N. Sonnabend, C. Sander, R. Mergl, M. L. Schroeter, J. Schroeder, P. Schonknecht

Date Published: 10th Oct 2013

Publication Type: Not specified

Human Diseases: mental depression

The pore size of PLGA bone implants determines the de novo formation of bone tissue in tibial head defects in rats
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE\backslashr\backslashnThe influence of the pore size of biodegradable poly(lactic-co-glycolic acid) scaffolds on bone regeneration was investigated.\backslashr\backslashnMETHODS\backslashr\backslashnCylindrical … poly(lactic-co-glycolic acid) scaffolds were implanted into a defect in the tibial head of rats. Pore sizes of 100-300, 300-500, and 500-710 \textgreekmm were tested and compared to untreated defects as control. Two and four weeks after implantation, the specimens were explanted and defect regeneration and de novo extracellular matrix generation were investigated by MRI, quantitative solid-state NMR, and mass spectrometry.\backslashr\backslashnRESULTS\backslashr\backslashnThe pore size of the scaffolds had a pronounced influence on the quantity of the extracellular matrix synthesized in the graft; most collagen was synthesized within the first 2 weeks of implantation, while the amount of hydroxyapatite increased in the second 2 weeks. After 4 weeks, the scaffolds contained large quantities of newly formed lamellar bone while the control defects were filled by inhomogenous woven bone. Best results were obtained for scaffolds of a pore size of 300-500 \textgreekmm.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur analysis showed that the structure and dynamics of the regenerated extracellular matrix was very similar to that of the native bone, suggesting that biomineralization was significantly enhanced by the choice of the most appropriate implant material.

Authors: Anja Penk, Yvonne Förster, Holger A. Scheidt, Ariane Nimptsch, Michael C. Hacker, Michaela Schulz-Siegmund, Peter Ahnert, Jürgen Schiller, Stefan Rammelt, Daniel Huster

Date Published: 1st Oct 2013

Publication Type: Journal article

Behandlung der Patienten mit einem Venenastverschluss in Abhängigkeit von der Verschlussdauer
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE\backslashr\backslashnThe aim of this study was to evaluate the effects of intravitreal treatment with bevacizumab (IVB) compared with triamcinolone (IVT) in patients with macular edema due to … branch retinal vein occlusion (BRVO) depending on the duration of BRVO.\backslashr\backslashnMETHODS\backslashr\backslashnA total of 65 BRVO patients were divided into 2 subgroups: group 1 with early treatment (≤ 3 months since onset of BRVO) and group 2 with late treatment (\textgreater 3 months since onset). For the two groups IVB was injected into 17 eyes as early (IVB1) and into 18 eyes as late (IVB2) treatment. For comparison IVT was injected into 14 eyes as early (IVT1) and into 16 eyes as late (IVT2) treatment. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were analyzed at baseline, 1, 3 and 6 months after treatment.\backslashr\backslashnRESULTS\backslashr\backslashnIn both subgroups a significant improvement of BCVA and CRwas observed. After 6 months, for patients with early treatment, IVB1 showed better results than IVT1 (BCVA: p = 0.008, CRT: p = 0.021). In the late treatment no significant differences between IVT2 and IVB2 were found.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnBevacizumab and triamcinolone significantly improved BCVA and CRT in patients with BRVO. The best BCVA was found if bevacizumab was used as early treatment. In the late treatment no significant differences between bevacizumab and triamcinolone were observed.

Authors: Matus Rehak, E. Spies, Markus Scholz, Peter Wiedemann

Date Published: 1st Oct 2013

Publication Type: Journal article

The comprehensive IT-Infrastructure for epidemiological Research in LIFE
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Introduction LIFE is a large epidemiological study aiming at causes of common civilization diseases including adiposity, dementia, and depression. Participants of the study are probands and patients. … Probands are randomly selected and invited from the set of Leipzig (Germany) inhabitants while patients with known diseases are recruited from several local hospitals. The management of these participants, their invitation and contact after successful attendance as well as the support of nearly all ambulance processes requires a complex ambulance management. Each participant is examined by a set of investigation instruments including interviews, questionnaires, device-specific investigations, specimen extrac- tions and analyses. This necessitates a complex management of the participantspecific examination program but also specific input forms and systems allowing to capture administrative (measurement and process environment or specific set-ups) and scientific data. Additionally, the taken and prepared specimens need to be labeled and registered from which participant they stem and in which fridge or bio-tank they are stored. At the end, all captured data from ambu- lance management, investigation instruments and laboratory analyses need to be integrated before they can be analyzed. These complex processes and requirements necessitate a comprehensive IT-infrastructure. Methods Our IT-infrastructure modularly consists of several software applications. A main application is responsible for the complex participant and ambulance man- agement. The participant management cope with selected participant data and contact information. To protect participant’s privacy, a participant identifier (PID) is created for each participant that is associated to all data which is managed and captured in the following. In ambulance management, each participant is associated with a predefined investigation program. This investigation program is represented in our systems by a tracking card that is available as print-out and electronically. The electronic version of tracking cards is utilized by two software applications, the Assessment Battery and the CryoLab. The former system coordinates the input of scientific data into online input forms. The input forms are designed in the open source system LimeSurvey. Moreover, the Assessment Battery is used to monitor the input process, i.e., it shows which investigations are already completed and which of them are still to do. The Cryolab system registers and tracks all taken specimens and is used to annotate extraction and specific preparation processes, e.g., for DNA isolation. Moreover, it tracks specimen storage in fridges and bio-tanks. A central component is the metadata repository collecting metadata from ambulance management and data input systems. It is the base for the integra- tion of relevant scientific data into a central research database. The integration follows a mapping-based approach. The research database makes raw data and special pre-computations called derivatives available for later data analysis. Results & Discussion We designed and implemented a complex and comprehensive IT-infrastructure for the epidemiological research in LIFE. This infrastructure consists of several software applications which are loosely coupled over specified interfaces. Most of the software applications are new implementations; only for capturing scientific data external software application are applied.

Authors: Toralf Kirsten, A. Kiel, M. Kleinert, R. Speer, M. Rühle, Hans Binder, Markus Löffler

Date Published: 30th Sep 2013

Publication Type: Not specified

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