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Transplantation of placenta-derived mesenchymal stromal cells upon experimental stroke in rats
Genetical Statistics and Systems Biology

Abstract (Expand)

The beneficial effects of bone marrow-derived mesenchymal stromal cell (MSC) administration following experimental stroke have already been described. Despite several promising characteristics, … placenta-derived MSC have not been used in models of focal ischemia. The aim of the current study is to investigate the impact of intravenously transplanted placenta-derived MSC on post-stroke recovery. Permanent occlusion of the middle cerebral artery was induced in spontaneously hypertensive rats. MSC were obtained from the human maternal or fetal placenta and intravenously administered after 24 h (single transplantation) or after 8 h and 24 h (dual transplantation). Sensorimotor deficits were quantified for 60 days using the beam walk test and the modified Neurological Severity Score system. Infarct volume was determined in vivo by means of magnetic resonance imaging on days 1, 8, 29 and 60. Astroglial reactivity was semiquantitatively ascertained within a small and a broad region adjacent to the lesion border. The double infusion of placental MSC was superior to single transplantation in the functional tests. However, a significant difference to the control group in all outcome parameters was observed only for maternally derived MSC. These findings suggest that placental tissue constitutes a promising source for experimental stroke therapies. The beneficial effects of bone marrow-derived mesenchymal stromal cell (MSC) administration following experimental stroke have already been described. Despite several promising characteristics, placenta-derived MSC have not been used in models of focal ischemia. The aim of the current study is to investigate the impact of intravenously transplanted placenta-derived MSC on post-stroke recovery. Permanent occlusion of the middle cerebral artery was induced in spontaneously hypertensive rats. MSC were obtained from the human maternal or fetal placenta and intravenously administered after 24 h (single transplantation) or after 8 h and 24 h (dual transplantation). Sensorimotor deficits were quantified for 60 days using the beam walk test and the modified Neurological Severity Score system. Infarct volume was determined in vivo by means of magnetic resonance imaging on days 1, 8, 29 and 60. Astroglial reactivity was semiquantitatively ascertained within a small and a broad region adjacent to the lesion border. The double infusion of placental MSC was superior to single transplantation in the functional tests. However, a significant difference to the control group in all outcome parameters was observed only for maternally derived MSC. These findings suggest that placental tissue constitutes a promising source for experimental stroke therapies.

Authors: Alexander Kranz, Daniel-Christoph Wagner, Manja Kamprad, Markus Scholz, Uwe Richard Schmidt, Franziska Nitzsche, Zami Aberman, Frank Emmrich, Ute-Maria Riegelsberger, Johannes Boltze

Date Published: 1st Feb 2010

Publication Type: Journal article

Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. … Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C\textgreaterT, rs2981745, located in the DMBT1 promoter; and DMBT1 c.124A\textgreaterC, p.Thr42Pro, rs11523871(odds ratio [OR]=1.66, 95% confidence interval [CI]=1.21-2.29, P=0.0017; and OR=1.66; 95% CI=1.21-2.28, P=0.0016, respectively), based on 1,195 BRCA1/2 mutation-negative German breast cancer families and 1,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5’-region are associated with increased breast cancer risk. In accordance with previous results, these data link decreased DMBT1 levels to breast cancer risk.

Authors: Sandrine Tchatchou, Angela Riedel, Stefan Lyer, Julia Schmutzhard, Olga Strobel-Freidekind, Sabine Gronert-Sum, Carola Mietag, Mauro D’Amato, Bettina Schlehe, Kari Hemminki, Christian Sutter, Nina Ditsch, Anneke Blackburn, Linda Zhai Hill, D. Joseph Jerry, Peter Bugert, Bernhard H. F. Weber, Dieter Niederacher, Norbert Arnold, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Rita K. Schmutzler, Christoph Engel, Alfons Meindl, Claus R. Bartram, Jan Mollenhauer, Barbara Burwinkel

Date Published: 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

To validate common low-risk variants predisposing for breast cancer (BC) in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1,415 cases and 1,830 healthy … women by MALDI-TOF in 105 candidate SNPs. Significantly higher ORs than previously reported for heterozygous unselected cases were found for the minor allele in FGFR2 (OR = 1.43, 95% CI 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% CI 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% CI 1.68-2.51, LSP1 (OR = 0.49, 95% CI 0.28-0.86) and TNRC9 (OR = 1.62, 95% CI 1.27-2.07). Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel susceptibility alleles within the LSP1 gene (OR = 0.73, 95% CI 0.61-0.87, p-value = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low-risk variant located at 6q22.33 (rs6569479) is associated with estrogen receptor negative BC in familial cases (OR = 1.33, 95% CI 1.06-1.66; p-value = 0.012). Our data confirm the impact of the previously identified susceptibility loci and provide preliminary evidence for novel susceptibility loci in familial BC cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.

Authors: Kari Hemminki, Bertram Müller-Myhsok, Peter Lichtner, Christoph Engel, Bowang Chen, Barbara Burwinkel, Asta Försti, Christian Sutter, Barbara Wappenschmidt, Heide Hellebrand, Thomas Illig, Norbert Arnold, Dieter Niederacher, Bernd Dworniczak, Helmut Deissler, Karin Kast, Dorothea Gadzicki, Thomas Meitinger, H-Erich Wichmann, Marion Kiechle, Claus R. Bartram, Rita K. Schmutzler, Alfons Meindl

Date Published: 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Comparison of estimators for measures of linkage disequilibrium
Genetical Statistics and Systems Biology

Abstract (Expand)

The measurement of biallelic pair-wise association called linkage disequilibrium (LD) is an important issue in order to understand the genomic architecture. A plethora of measures of association in two … by two tables have been proposed in the literature. Beside the problem of choosing an appropriate measure, the problem of their estimation has been neglected in the literature. It needs to be emphasized that the definition of a measure and the choice of an estimator function for it are conceptually unrelated tasks. In this paper, we compare the performance of various estimators for the three popular LD measures D’, r and Y in a simulation study for small to moderate samples sizes (N\textless=500). The usual frequency-plug-in estimators can lead to unreliable or undefined estimates. Estimators based on the computationally expensive volume measures have been proposed recently as a remedy to this well-known problem. We confirm that volume estimators have better expected mean square error than the naive plug-in estimators. But they are outperformed by estimators plugging-in easy to calculate non-informative Bayesian probability estimates into the theoretical formulae for the measures. Fully Bayesian estimators with non-informative Dirichlet priors have comparable accuracy but are computationally more expensive. We recommend the use of non-informative Bayesian plug-in estimators based on Jeffreys’ prior, in particular when dealing with SNP array data where the occurrence of small table entries and table margins is likely.

Authors: Markus Scholz, Dirk Hasenclever

Date Published: 2010

Publication Type: Journal article

Designing a Concept for an IT-Infrastructure for an Integrated Research and Treatment Center
Management of health information systems

Abstract (Expand)

Healthcare and medical research in Germany are heading to more interconnected systems. New initiatives are funded by the German government to encourage the development of Integrated Research and Treatment … Centers (IFB). Within an IFB new organizational structures and infrastructures for interdisciplinary, translational and trans-sectoral working relationship between existing rigid separated sectors are intended and needed. This paper describes how an IT-infrastructure of an IFB could look like, what major challenges have to be solved and what methods can be used to plan such a complex IT-infrastructure in the field of healthcare. By means of project management, system analyses, process models, 3LGM\textlesssup\textgreater2\textless/sup\textgreater-models and resource plans an appropriate concept with different views is created. This concept supports the information management in its enterprise architecture planning activities and implies a first step of implementing a connected healthcare and medical research platform.

Authors: Sebastian Stäubert, Alfred Winter, R. Speer, M. Loffler

Date Published: 2010

Publication Type: InCollection

Das IHE XDS Integration Profile besser verstehen und umsetzen durch Darstellung als 3LGM^2-Modell
Management of health information systems

Abstract

Not specified

Authors: F. Stephan, R. Hussein, Alfred Winter, Franziska Jahn, Sebastian Stäubert, Alexander Strübing

Date Published: 2010

Publication Type: InCollection

3LGM^2 V3 – Das überarbeitete und erweiterte Drei-Ebenen-Metamodell
Management of health information systems

Abstract

Not specified

Authors: Franziska Jahn, Alfred Winter, A. Strübing, L. Ißler, T. Wendt

Date Published: 2010

Publication Type: InCollection

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