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251 Publications visible to you, out of a total of 251
Circulating Nampt and RBP4 levels in patients with carotid stenosis undergoing carotid endarterectomy (CEA)
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnObesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase … (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications.\backslashr\backslashnMETHODS\backslashr\backslashnWe determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics.\backslashr\backslashnRESULTS\backslashr\backslashnNampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p\textless0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity. BACKGROUND Obesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications. METHODS We determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics. RESULTS Nampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p\textless0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis. CONCLUSION Our data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity.

Authors: Gabriela Aust, Migle Uptaite-Patapoviene, Markus Scholz, Olaf Richter, Silvio Rohm, Matthias Blüher

Date Published: 1st Jun 2011

Publication Type: Journal article

Increased CD64 expression on polymorphonuclear neutrophils indicates infectious complications following solid organ transplantation
Genetical Statistics and Systems Biology

Abstract (Expand)

The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the … postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients. The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients.

Authors: Daniel Grey, Ulrich Sack, Markus Scholz, Heike Knaack, Stephan Fricke, Christoph Oppel, Daniel Luderer, Josef Fangmann, Frank Emmrich, Manja Kamprad

Date Published: 1st Jun 2011

Publication Type: Journal article

Intracranial hemangiopericytoma: Case study with cytogenetics and genome wide SNP-A analysis
Genetical Statistics and Systems Biology

Abstract (Expand)

The tumor entity of hemangiopericytoma is not universally recognized as a nosological entity by pathologists, and there is a trend toward reassigning it to other categories gradually. However, … hemangiopericytomas occurring in the nervous system are included in the new WHO classification of brain tumors, and are distinguished from both meningioma and fibrous tumors. Since there are few genetic studies, we performed a comprehensive cytogenetic analysis of an infratentorial hemangiopericytoma in a 55-year-old female. It was originally classified as a grade II tumor but recurred as a grade III tumor with a proliferation index of 20%. Using trypsin-Giemsa staining (GTG-banding) and multicolor fluorescence in situ hybridization (M-FISH), we could confirm the loss of chromosomal material 10q, which has been previously described in hemangiopericytoma, and we identified de novo chromosomal aberrations on chromosome 8. Applying genome-wide high-density single nucleotide polymorphism array (SNP-A) analysis, we detected segments with loss or gain, as well as clonal deletions or regions suggestive of segmental uniparental disomy. These findings, together with the results of conventional histological and immunohistochemical characterization, provide additional evidence for the nosological separation of hemangiopericytoma in the central nervous system as a biologically different entity.

Authors: Heidrun Holland, Michela Livrea, Peter Ahnert, Ronald Koschny, Holger Kirsten, Jürgen Meixensberger, Manfred Bauer, Ralf Schober, Dominik Fritzsch, Wolfgang Krupp

Date Published: 1st May 2011

Publication Type: Journal article

Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells
Genetical Statistics and Systems Biology

Abstract (Expand)

Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both … the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded. Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

Authors: Jutta Jahns, Ulf Anderegg, Anja Saalbach, Britt Rosin, Ina Patties, Annegret Glasow, Manja Kamprad, Markus Scholz, Guido Hildebrandt

Date Published: 1st May 2011

Publication Type: Journal article

Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning
Genetical Statistics and Systems Biology

Abstract (Expand)

Relapse of malignant disease remains the major complication in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) with … reduced-intensity conditioning (RIC). In this study, we investigated the predictive value of disease-specific markers (DSMs), donor chimerism (DC) analysis of unsorted (UDC) or CD34(+) sorted cells and Wilms’ tumor gene 1 (WT1) expression. Eighty-eight patients with AML or MDS were monitored after allogenic HCT following 2 Gy total-body irradiation with (n=84) or without (n=4) fludarabine 3 \times 30 mg/m(2), followed by cyclosporin A and mycophenolate mofetil. DSMs were determined by fluorescence in situ hybridization (FISH) and WT1 expression by real-time polymerase chain reaction. Chimerism analysis was performed on unsorted or CD34(+) sorted cells, by FISH or short tandem repeat polymerase chain reaction. Twenty-one (24%) patients relapsed within 4 months after HCT. UDC, CD34(+) DC and WT1 expression were each significant predictors of relapse with sensitivities ranging from 53 to 79% and specificities of 82-91%. Relapse within 28 days was excluded almost entirely on the basis of WT1 expression combined with CD34(+) DC kinetics. Monitoring of WT1 expression and CD34(+) DC predict relapse of AML and MDS after RIC-HCT.

Authors: T. Lange, M. Hubmann, Ralph Burkhardt, G-N Franke, M. Cross, Markus Scholz, S. Leiblein, H. K. Al-Ali, J. Edelmann, Joachim Thiery, D. Niederwieser

Date Published: 1st Mar 2011

Publication Type: Journal article

Impact of first- and second-line treatment for Hodgkin’s lymphoma on the incidence of AML/MDS and NHL–experience of the German Hodgkin’s Lymphoma Study Group analyzed by a parametric model of carcinogenesis
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnUsing a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin’s disease on secondary … neoplasias.\backslashr\backslashnPATIENTS AND METHODS\backslashr\backslashnWe analyze eight randomized trials of the German Hodgkin’s lymphoma study group [5357 individuals, 67 secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and 97 secondary non-Hodgkin’s lymphoma (NHL)]. Primary therapies were divided into four groups: radiotherapy alone, moderately dosed COPP/ABVD-like chemotherapies for intermediate and advanced stages and BEACOPP escalated.\backslashr\backslashnRESULTS\backslashr\backslashnFor secondary AML/MDS, the hazards after primary therapies are proportional (maximum at 3.4 years), while the hazard after relapse therapy is more peaked (maximum at 1.8 years). Intermediate and advanced stage chemotherapy resulted in a cumulative risk of 1.5%, while the risk after BEACOPP escalated is higher (4.4%, P = 0.004) and comparable with that after relapse therapy (4.5%). For secondary NHL, there are no differences in cumulative risk between the primary therapies (2.9%), while the risk after relapse therapy is increased (6.6%, P = 0.002).\backslashr\backslashnCONCLUSIONS\backslashr\backslashnBEACOPP escalated moderately increases the risk of secondary AML/MDS but not NHL. No differences were found between other chemotherapies of advanced stages and intermediate stages. Secondary AML/MDS occurs faster after relapse treatment than after primary treatment.

Authors: Markus Scholz, A. Engert, J. Franklin, A. Josting, V. Diehl, Dirk Hasenclever, Markus Loeffler

Date Published: 1st Mar 2011

Publication Type: Journal article

Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnThe Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently … analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples.\backslashr\backslashnRESULTS\backslashr\backslashnThe degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies. Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnSorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable. Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses. BACKGROUND The Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples. RESULTS The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies. Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses. CONCLUSIONS Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable. Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses. BACKGROUND The Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples. RESULTS The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies. Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses. CONCLUSIONS Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable. Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses.

Authors: Arnd Gross, Anke Tönjes, Peter Kovacs, Krishna R. Veeramah, Peter Ahnert, Nab R. Roshyara, Christian Gieger, Ina-Maria Rueckert, Markus Loeffler, Mark Stoneking, Heinz-Erich Wichmann, John Novembre, Michael Stumvoll, Markus Scholz

Date Published: 2011

Publication Type: Journal article

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