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251 Publications visible to you, out of a total of 251
Multiple meningioma with different grades of malignancy: case report with genetic analysis applying single-nucleotide polymorphism array and classical cytogenetics
Genetical Statistics and Systems Biology

Abstract (Expand)

Multiple meningiomas with synchronous tumor lesions represent only 1-9% of all meningiomas and usually show a uniform histology. The simultaneous occurrence of different grades of malignancy in these … nodules is observed in only one third of multiple meningiomas. We report a case of a sporadic multiple meningioma presenting with different histopathological grades (WHO I and II). The tumor genome of both nodules was analyzed by GTG-banding, spectral karyotyping (SKY), locus-specific FISH, and single nucleotide polymorphism array (SNP-A) karyotyping. GTG-banding and SKY revealed 25 structural and 33 numerical aberrations with a slightly increased aberration frequency in the WHO grade II nodule. We could confirm terminal deletions on chromosomes 1p [ish del(1)(p36)(p58-,pter-) 16.5% WHO grade I and 20.9% WHO grade II], partial deletions on 22q, and/or monosomy 22 (monosomy 22 14% WHO grade I and 34% WHO grade II) as the most frequent aberrations in both meningioma nodules. In the meningioma WHO grade II, in addition, a de novo paracentric inversion within chromosomal band 1p36 was detectable. Furthermore, for meningiomas de novo, dicentric chromosomes 4 could be identified in both tumor nodules. We also detected previously published segmental uniparental disomy regions 1p31.1, 6q14.1, 10q21.1, and 14q23.3 in normal control DNA of the patient and in both tumor nodules. Taken together, we describe a very rare case of multiple meningioma with overlapping but also distinct genetic aberration patterns in two nodules of different WHO grades of malignancy.

Authors: Kristin Mocker, Heidrun Holland, Peter Ahnert, Ralf Schober, Manfred Bauer, Holger Kirsten, Ronald Koschny, Jürgen Meixensberger, Wolfgang Krupp

Date Published: 2011

Publication Type: Journal article

Harmonization of growth hormone measurements with different immunoassays by data adjustment
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnThe aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, … we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation.\backslashr\backslashnMETHODS\backslashr\backslashnIn archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and {\textquotedblIn house{\textquotedbl-RIA (Tübingen).\backslashr\backslashnRESULTS\backslashr\backslashnThe assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean \pm SD) of values within the cut-off range was 24.3% \pm 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and \textless1%, respectively.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnhGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence.

Authors: Anne Müller, Markus Scholz, Oliver Blankenstein, Gerhard Binder, Roland Pfäffle, Antje Körner, Wieland Kiess, Annegret Heider, Martin Bidlingmaier, Joachim Thiery, Jürgen Kratzsch

Date Published: 2011

Publication Type: Journal article

Spectral iEEG markers precede SSEP events during surgery for subarachnoid hemorrhage
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVE\backslashr\backslashnDuring neurosurgical intracranial vascular manipulations, surgeons need early feed-back on the effects of temporary vascular occlusion. In surgical practice, commonly the … amplitude of somatosensory evoked potentials (SSEP) is monitored. However, the latency between an ischemic event and the drop of SSEP amplitude may amount to several minutes. Therefore intracranial electroencephalogram (iEEG) is tested for its predictive value.\backslashr\backslashnMETHODS\backslashr\backslashnDuring surgery in 13 patients, SSEP was recorded simultaneously with iEEG. iEEG was analyzed real-time in the frequency domain. Spectral observables of the iEEG were validated on the basis of SSEP by computing the statistical correlation first for the whole data set, then for salient events occurring in the SSEP in the group of patients, and finally for salient events occurring in single patients.\backslashr\backslashnRESULTS\backslashr\backslashnPlacement of subdural strip electrodes was compatible with standard surgical routine. Maximal correlation between time series of iEEG and SSEP was found for relative alpha power, which preceded the drop of SSEP by 7min.\backslashr\backslashnCONCLUSIONS\backslashr\backslashniEEG is feasible during neurosurgical intracranial vascular manipulations. Monitoring relative alpha power detects salient events earlier than SSEP.\backslashr\backslashnSIGNIFICANCE\backslashr\backslashnEarly detection of salient events facilitates early reaction of the surgeon and may thereby aid to further reduce intraoperative morbidity.

Authors: Christian Wess, Johannes Sarnthein, Niklaus Krayenbühl, Markus Scholz, Ekkehard Kunze, Jürgen Meixensberger

Date Published: 1st Dec 2010

Publication Type: Journal article

WHO grade-specific comparative genomic hybridization pattern of astrocytoma - a meta-analysis
Genetical Statistics and Systems Biology

Abstract (Expand)

To detect novel genetic alterations, many astrocytomas have been investigated by comparative genomic hybridization (CGH). To identify aberration profiles characteristic of World Health Organization … (WHO) grade I, II, III, and IV astrocytoma, we performed a meta-analysis of detailed genome wide CGH data of all 467 cases published so far. After expansion of all given aberrations to the maximum of 850 GTG-band resolution, the frequencies of genetic imbalances were calculated for each chromosomal band, separately for all four WHO grades. Low-grade astrocytoma has already demonstrated one characteristic of glioblastoma multiforme, gain of chromosome 7 with a hot spot at 7q32, but without loss of chromosome 10. In anaplastic astrocytoma, a more complex aberration pattern emerges from diffuse genetic imbalances. Gains of 7q32-q36 and 7p12 become the most frequent aberrations at chromosome 7. In glioblastoma multiforme, coarse aberrations like +7, -9p, -10, and -13 represent the most frequent aberrations as a characteristic pattern. In contrast to lower tumor grades, glioblastoma multiforme demonstrates +7p12 as the most frequently affected band on chromosome 7. To quantify the gradual transition from WHO grade II-IV astrocytoma, we calculated the relative increase and decrease in frequency for each detected aberration of the tumor genome. The most pronounced and diverse changes of genetic material occur at the virtual transition from low-grade to anaplastic astrocytoma. Further transition to glioblastoma multiforme is characterized by gain of 1p, chromosome 7, and loss of chromosome 10. Summing up, the expansion of the CGH results to the 850 GTG-band resolution enabled a meta-analysis to visualize WHO grade-specific aberration profiles in astrocytoma.

Authors: Heidrun Holland, Thomas Koschny, Peter Ahnert, Jürgen Meixensberger, Ronald Koschny

Date Published: 1st Oct 2010

Publication Type: Journal article

Genetic regulation of serum phytosterol levels and risk of coronary artery disease
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnPhytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We … used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD).\backslashr\backslashnMETHODS AND RESULTS\backslashr\backslashnA genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (n=1495) with subsequent replication in 2 additional samples (n=1157 and n=1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined P=1.6 x 10(-50) and 6.2 x 10(-25), respectively; n=4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (P=0.009). Effects at the ABO locus were related to SNP rs657152 (combined P=9.4x10(-13)). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; P=2.2 x 10(-6); rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; P=9.4 x 10(-6)), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; P=1.3 x 10(-5)).\backslashr\backslashnCONCLUSION\backslashr\backslashnCommon variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD.

Authors: Daniel Teupser, Ronny Baber, Uta Ceglarek, Markus Scholz, Thomas Illig, Christian Gieger, Lesca Miriam Holdt, Alexander Leichtle, Karin H. Greiser, Dominik Huster, Patrick Linsel-Nitschke, Arne Schäfer, Peter S. Braund, Laurence Tiret, Klaus Stark, Dorette Raaz-Schrauder, Georg M. Fiedler, Wolfgang Wilfert, Frank Beutner, Stephan Gielen, Anika Grosshennig, Inke R. König, Peter Lichtner, Iris M. Heid, Alexander Kluttig, Nour E El Mokhtari, Diana Rubin, Arif B. Ekici, André Reis, Christoph D. Garlichs, Alistair S. Hall, Gert Matthes, Christian Wittekind, Christian Hengstenberg, Francois Cambien, Stefan Schreiber, Karl Werdan, Thomas Meitinger, Markus Loeffler, Nilesh J. Samani, Jeanette Erdmann, Heinz-Erich Wichmann, Heribert Schunkert, Joachim Thiery

Date Published: 1st Aug 2010

Publication Type: Journal article

Transapical aortic valve implantation in 100 consecutive patients: comparison to propensity-matched conventional aortic valve replacement
Genetical Statistics and Systems Biology

Abstract (Expand)

AIMS\backslashr\backslashnTo evaluate the outcome of transapical aortic valve implantation (TA-AVI) in comparison to conventional surgery.\backslashr\backslashnMETHODS AND RESULTS\backslashr\backslashnOne … hundred consecutive high-risk patients with symptomatic aortic valve stenosis received TA-AVI using the Edwards SAPIEN pericardial xenograft between February 2006 and January 2008. Patient age was 82.7 +/- 5 years, 77 were females, logistic EuroSCORE predicted risk of mortality was 29.4 +/- 13% and Society Thoracic Surgeons score risk for mortality was 15.2 +/- 8.3%. Propensity score analysis was used to identify a control group of patients that underwent conventional aortic valve replacement (C-AVR). Transapical aortic valve implantation was performed successfully in 97 patients, whereas three patients required early conversion. There were no new onset neurological events in the TA-AVI group and early extubation was performed in 82 patients. Echocardiography revealed good valve function with low transvalvular gradients in all patients. Thirty-day survival was 90 +/- 3 vs. 85 +/- 4% for TA-AVI vs. C-AVR, and 1-year survival was 73 +/- 4 vs. 69 +/- 5% (P = 0.55).\backslashr\backslashnCONCLUSION\backslashr\backslashnTransapical aortic valve implantation is a safe, minimally invasive, and off-pump technique to treat high-risk patients with aortic stenosis. Results of the initial 100 patients are good and compare favourably to conventional surgery.

Authors: Thomas Walther, Gerhard Schuler, Michael Andrew Borger, Joerg Kempfert, Jörg Seeburger, Yvonne Rückert, Joerg Ender, Axel Linke, Markus Scholz, Volkmar Falk, Friedrich Wilhelm Mohr

Date Published: 1st Jun 2010

Publication Type: Journal article

Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced apoptosis
Genetical Statistics and Systems Biology

Abstract (Expand)

TNF-related apoptosis-inducing ligand (TRAIL), a promising novel anti-cancer cytokine of the TNF superfamily, and Bortezomib, the first-in-class clinically used proteasome inhibitor, alone or in … combination have been shown to efficiently kill numerous tumor cell lines. However, data concerning primary human tumor cells are very rare. Using primary esthesioneuroblastoma cells we analyzed the anti-tumor potential and the mechanism employed by Bortezomib in combination with TRAIL for the treatment of this rare but aggressive tumor. Expression of components of the TRAIL pathway was analyzed in tumor specimens and isolated primary tumor cells at the protein level. Cells were treated with TRAIL, Bortezomib, and a combination thereof, and apoptosis induction was quantified. Clonogenicity assays were performed to elucidate the long-term effect of this treatment. Despite expressing all components of the TRAIL pathway, freshly isolated primary esthesioneuroblastoma cells were completely resistant to TRAIL-induced apoptosis. They could, however, be very efficiently sensitized by subtoxic doses of Bortezomib. The influence of Bortezomib on the TRAIL pathway was analyzed and showed upregulation of TRAIL death receptor expression, enhancement of the TRAIL death-inducing signaling complex (DISC), and downregulation of anti-apoptotic proteins of the TRAIL pathway. Of clinical relevance, TRAIL-resistant primary tumor cells could be repeatedly sensitized by Bortezomib, providing the basis for repeated clinical application schedules. This is the first report on the highly synergistic induction of apoptosis in primary esthesioneuroblastoma cells by Bortezomib and TRAIL. This combination, therefore, represents a promising novel therapeutic option for esthesioneuroblastoma.

Authors: Ronald Koschny, Heidrun Holland, Jaromir Sykora, Hande Erdal, Wolfgang Krupp, Manfred Bauer, Ulrike Bockmuehl, Peter Ahnert, Jürgen Meixensberger, Wolfgang Stremmel, Henning Walczak, Tom M. Ganten

Date Published: 1st Apr 2010

Publication Type: Journal article

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