Biomedical subjects

Hans A Kestler

Publications and source records attributed to Hans A Kestler.

18 recordsLinked to original sources

PubMed2006

Visualization of genomic aberrations using Affymetrix SNP arrays.

MOTIVATION: DNA copy number aberrations are frequently found in different types of cancer. Recent developments of microarray-based approaches have broadened the knowledge on number and structure of such aberrations. High-density single nucleotide polymorphism (SNP) microarrays provide an extremely high resolution with up to 500,000 SNPs per genome. Owing to the enormous amount of data the detection of common aberrations in large datasets is a great challenge. We describe a novel open source software tool--IdeogramBrowser--which was specifically designed for use with the Affymetrix SNP arrays. It provides an interactive karyotypic visualization of multiple aberration profiles and direct links to GeneCards. Visualization of consensus regions together with gene representation allows the explorative assessment of the data. AVAILABILITY: IdeogramBrowser and its source code are freely available under a creative commons license and can be obtained from http://www.informatik.uni-ulm.de/ni/staff/HKestler/ideo/. IdeogramBrowser is a platform independent Java application.

Algorithms↗

PubMed2006

Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization.

PURPOSE: To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances. PATIENTS AND METHODS: Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases. RESULTS: Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24). CONCLUSION: In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.

Acute Disease↗

PubMed2006

Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale.

OBJECTIVES: We studied the value of cardiac magnetic resonance imaging (CMRI) before and after closure of patent foramen ovale (PFO) in patients with cryptogenic ischemic events. BACKGROUND: Cardiac magnetic resonance imaging is a powerful noninvasive tool for detailed assessment of cardiac anatomy and function. The relevance of CMRI compared with transesophageal echocardiography (TEE) in patients undergoing transcatheter PFO closure has not been evaluated so far. METHODS: Contrast-enhanced CMRI and TEE were performed in 75 patients before and after PFO closure. Twelve months after PFO closure, both imaging techniques were repeated in 61 patients with contrast application. To determine provokable atrial right-to-left shunting in CMRI, we applied a contrast-enhanced perfusion imaging technique. Detection of atrial septal aneurysm (ASA) was achieved by means of a high-resolution cine imaging technique. RESULTS: Before PFO closure, ASA was seen with CMRI in 28 of 75 cases (37.3%), compared with 47 of 75 (62.7%) cases using TEE. There were a total of 211 CMRI studies with a corresponding TEE performed in 75 patients. No shunt was present in 107 of 211 studies with both techniques. Contrast-enhanced right-to-left shunting was detected by CMRI in 48 of 72 (66.6%) cases with moderate or severe shunts seen with TEE, but only in 6 of 32 (18.8%) studies with mild shunts with TEE. Anomalous venous returns were excluded in all patients. In two patients, coronary anomalies were seen. CONCLUSIONS: The present CMRI technique is inferior to TEE in detection of contrast-enhanced right-to-left shunting and identification of ASA.

Adult↗

PubMed2006

Myocardial perfusion reserve in cardiovascular magnetic resonance: Correlation to coronary microvascular dysfunction.

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

Acetylcholine↗

PubMed2005

Specialized DNA arrays for the differentiation of pancreatic tumors.

PURPOSE: Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of < or =80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array. EXPERIMENTAL DESIGN: Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system. RESULTS AND CONCLUSIONS: Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.

Adenocarcinoma↗

PubMed2005

Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions.

Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.

Base Sequence↗

PubMed2005

Transcriptome analysis of human hepatic and pancreatic stellate cells: organ-specific variations of a common transcriptional phenotype.

Pancreatic stellate cells (PSCs) are thought to be the primary source of the extensive fibrotic reaction characteristic of pancreatic cancer and chronic pancreatitis in humans. PSCs share many morphological and functional characteristics with hepatic stellate cells (HSCs), whose central role in liver fibrosis is well established. However, it has remained unclear if hepatic and pancreatic stellate cells are derived from a common cell lineage and if they are completely similar or if they possess organ-specific features. We have analysed the transcriptomes of HSCs, PSCs and skin fibroblasts to assess how the transcriptional phenotype of stellate cells differs from that of a typical fibroblast lineage cell and if there is evidence for a common stellate cell precursor. To this end, we have performed expression profiling of primary cultures of human HSCs, PSCs and skin fibroblasts using 23,000-feature 'whole genome' oligonucleotide micro-arrays. Expression data were verified using real-time PCR. The expression profiles of HSCs and PSCs displayed a great extent of similarity, clearly separating them from the fibroblasts. Predominantly extracellular and cell surface genes, but also signalling molecules, transcription factors and novel neural markers, were concordantly expressed in both stellate cell types. Despite this high degree of similarity, distinct differences in expression patterns were observed between HSCs and PSCs, reflecting organ-specific variations of the common stellate cell-specific phenotype.

Cell Lineage↗

PubMed2005

Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging.

AIMS: Because of its high spatial resolution and tissue contrast, magnetic resonance imaging (MRI) was used to assess cardiac structure and function in a large population of patients with acute myocardial infarction (AMI). METHODS AND RESULTS: One hundred and ten patients were studied by MRI 6.1 +/- 2.2 days after AMI. Infarct size (IS), persistent microvascular obstruction (PMO), left and right ventricular (LV/RV) volumes, and functions were measured. The same MRI measurements were repeated in 89 patients after a mean follow-up period of 225 +/- 92 days. IS was 11.9 +/- 7.3% of total LV muscle mass. PMO was detected in 51/110 (46.4%) patients and comprised 15.6 +/- 8.5% of IS and 2.8 +/- 2.3% of LV muscle mass. Papillary muscle infarct was seen in 26%, RV infarction in 16%, pericarditis in 40%, and pericardial effusion in 66% of the patients. During follow-up, there were 16 major adverse cardiac events (MACE) including seven deaths. IS, PMO, and amount of transmural infarction were predictive for LV adverse remodelling defined as > 20% increase in LV end-diastolic volume. Multivariable analysis revealed LV end-diastolic volume, LV ejection fraction, and PMO as significant predictors for the occurrence of MACE. CONCLUSION: MRI is a highly sensitive and reliable tool to detect morphologic and functional sequelae of AMI providing baseline MRI parameters with relevant predictive power for LV adverse remodelling and occurrence of MACE.

Aged↗

PubMed2004

Generalized Venn diagrams: a new method of visualizing complex genetic set relations.

MOTIVATION: Microarray experiments generate vast amounts of data. The unknown or only partially known functional context of differentially expressed genes may be assessed by querying the Gene Ontology database via GOMiner. Resulting tree representations are difficult to interpret and are not suited for visualization of this type of data. Methods are needed to effectively visualize these complex set relationships. RESULTS: We present a visualization approach for set relationships based on Venn diagrams. The proposed extension enhances the usual notion of Venn diagrams by incorporating set size information. The cardinality of the sets and intersection sets is represented by their corresponding circle (polygon) sizes. To avoid local minima, solutions to this problem are sought by evolutionary optimization. This generalized Venn diagram approach has been implemented as an interactive Java application (VennMaster) specifically designed for use with GOMiner in the context of the Gene Ontology database. AVAILABILITY: VennMaster is platform-independent (Java 1.4.2) and has been tested on Windows (XP, 2000), Mac OS X, and Linux. Supplementary information and the software (free for non-commercial use) are available at http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/vennm together with a user documentation. CONTACT: hans.kestler@medizin.uni-ulm.de.

Algorithms↗

PubMed2004

Genomic DNA-chip hybridization reveals a higher incidence of genomic amplifications in pancreatic cancer than conventional comparative genomic hybridization and leads to the identification of novel candidate genes.

Genomic analyses aimed at the detection of high-level DNA amplifications were performed on 13 widely used pancreatic cancer cell lines and 6 pancreatic tumor specimens. For these analyses, array-based comparative genomic hybridization (Matrix-CGH) onto dedicated microarrays was used. In comparison with chromosomal CGH (eight amplifications), a >3-fold number of DNA amplifications was detected (n = 29). The most frequent amplifications mapped to 7p12.3 (three pancreatic cancer cell lines and three pancreatic tumor specimens), 8q24 (four pancreatic cancer cell lines and one pancreatic tumor specimen), 11q13 (three pancreatic cancer cell lines and three pancreatic tumor specimens), and 20q13 (four pancreatic cancer cell lines and three pancreatic tumor specimens). Genes contained in the consensus regions were MYC (8q24), EGFR (7p12.3), and FGF3 (11q13). In six of seven pancreatic cancer cell lines and pancreatic tumor specimens with 20q13 amplifications, the novel candidate gene NFAT C2, which plays a role in the activation of cytokines, was amplified. Other amplifications also affected genes for which a pathogenetic role in pancreatic carcinoma has not been described, such as BCL10 and BCL6, two members of the BCL family. A subset of amplified genes was checked for overexpression by means of real-time PCR, revealing the highest expression levels for BCL6 and BCL10. Thus, Matrix-CGH allows the detection of a high number of amplifications, resulting in the identification of novel candidate genes in pancreatic cancer.

Aged↗

PubMed2004

Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions.

Tumor samples of 53 patients with t(11;14)-positive mantle cell lymphomas (MCLs) were analyzed by matrix-based comparative genomic hybridization (matrix-CGH) using a dedicated DNA array. In 49 cases, genomic aberrations were identified. In comparison to chromosomal CGH, a 50% higher number of aberrations was found and the high specificity of matrix-CGH was demonstrated by fluorescence in situ hybridization (FISH) analyses. The 11q gains and 13q34 deletions, which have not been described as frequent genomic aberrations in MCL, were identified by matrix-CGH in 15 and 26 cases, respectively. For several genomic aberrations, novel consensus regions were defined: 8p21 (size of the consensus region, 2.4 megabase pairs [Mbp]; candidate genes: TNFRSF10B, TNFRSF10C, TNFRSF10D); 10p13 (2.7 Mbp; BMI1); 11q13 (1.4 Mbp; RELA); 11q13 (5.2 Mbp; CCND1); 13q14 (0.4 Mbp; RFP2, BCMSUN) and 13q34 (6.9 Mbp). In univariate analyses correlating genomic aberrations and clinical course, 8p- and 13q14- deletions were associated with an inferior overall survival. These data provide a basis for further studies focusing on the identification of pathogenetically or clinically relevant genes in MCL.

Chromosome Aberrations↗

PubMed2004

Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations.

B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix-CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression.

Automation↗

PubMed2004

Expression profiling of the influence of RAS mutants on the TGFB1-induced phenotype of the pancreatic cancer cell line PANC-1.

Expression profiling analyses were used to elucidate the functional relevance of RAS proteins in mediating the effect of TGFB1 on the transcriptional phenotype of the pancreatic cancer cell line PANC-1. Despite the presence of one mutated KRAS2 allele in parental PANC-1 pancreatic cancer cells, RAS-dependent signal transduction remained susceptible to stimulation by EGF and TGFB1. To analyze the impact of RAS proteins on the TGFB1-induced transcriptional phenotype, we used PANC-1 cells stably transfected with a dominant negative HRAS(S17N) mutant or with a constitutively active KRAS2(G12V) mutant. TGFB1 treatment of mock-transfected PANC-1 cells led to an expression profile suggestive of epithelial-mesenchymal transdifferentiation (EMT). Profiling of the HRAS(S17N)-expressing clone demonstrated that induction of endogenous RAS activity by TGFB1 is required for the development of the TGFB1-induced transcriptional phenotype of PANC-1 cells. The expression of the KRAS2(G12V) mutant by itself repressed transcription of markers of epithelial differentiation and induced transcription of several extracellular matrix-associated genes. This effect was not enhanced further by TGFB1 treatment. In contrast, transcript levels of genes associated with proliferation and cell cycle progression did not appear to be the primary targets of the synergism between the RAS- and TGFB1-dependent cascades. The introduction of the dominant negative and the constitutively active RAS mutants induced partly overlapping and partly inverse effects on the TGFB1-induced expression profile of PANC-1 cells. Additional mechanisms such as the induction of autocrine loops and the use of different RAS isoforms or alternate, ERK-independent signaling pathways may be involved in the interaction between the RAS- and the TGFB1-dependent signaling cascades.

Amino Acid Substitution↗

PubMed2004

Re-angioplasty of in-stent restenosis versus balloon restenoses--a matched pair comparison.

BACKGROUND: Despite different biological mechanisms involved in the restenotic process of in-stent restenosis and restenosis after balloon angioplasty alone, the occurrence of a second restenosis has been reported in the same range. There are no data available comparing the outcome after re-angioplasty of such lesions. We analyzed in a matched pair comparison the clinical outcome and angiographic long-term result of patients with balloon angioplasty of a first in-stent restenosis versus patients with balloon re-angioplasty of a first balloon restenosis. METHODS: Both groups consisted of 74 lesions matched by treated vessel, lesion location differentiated in proximal and non-proximal, and angiographic appearance of coronary artery disease differentiated in singular stenosis, diffuse or mixed pattern. Clinical follow-up was 100%. Angiographic follow-up was 78.4% after median 174 days. RESULTS: Angiographic restenosis rate in matched pairs of patients (n=46/74) was significantly higher in the balloon restenosis group (41.3%, n=19/46) compared to the in-stent restenosis group (21.7%, n=10/46, p<0.042). There was no death or myocardial infarction. After clinical follow-up, target lesion revascularization rate was significantly lower in the in-stent restenosis group compared to the balloon restenosis group (12.1%, n=9/74 versus 27.0%, n=20/74; difference between groups 14.9%, 95% confidence interval 2.0-27.3%, p<0.023). Multivariate logistic regression analysis revealed as predictors for a second restenosis unstable angina pectoris, non-proximal lesion, restenosis after balloon angioplasty and the occurrence of the first restenosis within 90 days after initial intervention. CONCLUSION: Clinical and angiographic outcome after balloon angioplasty of a first in-stent restenosis was significantly better compared with balloon re-angioplasty of a first balloon restenosis.

Angioplasty, Balloon↗

PubMed2004

Classification of incidental carcinoma of the prostate using learning vector quantization and support vector machines.

The subclassification of incidental prostatic carcinoma into the categories T1a and T1b is of major prognostic and therapeutic relevance. In this paper an attempt was made to find out which properties mainly predispose to these two tumor categories, and whether it is possible to predict the category from a battery of clinical and histopathological variables using newer methods of multivariate data analysis. The incidental prostatic carcinomas of the decade 1990-99 diagnosed at our department were reexamined. Besides acquisition of routine clinical and pathological data, the tumours were scored by immunohistochemistry for proliferative activity and p53-overexpression. Tumour vascularization (angiogenesis) and epithelial texture were investigated by quantitative stereology. Learning vector quantization (LVQ) and support vector machines (SVM) were used for the purpose of prediction of tumour category from a set of 10 input variables (age, Gleason score, preoperative PSA value, immunohistochemical scores for proliferation and p53-overexpression, 3 stereological parameters of angiogenesis, 2 stereological parameters of epithelial texture). In a stepwise logistic regression analysis with the tumour categories T1a and T1b as dependent variables, only the Gleason score and the volume fraction of epithelial cells proved to be significant as independent predictor variables of the tumour category. Using LVQ and SVM with the information from all 10 input variables, more than 80 of the cases could be correctly predicted as T1a or T1b category with specificity, sensitivity, negative and positive predictive value from 74-92%. Using only the two significant input variables Gleason score and epithelial volume fraction, the accuracy of prediction was not worse. Thus, descriptive and quantitative texture parameters of tumour cells are of major importance for the extent of propagation in the prostate gland in incidental prostatic adenocarcinomas. Classical statistical tools and neuronal approaches led to consistent conclusions.

Adenocarcinoma↗

PubMed2003

Classification of prostatic carcinoma with artificial neural networks using comparative genomic hybridization and quantitative stereological data.

Staging of prostate cancer is a mainstay of treatment decisions and prognostication. In the present study, 50 pT2N0 and 28 pT3N0 prostatic adenocarcinomas were characterized by Gleason grading, comparative genomic hybridization (CGH), and histological texture analysis based on principles of stereology and stochastic geometry. The cases were classified by learning vector quantization and support vector machines. The quality of classification was tested by cross-validation. Correct prediction of stage from primary tumor data was possible with an accuracy of 74-80% from different data sets. The accuracy of prediction was similar when the Gleason score was used as input variable, when stereological data were used, or when a combination of CGH data and stereological data was used. The results of classification by learning vector quantization were slightly better than those by support vector machines. A method is briefly sketched by which training of neural networks can be adapted to unequal sample sizes per class. Progression from pT2 to pT3 prostate cancer is correlated with complex changes of the epithelial cells in terms of volume fraction, of surface area, and of second-order stereological properties. Genetically, this progression is accompanied by a significant global increase in losses and gains of DNA, and specifically by increased numerical aberrations on chromosome arms 1q, 7p, and 8p.

Adenocarcinoma↗

PubMed2003

Optimal acquisition parameters for contrast enhanced magnetic resonance imaging after chronic myocardial infarction.

The aim of this study was to simplify the imaging of myocardial infarction based on theoretical aspects and patient variables and to define the optimal time for image acquisition. Thirteen patients with chronic myocardial infarction underwent magnetic resonance imaging. After injection of 0.2 mmol/kg body weight Gd-DTPA an inversion recovery turbo gradient echo sequence with different prepulse delays was applied every 3 to 5 minutes within an interval of 3 to 30 minutes. As parameters of investigation, the area of signal enhancement and the contrast between enhanced and nonenhanced myocardium were used. There was no influence of prepulse delay or time after contrast injection on the enhanced area. The contrast between enhanced and normal myocardium showed a peak at 6 minutes post Gd-DTPA injection and remained high. The contrast between blood and enhanced myocardium was best at 6 and 25 minutes with best intra- and interobserver variability. In conclusion, if a suitable contrast was achieved, the area of enhancement is independent of prepulse delay or imaging time. In most patients the highest contrast between blood, enhanced and normal myocardium is achieved 6 minutes and 25 minutes after contrast injection.

Aged↗

PubMed2002

Chromosomal regions in prostatic carcinomas studied by comparative genomic hybridization, hierarchical cluster analysis and self-organizing feature maps.

Comparative genomic hybridization (CGH) is an established genetic method which enables a genome-wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that place. Therefore, large amounts of data quickly accumulate which must be put into a logical order. Cluster analysis can be used to assign individual cases (samples) to different clusters of cases, which are similar and where each cluster may be related to a different tumour biology. Another approach consists in a clustering of chromosomal regions by rewriting the original data matrix, where the cases are written as rows and the chromosomal regions as columns, in a transposed form. In this paper we applied hierarchical cluster analysis as well as two implementations of self-organizing feature maps as classical and neuronal tools for cluster analysis of CGH data from prostatic carcinomas to such transposed data sets. Self-organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule. We studied a group of 48 cases of incidental carcinomas, a tumour category which has not been evaluated by CGH before. In addition we studied a group of 50 cases of pT2N0-tumours and a group of 20 pT3N0-carcinomas. The results show in all case groups three clusters of chromosomal regions, which are (i) normal or minimally affected by losses and gains, (ii) regions with many losses and few gains and (iii) regions with many gains and few losses. Moreover, for the pT2N0- and pT3N0-groups, it could be shown that the regions 6q, 8p and 13q lay all on the same cluster (associated with losses), and that the regions 9q and 20q belonged to the same cluster (associated with gains). For the incidental cancers such clear correlations could not be demonstrated.

Chromosome Mapping↗