The symptomatic pelvic kidney: a new source of organs for living donor kidney transplantation?
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Adult↗
Biomedical subjects
Thomas Otto
Publications and source records attributed to Thomas Otto.
DNA methylation profiling of human chromosomes 6, 20 and 22.
DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of six annotation categories showed that evolutionarily conserved regions are the predominant sites for differential DNA methylation and that a core region surrounding the transcriptional start site is an informative surrogate for promoter methylation. We find that 17% of the 873 analyzed genes are differentially methylated in their 5' UTRs and that about one-third of the differentially methylated 5' UTRs are inversely correlated with transcription. Despite the fact that our study controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.
5' Untranslated Regions↗
Laparoscopic inguinal hernia repair as a potential complicating factor in kidney transplantation.
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Anorexia↗
DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.
The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data.
CpG Islands↗
EURADOS database of facilities and equipment for dosimetry research in Europe.
EURADOS (European Radiation Dosimetry Group) has implemented a database of facilities and equipment for dosimetry research in the European Union. The database can be accessed freely by interested scientists via a user-friendly World Wide Web interface. Interested operators and owners of facilities can make information available to the dosimetric community by using a standardised format for information collection. The submitted data is completely in the hands of the information provider.
Databases, Factual↗
Influence of pertussis toxin on superficial bladder carcinoma in rats.
The proliferation and migration of cells is a fundamental process for the metastasis of malignant tumour cells. In several in vitro studies, pertussis toxin (PTX) inhibited cell proliferation and cell motility in the human transitional cell carcinoma cell line J82. The present study investigated the effect of the intravesical application of PTX on the development of superficial bladder cancer in rats. We used the model of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, 0.05% via drinking water x10 weeks) to induce superficial bladder carcinomas in 40 female rats. After 16 weeks the rats were treated in two groups with 0.4 ml PTX (1 microg/ml) or 0.4 ml phosphate buffered saline (PBS) by intravesical application (once a week for 10 weeks). In the 25th week urine cytology was determined and all rats were killed at week 26 followed by histological evaluation. In the control group, the urine cytology was positive for G2/G3 cells in ten of 17 rats. In the PTX group G2/G3 cells were determined in five of 20 rats ( P two tailed <0.05). Histopathologically 12 rats (71%) of the control group and 11 rats (55%) of the PTX group developed T1-T2 transitional-cell carcinomas. No local or systemic side effects were disclosed. PTX treatment reduces the development of G3 transitional cell carcinomas in rats and may represent a new approach for local therapy in superficial bladder cancer.
Animals↗
Tumour class prediction and discovery by microarray-based DNA methylation analysis.
Aberrant DNA methylation of CpG sites is among the earliest and most frequent alterations in cancer. Several studies suggest that aberrant methylation occurs in a tumour type-specific manner. However, large-scale analysis of candidate genes has so far been hampered by the lack of high throughput assays for methylation detection. We have developed the first microarray-based technique which allows genome-wide assessment of selected CpG dinucleotides as well as quantification of methylation at each site. Several hundred CpG sites were screened in 76 samples from four different human tumour types and corresponding healthy controls. Discriminative CpG dinucleotides were identified for different tissue type distinctions and used to predict the tumour class of as yet unknown samples with high accuracy using machine learning techniques. Some CpG dinucleotides correlate with progression to malignancy, whereas others are methylated in a tissue-specific manner independent of malignancy. Our results demonstrate that genome-wide analysis of methylation patterns combined with supervised and unsupervised machine learning techniques constitute a powerful novel tool to classify human cancers.
Algorithms↗
Occurrence of phthalates and bisphenol A and F in the environment.
Certain xenoestrogens, namely bisphenol A (BPA), bisphenol F (BPF), butylbenzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl)phthalate (DEHP), were measured in various compartments (surface water, sediments, sewage treatment plant effluents, sewage sludge, dump water, liquid manure) in order to contribute to a better understanding of exposure to these compounds in different environments. Hundred and sixteen surface-water samples and 35 sediments from rivers, lakes and channels, 39 sewage effluents, and 38 sewage sludges were collected in Germany. Furthermore, ten liquid manure, two waste-dump and two compost-runoff water samples were also analysed. BPA measurements showed low concentrations from 0.0005 to 0.41 microg L(-1) in surface water, in sewage effluents from 0.018 to 0.702 microg L(-1), in sediments from 0.01 to 0.19 mgkg(-1) and in sewage sludge from 0.004 to 1.363mgkg(-1) dw. Measured concentrations of BPF were clearly lower than BPA in all environmental media. DEHP dominated the phthalate concentrations, which ranged from 0.33 to 97.8 microg L(-1) (surface water), 1.74 to 182 microg L(-1) (sewage effluents), 27.9 to 154 mgkg(-1) dw (sewage sludge) and 0.21 to 8.44 mgkg(-1) (sediment). DBP was found only in minor concentrations and BBP, only in a few samples in low amounts. Very high concentrations of BPA and phthalates were confirmed in waste dump water and compost water samples as well as in the liquid manure samples.
Animals↗
Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial.
PURPOSE: The indication for topic chemotherapy or immunotherapy for well differentiated, noninvasive superficial bladder cancer remains controversial. Side effects of these treatments promoted use of unconventional therapies with cytokines, immunomodulators and mistletoe extracts. However, there are no controlled clinical data available on the efficacy of these extracts for bladder cancer. We evaluate the influence of subcutaneously applicated mistletoe lectin on bladder tumor recurrence after transurethral resection. MATERIALS AND METHODS: The study consists of 45 patients with pTa G1-2 bladder cancer treated with transurethral resection during a 3-year period. Median patient age was 65 years and 33 patients were male. The study cohort was randomly divided into a treatment group receiving adjuvant therapy with mistletoe lectin and a control group receiving no additional treatment. Patients in the treatment group received mistletoe lectin according to schedule 2 weeks after transurethral resection. Clinical followup was assessed 3, 6, 9, 12 and 18 months after the initial resection, and included uretherocystoscopy. RESULTS: Both study arms comprised similar patients with regard to total number of previous tumors (mean 2.6 versus 2.9), number of primary lesions (14 versus 12) and number of recurrent tumors (8 versus 11). After followup of 18 months the recurrence-free interval in both study arms was similar (p = 0.76) and the total number of recurrences comparable (p = 0.48). CONCLUSIONS: Subcutaneous use of mistletoe lectin as adjuvant treatment after transurethral resection does not seem to affect the time to first recurrence, total number of recurrences or recurrence-free outcome.
Aged↗