Biomedical subjects

A Dehmel

Publications and source records attributed to A Dehmel.

4 recordsLinked to original sources

PubMed2001

A database generator for human brain imaging.

Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogeneous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.

Brain↗

PubMed1990

Interindividual concordance of methylation profiles in human genes for tumor necrosis factors alpha and beta.

The DNA in mammalian genomes is characterized by complex patterns of DNA methylation that reflect the states of all genetic activities of that genome. The modified nucleotide 5-methyldeoxycytidine (5mdC) can affect the interactions of specific proteins with DNA sequence motifs. The most extensively studied effect of sequence-specific methylations is that of the long-term silencing of eukaryotic (mammalian) promoters. We have initiated studies on the methylation status of parts of the human genome to view patterns of DNA methylation as indicators for genetic activities. In this report, analyses using both restriction enzyme--Southern blotting and the very precise genomic sequencing technique have been done. The genes for tumor necrosis factors (TNF) alpha and beta--in particular, their 5'-upstream and promoter regions--have been investigated in DNA isolated from human lymphocytes, granulocytes, and sperm. The results are characterized by a remarkable interindividual concordance of DNA methylation in specific human cell types. The patterns are identical in the DNA from one cell type for different individuals even of different genetic origins but different in the DNA from different cell types. As an example, in the DNA from human granulocytes of 15 different individuals (ages 20-48 yr, both sexes), 5mdC residues have been localized by the genomic sequencing technique in three identical sequence positions in the 5'-upstream region and in one downstream position of the gene encoding TNF-alpha. The promoter of this gene is free of 5mdC, and TNF-alpha is expressed in human granulocytes. The TNF-beta promoter is methylated in granulocytes from 9 different individuals, and TNF-beta is not expressed. In human lymphocytes, the main source of TNF-beta, the TNF-beta promoter is free of 5mdC residues. All 5'-CG-3' sites studied in the TNF-alpha and -beta genes are methylated in DNA from human sperm. In human cell lines HL-60, Jurkat, and RPMI 1788, the extent of DNA methylation in TNF-alpha and -beta genes has also been studied.

5-Methylcytosine↗

PubMedDate not supplied

Expression of CD44 isoforms in human breast carcinoma xenografts is not influenced by the treatment of mice with cytostatics or (anti-)hormones.

CD44 standard (s) and variant (v) isoforms have been discussed to be implicated in progression and metastasis of different malignomas. For breast carcinomas, the results of different studies are contradictory. These apparent discrepancies suggest that CD44 isoforms are not available on the tumour cell surface, but could be regulated by different endogenous and exogenous factors. Here we report the regulation of CD44 isoforms in xenografted breast cancer cell lines by cytostatics, hormones and antihormones. The human breast cancer models MDA-MB 435, MCF-7, NCI/ADR, 4296, 4151 and 4134 were transplanted into the mammary fat pad of nude mice. When tumours reached a palpable size, animals were treated with farmorubicine, cyclophosphamide, estradiol, tamoxifen or progesterone, respectively. At different times after treatment, serum and tumours were taken. The expression of CD44 and its isoforms was determined by immunohistochemistry and RT-PCR, serum levels were measured by human specific ELISA kits. Serum levels of CD44s and v6 varied among the tumours. For 3/6 tumours we found differences between control groups and treated animals. Immunohistochemical results remained unchanged: each tumour showed a specific pattern of CD44 expression, but this pattern did not change when the animals received cytostatics, hormones or antihormones. The same held true for RT-PCR-results. Also, the time of tumour collection had no influence on CD44 expression. Therefore, it can be concluded, that in the xenografted breast cancer cell lines a regulation of CD44 isoforms by farmorubicine, cyclophosphamide, estradiol, progesterone or tamoxifen could not be found, while serum levels were influenced in some cases probably due to tumour cell kill and shedding of surface proteins into blood stream.

Animals↗

PubMedDate not supplied

Expression of CD44 standard and isoforms in human breast cancer xenografts and shedding of soluble forms into serum of nude mice.

Standard CD44 (CD44s) and variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas. In this work we addressed the question of whether these molecules are also expressed on xenografted human breast carcinomas and if certain expression patterns are correlated with biological parameters like tumour size, hormone receptor status, histology, growth rate, chemoresistance and microenvironment. Additionally, we were interested in the shedding of soluble CD44 (sCD44) into the blood circulation of tumour bearing nude mice. The human breast carcinomas MCF-7, MCF-7/ADR, 4296 and MDA-MB435, 4134 and 4151 were transplanted subcutaneously (sc.) or into the mammary fat pad (mfp.) of nude mice. The expression of the CD44s, -v6, and -v9 isoforms was determined at different time points on tissue samples by immunohistochemistry or RT-PCR employing human-specific antibodies or primers, respectively. The serum concentration of CD44s and -v6 was measured by human specific ELISAs. All tumours expressed CD44s. The lowest level was observed in the MCF-7 cancer. The CD44v6 and -v9 sequences and epitopes were distinctly expressed in MCF-7/ADR. MDA-MB435, 4134, 4151 and 4296, while MCF-7 lacked these isoforms. The highest serum concentration of the v6 isoform was detected in mice bearing the tumour 4296 with a high tendency for lymphogenic metastasis. The serum levels of sCD44 were in 5/6 xenografts linearly correlated with the tumour size. Interestingly, there was a remarkable difference between the two sublines MCF-7 and MCF-7/ADR: Both the tissue and serum levels of CD44 isoforms indicated that the development of multidrug resistance is accompanied by an alteration in the expression of membrane proteins discussed to be involved in metastasis. There was no relation of tissue expression with the transplantation site and the hormone receptor status of the tumour lines. CD44s and its variant isoforms are expressed in human xenotransplanted breast cancers in very different levels and patterns. The highest expression in the tumour 4296 is related to lymphogenic metastasis while the absence of isoforms in the model MCF-7 is related to non-metastatic behaviour. CD44 is shed into the serum and can be used for monitoring of tumour growth.

Alternative Splicing↗