Biomedical subjects

S Winkler

Publications and source records attributed to S Winkler.

At least 19 recordsLinked to original sources

PubMed2006

Gef10--the third member of a Rho-specific guanine nucleotide exchange factor subfamily with unusual protein architecture.

According to cDNA sequence homologies, Gef10 is related to the Rho-specific guanine nucleotide exchange factors GrinchGEF and p164-RhoGEF. Like these GEFs, Gef10 exhibits only weak homology to known pleckstrin homology domains, but contains a putative WD40-like domain. As detected by RT-PCR, Gef10 is transcribed in at least two splice variants in different human tissues. Although the Gef10 sequence contains two putative transmembrane segments, recombinantly expressed Gef10 displays a cytosolic localisation. As detected by guanine nucleotide exchange activity assay, precipitation assay of GTP-bound Rho proteins and serum response element dependent gene transcription Gef10 activates RhoA-C, but not Rac1 or Cdc42. In the reporter gene assay, Gef10 preferentially activated RhoB. When expressed in NIH3T3 cells, Gef10 induced actin stress fibre, but not lamellipodia or filopodia formation. We conclude that Gef10 is the third member of a Rho-specific GEF family with unusual protein architecture.

Animals↗

PubMed2005

RAS gene hot-spot mutations in canine neoplasias.

Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs.

Animals↗

PubMed2005

Establishment of a cell line derived from a canine prostate carcinoma with a highly rearranged karyotype.

Akin to the situation in humans, dogs are frequently affected by tumors of the prostate. The malignancies share many similarities between both species, for example, median age at the onset of the disease and metastatic behavior. In human prostatic tumor samples, investigations of prepared metaphase spreads showed a variety of chromosomal aberrations, with trisomies of chromosomes 7, 8, and 17 as the leading cytogenetic abnormalities. In this article we present one case of a canine adenocarcinoma of the prostate, including clinical examination and establishment of a cell line from a tumor sample obtained from the affected 10-year-old male Briard. Searching for similarities between both species in respect to chromosomal changes within the tumor samples, we investigated prepared metaphases of the canine cell line cytogenetically. These investigations presented a highly rearranged karyotype showing a large biarmed marker consisting of material from chromosomes 1 and 2 in addition to centromeric fusions between dog chromosomes 1 and 5 that both could be identified in every metaphase investigated, while centric fusions of chromosomes 4 and 5 occurred in up to 50% of the metaphases. The cell line grew very well and showed evidence of being spontaneously immortalized when it crossed the 20th passage.

Adenocarcinoma↗

PubMed2005

"Best friends" sharing the HMGA1 gene: comparison of the human and canine HMGA1 to orthologous other species.

HMGA1 nonhistone proteins are reported to participate in various cellular processes including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the induction of neoplastic transformation and promotion of metastatic progression of cancer cells. Overexpression of HMGA1 was shown to be characteristic for various malignant tumors, suggesting a relation between the neoplastic phenotype and a high titer of the protein. Also chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in several tumors, e.g., uterine leiomyomas, pulmonary chondroid hamartomas, and follicular thyroid adenomas. We characterize the molecular structure of the canine HMGA1 cDNA, its splice variants, and predicted proteins HMGA1a and HMGA1b. Furthermore, we compared the CDS of both splice variants for 12 different breeds, screened them for SNPs, characterised a basic expression pattern, and mapped the gene via FISH. Additionally, we compared the known human, canine, murine, rat, hamster, bovine, pig, Xenopus, and chicken HMGA1 transcripts.

Animals↗

PubMed2005

Continuous monitoring in sewer networks an approach for quantification of pollution loads from CSOs into surface water bodies.

Different approaches for quantification of pollution loads discharged from combined sewer networks into surface water bodies have been observed over the last few years and decades, but a large number of unresolved problems still remain. Many monitoring campaigns have been based on manual or automated spot sampling - with the long known limitations of this method such as sampling errors and errors due to sample conservation, transport and preparation. On the other hand, only recently have sensors became available which are suitable for continuous application in sewer networks. A large number of practical problems still have to be solved before continuous monitoring in sewer networks will be successful. Additionally, most of the applicable sensors are based on surrogate methods which results in a considerable effort for reference measurements for sensor calibration. Finally, it has to be considered that, depending on the sewer network topography, deposition and remobilisation of pollutants varies considerably, which limits the generality of monitoring results and, subsequently, their applicability as a base for the design of storm water tanks or combined sewer overflows (CSO). A monitoring station for continuous monitoring of load discharges from a CSO has been installed and operated for more than one year. The design and equipment of the measurement station, operational experiences and results are given in this paper.

Calibration↗

PubMed2004