The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.
Response repetitions aid performance when a task repeats but impair performance when a task switches. Although this interaction is robust, theoretical accounts remain controversial. Here, we used an un-cued, predictable task-switching paradigm with univalent targets to explore whether a simple bias to switch the response when the task switches can explain the interaction. In Experiment 1A (n = 40), we replicated the basic interaction in a two-choice task. In Experiment 1B (n = 60), we observed the same interaction in a three-choice task, wherein a bias to switch the response when the task switches cannot prime a specific alternative response because both remaining response alternatives are equally likely. Exploratory comparisons revealed a larger interaction between task repetition and response repetition in the three-choice task than in the two-choice task for mean response time (RT) and the opposite pattern for mean error rate (ER). Critically, in the three-choice task, response-repetition costs in task switches were significant in both RT and ER. Since a bias to switch the response cannot prime a specific response alternative in a three-choice task, we conclude that such a bias cannot account for response-repetition costs in task-switch trials.
The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.
In a randomized, double blind parallel group comparison the antiphlogistic and analgetic efficacy of high-dosed vitamin E (3 x 400 mg RRR-alpha-Tocopherolacetat/d) versus diclofenac-sodium has been investigated in hospitalized patients with established chronic rheumatoid arthritis. After 3 weeks of treatment the vitamin E group (n = 42) as well as the diclofenac group (n = 43) showed a significant improvement of all assessed clinical parameters. Duration of morning stiffness could be reduced under vitamin E treatment from 90 min to 68 min and under diclofenac treatment from 68 min to 30 min. The joint index according to Richie declined from 56 to 46 (vitamin E) and 49 to 34 (diclofenac). Grip strength increased in the vitamin E group as well as in the diclofenac group. In addition, the degree of pain, assessed by a 10 cm visual analogue scale, reduced significantly under vitamin E as well as under diclofenac. Regarding the therapeutical result both, physicians and patients, considered both drugs to be similarly effective. Especially regarding the risk profile of NSAR in long-term treatment of chronic rheumatoid arthritis intake of high-dosed vitamin E is a possible alternative in the treatment of inflammatory rheumatoid diseases.
Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
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