Biomedical subjects

D A McDonald

Publications and source records attributed to D A McDonald.

12 recordsLinked to original sources

PubMed1992

Post-transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells.

The regulation of urokinase plasminogen activator (uPA) expression was investigated in 2 highly metastatic rat mammary adenocarcinoma cell lines, BC1 and MAT 13762. BC1 cells were observed to synthesize, on average, 10 times less uPA enzyme and mRNA than MAT 13762 cells; however this difference was not accounted for by differences in uPA gene copy number/structure or in the rate of uPA gene transcription in the cell lines studied. Moreover, Northern blot analysis of invasive sub-populations derived in vitro from the BC1 cell line revealed levels of uPA expression similar to those of the parent, but a 3-fold elevation in expression of the metalloprotease gene, transin. Further investigation showed that treatment of BC1 cells with either of the protein synthesis inhibitors, cycloheximide or anisomycin, increased the level of both nuclear and cytoplasmic uPA RNA 6- to 18-fold in 4 hr, whilst inducing a maximum 2.6-fold increase in the rate of uPA gene transcription. This increase in uPA gene expression may therefore reflect, in part, an increase in the stability and/or processing of nuclear uPA transcripts. These results suggest that the degree of uPA gene expression does not correlate directly with BC1 tumor-cell invasion in vitro, and that the uPA gene is down-regulated, at least in part, post-transcriptionally in the nucleus of BC1 mammary tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Reliability, validity and utility of the Fitness Interview Test.

Psychiatrists are being asked more and more often by the courts to determine whether or not criminal defendants are fit to stand trial. However, the Criminal Code provides few statutory guidelines on what constitutes fitness to stand trial. Perhaps as a result of the lack of standards, psychiatrists have typically relied on traditional clinical assessment procedures in determining whether or not an individual is fit to stand trial. In an effort to improve the quality and consistency of forensic assessments, researchers have designed instruments to assess fitness to stand trial. In Canada, the Fitness Interview Test (FIT) was developed for this purpose. This study evaluated the FIT for its validity, reliability and utility in the assessment of fitness. The FIT was found to have excellent interrater reliability and scale homogeneity. In addition, it was able to discriminate between groups of defendants rates as being fit and or unfit to stand trial. The scale did not seem to be differentially sensitive to the diverse facets of fitness, which may be attributed to the format and content of the scale items. Caution is advised in the use of the FIT pending revision of the scale.

Adult↗

PubMed1989

Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells.

We have investigated differences in gene expression between a metastatic and nonmetastatic clone of the DMBA-8 rat mammary adenocarcinoma cell line and have previously identified a differentially expressed gene WDNM1 (T.N. Dear, I.A. Ramshaw, and R.F. Kefford, Cancer Res., 48: 5203-5209, 1988). To further investigate differences in mRNA expression between these cell lines, a complementary DNA library from the nonmetastatic cell line was probed with labeled complementary DNA enriched for sequences specific to this line. We report here the identification in nonmetastatic cells of a second gene, WDNM2, which encodes a 1.7-kilobase mRNA corresponding to a protein (Mr 28,000-30,000) the expression of which shows a positive correlation with the nonmetastatic phenotype in three independently derived rat mammary adenocarcinoma cell lines and is regulated transcriptionally. Homologous sequences in the human genome have been identified. The function of this new gene may relate to regulation of the metastatic phenotype in this tumor.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1983

Dehydroepiandrosterone sulfotransferase localization in human adrenal glands: a light and electron microscopic study.

Dehydroepiandrosterone sulfate is the major secretory product of the human adrenal cortex. The enzyme responsible for the sulfurylation, which has been isolated previously, possesses kinetic properties suggesting that it plays an important regulatory role in dehydroepiandrosterone sulfate secretion. In order to study the localization of the enzyme in the respective zones and cells of the cortex, an antibody to the pure enzyme was raised and the immunoglobulin G fraction employed in the peroxidase-antiperoxidase method. Staining was confined to the zona reticularis but was unevenly distributed throughout the cells. Electron microscopic examination of sections prepared from fresh adrenal tissue fixed in glutaraldehyde, revealed that the enzyme was predominantly clustered around lipid droplets. It is suggested that this may reflect an association of organelles, cholesterol being transported from lipid droplets to surrounding mitochondria, and pregnenolone then being converted to dehydroepiandrosterone in the adjacent endoplasmic reticulum and thence immediately sulfurylated.

Adrenal Glands↗

PubMed1973