Biomedical subjects

D A McDonald

Publications and source records attributed to D A McDonald.

16 recordsLinked to original sources

PubMed1994

Isolation and preliminary characterisation of an X-ray-sensitive mammalian mutant cell line (WMXRS-1).

Mammalian cell lines that are sensitive to particular genotoxic agents have proved the most effective starting point for the cloning of human DNA-repair genes. After ethyl methanesulphonate mutagenesis of the parent murine fibroblast L-cell line, a new mammalian X-ray-sensitive cell line (WMXRS-1) was isolated. For selection of the mutant, a novel detection method was used: putative X-ray-sensitive clones were identified by their lack of incorporation of the DNA precursor, bromodeoxyuridine, after irradiation. The WMXRS-1 cell line was collaterally sensitive to ultraviolet radiation and some other agents known to be removed from DNA by the nucleotide excision repair pathway, but not to bleomycin or hydrogen peroxide. In relation to the wild-type strain, WMXRS-1 showed a similar pattern of induction of micronuclei up to an X-ray dose of 4 Gray and a similar DNA double-strand break (dsb) induction profile. The overall level of dsb rejoining was the same in the parent and mutant lines. However, WMXRS-1 demonstrated a reduced initial rate of dsb-rejoining, perhaps accounting for its radiosensitivity. WMXRS-1 also showed a greater G2 cell cycle phase accumulation after treatment with mitomycin-C. The cross-sensitivity profile and strand-break rejoining deficiency phenotype of WMXRS-1 is unique amongst previously characterised mammalian mutant cell lines.

Animals↗

PubMed1994

Use of archival and fresh cytologic material for the polymerase chain reaction. Detection of the bcl-2 oncogene in lymphoid tissue obtained by fine needle biopsy.

A technique for extracting DNA from archival and fresh tissue from fine needle biopsy (FNB) samples for the polymerase chain reaction (PCR) is described. The method was used to detect the bcl-2 oncogene in various cytologic lymphoid preparations. The DNA was amplified with primers specific for the major break point region of the t(14;18) translocation, and the presence of the bcl-2 oncogene was correlated with clinical, cytomorphologic, histologic and immunologic findings. Thirty patients who had FNB of lymphoid tissue were randomly selected, 18 retrospectively and 12 prospectively. Bcl-2 was present in 3 of 8 cases of reactive lymphadenopathy and 9 of 22 cases of non-Hodgkin's lymphoma. Of these, seven had follicular small cleaved cell lymphoma, and two had large cell lymphoma. Smears, both archival and fresh, and cell suspensions provided sufficient DNA for PCR amplification. The technique has potential applications in several areas of cytologic and hematologic practice.

Adolescent↗

PubMed1993

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): cytologic diagnosis by fine-needle biopsy.

A cytologic diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi's lymphadenitis) was made in a 14-yr-old female with cervical lymphadenopathy, fever, neutropenia, and hepatosplenomegaly. A predominance of reticulum cells, foamy macrophages, and karyorrhectic debris are clues to the diagnosis in the fine-needle biopsy smears. Subsequent histology confirmed the diagnosis of Kikuchi's lymphadenitis. The differential diagnoses are discussed including malignant lymphoma, which was excluded by morphology as well as flow cytometry and polymerase chain reaction (PCR) studies.

Adolescent↗

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