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Biomedical subjects

L McMorrow

Publications and source records attributed to L McMorrow.

6 recordsLinked to original sources

Chromosomes exhibit preferential positioning in nuclei of quiescent human cells.

The relative spatial positioning of chromosomes 7, 8, 16, X and Y was examined in nuclei of quiescent (noncycling) diploid and triploid human fibroblasts using fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes and digital imaging. In quiescent diploid cells, interhomolog distances and chromosome homolog position maps revealed a nonrandom, preferential topology for chromosomes 7, 8 and 16, whereas chromosome X approximated a more random distribution. Variations in the orientation of nuclei on the culture substratum tended to hinder detection of an ordered chromosome topology at interphase by biasing homolog position maps towards random distributions. Using two chromosome X homologs as reference points in triploid cells (karyotype = 69, XXY), the intranuclear location of chromosome Y was found to be predictable within remarkably narrow spatial limits. Dual-FISH with various combinations of chromosome-specific DNA probes and contrasting fluorochromes was used to identify adjacent chromosomes in mitotic rosettes and test whether they are similarly positioned in interphase nuclei. From among the combinations tested, chromosomes 8 and 11 were found to be closely apposed in most mitotic rosettes and interphase nuclei. Overall, results suggest the existence of an ordered interphase chromosome topology in quiescent human cells in which at least some chromosome homologs exhibit a preferred relative intranuclear location that may correspond to the observed spatial order of chromosomes in rosettes of mitotic cells.

Cell Cycle↗

Precise spatial positioning of chromosomes during prometaphase: evidence for chromosomal order.

The relative locations of several chromosomes within wheel-shaped prometaphase chromosome rosettes of human fibroblasts and HeLa cells were determined with fluorescence hybridization. Homologs were consistently positioned on opposite sides of the rosette, which suggests that chromosomes are separated into two haploid sets, each derived from one parent. The relative locations of chromosomes on the rosette were mapped by dual hybridizations. The data suggest that the chromosome orders within the two haploid sets are antiparallel. This chromosome arrangement in human cells appears to be both independent of cell type- and species-specific and may influence chromosome topology throughout the cell cycle.

Cells, Cultured↗

Epigenetic lesions at the H19 locus in Wilms' tumour patients.

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.

Alleles↗

Distribution of heavy metals in Gove Harbour, Northern Territory, Australia.

The concentration of four metals in waters and eight metals in oysters and sediments from Gove Harbour, Northern Territory, were determined during the dry season of 1987. The measured concentrations of zinc, cadmium, copper and lead in unfiltered waters were: 1.10-7.28, 0.10-2.20, 0.25-3.45 and 0.15-2.87 micrograms l-1, and zinc, cadmium, copper, lead, aluminium, nickel, manganese and iron in oysters, 60.1-970, 0.14-4.07, 3.77-30.67, ND-0.46, 6.50-1123.0, 0.02-0.44, 0.24-2.04 and 4.28-981.3 micrograms g-1 wet weight, and in sediments, 0.09-22.24, ND-0.45, ND-5.95, ND-2.98, 229.98-16053.5, 0.21-7.70, 13.77-50.24 and 759.5-2659.6 micrograms g-1 dry weight. Concentrations of zinc, aluminium and cadmium were higher in the oysters. The level of cadmium exceeded the National Health and Medical Research Council (NHMRC) recommended limit. In general, levels of these and other metals were higher near a bauxite treatment plant.

Animals↗

Growth of granulopoietic bone marrow cells of RF mice.

Mice of the RF strain are unusually susceptible to the development of leukemia, both spontaneously and after whole body irradiation. Cell culture and transplantation techniques were used to study the proliferative capacity of hematopoietic tissues of these mice. The growth characteristics of granulopoietic cells of young, non-irradiated RF mice were compared with those from a leukemia-resistant strain, C57BL/6J (B6). Marrow from RF mice showed a substantial reduction in the number of colony-forming units in culture (CFUC). The numbers of marrow cells capable of forming colonies in the spleen of lethally irradiated syngeneic mice (CFUS) were also reduced. The spleens from non-irradiated RF mice were almost twice the size of those from B6 mice. Despite these differences the numbers of circulating peripheral leukocytes and percent of polymorphonuclear leukocytes were similar in the two strains. Bone marrow from RF mice may be analogous to that of certain human "preleukemic" states in which alterations in marrow cells are demonstrable in culture.

Animals↗