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Biomedical subjects

P Simpson

Publications and source records attributed to P Simpson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Frequencies of complex chromosome exchange aberrations induced by 238Pu alpha-particles and detected by fluorescence in situ hybridization using single chromosome-specific probes.

We undertook an analysis of chromosome-type exchange aberrations induced by alpha-particles using fluorescence in situ hybridization (FISH) with whole chromosome-specific probes for human chromosomes 1 or 4, together with a pan-centromeric probe. Contact-inhibited primary human fibroblasts (in G1) were irradiated with 0.41-1.00 Gy 238Pu alpha-particles and aberrations were analysed at the next mitosis following a single chromosome paint. Exchange and aberration painting patterns were classified according to Savage and Simpson (1994a). Of exchange aberrations, 38-47% were found to be complex derived, i.e. resulting from three or more breaks in two or more chromosomes, and the variation with dose was minimal. The class of complex aberrations most frequently observed were insertions, derived from a minimum of three breaks in two chromosomes. There was also an elevated frequency of rings. The high level of complex aberrations observed after alpha-particle irradiation indicates that, when chromosome domains are traversed by high linear energy transfer alpha-particle tracks, there is an enhanced probability of production of multiple localized double-strand breaks leading to more complicated interactions.

Alpha Particles↗
PubMed1994

On the scoring of FISH-"painted" chromosome-type exchange aberrations.

The effectiveness of FISH painting for easy detection of radiation-induced chromosome aberrations lies, principally, in the fact that only part of any exchange event is highlighted. However, this partial detection imposes certain limitations when the technique is applied to fundamental studies with primary aberrations, particularly at higher doses, when Complex exchanges are present. Some of these limitations are discussed in this paper.

Animals↗
PubMed1994

Alterations in plasma phosphorus, red cell 2,3-diphosphoglycerate and P50 following open heart surgery.

OBJECTIVES: To evaluate changes in and the correlation between plasma phosphorus, red cell 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP), and P50 in children following heart surgery. EXPERIMENTAL DESIGN: Prospective, observational study with factorial design. SETTING: A pediatric intensive care unit in a university hospital. PATIENTS: Twenty children undergoing open heart surgery for congenital heart defects. INTERVENTIONS: None. MEASURES: Red cell 2,3-DPG and ATP, P50, plasma phosphorus, and arterial lactate were obtained before and at 1, 8, 16, 24, 48, and 72 hours after surgery. The amount of intravenous fluid and glucose administered, and age of blood utilized were documented. Variables were analyzed by repeated measure analysis of variance followed by paired t-tests. To investigate the relationship between variables at each time point, scatterplot matrices and correlation coefficients were obtained. RESULTS: There was a reduction in plasma phosphorus, red cell 2,3-DPG, and P50 and an increase in arterial lactate at 1, 8, 16, 24, 48, and 72 hours after surgery. Red cell 2,3-DPG correlated with P50 at 1, 8 and 16 hours. The decrease in the plasma phosphorus correlated with the amounts of intravenous fluid and glucose administered on the day of surgery and on the first and second postoperative days. The age of the blood utilized correlated with the decrease in red cell 2,3-DPG on the day of surgery. CONCLUSIONS: Reduction in red cell 2,3-DPG, P50, and plasma phosphorus occurs after open heart surgery in children. These changes can potentially contribute to impaired oxygen utilization in the postoperative period, when adequacy of tissue oxygenation is critical.

2,3-Diphosphoglycerate↗
PubMed1993

Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch.

During neurogenesis in Drosophila, groups of equipotential, neurally competent cells choose between epidermal and neural fates. Notch, a phylogenetically conserved transmembrane protein, may act as a receptor in a lateral signalling pathway in which a single neural precursor is chosen from each group and the neural fate of the other cells is inhibited, causing them to differentiate into epidermis. Possible intracellular transduction events mediating signals from Notch are, however, unknown. shaggy is also required for the lateral signal and encodes serine/threonine protein kinases with homology to the glycogen synthase kinase-3 (GSK-3) enzymes that act in signal transduction pathways in vertebrates. We report here that, in transgenic flies, GSK-3 beta can substitute for shaggy, and we also present a study of epistatic relationships between shaggy and gain and loss of function alleles of Notch. The results indicate that shaggy/GSK-3 is part of a signalling pathway downstream of Notch.

Animals↗
PubMed1993

Functional significance of a family of protein kinases encoded at the shaggy locus in Drosophila.

The characterization of the structurally complex gene shaggy is presented. This gene encodes multiple proteins with putative serine/threonine kinase activity thought to be involved in signal transduction mechanisms that take place during several patterning events throughout Drosophila development. The gene comprises two transcription units that give rise to 10 transcripts and five different proteins with a common kinase catalytic domain and overlapping patterns of expression during development. Mutational analysis of shaggy defines a single complementation group, lethality of which is associated with the loss of two major shaggy proteins. These studies allow the first definition of a true null allele. Two proteins may fulfill maternal requirements. Phenotypes of flies expressing individual shaggy proteins revealed that although there is some redundancy between the different forms they do not all carry out identical functions in vivo. However, under experimental conditions, a single form of the protein was able to carry out all known requirements. This protein probably also functions as part of a signal transduction cascade in the imaginal neuroepithelium, where cells have to choose between epidermal and neural fates.

Age Factors↗
PubMed1993

Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster.

A cytogenetic analysis of the 43A-E region of chromosome 2 in Drosophila melanogaster is presented. Within this interval 27 complementation groups have been identified by extensive F2 screens and ordered by deletion mapping. The region includes the cellular polarity genes prickle and spiny-legs, the segmentation genes costa and torso, the morphogenetic locus sine oculis and is bounded on its distal side by the eye-color gene cinnabar. In addition 19 novel lethal complementation groups and two semi-lethal complementation groups with morphogenetic escaper phenotypes are described.

Alleles↗
PubMed1993

Linking family theory and practice: a family nursing program.

Family nursing, always a component of nursing, has been recently receiving increased attention through publications, educational programs, clinical practice settings and family nursing research. Nurses are in the best position to assist families experiencing the illness of a loved one, but often lack the skills and confidence necessary to assist with the psychosocial needs. The purpose of this paper is to describe the development and implementation of a family nursing program within a large, tertiary care facility. The program's evaluation is ongoing but early outcomes indicate that day-to-day nursing practice has been positively influenced and improved job satisfaction may result.

Alberta↗
PubMed1993

High-resolution cytogenetic analysis of X-ray induced mutations of the HPRT gene of primary human fibroblasts.

We report cytogenetic analysis of X-ray induced mutants of the HPRT gene isolated from a primary human fibroblast line. The mutants were shown previously by molecular analysis to have total or partial HPRT gene deletions. Detailed analysis of the chromosomal region containing HPRT (the cytogenetic band Xq26) identified Xq26 aberrations in five of five total HPRT gene deletions but failed to detect any changes in two of two partial gene deletions. Four microdeletions were verified and quantified by a method termed the band ratio, which compares the distance between bands encompassing Xq26 and an adjacent X-chromosome region in elongated chromosomes. These measurements were supported by the presence or absence of the sub-band Xq26.2. One total HPRT gene deletion was also associated with an X;11 translocation involving band Xq26. The data strengthen earlier findings on the tolerance of the Xq26 region to large genetic changes (> 1 Mb), but also indicate that some mutations are more complex than simple deletion of DNA sequence.

Cells, Cultured↗
PubMed1993

Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions.

In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

Animals↗
PubMed1993

pannier, a negative regulator of achaete and scute in Drosophila, encodes a zinc finger protein with homology to the vertebrate transcription factor GATA-1.

The gene pannier acts as a repressor of achaete and scute, two transcription factors expressed in discrete subsets of cells at the sites where neural precursors develop. Molecular analysis of mutant alleles revealed the presence of two functional domains within the pannier protein: a zinc finger domain showing homology to the GATA-1 family of vertebrate transcription factors and a domain comprising two putative amphipathic helices. Mutants associated with lesions in the zinc finger domain display an overexpression of achaete and scute and the development of extra neural precursors. Mutant proteins in which the domain including the putative helices is deleted act as hyperactive repressor molecules causing a loss of achaete/scute expression and a loss of neural precursors. Other results suggest that the activity of pannier may be modulated by association with position-specific factors.

Amino Acid Sequence↗
PubMed1993

A dual role for the protein kinase shaggy in the repression of achaete-scute.

achaete and scute are expressed in a spatially restricted pattern and provide neural potential to cells. The domains of expression depend partly on extramacrochaetae whose product is itself spatially restricted and acts as a negative post-translational regulator of achaete and scute. The protein kinase shaggy also represses achaete and scute at many sites but may act via intermediate transcription factors. However shaggy and extramacrochaetae act synergistically and molecular studies suggest that they may be part of the same pathway. shaggy is functionally homologous to the mammalian glycogen synthase kinase-3 and analogy with the known physiology of this enzyme, suggests that this function of shaggy may result from the "constitutive" activity. At the site where a single neural precursor will develop, achaete and scute are initially expressed in a group of equivalent cells. The genes Notch and Delta are part of a lateral signal required to single out one precursor cell and to silence achaete and scute expression in the other cells. shaggy is required downstream of Notch for transduction of the inhibitory signal. This second role of shaggy may be due to modulation of enzymatic activity during signalling.

Animals↗