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Biomedical subjects

L Arthur

Publications and source records attributed to L Arthur.

14 recordsLinked to original sources

An assessment of exposure indices in computed radiography for the posterior-anterior chest and the lateral lumbar spine.

Studies have indicated that computed radiography (CR) can increase radiation dose to the patient, leading to potential biological effects. Although manufacturers have set parameters to safeguard against overexposure, it is unclear whether these are being used by radiographers or if their recommended values are consistent with the ALARA principle. The research aims are to investigate (i) whether radiographers are producing images with exposure indices within the manufacturers recommended range (MRR); (ii) the phenomenon of exposure creep, and (iii) the relationship between exposure indices (EIs) and radiation dose. A retrospective analysis of exposure indices over an 18-month period for the posteroanterior (PA) chest and lateral (LAT) lumbar spine at two centres using Kodak 800 and 850 CR systems was conducted. A phantom study was performed to assess the relationship between EI and entrance surface dose (ESD) for fixed and varying tube potentials. Kodak recommends that images have EIs between 1700 and 1900. Thirty percent of LAT lumbar spine examinations at hospital B and 38% of PA chest examinations at hospital A were produced with EIs below 1700. In the phantom study, when using a varied tube potential (70-125 kVp) and maintaining a constant EI of 1550, ESD was reduced by 56%. All clinical and phantom images were assessed to be of a diagnostic quality. The retrospective results indicate that there is a potential to reduce the MRR and optimize patient dose. There is also evidence to suggest that EI is not a reliable indicator of patient dose. The authors recommend that staff training is essential on these newer systems.

Body Burden↗

Lectin-mediated transport of nanoparticles across Caco-2 and OK cells.

Recent experiments by a number of workers have suggested that it may be possible to use various targeting molecules, which bind to the intestinal epithelium, to promote the uptake and transport of nanoparticles from the intestine to the circulation. We have used commercial nanoparticles to examine the effect of size, density and inhibitors on uptake of lectin-coated nanoparticles by epithelial cells. The degree of uptake was most influenced by the density of lectin on the particle, with size and type of lectin being less important. Uptake could be inhibited by the presence of specific sugars or free lectin. These studies should provide a good basis for the design of targetable biodegradable drug-loadable particles suitable for oral delivery.

Acetylglucosamine↗

Vitamin B12-mediated transport of nanoparticles across Caco-2 cells.

Several studies have shown that Caco-2 cells have the capability to transport peptides and proteins from their apical to basal surfaces when these molecules are linked to vitamin B12 (VB12). In this study we have extended these studies and have shown that Caco-2 cells are also able to internalize and transport VB12-modifed nanoparticles from their apical to basal surfaces. Uptake and transport of nanoparticles was found to occur in both a VB12-dependent intrinsic factor (IF)-independent manner as well as in a VB12-dependent IF-dependent manner. Both IF-independent and IF-dependent VB12-mediated uptake and transport were dependent upon the surface density of VB12 as a reduction in surface modification of the nanoparticles with VB12 resulted in a reduced level of both VB12-mediated and IF-mediated uptake. At lower levels of VB12 modification there was no apparent non-IF-mediated uptake; however, VB12-IF-mediated uptake was still measurable. These studies show that Caco-2 cell cultures are a suitable model for the study of VB12-mediated uptake and transport of nanoparticles, and suggest that for effective oral uptake of VB12-coated nanoparticles high surface densities of VB12 are required.

Biological Transport↗

The essential role of yeast topoisomerase III in meiosis depends on recombination.

Yeast cells mutant for TOP3, the gene encoding the evolutionary conserved type I-5' topoisomerase, display a wide range of phenotypes including altered cell cycle, hyper-recombination, abnormal gene expression, poor mating, chromosome instability and absence of sporulation. In this report, an analysis of the role of TOP3 in the meiotic process indicates that top3Delta mutants enter meiosis and complete the initial steps of recombination. However, reductional division does not occur. Deletion of the SPO11 gene, which prevents recombination between homologous chromosomes in meiosis I division, allows top3Delta mutants to form viable spores, indicating that Top3 is required to complete recombination successfully. A topoisomerase activity is involved in this process, since expression of bacterial TopA in yeast top3Delta mutants permits sporulation. The meiotic block is also partially suppressed by a deletion of SGS1, a gene encoding a helicase that interacts with Top3. We propose an essential role for Top3 in the processing of molecules generated during meiotic recombination.

Amino Acid Sequence↗

The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase.

We have previously shown that cells mutant for TOP3, a gene encoding a prokaryotic-like type I topoisomerase in Saccharomyces cerevisiae, display a pleiotropic phenotype including slow growth and genome instability. We identified a mutation, sgs1 (slow growth suppressor), that suppresses both the growth defect and the increased genomic instability of top3 mutants. Here we report the independent isolation of the SGS1 gene in a screen for proteins that interact with Top3. DNA sequence analysis reveals that the putative Sgs1 protein is highly homologous to the helicase encoded by the Escherichia coli recQ gene. These results imply that Sgs1 creates a deleterious topological substrate that Top3 preferentially resolves. The interaction of the Sgs1 helicase homolog and the Top3 topoisomerase is reminiscent of the recently described structure of reverse gyrase from Sulfolobus acidocaldarius, in which a type I DNA topoisomerase and a helicase-like domain are fused in a single polypeptide.

Amino Acid Sequence↗

Genome rearrangement in top3 mutants of Saccharomyces cerevisiae requires a functional RAD1 excision repair gene.

Saccharomyces cerevisiae cells that are mutated at TOP3, a gene that encodes a protein homologous to bacterial type I topoisomerases, have a variety of defects, including reduced growth rate, altered gene expression, blocked sporulation, and elevated rates of mitotic recombination at several loci. The rate of ectopic recombination between two unlinked, homologous loci, SAM1 and SAM2, is sixfold higher in cells containing a top3 null mutation than in wild-type cells. Mutations in either of the two other known topoisomerase genes in S. cerevisiae, TOP1 and TOP2, do not affect the rate of recombination between the SAM genes. The top3 mutation also changes the distribution of recombination events between the SAM genes, leading to the appearance of novel deletion-insertion events in which conversion tracts extend beyond the coding sequence, replacing the DNA flanking the 3' end of one SAM gene with nonhomologous DNA flanking the 3' end of the other. The effects of the top3 null mutation on recombination are dependent on the presence of an intact RAD1 excision repair gene, because both the rate of SAM ectopic gene conversion and the conversion tract length were reduced in rad1 top3 mutant cells compared with top3 mutants. These results suggest that a RAD1-dependent function is involved in the processing of damaged DNA that results from the loss of Top3 activity, targeting such DNA for repair by recombination.

Cell Division↗

Characterization of immunostimulating complexes (ISCOMS) of HIV-1.

HIV-1, strain HTLV-III, propagated in H9 cells and purified by sucrose gradient centrifugation, was used as native antigen source for the preparation of immunostimulating complexes, HIV-iscoms. The major antigen detected in the iscom was the cell-derived HLA-DR, which readily could be removed from the virus lysate by immunosorbent. In the iscoms the HIV structural proteins MA p17, p55 and TM gp41 were identified; SU gp120 was present in only minute amounts in the virus lysate. The iscom particles appeared well preserved after freeze drying with a round shape, approximately 35 nm in diameter, comprising morphological subunits, assembled with icosahedral symmetry. Immunization experiments in mice reflected the antigen content of the iscoms. High antibody response was induced to HLA-DR in non-depleted iscoms. Major humoral responses were observed to the viral structural proteins MA p17, CA p24, p55, and also to TM gp41. A low or negligible antibody response to SU gp120 was induced by the HIV-iscoms. The negligible response was, however, overcome by the addition of recombinant gp160 to the virus lysate prior to formation of iscoms, resulting in a preparation evoking a clear serum antibody to gp160.

Animals↗

Specific cellular immune response and neutralizing antibodies in goats immunized with native or recombinant envelope proteins derived from human T-lymphotropic virus type IIIB and in human immunodeficiency virus-infected men.

Animals immunized with native or recombinant envelope proteins from the human immunodeficiency virus (HIV, formerly referred to as human T-lymphotropic virus type III) human T-lymphotropic virus type IIIB and naturally HIV-infected men were assessed for neutralizing antibodies and cell-mediated immunity toward the virus. Immunization of rabbits or goats with the native external envelope glycoprotein gp120 or with corresponding recombinant proteins elicited strictly type-specific neutralizing antibodies. A broad, group-specific cellular immune response to gp120 and to three different HIV isolates was seen in goats immunized with the native gp120 but not in animals immunized with the nonglycosylated recombinant envelope proteins. In HIV-infected people, no T-cell response was seen, even though their T-cell response toward other foreign antigens was intact. The results show type- and group-specific epitopes on gp120, some of which may be of importance for the development of a vaccine against HIV infection.

Acquired Immunodeficiency Syndrome↗

An astrocytoma.

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Astrocytoma↗

Characterization of a retravirus isolated from squirrel monkeys.

A new retravirus (SMRV) isolated from a squirrel monkey, Saimiri sciureus, has an Mg2+-dependen reverse transcriptase and a buoyant density of 1.17 g/cm3 in sucrose and 1.21 g/cm3 in cesium chloride, similar to the mouse mammary tumor virus and the Mason-Pfizer monkey virus. The polypeptide patter of SMRV as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was distinct from the reported polypeptide patterns of known retraviruses. Four major polypeptides of molecular weights 40,000, 20,000, 14,000 and 8,000 were resolved in virus propagated in human, mink, and canine cells. In A204 human rhabdomyosarcoma cells, a protein of 73,000 daltons (gp73) represented the major viral glycoprotein as determined by [3H]glucosamine labeling. Additional proteins were also observed, but their presence depended on the cell type in which the virus was propagated. In both species-and interspecies-specific assays, no antigenic relatedness was observed between SMRV and Mason-Pfizer monkey virus, mouse mammary tumor virus, baboon endogenous virus (BaLV), woolly monkey virus (SSV-1), murine leukemia virus, endogenous feline type C virus (RD-114), bovine leukemia virus, and equine infectious anemia virus. These findings indicate that SMRV represents a new retravirus and the first isolate from a New World monkey.

Animals↗

The deformed child.

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Congenital Abnormalities↗

[Chronic infection caused by the simian Mason-Pfizer virus in primate cell cultures].

Cell cultures of monkey prepuce (Rhfs) and African green monkey kidney (BSC-1) were infected once with simian Mason-Pfizer virus (MPV) and virus expression in the course of establishment of chronic infection was studied. The productive infection was characterized by changes in the cell metabolism (DNA synthesis increased 2-3-fold as early as the "zero" passage), the appearance of gs-antigen, formation of virions of type D and high activity of RNA-dependent DNA-polymerase. Multinuclear giant cells appeared only in the infected Rhfs cell culture most sensitive to MPV. In human embryo kidney culture (HEK) productive infection was also established however, HEK cultures did not survive after 3-4 passages. No signs of transformation could be found in any of the cultures studied.

Animals↗