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Biomedical subjects

A Pearson

Publications and source records attributed to A Pearson.

At least 19 recordsLinked to original sources

Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster.

Mammalian class A macrophage-specific scavenger receptors (SR-A) exhibit unusually broad binding specificity for a wide variety of polyanionic ligands. The properties of these receptors suggest that they may be involved in atherosclerosis and host defense. We have previously observed a similar receptor activity in Drosophila melanogaster embryonic macrophages and in the Drosophila macrophage-like Schneider L2 cell line. Expression cloning was used to isolate from L2 cells a cDNA that encodes a third class (class C) of scavenger receptor, Drosophila SR-CI (dSR-CI). dSR-CI expression was restricted to macrophages/hemocytes during embryonic development. When expressed in mammalian cells, dSR-CI exhibited high affinity and saturable binding of 125I-labeled acetylated low density lipoprotein and mediated its chloroquine-dependent, presumably lysosomal, degradation. Although the broad polyanionic ligand-binding specificity of dSR-CI was similar to that of SR-A, their predicted protein sequences are not similar. dSR-CI is a 609-residue type I integral membrane protein containing several well-known sequence motifs, including two complement control protein (CCP) domains and somatomedin B, MAM, and mucin-like domains. Macrophage scavenger receptors apparently mediate important, well-conserved functions and may be pattern-recognition receptors that arose early in the evolution of host-defense mechanisms. Genetic and physiologic analysis of dSR-CI function in Drosophila should provide further insights into the roles played by scavenger receptors in host defense and development.

Amino Acid Sequence

Pressure ulcer prophylaxis in elderly patients using polyurethane foam or Jay wheelchair cushions.

A significantly lower proportion of the patients in the Jay group (25%) experienced pressure ulcer formation during the three months of observation as compared to the foam group (41%). No statistically significant differences were found between groups on the location, severity, or healing duration of the pressure ulcers. Most lesions (65%) were limited to persistent erythema of intact skin, and healed in three to four weeks. Significantly higher proportions of patients in the Jay groups (7%) rejected their cushion because of discomfort as compared to foam (1%). The incidence of pressure ulcers was significantly higher among those patients who experienced peak interface pressures recorded at 60 mmHg or higher, had low Norton scores (< or = 11), or were malnourished.

Aged

Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53.

Acidic transcriptional activation domains function well in both yeast and mammalian cells, and some have been shown to bind the general transcription factors TFIID and TFIIB. We now show that two acidic transactivators, herpes simplex virus VP16 and human p53, directly interact with the multisubunit human general transcription factor TFIIH and its Saccharomyces cerevisiae counterpart, factor b. The VP16- and p53-binding domains in these factors lie in the p62 subunit of TFIIH and in the homologous subunit, TFB1, of factor b. Point mutations in VP16 that reduce its transactivation activity in both yeast and mammalian cells weaken its binding to both yeast and human TFIIH. This suggests that binding of activation domains to TFIIH is an important aspect of transcriptional activation.

Fungal Proteins

Mouse micronucleus assays of sporidesmin, the toxin associated with facial eczema in ruminants.

Sporidesmin, a fungal toxin with widespread distribution within New Zealand, was previously shown to be a potent clastogen in Chinese hamster cells in vitro, but not in peripheral blood lymphocytes of sheep in vivo. In mice, massive oral doses led only to slight increases in micronucleus levels in the bone marrow, despite highly significant changes to other toxicological parameters. It would appear that the intact animal is protected in some fashion from the clastogenic effects of sporidesmin, although this substance must still be considered a potential human genotoxic agent.

Animal Diseases

Staff in Australian nursing homes: their qualifications, experience and attitudes.

This paper is based upon findings from a study carried out by the Institute of Nursing Research between 1989 and 1990. The major objective of the study was to determine the impact of staffing mix on nursing home residents' quality of care and life as measured against the standards set out in 'Living in a Nursing Home'. An additional objective was to identify if there are any factors which may constrain or influence optimality. 'Skills mix' is sometimes used to describe the ratio of different levels of staff in terms of qualifications. The literature suggests, however, that such factors are only one dimension of skills mix in terms of the skills which people bring into their work in nursing homes. Other factors include the numbers of staff; the mix of staff in terms of level of qualification; the life experience of staff; and the educational experience of staff. This paper examines the findings of the study in the light of staff characteristics based on the criteria identified.

Attitude of Health Personnel

Photo-enhancement of the mutagenicity of 9-anilinoacridine derivatives related to the antitumour agent amsacrine.

The frameshift mutagenicity of the DNA intercalating drug proflavine is known to be enhanced by photoirradiation of bacterial cultures. To determine whether this phenomenon was also present in acridine-derived antitumour drugs, cultures of Salmonella typhimurium were exposed to the antileukaemia agent amsacrine and the experimental agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide dihydrochloride (acridine carboxamide) in the presence or absence of visible light. A small increase in mutagenicity was observed with amsacrine but not with acridine carboxamide. A series of analogues of amsacrine were then tested, and a striking relationship was found between the minimum drug concentration for mutagenicity and DNA binding affinity. In each case, photoirradiation was associated with a small increase in mutagenicity. Each of the compounds showing the photo-enhancement effect was capable of reversible one-electron oxidation. It is suggested that this oxidation occurs in bacteria, and that the DNA binding constant of the resulting acridine radical species will increase because of the extra positive charge. This increased DNA binding would be sufficient to explain the photo-enhancement of mutagenicity of these drugs.

Acridines

Chromosomal changes in Chinese hamster AA8 cells caused by podophyllin, a common treatment for genital warts.

Podophyllin, a plant derivative of variable composition, is used widely within New Zealand as a treatment for genital warts. One local source of podophyllin has been tested for ability to cause mutagenic effects in Salmonella typhimurium as well as for effects on chromosomes of Chinese hamster AA8 cells. Although only weakly mutagenic in one strain of Salmonella, podophyllin caused structural aberrations as well as changes in chromosome number in the Chinese hamster cells. The range of aberrations was similar to those caused by teniposide, a close structural relative of the major component, which was used as a positive control in the Chinese hamster cell experiments. A literature review revealed that podophyllin was shown to cause changes of chromosome number in the mouse cervix in vivo, although aberrations were not studied. Patients treated with podophyllin will usually possess one form of the papilloma virus, and this itself may have some oncogenic potential. We suggest that podophyllin could potentiate these effects and question its continued widespread use.

Animals

In vitro and in vivo mutagenicity studies on sporidesmin, the toxin associated with facial eczema in ruminants.

Sporidesmin, a fungal toxin with widespread distribution within New Zealand, is thought to exert toxic effects through oxidative damage. The purified chemical was tested for its ability to cause point mutations in four strains of Salmonella typhimurium (TA98, TA100, TA102 and TA1537), in the presence and absence of exogenous metabolic activation. Although toxic effects were seen at concentrations exceeding 400 mu gl/plate, there were no significant increases in revertant colonies. In strain TA102, these results were not modified by the presence of glutathione. In AA8 Chinese hamster cells, sporidesmin acted as a potent clastogen, causing chromosomal breaks at concentrations as low as 3 ng/ml, where there was very little reduction in cell viability. Effects were primarily at the chromatid level, but some chromosomal events were also seen. Following low doses, the most common events were chromatid deletions and induction of double minute chromosomes. Interchange events occurred at concentrations of 10 ng/ml and above. The most common of these events was an incomplete chromatid interchange, although some examples of complete chromatid and chromosomal interchange were seen. These in vitro experiments were subsequently extended to an in vivo study of sporidesmin-induced lymphocytic micronuclei (MN) in sheep. In a double blind experiment, 5 sheep were treated with a single high dose of sporidesmin. Blood samples were taken from these, and from 5 untreated sheep, at various intervals before and after treatment. Peripheral blood lymphocytes cultures were harvested and scored for MN in cytokinesis-blocked cells, as a measure of clastogenic activity of sporidesmin in vivo. Following decoding, statistical analysis of the data revealed no significant differences between the MN levels in peripheral blood lymphocytes of sporidesmin-treated and untreated sheep. Although the possibility still exists that clastogenic effects could occur in other species, the data indicate that sporidesmin is not a clastogen in sheep, even though this species is highly susceptible to the toxic effects of sporidesmin.

Animals

Skills mix in Australian nursing homes.

This study investigated the relationships between skills mix, resident dependency and the quality of care and life of residents in a stratified random sample of 200 non-government homes in four Australian states. The study considered various measures of skills mix including the qualifications of the staff (staffing mix), the exposure of staff to in-service training and the leadership style of the director of nursing. The only relationships found between staffing mix (that is, the proportion of qualified and unqualified staff) related to the positive effect of therapy staff on the variety of experience of residents. Significant relationships between a number of other components of skills mix and the outcomes of care were found. Specifically, exposure to in-service training of staff and the leadership style of the director of nursing affected quality of care. State enrolled nurses were found to be significantly less satisfied with their work than registered nurses or untrained nurse assistants. Further studies are suggested in these areas and a review of skills mix in relation to them is recommended.

Activities of Daily Living

Management and leadership in Australian nursing homes.

This paper is based on the outcomes of a study undertaken by Deakin Institute of Nursing Research for the Department of Community Services and Health between 1988 and 1990 (1). The study, which looked at the relationship between skills mix and resident outcomes, involved gathering data from 200 nursing homes in four Australian states using questionnaires and a case study approach. One of the major findings related to the importance of the management and leadership style on the outcome of quality of care and life within the nursing home. The pivotal role of the senior nurse (ie the director of nursing or charge nurse) in affecting high quality is consistently reported in the literature and this was confirmed by the study. Factors drawn from the quantitative and qualitative parts of the study, which make an important contribution to the quality of care experienced by residents, included the director of nursing's attitude, commitment and interpersonal skills. Also important were the ideology of the staff, team cohesiveness and positive attitude and an overall staffing environment which adheres to an agreed philosophy and is stable, satisfied and friendly. All of these were found to be influenced by the senior nurse.

Aged

A comparison of quality of care using Phaneuf's Nursing Audit.

The quality of nursing care delivered to two groups of patients suffering from diabetes mellitus was examined. Using Phaneuf's Nursing Audit, a retrospective audit of the nursing documentation regarding the care of all patients was carried out, and a comparison made of the numeric scores obtained. The nursing care of the group of patients from the Professional Nursing Unit (PNU) obtained mean scores which were 26.4% higher than those obtained by the group from the general hospital wards. There are major variations in scores in specific areas. These give rise to some questions regarding the value to nurses of the caring and nurturing component of nursing work, and how this is affected by differing philosophies and environments.

Adolescent

The 5' noncoding region sequence of the Choristoneura biennis entomopoxvirus spheroidin gene functions as an efficient late promoter in the mammalian vaccinia expression system.

About 100 nucleotides of DNA sequence at the 5' noncoding region of the Choristoneura biennis entomopoxvirus spheroidin gene was chemically synthesized and inserted into a vaccinia expression vector, interrupting the vaccinia thymidine kinase gene. When the bacterial beta-galactosidase gene was introduced downstream of this sequence and a recombinant vaccinia virus containing these inserts was obtained by homologous recombination, beta-galactosidase was shown to be expressed at a high level late in the vaccinia infection cycle. The level of beta-galactosidase expression was four- to fivefold higher with this spheroidin-vaccinia recombinant virus than with a similar recombinant in which the beta-galactosidase gene was under the control of the vaccinia 7.5-kDa promoter. Primer extension and S1 mapping of the 5' terminus of the beta-galactosidase transcript located the transcription initiation site within the spheroidin DNA sequence, confirming the promoter nature of this DNA sequence in the vaccinia system. Dot blot analysis indicated that the difference in beta-galactosidase expression with these two recombinant viruses can be attributed to the difference in their transcript levels. We also demonstrated that full promoter activity encoded in the spheroidin 5' noncoding sequence was contained within a 38-nucleotide DNA fragment.

Animals