PubMed Health⌕ Search

Biomedical subjects

P Nugent

Publications and source records attributed to P Nugent.

At least 19 recordsLinked to original sources

Undergraduate pre-registration nursing education in Australia: a longitudinal examination of enrollment and completion numbers with a focus on students from rural and remote campus locations.

INTRODUCTION: There is much evidence to indicate a shortage of Registered Nurses (RNs) in Australia and to suggest that the shortage may be more pronounced in rural and remote locations. Attracting RNs to work in rural and remote areas may not be as simple as increasing the intake of students into university undergraduate pre-registration nursing courses. There is some evidence indicating that student nurses may be more likely to enter the nursing workforce in rural and remote locations if they have existing associations with rural and remote areas and/or their undergraduate education provides opportunities to undertake supported placements in rural and remote settings. Two important difficulties have been associated with measuring outcomes in relation to rural and remote pre-registration nursing students. One is defining what constitutes a rural or remote location and the other is suspect data on the number of nursing students enrolled in, and completing, nursing courses. The aims of this study were to provide a longitudinal profile of the number of domestic students studying and completing undergraduate pre-registration nursing courses in Australia, with a particular emphasis on identifying those at rural and remote university campuses, and to compare results across States and Territories. METHODS: This study presents the combined findings from two investigative reports. Data on undergraduate pre-registration nursing student numbers were collected via electronic survey instruments completed by staff at all Australian educational institutions offering undergraduate pre-registration nursing education programs in 2001 and 2002. Australian domestic students were the focus of this study. Data included the total number of domestic students enrolled in undergraduate pre-registration nursing courses in 2001 and 2002, the number of domestic students who successfully completed courses in 1999, 2000 and 2001, and estimates for the number expected to complete in 2002. Surveys were sent to course coordinators or other staff nominated by heads of divisions of nursing at each institution. RESULTS: There was a 100% response rate. Twenty-four rural and remote campus locations were identified using an adjusted form of the Rural, Remote and Metropolitan Areas (RRMA) classification system. The Australian Capital Territory and the Northern Territory did not have any rural or remote campus locations. In contrast, undergraduate pre-registration nursing in Tasmania was offered at a rural campus only (for the first 2 years). From 2001 to 2002, there was an increase of just over 5% in the total number of domestic students enrolled in undergraduate pre-registration nursing courses in Australia (2002 total = 22,811 students). Rural and remote location students accounted for slightly more than 25% of these students in 2001, and almost 27% in 2002. The States Victoria, New South Wales and Queensland had the highest percentage of students enrolled at rural and remote campus locations, greater than the Australian average for both years. In contrast, South Australia and Western Australia had less than 11% of students enrolled at rural and remote campus locations for each year. Total undergraduate pre-registration course completions increased by approximately 16% across Australia between 1999 (n = 4868) and 2002 (n = 5667), although for 2002, the figure was projected. Of these total course completions, the percentage of students completing at rural and remote campus locations increased from almost 23% to nearly 28% during the same period. Of the States/Territories with both metropolitan and rural/remote campus locations, only Victoria and Queensland had more than 25% of their total student completions consisting of students enrolled at rural and remote campus locations for each year. In contrast, South Australia and Western Australia had approximately 6% of student completions consisting of students enrolled at rural and remote campus locations in 1999, increasing to approximately 12% projected for 2002. CONCLUSIONS: In this study, the authors attempted to improve the accuracy of data collection in relation to the number of domestic undergraduate pre-registration nursing students in Australia, which is representative of the potentially new Australian domestic RN workforce. There was a trend towards an increasing number of students being enrolled in undergraduate pre-registration nursing courses, and also toward an increasing number of course completions. From the perspective of the rural and remote RN workforce, the percentage of students enrolled and completing courses at rural and remote campus locations was found to be increasing. However, there may be some areas of concern for education and workforce planners in States and Territories that are providing a smaller percentage of their undergraduate pre-registration nursing courses in rural and remote areas. Several study limitations are discussed and suggestions made for future research.

Journal Article↗

Convergence of cAMP, TGF-beta and retinoic acid signaling pathways in cells of the embryonic palate.

We have previously described bi-directional cross-talk between the retinoic acid (RA) and transforming growth factor beta (TGF-beta) signal transduction pathways in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. In this paper we identify interactions between the TGF-beta1, cyclic adenosine 3', 5'-monophosphate (cAMP) and RA signaling systems. TGF-beta1 and forskolin, an activator of the cAMP pathway, inhibited RA-induced expression of RAR-beta mRNA in MEPM cells, though only TGF-beta1 inhibited RA-induced RAR-beta protein expression. Forskolin, but not TGF-beta1, abrogated RA-induced expression of a reporter construct containing 900 base pair (bp) of the RAR-beta gene promoter, transfected into MEPM cells, suggesting that this portion of the promoter contains the forskolin-responsive, but not the TGF-beta-responsive, element. Thus, a putative TGF-beta Inhibitory Element (TIE) adjacent to the retinoic acid response element (RARE) in the RAR-beta promoter is either non-functional, or requires promoter/enhancer elements not present in the promoter construct used in these experiments. These studies further clarify the complex interactions among signal transduction pathways in the regulation of retinoic acid receptor gene expression.

Animals↗

PCR-IMS detection and molecular typing of Cryptosporidium parvum recovered from a recreational river source and an associated mussel (Mytilus edulis) bed in Northern Ireland.

PCR-IMS was used to detect Cryptosporidium spp. in environmental water samples in Northern Ireland which had previously tested negative by a conventional IFA staining method. Oocysts of C. parvum detected in river water and final treated sewage effluent collected from various sites along the river Lagan were identified as genotype 2 (animal origin) based on polymorphisms observed at the thrombospondin related adhesion protein gene locus. Similarly, genotype 1 (human origin) oocysts of C. parvum were detected in the marine filter feeder mussel, Mytilus edulis, collected from the shores of Belfast Lough. Detection of the human genotype of Cryptosporidium in mussels destined for human consumption identifies the organism's serious potential as a foodborne pathogen. This work highlights the possible value of monitoring filter feeder systems, in conjunction with specific molecular epidemiological tools, as an alternative monitoring system for the parasite within the aquatic environment.

Animals↗

Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I.

The structure and biological activities of two disulphide isomers of a C-region deletion mutant of insulin-like growth factor-I (IGF-I) which has an Asn--Gly link engineered at the junction of the A- and B-regions were studied before and after chemical cleavage. Circular dichroism (CD) spectra and binding affinity to IGF binding protein 3 (IGFBP3) indicated that the treatment with hydroxylamine did not disrupt the overall tertiary fold of the hormones. Cleavage restored some binding affinity for the IGF-I receptor in both isomers and weakly restored the ability to stimulate incorporation of tritiated thymidine into DNA in NIH 3T3 fibroblasts transfected with the human IGF-I receptor. Cleavage also restored metabolic capacity, as measured by the ability of the isomers to promote lipogenesis in isolated rat adipocytes through the insulin receptor. These results are consistent with the theory that binding of IGF-I to the IGF-I receptor requires a conformational change similar to that involved in insulin binding the insulin receptor. The weak affinity for the IGF-I receptor after cleavage is consistent with the belief that residues in the C-region interact with the IGF-I receptor. This structural difference between insulin and IGF-I gives each a higher binding affinity for its own receptor.

3T3 Cells↗

Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic postmenopausal women with breast cancer receiving tamoxifen.

PURPOSE: To determine performance characteristics of transvaginal ultrasonography (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND METHODS: The authors prospectively examined 138 women receiving tamoxifen by using transvaginal US, hysterosonography, and office hysteroscopy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of transvaginal US and hysterosonography were calculated. RESULTS: All 138 women underwent transvaginal US; 104, successful hysterosonography; and 117, successful hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with polyps and two with submucosal fibroids. Receiver operating characteristic curve analysis revealed 6 mm to be the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a focal endometrial finding was considered abnormal, transvaginal US had a sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508) than transvaginal US. When women with abnormal transvaginal US findings were further examined with hysterosonography, the sequential combination of transvaginal US and hysterosonography was more specific (77.1%) than transvaginal US alone (P <.001), without a significant decrease in sensitivity (78.7%; P =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm is the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities with transvaginal US. Further examination with hysterosonography can improve specificity by reducing the high false-positive rate of transvaginal US.

Antineoplastic Agents, Hormonal↗

The problem of erectile dysfunction following myocardial infarction.

The causes of erection problems after an MI can be physical, psychological, a result of medication or a combination of these factors. This paper examines the causes and considers ways in which nurses can help men experiencing this problem, who may still feel embarrassed to broach this subject even though it is now more publically discussed.

Erectile Dysfunction↗

Expression of the E2F family of transcription factors during murine development.

The E2F family of transcription factors plays a crucial role in the control of cell cycle progression and regulation of cellular proliferation, both processes fundamental to mammalian development. In the present study, we have examined the levels of expression of the six currently identified E2F proteins in murine embryos/fetuses as a function of gestational age, compared the expression of these six proteins in selected developing and adult tissues, and examined E2F expression in the embryonic murine palate, a tissue in which perturbation of proliferation is associated with induction of cleft palate. Our results indicate that: 1) multiple forms of individual E2F family members are present in embryonic, fetal and adult cells/tissues; 2) each of the six E2Fs is expressed in a tissue specific manner in both adult and embryonic/fetal organs; 3) certain forms of individual E2F family members are preferentially detected in adult tissues, whereas others are preferentially expressed in embryonic/fetal tissues; 4) expression of the various E2Fs and their isoforms follows distinct temporal patterns during murine gestation; and 5) individual E2F family members also exhibit differential patterns of temporal expression during murine palatogenesis.

Animals↗

Differential display identification of plunc, a novel gene expressed in embryonic palate, nasal epithelium, and adult lung.

We have identified a novel gene transcript of approximately 1.1 kilobases in length that is expressed in the presumptive nasal epithelium of the mouse embryo. In situ hybridization analysis shows discrete regions of expression associated with the palate, nasal septum, and nasal conchae. This transcript is also expressed strongly in the trachea and bronchi of the adult lung. Screening of a mouse heart cDNA library yielded several overlapping clones to give a continuous sequence of 1113 bases, containing an open reading frame of 278 codons comprising the complete mRNA. No significant homologies with known genes were observed at the nucleotide level; limited amino acid homology with two salivary gland-specific proteins was noted. A search for functionally significant protein motifs revealed consensus sequences for N-glycosylation, protein kinase C and casein kinase phosphorylation, and a leucine zipper. Additionally, we observed a unique amino acid sequence pattern, consisting of the residues Gly-(Leu/Pro/Gln)-(Pro/Leu)-Leu-Pro-Leu, repeated four times near the amino-terminal portion of the protein with two amino acid residues separating the repeats. Based on these observations, we propose that we have identified a new gene, which we call plunc (for palate, lung, and nasal epithelium clone; GenBankTM accession number U69172).

Amino Acid Sequence↗

Fluorescent excitation transfer immunoassay for the determination of spinosyn A in water.

A fluorescent excitation transfer immunoassay for spinosyn A, a fermentation derived insect control agent, has been developed and applied to the analysis of tap water and wastewater effluent from manufacturing plants. Fluorescein (F) and tetramethylrhodamine (TMR) were chosen as donor and quencher, respectively, for the excitation transfer. Fluorescence quenching was observed from the binding of F-labeled antigen to TMR-labeled antibody. By employing nonlabeled antigen in a competitive immunoassay format, we reversed fluorescence quenching. The assay provides a limit of detection of 0. 01 ppb and a working range of 0.05-1 ppb and allows for the rapid determination of spinosyn A in water with recovery values ranging from 96% to 120%. With the exploitation of the small size of optical fibers, fluorescence from an assay volume of 24 microL could be measured without special vessels.

Anti-Bacterial Agents↗

The role of RXR-alpha in retinoic acid-induced cleft palate as assessed with the RXR-alpha knockout mouse.

Treatment of pregnant mice with retinoic acid (RA) in mid-gestation produces cleft palate and limb defects in the fetuses. RXR-alpha has been previously shown to mediate the teratogenic effects of RA in the limb. In this study, we show that RXR-alpha is also involved in retinoid-induced palatal clefting. Treatment of RXR-alpha knockout mice with a teratogenic dose of RA on gestation day 11 or 12 induces cleft palate at a lower frequency than that seen in wild-type animals.

Animals↗

Differential expression and biological activity of retinoic acid-induced TGFbeta isoforms in embryonic palate mesenchymal cells.

The effect of retinoic acid (RA) on TGF-beta mRNA expression and protein production in murine embryonic palate mesenchymal (MEPM) cells was examined by Northern blotting and TGF-beta bioassay in association with TGF-beta isoform-specific neutralizing antibodies. Heat or acid activation was used to distinguish between latent and active TGF-beta protein released into the culture medium. RA had little or no effect on TGF-beta1 mRNA expression and protein production. In contrast, RA increased TGF-beta2 and beta3 protein released into the culture medium, the protein being mostly in an inactive or latent form. The amount of active TGF-beta released was increased relative to the total increase in TGF-beta released, suggesting that RA treatment stimulated activation of latent TGF-beta. RA also increased TGF-beta2 mRNA expression; we have previously shown that RA upregulates TGF-beta3 mRNA in these cells. RA and TGF-beta individually inhibited 3H-thymidine incorporation into MEPM cell DNA, while, when administered simultaneously, they inhibited proliferative activity to a greater extent. Heat- or acid-activated conditioned medium (CM) from MEPM cells treated with RA was able to inhibit 3H-thymidine incorporation into MEPM cell DNA to an extent greater than seen with RA treatment alone. Coincubation of heat-activated CM from RA-treated MEPM cells with pan-specific or TGF-beta2 or beta3-specific neutralizing antibodies partially relieved the inhibitory effect on 3H-thymidine incorporation, suggesting that this proliferative response was due to RA-induced TGF-beta. Simultaneous treatment with RA and TGF-beta also stimulated gycosaminoglycan (GAG) synthesis to an extent greater than that seen with TGF-beta treatment alone, this despite the ability of RA to inhibit GAG synthesis. These data demonstrate a role for RA and RA-induced TGF-beta in the regulation of palate cell proliferation and GAG synthesis and suggest a role for TGF-beta in retinoid-induced cleft palate.

Animals↗

A 2.3 A resolution structure of chymosin complexed with a reduced bond inhibitor shows that the active site beta-hairpin flap is rearranged when compared with the native crystal structure.

In the crystal structure of uncomplexed native chymosin, the beta-hairpin at the active site, known as 'the flap', adopts a different conformation from that of other aspartic proteinases. This conformation would prevent the mode of binding of substrates/inhibitors generally found in other aspartic proteinase complexes. We now report the X-ray analysis of chymosin complexed with a reduced bond inhibitor CP-113972 ¿(2R,3S)-isopropyl 3-[(L-prolyl-p-iodo-L-phenylalanyl-S-methyl-cysteinyl)amino-4]-cyclohexy l-2-hydroxybutanoate¿ at 2.3 A resolution in a novel crystal form of spacegroup R32. The structure has been refined by restrained least-squares methods to a final R-factor of 0.19 for a total of 11 988 independent reflections in the resolution range 10 to 2.3 A. The extended beta-strand conformation of the inhibitor allows hydrogen bonds within the active site, while its sidechains make both electrostatic and hydrophobic interactions with residues lining the specificity pockets S4-->S1. The flap closes over the active site cleft in a way that closely resembles that of other previously determined aspartic proteinase inhibitor complexes. We conclude that the usual position and conformation of the flap found in other aspartic proteinases is available to native chymosin. The conformation observed in the native crystal form may result from intermolecular interactions between symmetry-related molecules in the crystal lattice.

Animals↗

Mutagenesis, biochemical characterization and X-ray structural analysis of point mutants of bovine chymosin.

Chymosin B point mutants, A115T and G243D (chymosin A), were expressed in Escherichia coli and Trichoderma reesei respectively, characterized biochemically, crystallized and studied by X-ray analysis at 2.3 and 2.8 angstroms resolutions respectively. The three-dimensional structures showed that the mutations gave rise to local conformational changes only when compared with that of chymosin B. Kinetic analysis of the A115T mutant with a six residue synthetic peptide revealed a reduction in Km with respect to the wild type, possibly caused by the small local changes in the vicinity of S1 and S3. Although, kinetic analyses of the G243D mutant using the short substrate showed reduced catalytic activity, use of a 15 residue substrate based on residues 98-112 of kappa-casein, the natural substrate, revealed an increase in the kcat compared with chymosin B, probably a consequence of the charge introduced that may interact with the substrate between P4 and P8.

Amino Acid Sequence↗

Effects of dexamethasone on the expression of transforming growth factor-beta in mouse embryonic palatal mesenchymal cells.

The central role of TGF-beta in the development of the embryonic palate has been well characterized. TGF-beta inhibits mesenchymal cell proliferation, induces medial edge epithelial cell differentiation, and modulates the expression of extracellular matrix proteins as well as the proteases that act upon them. Mechanisms by which TGF-beta expression itself is regulated are less well understood. Glucocorticoids are recognized in several cellular systems as able to regulate the expression of TGF-beta. This study was therefore designed to examine whether glucocorticoids affect the expression of TGF-beta isoforms in embryonic palatal cells. Based on flow cytometric analysis and viability determination, confluent primary cultures of mouse embryonic palate mesenchymal (MEPM) cells exposed to up to 10(-6) M dexamethasone (dex) exhibited no signs of cytotoxicity after 24 hours of exposure. Northern blot analyses revealed that dexamethasone reduced steady-state mRNA levels of TGF-beta 3 in a dose-dependent manner as early as 4 hours after treatment but had little effect on TGF-beta 1 and TGF-beta 2 expression up to 24 hours of dex exposure. Dex also reduced the synthesis of both latent and mature forms of TGF-beta protein by approximately four-fold as determined by the mink lung epithelial cell growth inhibition bioassay. Assessment of the ratio of mature to latent protein found in conditioned medium of control compared to dex-treated cultures indicated that dexamethasone may reduce the activation of latent TGF-beta to mature biologically active TGF-beta. Dexamethasone inhibited the proliferation of MEPM cells despite the down-regulation of TGF-beta suggesting that dex-induced growth inhibition of MEPM cells is not mediated by TGF-beta. These data suggest that dex modulates TGF-beta signaling pathways directly by down-regulating TGF-beta expression and possibly indirectly by altering the availability of mature TGF-beta necessary to exert its biological effects in the developing palate.

Animals↗

Inhibition of retinoic-acid-induced gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The polychlorinated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as dioxin or TCDD, has been shown to cause cleft palate in mice. TCDD displays an interesting interaction with another cleft palate teratogen, retinoic acid (RA): when mice are treated with TCDD and RA simultaneously, palatal clefts can be observed in 100% of offspring of mothers at dose levels far below those required for either agent to produce clefting if given singly. This synergy strongly suggests that the pathways controlled by these agents converge at one or more points in cells of the developing palate. In this study, we examined the effects of TCDD on induction of the type II cellular retinoic acid binding protein (CRABP-II) and the retinoic acid receptor beta (RAR beta) by RA in murine embryonic palate mesenchyme (MEPM) cells. While TCDD alone had no effect on basal levels of expression of either gene, the induction of both genes by RA was strongly inhibited by TCDD. These results represent the first evidence for a direct molecular interaction between the RA and TCDD-mediated signaling pathways.

Animals↗