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Biomedical subjects

P Worley

Publications and source records attributed to P Worley.

At least 19 recordsLinked to original sources
PubMed2000

The parallel rural community curriculum: an integrated clinical curriculum based in rural general practice.

INTRODUCTION: In an attempt to address the rural medical workforce maldistribution and the concurrent inappropriate caseload at the urban tertiary teaching hospitals, Flinders University and the Riverland Division of General Practice decided to pilot, in 1997, an entire year of undergraduate clinical curriculum in Australian rural general practice. This program is called the Parallel Rural Community Curriculum (PRCC). This paper is a discussion of the aims of the programme; student selection; practice recruitment; curriculum structure, and academic content, together with lessons learnt from the evaluation of the first cohort of students' experience of the course. METHODS: Independent external evaluators undertook a thematic analysis of a series of structured interviews of students and faculty involved in both the PRCC and the traditional curriculum. The mean examination results were determined and a rank order comparison of student academic performance was undertaken. RESULTS: The eight selected volunteer students reported greater access to patients and clinical learning opportunities than their mainstream counterparts and learned clinical decision making in the context of the whole patient, their family, and the available community resources. They identified patients with 'core' clinical conditions and had a longitudinal exposure to common diseases, whereas hospital-based peers had a cross-sectional exposure to highly filtered illness. The PRCC students' academic performance improved in comparison with that of their tertiary hospital peers' and in comparison to their own results in previous years. CONCLUSION: The PRCC curriculum has cut across the traditional clinical discipline boundaries by teaching in an integrated way in rural general practice. It has affirmed the potential role of true generalist physicians in undergraduate medical education.

Community Medicine↗
PubMed2000

The activity-regulated cytoskeletal-associated protein arc is expressed in different striosome-matrix patterns following exposure to amphetamine and cocaine.

The activity-regulated, cytoskeletal-associated gene, arc, is a brain-enriched immediate-early gene whose expression is rapidly induced in the striatum by dopamine receptor agonists. This rapid induction of arc in the striatum is similar to that of other early response genes such as c-fos, junB, deltafosB, fra, and NGFI-A, which code for transcription factors. Unlike these proteins, however, Arc is a cytoskeletal protein expressed not only in the nucleus of neurons but also in their dendrites. We investigated the patterns of Arc expression evoked in the rat striatum by acute exposures to two psychomotor stimulants, cocaine and amphetamine. Cocaine induced arc in striatal neurons that were broadly distributed within both striosome and matrix compartments of the caudoputamen. Amphetamine also evoked Arc expression in striatal projection neurons, but these were heavily concentrated in the striosomal compartment and only sparsely in the matrix compartment in the rostral striatum. The contrasting patterns of Arc expression evoked by cocaine and amphetamine parallel those of c-Fos, JunB, FRA, and NGFI-A expression induced by these two psychomotor stimulants. This difference in the action of cocaine and amphetamine at the level of protein expression may be linked to the different effects of these psychomotor stimulants on behavior.

Amphetamine↗
PubMed1999

Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.

Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

Action Potentials↗
PubMed1999

Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp.

Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demonstrate that Narp possesses several properties that make it likely to play a key role in excitatory synaptogenesis. Narp is shown to be selectively enriched at excitatory synapses on neurons from both the hippocampus and spinal cord. Overexpression of recombinant Narp increases the number of excitatory but not inhibitory synapses in cultured spinal neurons. In transfected HEK 293T cells, Narp interacts with itself, forming large surface clusters that coaggregate AMPA receptor subunits. Moreover, Narp-expressing HEK 293T cells can induce the aggregation of neuronal AMPA receptors. These studies support a model in which Narp functions as an extracellular aggregating factor for AMPA receptors.

Animals↗
PubMed1998

Identification of a Torpedo homolog of Sam68 that interacts with the synapse organizing protein rapsyn.

Nicotinic acetylcholine receptors (nAChRs) are initially expressed diffusely on the surface of myotubes and, in response to neuronally derived factors, cluster at the endplate to a final concentration of approximately 10000/microm2. The synaptic peripheral membrane protein rapsyn has been shown to mediate clustering of nAChRs in several systems. Here we describe the use of the yeast two-hybrid system to identify proteins that can interact with rapsyn. One of the clones we have identified is a Torpedo californica homolog of the Src-associated in mitosis protein (Sam68). We further show that Sam68, like rapsyn, is localized at the neuromuscular junction.

Amino Acid Sequence↗
PubMed1998

Undergraduate education in anaesthesia: the influence of role models on skills learnt and career choice.

Undergraduate teaching of anaesthesia occurs in about two-thirds of Australian departments of anaesthesia: however, student contact hours are limited compared with those of other disciplines. Seventy-five directors of anaesthesia were surveyed by written questionnaire concerning the time devoted in their department to undergraduate study and teaching of practice/skills to undergraduate students (40 responded). One hundred and sixty final year students were surveyed regarding career choice, anaesthesia skills taught them and role models identified during their training (101 responded). Most final year students had been taught and had learnt the basic skills of life support such as bag and mask ventilation, cardiopulmonary resuscitation and intravenous cannulation. However, fewer were taught more specialized skills such as induction of anaesthesia and spinal anaesthesia. Positive role models in teaching anaesthetists were identified by 66% of students, more commonly if they were taught advanced skills, and were significantly associated with satisfaction with theoretical and practical training. For those students intending a career in anaesthesia (18%), 94% identified a positive role model compared to 65% who did not (P = 0.03).

Anesthesiology↗
PubMed1997

Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin.

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.

Animals↗
PubMed1997

Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain.

Huntington's disease (HD) occurs when the widely expressed protein huntingtin contains an expanded glutamine repeat. The selective degeneration and neuronal morphologic abnormalities of HD may involve interactions with proteins that bind to huntingtin, such as HAP1. The biological significance of this interaction is unclear because neither HAP1 nor huntingtin have significant homology to known proteins. Therefore, we sought to identify HAP1-binding proteins. Using the yeast two-hybrid system, we isolated a rat cDNA encoding part of a protein that interacts with HAP1, and we confirmed the specificity of this interaction using an in vitro protein-binding assay. We called the protein Duo because it is closely related to the human protein Trio but is shorter. Northern blot analysis indicates brain-specific expression of Duo. Human Duo contains a guanine nucleotide exchange factor (GEF) domain that is likely to be rac1-specific, a pleckstrin homology (PH) domain and spectrin-like repeat units. These data support the hypothesis that huntingtin is involved in vesicle trafficking and cytoskeletal functions, and raise the possibility of a role for huntingtin in the regulation of a ras-related signaling pathway.

Amino Acid Sequence↗
PubMed1997

Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I.

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva has not been proven. Consistent with these observations, we recently identified an endogenous 12 kD protein, secretory leukocyte protease inhibitor (SLPI), in saliva which blocks HIV-1 infection in vitro. Whereas other salivary proteins tested were inactive, purified native or recombinant SLPI inhibited HIV-1 infection of human monocytes at 100 ng ml-1. Levels of SLPI quantitated by ELISA in saliva from control and HIV-1 infected individuals exceeded this level, consistent with in vivo antiviral activity. As in saliva, levels of SLPI mRNA determined by Northern hybridization, and protein as assessed by immunohistochemistry in the salivary glands of control and infected populations were comparable. In contrast to adults, oral transmission occurs in infants, possibly due to their lack of fully developed salivary glands. To determine whether the inadequate antiviral protection might be compensated for by maternal sources, we evaluated breast milk samples obtained 6 months postpartum. Levels of SLPI were significantly lower than in saliva and not sufficient to provide antiviral protection in contrast to colostrum samples in which SLPI levels were equivalent to those in saliva and able to inhibit HIV-1 infection when tested in vitro. These data suggest that breast milk may provide transient antiviral activity in the newborn, but that this maternal source of SLPI is of insufficient duration to maintain protection against mucosal transmission of the virus over time. The high functional levels of SLPI in saliva and the low levels in mature breast milk correlate with negligible rates of HIV-1 transmission by saliva and higher rates by breast feeding.

Adult↗
PubMed1997

Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues.

The rarity of oral transmission of human immunodeficiency virus (HIV)-1 by saliva suggests the absence of HIV-1 in the oral cavity and/or the presence of viral inhibitory molecules. We analyzed salivary gland tissues from 55 individuals with acquired immune deficiency syndrome (AIDS) for the presence of HIV-1 by in situ hybridization and detected the virus in more than 30% of these salivary glands. These data, together with previous demonstrations of HIV-1 in oral secretions, implicate a key role for an anti-viral molecule(s) in suppressing transmission. Thus, we focused on the characterization and localization of the endogenous antiviral molecule secretory leukocyte protease inhibitor (SLPI), which inhibits HIV-1 infection in vitro. Expression of SLPI transcripts was evident in submandibular, parotid, and minor salivary glands from both HIV-1-infected and seronegative subjects. Gene expression was reflected by similar levels of SLPI protein by immunohistochemical analysis in the tissues and by enzyme-linked immunosorbent assay in the saliva. However, although SLPI accumulated in acinar cells or ductal epithelium, HIV-1 transcripts did not, and these viral transcripts were identified only in mononuclear cells within the salivary gland stroma. By in situ hybridization, we found no evidence of productive HIV-1 infection of salivary gland epithelium. Thus, HIV-1 was frequently identified in salivary gland tissue, but the virus was found in interstitial mononuclear cells only and did not co-localize with SLPI. Once within the oral cavity, HIV-1 exposure to antiviral levels of SLPI may impede infection of additional target cells, contributing to the virtual absence of oral transmission of HIV-1 by saliva. These studies emphasize the importance of innate, endogenous inhibitors of HIV-1, particularly SLPI, as effective inhibitors of HIV-1 transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Attitudes of rural general practitioners towards undergraduate medical student attachments.

OBJECTIVE: Increasing exposure of undergraduate medical students to rural practice is a key component of the national effort in Australia to redress the rural workforce shortage. For this exposure to be successful, willing cooperation of current rural general practitioners is essential. To date there has been no formal assessment of rural general practitioners' attitudes to having undergraduate medical students attached to their practice. METHOD: A descriptive survey, using a mailed questionnaire was sent to all 316 general practitioners currently practising in rural areas of South Australia, as identified from the database maintained by the South Australian Rural Practice Training Unit. RESULTS: A 71.5% response rate (n = 225) was achieved, of which 203 were eligible for inclusion. Of these, 176 doctors had medical student attachments in their practice on at least one occasion; 74.4% of whom (n = 131) perceived the attachments to have a positive experience on their continuing medical education experience, and 81.1% (n = 142) described a positive experience on their professional development. However, 52.6% (n = 92) felt the attachments had a negative effect on their income. Almost all the doctors who were included in the survey (94.6%, n = 192) were willing to have students attached to their practice in the future for between one to two weeks. Of these, 169 wanted quality assurance points, 112 wanted financial reimbursement, and 108 wanted 'academic status' with a university. CONCLUSION: The results suggest that rural general practitioners are willing to have students attached to their practice for periods between one to two weeks, providing they receive quality assurance points, and to a lesser extent, financial reimbursement and academic status.

Attitude of Health Personnel↗
PubMed1996

A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled.

In Drosophila melanogaster, the frizzled gene plays an essential role in the development of tissue polarity as assessed by the orientation of cuticular structures. Through a combination of random cDNA sequencing, degenerate polymerase chain reaction amplification, and low stringency hybridization we have identified six novel frizzled homologues from mammals, at least 11 from zebrafish, several from chicken and sea urchin, and one from Caenorhabditis elegans. The complete deduced amino acid sequences of the mammalian and nematode homologues share with the Drosophila frizzled protein a conserved amino-terminal cysteine-rich domain and seven putative transmembrane segments. Each of the mammalian homologues is expressed in a distinctive set of tissues in the adult, and at least three are expressed during embryogenesis. As hypothesized for the Drosophila frizzled protein, the frizzled homologues are likely to act as transmembrane receptors for as yet unidentified ligands. These observations predict the existence of a family of signal transduction pathways that are homologous to the pathway that determines tissue polarity in Drosophila.

Amino Acid Sequence↗
PubMed1995

A huntingtin-associated protein enriched in brain with implications for pathology.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanding polyglutamine repeat in the IT15 or huntingtin gene. Although this gene is widely expressed and is required for normal development, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins. Here we report the identification of a protein (huntingtin-associated protein (HAP)-1) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.

Amino Acid Sequence↗
PubMed1989

Autoradiographic distribution of forskolin and phorbol ester binding sites in the retina.

We have localized the distribution of [3H]forskolin and [3H]phorbol dibutyrate binding sites autoradiographically in the rat, monkey, and human retina. In the rat and monkey retina, forskolin binding was enriched in the inner plexiform layer, in the inner and outer segments of the photoreceptors, and in the retinal pigment epithelium. In the human retina, forskolin binding sites were uniformly distributed and higher in density. Forskolin binding was also detected over the ciliary body, the ciliary epithelium, and the iris sphincter. The distribution of phorbol ester binding sites was similar in the rat, monkey, and human retina. The inner plexiform layer contained the highest density followed by the inner nuclear and outer plexiform layers, and the ganglion cell layer. In the rat, phorbol ester binding was present in the iris, the ciliary body, and the ciliary epithelium. The monkey and human ciliary body also contained a low density of phorbol ester binding sites.

Animals↗
PubMed1986

Pediatric nurse triage. Its efficacy, safety, and implications for care.

This study evaluates emergency room (ER) triage at a large urban children's hospital, in which patients are routinely referred outside of the institution for care. Seven hundred forty-eight children from 1 week to 17 years of age were enrolled in the study over a six-week period. Nearly two thirds (61%) of the patients were sent outside of the hospital for care; 31% of the patients were sent to community health centers, 17% were sent to private physicians' offices, 13% were sent home (self-care), and only 9% were treated in the ER. Ninety-four percent of appointments--of which 74% were kept--were for care within two days of the triage visit, with patients who were sent to the ER or hospital clinics keeping more appointments than those who were sent outside the hospital for care (97% vs 89% vs 62%). Patients who had an appointment on the same day kept it better than those who waited one to three days, who in turn had a higher rate of appointment-keeping than those who waited more than three days (81% vs 63.4% vs 41.2%). The physician's diagnosis agreed with the triage nurse's diagnosis or was less serious than the nurse's diagnosis in 93.4% of patients. At two weeks after triage, nearly all patients had completely recovered, with no correlation of symptoms with level or site of care. This study indicates that nurse triage of pediatric walk-in patients, in which three of five patients are referred outside of the hospital for care, is a safe and effective alternative to care in the ER and, at the same time, serves to reinforce community health centers as the appropriate setting for primary care.

Child↗
PubMed1981

Electrophoretic determination of charge on carrier-free 99mTc-labeled complexes.

A new method for determining the charge on carrier-free 99mTc-labeled complexes is described. This method and mixed-ligand experiments were used to determine if the charge on the technetium 99m complex of N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (I) is - 1 and if the ligand to technetium ratio in the complex is 2:1. The preparation of an iodinated analog (II) of I and its 99mTc-labeled complex is described, as is the biodistribution of the 99mTc-labeled complex in mice. The synthesis of the 51Cr(III)- and 57Co(III)-labeled complexes also are described. The net biliary excretion in mice of both the 99mTc- and 51Cr-labeled complexes of II was significantly greater than that of the 99mTc-labeled complex of I.

Animals↗
PubMed1979

A new electrophoretic method for determining ligand: technetium stoichiometry in carrier free 99mTc-radiopharmaceuticals.

An electrophoretic procedure is outlined for the determination of the number of ligands bound to technetium-99m radiopharmaceuticals. The approach involves use of ligands that will complex technetium in a similar fashion but that differ in charge. This approach was applied experimentally to dimercapto ligands in which the ligating sulfur atoms are separated by a flexible three-carbon chain (1,3-dimercapto compounds). Two such ligands studied are 1,3-dimercaptopropane (DMP) and dihydrothioctic acid (DHTA). The Tc compound of DHTA migrates much farther on electrophoresis than the Tc complex of DMP. However, when TcO4- is reduced by SnCl2 or NaBH4 in the presence of equimolar quantities of DHTA and DMP, a new compound is formed being twice as abundant as either the TcDMP or the TcDHTA compound and migrating an intermediate distance. The formation of this new complex and the 1:2:1 distribution indicates that two 1,3-dimercapto compounds are attached to the Tc-center in all three compounds.

Chemical Phenomena↗