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Biomedical subjects

P A Bennett

Publications and source records attributed to P A Bennett.

At least 19 recordsLinked to original sources
PubMed2004

Endotaxial silicide nanowires.

We demonstrate the growth of self-assembled nanowires of cobalt silicide on Si(111), (100), and (110) substrates during deposition of Co onto a heated Si substrate. Silicide islands form via an endotaxial mechanism, growing into the substrate along inclined Si{111} planes, which breaks the symmetry of the surface and leads to a long, thin nanowire shape. During growth, both the length and width of the islands increase with time in a fixed proportion that varies strongly with growth temperature, which shows that the nanowire shape is kinetically determined. It is expected that nanowires could form in many other overlayer/substrate systems via this mechanism.

Journal Article↗
PubMed2003

Selective nucleation and controlled growth: quantum dots on metal, insulator and semiconductor surfaces.

Nucleation and growth models are well developed for nucleation on homogeneous substrates, and they can typically be described in terms of three energy parameters. Nucleation on substrates containing point-defect traps has been investigated, at the cost of introducing more energy parameters. This paper outlines the quantitative description of such growth models, using rate and rate-diffusion equations, in terms of energies for individual surface processes, with examples taken from metal-metal, metal-insulator and semiconductor growth. The challenge to modelling is to describe the large range of length and time-scales in thin-film fabrication and degradation, without relying on too many (unknown) material parameters, which often occur in combination. Separating them into elementary processes often proves to be a challenge. One typically requires selective nucleation using patterned substrates, in combination with controlled, self-organized, growth for reliable nanotechnology. Reconstructed semiconductor surfaces offer both a further challenge to modelling and an opportunity for future technology; these paradoxes are discussed briefly.

Journal Article↗
PubMed2002

Structure of quantum wires in Au/Si(557).

The structure of the Au/Si(557) surface is determined from three-dimensional x-ray diffraction measurements, which directly mandate a single Au atom per unit cell. We use a "heavy atom" method in which the Au atom images the rest of the structure. Au is found to substitute for a row of first-layer Si atoms in the middle of the terrace, which then reconstructs by step rebonding and adatoms. The structure is consistent with the 1D metallic behavior seen by photoemission.

Journal Article↗
PubMed2001

Island nucleation in a reactive two-component system.

The flux and temperature dependence of titanium silicide islands formed by reactive deposition near 500 degrees C indicate a critical nucleus containing 2 Ti atoms and a single activation energy of E(d) + 1/2E(2) = 1.4 +/- 0.2 eV, where E(d) and E(2) are the surface diffusion and cluster binding energies, respectively. These values are not consistent with STM observations of Ti dimer-vacancy hopping at lower temperatures and show that silicide island nucleation involves a different, highly mobile Ti species.

Journal Article↗
PubMed2001

Leptin receptor 5'untranslated regions in the rat: relative abundance, genomic organization and relation to putative response elements.

Hypothalamic sensitivity to leptin has been suggested to be important for regulation of body fat mass. Mice heterozygous for a mutation in the leptin receptor (leptin-R) have an increased body fat mass suggesting that the abundance of leptin-R may be an important determinator of leptin sensitivity. Leptin-R cDNAs from several species contain alternative 5'untranslated regions (5'UTRs), suggesting that several distinct regulatory regions may exist. To investigate possible mechanisms by which leptin-R expression may be regulated, we searched for possible alternative 5'UTRs of the leptin-R in the rat and determined their location in relation to putative response elements. Four leptin-R 5'UTRs (exons 1A-1D), which diverged 23 bp upstream of the start codon, were identified by 5'Rapid Amplification of cDNA Ends (5'RACE) and sequencing. Exons 1B and 1C were present in 31 and 61%, respectively, of all leptin-R transcripts in the hypothalamus as determined by a ribonuclease protection assay. Analysis of the 5' flanking genomic sequences revealed an imperfect estrogen response element (ERE), two Spl-sites, three CCAAT-boxes and one octamer. Exons 1A and 1D corresponded to a putative second gene, encoding the OB-Receptor Gene Related Protein (OB-RGRP), which is transcribed from a promoter shared with the leptin-R. DNA sequencing revealed that the rat OB-RGRP had 98 and 97% homology with the mouse and human sequence, respectively. We report here that transcription of the rat leptin-R gene may generate transcripts with four alternative 5'UTRs. The presence of a putative ERE, close to the most frequently used transcriptional start sites of the leptin-R gene in the hypothalamus, provides a possible mechanism by which estrogen may exert its effects on food intake.

5' Untranslated Regions↗
PubMed2000

Glucocorticoid regulation of growth hormone (GH) secretagogue-induced growth responses and GH secretagogue receptor expression in the rat.

Synthetic GH-releasing peptides such as GHRP-6 are potent GH secretagogues (GHSs) in several species, but attempts to stimulate growth by continuous GHS exposure have had limited success. GHSs also release ACTH and adrenal steroids. Since glucocorticoid excess is associated with poor linear growth, stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by continuous GHS administration may compromise their growth-promoting effects. We have now examined the effects of continuous GHRP-6 infusion (100 mg/day, s.c. for 14 days) in normal 150-day-old female rats, and in adrenalectomized (Adx) rats with or without dexamethasone (Dex) replacement. Infusion of GHRP-6 did not significantly affect body weight gain compared with excipient-treated controls in either intact rats (controls, 9.0 +/- 1.6 vs GHRP-6, 11.8 +/- 0.9 g) or Adx rats (4.4 +/- 1.5 vs 7.9 +/- 2.7 g). However, GHRP-6 significantly increased weight gain in Adx rats treated with Dex (controls, 3.5 +/- 1.4 vs GHRP-6, 15.4 +/- 1.6 g;P<0.01). Adrenalectomy decreased plasma triglycerides (P<0.01), and Dex treatment increased plasma cholesterol (P<0.001), GHRP-6 treatment did not affect these plasma lipids. Dex treatment also reduced plasma GH-binding protein levels and hepatic GH binding (P<0.05). Pituitary GH content was decreased in Adx rats (P<0.05) but not in Dex-treated Adx rats. Adrenalectomy markedly decreased GHS-receptor mRNA expression in the arcuate (P<0. 001) and ventromedial nuclei (P<0.01), whilst Dex treatment normalized GHS-receptor expression. These results suggest that adrenal steroids are necessary for normal GHS-receptor expression and GHRP-6-induced weight gain, but long-term stimulation of the HPA axis by continuous GHS exposure may be detrimental to the growth response.

Adrenal Glands↗
PubMed1999

Cyclical variations in the abundance of leptin receptors, but not in circulating leptin, correlate with NPY expression during the oestrous cycle.

We have demonstrated previously that pharmacological doses of oestradiol decreased leptin receptor expression in the hypothalamus. We therefore analysed leptin receptor expression during the oestrous cycle in the rat, to establish if acute changes in oestradiol affect leptin receptor expression under physiological conditions. Radioactive in situ hybridization histochemistry was used to measure the gene expression under investigation. Total leptin receptor transcript levels were lowest in pro-oestrus in the choroid plexus, these changes correspond inversely with levels of circulating oestradiol in the rat 4-day oestrous cycle. In contrast full-length leptin receptor levels in both arcuate and ventromedial nuclei did not correspond to the levels of total leptin receptor in the same areas of the hypothalamus or serum levels of oestradiol. Full-length leptin receptor expression in the arcuate nucleus was negatively correlated with neuropeptide Y (NPY) expression (r = 0.447, p < 0. 05) in the same nucleus. Arcuate nucleus NPY expression did not correlate significantly with the expression of total leptin receptors in the arcuate nucleus (r = 0.080) or serum leptin levels (r = 0.251). Our results demonstrate that leptin receptor expression is regulated during the oestrous cycle. The unchanged serum leptin levels during the oestrous cycle together with the correlation between the expression of leptin-RL and NPY provide circumstantial evidence that regulation of leptin receptor abundance in the hypothalamus governs the biological actions of leptin.

Animals↗
PubMed1999

Large scale implementation of a respiratory therapist-driven protocol for ventilator weaning.

We prospectively investigated the large-scale implementation of a respiratory-therapist-driven protocol (TDP) that included 117 respiratory care practitioners (RCPs) managing 1,067 patients with respiratory failure over 9,048 patient days of mechanical ventilation. During a 12-mo period, we reintroduced a previously validated protocol that included a daily screen (DS) coupled with spontaneous breathing trials (SBTs) and physician prompt, as a TDP without daily input from a physician or "weaning team." With graded, staged educational interventions at 2-mo intervals, RCPs had a 97% completion rate and a 95% correct interpretation rate for the DS. The frequency with which patients who passed the DS underwent SBTs increased throughout the implementation process (p < 0.001). As the year progressed, RCPs more often considered SBTs once patients had passed a DS (p < 0.001), and physicians ordered more SBTs (46 versus 65%, p = 0.004). Overall, SBTs were ordered more often on the medicine than on the surgical services (81 versus 63%, p = 0.001), likely reflecting medical intensivists' prior use of this protocol. Important barriers to protocol compliance were identified through a questionnaire (89 respondents, 76%), and included: Physician unfamiliarity with the protocol, RCP inconsistency in seeking an order for an SBT from the physician, specific reasons cited by the physician for not advancing the patient to a SBT, and lack of stationary unit assignments by RCPs performing the protocol. We conclude that implementation of a validated weaning strategy is feasible as a TDP without daily supervision from a weaning physician or team. RCPs can appropriately perform and interpret DS data more than 95% of the time, but significant barriers to SBTs exist. Through a staged implementation process, using periodic reinforcement of all participants in ventilator management, improved compliance with this large-scale weaning protocol can be achieved.

Clinical Protocols↗
PubMed1998

Differential expression and regulation of leptin receptor isoforms in the rat brain: effects of fasting and oestrogen.

Leptin affects body weight and reproduction mainly via receptors in the central nervous system. Different isoforms of the leptin receptor (leptin-R) exist, including a long isoform (leptin-RL) with signalling capacity and short isoforms (leptin-RS) with unknown function. The aim of this study was to examine leptin-R gene expression in different regions of the brain under conditions with altered body weight, in the female rat, including ovariectomy (OVX), oestradiol (E2) treatment, fasting and a genetic model of obesity (Zucker fa/fa). Leptin-R gene expression was analysed by in situ hybridization using probes recognizing all receptor isoforms (leptin-R) or specifically leptin-RL. Transcripts recognized by the leptin-R probe were abundant in the choroid plexus (CP), arcuate nucleus (ARC), ventromedial nucleus (VMN), thalamus (TH) and piriform cortex (PC). Leptin-RL transcripts were detected in the ARC, VMN, TH and PC but not in the CP. Although no sex difference was observed, leptin-R gene expression was reduced by E2 administration and increased by OVX. Administration of E2 reduced leptin-RL gene expression in the ARC and VMN but did not alter the expression in the TH or PC. OVX had no effect on the expression of leptin-RL mRNA. Fasting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-RL transcripts in the TH despite a decrease in leptin-R in this area. Obese Zucker rats had a similar pattern of expression with an increased expression of leptin-RL transcripts in all brain areas analysed and a decrease in leptin-R gene expression. These results demonstrate a differential regulation of leptin-RL and leptin-RS which could provide a mechanism for regulating access to, and sensitivity of, discrete regions of the brain for circulating leptin. We suggest that fasting and E2 alter the balance between leptin-RL and leptin-RS and that this could increase tissue sensitivity to leptin.

Animals↗
PubMed1998

Effects of growth hormone secretagogues on prolactin release in anesthetized dwarf (dw/dw) rats.

In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1-2.5 microg, i.v.) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.

Anesthesia↗
PubMed1997

Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated by growth hormone in the rat.

Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that for GH-releasing hormone (GHRH). We have studied the hypothalamic expression and regulation of this receptor by in situ hybridization using a homologous riboprobe for rat GHS-R. GHS-R mRNA is prominently expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in hippocampus, but not in the periventricular nucleus. Little or no specific hybridization could be observed in the pituitary under the conditions that gave strong signals in the hypothalamus. No sex difference in GHS-R expression was found in ARC or hippocampus, though expression in VMN was lower in males than in females. Compared with GHRH and neuropeptide Y (NPY), GHS-R was expressed in a distinct region of ventral ARC, and in regions of VMN not expressing GHRH or NPY. GHS-R expression was highly sensitive to GH, being markedly increased in GH-deficient dw/dw dwarf rats, and decreased in dw/dw rats treated with bovine GH (200 microg/day) for 6 days. Similar changes were observed in GHRH expression, whereas NPY expression was reduced in dw/dw rats and increased by bGH treatment. Continuous sc infusion of GHRP-6 in normal female rats did not alter ARC or VMN GHS-R expression. Our data implicate ARC and VMN cells as major hypothalamic targets for direct GHS action. The sensitivity of ARC GHS-R expression to modulation by GH suggests that GHS-Rs may be involved in feedback regulation of GH.

Animals↗
PubMed1996

Differential regulation of the growth hormone receptor gene: effects of dexamethasone and estradiol.

GH receptor (GHR) expression differs during development between central and peripheral tissues. Peripheral GHR expression is known to be sensitive to gonadal and adrenal steroids, but little is known about their effects on GHR in the central nervous system. We have now studied the effects of estradiol (E2) or dexamethasone on GHR expression in rat arcuate nucleus (ARC) and hippocampus, using quantitative in situ hybridization. Dexamethasone, which strongly down-regulates hepatic GHR expression, had no effect on central GHR transcript abundance, whereas E2 treatment, which stimulates hepatic GHR expression, significantly reduced ARC GHR messenger RNA (mRNA) levels. E2 also increased somatostatin (SS) expression significantly in both ARC and periventricular nuclei but did not reduce ARC GH-releasing hormone (GHRH) mRNA levels. Ovariectomy stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS expression. E2 replacement in ovariectomized animals restored GHRH and SS mRNA levels to control values. Hippocampal GHR mRNA transcripts showed the same response to these endocrine manipulations as seen in the ARC. The induction of hepatic GHR expression by E2 is known to involve the transcription of an alternate 5' untranslated first exon, GHR1. This was readily detectable in the liver using a specific GHR1 probe but could not be detected in any CNS area. Our results show that GHR expression in the CNS is sensitive to regulation by peripheral steroids but that CNS and hepatic expression of GHR is differentially regulated by the same treatments.

Animals↗
PubMed1995

Hypothalamic GH receptor gene expression in the rat: effects of altered GH status.

GH synthesis and release from the anterior pituitary is governed by the opposing actions of somatostatin (SS) and GH-releasing factor (GRF), derived from the periventricular and arcuate nucleus (ARC) of the hypothalamus respectively. GH is known to regulate its own release by hypothalamic autofeedback mechanisms, but the extent to which this is a direct effect rather than indirectly via the generation of IGFs is still a subject of debate. GH receptors are known to be present in the hypothalamus, but their physiological regulation is poorly understood. We therefore used in situ hybridization histochemistry to investigate the effects of GH status on hypothalamic GH receptor gene expression, using hypophysectomized normal and dw/dw dwarf rats as models of acquired and congenital GH deficiency. Hypophysectomy resulted in a time-dependent reduction in GH receptor gene expression. ARC GH receptor transcripts in untreated dw/dw dwarf rats were half those found in normal animals of the same background strain (16.8 +/- 1.7 vs 9.3 +/- 1.9 d.p.m./mg, P < 0.05). Increasing circulating GH by peripheral infusion of 200 micrograms human GH (hGH)/day for 6 days increased ARC GH receptor expression in dw/dw rats to normal. In contrast, central infusions of hGH at 26.4 and 79.2 micrograms/day for 6 days in normal rats lowered ARC GH receptor gene expression. The sensitivity of GH receptor gene expression within the central nervous system to peripheral and central GH levels suggests that feedback regulation of GRF and/or SS may be mediated directly by these receptors, and that the sensitivity to GH feedback is also subject to autoregulation by GH altering its own receptor expression.

Animals↗
PubMed1995

Tyrosine phosphatase antagonist-induced activation of the neutrophil NADPH oxidase: a possible role for protein kinase C.

To investigate the role of tyrosine phosphorylation in polymorphonuclear leucocyte (PMN) activation we have examined the effect of the potent tyrosine phosphatase (PTPase) inhibitor, vanadyl hydroperoxide, on PMN function. Western blotting of vanadyl hydroperoxide-treated PMN showed that there was a rapid dose-dependent increase in tyrosine-phosphorylated proteins. Vanadyl hydroperoxide also induced superoxide production in PMN over the range 10-100 microM, similar to the concentrations that also induced tyrosine phosphorylation. The tyrosine kinase inhibitor erbstatin totally inhibited the respiratory burst induced by vandyl hydroperoxide, showing that tyrosine kinase activity was necessary for superoxide production. The protein kinase C (PKC) inhibitors chelerythrine and bisidolylmaleimide inhibited the vanadyl hydroperoxide-induced respiratory burst with an inhibitory concentration of 50% (IC50) close to that for PKC inhibition without affecting tyrosine phosphorylation. These results indicate a possible role for PKC in vanadyl hydroperoxide-mediated superoxide production, and that any PKC involvement is downstream of tyrosine phosphorylation. These results further demonstrate that inhibition of phosphotyrosine phosphatases results in the activation of a functional response, indicating a critical role for phosphotyrosine phosphatases in PMN stimulation.

Animals↗
PubMed1993

The phosphotyrosine phosphatase inhibitor vanadyl hydroperoxide induces morphological alterations, cytoskeletal rearrangements and increased adhesiveness in rat neutrophil leucocytes.

The functional consequences of treating rat neutrophils with the potent tyrosine phosphatase inhibitor vanadyl hydroperoxide (pervanadate) has been investigated. Pervanadate induced rapid increases in cellular protein phosphotyrosine content in a dose-dependent manner. This treatment also resulted in a change in morphology of the cells from a rounded to a polarised morphology, with many cells exhibiting uropods, pseudopodia and increased membrane activity. Pervanadate induced a transient actin polymerisation and reorganisation similar to that in agonist-stimulated cells. The pervanadate-induced increases in tyrosine phosphorylation, shape change and actin polymerisation were inhibited by the tyrosine kinase inhibitors tyrphostin and erbstatin, indicating that these phenomena were mediated by the constitutive activity of cellular tyrosine kinases. Double fluorescence experiments demonstrated that there was a co-localisation of tyrosine phosphorylated proteins with F-actin in both pervanadate- and agonist-stimulated neutrophils. Pervanadate also induced spreading of neutrophils on tissue culture substrata with concurrent changes in F-actin localisation including unusual F-actin-containing structures. These results demonstrate that morphological changes and cytoskeletal reorganisation in neutrophils are regulated by tyrosine phosphorylation, and that inhibition of tyrosine phosphatase activity in neutrophils is sufficient to activate motile machinery of these cells. These results suggest that an alternative pathway involved in neutrophil stimulation might be via inhibition of endogenous tyrosine phosphatases rather than activation of tyrosine kinases.

Actins↗
PubMed1990

Age and severe mental disorders in homeless and disaffiliated people in inner Melbourne.

Trained clinicians interviewed 346 people who were representative of those aged 15 to 60 years staying in crisis accommodation centres for the homeless and cheap single-room accommodations in inner Melbourne. The interviewers used a standardised diagnostic instrument, the structured clinical interview for DSM III-R. (Diagnostic and statistical manual of mental disorders - revised), to diagnose a range of severe mental disorders, including psychotic, affective, and substance-related disorders. Almost half the people interviewed received diagnoses of current disorders and over 70% received diagnoses of lifetime disorders. The prevalences of lifetime and current disorders in all categories were as high in young as in older men. Only small numbers of women were seen. The relatively high prevalence of disorder in younger men may be related to selective factors in the survey, to a cohort effect, or to recovery or death of older men with a history of mental disorder. From a practical point of view the important issue is the effect of varying systems of mental health care, and of welfare and housing policies, on the course and outcome of the various disorders, and on the likelihood of individuals living impoverished and disaffiliated lives.

Adolescent↗