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Biomedical subjects

H Richardson

Publications and source records attributed to H Richardson.

At least 19 recordsLinked to original sources
PubMed2006

Nitric oxide stimulates insulin gene transcription in pancreatic beta-cells.

Recent studies have identified a positive role for nitric oxide (NO) in the regulation of pancreatic beta-cell function. The aim of this study was to determine the effects of short-term exposure to NO on beta-cell gene expression and the activity of the transcription factor PDX-1. NO stimulated the activity of the insulin gene promoter in Min6 beta-cells and endogenous insulin mRNA levels in both Min6 and isolated islets of Langerhans. Addition of wortmannin prior to NO stimulation blocked the observed increases in insulin gene promoter activity. Although NO addition stimulated the phosphorylation of p38, inhibition by SB203580 did not block the effect of NO on the insulin gene promoter. NO addition also stimulated both the nuclear accumulation and the DNA binding activity of PDX-1. This study has shown that over 24h, NO stimulates insulin gene expression, PI-3-kinase activity and the activity of the critical beta-cell transcription factor PDX-1.

Androstadienes↗
PubMed2006

Effects of rosiglitazone and metformin on pancreatic beta cell gene expression.

AIMS/HYPOTHESIS: Rosiglitazone and metformin are two oral antihyperglycaemic drugs used to treat type 2 diabetes. While both drugs have been shown to improve insulin-sensitive glucose uptake, the direct effects of these drugs on pancreatic beta cells is only now beginning to be clarified. The aim of the present study was to determine the direct effects of these agents on beta cell gene expression. METHODS: We used reporter gene analysis to examine the effects of rosiglitazone and metformin on the activity of the proinsulin and insulin promoter factor 1 (IPF1) gene promoters in the glucose-responsive mouse beta cell line Min6. Western blot and gel retardation analyses were used to examine the effects of both drugs on the regulation of IPF1 protein production, nuclear accumulation and DNA binding activity in both Min6 cells and isolated rat islets of Langerhans. RESULTS: Over 24 h, rosiglitazone promoted the nuclear accumulation of IPF1 and forkhead homeobox A2 (FOXA2), independently of glucose concentration, and stimulated a two-fold increase in the activity of the Ipf1 gene promoter (p<0.01). Stimulation of the Ipf1 promoter by rosiglitazone was unaffected by the presence of the peroxisome proliferator activated receptor gamma antagonist GW9662. No effect of either rosiglitazone or metformin was observed on proinsulin promoter activity. Metformin stimulated IPF1 nuclear accumulation and DNA binding activity in a time-dependent manner, with maximal effects observed after 2 h. CONCLUSIONS/INTERPRETATION: Metformin and rosiglitazone have direct effects on beta cell gene expression, suggesting that these agents may play a previously unrecognised role in the direct regulation of pancreatic beta cell function.

Active Transport, Cell Nucleus↗
PubMed2005

Otic barotrauma from air travel.

Otic barotrauma occurring during air travel involves traumatic inflammation of the middle ear, caused by a pressure difference between the air in the middle ear and the external atmosphere, developing after ascent or more usually descent. The pressure difference occurs because of failure of the eustachian tube to equilibrate middle ear and atmospheric pressures. It is a common problem, presenting with ear fullness, otalgia and deafness. Severe cases may result in tympanic membrane perforation and even round window membrane rupture. Of three randomized controlled trials, one showed that oral pseudoephedrine decongestants reduced otalgia in adults with recurrent ear pain during air travel, whilst another found that oral pseudoephedrine did not decrease in-flight ear pain in children. The third trial showed that oxymetazoline decongestant nasal spray, taken 30 minutes before descent, did not produce a statistically significant reduction in symptoms of barotrauma in adults with recurrent ear pain during air travel. We review the causes, prevention and treatment of this condition.

Adult↗
PubMed2004

Thickness dependence of structural relaxation in spin-cast, glassy polymer thin films.

The isothermal structural relaxation of glassy, spin-cast polymer thin films has been investigated. Specifically, the thickness h of freshly cast poly(methyl methacrylate) thin films was measured over time using spectroscopic ellipsometry. The spin-cast films exhibit a gradual decrease in thickness, which is attributed to structural relaxation of the glass combined with simultaneous solvent loss. In all cases, h was found to be greater than the equilibrium thickness h(infinity) , which is obtained by cooling slowly from the melt. It is observed that both the rate of the volume relaxation and the fractional departure from h(infinity) (referred to as delta(0) ) increase with increasing film thickness. In the limit of very thin films, the initial h is close to h(infinity) , and delta(0) is small, whereas in thick films (>500 nm) , a plateau value of delta(0) of 0.16 is observed, which is close to the volume fraction of the solvent at the vitrification point. This dependence of delta(0) on thickness is observed regardless of the substrate, polymer molecular weight, or angular velocity during spin casting. Enhanced mobility near film surfaces could be leading to greater relaxation in thinner films prior to, and immediately after, the vitrification of the polymer during the deposition process.

Journal Article↗
PubMed2004

Structural relaxation of spin-cast glassy polymer thin films as a possible factor in dewetting.

Reiter has recently reported a situation in which the dewetting of quasi-solid films is linked to plastic deformation--rather than viscous flow--resulting from capillary forces. Herein we propose that, in thin films of some glassy polymers--especially poly(methyl methacrylate) (PMMA)--prepared by spin-casting from solvent, structural relaxation might impart sufficient stress to cause plastic deformation. We find that PMMA films decrease in thickness by several percent, which is sufficient to create significant stress in those cases in which the film is attached to a rigid substrate. The floating technique, which can take tens of minutes, might allow most of the structural relaxation to occur prior to dewetting experiments.

Journal Article↗
PubMed2003

Influence of the glass transition on solvent loss from spin-cast glassy polymer thin films.

The interdependence of solvent loss and vitrification in spin-cast poly(methyl methacrylate) thin films is explored. Fast measurements of decreases in film thickness, achieved with ellipsometry, indicate that the rate of solvent (toluene) loss decreases sharply when the solvent volume fraction phi(solv) falls below about 0.15 and the film vitrifies. Ellipsometry and microgravimetry show that solvent is lost from a glassy thin film (150 nm thick) over of a period of more than ten hours, which is much longer than would be required if it was limited by diffusion in the glass. These results support the recently-proposed idea that the compression of the glass creates an energy barrier that slows down solvent loss.

Journal Article↗
PubMed2003

A comparison of physician and patient perception of the problems of habitual snoring.

Assumptions are often made by doctors about the nature of the impact of uncomplicated snoring. The aim of this study was to provide a comprehensive view of the problems experienced by snoring patients, and to compare these with the perceptions of otolaryngologists. Part 1: 121 snorers and 419 otolaryngologists completed open-ended problems lists; Part 2: 56 snorers and 63 matched controls completed a mood questionnaire and the Golombok Rust Inventory of Marital State (GRIMS.) There was a clear agreement between snorers and otolaryngologists that sleep-related difficulties comprise the most frequent category of problems that may result from snoring. Snorers report a significantly greater number of physical problems and significantly fewer relationship problems than perceived by otolaryngologists. GRIMS scores were similar in patients and controls. Snorers, however, were significantly more depressed. Doctors appear to address snoring from the twin perspectives of damaged relationships and possible sleep apnoea. Their patients are more concerned about disturbing the sleep of others, and are subject to low mood. The snorers' 25 different responses are now being used as the basis for a Snoring Symptom Index.

Attitude↗
PubMed2003

Assessment of an electronic daily diary in patients with overactive bladder.

OBJECTIVE: To assess the effectiveness of a portable electronic diary as a data collection device for overactive bladder symptoms, and to evaluate its level of patient acceptability compared with a conventional paper-based voiding diary. PATIENTS AND METHODS: Patients were identified through USA and UK hospital incontinence clinics. Patients were trained in the use of paper and electronic diaries before randomization, to complete either diary for 7 days. The diaries were then collected and, after a further training session, patients completed the other diary type for 7 days. RESULTS: In all, 35 patients were recruited into the trial; overall, patients using the paper diaries (35) and electronic diaries (33) recorded similar data for the median number of incontinent episodes per week (8.2 and 7.0, respectively) and for the median number of significant leaks per day (0.4 and 0.5, respectively). However, the number of daily micturitions was slightly lower for the electronic than for the paper diary (7.3 vs 8.5, respectively). The frequency of urgency recorded in the electronic diary was higher than that recorded in the paper diary (5.8 vs 4.7). As 94% of patients found the electronic diary easy to use, and the electronic diary reflects real-time data entries, the electronic diary data may provide a more accurate reflection of patient symptoms. CONCLUSION: We confirmed that the electronic diary is a novel method of collecting clinically relevant symptom data from patients with an overactive bladder. In addition, the ease-of-use ratings support the use of the electronic diary as a superior alternative to paper diaries, providing real-time data which can be rapidly analysed, and thus allowing a speedy review of data during ongoing clinical studies.

Adult↗
PubMed2001

The Drosophila Geminin homolog: roles for Geminin in limiting DNA replication, in anaphase and in neurogenesis.

We have identified a Drosophila homolog of the DNA replication initiation inhibitor Geminin (Dm geminin) and show that it has all of the properties of Xenopus and human Geminin. During Drosophila development, Dm Geminin is present in cycling cells; protein accumulates during S phase and is degraded at the metaphase to anaphase transition. Overexpression of Dm geminin in embryos inhibits DNA replication, but cells enter mitosis arresting in metaphase, as in dup (cdt1) mutants, and undergo apoptosis. Overexpression of Dm Geminin also induces ectopic neural differentiation. Dm geminin mutant embryos exhibit anaphase defects at cycle 16 and increased numbers of S phase cells later in embryogenesis. In a partially female-sterile Dm geminin mutant, excessive DNA amplification in the ovarian follicle cells is observed. Our data suggest roles for Dm Geminin in limiting DNA replication, in anaphase and in neural differentiation.

Amino Acid Sequence↗
PubMed2001

Characterization of the Drosophila caspase, DAMM.

Caspases are main effectors of apoptosis in metazoans. Genome analysis indicates that there are seven caspases in Drosophila, six of which have been previously characterized. Here we describe the cloning and characterization of the last Drosophila caspase, DAMM. Similar to mammalian effector caspases, DAMM lacks a long prodomain. We show that the DAMM precursor, along with the caspases DRONC and DECAY, is partially processed in cells undergoing apoptosis. Recombinant DAMM produced in Escherichia coli shows significant catalytic activity on a pentapeptide caspase substrate. Low levels of damm mRNA are ubiquitously expressed in Drosophila embryos during early stages of development. Relatively high levels of damm mRNA are detected in larval salivary glands and midgut, and in adult egg chambers. Ectopic expression of DAMM in cultured cells induces apoptosis, and similarly, transgenic overexpression of DAMM, but not of a catalytically inactive DAMM mutant, in Drosophila results in a rough eye phenotype. We demonstrate that expression of the catalytically inactive DAMM mutant protein significantly suppresses the rough eye phenotype due to the overexpression of HID, suggesting that DAMM may be required in a hid-mediated cell death pathway.

Amino Acid Sequence↗
PubMed2001

STRICA, a novel Drosophila melanogaster caspase with an unusual serine/threonine-rich prodomain, interacts with DIAP1 and DIAP2.

The recently published genome sequence of Drosophila melanogaster predicts seven caspases in the fly. Five of these caspases have been previously characterised. Here, we describe the Drosophila caspase, STRICA. STRICA is a caspase with a long amino-terminal prodomain that lacks any caspase recruitment domain or death effector domain. Instead, the prodomain of STRICA consists of unique serine/threonine stretches. Low levels of strica expression were detected in embryos, larvae, pupae and adult animals. STRICA is a cytoplasmic protein that, upon overexpression, caused apoptosis in cultured Drosophila SL2 cells that was partially suppressed by DIAP1. Interestingly, unlike other fly caspases, STRICA showed physical association with DIAP2, in cotransfection experiments. These results suggest that STRICA may have a unique cellular function.

Amino Acid Sequence↗
PubMed2001

Surgical outcomes of a randomized prospective trial involving patients with a proximal femoral fracture.

BACKGROUND: An orthopaedic management/patient-focused care unit (OMPFCU) involving a dedicated orthopaedic-geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures. METHODS: The surgical outcomes of the patients were monitored in order to determine whether accelerated rehabilitation had any significant adverse effects on the surgical outcomes, measured by mortality, readmission to hospital, deep wound infection, fracture union delay, mobility and the revision surgery rate. RESULTS: No significant difference was recorded in mortality and morbidity, deep wound infection and revision surgery rates between patients in the Royal Brisbane Hospital OMPFCU and those in standard care in the orthopaedic surgery wards. CONCLUSION: Accelerated rehabilitation for patients with a proximal femoral fracture in a major teaching hospital can be accomplished safely.

Canes↗
PubMed2001

Nonisotopic detection of human papillomavirus DNA in clinical specimens using a consensus PCR and a generic probe mix in an enzyme-linked immunosorbent assay format.

We assessed the value of a new digoxigenin (DIG)-labeled generic probe mix in a PCR-enzyme-linked immunosorbent assay format to screen for the presence of human papillomavirus (HPV) DNA amplified from clinical specimens. After screening with this new generic assay is performed, HPV DNA-positive samples can be directly genotyped using a reverse blotting method with product from the same PCR amplification. DNA from 287 genital specimens was amplified via PCR using biotin-labeled consensus primers directed to the L1 gene. HPV amplicons were captured on a streptavidin-coated microwell plate (MWP) and detected with a DIG-labeled HPV generic probe mix consisting of nested L1 fragments from types 11, 16, 18, and 51. Coamplification and detection of human DNA with biotinylated beta-globin primers served as a control for both sample adequacy and PCR amplification. All specimens were genotyped using a reverse line blot assay (13). Results for the generic assay using MWPs and a DIG-labeled HPV generic probe mix (DIG-MWP generic probe assay) were compared with results from a previous analysis using dot blots with a radiolabeled nested generic probe mix and type-specific probes for genotyping. The DIG-MWP generic probe assay resulted in high intralaboratory concordance in genotyping results (88% versus 73% agreement using traditional methods). There were 207 HPV-positive results using the DIG-MWP method and 196 positives using the radiolabeled generic probe technique, suggesting slightly improved sensitivity. Only one sample failed to test positive with the DIG-MWP generic probe assay in spite of a positive genotyping result. Concordance between the two laboratories was nearly 87%. Approximately 6% of samples that were positive or borderline when tested with the DIG-MWP generic probe assay were not detected with the HPV type-specific panel, perhaps representing very rare or novel HPV types. This new method is easier to perform than traditional generic probe techniques and uses more objective interpretation criteria, making it useful in studies of HPV natural history.

Cervix Uteri↗
PubMed2001

Easing the path back to nursing practice.

With staff shortages reaching crisis level, the government is keen to encourage back nurses who have taken a career break. For one nurse, this has worked well.

Education, Nursing↗
PubMed2000

An essential role for the caspase dronc in developmentally programmed cell death in Drosophila.

Dronc is a caspase recruitment domain-containing Drosophila caspase that is expressed in a temporally and spatially restricted fashion during development. Dronc is the only fly caspase known to be regulated by the hormone ecdysone. Here we show that ectopic expression of dronc in the developing fly eye leads to increased cell death and an ablated eye phenotype that can be suppressed by halving the dosage of the genes in the H99 complex (reaper, hid, and grim) and enhanced by mutations in diap1. In contrast to previous reports, we show that the dronc eye ablation phenotype can be suppressed by coexpression of the baculoviral caspase inhibitor p35. Dronc also interacts, both genetically and biochemically, with the CED-4/Apaf-1 fly homolog, Dark. Furthermore, extracts made from Dark homozygous mutant flies have reduced ability to process Dronc, showing that Dark is required for Dronc processing. Finally, using the RNA interference technique, we show that loss of Dronc function in early Drosophila embryos results in a dramatic decrease in cell death, indicating that Dronc is important for programmed cell death during embryogenesis. These results suggest that Dronc is a key caspase mediating programmed cell death in Drosophila.

Animals↗
PubMed2000

Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.

Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

Amino Acid Sequence↗