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Biomedical subjects

S Wilson

Publications and source records attributed to S Wilson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care.

OBJECTIVE: To determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia. DESIGN: Randomised controlled trial. SETTING: 31 UK primary care centres. PARTICIPANTS: 478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration. INTERVENTIONS: Near patient testing for H pylori and open access endoscopy for patients with positive results. Control patients received acid suppressing drugs or specialist referral at general practitioner's discretion. MAIN OUTCOME MEASURES: Cost effectiveness based on improvement in symptoms and use of resources at 12 months; quality of life. RESULTS: 40% of the study group tested positive for H pylori. 45% of study patients had endoscopy compared with 25% of controls. More peptic ulcers were diagnosed in the study group (7.4% v 2.1%, P=0.011). Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups. No significant differences were observed in rates of prescribing, consultation, or referral. Costs were higher in the study group ( 367.85 pound sterling v 253.16 pound sterling per patient). CONCLUSIONS: The test and endoscopy strategy increases endoscopy rates over usual practice in primary care. The additional cost is not offset by benefits in symptom relief or quality of life.

Adolescent↗
PubMed2001

A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes.

Intercellular signaling by fibroblast growth factors plays vital roles during embryogenesis. Mice deficient for fibroblast growth factor receptors (FgfRs) show abnormalities in early gastrulation and implantation, disruptions in epithelial-mesenchymal interactions, as well as profound defects in membranous and endochondrial bone formation. Activating FGFR mutations are the underlying cause of several craniosynostoses and dwarfism syndromes in humans. Here we show that a heterozygotic abrogation of FgfR2-exon 9 (IIIc) in mice causes a splicing switch, resulting in a gain-of-function mutation. The consequences are neonatal growth retardation and death, coronal synostosis, ocular proptosis, precocious sternal fusion, and abnormalities in secondary branching in several organs that undergo branching morphogenesis. This phenotype has strong parallels to some Apert's and Pfeiffer's syndrome patients.

Acrocephalosyndactylia↗
PubMed2001

Molecular cloning and functional characterization of MCH2, a novel human MCH receptor.

Melanin-concentrating hormone (MCH) is involved in the regulation of feeding and energy homeostasis. Recently, a 353-amino acid splice variant form of the human orphan receptor SLC-1 () (hereafter referred to as MCH(1)) was identified as an MCH receptor. This report describes the cloning and functional characterization of a novel second human MCH receptor, which we designate MCH(2), initially identified in a genomic survey sequence as being homologous to MCH(1) receptors. Using this sequence, a full-length cDNA was generated with an open reading frame of 1023 base pairs, encoding a polypeptide of 340 amino acids, with 38% identity to MCH(1) and with many of the structural features conserved in G protein-coupled receptors. This newly discovered receptor belongs to class 1 (rhodopsin-like) of the G protein-coupled receptor superfamily. HEK293 cells transfected with MCH(2) receptors responded to nanomolar concentrations of MCH with an increase in intracellular Ca(2+) levels and increased cellular extrusion of protons. In addition, fluorescently labeled MCH bound with nanomolar affinity to these cells. The tissue localization of MCH(2) receptor mRNA, as determined by quantitative reverse transcription-polymerase chain reaction, was similar to that of MCH(1) in that both receptors are expressed predominantly in the brain. The discovery of a novel MCH receptor represents a new potential drug target and will allow the further elucidation of MCH-mediated responses.

Amino Acid Sequence↗
PubMed2001

Retention of the Alzheimer's amyloid precursor fragment C99 in the endoplasmic reticulum prevents formation of amyloid beta-peptide.

gamma-Secretase is a membrane-associated endoprotease that catalyzes the final step in the processing of Alzheimer's beta-amyloid precursor protein (APP), resulting in the release of amyloid beta-peptide (Abeta). The molecular identity of gamma-secretase remains in question, although recent studies have implicated the presenilins, which are membrane-spanning proteins localized predominantly in the endoplasmic reticulum (ER). Based on these observations, we have tested the hypothesis that gamma-secretase cleavage of the membrane-anchored C-terminal stump of APP (i.e. C99) occurs in the ER compartment. When recombinant C99 was expressed in 293 cells, it was localized mainly in the Golgi apparatus and gave rise to abundant amounts of Abeta. Co-expression of C99 with mutant forms of presenilin-1 (PS1) found in familial Alzheimer's disease resulted in a characteristic elevation of the Abeta(42)/Abeta(40) ratio, indicating that the N-terminal exodomain of APP is not required for mutant PS1 to influence the site of gamma-secretase cleavage. Biogenesis of both Abeta(40) and Abeta(42) was almost completely eliminated when C99 was prevented from leaving the ER by addition of a di-lysine retention motif (KKQN) or by co-expression with a dominant-negative mutant of the Rab1B GTPase. These findings indicate that the ER is not a major intracellular site for gamma-secretase cleavage of C99. Thus, by inference, PS1 localized in this compartment does not appear to be active as gamma-secretase. The results suggest that presenilins may acquire the characteristics of gamma-secretase after leaving the ER, possibly by assembling with other proteins in peripheral membranes.

Alzheimer Disease↗
PubMed2001

Food restriction selectively increases hypothalamic orexin-B levels in lactating rats.

Orexins are hypothalamic peptides implicated in the regulation of ingestive and other behaviours. Here we investigated prepro-orexin expression and hypothalamic orexin-A and -B levels in lactating rats, which display marked hyperphagia, with or without food restriction for 2 days or treatment with bromocriptine, which inhibits milk production and thus reduces the energy losses of lactation. Neither prepro-orexin gene expression nor hypothalamic orexin-A peptide levels were changed in any of these lactating groups compared with age-matched virgin controls. However, hypothalamic orexin-B levels were significantly higher in lactating rats that were food-restricted for 2 days (P<0.05) compared with non-lactating controls and with lactating rats that were either freely-fed or bromocriptine-treated. Thus, food restriction superimposed on lactation selectively increases hypothalamic orexin-B levels, suggesting that orexin-A and -B may be differentially released or cleared. Changes in orexin-B availability may influence physiological activities other than energy homeostasis, perhaps inducing arousal.

Animals↗
PubMed2001

Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy.

Oligomerization of the human delta-opioid receptor and its regulation by ligand occupancy were explored following expression in HEK293 cells using each of co-immunoprecipitation of differentially epitope-tagged forms of the receptor, bioluminescence resonance energy transfer and time-resolved fluorescence resonance energy transfer. All of the approaches identified constitutively formed receptor oligomers, and the time-resolved fluorescence studies confirmed the presence of such homo-oligomers at the cell surface. Neither the agonist ligand [d-Ala(2),d-Leu(5)]enkephalin nor the inverse agonist ligand ICI174864 were able to modulate the oligomerization status of this receptor. Interactions between co-expressed delta-opioid receptors and beta(2)-adrenoreceptors were observed in co-immunoprecipitation studies. Such hetero-oligomers could also be detected using bioluminescence resonance energy transfer although the signal obtained was substantially smaller than for homo-oligomers of either receptor type. Signal corresponding to the delta-opioid receptor-beta(2)-adrenoreceptor hetero-oligomer was increased in the presence of agonist for either receptor. However, substantial levels of this hetero-oligomer were not detected at the cell surface using time-resolved fluorescence resonance energy transfer. These studies demonstrate that, following transient transfection of HEK293 cells, constitutively formed oligomers of the human delta-opioid receptor can be detected by a variety of approaches. However, these are not regulated by ligand occupancy. They also indicate that time-resolved fluorescence resonance energy transfer represents a means to detect such oligomers at the cell surface in populations of intact cells.

Blotting, Western↗
PubMed2001

Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIA.

Hepatitis B virus (HBV) genotyping and hepatitis B surface antigen (HBsAg) subtyping were carried out on sera from 196 HBsAg-positive patients, including 151 refugees entering the United States and 45 injection drug users in Seattle. HBsAg subtyping was performed by enzyme immunoassay (EIA) using a panel of monoclonal antibodies and the HBV genotype was determined by polymerase chain reaction (PCR) followed by detection of amplified HBV DNA by a reverse-phase hybridization line probe assay (LiPA) using genotype-specific probes. HBV DNA was detected by PCR in 155 (79%) of the 196 sera and all 155 were genotyped by LiPA. Samples from Southeast Asia were predominantly genotype B/subtype ayw1 and genotype C/adr; samples from the former Soviet Union and eastern Europe were mostly genotype D/ayw2 and genotype D/ayw3; samples from east Africa were mainly genotype A/adw2 and genotype D/ayw2; and samples from injection drug users were mostly genotype D/ayw3 and genotype A/adw2. Some strains of ayw3 gave atypical monoclonal antibody reactivity patterns in the subtyping assay due to a Val/Ala instead of a Thr at amino acid residue 118 and a Thr instead of a Met at residue 125. A strain of ayw2 also gave an atypical monoclonal antibody reactivity pattern due to an Ala instead of a Thr at amino acid residue 123. LiPA genotyping and monoclonal EIA subtyping can provide useful information for epidemiological studies.

Africa, Eastern↗
PubMed2001

Influence of photoperiod on N-acetyltransferase activity and melatonin in the fiddler crab Uca pugilator.

Melatonin and N-acetyltransferase (NAT) activity were measured in the eyestalks of fiddler crabs acclimated to various photoperiods: constant light, a L:D 12:12 h photoperiod, or constant dark. Following acclimation, eyestalks were collected every 3 h over a 24-h period; they were assayed for melatonin with a radioimmunoassay and for NAT activity with a radioenzymatic assay. In constant light, melatonin levels increased at 1300 h, from 142 to 431 pg x mg(-1) eyestalk; NAT activity increased concurrently, from 97 to 203 pmol x h(-1) x mg(-1) eyestalk, and both remained elevated until 0400 h. In the L:D 12:12 h photoperiod, melatonin levels increased at 1300 h from 28 to 230 pg x mg(-1) eyestalk, and though NAT activity increased significantly, from 80 to 122 pmol x h(-1) x mg(-1) eyestalk, an even greater increase occurred at 0400 h, when melatonin levels were low. In constant dark, melatonin levels increased at 1600 h, from 22 to 196 pg x mg(-1) eyestalk, with a concurrent increase in NAT activity from 93 to 140 pmol x mg(-1) x h(-1) eyestalk. However, the second peak in melatonin (111 pg x mg(-1)), occurring at 0400 h, was out of phase with the second peak of NAT activity (113 pmol x mg(-1) x h(-1) eyestalk) which occurred at 0700 h. NAT may be a rate-limiting step in melatonin synthesis in fiddler crabs under some conditions (constant light and the 1300 h peak in constant dark); however, NAT activity correlates poorly with melatonin levels in a L:D 12:12 h photoperiod and in constant dark relative to the 0400 h melatonin peak.

Animals↗
PubMed2001

Cloning, pharmacology, and tissue distribution of G-protein-coupled receptor GPR105 (KIAA0001) rodent orthologs.

It has recently been shown that UDP-glucose is a potent agonist of the orphan G-protein-coupled receptor (GPCR) KIAA0001. Here we report cloning and analysis of the rat and mouse orthologs of this receptor. In accordance with GPCR nomenclature, we have renamed the cDNA clone, KIAA0001, and its orthologs GPR105 to reflect their functionality as G-protein-coupled receptors. The rat and mouse orthologs show 80% and 83% amino acid identity, respectively, to the human GPR105 protein. We demonstrate by genomic Southern blot analysis that there are no genes in the mouse or rat genomes with higher sequence similarity. Chromosomal mapping shows that the mouse and human genes are located on syntenic regions of chromosome 3. Further analyses of the rat and mouse GPR105 proteins show that they are activated by the same agonists as the human receptor, responding to UDP-glucose and closely related molecules with similar affinities. The mouse and rat receptors are widely expressed, as is the human receptor. Thus we conclude that we have identified the rat and mouse orthologs of the human gene GPR105.

Amino Acid Sequence↗
PubMed2001

Clinical pathways--can they be used in trauma care. An analysis of their ability to fit the patient.

This study prospectively evaluated the appropriateness and ability of clinical pathways to fit trauma patients in five key conditions, severe head injury, fractured ribs, fractured pelvis, fractured femur and blunt abdominal trauma, who were admitted to a single Level 1 Trauma Centre, between February and July 1999. Each pathway consisted of 14 elements of care divided into observable outcomes. Failure to achieve an outcome resulted in a variance or deviation from the pathway, which was assessed by the number of non-applicable variances. Appropriateness of clinical pathways was assessed by the applicability index (the number of non-applicable variances divided by the potential variances). Critical mismatches occurred when non-applicable variances exceeded 50% of potential variances. 146 patients, with the mean age 41.9 years (S.D. 20.7), mean ISS 11.1 (S.D. 10.7) were enrolled; 18 with severe head injury, 59 with fractured ribs, 13 with fractured pelvis, 20 with fractured femur and 36 with blunt abdominal trauma. Critical mismatch occurred in seven patients. Applicability indexes were 87 for head, 93 for ribs, 92 for blunt abdominal trauma, 91 for femur and 92 for the pelvic pathway. Patient assessment, pain management, skin integrity and patient education were the most appropriate key elements of care, discharge planning, patient satisfaction, treatment and activity were least applicable. This study identified, for the first time, that clinical pathways are clinically appropriate for major trauma conditions.

Abdominal Injuries↗
PubMed2001

On 'infinite basis set limits' in molecular electronic structure calculations.

Sequences of basis sets can be constructed so as to approach the 'infinite basis set limit' in molecular electronic structure calculations. Extrapolation procedures can also be devized to provide accurate values of this limit. However, some care is required since the 'infinite basis set limit' may not correspond to the limit supported by a complete basis set. Extrapolation procedures can then lead to limiting values, which are not estimates of the exact solutions.

Journal Article↗
PubMed2001

Investigation of the sleep electrocorticogram of the common marmoset (Callithrix jacchus) using radiotelemetry.

OBJECTIVE: To evaluate the use of a totally implantable radiotelemetry system for recording the sleep electrocorticogram (ECoG) of a small new world primate, the common marmoset (Callithrix jacchus) without restraint during data collection. METHODS: Under anaesthesia a telemetry transmitter, which allowed the recording of a single ECoG channel, was implanted intraperitoneally. This system allowed ECoG data to be recorded overnight from animals living in pairs within their habitual laboratory environment over a period of 12 months. Data were subsequently scored using modified Rechtschaffen and Kales criteria (A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Los Angeles, UCLA Brain Information Service/Brain Research Institute, 1968) into stages of waking, light sleep, deep sleep and probable rapid eye movement sleep (pREM). Concurrent video recording was used to assist in the categorising of pREM. RESULTS: Results showed that, as in man, the marmoset exhibits sleep cycles with stages alternating between non-REM (deep sleep and light sleep) and pREM sleep throughout the night. In common with other non-human primates the duration of each of the sleep stages was relatively short and punctuated with frequent waking. CONCLUSIONS: These data suggest that sleep in marmosets housed under laboratory conditions (a) can be recorded without restraint and (b) has potential to be used as a model for human sleep.

Animals↗
PubMed2001

Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats.

The effects of centrally injected orexin-A on plasma adrenocorticotropin (ACTH) and corticosterone levels and corticotropin releasing factor (CRF) and arginine vasopressin (AVP) mRNA in the parvocellular cells of the paraventricular nucleus (PVN) of the rat were investigated. In animals implanted previously with a lateral brain ventricle and femoral artery cannula, a single i.c.v. injection of orexin-A (10 microg/rat) resulted in a rapid, significant increase in plasma ACTH and corticosterone concentrations. Plasma ACTH reached a peak (12.5-fold greater than basal levels) at 30 min, which was maintained over 120 min before declining towards control levels by 240 min. Plasma corticosterone concentrations reached a peak (6.7-fold greater than basal levels) at 30 min. Orexin-A at a higher dose (30 microg/rat) also produced a rapid increase in plasma ACTH and corticosterone concentrations. The area under the curve for plasma levels of ACTH was similar for both doses of orexin-A. In a second study, orexin-A (10 microg/rat) was injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In situ hybridization histochemistry revealed that CRF and AVP mRNA levels were significantly increased in the parvocellular cells of the PVN. Pro-opiomelanocortin mRNA levels in the pituitary gland were not significantly elevated in response to orexin-A. These results suggest that orexin-A is able to act centrally to activate the hypothalamic-pituitary-adrenal axis involving stimulation of both CRF and AVP expression.

Adrenocorticotropic Hormone↗
PubMed2001

General practitioner-hospital communications: a review of discharge summaries.

The objective of this study was to examine the reliability, effectiveness, accuracy and timeliness of hospital to general practitioner (GP) information transfer by discharge summaries produced in a general public hospital in New South Wales, Australia. A retrospective audit of 569 patient discharge summaries and related medical records with a targeted GP interview was performed to determine receipt and clinical value of the recorded information. The main outcome measure was the number and quality of discharge summaries received by patient-nominated GPs. Summaries written for patients discharged from hospital were estimated to be received by the patient-nominated GP in 27.1% of cases. Discharge summaries audited were rated as being 63.6% accurate, with errors occurring in all facets of production. The current method of discharge summary production and distribution is unacceptable. The high number of errors (36.4%) and the low rate of receipt (27.1%), indicates that resources invested in the production of the discharge summary could be better utilized to improve information transfer.

Communication↗
PubMed2001

Visualizing differences in ligand-induced beta-arrestin-GFP interactions and trafficking between three recently characterized G protein-coupled receptors.

beta-Arrestin 1-GFP or beta-arrestin 2-GFP were coexpressed transiently with G protein-coupled receptor kinase 2 within cells stably expressing the orexin-1, apelin or melanin-concentrating hormone (MCH), receptors. In response to agonist ligands both the orexin-1 and apelin receptors were able to rapidly translocate both beta-arrestin 1-GFP and beta-arrestin 2-GFP from cytoplasm to the plasma membrane. For the MCH receptor this was only observed for beta-arrestin 2-GFP. beta-Arrestin 1-GFP translocated by the apelin receptor remained at the plasma membrane during prolonged exposure to ligand even though the receptor became internalized. By contrast, for the orexin-1 receptor, internalization of beta-arrestin 1-GFP within punctate vesicles could be observed for over 60 min in the continued presence of agonist. Co-internalization of the orexin-1 receptor was observed by monitoring the binding and trafficking of TAMRA-(5- and 6-carboxytetramethylrhodamine) labelled orexin-A. Subsequent addition of an orexin-1 receptor antagonist resulted in cessation of incorporation of beta-arrestin 1-GFP into vesicles at the plasma membrane and a gradual clearance of beta-arrestin 1-GFP from intracellular vesicles. For the melanin-concentrating hormone receptor the bulk of translocated beta-arrestin 2-GFP was maintained at concentrated foci close to, or at, the plasma membrane. These results demonstrate very distinct features of beta-arrestin-GFP interactions and trafficking for three G protein-coupled receptors for which the natural ligands have only recently been identified and which were thus previously considered as orphan receptors.

Animals↗
PubMed2001

Macarthur model for ambulatory services.

The Macarthur Health Sector has embraced the concept of Ambulatory Care within all clinical streams. The Macarthur Model for Ambulatory Services is multi faceted and has sought to encompass and combine the best features of many established services throughout Australia and the world. The results is one integrated, cohesive model that allows patients multiple points of entry and exit. Ambulatory Care has developed an essential link in the continuum of care from acute 'illness' hospital-based to maintenance community 'health' care. The philosophy of shared responsibility between patient, carer, general practitioner and a hospital specialist team underpins the model developing in Macarthur.

Aftercare↗