PubMed Health⌕ Search

Biomedical subjects

C Sinclair

Publications and source records attributed to C Sinclair.

At least 19 recordsLinked to original sources
PubMed2006

A sample distribution programme for erythropoietin.

A survey was sent to laboratories participating in the United Kingdom External Quality Assessment Service (UKNEQAS) Haematinics Scheme about the measurement of serum erythropoietin (EPO). Six laboratories, from a total of 120 that returned the survey, were measuring serum EPO concentrations by commercially available immunoassays on site in the United Kingdom. The workload of the laboratories varied from up to 100 specimens per month to more than 100 specimens analysed per week. All laboratories included control material in the assays and none of the laboratories was participating in an external quality assessment scheme for serum EPO. Four laboratories agreed to take part in the first sample distribution programme, with five and six laboratories participating in distributions 2 and 3 respectively. The results from eight kits were compared from the three distributions over a 2-year period. The serum EPO concentrations for the methods showed some variation across the range of 2.9-200 U/l when the serum EPO concentrations for each method were compared with the whole method mean. The results from this scheme have identified a role for an external quality assessment scheme for serum EPO measurements.

Benchmarking↗
PubMed2005

Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays.

Tissue microarrays assembled from control and multiple sclerosis (MS) brain tissue have been used to assess the expression patterns and cellular distribution of two antigens, the proinflammatory cytokine osteopontin and the inducible heat shock protein alphaBeta-crystallin, which have previously been implicated in MS pathogenesis. Tissue cores were taken from paraffin-embedded donor blocks containing chronic active or chronic inactive plaques and normal-appearing white matter (NAWM) in seven MS cases, and white matter (WM) in five control cases. Expression patterns of both proteins were assessed against myelin density and microglial activation in the different tissue categories. Both proteins showed increased expression in all categories of MS tissue compared with control WM. The results indicate progressive up-regulation of expression of osteopontin with increased plaque activity, while elevation of alphaBeta-crystallin expression in MS tissue was independent of demyelination. In MS NAWM a significant correlation was observed between high levels of expression of osteopontin and alphaBeta-crystallin. Osteopontin expression was predominantly confined to astrocytes throughout MS tissues. alphaBeta-crystallin was expressed on astrocytes, oligodendrocytes and occasionally on demyelinated axons. Taken together, these data indicate a wider distribution of osteopontin and alphaBeta-crystallin in MS tissues than previously described and support their proposed role in MS pathogenesis.

Astrocytes↗
PubMed2004

Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children under two years.

BACKGROUND: Gastro-esophageal reflux (GER) is the refluxing of gastric contents into the esophagus. Fifty per cent of all infants 0 to 3 months regurgitate at least once a day. This drops to 5% once infants are 10 to 12 months old. Three per cent of parents of 10 to 12 month old infants view this as a problem. OBJECTIVES: To investigate the effectiveness of thickened feeds, positioning, and metoclopramide as compared to placebo in improving the outcome of GER in developmentally normal infants aged one month to two years. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2003), MEDLINE (January 1966 to 23 January 2003), EMBASE (January 1985 to 27 January 2003), and reference lists of articles. SELECTION CRITERIA: Randomised studies (parallel or cross over) which evaluated thickened feeds, positional alternations or metoclopramide for the treatment of GER in children between the age of one month and two years who were developmentally normal. DATA COLLECTION AND ANALYSIS: All three reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty trials involving 771 children met the inclusion criteria: eight dealt with thickened feeds, five with positioning, and seven with metoclopramide. Few comparisons could be made, and so summary measures were often made with two or three studies. Thickened feeds reduce the regurgitation severity score (standardized mean difference (SMD) -0.94;95% confidence interval -1.35 to -0.52), as well as the frequency of emesis (SMD -0.91; confidence interval -1.22 to -0.61). The reflux index was not reduced (weighted mean difference (WMD) 0.48%; 95% confidence interval-3.27 to 4.23). All five positioning studies utilized esophageal pH monitoring as their outcome measure. Elevating the head of the crib for treating reflux in the supine position is not justifiable. The seven metoclopramide studies used a variety of outcomes. Compared to placebo, metoclopramide appears to reduce daily symptoms ( SMD -0.73; 95% confidence interval -1.16 to -0.30), and reduce the reflux index (WMD -2.80%; 95% confidence interval -5.58 to -0.01). It does increase side effects. REVIEWERS' CONCLUSIONS: Thickened feeds are helpful in reducing the symptoms of GER. Elevating the head of the crib in the supine position does not have any effect. Metoclopramide may have some benefit in comparison to placebo in the symptomatic treatment for GER, but that must be weighed against possible side effects. .

Dopamine Antagonists↗
PubMed2001

Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties.

(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca(2+)](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.

Alanine↗
PubMed2001

Mechanical and pathologic consequences of induced concentric anular tears in an ovine model.

STUDY DESIGN: Relations between induced concentric tears in the sheep disc and the mechanics of the intervertebral joint and vertebral body bone were analyzed. OBJECTIVE: To examine the effect of concentric disc tears on the mechanics of the spine. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc results in changes to the mechanics and morphology of the spine, but the effect of concentric disc tears is unknown. METHODS: In this study, 48 merino wethers were subjected to surgery, and discs were randomly selected for either a needlestick injury or induction of a concentric tear in the anterior and left anterolateral anulus. Sheep were randomly assigned to groups for killing at 0, 1, 3, 6, 12, and 18 months. From each sheep, two spine segments were mechanically tested: one with a needlestick injury and one with a concentric tear. Macroscopic disc morphology was assessed by three axial slices of the disc. Sagittal bone slices were taken from cranial and caudal vertebral bodies for histologic analysis. RESULTS: Induced concentric tears decrease the stiffness of intact spine segments in left bending and the disc alone in flexion. In all other mechanical tests, the needlestick injury had the same effect as the induced concentric tear. In the isolated disc, the disc stiffness at 6 months was increased for right bending, as compared with the response at 1 month. This was associated with increased anterior lamellar thickening and increased vertebral body bone volume fraction. CONCLUSIONS: Concentric tears and needlestick injury in the anterior anulus lead to mechanical changes in the disc and both anular lamellar thickness and vertebral body bone volume fraction. A needlestick injury through the anulus parallel to the lamellae produces progressive damage.

Animals↗
PubMed2001

Structural analysis of the 17q22-23 amplicon identifies several independent targets of amplification in breast cancer cell lines and tumors.

A novel region of amplification in breast tumors has recently been identified on chromosome 17q22-23. In an effort to identify the oncogenes in the region that are targeted by the amplification process, we determined the structure of the amplicon in breast cancer cell lines and tumors. Physical and transcription maps of the approximately 3.5-Mb region were established and used as the basis for copy number analysis within the region by Southern blot and fluorescence in situ hybridization. Seven specific and independent amplification maxima were identified in breast cancer cell lines and breast tumors. We present correlative amplification and overexpression studies for the FLJ21316 and Hs.6649 genes suggesting a role for these candidates as amplification-dependent oncogenes.

Amino Acid Sequence↗
PubMed2001

Levels of variation in stress resistance in drosophila among strains, local populations, and geographic regions: patterns for desiccation, starvation, cold resistance, and associated traits.

Stress resistance traits in Drosophila often show clinal variation. Although these patterns suggest selection, there is generally no attempt to test how large differences at the geographical level are relative to levels of variation within and between local populations. Here we compare these levels in D. melanogaster from temperate Tasmania versus tropical northern Queensland by focusing on adult resistance to desiccation, cold and starvation stress, as well as associated traits (size, lipid content). For starvation and desiccation resistance, levels of variation were highest among strains from the same population. whereas there was little differentiation among local populations and a low level of differentiation at the geographic level. For adult cold resistance, there was local differentiation and strain variation but no geographic variation. For size (thorax length), geographic differentiation was higher despite some overlap among strains from the tropical and temperate locations. Finally, for lipid levels there was only evidence for variation among strains. The low level of differentiation among geographic locations for stress resistance was further verified with the characterization of isofemale strains from 18 locations along a coastal transect extending from Tasmania to northern Queensland. Crosses among some of the isofemale strains showed that results were not confounded by inbreeding effects. Strains derived from a cross between a tropical and temperate strain differed for all traits, and variation among strains for body size was higher than strain variation within the geographic regions. Unlike in previous studies, lipid content and starvation resistance were not correlated in any set of strains, but there was a correlation between cold resistance and lipid content. There was also a correlation between desiccation resistance and size but only in the geographic cross strains. These findings suggest a large amount of variation in stress resistance at the population level and inconsistent correlation patterns across experimental approaches.

Analysis of Variance↗
PubMed2001

Rapid loss of stress resistance in Drosophila melanogaster under adaptation to laboratory culture.

We investigate changes in resistance to desiccation and starvation during adaptation of Drosophila melanogaster to laboratory culture. We test the hypothesis that resistance to environmental stresses is lost under laboratory adaptation. For both traits, there was a rapid loss of resistance over a three-year period. The rapidity of the response suggested that mutation accumulation could not account for it. Rather, resistance to environmental stresses appeared to be lost as a correlated response to selection on another trait, such as early fertility, with which stress resistance is negatively genetically correlated. These results suggest that caution is needed when extrapolating from evolution of stress resistance in long-established laboratory stocks to patterns of responses and correlated responses in natural populations.

Adaptation, Physiological↗
PubMed2001

Slip! Slop! Slap! and SunSmart, 1980-2000: Skin cancer control and 20 years of population-based campaigning.

The Anti-Cancer Council of Victoria has been running sun protection programs for more than 20 years: Slip! Slop! Slap! from 1980 to 1988 and SunSmart from 1988 to the present. The Victorian Health Promotion Foundation has provided funding for the SunSmart program for the past 13 years. These programs have played an important role in changing the whole society's approach to the sun and have resulted in marked reductions in sun exposure. This article describes the social, political, economic, and organizational context within which these programs developed. Then 10 areas are discussed that illustrate a critical aspect of the development and implementation of this successful systemwide health promotion program. These areas focus on key aspects of the context within which the program operates and on issues that derive from the experience of implementing program strategies. In summary, the success of the two programs is described as having been built on two key foundations: the vital integration of research and evaluation, on one hand, and a strong basis of consistency and continuity, on the other.

Adolescent↗
PubMed1999

The tetratricopeptide repeat domain and a C-terminal region control the activity of Ser/Thr protein phosphatase 5.

Protein Ser/Thr phosphatase 5 is a 58-kDa protein containing a catalytic domain structurally related to the catalytic subunits of protein phosphatases 1, 2A, and 2B and an extended N-terminal domain with three tetratricopeptide repeats. The activity of this enzyme is stimulated 4-14-fold in vitro by polyunsaturated fatty acids and anionic phospholipids. The structural basis for lipid activation of protein phosphatase 5 was examined by limited proteolysis and site-directed mutagenesis. Trypsinolysis removed the tetratricopeptide repeat domain and increased activity to approximately half that of lipid-stimulated, full-length enzyme. Subtilisin removed the tetratricopeptide repeat domain and 10 residues from the C terminus, creating a catalytic fragment with activity that was equal to or greater than that of lipid-stimulated, full-length enzyme. Catalytic fragments generated by proteolysis were no longer stimulated by lipid, and degradation of the tetratricopeptide repeat domain was decreased by association with lipid. A truncated mutant missing 13 C-terminal residues was also insensitive to lipid and was as active as full-length, lipid-stimulated enzyme. These results suggest that the C-terminal and N-terminal domain act in a coordinated manner to suppress the activity of protein phosphatase 5 and mediate its activation by lipid. These regions may be targets for the regulation of protein phosphatase 5 activity in vivo.

Amino Acid Sequence↗
PubMed1999

Haloalcohols deplete glutathione when incubated with fortified liver fractions.

1. This study has examined the ability of dichloropropanols, haloalcohols and their putative metabolites to deplete glutathione when incubated with liver fractions obtained from untreated and differentially induced rats. 2. 1,3-Dichloropropan-2-ol and 2,3-dichloropropan-1-ol (0-1000 microM) both depleted glutathione in a dose-dependent manner when incubated with cofactors (NADPH generating system) and liver microsomes from the untreated rat. 3. The extent of GSH depletion was significantly enhanced when liver microsomes from the isoniazid- or isosafrole-treated rat were used. 4. Epichlorohydrin produced a moderate, dose-dependent depletion of GSH. By contrast, 1,3-dichloroacetone (identified by TLC as a metabolite of 1,3-dichloropropanol) was a potent depletor of glutathione. 5. N-acetylcysteine was less efficient than glutathione as a nucleophile trap for epichlorohydrin, 1,3-dichloroacetone or reactive metabolites derived from 1,3-dichloropropan-2-ol. 6. 1,3-Dibromopropan-2-ol and 1,4-dibromobutan-2-ol were potent depletors of GSH but 1-bromopropan-2-ol produced less GSH depletion. Both dibromoalcohols depleted GSH when incubated with dialysed cytosol derived from the livers of untreated rats. 7. The GSH depletion mediated by 1,3-dichloropropan-2-ol, 1,3-dibromopropan-2-ol, 1,4-dibromobutan-2-ol and 1-bromopropan-2-ol was inhibited by inclusion of pyridine (1 mM) or cofactor omission. 1,3-Difluoropropanol did not deplete GSH under any of the conditions examined.

Acetylcysteine↗
PubMed1999

Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda5-VpreB1 locus control region.

The murine lambda5-VpreB1 locus encodes two proteins that form part of the pre-B-cell receptor and play a key role in B-lymphocyte development. We have identified a locus control region (LCR) which is responsible for coordinate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies of transgenes shows a clear difference in the expression behavior of the genes depending on the transgene copy number. While expression of both lambda5 and VpreB1 in single- and two-copy integrations requires the presence of a set of DNase I hypersensitive sites located 3' of the lambda5 gene, small fragments containing the genes have LCR activity when arranged in multiple-copy tandem arrays, indicating that additional components of the LCR are located within or close to the genes. The complete LCR is capable of driving efficient copy-dependent expression of a lambda5 gene in pre-B cells even when it is integrated into centomeric gamma-satellite DNA. The finding that activation of expression of the locus by positively acting factors is fully dominant over the silencing effect of heterochromatin has implications for models for chromatin-mediated gene silencing during B-cell development.

Animals↗
PubMed1998

Call to needle times after acute myocardial infarction in urban and rural areas in northeast Scotland: prospective observational study.

OBJECTIVE: To determine call to needle times and consider how best to provide timely thrombolytic treatment for patients with acute myocardial infarction. DESIGN: Prospective observational study. SETTING: City, suburban, and country practices referring patients to a single district general hospital in northeast Scotland. SUBJECTS: 1046 patients with suspected acute myocardial infarction given thrombolytic treatment. MAIN OUTCOME MEASURES: Time from patients' calls for medical help until receipt of opiate or thrombolytic treatment, measured against a call to needle time of 90 minutes or less, as proposed by the British Heart Foundation. RESULTS: General practitioners were the first medical contact in 97% (528/544) of calls by country patients and 68% (340/502) of city and suburban patients. When opiate was given by general practitioners, median call to opiate time was about 30 minutes (95% within 90 minutes) in city, suburbs, and country; call to opiate delay was about 60 minutes in city and suburban patients calling "999" for an ambulance. One third of country patients received thrombolytic treatment from their general practitioners with a median call to thrombolysis time of 45 minutes (93% within 90 minutes); this compares with 150 minutes (5% within 90 minutes) when this treatment was deferred until after hospital admission. In the city and suburbs, no thrombolytic treatment was given outside hospital, and only a minority of patients received it within 90 minutes of calling; median call to thrombolysis time was 95 (46% within 90 minutes) minutes. CONCLUSIONS: The first medical contact after acute myocardial infarction is most commonly with a general practitioner. This contact provides the optimum opportunity to give thrombolytic treatment within the British Heart Foundation's guideline.

Acute Disease↗
PubMed1998

Audit of prehospital thrombolysis by general practitioners in peripheral practices in Grampian.

BACKGROUND: In the Grampian region early anistreplase trial (GREAT), domiciliary thrombolysis by general practitioners was associated with a halving of one year mortality compared with hospital administration. However, after completion of the trial and publication of the results, the use of this treatment by general practitioners declined sharply. OBJECTIVE: To increase the proportion of eligible patients receiving timely thrombolytic treatment from their general practitioners. SETTING: Practices in Grampian located > or = 30 minutes' travelling time from Aberdeen Royal Infirmary, where patients with suspected acute myocardial infarction were referred after being seen by general practitioners. AUDIT STANDARD: A call-to-needle time of 90 minutes, as proposed by the British Heart Foundation (BHF). METHODS: Findings of this audit of pre-hospital management of acute myocardial infarction were periodically fed back to the participating doctors, when practice case reviews were also conducted. RESULTS: Of 414 administrations of thrombolytic treatment, 146 (35%) were given by general practitioners and 268 (65%) were deferred until after hospital admission. Median call-to-needle times were 45 (94% < or = 90) and 145 (7% < or = 90) minutes, respectively. Survival at one year was improved with prehospital compared with hospital thrombolysis (83% v 73%; p < 0.05). The proportion of patients receiving thrombolytic treatment from their general practitioners did not increase during the audit. CONCLUSIONS: In practices > or = 30 minutes from hospital, the BHF audit standard was readily achieved if general practitioners gave thrombolytic treatment, but not otherwise. Knowledge of the benefits of early thrombolysis, and feedback of audit results, did not lead to increased prehospital thrombolytic use. Additional incentives are required if general practitioners are to give thrombolytic treatment.

Aged↗
PubMed1997

Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5.

An arachidonic acid-stimulated Ser/Thr phosphatase activity was detected in soluble extracts prepared from rat pituitary clonal GH4C1 cells, rat or bovine brain, and bovine heart. The enzyme activity was purified to homogeneity from bovine brain as a monomer with a Mr of 63,000 and a specific activity of 32 nmol of Pi released per min/mg of protein when assayed in the presence of 10 microM phosphocasein in the absence of lipid. Arachidonic acid stimulated activity 4-14-fold, with half-maximal stimulation at 50-100 microM, when assayed in the presence of a variety of phosphosubstrates including casein, reduced carboxamidomethylated and maleylated lysozyme, myelin basic protein, and histone. Oleic acid, linoleic acid, and palmitoleic acid also stimulated activity; however, saturated fatty acids and alcohol or methyl ester derivatives of fatty acids did not significantly affect activity. The lipid-stimulated phosphatase was identified as the bovine equivalent of protein phosphatase 5 or a closely related homolog by sequence analysis of proteolytic fragments generated from the purified enzyme. When recombinant rat protein phosphatase 5 was expressed as a cleavable glutathione S-transferase fusion protein, the affinity-purified thrombin-cleaved enzyme exhibited a specific activity and sensitivity to arachidonic acid similar to those of the purified bovine brain enzyme. These results suggest that protein phosphatase 5 may be regulated in vivo by a lipid second messenger or another endogenous activator.

Amino Acid Sequence↗
PubMed1997

The effect of glossopharyngeal nerve block on pain after elective adult tonsillectomy and uvulopalatoplasty.

This controlled, randomised, double-blind study compared whether glossopharyngeal nerve block and intravenous morphine administered peri-operatively, decreased pain following elective adult tonsillectomy and uvulopalatoplasty more than morphine alone. Sixteen of 30 patients undergoing uvulopalatoplasty and 38 of 78 patients having tonsillectomy received bilateral glossopharyngeal nerve blocks, using bupivacaine 0.5% and adrenaline 1:200,000, or no intervention. There were no differences in postoperative analgesic consumption between the two groups. Visual analogue pain scores measured during swallowing in the recovery room and on the ward postoperatively were significantly less overall in uvulopalatoplasty patients who had received a block (p = 0.004). This difference was not found for tonsillectomy. We found no significant differences between groups, in pain scores recorded during the first 5 days at home. We conclude that glossopharyngeal block does not improve analgesia following tonsillectomy although there is short-lived benefit following uvulopalatoplasty.

Adult↗