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Biomedical subjects

J Reid

Publications and source records attributed to J Reid.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of gene expression identifies PLAB as a mediator of the apoptotic activity of fenretinide in human ovarian cancer cells.

Fenretinide (4-HPR) is a synthetic retinoid with antitumor activity, which induces apoptosis in cancer cell lines of different histotypes. To identify genes contributing to its apoptotic activity in ovarian cancer cells, we monitored, by cDNA arrays, gene expression changes after 4-HPR exposure in A2780, a human ovarian carcinoma cell line sensitive to the retinoid. Among the differentially expressed transcripts, PLAcental Bone morphogenetic protein (PLAB), a proapoptotic gene, was the most highly induced. In a panel of ovarian carcinoma cell lines with different 4-HPR sensitivities, PLAB upregulation was associated with cellular response to 4-HPR, its overexpression increased basal apoptosis and its silencing by small interfering RNA decreased the ability of 4-HPR to induce apoptosis. PLAB induction by 4-HPR was p53- and EGR-1 independent and was regulated, at least in part, by increased stability of PLAB mRNA. PLAB up-modulation by 4-HPR also occurred in vivo: in ascitic cells collected from patients with ovarian cancer before and after 4-HPR treatment, PLAB was upmodulated in 2/4 patients. Our results in certain ovarian cancer cell lines indicate a role for PLAB as a mediator of 4-HPR-induced apoptosis. The correlation of increased PLAB in vivo with antitumor activity remains to be established.

Antineoplastic Agents↗
PubMed2006

Continuous passive motion following total knee replacement: a prospective randomized trial with follow-up to 1 year.

We have carried out a prospective randomised, single blind clinical trial to investigate the effect of continuous passive motion on range of knee flexion, lack of extension, pain levels and analgesic use after total knee replacement surgery. 85 subjects were randomly allocated to control or study group. All subjects followed the existing rehabilitation protocol, which permits immediate active range of motion exercises and mobilisation with the study group using continuous passive motion for 1 h, twice a day. Outcome measures employed were range of motion, pain assessed on a visual analogue scale and analgesic use according to the WHO ladder. Blinded evaluation was carried out preoperatively, at time of discharge from hospital, 6 weeks, 6 and 12 months postoperation. No significant difference was observed between groups at all time intervals for each outcome variable using Wilcoxon Rank sum tests. The results substantiate previous findings that short duration continuous passive motion following total knee arthroplasty does not influence outcome of range of motion or reported pain.

Aged↗
PubMed2006

Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial.

OBJECTIVES: To evaluate the effect of intensive lipid-lowering treatment on coronary artery calcification in a substudy of a trial recruiting patients with calcific aortic stenosis. METHODS: In a double blind randomised controlled trial, 102 patients with calcific aortic stenosis and coronary artery calcification were randomly assigned by the minimisation technique to atorvastatin 80 mg daily or matched placebo. Coronary artery calcification was assessed annually by helical computed tomography. RESULTS: 48 patients were randomly assigned to atorvastatin and 54 to placebo with a median follow up of 24 months (interquartile range 24-30). Baseline characteristics and coronary artery calcium scores were similar in both groups. Atorvastatin reduced serum low density lipoprotein cholesterol (-53%, p < 0.001) and C reactive protein (-49%, p < 0.001) concentrations whereas there was no change with placebo (-7% and 17%, p > 0.95 for both). The rate of change in coronary artery calcification was 26%/year (0.234 (SE 0.037) log arbitrary units (AU)/year; n = 39) in the atorvastatin group and 18%/year (0.167 (SE 0.034) log AU/year; n = 49) in the placebo group, with a geometric mean difference of 7%/year (95% confidence interval -3% to 18%, p = 0.18). Serum low density lipoprotein concentrations were not correlated with the rate of progression of coronary calcification (r = 0.05, p = 0.62). CONCLUSION: In contrast to previous observational studies, this randomised controlled trial has shown that, despite reducing systemic inflammation and halving serum low density lipoprotein cholesterol concentrations, statin treatment does not have a major effect on the rate of progression of coronary artery calcification.

Adult↗
PubMed2006

Secreted factors from ventral telencephalon induce the differentiation of GABAergic neurons in cortical cultures.

It is widely believed that the pyramidal cells and interneurons of the cerebral cortex are distinct in their origin, lineage and genetic make up. In view of these findings, the current thesis is that the phenotype determination of cortical neurons is primarily directed by genetic mechanisms. Using in vitro assays, the present study demonstrates that secreted factors from ganglionic eminence (GE) of the ventral telencephalon have the potency to induce the differentiation of a subset of cortical neurons towards gamma-aminobutyric acid (GABA)ergic lineage. Characterization of cortical cultures that were exposed to medium derived from GE illustrated a significant increase in the number of GABA-, calretinin- and calbindin-positive neurons. Calcium imaging together with pharmacological studies showed that the application of exogenous medium significantly elevated the intracellular calcium transients in cortical neurons through the activation of ionotropic glutamate receptors. The increase in GABA+ neurons appeared to be associated with the elevated calcium activity; treatment with blockers specific for glutamate receptors abolished both the synchronized transients and reduced the differentiation of GABAergic neurons. Such studies demonstrate that although intrinsic mechanisms determine the fate of cortical interneurons, extrinsic factors have the potency to influence their neurochemical differentiation and contribute towards their molecular diversity.

Animals↗
PubMed2005

Pitavastatin.

The growing number of trials that have highlighted the benefit of intensive lowering of total- and low density lipoprotein (LDL)-cholesterol levels especially with statins has created a need for more efficacious agents. Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin; although, head-to-head studies are yet to be conducted.

Animals↗
PubMed2005

Timing of aspirin and secondary preventative therapies in acute stroke: support for use of stroke units.

BACKGROUND: We aimed to study the timing of aspirin prescription in ischaemic stroke comparing patients admitted to an acute stroke unit (ASU) directly or via a general medical ward. We also analysed prescription of secondary preventive therapies in stroke patients in an ASU. METHODS: Retrospective analysis was made of medical notes and prescription records of 69 patients admitted to an ASU over a three month period to establish timing of aspirin prescription with respect to onset of stroke symptoms, CT brain scan and route of admission to the ASU. RESULTS: CT brain scans were obtained at a median of 2.1 days post stroke (IQ range 1.3-4.3). Patients directly admitted to the ASU received aspirin earlier post admission compared to those admitted via a medical ward (0.7 vs 2.2 days, p < 0.01) and were also more likely to receive aspirin prior to CT scan being performed (57% vs 19%, p = 0.02). 86% of stroke patients were discharged on an antiplatelet therapy, 79% on a statin, 37% on a thiazide diuretic and 32% on an ACE inhibitor or angiotensin II antagonist. CONCLUSION: Aspirin was given more promptly in acute stroke and more commonly prior to CT scanning in an ASU compared to a medical ward. Statin therapy is used extensively in stroke but there is a much lower rate of initiation of other secondary preventive therapies (e.g. anti-hypertensive therapy) in hospital. These findings demonstrate a hesitancy in early use of aspirin amongst general physicians and lends support for the use of stroke units.

Aged↗
PubMed2004

Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate.

BACKGROUND: Cleft lip and cleft palate are common birth defects, affecting about one baby of every 700 born. Feeding these babies is an immediate concern and there is evidence of delay in growth of children with a cleft as compared to those without clefting. In an effort to combat reduced weight for height, a variety of advice and devices are recommended to aid feeding of babies with clefts. OBJECTIVES: This review aims to assess the effects of these feeding interventions in babies with cleft lip and/or palate on growth, development and parental satisfaction. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials register (June 2001), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to May 24th 2004), EMBASE (1980 to August 7th 2002), CINAHL (1982 to August 7th 2002), PsychINFO (1967 to August 13th 2002), AMED (1985 to August 13th 2002). Attempts were made to identify both unpublished and ongoing studies. There was no restriction with regard to language of publication. SELECTION CRITERIA: Studies were included if they were randomised controlled trials (RCTs) of feeding interventions for babies born with cleft lip, cleft palate or cleft lip and palate up to the age of 6 months (from term). DATA COLLECTION AND ANALYSIS: Studies were assessed for relevance independently and in duplicate. All studies meeting the inclusion criteria were data extracted and assessed for validity independently by each member of the review team. Authors were contacted for clarification or missing information whenever possible. MAIN RESULTS: Four RCTs with a total of 232 babies, were included in the review. Comparisons made within the RCTs were squeezable versus rigid feeding bottles (two studies), breastfeeding versus spoon-feeding (one study) and maxillary plate versus no plate (one study). No statistically significant differences were shown for any of the primary outcomes when comparing bottle types, although squeezable bottles were less likely to require modification. No statistically significant difference was shown for infants fitted with a maxillary plate compared to no plate. A statistically significant difference in weight (kg) at 6 weeks post-surgery was shown in favour of breastfeeding when compared to spoon-feeding (mean difference 0.47; 95% CI: 0.20, 0.74). REVIEWERS' CONCLUSIONS: Squeezable bottles appear easier to use than rigid feeding bottles for babies born with clefts of the lip and/or palate, however, there is no evidence of a difference in growth outcomes between the bottle types. There is weak evidence that babies should be breastfed rather than spoon-fed following surgery for cleft lip. No evidence was found to assess the use of any types of maternal advice and/or support for these babies.

Cleft Lip↗
PubMed2004

The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential.

Aged↗
PubMed2004

A survey of small-scale broiler production systems in Botswana.

Aspects of husbandry, productivity parameters, diseases, marketing and farmer attitudes in small-scale broiler farms in Botswana were studied using a questionnaire-based survey. The number of broilers per production cycle in small-scale operations ranged from 100 to 2000, with an average of 640. On average, small-scale producers had 4-5 production cycles per annum with an interval of 2-3 weeks between batches. The average marketing age was 48.3 days at a live weight of 1.79 kg and a carcase weight of 1.42 kg. The average feed conversion ratio was estimated to be 2.72 (kg feed/kg live weight) and the average mortality was 9.15%. Overall, the performance indices of broilers under small-scale farm conditions were much poorer than those obtained elsewhere under improved management conditions, but these lower performance levels are suggestive of the potential that exists for further improvement. The survey also identified several areas of concern that constrain the realization of the full potential of this sector. Factors contributing to the poor performance under small-scale farm conditions are complex, but feed supply and quality, chick quality and farmer training appear to be areas for immediate improvement.

Agriculture↗
PubMed2004

Trends in childhood and parental asthma prevalence in Merseyside, 1991-1998.

OBJECTIVE: To determine changes in childhood and parental asthma prevalence in Merseyside between 1991 and 1998. METHODS: Three standardized cross-sectional respiratory health surveys using a parent-completed questionnaire were completed in 1991 (n = 1171), 1993 (n = 2368) and 1998 (n = 1964) amongst primary school children (5-11 years) attending the same 10 schools. The main outcome measures were prevalence of reported doctor diagnosed asthma, the symptom triad of cough, wheeze and breathlessness (C+W+B+) and parental asthma. RESULTS: Significant changes in prevalence for all respiratory variables occurred between 1991 and 1998, except for the symptom triad C+W+B+. Between 1991 and 1998 the prevalence of reported doctor diagnosed asthma increased from 17.7 to 29.8 per cent (p < 0.001), history of wheezing increased from 22.5 to 29.4 per cent (p < 0.001). The symptom triad of C+W+B+ changed from 9.6 to 9.9 per cent (p = 0.78). Childhood reported hospital admissions for respiratory illness increased from 5.5 to 10.7 per cent (p < 0.001). Paternal asthma increased from 6.5 per cent in 1991, to 8.6 per cent in 1998 (p = 0.031), and maternal asthma almost doubled in the same period from 6.6 to 11.2 per cent (p < 0.001). Children living in poorer areas (Townsend score 8-11) were more likely to have doctor diagnosed asthma (OR = 2.99, 95 per cent CI, 2.06 to 4.33) and C+W+B+ (OR = 2.17, CI 1.13 to 4.18). Childhood obesity was significantly associated with increased risk of both doctor diagnosed asthma (OR = 1.74, 95 per cent CI, 1.29 to 2.37) and C+W+B+ (OR = 1.88, 95 per cent CI, 1.21 to 2.90). CONCLUSION: A rising prevalence of reported doctor diagnosed asthma, but not C+W+B+ was observed during the 1990s in a low socio-economic area of Liverpool. Asthma prevalence was related to socio-economic deprivation and was associated with obesity. The rising prevalence of reported doctor diagnosed asthma is likely to be attributable to several factors, including changes in diagnostic labelling and the distribution of factors related to socio-economic status.

Adult↗
PubMed2003

Aortic valve calcification on computed tomography predicts the severity of aortic stenosis.

AIM: Incidental aortic valve calcification is often detected during computed tomography. The aim was to compare the severity of valvular stenosis and calcification in patients with aortic stenosis. MATERIALS AND METHODS: One hundred and fifty-seven patients aged 68+/-11 years (range: 34-85) with aortic valve stenosis underwent multislice helical computed tomography and Doppler echocardiography performed by independent, blinded observers. The aortic valve calcium score was determined using automated computer software calibrated with a phantom. RESULTS: Doppler echocardiography demonstrated a post-valve velocity of 3.45+/-0.66 m/s and a peak gradient of 49+/-11 mmHg. Computed tomography showed excellent reproducibility and the median aortic valve calcium score was 5858 AU (interquartile range, 1555-14,596). The computed tomography aortic valve calcium score positively correlated with the Doppler post-valve velocity and peak gradient (r=0.54, p<0.0001 for both) of the aortic valve. All patients with severe aortic stenosis had a calcium score of >3700 AU. CONCLUSION: Calcification of the aortic valve is closely associated with the severity of aortic stenosis, and heavy calcification suggests the presence of severe aortic stenosis that requires urgent cardiological assessment. Patients with lesser degrees of aortic valve calcification should be screened for aortic stenosis and monitored for disease progression.

Adult↗
PubMed2003

Structure and composition of silicon-stabilized tricalcium phosphate.

Silicon stabilized tricalcium phosphate [Si-TCP] is formed within the calcium hydroxyapatite (HA)-tricalcium phosphate (TCP) system when a stoichiometric precipitate of hydroxyapatite is fired at 1,000 degrees in the presence of SiO(2). This paper proposes a composition range and crystallographic structure for Si-TCP. Reitveld XRD powder diffraction, transmission electron microscopy, infrared and proton nuclear magnetic resonance measurements show that crystalline Si-TCP is associated with the displacement of OH from an initial hydroxyapatite structure. The resulting calcium phosphate is modified by the incorporation of silicon into its structure with excess silica contributing to an amorphous component. Si-TCP has a monoclinic structure with a space group P2(1)/a akin to alpha-TCP with estimated lattice constants of a=12.863+/-0.004 A, b=9.119 +/-0.003 A, c=15.232+/-0.004 A, beta=126.3+/-0.1 degrees. It is proposed that Si(4+) substitutes for P(5+)in the TCP lattice with the average chemical composition of Si-TCP set primarily by the mechanisms available for charge compensation. While the formation of OH vacancies in HA initiates the transformation to Si-TCP, two mechanisms of charge compensation in the Si-TCP structure are plausible. If O(2-) vacancies provide charge compensation, the composition of Si-TCP is Ca(3)(P(0.9)Si(0.1)O(3.95))(2) derived for the addition of 0.33 mol SiO(2):mol HA. If excess Ca(2+) compensates, the composition is Ca(3.08)(P(0.92)Si(0.08)O(4))(2) derived for the addition of 0.25 mol SiO(2):mol HA. The reaction occurs most effectively when SiO(2) is added as a colloidal suspension rather than by the in-situ thermal decomposition of a silicon metallorganic compound. The material is a bioceramic of major biological interest because of its osteoconductivity and unique influence on skeletal tissue repair and remodeling.

Absorption↗
PubMed2003

The androgen receptor transactivation domain: the interplay between protein conformation and protein-protein interactions.

The AR (androgen receptor) belongs to the nuclear receptor superfamily and directly regulates patterns of gene expression in response to the steroids testosterone and dihydrotestosterone. Sequences within the large N-terminal domain of the receptor have been shown to be important for transactivation and protein-protein interactions; however, little is known about the structure and folding of this region. Folding of the AR transactivation domain was observed in the presence of the helix-stabilizing solvent trifluorethanol and the natural osmolyte TMAO (trimethylamine N-oxide). TMAO resulted in the movement of two tryptophan residues to a less solvent-exposed environment and the formation of a protease-resistant conformation. Critically, binding to a target protein, the RAP74 subunit of the general transcription factor TFIIF, resulted in a similar resistance to protease digestion, consistent with induced folding of the receptor transactivation domain. Our current hypothesis is that the folding of the transactivation domain in response to specific protein-protein interactions creates a platform for subsequent interactions, resulting in the formation of a competent transcriptional activation complex.

Hormones↗
PubMed2002

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Alternative Splicing↗
PubMed2002

Changes in the Doppler waveform of the ovine femoral artery following infusion of vasoactive agents: a preliminary study.

The aim of this study was to investigate whether femoral artery pulsatility index (PI) can be used as an indicator of vasomotor tone in the digit of an ungulate species by measuring the change in PI induced by infusion of vasoactive agents in halothane-anaesthetised sheep. Intra-arterial infusion of the vasoconstrictor phenylephrine (9 microg min(-1)) tended to increase waveform PI (3.89-6.24, n=4, P=0.100). Infusion of a low dose (3 microg min(-1)) of the vasodilator sodium nitroprusside did not alter femoral artery PI, however infusion of a higher dose (30 microg min(-1)) tended to increase PI (5.39-6.70, n=5, P=0.059). During these studies heart rate, mean ABP and p(a)CO(2) did not change significantly. The tendency for PI to increase in response to vasodilation was unexpected and the mechanism involved is unclear. It appears that femoral artery PI cannot be used to predict vasomotor tone in the digit of the anaesthetised sheep.

Anesthetics, Inhalation↗