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Biomedical subjects

A D Wilson

Publications and source records attributed to A D Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass responses to Culicoides nubeculosus salivary gland extract.

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The allergens causing IBH are probably salivary gland proteins from these insects, but they have not yet been identified. The aim of our study was to identify the number and molecular weight of salivary gland extract (SGE) proteins derived from Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera of IBH-affected horses. Additionally, we sought to investigate the IgG subclass (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic horses born in Iceland, Icelandic horses and horses from different breeds born in mainland Europe). Additionally, the specific antibody response was studied before exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of 10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32, 22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001). Similarly, more IBH-affected than healthy horses had IgGa ab binding to the Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more protein bands than the sera of the healthy horses. The cohort of 10 Icelandic horses confirmed these results and showed that Culicoides SGE specific IgE correlates with onset of IBH. IBH-affected horses that were born in Iceland had IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly higher number of SGE proteins than IBH-affected horses born in mainland Europe. The present study shows that Culicoides SGE contains at least 10 potential allergens for IBH and that IBH-affected horses show a large variety of IgE-binding patterns in immunoblots. These findings are important for the future development of a specific immunotherapy with recombinant salivary gland allergens.

Animals↗
PubMed2006

Effects of interventions aimed at changing the length of primary care physicians' consultation.

BACKGROUND: Observational studies have shown differences in process and outcome between the consultations of primary care physicians whose average consultation lengths differ. These differences may be due to self selection. OBJECTIVES: To assess the effectiveness and efficiency of interventions to alter the length of primary care physicians' consultations. SEARCH STRATEGY: The following electronic databases were searched: Cochrane Effective Practice and Organisation of Care Group (EPOC) Specialised Register (October 2002); CENTRAL (The Cochrane Library June 2003); MEDLINE (1966 to October 2002);EMBASE (1981 to October 2002); NHS National Research Register (June 2003). The search strategies combined subject terms for 'general practice', 'consultation' and 'length' with methodological filters. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) of interventions to alter the length of primary care physicians' consultations. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors using agreed criteria. Disagreements were resolved by discussion. Where data were missing attempts were made to contact authors. Given the heterogeneity of studies meta-analysis was not attempted, and results are presented as a narrative summary. MAIN RESULTS: Six articles describing four UK trials met the inclusion criteria. All tested short term changes in the consultation time allocated to each patient and all had methodological weaknesses, particularly due to non-random allocation of patients. Altering appointment length resulted in modest changes in average length of consultation. There were no consistent differences in problem recognition, examination, prescribing, referral or investigation rates. There was some evidence that blood pressure was checked and smoking discussed more often when more time was available. None of the interventions were associated with differences in patient satisfaction. No trials examined efficiency. AUTHORS' CONCLUSIONS: The findings of this review do not provide sufficient evidence to support or resist a policy of altering the lengths of primary care physicians' consultations. Further trials are needed that focus on health outcomes and cost effectiveness.

Appointments and Schedules↗
PubMed2004

Increased heterozygosity and allele variants are seen in Texel compared to Suffolk sheep.

In this study, the Suffolk and Texel sheep breeds were compared for microsatellite marker heterozygosity throughout seven chromosomal regions in the sheep genome. A total of 623 Texel animals and 489 Suffolk animals in five and three half-sib families, respectively, were genotyped for microsatellite markers across the seven different chromosomes. Using the observed allele frequencies, the expected levels of heterozygosity were calculated for each family. The expected levels of heterozygosity did not significantly differ between the breeds across all regions studied. However, levels of expected heterozygosity were 32% higher in Texel animals on chromosome 4 due to a region of increased heterozygosity between BMS648 and BM3212. The number of allelic variants significantly differed between the breeds, solely due to a region of increased number of alleles on chromosome 20. This region of higher numbers of allele variants in the Texel breed extended from the MHC to c. 15 cM distal to the MHC region incorporating markers OMHC1, CSRD226, TGLA387 and BM1818, which had 3.30, 7.02, 3.09 and 6.75 more alleles in Texel than in Suffolk animals, respectively. No difference was observed in the variance of allele frequency between the two breeds. It is proposed that previous selective sweeps may have reduced numbers of alleles and levels of heterozygosity in the Suffolk breed.

Animals↗
PubMed2004

Mapping of quantitative trait loci for growth and carcass traits in commercial sheep populations.

Quantitative trait loci analyses were applied to data from Suffolk and Texel commercial sheep flocks in the United Kingdom. The populations comprised 489 Suffolk animals in three half-sib families and 903 Texel animals in nine half-sib families. Phenotypic data comprised measurements of live weight at 8 and 20 wk of age and ultrasonically measured fat and muscle depth at 20 wk. Lambs and their sires were genotyped across candidate regions on chromosomes 1, 2, 3, 4, 5, 6, 11, 18, and 20. Data were analyzed at the breed level, at the family level, and across extended families when families were genetically related. The breed-level analyses revealed a suggestive QTL on chromosome 1 in the Suffolk breed, between markers BM8246 and McM130, affecting muscle depth, although the effect was only significant in one of the three Suffolk families. A two-QTL analysis suggested that this effect may be due to two adjacent QTL acting in coupling. In total, 24 suggestive QTL were identified from individual family analyses. The most significant QTL affected fat depth and was segregating in a Texel family on chromosome 2, with an effect of 0.62 mm. The QTL was located around marker ILSTS030, 26 cM distal to myostatin. Two of the Suffolk and two of the Texel sires were related, and a three-generation analysis was applied across these two extended families. Seven suggestive QTL were identified in this analysis, including one that had not been detected in the individual family analysis. The most significant QTL, which affected muscle depth, was located on chromosome 18 near the callipyge and Carwell loci. Based on the phenotypic effect and location of the QTL, the data suggest that a locus similar to the Carwell locus may be segregating in the United Kingdom Texel population.

Adipose Tissue↗
PubMed2002

Study of crib-biting and gastric inflammation and ulceration in young horses.

Nineteen young horses that had recently started to perform the stereotypy of crib-biting were compared with 16 non-stereotypic horses for 14 weeks. After initial observations of their behaviour and an endoscopic examination of the condition of their stomachs, the horses were randomly allocated to a control or an antacid diet At the start of the trial, the stomachs of the crib-biting foals were significantly more ulcerated and inflamed than the stomachs of the normal foals. In addition, the faecal pH of the crib-biting foals (6.05) was significantly lower than that of the normal foals (6.58). The antacid diet resulted in a significant improvement in the condition of the horses' stomachs. The crib-biting behaviour declined in most of the foals, regardless of their diet, but tended to decline to a greater extent in the foals on the antacid diet.

Animal Husbandry↗
PubMed2001

Variations in the compressive strength of dental cements stored in ionic or acidic solutions.

The compressive strengths of various dental cements (a zinc polycarboxylate, a zinc phosphate, a glass-ionomer and two resin-modified glass ionomers, RMGICs) have been determined following storage in pure water, 0.9% sodium chloride solution or 20 mmol dm(-3) lactic acid solution for periods of time ranging from 24 h to 3 months. The glass-ionomer cement showed no differences between different storage solutions or at different storage times, whereas the zinc polycarboxylate, zinc phosphate and the resin-modified glass ionomer cements showed significant differences following storage in the solutions for 24 h compared with pure water. The zinc polycarboxylate cement was significantly weaker at 24 h in 0.9% NaCl and lactic acid than in pure water, whereas most of the other cements were significantly stronger in both 0.9% NaCl and lactic acid. One of the RMGICs (Vitremer luting, ex. 3M), however, was significantly stronger only in the NaCl solution, not in the lactic acid. In general, by 1 week, the strengths all reverted to being essentially the same as for specimens stored in pure water for most subsequent storage times, and did not change significantly on storage for up to 3 months. This effect of storage medium on the early strength has not been reported previously and since the media were chosen to model certain characteristics of natural saliva, the changes observed seem likely to occur in vivo. It is concluded that pure water is not the best medium for storing these cements if they are to behave as they do under clinical conditions.

Journal Article↗
PubMed2001

In vitro cytokine production and growth inhibition of lymphoblastoid cell lines by CD4+ T cells from Epstein-Barr virus (EBV) seropositive donors.

In vitro stimulation of peripheral blood lymphocytes (PBL) from healthy Epstein-Barr Virus (EBV) seropositive individuals with autologous lymphoblastoid cell lines (LCL) gives rise to CD4+ and CD8+ T cells both of which are cytotoxic for autologous lymphoblastoid cells. Activated EBV-specific CD4+ T cells are cytotoxic towards autologous LCL but, paradoxically, CD4+ T cells have also been shown to enhance tumour formation in SCID/Hu mice. Here, we show that despite being cytotoxic, CD4+ T-cell lines from different donors show considerable variation in their ability to inhibit the long-term growth of autologous LCLs in vitro. Following re-stimulation in vitro with PMA and ionomycin, CD4+ T cells produced IFNgamma, TNFalpha, TNFbeta, IL-2, IL-4, IL-10 and IL-13. TNFalpha, TNFbeta and IL-10 production were also detected in LCL. IL-6 was only detected in trace amounts in either cell type. The ratio of IFNgamma to IL-4 production varied between the CD4+ T-cell lines, indicating differences in the Th1/Th2 balance of the response. When CD4+ T cells were re-stimulated using autologous LCL as antigen-presenting cells, they produced more IL-4 and less IFNgamma or IL-13 when compared with cells re-stimulated by phorbol myristate acetate (PMA) and ionomycin. Using two colour cytokine staining, we showed that many individual CD4+ T cells produced IFNgamma along with either IL-4 or IL-13. Purified CD4+ T cells completely inhibited the outgrowth of autologous LCL in five out of nine cases, and partially inhibited outgrowth in the remaining four. There was no correlation between the pattern of CD4+ T-cell cytokine production and the capacity to inhibit outgrowth of autologous LCL. The killing of LCLs was contact-dependant and not mediated by soluble factors. We conclude that the ability of CD4+ T cells to inhibit autologous LCL growth is not directly related to T-helper cell cytokine production, but may depend on cytoxicity through surface ligands such as CD95L (FasL) and TNFalpha-related apoptosis-inducing ligand (TRAIL).

Antibodies, Viral↗
PubMed2001

Detection of IgG and IgE serum antibodies to Culicoides salivary gland antigens in horses with insect dermal hypersensitivity (sweet itch).

We postulated that all horses exposed to the bites of Culcoides (midges) would have an antibody response to the antigen secreted in Culcoides saliva, but that IgE antibody would be restricted to allergic individuals. Using immunohistology on sections of fixed Culicoides, we have demonstrated the presence of antibodies in horse serum which recognise Culicoides salivary glands. Antibodies were detected in the serum of horses with insect dermal hypersensitivity and in the serum of normal horses exposed to Culicoides bites. In contrast, no antibodies were detected in serum from native Icelandic ponies which had not been exposed to Culicoides. Anti-salivary gland IgG antibodies were detected in serum from both allergic and healthy horses exposed to Culicoides. IgE antibodies were only detected in horses with signs of insect dermal hypersensitivity, they were not found in serum of healthy controls nor in the serum of horses with a history of hypersensitivity but in remission at the time of sampling. Using western blotting we confirmed the presence of antibodies to Culicoides antigens and demonstrated that individual horses react to different numbers of antigens. This paper demonstrates the ability of serum from allergic horses to detect Culcoides antigens and will enable further studies to isolate and characterise the allergens.

Animals↗
PubMed2000

The effect of storage in aqueous solutions on glass-ionomer and zinc polycarboxylate dental cements.

Cylindrical specimens (dimensions 6 mm diameter x 12 mm height) of glass-ionomer and of zinc polycarboxylate dental cement have been stored in aqueous solutions for periods of 24 h, 1 week and 1 month. The solutions were of varying composition and affinity for water, and storage in them resulted in fluctuations in mass of the cements, an effect which was attributed to differences in the partitioning of water between the solutions and the cement specimens. Unlike the zinc polycarboxylate, the glass-ionomer gained mass in most of the solutions examined (except Na(2)SO(4)), showing it to have a much greater affinity for water than the zinc polycarboxylate. Despite the fluctuations in water uptake by the glass-ionomer, and loss of water by the zinc polycarboxylate, no statistically significant differences in compressive strength were recorded in any solution at any storage time. This contrasts with results reported previously for zinc polycarboxylates using smaller specimens, showing that specimen size has an influence on the interaction of cements with storage solutions.

Journal Article↗
PubMed1999

The major Epstein-Barr virus (EBV) envelope glycoprotein gp340 when incorporated into Iscoms primes cytotoxic T-cell responses directed against EBV lymphoblastoid cell lines.

A recombinant form of the EBV envelope glycoprotein and vaccine candidate gp340, lacking its hydrophobic transmembrane region, was incorporated into Iscoms after coupling to phosphatidyl ethanolamine via carbohydrate residues. Coupling by partial oxidation of gp340 carbohydrate with sodium periodate partly denatured the incorporated gp340 as indicated by its reduced reactivity with monoclonal antibodies that recognise the major neutralising epitope. Immunisation of cottontop tamarins with these Iscoms elicited antibody responses to gp340, but these antibodies only poorly recognised the major neutralising epitope in a competition ELISA and were unable to neutralise EBV in vitro. Despite the lack of neutralising antibody, immunisation with these Iscoms primed significant in vitro proliferative responses to soluble gp340 in lymphocytes from the draining lymph nodes and spleen. T-cell lines were raised from both immunised and control animals by in vitro stimulation of peripheral blood lymphocytes or spleen cells with autologous EBV-transformed lymphoblastoid cell lines. The T-cell lines from control animals had higher numbers of CD4+ T-cells than CD8+ T-cells and were not cytotoxic for autologous lymphoblastoid cell lines (LCL). In contrast the lines from immunised animals contained more CD8+ T-cells than CD4+ T-cells and had marked cytotoxicity for autologous LCL.

Animals↗
PubMed1998

Long-term follow-up results of balloon angioplasty of postoperative aortic recoarctation.

Immediate- and short-term follow-up results of balloon dilatation of aortic recoarctation following surgery have been well documented, but there is sparse data on long-term follow-up. During a 10-year period ending in August 1995, 33 children, aged 2 months to 14 years old, underwent balloon angioplasty of aortic recoarctation. Prior surgery included resection and end-to-end anastomosis (n = 9), subclavian flap (n = 16) or prosthetic (Dacron or Gore-Tex) patch (n = 5) angioplasty, and repair of an interrupted aortic arch (n = 3). Recoarctation developed 1 month to 14 years (mean +/- SD 29 +/- 44 months) after surgery. The indications for angioplasty were peak-to-peak systolic gradients > 20 mm Hg and systemic hypertension and/or congestive heart failure. After balloon angioplasty, the peak-to-peak systolic pressure gradient across the coarctation decreased from 48 +/- 22 to 13 +/- 15 mm Hg (p <0.01), and the size of the coarcted segment increased from 3.3 +/- 1.4 to 6.5 +/- 2.3 mm (p <0.01). Follow-up angiography and/or magnetic resonance imaging were performed in 20 children 17 +/- 12 months after angioplasty. No aneurysms were observed and improvement in the diameter of the coarcted aortic segment (9 +/- 3 mm) persisted. One- to 10-year (median 5) clinical follow-up was available in 32 children. During follow-up, 2 children required surgery to repair a long tubular isthmic narrowing. The residual gradients, determined by arm-leg systolic blood pressure difference, were 5 +/- 8 mm Hg. No patient was symptomatic and only 1 patient (3%) was hypertensive, controlled with antihypertensive medications. We conclude that balloon angioplasty of aortic recoarctation following all types of surgical repair is feasible, safe, and effective with good long-term results. We recommend balloon angioplasty as the procedure of choice in the management of postsurgical recoarctation with hypertension and/or congestive heart failure.

Adolescent↗
PubMed1998

Traumatic left ventricular aneurysm and tricuspid insufficiency in a child.

We describe a rare combination of left ventricular aneurysm and severe tricuspid valve insufficiency in a 9-year-old boy who sustained blunt chest trauma in a motor vehicle accident. The child underwent successful aneurysmorrhaphy and tricuspid valve replacement 9 months after the accident.

Accidents, Traffic↗
PubMed1998

Indirect measurement of Epstein-Barr virus neutralising antibodies by ELISA.

A rapid and effective ELISA for measuring Epstein-Barr virus (EBV)-neutralizing antibodies in human sera was devised to replace the existing cumbersome method involving the inhibition of fetal cord blood B-cell transformation by the virus. The new method will be invaluable for assessing antibody responses in human subjects participating in EBV gp340 vaccine trials. The ELISA developed uses the human serum antibody to be tested to inhibit standardised binding of an EBV-neutralizing monoclonal antibody (mAb) to gp340 itself or its recombinant derivatives. A serum which has high EBV-neutralizing antibody titres inhibits the binding of neutralizing mAb to gp340 more than a serum with low levels. EBV neutralisation antibody titres obtained by the new inhibition ELISA correlate well with values obtained using the lengthy conventional assay where inhibition of B-cell transformation is assessed. The new assay can be carried out in a few hours compared to 4-5 weeks for the conventional test and could be automated for processing very large sample numbers in vaccine trials.

Antibodies, Blocking↗
PubMed1998

CD4+ T cells inhibit growth of Epstein-Barr virus-transformed B cells through CD95-CD95 ligand-mediated apoptosis.

Greater than 90% of the human population acquire Epstein-Barr virus (EBV) in infancy and retain a lifelong latent infection without any clinical consequences. Nevertheless EBV has been identified as the causal agent of infectious mononucleosis, and is associated with several tumours including endemic Burkitt's lymphoma and B cell lymphomas in immunosupressed patients. B cells infected with EBV are transformed in vitro and grow continuously as lymphoblastoid cell lines. The growth of EBV-transformed B cells in vivo is controlled by the immune system. Studies on immunity to EBV have mainly focused on MHC class I-restricted CD8+ cytotoxic T cells specific for viral latent antigens. Here it is reported that in vitro stimulation of peripheral blood lymphocytes by autologous EBV-infected B cells, which have been induced to express lytic cycle antigens, gives rise to a predominantly CD4+ T cell response. Furthermore, the growth of EBV-infected B cells can also be regulated by these activated CD4+ T cells through apoptosis mediated by CD95-CD95 ligand (CD95L). CD95-CD95L-mediated apoptosis is an important mechanism of normal B cell growth regulation. As EBV-transformed B cells remain susceptible to this mechanism, the control of EBV in vivo may be not only by virus-specific CD8+ cytotoxic T cell immunity but also by normal mechanisms of immune regulation of B cell growth.

Acyclovir↗
PubMed1998

Results of three to 10 year follow up of balloon dilatation of the pulmonary valve.

BACKGROUND: The results of immediate and short term follow up of balloon dilatation of the pulmonary valve have been well documented, but there is limited information on long term follow up. OBJECTIVE: To evaluate the results of three to 10 year follow up of balloon dilatation of the pulmonary valve in children and adolescents. SETTING: Tertiary care centre/university hospital. DESIGN: Retrospective study. METHODS AND RESULTS: 85 patients (aged between 1 day and 20 years, mean (SD) 7.0 (6.4) years) underwent balloon dilatation of the pulmonary valve during an 11 year period ending August 1994. There was a resultant reduction in the peak to peak gradient from 87 (38) to 26 (22) mm Hg. Immediate surgical intervention was not required. Residual gradients of 29 (17) mm Hg were measured by catheterisation (n = 47) and echo Doppler (n = 82) at intermediate term follow up (two years). When individual results were scrutinised, nine of 82 patients had restenosis, defined as a peak gradient of 50 mm Hg or more. Seven of these patients underwent repeat balloon dilatation of the pulmonary valve: peak gradients were reduced from 89 (40) to 38 (20) mm Hg. Clinical evaluation and echo Doppler data of 80 patients showed that residual peak instantaneous Doppler gradients were 17 (15) mm Hg at long term follow up (three to 10 years, median seven), with evidence for late restenosis in one patient (1.3%). Surgical intervention was necessary to relieve fixed infundibular stenosis in three patients and supravalvar pulmonary stenosis in one. Repeat balloon dilatation was performed to relieve restenosis in two patients. Actuarial reintervention free rates at one, two, five, and 10 years were 94%, 89%, 88%, and 84%, respectively. Pulmonary valve regurgitation was noted in 70 of 80 patients at late follow up, but neither right ventricular dilatation nor paradoxical interventricular septal motion developed. CONCLUSIONS: The results of late follow up of balloon dilatation of the pulmonary valve are excellent. Repeat balloon dilatation was performed in 11% of patients and surgical intervention for subvalvlar or supravalvar stenosis in 5%. Most patients had mild residual pulmonary regurgitation but right ventricular volume overload was not required. Balloon dilatation is the treatment of choice in the management of moderate to severe stenosis of the pulmonary valve. Further follow up studies should be undertaken to evaluate the significance of residual pulmonary regurgitation.

Adolescent↗