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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Follow-up results of balloon aortic valvuloplasty in children with special reference to causes of late aortic insufficiency.

The purpose of this study was to report on 3- to 9-year follow-up data after balloon aortic valvuloplasty in children and to investigate causes of aortic insufficiency at late follow-up. Although the immediate and short-term results of balloon aortic valvuloplasty have been well documented, little information is available on long-term follow-up results. During a 7.3-year period ending December 1992, 26 young patients, aged 6 weeks to 20 years, underwent balloon aortic valvuloplasty with resultant reduction of peak-to-peak aortic valvar gradient from 71 +/- 20 (mean +/- SD) to 25 +/- 12 mm Hg (p < 0.001). None required immediate surgical intervention. At intermediate-term follow-up, 6 (23%) of 26 had restenosis develop and underwent surgical (4 patients) or repeat balloon valvuloplasty (2 patients). Clinical and echo-Doppler data 3 to 9 years (median 6 years) after balloon valvuloplasty revealed residual peak instantaneous Doppler gradients of 26 +/- 13 mm Hg (p < 0.001), without restenosis beyond what was observed at intermediate-term follow-up. Aortic insufficiency progressed in seven patients. However, none required intervention. Actuarial intervention-free rates at 1, 2, 5, and 9 years were 80%, 76%, 76%, and 76%, respectively. Logistic regression analysis suggested that the degree of Doppler-quantitated aortic insufficiency 1 day after valvuloplasty predicts persistent aortic insufficiency at late follow-up. These data indicate that immediately successful balloon aortic valvuloplasty in children yields a residual gradient of < or = 36 mm Hg at a median of 6 years of follow-up in most patients and an intervention-free rate at 9 years of 76%. Restenosis occurs but can be treated with a repeat intervention with good results. Aortic insufficiency remains stable and does not appear to require intervention, at least during the first decade after balloon dilatation.

Adolescent↗

In a very different voice: unmasking moral hypocrisy.

Across 3 small studies, 80 female undergraduates were confronted with the dilemma of deciding whom-themselves or another research participant-to assign to a positive consequences task, leaving the other to do a dull, boring task. In Study 1, where morality was not mentioned, 16 of 20 assigned themselves to the positive consequences task, even though in retrospect only 1 said this was moral. In Studies 2 and 3, a moral strategy was suggested: either flipping a coin or accepting task assignment by the experimenter. In Study 2, 10 of 20 participants flipped a coin, but of these, 9 assigned themselves the positive consequences task. In Study 3, participants were significantly more likely to accept the experimenter's assignment when it gave them the positive consequences task. Overall, results suggested motivation to appear moral yet still benefit oneself. Such motivation is called moral hypocrisy.

Adolescent↗

Five- to nine-year follow-up results of balloon angioplasty of native aortic coarctation in infants and children.

OBJECTIVES: To evaluate the usefulness of balloon angioplasty for relief of native aortic coarctation, we reviewed our experience with this procedure, with special emphasis on follow-up results. BACKGROUND: Controversy exists with regard to the role of balloon angioplasty in the treatment of native aortic coarctation. METHODS: During an 8.7-year period ending September 1993, 67 neonates, infants and children underwent balloon angioplasty for native aortic coarctation. A retrospective review of this experience with emphasis on long-term follow-up forms the basis of this study. RESULTS: Balloon angioplasty produced a reduction in the peak-to-peak coarctation gradient from 46 +/- 17 (mean +/- SD) to 11 +/- 9 mm Hg (p < 0.001). No patient required immediate surgical intervention. At intermediate-term follow-up (14 +/- 11 months), catheterization (58 patients) and blood pressure (2 patients) data revealed a residual gradient of 16 +/- 15 mm Hg (p > 0.1). When individual results were scrutinized, 15 (25%) of 60 had recoarctation, defined as peak gradient > 20 mm Hg. Recoarctation was higher (p < 0.01) in neonates (5 [83%] of 6) and infants (7 [39%] of 18) than in children (3 [8%] of 36), respectively. Two infants in our early experience had surgical resection with excellent results. Three patients had no discrete narrowing but had normal arm blood pressure and had no intervention. The remaining 10 patients had repeat balloon angioplasty with reduction in peak gradient from 52 +/- 13 to 9 +/= 8 mm Hg (p < 0.001). Reexamination 31 +/- 18 months after repeat angioplasty revealed a residual gradient of 3 to 19 mm Hg (mean 11 +/- 6). Three (5%) of 58 patients who underwent follow-up angiography developed an aneurysm. Detailed evaluation of the femoral artery performed in 51 (88%) of 58 patients at follow-up catheterization revealed patency of the femoral artery in 44 (86%) of 51 patients. Femoral artery occlusion, complete in three (6%) and partial in four (8%), was observed, but all had excellent collateral flow. Blood pressure, echocardiography-Doppler ultrasound and repeat angiographic or magnetic resonance imaging data 5 to 9 years after angioplasty revealed no new aneurysms and minimal (2%) late recoarctation. CONCLUSIONS: On the basis of these data, it is concluded that balloon angioplasty is safe and effective in the treatment of native aortic coarctation; significant incidence of recoarctation is seen in neonates and infants; repeat balloon angioplasty for recoarctation is feasible and effective; and the time has come to consider balloon angioplasty as a therapeutic procedure of choice for the treatment of native aortic coarctation.

Adolescent↗

Feasibility and effectiveness of repeated balloon dilatation of restenosed congenital obstructions after previous balloon valvuloplasty/angioplasty.

Balloon dilatation of congenital stenotic lesions of the heart and great vessels has been used for more than a decade. Varying incidence of residual obstruction or recurrence, hereafter referred to as restenosis, has been observed at follow-up. The purpose of this study was to evaluate the feasibility and effectiveness of repeated balloon dilatation of restenosed lesions after previous balloon dilatation for pulmonic (PS) and aortic (AS) stenosis and native aortic coarctation (AC). Neonates, infants, and children (n = 178) underwent balloon valvoplasty/angioplasty with reduction (p < 0.001) or peak-to-peak systolic pressure gradients from 91 +/- 41 (mean +/- SD) mm Hg to 25 +/- 19 mm Hg, from 70 +/- 20 mm Hg to 26 +/- 12 mm Hg, and from 48 +/- 17 mm Hg, to 11 +/- 9 mm Hg in patients with PS, AS, and AC, respectively. Repeated catheterization or echo-Doppler studies or both were performed from 3 months to 5 years after initial balloon dilatation. Residual gradients at follow-up were 26 +/- 26 mm Hg, 34 +/- 20 mm Hg, and 16 +/- 15 mm Hg, respectively, for PS, AS, and AC and remained significantly lower (p < 0.01) compared with gradients before the balloon dilatation. However, when results of individual patients were scrutinized, 9 (11%) of 80 patients with PS, 6 (23%) of 26 patients with AS, and 16 (27%) of 60 patients with AC had restenosis, on the basis of standard criteria. Repeated balloon dilatation was performed with reduction (p < 0.05 to < 0.001) of peak-to-peak gradients from 89 +/- 40 mm Hg to 38 +/- 20 mm Hg in 9 patients with PS, from 77 mm Hg to 13 mm Hg and 66 mm Hg to 6 mm Hg, respectively, in 2 patients with AS, and from 38 +/- 11 mm Hg to 10 +/- 6 mm Hg in 12 patients with AC. Echo-Doppler studies, 2 to 6.5 years after repeated balloon dilatation, indicated excellent results, with residual peak instantaneous Doppler gradients of 24 +/- 13 mm Hg in PS, 43 +/- 20 mm Hg in AS, and 11 +/- 6 mm Hg in AC groups, respectively. This improvement is irrespective of the cause of restenosis after initial balloon valvuloplasty/angioplasty. From this experience, we conclude that repeated balloon dilatation is feasible and effective in relieving restenosis after initial balloon valvuloplasty/angioplasty.

Adolescent↗

Acidobasicity of oxide glasses used in glass ionomer cements.

OBJECTIVES: The purpose of this study was to provide a theoretical basis for assessing the cement-forming ability of oxide ionomer glasses based on concepts of glass acidobasicity. METHODS: Theoretical concepts of acidobasicity of ionomer glasses were developed based respectively on ionization potential, field strength and electronegativity. Calculations of acidobasicities were made for a range of glasses of the CaO-Al2O3-SiO2 type. These results were compared with experimental values obtained for the setting times of cements prepared from these glasses. RESULTS: Regression analysis showed a 99.96% correlation between acidobasicity values based on ionization potential with those based on field strength. There was only moderate correlation between these acidobasicity values and those based on electronegativity. Setting time was found to increase slowly as glass basicity decreased until a critical point was reached when setting time increased sharply. A Spearman rank correlation test was applied, and it was found that setting times correlated with acidobasicity values based on ionization potential and field strength with a coefficient of 98.7%. SIGNIFICANCE: Results show that calculated acidobasicity values of CaO-Al2O3-SiO2 glasses can be used to distinguish between glasses that form cements from those that do not. They are divided by a critical acidobasicity value. It was not found possible to relate setting time to acidobasicity by means of an equation because of this critical feature in the relationship. The critical acidobasicity value replaces the more complex criteria of Hill and Wilson (1988) using triangular diagrams.

Aluminum Oxide↗

Virus-specific cytotoxic T cell responses are associated with immunity of the cottontop tamarin to Epstein-Barr virus (EBV).

The cytotoxic responses of peripheral blood lymphocytes from cottontop tamarins to in vitro restimulation with autologous lymphoblastoid cell lines (LCL) were assayed. Lymphocytes from immune tamarins that had recovered from EBV challenge developed potent cytotoxicity for natural killer (NK) cell targets and for autologous LCL. The cytotoxicity for LCL targets was EBV-specific, as B cell blasts uninfected with EBV were not killed. The cell lines could be maintained by repeated stimulation with LCL and the addition of IL-2. Flow cytometry showed that they were T cell lines expressing CD2, CD3, CD4, CD8 and CD25. Dual-colour flow cytometry revealed two subpopulations, one CD4+ CD8+ population and the other CD4- CD8+. After separation by magnetic cell sorting both subpopulations were shown to be cytotoxic and the CD4+ CD8+ fraction was also shown to be MHC class II-restricted; the MHC restriction of the CD8+ subpopulation could not be determined. The unseparated T cells and both the subpopulations were able to inhibit LCL outgrowth in vitro. In contrast, PBL from naive tamarins stimulated by autologous LCL developed less NK cell cytotoxicity and little cytotoxicity for LCL. The cytotoxic response was enhanced at higher levels of LCL stimulation, but the cells were unable to inhibit LCL outgrowth in vitro. We conclude that cytotoxic responses capable of inhibiting LCL growth in vitro correlate with in vivo immunity in the tamarin model and provide a basis for understanding the mechanism of vaccine-induced immune protection.

Animals↗

Expression of major histocompatibility complex class II antigens on normal porcine intestinal endothelium.

A novel monoclonal antibody (MIL 11) specific for an antigen expressed on porcine endothelial cells is described. The antigen recognized by MIL 11 is most strongly expressed in the intestine but is also expressed on the capillary endothelium of a wide range of tissues. Using two- and three-colour immunofluorescence microscopy we demonstrated the extensive coexpression of MIL 11 and major histocompatibility complex (MHC) class II antigens on normal porcine capillary endothelium in the intestine, trachea, thymus and small veins, while endothelium of large vessels and the heart were negative for MHC class II. In contrast to humans and rodents, available reagents do not detect MHC class II on the intestinal epithelium of pigs. However, porcine intestinal endothelium expressed both DR and DQ antigens. A population of strongly class II-positive cells was also detected immediately adjacent to the endothelium in the lamina propria. Three-colour immunofluorescence microscopy highlighted the close association between endothelium and intestinal CD4+ T cells. Lamina propria T cells were mainly MHC class II positive, whereas those in the epithelial compartment were MHC class II negative.

Animals↗