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Biomedical subjects

A D Wilson

Publications and source records attributed to A D Wilson.

At least 55 records · Page 3Linked to original sources

The separation and identification by monoclonal antibodies of dog IgG fractions.

Four fractions of IgG from normal dog serum have been successfully isolated by gel filtration followed by protein A and protein G affinity chromatography using the fast protein liquid chromatography (FPLC) system. Protein A chromatography produced three peaks: peak 1 was fallthrough material consisting of components which did not bind to protein A, peak 2 consisted of bound material eluting at pH 6, and peak 3 contained bound material eluting at pH 3.5. The three peaks were then subjected individually to protein G affinity chromatography. Peak 1 from protein A chromatography produced a fallthrough peak followed by a weakly binding component which eluted at pH 8, and was called peak w. Peak 2 from protein A chromatography bound to protein G and eluted as a single peak at pH 3.8, and was called peak x. Peak 3 from protein A chromatography emerged as two separate peaks (y and z) off the protein G column; peak y bound and eluted at pH 4.1, and peak z bound weakly to protein G and emerged as a broad band at pH 8. Peaks w, x, y and z have been named gamma w, gamma x, gamma y and gamma z, respectively, and there purified IgG fractions were used to immunize mice for the preparation of monoclonal antibodies (McAbs). To date, two sets of McAbs have been produced: one which recognizes an epitope present in both gamma w and gamma z fractions and another set of McAbs which recognizes an epitope in the gamma x and gamma y fractions.

Animals↗

Preliminary study of factors affecting the fluoride release from glass-ionomer cements.

A study has been made on the release of fluoride from three glass-ionomer cements. The effect of the maturity of cements at the time of immersion and powder/liquid ratio were examined. It was found that fluoride release from immature cements was dependent on cement and powder/liquid ratio and that the effect was permanent. The effect of cement type and powder/liquid ratio lessened as cements were allowed to mature prior to immersion. It appears that fluoride release was dependent on the strength and maturity of the cement matrix and not fluoride content. It was concluded that the rate of fluoride release would depend largely on clinical factors rather than cement type.

Chemistry, Pharmaceutical↗

Expression of major histocompatibility complex (MHC) class II antigens in the murine mammary gland.

Major histocompatibility complex (MHC) class II antigens were identified on cells within mammary gland connective tissue of lactating mice using a paraformaldehyde-lysine-periodate-gluteraldehyde fixative and an immunoperoxidase staining method. The distribution of class II expressing cells within interalveolar and interlobular connective tissue was similar both throughout lactation and in successive lactations. Epithelial cells within secretory alveoli and mammary ducts did not express class II antigens.

Animals↗

Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigen.

The ability of cholera toxin B-subunit to bind to intestinal epithelium and in particular the dome epithelium of the Peyer's patch can account for its potency as an immunogen. However, pure B-subunit is a less effective immunogen than whole cholera toxin. The immunogenicity of B-subunit may be restored by the addition of either traces of whole toxin or by pertussis toxin. Cholera toxin and pertussis toxin were both able to stimulate a response when fed in conjunction with keyhole limpet haemocyanin, whereas recombinant B- subunit of heat-labile toxin from Escherichia coli had no effect, demonstrating that the adjuvant action is a property of the enzymically active A-subunits. The adjuvant activity of both pertussis toxin and cholera toxin may be due to their ability to cause an increase in the activity of adenylate cyclase via their action on GTP-binding regulatory proteins. However, feeding of forskolin, a direct activator of adenylate cyclase, had no effect on the mucosal immune response, indicating a role for cholera and pertussis toxin which is independent of enhancement of adenylate cyclase activity in the regulation of the immune response. Antibody to pertussis toxin was not detected, which was attributed to inadequate absorption of pertussis toxin.

Adenylate Cyclase Toxin↗

Transcatheter occlusion of patent ductus arteriosus with adjustable buttoned device. Initial clinical experience.

BACKGROUND: Several devices are available for transcatheter occlusion of patent ductus arteriosus. Most of these devices either require complicated intracardiac maneuvering, have not been tried in humans, or need a large-sized sheath for implantation of the device. METHODS AND RESULTS: During a 26-month period ending November 1992, 14 patients underwent transcatheter closure of patent ductus arteriosus with an adjustable buttoned device delivered via a 7F sheath under an institutional review board-approved custom-made device protocol. The children were 15 months to 8 years of age with weight range of 7.2 to 19 kg. The patent ductus arteriosus measured from 2 to 7.5 mm (median, 3 mm) at the narrowest diameter and was conical, short, or tubular. They were occluded with devices measuring 15 to 20 mm. The ratio of pulmonary to systemic flow decreased (P < .01) from 1.9 +/- 0.6 (mean +/- SD; range, 1.3 to 3.2) to 1.05 +/- 0.1 (1 to 1.3). Continuous murmur of patent ductus arteriosus disappeared in all except 1 patient. Small residual shunts were detected by color Doppler studies in 4 of 14 patients (29%). All patients were followed for 1 to 24 months (mean, 6 +/- 7 months). The device was intact in all patients, and no breakage of the wires was noted. No shunts were seen in 12 of 14 patients (86%), and minute residual shunts were seen in 2 children. No major complications were encountered. CONCLUSIONS: It is concluded that transcatheter closure of patent ductus arteriosus with the adjustable buttoned device is feasible and effective and can be accomplished via small 7F sheaths; a 7F sheath is adequate for all ductal sizes; and the adjustable length of the loop accommodated all types of patent ductus arteriosus. Clinical trials on a larger number of patients are warranted.

Cardiac Catheterization↗

Dimensional changes occurring in a glass-ionomer cement.

The dimensional changes occurring when glass ionomer cements are exposed both to desiccating and moist conditions were investigated. All work was done at 23 degrees C. The effect of time allowed for cements to mature before exposure to the test conditions was studied as was the effect of adding cellulose ethers. The contraction of glass ionomer cements under desiccating conditions was far greater than the expansion by water absorption. Increase of the time allowed for the cements to mature reduced the extent of this effect markedly. The addition of cellulose ethers to cement mixes was only moderately effective in reducing dimensional change.

Analysis of Variance↗

Management of ophthalmic disease in general practice.

A study was undertaken to investigate the management of ophthalmic conditions in general practice in order to identify areas requiring education and training input. Management of patients with eye disease presenting to 17 Nottingham general practitioners was examined over a 12-month period. Of all patients registered with the participating doctors, 4% presented with eye problems, accounting for 1.5% of all general practice consultations. Children under five years of age had the highest consultation rates, female patients having higher consultation rates than male patients in all age groups. Infective conjunctivitis was responsible for 41% of consultations about eye problems and allergic conjunctivitis for a further 13%; 70% of consultations resulted in a prescription. Corticosteroids were prescribed in 3% of consultations for eye problems; this was considered inappropriate by the study ophthalmologist in over a third of these cases. Patients were referred for further management following 16% of consultations. Thirty nine per cent of referrals to the hospital ophthalmic service were either to an eye casualty department or requested an urgent clinic appointment. While most eye problems are managed solely by general practitioners there is clearly a need for ophthalmic services that can rapidly provide a specialist opinion. However, most eye disease seen in general practice involves the external eye or anterior segment, and the diagnosis may be confidently made using basic ophthalmic history taking and examination skills with non-specialist equipment. The acquisition of these skills should be emphasized at undergraduate level and built upon in later years in postgraduate training.

Adolescent↗

PROBIT: weighted probit regression analysis for estimation of biological activity.

PROBIT estimates biologic activity by weighted probit regression analysis and comparison with a known standard. The program is intended to speed up calculation of the concentration of cytokines in large numbers of cell supernatants. Data are input from either sequential or free-form text files created with a spreadsheet or text editor. This allows transfer of data from a beta-counter equipped with a suitable terminal without retyping. Results are displayed and/or printed as relative potency (% of standard) and 50% effective dose (ED50).

Cytokines↗

Transcatheter closure of atrial septal defect by "buttoned" devices.

During a 21-month period ending in August 1991, 12 patients underwent transcatheter closure of atrial septal defect (ASD) with a "buttoned" device through an 8Fr sheath, using an institutional review board-approved, custom-made device protocol initially, and Food and Drug Administration-approved clinical trials subsequently. Ten children had left-to-right shunts across the ASD and 2 adults had their patent foramen ovale closed to prevent recurrent paradoxical embolism (including cerebrovascular accidents). The device dislodged in 1 of the 4 patients in whom a first-generation device was used, and retrieval of the device, and surgical closure of the ASD were performed without incident. In the remaining 11 patients (age range 7 months to 45 years, weight 3.6 to 64 kg), the device remained intact, and pulmonary-to-systemic flow ratio decreased from 2.1 +/- 0.3 to 1.04 +/- 0.06. Follow-up chest x-ray and echo-Doppler studies were available in all patients 0.5 to 18 months after the procedure. The device was intact in all patients. Small residual shunt detected by color Doppler was seen in 2 children. Right ventricular size decreased (23 +/- 6 to 17 +/- 3 mm; p less than 0.01), and paradoxical septal motion disappeared in all patients. There was no recurrence of paradoxical embolism in the 2 adults. No complications occurred during follow-up. It is concluded that transcatheter closure of ASD with the buttoned device is feasible, effective and safe, and can be accomplished with small, 8Fr sheaths (even in infants weighing 3.6 kg), follow-up results are excellent, and clinical trials on a larger number of patients are needed.

Adolescent↗

Balloon pulmonary valvuloplasty in the management of cyanotic congenital heart defects.

Twenty-three children with cyanotic congenital heart defects, aged 3 days to 11.5 years, weighing 2.9 to 30 kg, underwent percutaneous balloon pulmonary valvuloplasty to improve pulmonary oligemia. The patients were divided into two groups: group I with intact ventricular septum and group II with ventricular septal defect. In 12 group I patients, there was an increase of systemic arterial oxygen saturation [83 +/- 8% (mean +/- SD) vs. 94 +/- 5%, P less than 0.001] and pulmonary-to-systemic flow ratio (0.7 +/- 0.1 vs. 1.0 +/- 0.2, P less than 0.001). Peak systolic pressure gradient across the pulmonary valve decreased (P less than 0.001) from 105 +/- 48 to 25 +/- 18 mm Hg. In 11 group II patients, arterial oxygen saturation (67 +/- 13 vs. 83 +/- 13%, P less than 0.01) and pulmonary-to-systemic flow ratio (0.7 +/- 0.4 vs. 1.2 +/- 0.5, P less than 0.02) increased following valvuloplasty. Peak systolic pressure gradient across the pulmonic valve (52 +/- 16 vs. 32 +/- 22 mm Hg, P less than 0.05) decreased while infundibular and total pulmonary outflow tract gradients were unchanged (P greater than 0.1). Immediate surgical intervention was avoided in all cases in both groups. On follow-up, 1 to 36 months after valvuloplasty, arterial oxygen saturation, pulmonary-to-systemic flow ratio, and pulmonary valve gradients remain improved in both groups. However, in group I, repeat balloon valvuloplasty was required in two children. In group II, six children with tetralogy of Fallot (TOF) underwent successful total surgical correction 4 months to 2 years after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗

Role of "buttoned" double-disc device in the management of atrial septal defects.

Sixteen patients seen over a 9-month period ending in August 1990 were offered transcatheter closure of their ASD with a custom-made "buttoned" double-disc device. The study was approved by the Institutional Review Board and informed consent was obtained in each case. The device consists of an occluder, a counteroccluder, and a loading wire and is delivered to the ASD site via an 8F sheath. Parents of two children elected surgical closure. In five children the stretched diameter of the ASD was too large (greater than 20 mm) and transcatheter closure was not attempted. These seven children underwent elective surgical closure without incident. In one child the defect measured 5 mm and the Qp:Qs was 1.4:1 and therefore ASD closure was not recommended. In the remaining eight children transcatheter closure was attempted. In two of the children the occluder pulled through the ASD and was successfully retrieved and the children later underwent uneventful elective surgical closure. The device was implanted across the ASD in six children. In one child the device dislodged from the ASD site within minutes after implantation and the child was sent to emergency surgery, where the device was removed and the ASD was closed. In the remaining five patients, aged 7 months to 45 years (weight 3.6 to 50 kg), with a Qp:Qs range of 1.3 to 2.3 and a stretched diameter of 10 to 19 mm, the ASD closure was successful with 25 to 40 mm size devices. Repeat echo-Doppler studies 2 weeks and 3 months after the procedure in all patients and 6 months later in two children did not reveal any residual shunt. It is concluded that (1) the custom-made "buttoned" double-disc device can be implanted across the ASD safely and effectively via an 8F sheath, thus making transcatheter ASD closure feasible even in very young infants; (2) measurement of stretched diameter of the ASD in the catheterization laboratory is a useful guide for selection of an appropriate-sized device; and (3) additional clinical trials are warranted to confirm the efficacy and safety of the device.

Adolescent↗

The formation and properties of metal oxide poly(vinylphosphonic acid) cements.

Aqueous solutions of poly(vinylphosphonic acid) have been found to form polyelectrolyte cements with a wide range of metal oxides. Poly(vinylphosphonic acid), PVPA, has a structure similar to that of poly(acrylic acid), PAA, but contains pendant phosphonic acid,--P(O)(OH)2, groups in place of the carboxylic acid,--COOH, groups of the zinc polycarboxylate, and glass polyalkenoate cements. It is a stronger acid than PAA, with a greatly increased reactivity toward metal oxides. The physical and mechanical properties of a number of metal oxide PVPA cements were studied and compared with those of zinc polycarboxylate cements. The faster acting of the metal oxide PVPA cement seems to produce a cement that is less susceptible to early hydrolysis.

Dental Cements↗

Depressed potential for interleukin-2 production following early weaning of piglets.

Spleen cells, but not mesenteric lymph node cells, from 3-week-old piglets abruptly weaned onto a soya-based diet, produced less interleukin-2 (IL-2) following non-specific activation with concanavalin A (Con A) than did cells from age- and litter-matched, unweaned controls. In contrast, the ability to express receptors for IL-2 was only marginally reduced. The effect on IL-2 production was most marked in animals weaned for as little as 24-48 h. Variation within groups increased with time after weaning, indicating differences between individuals in the longer-term effects of weaning. This finding may be due to endogenous production of steroids resulting in generalised impaired immune function or to retention of cells within intestinal sites owing to an active local immune response.

Animals↗

Primary antigen-specific T-cell proliferative responses following presentation of soluble protein antigen by cells from the murine small intestine.

To understand the local immune events which occur when a novel antigen is encountered in the gut it is necessary to know whether cells from the mucosal tissues are capable of initiating T-cell reactivity. We have examined the capacity of cells isolated from the Peyer's patches and the lamina propria of the murine small intestine to present keyhole limpet haemocyanin (KLH) to naive syngeneic splenic T cells in vitro. The properties of the gut antigen-presenting cells (APC) were compared with those of cells from the spleen and the mesenteric lymph nodes. Results clearly demonstrate that cells from the lamina propria as well as from the Peyer's patches, mesenteric lymph node and spleen can present KLH to naive T cells, inducing strong proliferative reactions comparable in magnitude and kinetics. All the APC populations tested induced interleukin-2 (IL-2) production in primary cultures, although minor differences were noted when lamina propria cells were used as APC. IL-4 was not detected in supernatants from cultures of non-immune T cells in the presence of APC from any tissue. Phenotypic analysis of the cells in cultures of naive T cells, with antigen and APC from different gut-associated tissues revealed important differences. Cells from Peyer's patch, mesenteric lymph node and spleen gave rise to cultures containing largely CD4+CD8- cells. However, cultures in which lamina propria cells acted as APC consisted primarily of CD4-CD8+ cells.

Animals↗