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Biomedical subjects

C J Taylor

Publications and source records attributed to C J Taylor.

At least 127 records · Page 7Linked to original sources

Association of autoimmunity and cicatricial pemphigoid: is there an immunogenetic basis?

A group of 34 patients with cicatricial pemphigoid was investigated for the presence of autoimmune disorders. Thirty-two percent of patients had autoimmune disease compared with 7% in the control population, a highly significant difference (p less than 0.002). Circulating autoantibodies were also significantly more common in patients (p less than 0.05). Twenty-four patients with cicatricial pemphigoid were typed for HLA. A statistically significant increase in the frequency of DR4 and DQw3 antigens was observed in these patients. These findings suggest a possible genetic basis for the autoimmune association and predisposition for development of cicatricial pemphigoid.

Adolescent↗

Sequence analysis of HLA-Bw53, a common West African allele, suggests an origin by gene conversion of HLA-B35.

In the West African population of the Gambia the class I antigen HLA-Bw53 is found at high frequency. We used the polymerase chain reaction to amplify cDNA from an individual homozygous for this allele and determined the nucleotide sequence of the polymorphic alpha 1 and alpha 2 domains. The HLA-Bw53 sequence is identical to HLA-B35 except for a short sequence at the 3' end of exon 2 (encoding the alpha 1 domain) which specifies a Bw4 rather than a Bw6 motif. This suggests an origin for HLA-Bw53 involving a gene conversion of HLA-B35 by an allele containing this Bw4 sequence. The alpha 2 domain shared by HLA-Bw53, -B35, and -Bw58 is particularly common in sub-Saharan Africans.

Adult↗

Production and characterization of human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient.

We have produced human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient by the generation of a mouse/human heterohybridoma. The antibodies are of the IgM class and react with the patient's autologous cells, the B-lymphoblastoid cell line producing the antibody, normal T and B lymphocytes, B cells from chronic lymphatic leukemia patients (CLL cells), and the autoantibody-sensitive cell line K562. Screening of the monoclonal antibodies (mAb) against panels of normal T and B cells and CLL cells demonstrated that different reactivity profiles could be generated at different dilutions of the mAb. These profiles were identical to those seen with autoantibodies from different renal patients and this suggests that these profiles do not imply different antibody specificities but differing target cell sensitivity. Reactivity profiles seen in the fluorescence binding assays suggest that the target cell sensitivity is dictated not by antigen density alone but also by antibody/antigen affinity. The results from studies of enzyme treatment of target cells and lectin inhibition of the molecular specificity suggest that the autoantibodies are polyreactive, capable of binding sialic acid-dependent epitopes and other negatively-charged cell surface molecules.

Animals↗

Measurement of intracellular mediators in enterocytes isolated from jejunal biopsy specimens of control and cystic fibrosis patients.

A method that maximises the yield of viable enterocytes has been developed for the isolation of enterocytes from human jejunal biopsy specimens. These enterocytes have been used to study the values of intracellular free calcium and the rises in adenosine 3'5'-cyclic monophosphate (cAMP) induced by secretagogues in normal and cystic fibrosis cells. Basal intracellular free calcium of cystic fibrosis enterocytes, measured fluorimetrically with fura-2, was within the range of the basal intracellular free calcium of non-cystic fibrosis enterocytes (cystic fibrosis 263 nmol/l; non-cystic fibrosis 287 nmol/l). Changes in intracellular free calcium were observed after exposure to ionomycin: a 100 nmol/l solution induced a 2.5 fold increase in intracellular free calcium in the cystic fibrosis enterocytes and a 2.2 fold increase in the intracellular free calcium concentration of the non-cystic fibrosis enterocytes. Basal cAMP values were not significantly different between cystic fibrosis and non-cystic fibrosis enterocytes (cystic fibrosis 575 fmol/100,000 cells; non-cystic fibrosis 716 fmol/100,000 cells, p greater than 0.05) and the enterocyte cAMP value increased in response to stimulation with prostaglandin E2 (7 mumol/l) (cystic fibrosis 2.2 fold increase over basal, p less than 0.05; non-cystic fibrosis 1.9 fold stimulation over basal, p less than 0.05) and vasoactive intestinal polypeptide (100 nmol/l) (cystic fibrosis 7.1 fold increase over basal, p less than 0.05; non-cystic fibrosis 5.8 fold increase over basal, p less than 0.05). There was no significant difference in the magnitude of the response between cystic fibrosis and non-cystic fibrosis enterocytes (p greater than 0.05). These results indicate that the cystic fibrosis defect in the small intestine, as in other affected epithelia, seems to be distal to the production of second messengers. The small intestine is therefore an appropriate model in which to study the biochemical defect in cystic fibrosis.

Animals↗

Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis.

The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium absorption in viable tissues, caused similar reductions in the short circuit current of both control and cystic fibrosis tissues (control = -37.7 (7.7) microA/cm2; cystic fibrosis = -44.0 (9.3) microA/cm2). Thus, the failure of chloride secretion observed in the small intestine also exists in the rectal mucosa. This observation could be used both to aid diagnosis and to study the basic defect.

Acetylcholine↗

Open access exercise electrocardiography: a service to improve management of ischaemic heart disease by general practitioners.

An initial study of the use of open access exercise electrocardiography by general practitioners (GPs) in South East Kent showed that patient selection and interpretation of test results was frequently incorrect. After issuing guidelines, modifying the request form and instituting registrar review of all requests, significant improvements in both referral pattern, result interpretation and patient management have resulted. Forty-nine GPs requested 110 exercise tests during 1988/89. Twelve per cent were not undertaken after discussion with the referring practitioner. Eighty-four per cent of those tested would have been referred to the district general hospital cardiology outpatient department in the absence of open access exercise electrocardiography service. Six per cent of patients were referred directly for invasive investigation. Thirty-five per cent were referred to the district general hospital cardiology outpatient department, whilst 42% were spared hospital referral based on the result of the investigation. Better use of the modified service was suggested by: referral of fewer patients with non-cardiac chest pains (P = 0.002); more patients with a moderate pre-test probability of ischaemic heart disease (P less than 0.05); fewer inappropriate requests (P less than 0.01); and fewer inappropriately undertaken tests (P less than 0.001) than in the previous study. All patients with strongly positive test results were appropriately managed. Open access exercise electrocardiography in the format investigated is potentially a cost-effective and useful tool to improve diagnosis and management of heart disease by GPs.

Adolescent↗

Measurement of hip prostheses using image analysis. The maxima hip technique.

A computer-based image analysis system has been developed as a research tool in total hip replacement. The system has been programmed to take multiple measurements from coronal plane radiographs. Poor quality radiographic images can be enhanced and standardised. The measurements which can be obtained include stem subsidence, cup migration, cup wear, and stem loosening. Reproducibility and accuracy were +/- 0.01 mm and +/- 0.5 mm respectively. The present application is in retrospective research, but prospective monitoring of radiographs is planned.

Hip Joint↗

An obsessive-compulsive view of obesity and its treatment.

It was hypothesized that some obese individuals who are obsessed with food and who eat compulsively may not respond to the stimulus control techniques widely used in treating obesity. Sixty-eight participants were administered a measure of obsessive tendencies and randomly assigned to three treatment modalities: (a) Exposure and response prevention; (b) Stimulus control; (c) Control. Results indicated that participants who scored high on the Eating Obsessive Compulsive questionnaire (EOC) maintained weight loss significantly better with exposure and response prevention (ERP) training than did either the stimulus control or the control group. It was concluded that for the obsessive-compulsive eater, ERP training is the treatment of choice.

Adult↗

Preparation and properties of brush-border membrane vesicles from human small intestine.

This study describes a simple and rapid method for the preparation of brush-border membrane vesicles from intestinal biopsies. The specific activities of sucrase, amino peptidase N, and alkaline phosphatase in these vesicles were the same as those in vesicles prepared from intestinal segments. The vesicles from all the regions of the small intestine can transport D-glucose in an Na+-dependent manner. The rates of transport of D-glucose presented here are far higher than previously reported. The method should have a wide applicability to studies of transport mechanisms and the distribution of transport processes within the intestine.

Adult↗

Bacterial reservoirs in cystic fibrosis.

To establish whether colonisation of the upper respiratory tract or bacterial contamination of inhaler devices or solutions predisposes to colonisation of the lower respiratory tract in patients with cystic fibrosis, bacterial isolates from groups of children who were positive (n = 13) or negative (n = 18) for Pseudomonas aeruginosa were studied. Cultures of swabs from inhaler devices, toothbrushes, and upper airways were compared with cough swabs or sputum cultures. No pathogens were obtained from inhaler equipment administering unit dose medications. Upper airway carriage of Staphylococcus aureus and Haemophilus influenzae was identified in both groups but correlated poorly with sputum isolates. P. aeruginosa was found only in the upper respiratory tract of children with established colonisation of the lower airways. No P aeruginosa isolates were obtained from the upper airways of the group with negative sputum, including one patient who became colonised by P aeruginosa during the study. Our results did not support the suggestion that colonisation of the upper respiratory tract by P aeruginosa predisposes to colonisation of the lower airways. Failure to isolate pathogenic organisms consistently from the upper airways in patients with positive sputum argues against a local epithelial factor predisposing to bacterial colonisation.

Adolescent↗

Isolated fructose malabsorption.

A patient with isolated fructose malabsorption presented with diarrhoea and colic during the first year of life and subsequently responded to a fructose free diet. Fructose malabsorption has been implicated in some cases of irritable bowel syndrome in adults and may also be an infrequently recognised cause of gastrointestinal symptoms in children.

Breath Tests↗

Enhanced intestinal glucose and alanine transport in cystic fibrosis.

The rise in short-circuit current associated with the active transport of glucose and alanine was measured in intestinal biopsy samples from children with cystic fibrosis. The glucose-induced increase in the short-circuit current was greater in the cystic fibrosis tissues than in control samples over the whole range of concentrations tested (2.5-35 mM), a reflection of an increased maximum rate of transport. Similar results were obtained with alanine. These findings suggest that active Na(+)-linked nutrient transport is enhanced in cystic fibrosis.

Adolescent↗

New diagnostic method for cystic fibrosis.

We report 3 cases where the diagnosis of cystic fibrosis (CF) was either confirmed or refuted by studies of chloride secretion in intestinal mucosal biopsies. In one case a heterozygous state was indicated and later confirmed by gene probe studies. The technique clearly distinguishes between CF and control patients and can provide a rapid diagnosis even in the neonatal period.

Child, Preschool↗

Intestinal transport in cystic fibrosis (CF).

Ion transport was measured in jejunal biopsies using short-circuit current (SCC) as an index of net electrogenic ion transport. Increases in SCC associated with stimulation of Cl- secretion were observed in control tissues, but CF tissues did not exhibit such a response, indicating a failure of intestinal Cl- secretion. The rise in SCC associated with Na(+)-linked glucose absorption was greater in CF tissues than in controls, reflecting an enhanced active absorption of glucose.

Biological Transport, Active↗

Abnormal jejunal potential difference in cystic fibrosis.

Transmucosal potential difference (PD) and intraluminal pressure were recorded from the same jejunal site in 15 healthy adult controls and 4 adults with cystic fibrosis. In the controls, runs of contractions were associated with wave-like changes in PD with, during phase III-like activity, a mean peak amplitude of -9.7 mV. Although there were no obvious differences in motor patterns, wave-like changes in PD were absent in patients with cystic fibrosis. Intraluminal boluses of 4 mg pilocarpine, or 0.1 mg prostaglandin E2, caused changes of -4.6 mV and -4.5 mV, respectively, in controls; these responses were not seen in patients with cystic fibrosis. There were no significant differences in basal PD and PD changes caused by altered concentrations of infused saline or glucose between patients and controls.

Action Potentials↗

Prosthetic hip failure: retrospective radiograph image analysis of the acetabular cup.

A method has been developed for quantifying movement and wear of the acetabular component (cup) of total hip replacements (THR) from routine postoperative and review radiographs. The method uses both interactive and automatic computer image analysis techniques. Dimensions of the prosthesis are used to scale the measurements and so overcome variation in radiographic alignment. The application of the method is illustrated by retrospective investigations of cup migration and wear using review radiographs taken over a follow-up of at least 12 years.

Acetabulum↗

Identification of the cause of separation (creaming) of lipid emulsions in intravenous infusion.

Over a 2-month period, white deposits were found in infusion sets delivering parenteral nutrition mixtures that included a lipid emulsion. When components of the infusion were mixed in the laboratory, separation (creaming) of the emulsion could be demonstrated, and this enabled us to predict the concentrations of the prescribed infusates that were likely to cream. Further investigations showed that creaming occurred when the lipid emulsion was mixed with heparin and calcium ions at concentrations above 1 U/ml and 1 mumol/ml, respectively.

Calcium↗