Biomedical subjects

G A Pyle

Publications and source records attributed to G A Pyle.

5 recordsLinked to original sources

PubMed1995

P53 and ploidy assessed by flow cytometry in bladder washings.

OBJECTIVE: To determine p53 expression in cells in bladder washings and to relate this to DNA content and clinical outcome. PATIENTS AND METHODS: Washings from 102 patients (41 with newly diagnosed superficial tumours [pTa and pT1], 49 with recurrent superficial tumours and 12 with carcinoma invading bladder muscle) were studied. In 39 cases, the primary bladder tumour was also analysed. The rates of tumour recurrence and progression were determined for the new superficial tumours and related to both p53 expression and DNA content. RESULTS: Cells positive for p53 were detected in 22 of 90 (24%) washings from patients with superficial bladder cancer. P53 expression correlated with tumour stage (P < 0.05), grade (P < 0.05) and abnormal DNA content (P < 0.05). The analysis of pure urothelial (cyto-keratin-positive) cells improved the detection of DNA abnormalities (P < 0.001). In 74% of cases where both washings and tumour were analysed, the results for DNA content agreed. Of 41 new superficial tumours, 27 (66%) recurred (11 were p53-positive, 16 were p53-negative, P = 0.221; 17 had abnormal DNA content, 10 were diploid, P = 0.069). Four patients progressed (one was p53-positive, P = 0.315 and all had abnormal DNA content, P = 0.072). CONCLUSION: P53-positive cells can be detected in washings using flow cytometry and were more commonly detected in association with aneuploid tumours. At short-term follow-up, flow cytometric analysis of DNA content in washings had greater predictive value than had p53 expression. Few washings contained aneuploid cells when the primary tumour contained diploid cells, although the collection of washings is a convenient way of sampling tumour cells.

Aged↗

PubMed1977

Interaction of thyrotrophin with the human thyrotrophin receptor.

The relationship between the binding of thyrotrophin (TSH) to receptors and the production of cyclic AMP has been investigated using crude human thyroid membranes. Receptor binding was studied by use of 125I-labelled bovine TSH, which had been purified by adsorption to and elution from human thyroid membranes. This 125I-labelled material showed the same biological activity as the unlabelled hormone. Binding studies at equilibrium indicated that the association constant of the TSH-membrane interaction decreased as the amount of TSH bound increased. Kinetic data did not provide definite evidence that this was due to an effect of increasing receptor occupancy on the dissociation rate constant. Detectable stimulation by TSH of cyclic AMP production by the membranes was observed with as little as 30 micromicron. (1 ng) hormone. Increasing amounts of TSH over the range 0-250 micromicron caused increases in the production of cyclic AMP, proportional to the amount of hormone bound. With larger amounts of TSH, increasingly greater amounts of bound hormone were required to give corresponding increases in cyclic AMP formation, and addition of TSH in amounts greater than 16 millimicron resulted in progressive inhibition of cyclic AMP formation. Kinetic studies indicated that receptor binding was not rate-limiting in the stimulation of cyclic AMP production by TSH.

Cyclic AMP↗

PubMed1977

Interaction of thyroid-stimulating antibodies with the human thyrotrophin receptor.

Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb-Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.

Antibodies↗

PubMed1976

Thyroid-stimulating immunoglobulins and the control of thyroid function.

Triiodothyronine (T3) suppression and thyrotropin-releasing hormone (TRH) tests were used to study thyroid function in 50 patients with thyroid disease. The results of the thyroid function tests were compared with the levels of serum thyroid-stimulating immunoglobulins (TSI) measured by a radio-receptor assay. In euthyroid and hyperthyroid patients, the presence of TSI corresponded with the absence of TSH control of thyroid function. However, in two hypothyroid patients with serum TSI levels readily detectable in the receptor assay, T3 suppression and TRH tests indicated that thyroid function was under TSH control.

Adult↗

PubMed1975

Relation of thyroid-stimulating immunoglobulins to thyroid function and effects of surgery, radioiodine, and antithyroid drugs.

Thyroid-stimulating immunoglobulins (T.S.I.) have been detected in the serum of all patients with untreated Graves' disease, and in these patients the levels of T.S.I. correlated significantly with the early uptake of 131I by the thyroid. The frequency of T.S.I. in patients treated solely by antithyroid drugs, by radioiodine, or by partial thyroidectomy was 53 per cent, 50 per cent, and 17 per cent, respectively. The reduced frequency of T.S.I. in the serum of patients treated by drugs or radioiodine was probably due to spontaneous remission, but in the case of partial thyroidectomy the operation itself clearly had a dramatic effect on the serum-T.S;I. These results accorded well with the reported frequency of thyroid autonomy in similar groups of patients and suggested that thyroid-stimulating immunoglobulins were responsible for hyperthyroidism in Graves' disease.

Adenylyl Cyclases↗