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D J Topliss

Publications and source records attributed to D J Topliss.

66 records · Page 4Linked to original sources

Effects of triiodothyronine and glucose on cultured rat hepatocyte gene expression.

Both thyroid hormone and carbohydrate feeding are known to influence hepatic gene expression in vivo. In order to determine whether these compounds act directly on the liver, we have utilized an isolated adult rat hepatocyte culture to examine the in vitro influence of either T3 or glucose on a wide range of mRNA activities. RNA was extracted from hepatocyte cultures, translated in the rabbit reticulocyte system, and the translated products separated by two-dimensional gel electrophoresis. We have found a strong similarity between the hepatic mRNA response to T3 administered either to the animal or added to the culture medium and between the response to high carbohydrate feeding and an increase in the medium glucose concentration. Our studies suggest that the isolated hepatocyte culture is a useful model for the study of the influence of hormones and metabolites on the expression of specific mRNA's.

Animals↗

Allosuppressor T lymphocytes abolish migration inhibition factor production in autoimmune thyroid disease: evidence from radiosensitivity experiments.

The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al. 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT.

Antigens↗

Familial euthyroid thyroxine excess: an appropriate response to abnormal thyroxine binding associated with albumin.

Responses of the pituitary-thyroid axis and T4 binding to plasma proteins were studied in three kindreds with familial euthyroid T4 excess, an autosomal dominant condition in which affected subjects have high concentrations of plasma T4 with a high free T4 index, but normal free T4 by equilibrium dialysis. Treatment of affected subjects with exogenous T4 or T3 led to gradual suppression of TSH secretion when the free level of T4 or T3 increased above normal. When total T4 was reduced toward normal by potassium iodide treatment or previous subtotal thyroidectomy, the findings suggested mild hormone deficiency. In affected subjects from all three families, equilibrium dialysis showed increased [125I]T4 binding, with evidence of abnormal high capacity binding when an excess of unlabeled T4 was added. In contrast, T3 binding showed no major abnormality. Serum concentrations of T4-binding globulin, prealbumin, and albumin were normal, but gel electrophoresis and immunoprecipitation of binding proteins indicated that 25-30% of tracer [125I]T4 was albumin bound (normal, 10-12%). Abnormal binding, studied by an adsorption separation system in the presence of T4 excess, was inhibited by increments of barbitone. These findings suggest that T4 excess is an appropriate response to abnormal T4 binding so as to maintain normal free T4. The excess bound T4 is associated with a normal quantity of albumin. The basis for increased T4-albumin binding remains to be determined.

Adolescent↗

Post-partum hypercalcemia in hereditary hyperphosphatasia (juvenile Paget's disease).

Hereditary hyperphosphatasia is a rare bone disorder characterized by increased bone turnover, elevated alkaline phosphatase (ALP) and bone deformity. We describe a patient with a mild form of hereditary hyperphosphatasia who was initially hypercalcemic in childhood with remission after puberty. Symptomatic hypercalcemia recurred during lactation after each of two pregnancies, associated with increased bone turnover (rise in ALP, osteocalcin, and urine hydroxyproline excretion) which appeared to be independent of changes in major calcium-regulating hormones. The mechanism for the development of post-partum hypercalcemia remains unclear but may relate to the relative estrogen deficiency of lactation. We postulate that acute estrogen withdrawal may result in hypercalcemia in the presence of markedly increased bone turnover.

Adult↗

Heterogeneity of amiodarone-induced thyrotoxicosis: evaluation of colour-flow Doppler sonography in predicting therapeutic response.

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) presents a therapeutic challenge because of its resistance to standard antithyroid therapy. In iodine-deplete environments, colour-flow Doppler sonography (CFDS) has allowed distinction between two types of AIT: (i) Type I AIT, associated with increased vascularity (CFDS I-III) and response to thionamide antithyroid drug and (ii) type II AIT, with no/little thyroid vascularity (CFDS 0) and prednisolone responsiveness. AIM: To clarify if CFDS patterns correlated with treatment outcomes in a retrospective study of 24 patients with AIT in an iodine-replete environment. METHODS: Medical records of patients who presented to a teaching hospital between January 1998 to December 2000 were reviewed. Results of CFDS, ultrasound measurement of thyroid size and technetium scanning of the thyroid were correlated with treatment responses, especially prednisolone responsiveness. RESULTS: Thirteen of 24 patients showed CFDS 0. Twelve of these 13 were evaluable for prednisolone responsiveness, of whom seven (58%) were prednisolone-responsive. Of 11 patients with CFDS I-III, four (36%) responded to antithyroid medication alone and only one of seven (14%) was prednisolone-responsive. Euthyroidism was achieved twice as rapidly in patients with CFDS 0 than those with CFDS I-III. Because of medical treatment failure, seven patients, from both CFDS groups, required urgent near-total thyroidectomy which was successful and uncomplicated in all cases. CONCLUSIONS: CFDS is useful in the management of AIT because CFDS 0 correlates better with prednisolone response (58%) than CFDS I-III (14%). However, unlike experience in iodine-deficient regions, the results of the present study revealed that treatment responses to thionamide or prednisolone were heterogeneous within uniform CFDS patterns. Thus, prednisolone--responsiveness was not consistently predicted by CFDS 0, but the presence of flow appeared to correlate with non-response to prednisolone.

Adult↗