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D P Rennie

Publications and source records attributed to D P Rennie.

11 recordsLinked to original sources
PubMed1991

The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin.

Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradiometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non-renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the renin-angiotensin-aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome.

Adult↗
PubMed1985

The production and characterization of monoclonal antibodies to the human thyroid microsome.

By suitable immunization of mice and fusion of their spleen cells with a non-secretor mouse myeloma line, monoclonal antibodies have been produced which react with the human thyroid microsomal (M) antigen. These monoclonal antibodies showed no reactivity by enzyme-linked immunoassay with liver microsomes or thyroglobulin and their specificity was confirmed by immunolocalization studies, in which they showed the staining characteristics of human M antibodies. All four monoclonal antibodies tested were immunoglobulin M; three were cytotoxic to thyroid cell monolayers. The lack of cytotoxicity with the fourth monoclonal supports the concept that certain epitopes of the M antigen may be partially or completely absent at the thyroid cell surface. These monoclonal antibodies should permit further characterization of the thyroid M antigen in view of their absence of cross-reactivity with thyroglobulin.

Animals↗
PubMed1985

The influence of cyclosporin A on the induction of experimental autoimmune thyroid disease in the PVG/c rat.

Using an experimental model of autoimmune thyroid disease we have investigated the influence of cyclosporin A (CyA) on the induction of the disease and its potential ability to prevent disease development. PVG/c rats (n = 80) neonatally thymectomized (day 21) and thence sublethally irradiated were divided into eight groups and received either no CyA or oral CyA (10 mg/kg body weight) for varying periods prior to and during disease induction. Serial serum measurements of thyrotropin (TSH) by radioimmunoassay and anti-thyroglobulin autoantibody by enzyme linked immunosorbent assay showed a progressive rise in untreated animals. The rise in serum TSH levels from 349 +/- 15 ng/ml (mean +/- s.e., normal less than 400 ng/ml) at 7 weeks of age to 526 +/- 61 ng/ml at 11 weeks and 820 +/- 54 ng/ml at 15 weeks was not significantly different in animals treated with CyA for periods ranging from 24 h prior to thymectomy to 7 days post-thymectomy. In contrast animals treated for 28 days post-thymectomy showed significantly lower levels of TSH at both 11 weeks (391 +/- 26; P less than 0.02) and 15 weeks (587 +/- 37; P less than 0.005) as compared with untreated animals. Similar though less dramatic changes were seen in intermediate groups. Autoantibody levels in untreated animals rose from initially undetectable levels to 0.451 +/- 0.07 OD (mean +/- s.e.) at 11 weeks and 0.581 +/- 0.041 OD at 15 weeks. Animals treated for at least 4 weeks after thymectomy with CyA had significantly lower levels of antibody at both 11 weeks (0.213 +/- 0.01; P less than 0.001) and 15 weeks (0.337 +/- 0.03; P less than 0.001) of age. Intermediate groups ranged in antibody levels depending on the duration of CyA treatment. Thyroid gland weight (12.7 +/- 2.4 mg/100 g body weight, mean +/- s.e.) and histological grade of thyroiditis (1.8 +/- 0.4, mean +/- s.e.) in the animals treated with CyA for 4 weeks, assessed when the animals were killed at 15 weeks, were smaller and had less severe thyroiditis than untreated thymectomized and irradiated animals (23.8 +/- 2.8 mg/100 g, P less than 0.02 and 2.9 +/- 0.2, P less than 0.05) killed at the same time. CyA given for long enough during induction of experimentally-induced autoimmune thyroid disease delayed the onset of disease and reduced its severity but could not prevent it given over time courses ranging from 48 h prior to thymectomy to 4 weeks after.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Enzyme-linked immunoassay of monoclonal and serum microsomal autoantibodies.

An automated enzyme-linked immunoassay for the detection of antibodies to human thyroid microsomes has been assessed. This assay correlated closely with the established commercial passive haemagglutination method. Variations in the purity of crude microsome preparations and the degree of thyroglobulin contamination make careful comparison of different preparations essential for meaningful interpretation of results, and attempts to circumvent these problems by further purification of microsome preparations using gel filtration are discussed. The application of this method for routine screening of serum samples is demonstrated using populations of normal subjects and patients with rheumatoid arthritis and anti-glomerular basement membrane disease. This assay has also permitted the establishment of murine hybrid myelomas secreting monoclonal antibodies to human thyroid microsomes.

Adult↗
PubMed1984

The role of the spleen in experimental autoimmune thyroiditis.

We have investigated the role of the spleen in the humoral and cellular immune response of rats with experimental autoimmune thyroiditis (EAT) induced by immunization with thyroglobulin and Freund's complete adjuvant. Animals subjected to splenectomy within 4 days of immunization developed lower thyroglobulin antibody levels and less severe thyroiditis compared to sham operated controls. There was no impairment in the ability of the animals to recover spontaneously from the disease after splenectomy. Together with the results obtained using splenocyte infusions, this suggests that suppressor cell production within the spleen plays only a small part in the normal immunological control which is presumably responsible for spontaneous regression of the disease.

Animals↗
PubMed1983

An immunotoxin of ricin A chain conjugated to thyroglobulin selectively suppresses the antithyroglobulin autoantibody response.

The autoantigen thyroglobulin has been conjugated with the A chain of the toxin ricin. In vitro this conjugated "immunotoxin" specifically suppressed the thyroglobulin autoantibody response of lymphocytes from patients with Hashimoto's thyroiditis. Neither total immunoglobulin synthesis nor the synthesis of autoantibody to thyroid microsomes by these lymphocytes was affected by the immunotoxin. The demonstration that an autoantigen coupled to a toxin can induce specific immunological unresponsiveness suggests that such immunotoxins could provide a novel and highly selective means for deleting autoantibody-secreting lymphocyte clones in patients with autoimmune disease.

Antitoxins↗
PubMed1983

The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat.

Experimental autoimmune thyroid disease was induced in August rats by immunization with rat thyroglobulin in complete Freund's adjuvant. Disease severity, assessed by thyroid histology and circulating levels of anti-TG antibody measured by an enzyme immunoassay, was maximal between 30 and 60 days after the initial immunization and thereafter waned. Thyroid function through the duration of the disease, assessed by measurement of serum TSH levels by RIA, remained normal. Once the natural history of the disease was established, groups of rats received methimazole (MMI) with or without T4 in their drinking water, either before or after disease induction. The animals were bled at regular intervals and killed on day 49 for histological grading of their thyroids. MMI alone (group 3) or with T4 (group 4) before disease induction significantly reduced the severity of the disease, although the effect on circulating antibody levels was less marked in the animals in group 4. In animals given MMI alone (group 5) or with T4 (group 6) after establishment of the disease, MMI again significantly reduced the severity of the established disease, although this effect was less marked in the T4 supplemented animals. MMI significantly impaired the induction and reduced the severity of experimental autoimmune thyroid disease in August rats. The ability of MMI to influence the autoimmune process may have important implications for the use of this and other agents that act on the immune system in the management of human autoimmune disease.

Animals↗
PubMed1982

Sites of autoantibody production in rats with thyroiditis.

We have developed a thyroglobulin-specific haemolytic plaque assay and investigated potential sites of autoantibody synthesis in good and poor responder strains of rats immunized with thyroglobulin and in rats subjected to thymectomy and sub-lethal irradiation which subsequently develop thyroiditis spontaneously. The bone marrow appears to be the most important site of thyroglobulin antibody synthesis in all groups, but spleen and cervical lymph nodes are also involved. No thyroglobulin plaque-forming cells could be found in the thyroid. These results imply widespread involvement of the humoral immune system in organ-specific autoimmune processes.

Animals↗
PubMedDate not supplied

The influence of cyclosporin a on experimental autoimmune thyroid disease in the rat.

Female PVG/c rats, thymectomized on weaning and given 4 courses of whole body irradiation to a total dose of 1000 rads, developed experimental autoimmune thyroid disease (EAITD) as assessed by histological evidence of thyroiditis and circulating levels of antithyroglobulin antibodies. Hypothyroidism resulted. Induction of the disease was associated with a highly significant fall in T lymphocyte numbers. Eight weeks after their last dose of irradiation the animals commenced treatment with Cyclosporin A (10 mg/kg rat/day, intragastrically) and were treated for varying time intervals thereafter. The reversal of the T lymphocyte helper: suppressor ratio on Cyclosporin A therapy was associated with a significant improvement in the disease process. The alterations in the T cell subsets and in the disease lasted only as long as the drug was administered and thereafter reverted towards that seen in the control groups of animals receiving no treatment.

Animals↗