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Biomedical subjects

W J Irvine

Publications and source records attributed to W J Irvine.

At least 19 recordsLinked to original sources
PubMed1987

Anti-muscle antibodies in Graves' ophthalmopathy.

The nature of the humoral immune response in patients with Graves' ophthalmopathy has been investigated using a solid phase 125I Protein A binding assay. Retro-orbital muscle (R.O.M.), skeletal muscle (Sk.M.), R.O.M.-membranes, thyroid, kidney, liver, harderian gland, acetylcholine receptors (AchR), actin and myosin were used as target antigens. No significant difference in antibody binding profile to R.O.M. and Sk.M. was found indicating that the ophthalmic immunoglobulins (OIgs) were not recognising a R.O.M. specific antigen(s). Comparison between R.O.M. and R.O.M.-membranes, however, revealed that these antigens were detecting very different antibody populations. Using the former, it appeared that the predominant antibody population being measured was anti-myosin whereas the latter appeared to be detecting primarily anti-AchR antibodies. Anti-actin antibodies were also present in some of the sera. Thus a spectrum of anti-R.O.M. antibodies appears to be present in Graves' ophthalmopathy but the cross-reactivity of these with non-R.O.M. skeletal muscle and their similarity to those found in myasthenia gravis prevent them as yet being used to explain the specific immunopathology observed in this disease.

Actins↗
PubMed1986

The lack of specificity of ophthalmic immunoglobulins in Graves' disease.

Immunoglobulins (Igs) binding to retro-orbital muscle (ROM) antigens, known as ophthalmic Igs (OIg), were measured using a 100,000 X g sediment of porcine ROM as antigen in a solid phase [125I]protein A binding assay. Serum samples from 50 control subjects bound from 0.60-2.42 times the amount of [125I]protein A as did the normal reference serum samples, defined as the OIg ratio. Serum from 95 patients with hyperthyroid Graves' disease had OIg ratios from 0.64-9.99, with 24 (25%) being positive [OIg ratio greater than 2.05 (mean + 2 SD of the normal group)]. Ten patients with euthyroid Graves' ophthalmopathy had OIg ratios from 1.01-6.33, with 6 (60%) being positive. Among those Graves' disease patients with ophthalmopathy (n = 19) and the euthyroid Graves' ophthalmopathy patients there was a good correlation between the severity of eye signs and the OIg ratio. The OIg-positive serum samples cross-reacted with skeletal muscle and thyroid as well as with ROM antigen. This lack of specificity contradicts previous reports, but does not rule out a role for these antibodies in the etiology of Graves' ophthalmopathy.

Adult↗
PubMed1986

Immunity in Graves' disease at diagnosis: correlation between activated T cells and humoral immune factors.

Activated T cells, T-cell subsets, thyrotropin receptor antibodies and immune complexes were evaluated in 31 patients with newly diagnosed Graves' disease. Activated T cells were assayed by monoclonal antibodies against early (4F2) and late activation surface lymphocyte antigens (different epitopes of class II antigens). In comparison with the normal population, Graves' patients showed a significant decrease in the suppressor cytotoxic T-cell subset. Significant increases of 4F2-positive cells (70% of patients studied), class II antigen-positive cells (65%), thyrotropin receptor antibodies (93%), Clq-immune complexeses (44%) and conglutinin-immune complexes (37%) were observed. A significant inverse correlation between the increase in 4F2-positive cells and thyrotropin receptor antibody values was also observed. Lymphocytes from Graves' patients were cultured in the presence of thyrotropin receptor antibody-positive or -negative sera, with or without mitogen stimulation. Thyrotropin receptor antibodies were shown not to interfere with the expression of activation antigens in cultured cells. The different patterns of humoral and cellular immune phenomena may indicate the existence of either different stages of Graves' disease or a heterogeneity of the immunopathogenesis in different patients.

Adolescent↗
PubMed1984

How effective is external pituitary irradiation for growth hormone-secreting pituitary tumors?

Forty-six patients with GH-secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (+/- SD) serum GH in the former group was 74.3 +/- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+/- SD) serum GH in the latter group was 265.4 +/- 209.3 mU/l before treatment, falling by 76% in the first year--a direct result of surgical removal of tumour--then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.

Acromegaly↗
PubMed1983

Immune abnormalities in diabetic patients not requiring insulin at diagnosis.

Islet cell antibodies (ICA), complement fixing islet cell antibodies, immune complexes and thyro-gastric autoantibodies were studied in newly diagnosed diabetic patients not requiring insulin at diagnosis. Particular attention was focussed on that minority of patients who are initially treated with diet or oral agents but show ICA in their serum. One hundred and six non-insulin-requiring patients were studied at clinical diagnosis. Seventeen who had ICA in their serum were compared with a control group of 89 who did not. The 17 ICA-positive diabetic patients were followed serologically for approximately 1 year from diagnosis. Patients were followed clinically for 3 years. Forty-seven percent of ICA-positive and 19% of ICA-negative patients had immune complexes in their serum. Eleven of the 17 ICA-positive patients also had serum complement fixing islet cell antibodies. Thyro-gastric antibodies were found in 29% of ICA-positive and 18% of ICA-negative diabetic patients. ICA, complement fixing antibody and immune complex positivity declined with time. Ten of the 7 ICA-positive and two of the 89 ICA-negative patients required insulin within 3 years of diagnosis. There was a positive trend for the presence of complement fixing islet cell antibodies at diagnosis to be associated with the early development of insulin dependency. The type of diabetes in ICA-positive patients not requiring insulin at diagnosis has strong immunological and clinical similarities to classical Type 1 (insulin-dependent) diabetes.

Antibodies↗
PubMed1983

A search for heterogeneity in insulin dependent diabetes mellitus (IDDM): HLA and autoimmune studies in simplex, multiplex and multigenerational families.

HLA antigens (A, B, C and DR loci), serum islet cell antibodies, thyrogastric antibodies, and insulin antibodies were studied in 77 families (25 simplex, 42 multiplex, and 10 multigenerational). In order to test for intrafamilial constancy and intergroup variation, we compared simplex with multiplex families, HLA identical and non identical siblings within families, as well as groups of families characterized by different DR alleles (DR3, DR4, and DR3/DR4) for various immunologic and clinical characteristics. These comparisons did not reveal all the distinct subgroups suggested by different cross-sectional population studies, but did provide evidence for a compound form having an aggregation of different high risk alleles. This study suggests that in many cases (and possibly especially in families with multiple affected individuals), there are several different genetic influences leading to IDDM.

Antibodies↗
PubMed1983

Natural history of thyroid function in diabetics with impaired thyroid reserve: a four year controlled study.

An attempt was made to compare the natural history of thyroid function in 80 diabetics having raised serum TSH concentrations (median 8.9 mU/l, range 5.8-46.3 mU/l) but serum T4 concentrations within the normal range (Group 1), and in 59 diabetics having normal serum TSH (median 1.9 mU/l, range 0.8-4.7 mU/l) and T4 concentrations (Group 2). Thyroid microsomal antibodies were present initially in 65% of patients in Group 1 and 15% of patients in Group 2. By 1981, 59 patients (74%) in Group 1 and 47 patients (80%) in Group 2 had been followed for a mean +/- SD duration of 4.2 +/- 1.8 and 4.2 +/- 1.5 years, respectively. Hypothyroidism developed in 9 patients in Group 1, but none from Group 2. Of patients in Group 1, hypothyroidism developed at a rate of 5% per annum in those with thyroid microsomal antibodies, but only 1% per annum in those without antibodies. Therefore, the risk of development of hypothyroidism is greatest in diabetics having both elevated serum TSH concentrations and thyroid microsomal antibodies and such patients should have regular review of thyroid function. Either risk factor alone appears to be a poor predictor of development of hypothyroidism.

Antibodies↗
PubMed1983

Circulating immune complexes in diabetics: the influence of sex, age, duration of disease and type of treatment.

The influence of sex, age, duration of diabetes and type of antidiabetic treatment on soluble immune complexes levels was investigated in the sera of 276 randomly selected diabetics. Immune complexes were detected by the solid phase C1q binding test. The prevalence of immune complexes was significantly higher in insulin treated than in non-insulin treated diabetics. Within the insulin treated group, the prevalence in diabetics of 11-20 yr duration was significantly higher than in the remainder. No difference in immune complexes levels was found between males and females. The age of the patients did not have any correlation with the levels of immune complexes. These findings suggest that some of the immune complexes detected in randomly selected diabetics are related to insulin treatment, reflecting either differences in the type of diabetes or the effects of heterologous insulin.

Adolescent↗
PubMed1983

Non-insulin-treated ICA positive and negative diabetics are equally insulin resistant.

Insulin action was assessed in 5 cytoplasmic islet cell antibody (ICA) positive non-diabetics, 8 ICA positive (type I) non-insulin-treated diabetics, 7 ICA negative insulin-treated diabetics by measurement of steady state plasma glucose (SSPG) levels during a combined intravenous infusion of propranolol, adrenaline, glucose and insulin. SPPG values of ICA positive and negative non-diabetics were similar and their combined value (4.0 +/- 0.5 mmol/l) was significantly lower (p less than 0.01 and less than 0.01) than those (11.5 +/- 1.9 and 11.3 +/- 2.2 mmol/l) of ICA positive and negative diabetics, indicating that both groups of diabetics were similarly insulin resistant. Similar correlations were observed between SSPG and HbA1 levels when considering all ICA positive subjects (r = 0.89, p less than 0.001) and all ICA negative subjects (r = 0.73, p less than 0.01). Conventional insulin treatment (2.6 months) in 4 ICA positive diabetics improved insulin action in each case with a reduction in mean SSPG concentration from 14.0 +/- 2.3 to 8.5 +/- 3.4 mmol/l. Thus, ICA positive and negative diabetics, of equivalent degree of carbohydrate intolerance, are equally insulin resistant. Insulin treatment may improve, but appears not to normalise, insulin action in ICA positive (type I) diabetics.

Adult↗
PubMed1983

Humoral immunity in type 1 diabetes mellitus: a prospective study.

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.

Adult↗
PubMed1982

Control of severe thyrotoxicosis with potassium iodide and propranolol.

Conventional preparation of thyrotoxic patients for surgery using thiouracils and iodides may not be possible because of either, inability to obtain satisfactory therapeutic levels of the drugs or idiosyncratic reactions to the drugs. An alterative regime using potassium iodide and propranolol in combination has previously been shown to be both safe and effective in the pre-operative control of mild to moderate thyrotoxicosis. The use of this combination in a patient with severe thyrotoxicosis is described. Potassium iodide and propranolol can be used successfully to prepare patients with all degrees of thyrotoxicosis for surgery.

Adult↗
PubMed1982

Progressive adrenal failure in polyglandular autoimmune disease.

We describe the clinical course of a boy who developed progressive adrenal failure, beginning with failure of the zona glomerulosa, as part of polyglandular autoimmune disease. Initially the patient presented with hypoparathyroidism and mucocutaneous candidiasis. ACTH tests at ages 8 and 11 yr resulted in a normal response of both mineralo- and glucocorticoids. The constellation of hyponatremia , hyperkalemia, and growth failure at age 14 yr prompted a reevaluation. A repeat ACTH test, assessing individual contributions of zone fasciculata and glomerulosa, showed normal plasma cortisol, desoxycorticosterone, and corticosterone responses and a normal urinary response of 18-hydroxydeoxycorticosterone and tetrahydrodeoxycorticosterone. Urinary 18-hydroxycorticosterone and urinary as well as plasma aldosterone were undetectable. PRA was markedly elevated. The ACTH response of adrenal androgens, presumably metabolic products of the zona reticularis, was also deficient. Antiadrenal antibodies against all three layers of the adrenal cortex were present. Mineralocorticoid therapy resulted not only in normalization of electrolytes and PRA but also in catch-up growth. Repeat testing of fasciculata function at age 19 yr now shows that the patient's cortisol response to ACTH response in abnormal. The course of this patient suggest that in addition to monitoring the electrolyte status, periodic tests for both mineralo- and glucocorticoid synthesis should be performed in children with polyglandular autoimmune disease because progressive adrenal insufficiency may go unrecognized.

Adrenal Glands↗
PubMed1982

Bovine complement: formation of a lytic system between heat-inactivated foetal calf serum and fractions from normal human serum.

Although heat-inactivated foetal calf serum is regularly used as an "inert" additive for culture media, reconstitution of complement activity occurred on the addition of fractions of human sera. The nature of these factors is discussed. Chicken erythrocytes (CRBC), the target cells used in the study, were directly shown to be susceptible to the lytic action of bovine serum, suggesting their potential use in the assay of bovine complement.

Animals↗
PubMed1981

Circulating immune complexes and autoantibodies in lung cancer.

The sera of 80 newly diagnosed lung-cancer patients have been examined for immune complexes and autoantibodies. Control subjects consisted of 20 bronchitic patients and 150 normal blood donors. Immune-complex measurements used 4 established and sensitive techniques (Raji cell assay, fluid and solid-phase C1q assays and conglutinin-binding assay) and a 5th newly devised technique based on the binding of polyethylene-glycol-precipitated immune-complex-rich serum fractions to Staphylococcus aureus. Using the Raji cell assay and the S. aureus binding assay to measure immune complexes, both newly diagnosed lung cancer patients and bronchitic patients had significantly higher prevalences of immune complexes than normal controls, but the two groups of patients did not differ significantly in either prevalence or quantity of immune complexes. When techniques which depend solely upon complement fixation (C1q assays and conglutinin binding) were used, only meagre quantities of immune complexes were found, and in at most 15% of newly diagnosed lung-cancer patients. The presence of autoantibodies in newly diagnosed cancer patients and controls appeared to correlate with the increase in the detectable prevalence of immune complexes.

Adolescent↗
PubMed1981

Patterns of plasma cortisol and ACTH concentrations in patients with Addison's disease treated with conventional corticosteroid replacement.

Plasma cortisol and adrenocorticotrophin hormone (ACTH) profiles were estimated in twelve patients with Addison's disease following randomized oral administration of either cortisone acetate (25 mg) or hydrocortisone (20 mg) alternately, at 0900 h on consecutive days. Normal corticosteroid replacement therapy was discontinued from 1200 h on the day prior to the study period. In four patients elevated basal plasma ACTH concentrations were not suppressed to the limit of detection following the administration of either drug, and in three of these no suppression was found following the prolonged administration of pharmacological doses of dexamethasone. Diminished sensitivity of pituitary ACTH secretion to cortisol inhibition may result from chronic loss of negative feedback before and/or after diagnosis and treatment. In three patients elevated basal plasma ACTH concentrations were suppressed adequately during the administration of either drug, but in five, low basal ACTH concentrations following corticosteroid withdrawal suggested chronic inhibition of anterior pituitary corticotrophs by over-replacement with glucocorticoid. However, further study is necessary to determine whether the estimation of ACTH profiles is a more accurate reflection of the adequacy of corticosteroid replacement than the estimation of cortisol profiles alone, and whether this estimation leads to an improvement in patient management. Hydrocortisone (20 mg) achieved higher mean cortisol levels and lower mean ACTH levels than cortisone acetate (25 mg), but either drug may be suitable for glucocorticoid replacement provided the dose is tailored to the individual needs.

Addison Disease↗
PubMed1981

Some studies on the polyethylene glycol turbidity method for detecting immune complexes in serum.

A rapid and simple method for detecting circulating immune complexes based on turbidity measurements following polyethylene glycol precipitation was studied with regard to its suitability as a routine assay in clinical laboratories. This method was found to have an acceptable degree of precision provided the temperature was carefully controlled. The mean value obtained with a group for 70 blood donors was 0.09 (SD 0.05) and the 90th percentile value was 0.16. There was no significant difference between values obtained from groups divided on the basis of age or sex. Of 70 diabetic sera assayed by the polyethylene glycol turbidity method, 20% gave positive values although only 10% were strongly positive. The corresponding figures for the solid phase Clq binding method were 15.7% and 14.3%, respectively. Correlation between the two methods was poor. It was concluded that although both methods have a similar likelihood of detecting immune complexes in randomly selected diabetics, it is probable that different immune complexes were being detected.

Antigen-Antibody Complex↗