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Biomedical subjects

D Andreani

Publications and source records attributed to D Andreani.

At least 73 records · Page 4Linked to original sources
PubMed1986

The relationship of soluble immune complexes, insulin antibodies and insulin-anti-insulin complexes to platelet and coagulation factors in type 1 diabetic patients with and without proliferative retinopathy.

The possible correlation between soluble immune factors and platelet and coagulation factors has been evaluated in Type 1 diabetic patients with and without proliferative retinopathy, and in non-diabetic controls. Soluble immune complexes, platelet factor IV (PF4), beta-thromboglobulin, fibrinogen, factor VIII related antigen and anti-thrombin III were significantly increased in Type 1 diabetic patients with retinopathy as compared to non-diabetic controls. Fibrinogen and anti-thrombin III were also higher in those patients with retinopathy compared to those without retinopathy. A significant correlation was found between positive values of soluble immune complexes and increased levels of PF4 and beta-thromboglobulin in diabetic patients with retinopathy. The presence of soluble immune complexes and insulin-anti-insulin complexes was associated with a significantly greater number of elevated haemostatic factors in retinopathic patients. Our findings suggest that the interaction of platelets and soluble immune complexes or insulin-anti-insulin complexes may be pathologically relevant to the development of diabetic retinopathy.

Adult↗
PubMed1986

Urinary immunoglobulin G: a routine and highly sensitive technique based on competitive binding.

The evaluation of both small amounts of urinary immunoglobulins and the albumin/immunoglobulin ratio are important indices during the early stages of diabetic nephropathy. For this reason there is at present a need for highly-sensitive and specific routine tests for urinary immunoglobulins. A technique has been designed based on the competition between radiolabelled immunoglobulin G and immunoglobulins in the urine to be tested in binding to an anti-immunoglobulin antibody in solid phase. The immunoglobulin fraction of a rabbit anti-human immunoglobulin antiserum in a basic Ca-carbonate buffer is left to coat highly adsorbent polystyrene microtitre tubes. After the antibody-coated tubes have been saturated with gelatine, a 1/5 dilution of the urine to be tested and an equal volume of purified and radiolabelled human immunoglobulin G are left to incubate and are then added to the antibody-coated tubes. After incubation and repeated washings, radioactivity is counted. This technique has the characteristics of a routine assay for the accurate detection of immunoglobulin G in the urine. It requires only a few microliters of urine, takes only 3 hr to complete (after having coated the tubes) and detects about 120 ng of immunoglobulin G/ml, well below what is needed to assess physiological or pathological values.

Binding, Competitive↗
PubMed1986

A fluid-phase routine method for the detection of insulin-anti-insulin complexes.

A fast routine method has been devised to measure circulating insulin-anti-insulin complexes. The principle lies in the calculation of the difference between the insulin binding capacity of the free antibody and that of the total amount of insulin antibody. The pH of 1 aliquot of serum was lowered to 3 by adding glycine-HCl buffer. Free insulin was removed by charcoal precipitation and the pH was again neutralized by the simple addition of NaOH; the final dilution of serum was 1/5. Radiolabelled insulin was added to this and to a second aliquot of serum, also diluted 1/5. Free and bound insulin were separated using either dextran charcoal or PEG 6000 at a final dilution of 14.3%. The first technique of separation was preferred. This method has been used in normal controls and in insulin-treated diabetic patients and the results have been compared to those obtained using other methods to detect insulin-anti-insulin complexes and insulin antibodies. Insulin-anti-insulin complexes tended to be more frequently observed in patients with high insulin antibody values. The technique described is much less laborious than other methods for detecting insulin complexes since it requires only a few hours to complete. It is reproducible and sensitive enough for clinical research. This method is of value when both free and bound insulin antibodies have to be evaluated.

Animals↗
PubMed1985

Activated T cells in Graves' disease before treatment.

The aim of this study was the definition of abnormalities occurring within T-cell subsets of thyrotoxic Graves' patients before treatment. Special emphasis was placed on the enumeration of activated T cells using a number of new monoclonal antibodies. Lymphocytes from 22 Graves' disease patients were examined. The total number, the percentage of 'helper/inducer' and 'suppressor/cytotoxic' positive cells were evaluated using the antibodies T3, T4 and UCHT4, whereas the cells with killer activity were defined by H25. Activated T cells were detected using the antibodies DA6.231, DA6.164, and L243 which bind different epitopes of the beta chains of class II surface antigens and 4F2, which binds a 120,000 molecular weight glycoprotein. The results show no significant change in the total T, helper or suppressor cell phenotype, but an increase in the killer cell percentage was noted. Of those patients tested, 19 of 22 showed an increase in activated T cells, 18 of 22 patients showed a significant increase of T cells bearing class II antigens, 11 of 22 showed an increase of T cells staining with another activated T cell antibody, 4F2. The anti-DR antibodies expressed different binding characteristics, the most striking difference being seen between the antibodies DA6.231 and L243. The results of this study suggest an heterogeneity of the immune response, or differences in activation stage in patients with Graves' disease before therapeutic intervention. An important role for these cells in the pathogenesis of this disorder can be inferred.

Adolescent↗
PubMed1985

Inhibition of the receptor for interleukin-2 induced by carbimazole: relevance for the therapy of autoimmune thyroid disease.

Evidence has been accumulated that the anti-thyroid drugs used in the treatment of Graves' disease may have immunosuppressive properties but the exact mechanism of action is still unclear. In the present study, we have investigated the in vitro effect of carbimazole (CBZ) on the expression of lymphocyte differentiation antigens and on suppressor cell activity. The incorporation of radiolabelled methimazole (35S-MMI, the active metabolite of CBZ) by resting and mitogen stimulated lymphocytes was also investigated. CBZ at concentrations of 60 microM significantly inhibited the expression of the receptor for interleukin-2 (as defined by the anti-TAC monoclonal antibody [MoAb]) by lymphocytes stimulated with phytohaemagglutinin. The expression of an early activation antigen (as characterized by the 4F2 MoAb) was not affected. Twenty-four hour pre-incubation of cells with different concentrations of CBZ or medium alone did not change the lymphocyte response to mitogenic stimulation, thus suggesting no effect of the compound on suppressor cell function. Finally, there were no significant differences in the uptake of 35S-MMI between resting and stimulated lymphocytes. These data suggest that the immunosuppressive effect of CBZ may be due to its effect of reducing the expression of the receptor for interleukin-2 on lymphocytes undergoing full activation. This property of CBZ could be of relevance in the therapy of autoimmune thyroid diseases (not only Graves' disease) which are characterised by the presence of activated T cells in the thyroid and in circulation.

Adult↗
PubMed1985

Humoral immunity in diabetic pregnancy: interrelationships with maternal/neonatal complications and maternal metabolic control.

The presence of islet cell antibodies (ICA), complement fixing islet cell antibodies (CF-ICA), other organ-specific autoantibodies, insulin antibodies and two different types of immune complexes (AgAb) in diabetic pregnant women treated with insulin during pregnancy was investigated and compared with maternal metabolic control and with the course and outcome of pregnancy. One hundred and eighteen pregnant diabetic women were grouped according to type of diabetes: 56 were insulin-dependent diabetic patients who had been previously treated with insulin (Group 1); 23 were non-insulin-dependent diabetic patients who had previously received diet or oral treatment (Group 2); 39 had gestational diabetes (Group 3). 94 patients were subjected to regular check-ups during pregnancy and blood samples were taken during the last month of pregnancy (phase A); some were treated with standard preparations of insulin, the remainder with purified insulins. 24 patients were treated with purified insulins (a bovine and porcine mixture) on entering the study and blood samples were taken at regular intervals during pregnancy (phase B). ICA were detected in 12% of the patients in Group 1 and in 5% of those in Group 3. There was no significant variation in the titre during the gestational period. ICA were not detected in the patients in Group 2. No CF-ICA were found in any of the patients. The positivity of the other organ-specific autoantibodies was similar to that the normal control group. Insulin antibodies were found in concentrations of 67%, 73% and 25% in Groups 1,2 and 3 respectively during the last month of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Insulin-anti-insulin complexes in diabetic women and their neonates.

It is known that insulin does not cross placenta, whereas maternal anti-insulin antibodies do. We have therefore investigated insulin antibodies and insulin-anti-insulin complexes both in pregnant diabetic women during pregnancy and in umbilical cord blood from their new-born infants. Forty-seven diabetic pregnant women and 23 new-born-infants of these diabetic women were studied. All the pregnant patients were studied at the end of pregnancy and in 27, at least on one other occasion during pregnancy. All the patients were treated with insulin during pregnancy: 26 had Type 1 (insulin-dependent) diabetes, 14 Type 2 (non-insulin-dependent) diabetes and seven had gestational diabetes. Insulin antibodies were found in 62% of the Type 1 diabetic patients, in 71% of the Type 2 diabetic patients and in 43% of the gestational diabetic patients. There were present in 48% of the infants studied. Insulin-anti-insulin complexes were found in 37% of the women with Type 1 diabetes, in 21% of those with Type 2 diabetes and in 14% of those with gestational diabetes. Complexes were found in 38% of the new-born infants. The presence of these complexes in the babies was more strongly correlated with their occurrence in their mothers at the beginning than at the end of pregnancy. Insulin-anti-insulin complexes are thus present in the neonatal circulation. They may differ from those in their mothers and they may have pathophysiological and clinical importance.

Antigen-Antibody Complex↗
PubMed1984

Lymphocyte subsets and immune complexes in long-standing diabetic patients: relation with the presence of microangiopathy.

Subsets of peripheral T lymphocytes by monoclonal antibodies and circulating immune complexes by two different methods were evaluated in 36 long-standing diabetic patients, 19 Type 1 (insulin dependent) and 17 Type 2 (non-insulin dependent). In all patients the presence of microangiopathy was assessed by retinal fluoroangiography, albuminuria and creatinine clearance. In patients with Type 1 diabetes a significant decrease of total T and of T cells with helper phenotype (T4), together with an increase of T cells with suppressor/cytotoxic phenotype (T8), were observed. No significant modifications in the percentage of T lymphocyte subsets were detected in patients with Type 2 diabetes. Immune complexes were found to be significantly increased in Type 1 compared with Type 2 diabetic patients. Patients with very high levels of T8+ cells did not have detectable immune complexes and had no evidence of microangiopathy. By contrast, patients with normal levels of these cells were found to have raised immune complexes and showed retinopathy of varying degree. The results of this study indicate that: (1) a relationship exists between cells with T8 phenotype, some immune complexes and the presence of microangiopathy; (2) the decrease of T4+ cells in Type 1 diabetics with long duration of disease may be responsible for the known susceptibility to infections in these patients.

Adolescent↗
PubMed1984

Glucose-induced GIP levels in patients with insulinoma.

Gastric inhibitory polypeptide (GIP) levels during an oral glucose tolerance test (OGTT) have been determined in eight patients suffering from a single benign beta-cell adenoma. GIP hypersecretion and an absent correlation between the insulin: glucose ratio and plasma GIP concentration have been observed. Our data show that the insulinotropic effect of GIP is almost abolished in insulinoma patients. This finding may help explain blood glucose levels and the inappropriate plasma insulin response to oral glucose often observed in these patients.

Adenoma, Islet Cell↗
PubMed1983

Aspects of humoral immunity in a prospective study of Type I (insulin-dependent) diabetic subjects treated with insulins of different purity.

In 41 Type 1 (insulin-dependent) diabetic patients, islet cell antibodies, anti-insulin antibodies, and immune complexes measured by two different methods (the C1q solid phase assay and the conglutinin binding test) were studied at diagnosis, and the influence of treatment with insulins of different purity was investigated during the first year of treatment. Twenty subjects were treated with conventional insulins (group 1) while 21 were treated with monocomponent porcine insulins (group 2). The prevalence of islet cell antibodies significantly decreased during the 12-month study period in the 41 patients. From the first month anti-insulin antibodies were always significantly higher in group 1 than in group 2. At diagnosis the prevalence of both types of immune complexes in the 41 patients was higher than in normal subjects. The immune complexes measured by the C1q solid phase method showed a significant and progressive reduction during the follow-up period, whereas the immune complexes assayed by conglutinin showed no significant variation in the same period. The presence of C1q immune complexes was found to correlate with the occurrence of islet cell antibodies both at diagnosis and during the follow-up period. The presence of conglutinin immune complexes, on the other hand, tended to parallel the increase of anti-insulin antibody levels.

Adolescent↗
PubMed1983

Tracking of indium-111-oxine labelled lymphocytes in autoimmune thyroid disease.

Peripheral lymphocytes (approximately 10(8)) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 microCi of indium-111-oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging. Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell-mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.

Adult↗
PubMed1983

Diazoxide infusion test in patients with single benign insulinoma.

The diazoxide infusion test (600 mg i.v. over a 1-hour period) was performed in 12 patients bearing single benign islet B-cell adenoma and in 6 normal subjects. Blood glucose, plasma insulin and glucagon concentrations were measured every 15 min during the infusion and thereafter up to 150 min. In insulinoma patients, blood glucose levels failed to increase significantly while in the control group a significant rise starting from 30 min persisted throughout the test (p less than 0.05 or less). Plasma insulin mean levels decreased significantly in normal subjects from 30 to 60 min (p less than 0.05), while they were significantly suppressed in hypoglycemic patients from 15 to 120 min (p less than 0.02). Diazoxide administration induced in the normal group a significant decrease in glucagon levels (p less than 0.02 from 30 to 150 min) whereas no such suppression occurred in patients. In our experience, insulin response to diazoxide infusion in patients with insulinoma may provide additional information for diagnosis.

Adenoma, Islet Cell↗
PubMed1983

Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: comparison with systemic corticosteroids alone.

The effects of different methods of treatment of Graves' ophthalmopathy were evaluated in a series of 48 patients. Thirty-six patients were given combined treatment with orbital cobalt irradiation and systemic 6 alpha-methylprednisolone (methylprednisolone). Included in this group were 12 of 24 consecutive patients who were randomly assigned to either combined therapy or systemic methylprednisolone alone. The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index) and clinical assessment. Of the 36 patients treated by combined therapy, 12 (33%) showed excellent responses, 14 (39%) showed good responses, 9 (25%) showed slight responses, and 1 (3%) had no response. Treatment was more effective for soft tissue involvement, newly developed ophthalmoplegia, and optic neuropathy, while proptosis and longstanding ophthalmoplegia were less responsive. There was an inverse relationship between the duration of ophthalmopathy and the efficacy of treatment, more favorable results being observed when symptoms had been present for less than 2 yr. Treatment with systemic methylprednisolone alone was also effective, but, in general, responses were less satisfactory; 4 of the 12 patients of this group (33%) had good responses, 6 (50%) had slight responses, and 2 (17%) had no response. The results obtained in the 24 patients randomly assigned to combined therapy or steroid treatment alone were compared by evaluating changes in the ophthalmopathy index. Mean initial ophthalmopathy indices (6.4 vs. 6.2, respectively) showed no significant differences between the 2 groups, whereas the mean decrease in the group receiving combined therapy (4.8) was significantly greater (P less than 0.05) than that in the other group (3.2). In conclusion, the present study indicates that both orbital cobalt irradiation combined with systemic methylprednisolone treatment and systemic methylprednisolone therapy alone are valuable methods of treatment for Graves' ophthalmopathy, but the combined therapy proved to be more effective.

Adolescent↗
PubMed1983

Monoclonal antibodies defined abnormalities of T-lymphocytes in type I (insulin-dependent) diabetes.

Peripheral T-lymphocytes subsets have been investigated in 36 patients with type I (insulin-dependent) diabetes of varying duration, 18 patients with type II (non-insulin-dependent) diabetes, and in 23 healthy subjects, using six different monoclonal antibodies. At the time of diagnosis of type I diabetes, there was evidence of an increase in cytotoxic T-lymphocytes, a decrease in suppressor T-lymphocytes, but a normal proportion of helper/inducer T-lymphocytes. In six of seven newly diagnosed cases studied, there was evidence of an increased number of activated T cells. An increase in activated T-cells was also found in 5 of 10 genetically susceptible islet cell antibody positive unaffected siblings in type I diabetic probands. In type I diabetes of long standing, the total T-cell population was decreased, largely due to a marked decrease in helper/inducer T-lymphocytes. Type II diabetic patients showed no abnormalities in T-lymphocyte subsets, making it unlikely that hyperglycemia was responsible for the changes observed. These results suggest that an imbalance of T-lymphocyte regulation is an important feature of type I diabetes and lend support for an immunologic role in its early pathogenesis.

Adolescent↗