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Biomedical subjects

U Di Mario

Publications and source records attributed to U Di Mario.

At least 127 records · Page 7Linked 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↗
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

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

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

The correlation between insulin antibodies and circulating immune complexes in diabetics with and without microangiopathy.

The relationship between immune complexes and insulin antibodies was evaluated in 237 insulin treated subjects with a duration of diabetes of more than 1 year. Ninety-seven diabetics were selected at random (group 1) whereas 140 according to the presence of diabetic microangiopathy (group 2). Immune complexes were evaluated by the solid phase C1q binding test in all patients and by conglutinin radioimmune assay in most of them. Insulin antibodies were determined by Christiansen's and Anderson's methods. Immune complexes as detected by the solid phase C1q method were found increased in group 1 and there was an inverse correlation between these complexes and insulin antibody levels. In group 2 patients with microangiopathy the amount of this kind of complex was significantly greater than in those without microvascular lesions and there was no correlation with insulin antibodies. Immune complexes as detected by conglutinin were found increased in group 2 patients and these were significantly correlated with the level of insulin antibodies. No increase in these immune complexes was found in patients with microangiopathy when compared with patients without microangiopathy. Insulin antibodies were not correlated with the presence of complications. Overall, immune complexes detected by C1q binding were significantly correlated with the presence of microangiopathy. In patients with high insulin antibody levels the complexes formed were not detected by C1q binding. The immune complexes detected by conglutinin are correlated with insulin antibodies, but not with the presence of microangiopathy.

Adolescent↗
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

Circulating immune complexes in diabetics with severe microangiopathy: evaluation by two different methods.

An investigation on circulating immune complexes (AgAb) was carried out in 80 diabetics with severe microangiopathy and in 71 diabetics without microvascular lesions. The duration of the disease, the type of diabetes, the type of treatment and the main localization of microangiopathy (retinopathy and nephropathy) were taken into account. AgAb were detected by two different methods: the solid phase Clq binding test (ClqSP) and the conglutinin binding test (KgBt). AgAb detected by ClqSP were increased both in prevalence and quantities in diabetics with severe microangiopathy regardless of the duration of the disease and the type of diabetes. Long standing diabetics without microangiopathy had similar prevalence of AgAb as normal controls. The presence of AGAb was not in correlation with the type of treatment and was similar in diabetics with retinopathy and in those with nephropathy. When AgAb were detected by KgBt, they were found with higher prevalence in diabetics than in normal controls but no correlation with microangiopathy was observed. AgAb, detected by KgBt, were higher in long standing type I diabetics. Since the two methods detect different AgAb it is concluded that AgAb present in diabetics seem to be heterogenous and part of them are related to the presence of microangiopathy.

Adult↗
PubMed1982

Impaired phagocytic function and increased immune complexes in diabetics with severe microangiopathy.

An increase in circulating immune complexes (AgAb) of medium size has been observed in diabetics with late complications. This increase may be related either to an increased formation or reduced clearance. Alternatively, both mechanisms may be involved. As medium-sized AgAb determined by the C1q solid phase method are mainly removed from circulation by the fixed phagocytes of the reticulo-endothelial system, we investigated the function of these cells using a colloid clearance test in diabetics with various degrees of microangiopathy. Microaggregated iodinated human serum albumin was injected into 30 diabetic volunteers with severe (group 1), moderate (group 2), and absent (group 3) microangiopathy, and into 40 normal volunteers. The colloid clearance was significantly reduced in diabetics with severe microangiopathy in comparison with patients who had no sign of microangiopathy, or with normal subjects. A significant correlation was found between reduced colloid clearance and increased levels of circulating AgAb determined by C1q solid phase method. Results of this study suggest that the increase in circulating AgAb observed in patients with severe microangiopathy may result from an impaired function of mixed phagocytes.

Adult↗