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Biomedical subjects

A Di Cerbo

Publications and source records attributed to A Di Cerbo.

8 recordsLinked to original sources
PubMed1995

Characterization of insulin autoantibodies in a patient with autoimmune hypoglycemia.

A 60-year-old man referred because of hypoglycemic bouts was found to have insulin autoantibodies. Total plasma insulin was as high as 1.44 nmol/l. Both plasma free insulin and C-peptide were in the normal range. The indirect immunofluorescence technique showed positivity for antinuclear antibodies. The T-lymphocyte populations in the peripheral blood were normal. When serum binding capacity for pork insulin was measured, antibodies binding pork insulin were not detected. The patient's serum bound 125I-insulin. The binding protein was identified to be an immunoglobulin G. The kinetics of dissociation, studied by the Scatchard analysis of the autoantibody, showed a curvilinear plot, which was analyzed in two components. Cold human insulin was able to compete with 125I-insulin for the antibody binding site (I.C.50 = 1.35 nmol/ml). These antibodies were apparently not associated with antibodies directed against the insulin receptor.

Autoantibodies↗
PubMed1995

Physiological concentrations of thyrotropin increase cytosolic calcium levels in primary cultures of human thyroid cells.

The activity of TSH, the main regulator of growth and differentiation in the thyroid, has been mainly related to the activation of the adenylyl cyclase cascade. TSH also activates phospholipase-C and -A2; these effects, however, have been reported to require concentrations of the hormone up to 1000-fold higher than those effective on adenylyl cyclase, suggesting that the main physiological mechanism involved in the action of TSH is the activation of this enzyme. Using primary cultures of human thyroids, we here show that physiological concentrations of TSH (0.01-10 mU/L) are also able to increase intracellular Ca2+ levels. Cells were loaded with the fluorescent Ca2+ probe fura-2 and analyzed by single cell Ca2+ recording. The basal Ca2+ level was 105 +/- 30 nmol/L, and physiological concentrations of TSH increased it by 2- to 7-fold. The Ca2+ increase was transient and lasted up to 10 min. It is also shown that the TSH-dependent Ca2+ increase involves both the activation of phospholipase-C and the entry of extracellular Ca2+. TSH (100-10000 mU/L) increased cAMP levels by up to 20-fold in parallel experiments performed on the same cell preparations. These data demonstrate that physiological concentrations of TSH are able to increase cytosolic Ca2+ levels, indicating that this second messenger might directly mediate the action of this hormone in the thyroid.

Adenosine Triphosphate↗
PubMed1995

Subgroups of Graves' patients identified on the basis of the biochemical activities of their immunoglobulins.

Graves' patient immunoglobulins (IgG) are known to activate adenylyl cyclase. Recently, we have shown that they also stimulate phospholipase A2 (PLA2). Here we analyze the relationship of these biochemical activities of Graves' IgG to thyroid growth in vitro ([3H]thymidine incorporation) and in vivo (patient goiter size) as well as to clinical indicators of severity of the disease, such as ophthalmopathy, T3 levels, T3/T4 molar ratio, and TSH binding-inhibiting IgG activity. A cluster analysis of the biochemical parameters referring to the whole population (158 subjects) led to the identification of 4 subgroups of Graves' patients based on the different capabilities of IgG to stimulate adenylyl cyclase, PLA2, and [3H]thymidine incorporation. Importantly, a trend of increasing severity of the disease from group 1 to group 4 could be identified. In particular, patients in group 4 (characterized by elevated stimulation of adenylyl cyclase, PLA2, and [3H]thymidine incorporation) had the largest goiter, highest serum concentration of T3, highest T3/T4 molar ratio, and highest prevalence of ophthalmopathy. These results indicate that Graves' IgG induce thyroid growth by stimulating both adenylyl cyclase and PLA2, and suggest a method for the subclassification of Graves' patients that identifies four groups with different degrees of severity of the disease. Moreover, this classification might lead to the targeted use of a novel therapeutic approach based on the inhibition of PLA2 and arachidonic acid metabolism.

Adult↗
PubMed1992

Transplacental passage of autoantibodies to triiodothyronine.

Autoantibodies to T3 (T3Ab) were detected by immunoprecipitation in a 18-year-old female patient affected by Graves' disease. The presence of these antibodies was constantly confirmed during a 7-year follow-up period, independently of therapy and functional thyroid status. Antithyroid microsomal antibodies (McAb) and TSH binding-inhibiting antibodies (TBII) were also present. The title of AbT3, McAb and TBII fluctuated, at times, independently of one another. The patient became pregnant; during pregnancy T3Ab concentration fell and went up again 4 months after delivery. A normal baby was born. T3Ab were present in the cord blood and declined during the following 2-8 months. The T3Ab of both mother and child belonged to the IgG class. The concentrations and the binding affinities of T3Ab in mother and child were identical. The presence of T3Ab in the child did not affect his thyroid function.

Adolescent↗
PubMed1992

Immunoglobulins from Graves' patients stimulate phospholipase-A2 in FRTL5 thyroid cells.

The well documented ability of immunoglobulins G (IgGs) from Graves' patients to stimulate cAMP production is believed to be involved in the pathophysiology of this disease. It is still under discussion whether other intracellular messengers known to regulate thyroid function might play a similar role. This study shows that phospholipase-A2, a signal pathway unrelated to cAMP, is activated by Graves' IgGs. The IgGs from 67 patients with active Graves' disease, 8 patients with Graves' disease in remission, 5 patients with idiopathic myxedema, 2 patients with Hashimoto's thyroiditis, 57 patients with nonautoimmune thyroid disease, and 65 normal subjects were tested for their ability to stimulate phospholipase-A2 activity, as measured by arachidonic acid release from FRTL5 thyroid cells. The IgGs from patients with active Graves' disease caused a significant increase in arachidonic acid release compared to those from normal subjects, patients with nonautoimmune thyroid diseases, and patients with Graves' disease in remission (P less than 0.0001). The IgGs from active Graves' patients were also able to increase cAMP accumulation in FRTL5 cells. This effect did not correlate with the ability of the same IgGs to induce arachidonic acid release, suggesting that Graves' IgGs stimulate these two pathways by separate mechanisms. Moreover, a subgroup of IgGs that stimulated phospholipase-A2 did not increase the cAMP levels in FRTL5 cells. Our data suggest a novel mechanism of action of Graves' IgGs, the activation of phospholipase-A2, well distinguishable from the known effect on cAMP accumulation. The assay we describe could be helpful in improving the diagnosis and therapy of Graves' disease and in distinguishing it from nonautoimmune thyroid diseases. It also supplies the basis for a prospective subclassification of the Graves' patients, which might become useful to clarify the pathophysiology of this disease.

Adolescent↗
PubMed1984

Interaction of basic compounds with coated vesicles.

The effect of poly- and dibasic amines, including chloroquine and quinacrine, on the dissociation of coated vesicles at pH 7.4 in 0.01 M 2-(N-morpholino)ethanesulfonic acid has been evaluated by light scattering and sucrose gradient centrifugation. The degree of inhibition of dissociation by the polybases is proportional to the number of amine groups in each compound. However, very little difference in effectiveness was found in a series of dibasic compounds, NH2(CH2)2-5NH2. Chloroquine and quinacrine contain dibasic aliphatic chains as well as aromatic ring systems. These two antimalarials are more effective in inhibiting dissociation of coated vesicles than the dibasic aliphatic amines. The ring systems therefore appear to be contributing, independently, to the free energy of stabilization of the coat structure of coated vesicles. It is suggested that the interaction of poly- or dibasic compounds with clathrin or coated vesicles could influence the turnover of ligands in receptor-mediated endocytosis.

Alkanesulfonates↗
PubMed1978

Endemic goitre and iodine metabolism in schoolchildren from the Daunia uplands (province of Foggia, Italy).

A study of endemic goitre was carried out in the western part of the province of Foggia (Daunia's pre-Appennines). About 50% of a total of 2719 children aged 6-15 years examined in the agricultural and hill towns of Accadia, Bovino, Candela, Deliceto and Sant'Agata di Puglia (500 to 800 m above sea level), presented a thyroid enlargement (usually of Grade 1). Urinary creatinine values were normal, while urinary iodine was low: 37.7 +/- 28.39 mug/g creatinine (mean +/- SD for 319 subjects). Serum levels of thyroid hormones were normal: T4 = 7.89 +/- 2.61 mug/dl; T3 = 114.72 +/- 40 ng/dl; T3 (T4 X 100) = 0.166 +/- 0.09. Subjects with Grade 2 thyroid enlargement had significant lower urinary iodine and serum T4, and higher T3 and T3/T4 ratio than children without goitre (Grade 0). Serum thyrotropin was rather high (3.79 +/- 4.17 muU/ml), but bore no straight relation to the thyroid size; in subjects with Grade 2 thyroids there was an inverse relationship between plasma T4 and TSH levels. Drinking water iodine was generally low (2-3 mug/l), though some richer sources (18, 38, 66 mug/l) were noted. Iodine contents of locally produced foodstuffs were below those found in food on Turin markets.

Adolescent↗