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Biomedical subjects

R Vigneri

Publications and source records attributed to R Vigneri.

At least 127 records · Page 7Linked to original sources
PubMed1987

The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area.

An analysis of thyroid cancer morbidity was carried out in two adjacent areas of Sicily differing in iodine intake. A consecutive series of 911 patients with "cold" nodules from an iodine-deficient area (IDA) and 2537 from a control area (CA) were examined by fine needle aspiration and selected for surgery and pathologic examination. Malignancies were found in 27 of the patients (2.96%) from the IDA and in 139 patients (5.48%) from the CA. Based on a population survey indicating that "cold" thyroid nodules were 2.5 times more frequent in the IDA with respect to the CA, we calculated a prevalence of 127 thyroid cancers per 10(5) inhabitants in the IDA versus 93 in the CA (P less than 0.001). Moreover, follicular and anaplastic carcinomas were three times more frequent in the IDA than in the CA (75 versus 24 cases per 10(5) inhabitants, respectively). These studies indicate that iodine deficiency may be one factor in the development of certain thyroid malignancies in man.

Adenocarcinoma↗
PubMed1987

Direct effects of biguanides on glucose utilization in vitro.

The effect of the biguanides metformin and phenformin on glucose utilization in isolated cells was studied with IM-9 human lymphocytes. Both agents stimulated glucose consumption from the incubation media. Detectable effects of metformin were seen at 33 mumol/L and detectable effects of phenformin were seen at 1.7 mumol/L. Both agents, at similar concentrations, also stimulated [3H] 2-deoxy-D-glucose uptake. Studies with phenformin indicated that biguanides increase the Vmax of uptake without changing the Km. In contrast to the biguanides, IM-9 cells insulin did not influence either glucose consumption or [3H] 2-deoxy-D-glucose uptake. These data provide evidence, therefore, that biguanides may directly influence the cellular utilization of glucose.

Blood Glucose↗
PubMed1987

Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus.

We studied total cell-associated A14-[125I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity; P less than 0.01]. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity; P less than 0.01). Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[125I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[125I]insulin, [125I]iodide, or [125I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity (P less than 0.01) after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% (P less than 0.01) after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.

Aged↗
PubMed1986

A14-[125I]monoiodoinsulin purified by different high-performance liquid chromatographic procedures and by polyacrylamide gel electrophoresis: preparation, immunochemical properties and receptor binding affinity.

Reversed-phase high-performance liquid chromatography (RP-HPLC) allows the rapid separation of A14-[125I]monoiodoinsulin directly from the iodination mixtures. It remains to be clarified, however, whether the RP-HPLC chromatographic conditions affect the properties of the purified tracer. In this study we prepared A14-[125I]insulin purified by polyacrylamide gel electrophoresis (PAGE) and by three different RP-HPLC mobile phases containing, respectively, ammonium acetate, sodium perchlorate and trifluoroacetic acid. The binding characteristics of all these tracers were examined using an insulin antiserum and insulin cell receptors. The specific radioactivity corresponded to the theoretical maximum for the RP-HPLC-purified tracers and was significantly lower for the PAGE-purified tracers. Significant differences were found in the binding of different tracers to the insulin antiserum: maximum binding ranged from 94 to 99% and was significantly lower for tracers purified by RP-HPLC eluents B and C; antiserum dilution giving 50% tracer binding was lower for tracers purified by RP-HPLC eluent B. The four insulin derivatives showed no difference in non-specific precipitation and in the affinity constant values calculated from the Scatchard analysis. No significant difference was found in the binding of the four insulin derivatives to the human-cultured IM-9 lymphocytes and to the human circulating monocytes. In conclusion, the present work demonstrates that the immunological properties of the A14-[125I]monoiodoinsulin purified by RP-HPLC may be partially affected by the composition of the mobile phase. In order to obtain a fully potent A14-[125I]insulin derivative and to have the possibility of comparing data from different laboratories, the chromatographic conditions must be taken into account.

Adult↗
PubMed1986

Regional variations of iodine nutrition and thyroid function during the neonatal period in Europe.

In order to evaluate further the possibility that transient hypothyroidism and hyperthyrotropinemia in newborn infants could result from a state of relative iodine deficiency, the urinary concentration of iodine, used as an index of the dietary intake of iodine was determined in casual urine samples collected in 1,076 full-term infants aged 3-6 days in 16 cities in 10 different European countries and in Toronto, Canada. In addition, the results obtained by programs of systematic neonatal screening for congenital hypothyroidism in the same areas were compared. There were marked regional differences in iodine nutrition during the neonatal period in Europe (median urinary iodine: 16.2 micrograms/dl in Rotterdam, the Netherlands, and 1.1 micrograms/dl in Freiburg, FRG. A low iodine supply in newborn populations was accompanied by, and probably explained, an elevated frequency of transient disorders of thyroid function in young infants. Iodine prophylaxis is urgently needed in some European countries not only for the prevention of goiter, but mostly for the prevention of impairment of thyroid function during the critical period of brain development.

Canada↗
PubMed1986

Serum thyroglobulin levels are elevated in newborns from iodine-deficient areas.

Newborn infants have elevated serum thyroglobulin (Tg) levels and reduced iodination of Tg. To determine whether a relationship exists between serum Tg levels and the degree of Tg iodination, 699 newborn infants were studied in 3 areas of Sicily: a normal iodine-sufficient (control) area and 2 iodine-deficient areas. In the iodine-sufficient area, the mean cord serum Tg level was 25.8 ng/ml (median, 18.0; n = 183). In the iodine-deficient areas, the serum Tg levels in newborns were significantly higher, with mean levels of 43.4 ng/ml (median, 29.7; n = 304; P less than 0.01) and 60.1 ng/ml (median, 48.0; n = 212; P less than 0.005), respectively. The higher serum Tg level at birth was not entirely due to increased cord serum TSH levels, since newborns from the iodine-deficient areas with serum TSH levels at birth similar to those in infants from the control area had higher serum Tg levels. Serum Tg levels correlated with the serum T3 to T4 ratio, but not with serum TSH, T4, or T3 levels. These data suggest that iodine availability, which affects the degree of thyroid Tg iodination, partially determines serum Tg levels at birth.

Fetal Blood↗
PubMed1986

Insulin internalization into monocytes is decreased in patients with type II diabetes mellitus.

We studied the internalization of [125I]insulin into circulating human monocytes, a cell type widely used for insulin binding studies. The internalization of [125I]insulin was assessed by both an acid extraction technique, which removes surface-bound insulin but not intracellular insulin, and by a trypsinization technique, which removes cell surface-bound hormone. After 5 h of incubation at 22 C, over 40% of the total cell-associated [125I]insulin was internalized into monocytes of normal subjects. This internalization was temperature dependent; the fraction of internalized hormone was progressively decreased when the incubation temperature was reduced from 37 to 4 C. Treatment of monocytes with increasing concentrations of 2,4-dinitrophenol also decreased [125I]insulin internalization, whereas dansylcadaverine, an inhibitor of transglutaminase, had no effect. Analysis by gel filtration of the internalized labeled hormone after 4 h of incubation at 22 C indicated that 50-60% of the label was degraded insulin, but detectable intact insulin was still present. Internalization of insulin was then studied in monocytes from eight obese patients (161% of ideal body weight) with type II diabetes mellitus. After 4 h of incubation at 22 C, the specific total monocyte-associated [125I]insulin was decreased compared to that in cells from 7 normal subjects [6.02 +/- 0.38% (+/- SE) vs. 3.91 +/- 0.31% of the total; P less than 0.001]. Moreover, the percentage of hormone that was internalized was also decreased from 41.4 +/- 1.2% of the total to 28.9 +/- 1.8% (P less than 0.001). In 20 nondiabetic obese subjects, specific cell-associated [125I]insulin was reduced to 3.9 +/- 0.3% (P less than 0.001). However, compared to that in normal subjects, the percentage of hormone that was internalized was not decreased (39.7 +/- 3.51% of the total). The present findings indicate that human circulating monocytes internalize [125I]insulin; this process is temperature and energy dependent; and monocytes from obese type II diabetic patients have a significantly decreased ability to internalize insulin. This decreased internalization may play a role in the cellular resistance to insulin that occurs in these patients.

Adult↗
PubMed1986

Prevention and treatment of endemic iodine-deficiency goiter by iodination of a municipal water supply.

A recently described method for the prevention and treatment of endemic iodine deficiency and goiter, introduction of iodine into a public water supply, was tested in Troina, a town of about 13,000 inhabitants in northeast Sicily. There, before initiation of the program, a goiter endemic of moderate severity was present, as evidenced by goiter prevalence of 55% in school children. Iodine deficiency in nongoitrous adults was indicated by daily urinary iodine excretion of 40.7 +/- 2.6 micrograms (mean +/- SE) and 24-h thyroid radioiodine uptake of 50.8 +/- 2.4%. Iodination of the water supply was initiated in November 1979 using a stream-splitting device that diverts a controlled fraction of the total water flow to a canister containing iodine crystals, where the water becomes saturated with iodine (approximately 300 mg/liter) before returning to the main stream. Except for a 15-month interruption during which governmental authorization of the program was being reconfirmed, treatment of the water has continued to the present time, initially at a level of 81 +/- 25 micrograms/liter (mean +/- SD) and since resumption at a level of 46.5 +/- 5 micrograms/liter. Iodination of the water was followed by a prompt and marked reduction in goiter prevalence, and by improvement in biochemical indices of iodine deficiency. By April 1983, overall goiter frequency in school children had declined to 6.1%, and large goiters (WHO Grade 2) had virtually disappeared. By January 1984, daily urinary iodine excretion had increased to 85.6 +/- 6.5 (SEM) micrograms and radioiodine uptake had decreased to 40.7 +/- 4.7%. Serum thyroid-related hormone concentrations were as follows (pretreatment vs. November-December 1983): T4, 5.8 +/- 0.3 vs. 8.4 +/- 0.3 microgram/dl; T3, 1.6 +/- 0.05 vs. 1.2 +/- 0.06 ng/ml; TSH, 3.7 +/- 0.2 vs. 2.2 +/- 0.1 microU/ml; all changes being statistically significant. By late 1983, serum T4, T3, and TSH values in Troina were almost identical to those in Catania, a community in which iodine deficiency is not present (goiter prevalence in school children, 2.2%). In contrast, in Troina serum T4 concentrations were significantly higher and serum TSH concentrations were significantly lower than those in Maniaci, a iodine-deficient town near Troina, in which the water was not iodinated. Iodinated water was well tolerated by the population of Troina, and no adverse effects of water iodination, including any increase in the frequency of hyperthyroidism, was observed. At present prices, the cost of the water iodination program in Troina would be approximately 4 cents (U.S.) per person per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

The effect of phenformin and other adenosine triphosphate (ATP)-lowering agents on insulin binding to IM-9 human cultured lymphocytes.

In the present study, we investigated the mechanism by which the antidiabetic drug phenformin increases insulin binding to its receptors in IM-9 human cultured lymphocytes. After a 24-hr preincubation, phenformin induced a twofold increase in specific 125I-insulin binding, and removal of phenformin was followed 6 hr later by a return in binding to control levels. This effect of phenformin on insulin binding was not a consequence of either inhibition of cell growth, changes in cellular cyclic adenosine monophosphate (AMP) levels, or changes in guanosine triphosphate (GTP) content. Since phenformin is known to inhibit various aspects of cellular energy metabolism, the relationship between 125I-insulin binding and energy metabolism in IM-9 cells was investigated. The phenformin-induced increase in insulin binding to IM-9 cells was related to a time- and dose-dependent decrease in ATP levels. Other agents that lowered ATP levels, including antimycin, dinitrophenol, and 2-deoxyglucose, also raised insulin binding. These studies indicated, therefore, that phenformin enhances insulin binding to receptors on IM-9 cells and that this effect on insulin receptors may be related to alterations in metabolic functions that are reflected by a lowering of ATP levels.

Adenosine Triphosphate↗
PubMed1984

ATP and other nucleoside triphosphates inhibit the binding of insulin to its receptor.

ATP, in a dose-dependent manner, inhibited the binding of 125I-insulin to its receptor in rat liver and human placental membranes. With rat liver plasma membranes an effect of ATP was detected at concentrations between 1.0 and 2.5 mmol/L, and maximal effects were seen at 10.0 mmol/L where binding was decreased by approximately 40%. The effect of ATP was one half-maximal within 10 minutes and maximal within 60 minutes. Scatchard analysis indicated that ATP was acting primarily to change the binding affinity of the insulin receptor. The effect of ATP was mimicked by CTP, GTP, and UTP, but not by ADP, 5'-AMP, 3'-AMP, 3'5'-cyclic AMP and adenosine. The ATP analog AMP-PNP had a potency approximately 10% that of ATP. The effect of ATP was not significantly influenced by inhibitors of phosphoprotein kinases and phosphoprotein phosphatases. In human placental membranes, ATP had a similar effect in inhibiting 125I-insulin binding to its receptor. Moreover, ATP was active in inhibiting insulin binding to purified human placental insulin receptors at 0.01 mmol/L, a concentration 1/100 of that needed for inhibiting binding to intact membranes. These studies indicate, therefore, that ATP and other nucleoside triphosphates influence the ability of the insulin receptor to bind insulin.

Adenosine Monophosphate↗
PubMed1984

Dual regulation of glycogen metabolism by insulin and insulin-like growth factors in human hepatoma cells (HEP-G2). Analysis with an anti-receptor monoclonal antibody.

Insulin and the insulinlike growth factors (IGF-I and IGF-II) are members of a family of hormones that regulate the metabolism and growth of many tissues. Cultured HEP-G2 cells (a minimal deviation human hepatoma) have insulin receptors and respond to insulin by increasing their glycogen metabolism. In the present study with HEP-G2 cells, we used 125I-labeled insulin, IGF-I, and IGF-II to identify distinct receptors for each hormone by competition-inhibition studies. Unlabeled insulin was able to inhibit 125I-IGF-I binding but not 125I-IGF-II binding. A mouse monoclonal antibody to the human insulin receptor that inhibits insulin binding and blocks insulin action inhibited 75% of 125I-insulin binding, but inhibited neither 125I-IGF-I nor 125I-IGF-II binding. When glycogen metabolism was studied, insulin stimulated [3H]glucose incorporation into glycogen in a biphasic manner; one phase that was 20-30% of the maximal response occurred over 1-100 pM, and the other phase occurred over 100 pM-100 nM. The anti-receptor monoclonal antibody inhibited the first phase of insulin stimulation but not the second. Both IGF-I and IGF-II stimulated [3H]glucose incorporation over the range of 10 pM-10 nM; IGF-I was three to fivefold more potent. The monoclonal antibody, however, was without effect on IGF regulation of glycogen metabolism. Therefore, these studies indicate that insulin as well as the IGFs at physiological concentrations regulate glycogen metabolism in HEP-G2 cells. Moreover, this regulation of glycogen metabolism is mediated by both the insulin receptor and the IGF receptors.

Animals↗
PubMed1984

Transient impairment of thyroid function in newborn from an area of endemic goiter.

Thyroid function was studied in newborn from 3 areas of Sicily in which iodine intake is normal (area A), moderately decreased (area B), and severely decreased (area C). In the latter 2 areas, there is a high incidence of goiter and in area C endemic cretinism is present. TSH and T4 were measured in the cord serum of 5673 newborn from area A, 2096 from area B, and 184 from area C. The mean TSH value was significantly higher in areas C (P less than 0.001) and B (P less than 0.005) when compared to area A; moreover, in both endemic goiter areas the mean cord serum T4 was significantly reduced (P less than 0.01). All infants with cord serum TSH levels above 50 microU/ml were recalled because of the suspicion of congenital hypothyroidism. Such values were found in 41 of the 7953 infants (0.52%) with an increasing frequency from area A (9:5673 = 0.16%) to area B (14:2096 = 0.67%) to area C (18:184 = 9.78%). At the time of the recall examination [mean age, 32 +/- 8 (SD) days], 3 of the 41 recalled infants had died. Of the remaining 38 infants, 3 patterns evolved: 1) 23 had normal serum TSH and T4 values and were not studied further (false positives). 2) Eleven had elevated serum TSH and normal T4 values. They were reevaluated again after 3-6 weeks: all had normal values (transient hyperthyropinemia ). 3) Four infants had both high serum TSH and low serum T4 values (2 from area A and 2 from area C). They were diagnosed as having congenital hypothyroidism and treated with T4. At 10-13 months of age, after treatment withdrawal, the 2 infants from area A had permanent congenital hypothyroidism due to thyroid agenesis whereas the 2 infants from area C were euthyroid (transient congenital hypothyroidism). The present studies indicate, therefore, that in newborn from areas of iodine deficiency there is a higher frequency of elevated TSH levels and low T4 values than is found in areas where iodine intake is normal. This frequency is correlated to the degree of the iodine deficiency. The data suggest that the impairment of thyroid function at birth may be a transient phenomenon. The duration and the severity of the transient neonatal hypothyroidism, however, is greatly variable and its evolution unpredictable.

Congenital Hypothyroidism↗
PubMed1984

Thyroglobulin release after graded endogenous thyrotropin stimulation in man: lack of correlation with thyroid hormone response.

The serum thyroglobulin (Tg), T3, and T4 responses to graded endogenous TSH stimulation were examined in 30 normal subjects for up to 96 h after TRH administration. Increasing TSH rises were elicited by TRH administration as follows: 1) 500 micrograms iv as a single bolus in 10 subjects [mean peak serum TSH, 14.3 +/- 1.8 (SE) microU/ml]; 2) 1000 micrograms infused iv in 2 h in 10 subjects (mean peak TSH, 25.5 +/- 2.6 microU/ml); 3) 40 mg orally in 10 subjects (mean peak TSH, 27.5 +/- 3.0 microU/ml, with a delayed and more prolonged rise). Nine subjects received saline and were used as controls. A significant serum T3 and T4 rise followed the TSH increase in all subjects, and the mean peak value was always reached 4 h after TRH. In contrast, a significant serum Tg increase occurred only in 3, 6, and 9 subjects after 500 micrograms, 1000 micrograms, and 40 mg TRH, respectively. In addition, the time of the Tg peak and its duration was extremely variable but it was always delayed in respect to serum T3 and T4 peaks, occurring 6 to 72 h after TRH administration. No correlation was found between serum Tg and T3 or T4 increases after TRH in any of the three groups. These studies indicate that a significant Tg release in man usually occurs only after intense and prolonged TSH stimulation of the thyroid. In addition, the Tg increase is delayed in respect to the thyroid hormone increase and it is not correlated with them.

Administration, Oral↗
PubMed1983

Solitary autonomously functioning thyroid nodules and iodine deficiency.

The prevalence, characteristics, and evolution of autonomously functioning thyroid nodules (AFTN) were studied in two population groups from northeastern Sicily. One group was living in an iodine-deficient area and another was living in an iodine-sufficient area. The prevalence of AFTN was significantly higher in the iodine-deficient area (4.4% of total patients vs. 2.7%). No significant difference between the two areas was observed in sex and age distribution and size of the nodules. In addition, a higher percentage of patients with toxic nodules (1.3%) was found in the group from the iodine-deficient area. Furthermore, in a selected group of patients followed for 1-6 yr, a higher percentage of patients from the iodine-deficient area had either an increase in the size of the lesion or an increase in thyroid hormone production leading to toxicity. These data suggest that iodine deficiency is one possible factor in the development of AFTN and that iodine deficiency may also be involved in the increased frequency of toxic evolution of these lesions.

Adolescent↗
PubMed1983

Metformin normalizes insulin binding to monocytes from obese nondiabetic subjects and obese type II diabetic patients.

In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally). Before drug administration, 125I-insulin binding to monocytes was decreased in obese subjects and diabetic patients. After metformin administration, an increase in insulin binding to peripheral monocytes was observed in seven of eight obese nondiabetic subjects (3.57 +/- 0.43 to 4.69 +/- 0.59% bound at 10(7) monocytes, mean +/- SEM, P less than 0.01) and in all diabetic patients (3.21 +/- 0.21 to 5.22 +/- 0.34, P less than 0.01). Scatchard plots indicated that the increased binding was due to an increase in the receptor number. In contrast, no significant change in insulin binding was found in normal controls after metformin administration (5.31 +/- 0.14 and 4.70 +/- 0.12). These studies indicate that metformin normalizes the binding of insulin to its receptor in obese subjects and diabetic patients. It is suggested, therefore, that the action of metformin on the insulin receptor may be one of the mechanisms of the antidiabetic effect of this drug.

Acetates↗
PubMed1982

Insulin stimulation of nucleoside triphosphatase activity in isolated nuclear envelopes.

The activity of nucleoside triphosphatase, an enzyme that regulates nuclear messenger RNA transport, was measured in highly purified nuclear envelopes isolated from rat liver. Addition of picomolar concentrations of insulin to freshly prepared nuclear envelopes directly increased the enzyme activity. The major effect of insulin on this enzyme was to increase the maximum velocity of its activity; no significant effects were seen on the affinity constant. These studies raise the possibility, therefore, that the nuclear envelope is a site where insulin regulates nuclear functions.

Animals↗