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R Vigneri

Publications and source records attributed to R Vigneri.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-alpha gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity.

In the present study we measured PC-1 content, tumour necrosis factor (TNF)-alpha gene expression, and insulin stimulation of insulin receptor tyrosine-kinase activity in adipose tissue from non-obese, non-diabetic subjects. These parameters were correlated with in vivo insulin action as measured by the intravenous insulin tolerance test (Kitt values). PC-1 content was negatively correlated with Kitt values (r = -0.5, p = 0.04) and positively with plasma insulin levels both fasting (r = 0.58, p = 0.009) and after 120 min during oral glucose tolerance test (OGTT) (r = 0.67, p = 0.002). Moreover, adipose tissue PC-1 content was higher in relatively insulin-resistant subjects (Kitt values lower than 6) than in relatively insulin-sensitive subjects (Kitt values higher than 6) (525 +/- 49 ng/mg protein vs 336 +/- 45, respectively, p = 0.012). Adipose tissue insulin receptor tyrosine-kinase activity in response to insulin was significantly lower at all insulin concentrations tested (p = 0.017, by two-way analysis of variance test) in insulin-resistant than in insulin-sensitive subjects (Kitt values lower or higher than 6, respectively). In contrast to PC-1, no significant correlation was observed between adipose tissue TNF-alpha mRNA content and Kitt values, and plasma insulin levels, both fasting and at after 120 min during OGTT. Also, no difference was observed in TNF-alpha mRNA content between subjects with Kitt values higher or lower than 6. These studies in adipose tissue, together with our previous studies in skeletal muscle raise the possibility that PC-1, by regulating insulin receptor function, may play a role in the degree of insulin sensitivity in non-obese, non-diabetic subjects.

Adipose Tissue↗
PubMed1997

The insulin receptor content is increased in breast cancers initiated by three different oncogenes in transgenic mice.

The Insulin Receptor (IR) is a potential oncogene for mammary epithelial cells since its content is increased in most human breast cancer specimens, and both ligand-dependent malignant transformation and ligand-dependent enhanced growth occurs in cultured breast cells overexpressing the IR. To better understand whether the IR plays a role in mammary carcinogenesis which is independent of other initiation factors, we measured IR content in transgenic mouse models of breast cancer induced by 3 known oncogenes (Wnt-1, Neu, and Ret). Insulin receptor content was measured by a specific radioimmunoassay. In normal mammary gland tissues IR content was 14.6 +/- 1.4 ng/mg of protein (mean +/- SEM, n = 6). In the 3 cancers IR content was elevated (Neu = 36.1 +/- 4.6, n = 8, p < 0.002; Wnt-1 = 38.3 +/- 2.6, n = 13, p < 0.001; and Ret = 53.6 +/- 7.1, n = 7, p < 0.001). These data indicate that IR overexpression, in addition to being a potential oncogene, is increased in mouse tumors initiated by other oncogenes, and therefore may also play a supportive role in the growth of breast cancers.

Animals↗
PubMed1997

In situ evidence of neoplastic cell phagocytosis by macrophages in papillary thyroid cancer.

We evaluated the occurrence, tissue distribution, and prognostic value of tumor-associated macrophages in 121 papillary thyroid carcinomas using immunohistochemical staining with anti-CD68 antibody in archival paraffin-embedded sections. Lymphocytic infiltration and dendritic cell presence were also evaluated. Three groups were identified according to the presence and characteristics of macrophages: 1) tumors without evidence of infiltrating macrophages: (n = 35); 2) tumors with infiltrating macrophages but no evidence of neoplastic cells phagocytosis (n = 68); and 3) tumors with infiltrating macrophages and in situ evidence of active neoplastic cell phagocytosis (n = 18). Neoplastic cell phagocytosis by macrophages was positively correlated with both lymphocytic infiltration and dendritic cells (P = 0.0000), whereas it was negatively correlated with vascular invasion (P = 0.0032). Distant metastases developed in none of the 18 tumors with neoplastic cell phagocytosis, but occurred in 15 of 103 of the remaining tumors (P = 0.0647) and were significantly and negatively associated with lymphocytic infiltration or dendritic cells. The present study indicates, therefore, that immune reaction, involving neoplastic cell phagocytosis by macrophages and lymphocytic infiltration, plays a role in the development of distant metastases in patients with papillary thyroid cancer.

Adult↗
PubMed1997

Early diagnosis by genetic analysis of differentiated thyroid cancer metastases in small lymph nodes.

We report a PCR-based technique for detecting thyroid cancer metastases in small nodes <1.5 cm diameter by the amplification of thyroid specific transcripts TSH-receptor and thyroglobulin. A 100% correspondence with the histopathological diagnosis was observed in the 41/46 nodes (89%) in which an adequate sample was obtained at fine needle aspiration. The genetic analysis resulted more sensitive and accurate than both the cytological analysis (28% inadequate samples, 17% false negative diagnoses) and the thyroglobulin measurement in the aspirates (39% false negatives). The PCR-based genetic analysis may provide a useful tool for diagnosis and follow-up of thyroid cancer.

Biopsy, Needle↗
PubMed1997

Negative/low expression of the Met/hepatocyte growth factor receptor identifies papillary thyroid carcinomas with high risk of distant metastases.

To investigate the clinical impact of Met/hepatocyte growth factor receptor (HGF-R) expression in thyroid cancer we studied 163 thyroid carcinomas (129 papillary, 21 follicular, and 13 anaplastic) from patients followed-up for 25-147 months postthyroidectomy. Forty-nine thyroid adenomas were also studied. Met/HGF-R expression was evaluated by semiquantitative immunohistochemistry, measuring both the proportion (scale of 0-5) and the intensity (scale, 0-5) of stained cells and calculating a total score (scale of 0-10). Met/HGF-R was absent in the normal thyroid tissue, absent or focally expressed in follicular and anaplastic tumors, and expressed at various levels in most papillary carcinomas, including microcarcinomas. Papillary carcinomas were thus categorized as having negative/low Met/HGF-R (n = 50; total score, < or = 5) or high Met/HGF-R expression (n = 70; total score, > 5). High Met/HGF-R was inversely associated with vascular invasion (P = 0.0308), but not with other prognostic factors. Negative/low Met/HGF-R expression was the most effective predictor by multivariate Cox analysis of distant metastases (hazard ratio = 9.71; P = 0.0036), higher than extrathyroid invasion (hazard ratio = 4.25; P = 0.0181), age (< or = 45 vs. > 45 yr; hazard ratio = 3.99; P = 0.0099), and vascular invasion (hazard ratio = 3.19; P = 0.0358). These findings suggest a role for Met/HGF-R in papillary thyroid cancer and its clinical use to select patients with a high risk of distant metastases.

Adenocarcinoma, Follicular↗
PubMed1997

Hexokinase shift to mitochondria is associated with an increased sensitivity to glucose in rat pancreatic islets.

When rat pancreatic islets are incubated in 5.5 or 16.7 mmol/l glucose for 3 h, an increased sensitivity is observed in islets pre-exposed to high glucose, as indicated by a shift to the left of the glucose dose-response curve (EC50 7.1 +/- 0.9 and 11.5 +/- 1.2 in high- and low-glucose-exposed islets, respectively; n = 5, P < 0.05). To investigate the mechanism(s) responsible for this effect, we measured hexokinase and glucokinase activity both in the cytosolic fraction and in a mitochondrion-enriched fraction, since binding to the outer mitochondrial membrane has been reported to result in an increased enzyme activity. In islets cultured at 16.7 mmol/l glucose, the cytosolic hexokinase activity was similar to control islets, but mitochondrial enzyme activity was significantly increased (124 +/- 7 vs. 51 +/- 9 nmol x microg(-1) x 90 min(-1), P < 0.01). As a consequence, the cytosolic:mitochondrial fraction ratio was altered in comparison with control islets. In contrast, glucokinase activity in the two groups of islets was similar in the cytosolic fraction and undetectable in the mitochondrial fraction. Hexokinase I quantitation by Western blot confirmed the enzyme translocation from the free cytosolic to the mitochondria-bound form in islets cultured at 16.7 mmol/l glucose. Glucose-induced alterations were reversible after 1 h exposure to 5.5 mmol/l glucose. Moreover, in islets exposed to 16.7 mmol/l glucose, inhibition of hexokinase binding to mitochondria by the addition of 20 nmol/l dicyclohexylcarbodiimide resulted in no increase of glucose sensitivity (EC50 10.9 +/- 0.4, n = 3, similar to that of control islets). These data indicate that after chronic exposure to high glucose, the beta-cell becomes more sensitive to glucose before eventually getting desensitized. This increased sensitivity is associated with (and may be due to) an increased hexokinase activity secondary to a subcellular shift of the enzyme from the free cytosolic to the mitochondria-bound, more active form.

Animals↗
PubMed1997

Insulin receptor expression and clinical outcome in node-negative breast cancer.

The insulin receptor (IR), a ligand-activated tyrosine kinase, is present in breast cancers, but its relationship to patient survival is unknown. The IR was measured in 584 tumor specimens from patients with node-negative breast carcinoma by frozen-section immunohistochemistry and light microscopy. The immunostaining signal was quantitated in relation to both the staining intensity and the proportion of positive malignant epithelial cells. Analyses indicated that patients with tumors with undetectable IR content in malignant epithelial cells (260 cases) had a relatively lower predicted 5-year disease-free survival (DFS) (69% +/- 3%) than did patients with tumors with detectable IR content (324 cases; DFS 76% +/- 3%, p = .032). The significance of IR content in these breast malignant epithelial cells was then analyzed along with patient age, tumor size, progesterone and estrogen receptor status, p53 accumulation, and S-phase. Multivariate analysis of these data revealed that after adjustment for these other variables, IR content was the strongest independent predictive factor for DFS (relative risk = 1.73, p = .005). Interestingly, in a small subset of patients with very high IR content (n = 62), DFS was decreased. These data indicate that IR content in node-negative breast cancers is a significant major predictor of reduced DFS. Moreover, they raise the possibility that the measurement of IR content might provide important information concerning breast cancer biology.

Adult↗
PubMed1996

PC-1 content in skeletal muscle of non-obese, non-diabetic subjects: relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity.

Insulin sensitivity varies widely in non-obese, non-diabetic subjects, and we have previously reported that in vivo insulin action correlates with in vitro insulin stimulated insulin receptor tyrosine-kinase activity in skeletal muscle. Plasma membrane glyco-protein PC-1 content is elevated in fibroblasts of insulin-resistant subjects, and expression of PC-1 cDNA in cultured cells reduces both insulin receptor tyrosine-kinase activity and the biological actions of insulin. In the present study we investigated non-obese, non-diabetic subjects and found a significant negative correlation between muscle PC-1 content and both in vivo insulin action as measured by the intravenous insulin tolerance test (r = -0.51, p = 0.035) and the sensitivity (ED50) of in vitro insulin stimulation of insulin receptor tyrosine-kinase activity (r = 0.66, p = 0.027). These studies indicate, therefore, that increased muscle PC-1 content is associated with reduced insulin action both in vivo and in vitro. Moreover, they suggest a possible role for PC-1 in regulating insulin receptor function in human skeletal muscle.

Blood Glucose↗
PubMed1996

Longitudinal study on goiter prevalence and goitrogen factors in northeastern Sicily.

A longitudinal study was carried out in an area of endemic goiter of north-eastern Sicily. Three different surveys (in 1977, 1983 and 1994) evaluated the epidemiological prevalence of goiter in schoolchildren of the endemic area (towns of Bronte, Troina and Maniaci) in comparison to an iodine sufficient control area (Catania). Biochemical studies were also performed on urinary iodine and thiocyanate (SCN) excretion and 131I thyroid uptake. In the town of Troina an experimental program of active iodine prophylaxis was carried out from 1979 to 1987 by iodinating the municipal water supply. The aim of this study was to evaluate the effect of an active iodine prophylaxis program in comparison to the "silent iodoprophylaxis" due to improved economic conditions and widespread introduction of industrially produced food. In the 1977-94 period a significant decrease of goiter prevalence in schoolchildren was observed in all areas where no active iodoprophylaxis had been introduced. An abnormal prevalence of goiter, however, was still present in Bronte (12.1%) and Maniaci (25.9%) schoolchildren in respect to Catania (0.7%). In Troina, goiter prevalence decreased from 52.2 to 6.1% after only five years of active iodine prophylaxis (1983). It increased to 8.4% seven years after the program was discontinued (1994). In all areas studied average urinary iodine excretion increased by 70-100 micrograms/day except in the more rural area at Maniaci. During the same period urinary SCN values decreased by 30-40% and were lower in Troina (non volcanic soil) than in other towns studied. The balance between iodine and SCN intake appears a relevant factor in the etiology of endemic goiter in these areas and the iodine/SCN ratio inversely correlated with goiter prevalence. The persistence of endemic goiter in spite of the important changes in life style and socio-economic conditions if compared to the dramatic amelioration obtained by an active iodine prophylaxis program, confirms the inadequacy of the silent iodine prophylaxis, and further supports the need of an immediate introduction of active iodine prophylaxis in the areas of endemic goiter in Sicily.

Antithyroid Agents↗
PubMed1996

Interleukin-1 blocks insulin and insulin-like growth factor-stimulated growth in MCF-7 human breast cancer cells by inhibiting receptor tyrosine kinase activity.

Interleukins-1 (IL-1s) are known to inhibit the growth of cultured breast cancer cells. We examined the effects of IL-1 alpha and IL-1 beta on insulin and insulin-like growth factor I (IGF-I) stimulation of cell growth and found that both IL-1s inhibited anchorage-dependent and independent growth of MCF-7 breast cancer cells. In cells incubated with IL-1 beta (100 U/ml), insulin receptor (IR) protein and messenger RNA were increased by 100%, while IGF-I receptor protein and transcript were not significantly changed. These data were confirmed by binding studies. Incubation of MCF-7 cells with IL-1s led, however, to a significant inhibition of IR and IGF-I receptor autophosphorylation (-55%) and phosphotransferase activity (-65%). Also, in 3T3/ HIR rat fibroblasts, transfected with and overexpressing IR, IL-1s decreased insulin-stimulated cell growth in soft agar and IR tyrosine kinase activity. The present findings suggest that IL-1s antagonize the insulin and IGF-I mitogenic effects in MCF-7 cells by blocking the receptor tyrosine kinase activity that is crucial for the mitogenic effect of these factors.

3T3 Cells↗
PubMed1996

Cold thyroid nodule reduction with L-thyroxine can be predicted by initial nodule volume and cytological characteristics.

In a previous study we demonstrated that a 1-yr treatment with L-T4 induces substantial nodule volume reduction (> or = 50%) in approximately 40% of patients with a benign solitary cold thyroid nodule. The present prospective study investigated whether it is possible to identify, before starting L-T4 treatment, nodules with a high probability to shrink in response to L-T4. We recorded several clinical and cytological features in a continuous series of 42 patients with a cold nodule and related them to the nodule volume response to 1-yr treatment with L-T4. Fisher discriminant analysis showed that a combination of some cytological features (colloid, degenerative changes, cellular hyperplasia, and fibrosis) and initial nodule volume can be used for predicting nodule volume reduction. In fact, although only 33% of all nodules shrank, 62% of colloid nodules and 57% of small degenerative nodules shrank. None of the hyperplastic or fibrotic nodules shrank. These results were validated in a different retrospective series of 46 patients and allowed us to predict nodule reduction in over 80% of the cases.

Humans↗
PubMed1996

Overexpression of membrane glycoprotein PC-1 in MDA-MB231 breast cancer cells is associated with inhibition of insulin receptor tyrosine kinase activity.

MDA-MB231 human breast cancer cells are unresponsive to insulin and contain a glycoprotein inhibitor of insulin-stimulated insulin receptor (IR) tyrosine kinase activity. Prior studies in both fibroblasts from insulin- resistant non-insulin-dependent diabetes mellitus patients and transfected cells indicate that overexpression of membrane glycoprotein PC-1 reduces IR tyrosine kinase activity. In the present study, we measured PC-1 content and activity in MDA-MB231 and four other human breast cancer cell lines. We observed that PC-1 expression was 3- to 30-fold higher in MDA-MB231 cells when compared with the other breast cell lines. Wheat germ agglutinin extracts of MDA-MB231 cells inhibited IR tyrosine kinase activity. Treatment of these extracts with an antibody to PC-1 significantly reduced their ability to inhibit insulin-stimulated IR tyrosine kinase activity. In addition, when cell clones with different PC-1 activity were selected from MDA-MB231 cells, we found an inverse correlation (r = -0.741, P = 0.006) between the PC-1 activity and the insulin-stimulated IR autophosphorylation. A similar inverse correlation was observed in cell clones derived from the insulin-responsive breast cancer cell line MCF-7. By both immunoprecipitation and cross-linking studies we found PC-1 to be associated with IR. These studies indicate, therefore, that overexpression of PC-1 in MDA-MB231 cells may account, at least in part, for the reduced IR tyrosine kinase activity and suggest that PC-1 is a specific modulator of the IR activity in breast cancer cells.

Breast Neoplasms↗
PubMed1996

Fast reversibility of glucose-induced desensitization in rat pancreatic islets. Evidence for an involvement of ionic fluxes.

The present study was done to achieve a better understanding of the role of ionic flux alterations in glucose-induced desensitization of pancreatic beta-cells. Moreover, we investigated the reversibility of glucose-induced desensitization after different times of exposure to high glucose to ascertain the time necessary for desensitization reversal and to determine whether it depends on the length of high glucose exposure. Glucose desensitization was obtained by incubating rat pancreatic islets for 6 h in CMRL medium containing 16.7 mmol/l glucose. At the end of this period, insulin release, 86Rb efflux, and 45Ca uptake were measured in parallel experiments. In islets cultured at 16.7 mmol/l glucose, maximal glucose-induced insulin release was reduced (848 +/- 97 pg x islet-1 x 30 min-1) in comparison to islets incubated at 5.5 mmol/l glucose (1,436 +/- 144, n = 7, P < 0.01). In contrast, insulin content was similar in the two groups, being 41.0 +/- 2.7 and 47.8 +/- 2.2 ng/islet in islets exposed to 16.7 or 5.5 mmol/l glucose, respectively (P = 0.167). The effect of glucose on both 86Rb efflux and 45Ca uptake was also significantly reduced in 16.7 mmol/l glucose-cultured islets. 86Rb efflux was inhibited only 19 +/- 4% in islets cultured at high glucose with respect to 56 +/- 7% in control islets (n = 5, P < 0.001). 45Ca uptake was 10.5 +/- 1.7 pmol/islet (mean +/- SE, n = 9) in islets cultured at high glucose with respect to 19.7 +/- 2.4 pmol/islet in control islets (P < 0.001). In contrast, the effect of glyburide (10 micromol/l) on insulin release, 86Rb efflux, and 45Ca uptake was similar in islets exposed to 5.5 or 16.7 mmol/l glucose. All the abnormalities observed in islets cultured at 16.7 mmol/l glucose were promptly and simultaneously reversible after islets were transferred in culture medium at 5.5 mmol/l glucose; both insulin secretion and glucose effects on 86Rb efflux and 45Ca uptake returned to values similar to control islets within 5 min. Also, islets exposed to high glucose for a longer period (24 h) recovered from both secretory and ionic abnormalities after 5 min of incubation in CMRL medium at 5.5 mmol/l glucose. Reversal from glucose desensitization was slower (45 - 60 min) when islets were incubated at 5.5 mmol/l glucose in Krebs-Ringer HEPES buffer instead of CMRL medium. The present data suggest that ion flux and consequent membrane-potential changes play a key role in the mechanism leading to glucose-induced desensitization of pancreatic beta-cells. Because a normal response to glyburide was observed in islets exposed to high glucose, a proximal signal defect for closure of K+ channels rather than an intrinsic defect in the channel is likely.

Animals↗
PubMed1995

Levothyroxine and potassium iodide are both effective in treating benign solitary solid cold nodules of the thyroid.

OBJECTIVE: To determine the effectiveness of levothyroxine and potassium iodide in treating patients with benign solitary cold thyroid nodules. DESIGN: Randomized controlled study. SETTING: Outpatient clinic at a university hospital. PATIENTS: 80 patients with solitary solid cold thyroid nodules found to be benign at cytologic examination were randomly assigned to no treatment, suppressive levothyroxine (thyroid-stimulating hormone level, < 0.3 mU/L), or low-dose potassium iodide (2 mg every 2 weeks). Seventy patients completed the 1-year study. After 1 year, patients receiving treatment discontinued drug therapy and were re-evaluated 4 months later; patients receiving no treatment were given levothyroxine and were followed for a second year. MEASUREMENTS: Nodule volume was measured by ultrasonography at 4-month intervals by an observer masked to treatment assignment. RESULTS: Mean nodule volume decreased by 40% of the basal volume in the 23 patients receiving levothyroxine (P < 0.001) and by 23% of the basal volume in the 25 patients receiving potassium iodide (P = 0.053). Volume slightly increased in the 22 untreated patients (P = 0.085). A clinically relevant reduction in nodule volume (> or = 50%) was observed in 9 of 23 patients treated with levothyroxine, in 5 of 25 patients treated with potassium iodide, and in none of 22 untreated patients (P = 0.004). Only nodules with a volume of 10 mL or less were reduced; nodules with volumes of 5 mL or less shrank most frequently. Nodule volume did not relevantly increase in treated patients but did increase in 3 of the 22 untreated patients. Drug withdrawal resulted in an increased mean nodule volume (P = 0.004) after 4 months. CONCLUSIONS: Levothyroxine and, to a lesser extent, potassium iodide are effective in arresting the growth or in reducing the volume of benign solitary solid cold thyroid nodules, especially small ones; discontinuation of therapy may result in resumed nodule growth.

Aged↗
PubMed1995

Insulin receptor overexpression in 184B5 human mammary epithelial cells induces a ligand-dependent transformed phenotype.

To determine the role of the insulin receptor overexpression in breast epithelial cell transformation, the 184B5 human breast epithelial cell line was transfected with human insulin receptor cDNA. In two cell lines transfected with and overexpressing human insulin receptors (IR) (223.8 and 184.5 ng IR/10(6) cells), but not in untransfected cells, insulin binding and tyrosine kinase activity were elevated, and insulin induced a dose-dependent increase in colony formation in soft agar.

Binding Sites↗
PubMed1995

Copper addition prevents the inhibitory effects of interleukin 1-beta on rat pancreatic islets.

Since copper [Cu(II)] is a necessary cofactor for both intra-mitochondrial enzymes involved in energy production and hydroxyl scavenger enzymes, two hypothesised mechanisms for action of interleukin-I beta (IL-1 beta), we studied whether Cu(II) addition could prevent the inhibitory effect of IL-1 beta on insulin release and glucose oxidation in rat pancreatic islets. Islets were incubated with or without 50 U/ml IL-1 beta, in the presence or absence of various concentrations of Cu(II)-GHL (Cu(II) complexed with glycyl-L-histidyl-L-lysine, a tripeptide known to enhance copper uptake into cultured cells). CuSO4 (1-1000 ng/ml) was used as a control for Cu(II) effect when present as an inorganic salt. At the end of the incubation period, insulin secretion was evaluated in the presence of either 2.8 mmol/l (basal insulin secretion) or 16.7 mmol/l glucose (glucose-induced release). In control islets basal insulin secretion was 92.0 +/- 11.4 pg.islet-1 h-1 (mean +/- SEM, n = 7) and glucose-induced release was 2824.0 +/- 249.0 pg.islet-1 h-1. In islets pre-exposed to 50 U/ml IL-1 beta, basal insulin release was not significantly affected but glucose-induced insulin release was greatly reduced (841.2 +/- 76.9, n = 7, p < 0.005). In islets incubated with IL-1 beta and Cu-GHL (0.4 mumol/l, maximal effect) basal secretion was 119.0 +/- 13.1 pg.islet-1 h-1 and glucose-induced release was 2797.2 +/- 242.2, (n = 7, p < 0.01 in respect to islets exposed to IL-1 beta alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗