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A Belfiore

Publications and source records attributed to A Belfiore.

At least 55 records · Page 3Linked to original sources
PubMed1993

The thymus hypocholesterolemic factor (TphF): a bovine thymic superoxide dismutase active on HMG-CoA reductase.

1. This work describes the further biochemical characterization of a new calf thymus protein (TphF) and its primary structure. 2. The amino acid sequences, obtained after sequence analysis of peptides derived from the endoproteinase Lys-C digestion, were subjected to a "Protein Data Bank Search" and were found to be identical with regions of bovine superoxide-dismutase (SOD). 3. These data together with those showing the identical electrophoretic migration of SOD and TphF, their same isoelectric point and their immunoreactivity with anti-SOD antibodies, confirm the similarity of these two proteins.

Amino Acid Sequence↗
PubMed1993

Effect of ascorbic acid administration on B and E apoproteins in rats fed a cholesterol enriched diet.

The effect of ascorbic acid on cholesterol metabolism is very well documented; it is ascribed to the activation of this vitamin on cholesterol 7 alpha-hydroxylase (EC 1.14) that activates the catabolism of cholesterol. In this paper we have studied the effect of the administration of ascorbic acid on B and E apoproteins of rats fed a diet enriched with 1.5% of cholesterol. The results obtained show that ascorbic acid is able to affect cholesterol metabolism by modifying the serum levels of apo B in total serum and in lipoprotein classes of density less than 1.050 g/ml. Moreover the ascorbic acid treatment reduced the amount of cholesterol and triglycerides in all lipoprotein classes examined. No significant change of total serum apo E was observed following ascorbic acid administration.

Animals↗
PubMed1993

Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity.

In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.

Breast Neoplasms↗
PubMed1993

Patterns of line bisection in patients suffering from unilateral spatial neglect.

Thirteen patients suffering from Unilateral Spatial Neglect and 6 Right Brain Damaged Control Patients were tested on a line bisection task in order to verify peculiar patterns of error. Stimuli were arranged in order to avoid confounding the effects of line length and line position in the space. Two parameters of rightward displacement of setting point were used: 1) the distance of patient's setting point from actual line midpoint, and 2) the deduced left end-point of the line that patient took into account. Results showed that: 1) the rightward extension of lines did not lead to a consistent rightward displacement of setting point; 2) error significantly increased as lines extended more than 10 cm in the left hemispace; 3) the USN severity amplified the degradation of leftmost portion of stimuli until the deduced left endpoint of all space/length conditions was aligned on the left of patient's sagittal midplane. The interpretation of these results points to the particular arrangement of neurons directing attention on specific portions of the visual field.

Attention↗
PubMed1992

Insulin receptor expression and function in human breast cancer cell lines.

We have previously reported that insulin receptor expression is increased in human breast cancer specimens (V. Papa et al., J. Clin. Invest., 85:1503-1510, 1990). In the present study, in order to further understand the role of the insulin receptor in breast cancer, insulin receptor expression and function were characterized in three human breast cancer cell lines, MCF-7, ZR-75-1, and T-47D, and compared to a nonmalignant human breast epithelial cell line, 184B5. Insulin receptor content, measured by radioimmunoassay, was elevated 5- and 3-fold in MCF-7 and ZR-75-1 breast cancer cell lines, respectively, when compared to the nonmalignant cell line 184B5. In contrast, the insulin receptor content of T-47D cells was not increased. The increase in insulin receptor content in MCF-7 and ZR-75-1 cells was not due to amplification of the insulin receptor gene. Also, total insulin receptor mRNA content was not increased in breast cancer cells in respect to nonmalignantly transformed 184B5 breast epithelial cells. However, significant differences in the content of receptor mRNA species were observed. The insulin receptors in the breast cancer cell lines were functional: (a) In all 4 cell lines, high-affinity insulin-binding sites were detected, and, in concert with the insulin receptor radioimmunoassay data, binding capacity was highest in MCF-7 and then in ZR-75-1 cells. (b) In all cell lines, insulin stimulated insulin receptor tyrosine kinase activity. However, the effect of insulin was greater in breast cancer cell lines than in nonmalignant breast cells. (c) In all cell lines, insulin at concentrations of 1 nM or less stimulated [3H]thymidine incorporation. This effect of insulin was inhibited by 50% in MCF-7 cells and by 60% in 184B5 cells when alpha-IR3, a monoclonal antibody to the insulin-like growth factor I receptor, was present. In these cells, therefore, insulin was active via both its own receptor and the IGF-I receptor. In contrast, alpha-IR3 antibody was without effect in T-47D and ZR-75-1 cells, suggesting that in these cell lines insulin acted only via its receptor. In the breast cancer cells, MA-5, an agonist monoclonal antibody to the insulin receptor, stimulated [3H]thymidine incorporation. This present study indicates therefore that in breast cancer cell lines there are functional insulin receptors that regulate breast cancer cell growth.

Breast Neoplasms↗
PubMed1992

Effect of TSH in human thyroid cells: evidence for both mitogenic and antimitogenic effects.

The well-known mitogenic effects of TSH observed in vivo on the thyroid are not always reproducible of human thyroid cells in vitro where conflicting results have been obtained. In order to clarify this issue, we have used primary cultures of human thyroid cells obtained from normal tissue and maintained in serum-free medium for several days. In this in vitro model we have studied the effect of TSH on growth by measuring three different parameters: [3H]-thymidine incorporation, cell counts, and DNA measurement. Monolayer cultures were plated at both low and high cell density (2 x 10(4) and 8 x 10(4) cells/25 mm well, respectively). Although at either cell density cultures were equally able to functionally respond to TSH in terms of cAMP accumulation a significant growth response to TSH was observed only in low density cultures. In high density cultures TSH had an antimitogenic effect. Moreover, TSH potentiated the mitogenic effect of insulin only in low density cultures. In contrast to TSH, FCS induced a similar proliferative response at both high and low cell density. Following TSH stimulation, cAMP content was always increased, paralleling the effect of growth in low density but not in high density cultures. The cAMP analogues dibutyryl-cAMP and 8-bromo-cAMP, as well as cholera toxin and forskolin, did not mimic the mitogenic effect of TSH but had an antiproliferative effect. In addition, these agents blunted the proliferative effect of insulin. These data suggest that in thyroid cells TSH is able to elicit both a mitogenic and an antimitogenic effect depending on the environmental conditions such as cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗
PubMed1992

Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity.

PURPOSE: We evaluated the frequency of thyroid cancer in patients with cold thyroid nodules in relation to iodine intake, sex, age, and multinodularity in a consecutive series of patients with nodular thyroid diseases. PATIENTS: In the period from 1980 to 1990, 5,637 patients were studied: 4,176 patients were from an iodine-sufficient area (ISA) and 1,461 from an adjacent iodine-deficient area (IDA). Surgery was performed in 792 patients on the basis of a suspicious or malignant finding at fine-needle aspiration biopsy. RESULTS: The overall thyroid cancer frequency was 4.6% (259 patients had cancer). Iodine intake affected the cancer rate in patients with cold nodules. The frequency of cancer in patients with cold thyroid nodules was 5.3% in the ISA and 2.7% in the IDA. This difference, however, was significant only in females. Sex had a major influence on the malignant rate of cold nodules; although female patients were more frequently observed (n = 5,028) than male patients (n = 609), the frequency of cancer was significantly lower in female patients with cold nodules (4.2%) than in males (8.2%). Age was an important factor in both sexes. The proportion of nodules that were malignant was smallest in patients of the 4th decade and was greatest in patients younger than 30 years or older than 60 years. Multivariate analysis showed that sex and age interact in determining the cancer risk in patients with thyroid nodules. Finally, the frequency of thyroid cancer in patients with a solitary nodule was not different from the frequency in patients with multiple nodules. CONCLUSION: Our study indicates that thyroid cancer risk in a patient with a nodular goiter varies markedly according to iodine intake, sex, and age but not in relation to multinodularity, as assessed by clinical examination. The knowledge of these epidemiologic aspects of thyroid cancer may increase the accuracy of the preoperative selection of patients with cold nodules of the thyroid.

Adult↗
PubMed1992

Opposite effects of cholestyramine and loxiglumide on gallbladder dynamics in humans.

The aim of this study was to conduct dose-response studies of the effect of cholestyramine, alone or in combination with a test meal, on gallbladder emptying studied by ultrasonography in 31 healthy volunteers. The role of cholecystokinin in mediating the effects of cholestyramine was studied using the cholecystokinin-receptor antagonist loxiglumide. In the absence of a test meal, cholestyramine produced a dose-dependent decrease in gallbladder volume; minimal residual volumes were 30% (2 g), 55% (4 g), and 110% (12 g) of the minimal volume produced by a test meal alone. Gallbladder volume was still only 50% of the initial volume, 24 hours after ingestion of 12 g cholestyramine. Cholestyramine also enhanced gallbladder emptying in response to the test meal (n = 7). Oral loxiglumide strongly inhibited gallbladder evacuation in response to either test meal (n = 6) or cholestyramine alone (n = 6) but partially blocked gallbladder emptying when the resin was added to the test meal (n = 12). It is concluded that (a) cholestyramine alone or in combination with a test meal produces a marked decrease in gallbladder volume and (b) the action of the resin itself on gallbladder motor function appears to be mainly, but not solely, mediated by cholecystokinin through the disinhibition of the luminal feedback mechanism between bile salts and the endogenous release of cholecystokinin.

Adult↗
PubMed1992

Characterization of the low density lipoprotein receptor activity in buffalo rat liver (BRL-3A) cells.

1. BRL-3A cells possess a specific LDL receptor with an apparent mol. wt of 160,000 that binds, with saturation, both human and rat 125I-LDL. 2. Like human fibroblasts, BRL-3A cells also bind, internalize and degrade 125I-hLDL but to a lesser extent. 3. BRL-3A cells also bind the monoclonal antibody against rat liver LDL receptor P1B3. Moreover the LDL receptor activity increases when cells are preincubated with medium containing 5% of LPDS. 4. As with human (h) fibroblasts, treatment of BRL-3A cells with 10(-7) M insulin enhances binding (30%), internalization (18%) and degradation (20%) of 125I-hLDL.

Animals↗
PubMed1992

Effects of a new calf thymus protein on 3-hydroxy-3-methylglutaryl-CoA reductase activity in rat (Rattus bubalus) hepatocyte cells (BRL-3A).

1. In a previous paper we described the purification steps of a new calf thymus protein able to activate the LDL receptor catabolism. 2. In this paper we examine the modulatory effect of this new calf thymus protein on 3HMG-CoA reductase activity in rat hepatocyte cells to better clarify the role of this protein on cholesterol metabolism. 3. The results obtained show that the calf thymus protein inhibits the HMG-CoA reductase, and support the hypothesis that the activation of LDL receptor catabolism is mediated by a decreased amount of cellular cholesterol following HMG-CoA reductase inhibition.

Animals↗
PubMed1992

Relation between steroid receptor status and body weight in breast cancer patients.

Obesity is known to adversely affect breast cancer prognosis. Since obesity is associated with increased oestrogen levels, and oestrogens are growth stimulators of oestrogen receptor (ER)-positive breast carcinomas, we evaluated the relationship between the ER and progesterone receptor (PR) status of the neoplastic tissue and obesity in a series of 615 breast cancer patients. Both ER and PR concentrations were significantly and positively correlated with obesity by multiple regression analysis. Furthermore, the estimated probability of having an ER+/PR+carcinoma was significantly higher in obese patients (odds ratio 2.65, 95% confidence interval 1.56-4.48). This association between receptor-positive status and obesity was observed both in premenopausal and postmenopausal patients. Our data suggest, therefore, that obesity plays a role in determining the ER status of breast cancer and raise the possibility that ER presence in breast carcinomas occurring in obese patients is not indicative of a favourable prognosis.

Adult↗
PubMed1992

Induction of intercellular adhesion molecule-1 but not of lymphocyte function-associated antigen-3 in thyroid follicular cells.

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) by thyrocytes and their regulation by cytokines. Immunofluorescence studies on cryostat sections and on freshly dispersed cell preparations showed that ICAM-1 and LFA-3 are barely detectable in non-autoimmune thyrocytes. However, thyrocytes acquired ICAM-1 expression in culture. IFN-gamma, IL-1 beta and TNF-alpha produced a clear enhancement of ICAM-1 expression. When tested in combination, IL-1 beta and TNF-alpha were additive to the IFN-gamma effect. LFA-3 expression was not modulated by these cytokines. In the HT93 thyroid cell line generated by transfection with SV40, ICAM-1 and LFA-3 were both constitutively expressed at high levels. Cytokines modulated ICAM-1 expression similarly, but to a greater extent than in normal thyrocytes. LFA-3 remained unmodified. These results support the notion that normal thyrocytes are immunologically silent cells. The capability of cytokines to induce ICAM-1 together with HLA class I and class II-expression on thyrocytes suggests that under their influence, these cells may express all the surface molecules required for antigen presentation and/or for being recognized as target cells in the context of thyroid autoimmune disease.

Antibodies, Monoclonal↗
PubMed1992

Gallbladder volume and emptying in diabetics: the role of neuropathy and obesity.

Gallbladder (GB) volume was monitored by real-time sonography in diabetics (n = 21) and healthy volunteers (n = 55) after a test meal. Seventeen controls and seven diabetics were obese; six patients had both autonomous and somatic neuropathy, and four had somatic neuropathy. Fasting GB volume was similar in controls and diabetics with and without autonomic neuropathy; it was correlated with body mass index (controls, r = 0.43, P less than 0.002; diabetics, r = 0.46, P less than 0.04), and was increased in obese subjects. Post-prandial GB emptying was decreased in diabetics. Those with autonomous neuropathy exhibited larger residual volumes than controls (P less than 0.03). Post-prandial GB emptying was slower and less complete in (non-diabetic) obese subjects and deteriorated further in diabetic obese subjects. GB fasting tone was normal, but GB kinetics were impaired in diabetics; obesity and autonomous neuropathy were correlated with GB hypomotility.

Adult↗
PubMed1992

Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas.

The receptor for Hepatocyte Growth Factor is a transmembrane tyrosine kinase encoded by the c-MET oncogene. We have previously shown that the Met protein is expressed in several human epithelial tissues. The receptor is barely detectable, however, in normal thyroids and in specimens from patients affected by non-neoplastic thyroid diseases. Now we report that the expression of the Met/HGF receptor is increased a hundred fold in 22 out of 41 human carcinomas derived from the thyroid follicular epithelium. A comprehensive analysis of 15 cases showed that the overexpressing carcinomas belong to histotype variants correlated with negative prognosis and in all but one case there were evidences of locally advanced disease and/or distant metastases. The 11 benign adenomas and the 5 medullary carcinomas tested were negative. Western blot analysis with monoclonal antibodies directed against either the intracellular or the extracellular receptor domains failed to reveal major structural alterations. Southern blot analysis also demonstrated that the c-MET gene was not amplified nor rearranged. These data suggest a role for the overexpression of c-MET oncogene in the pathogenesis and progression of thyroid tumors derived from the follicular epithelium.

Adolescent↗
PubMed1991

Evaluation of the fine needle aspiration biopsy in the preoperative selection of cold thyroid nodules.

From 1980 to 1988 the authors examined by fine needle aspiration biopsy (FNAB) 4609 patients with solitary thyroid nodules or multinodular goiters. A total of 5605 "cold" thyroid nodules were evaluated and classified, on the basis of the cytologic findings, as malignant, follicular lesions (probably malignant and probably benign) and benign. Then the authors compared the preoperative cytologic findings with the postoperative histologic results in 827 nodules from patients who underwent surgery. In the 805 thyroid nodules in which an adequate cytologic specimen was obtained, false-negative results were 2.3% and false-positive findings were 1.1% By comparing cytologic and histologic diagnoses, preoperative FNAB resulted in the ability to accurately assess the risk of cancer in a thyroid nodule; since 250 nodules were identified as malignant, the risk of a "cold" thyroid nodule being cancer was 4.46% in this series.

Adenoma↗
PubMed1991

Ultrasound scanning assessment of L-thyroxine treatment effectiveness in a group of children with diffuse goiter.

Ultrasound scanning is an accurate and objective method to assess thyroid volume; therefore it is useful to evaluate the effectiveness of L-thyroxine treatment in reducing goiter size, especially in children where clinical evaluation is inaccurate. In this prospectic study we evaluated the effectiveness of one-year L-thyroxine treatment in a group of children with nontoxic diffuse goiter coming from an area with low iodine intake. We examined 11 children (7 females, 4 males), age range 9-14 years. At clinical examination, 6 patients had a goiter classified Ia (according to WHO criteria), 4 had a class Ib and only 1 had a class II goiter. In order to achieve an accurate goiter evaluation, the thyroid volume was determined by ultrasonic scanning with a 5 MHz linear probe before and after treatment. Patients were given a dose of L-thyroxine (1.5-2.0 micrograms/kg/die) in order to significantly reduce serum TSH levels (from 1.8 +/- 0.6 to 0.8 +/- 0.5 mU/l, mean +/- SD). Patients were reexamined at 12 months of therapy and again at 10 months after therapy withdrawal. A significant reduction of the goiter volume (greater than 20%) was obtained in 6/11 (54%) patients, although serum TSH levels were fully suppressed only in one. The mean goiter size reduction in "responders" was -31.2 +/- 9.3% (m +/- SE). After therapy withdrawal goiter size increased in the majority of cases (in 4/11, greater than 20%). Our study demonstrates that L-thyroxine treatment is effective in reducing goiter size in the majority of children with a diffuse goiter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

De novo HLA class II and enhanced HLA class I molecule expression in SV40 transfected human thyroid epithelial cells.

Human thyroid follicular cells normally synthesize and express HLA Class I molecules but in glands affected by autoimmune or neoplastic diseases they express Class II molecules. We have investigated the effect of SV40 virus transformation on the expression of MHC molecules in human thyrocytes. Primary cultures of human thyroid from two different glands were transfected with the plasmid pX-8, containing the 'early' region of SV40 virus, and two continuous lines of thyrocytes were obtained. The cell lines maintained features of parental thyroid epithelial cells showing the characteristic cytokeratin filament network, microvillar protrusion and tight junctions. In addition, the SV40-transfected cells responded to graded doses of TSH with increased c-AMP production. Thyrocytes from both cell lines hyperexpressed Class I molecules and a significant proportion of them also acquired constitutive Class II expression, as determined by indirect immunofluorescence (IFL), flow cytometry and Northern blotting hybridization using a DR beta probe. These cells were found to be normally up-regulated by interferon (IFN)-gamma. Indirect IFL and flow cytometry analysis were used to detect and quantify the expression of HLA-DR, DP and DQ subregions. A co-ordinated expression (DR greater than DP much greater than DQ), reminiscent of the inappropriate HLA expression found in thyroid autoimmune disease in vivo and of the in vitro regulation in normal thyrocytes, was observed. Clones derived from these cell lines differed in their level of constitutive Class II expression and in their sensitivity to Class II induction by IFN-gamma. In conclusion, these thyroid cell lines could provide a useful tool for further investigation of HLA gene regulation in thyroid cells and for elucidating on the mechanism involved in the inappropriate HLA expression described in autoimmune and neoplastic diseases of the thyroid.

Autoantigens↗