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Biomedical subjects

A Belfiore

Publications and source records attributed to A Belfiore.

At least 73 records · Page 4Linked to original sources
PubMed1991

Overexpression of insulin receptors in fibroblast and ovary cells induces a ligand-mediated transformed phenotype.

To investigate whether overexpression of the insulin receptor results in altered cell growth we used NIH 3T3 cells transfected with a bovine papilloma virus/insulin receptor cDNA construct (3T3/HIR). These cells expressed high numbers of insulin receptors (mean +/- sd, 631.0 +/- 16.7 ng receptors/10(6) cells). Insulin significantly stimulated the growth of 3T3/HIR cells maintained in serum-free medium. Moreover, in these cells, insulin induced marked phenotypic changes, including alterations in cell shape, loss of contact inhibition, and focal growth. In contrast to 3T3/HIR cells, insulin was without effect in either wild-type 3T3 cells (3T3/wt), 3T3 cells transfected with the neomycin resistance gene (3T3/NEO), or the bovine papilloma virus (3T3/BPV). To assess the presence of anchorage-independent growth, cells were seeded in soft agar and inspected for colony formation. 3T3/HIR cells showed absent or minimal colony growth in the absence of insulin. However, there was a dose-dependent insulin-stimulated increase in both colony size and number. Insulin-stimulated colony formation was specifically inhibited by an insulin antagonist, monoclonal antibody MA-10. In the presence of 100 nM insulin, about 3% of cells formed large colonies. Insulin neither stimulated growth nor induced colony formation in 3T3/wt cells or 3T3/NEO cells. Insulin also stimulated colony formation in CHO cells transfected with an insulin receptor cDNA construct. In conclusion, overexpression of normal insulin receptors induces a ligand-dependent transformed phenotype. This phenomenon may have clinical relevance by conferring a selective growth advantage to tumor cells with high numbers of insulin receptors.

Agar↗
PubMed1990

The morphometric analysis of cell nuclei from fine needle aspirates of thyroid follicular lesions does not improve the diagnostic accuracy of traditional cytologic examination.

In order to evaluate the usefulness of the morphometric analysis in improving the accuracy of the traditional cytologic examination of follicular thyroid lesions, fine needle aspirates from 17 adenomatous goiters, 19 follicular adenomas and 18 follicular carcinomas were examined. In each case 20-50 follicles, accounting from 100 to 200 thyroid cells, were studied by operators unaware of the histologic diagnosis. Nuclear areas (mean, maximum and minimum area) were derived by means of a semiautomatic system and follicular thyroid lesions were classified into three groups (goiter, adenoma and follicular carcinoma) utilizing cut-off values. The results were then compared to the cytologic diagnosis carried out according to traditional (optic microscopy) criteria. Mean values of nuclear areas showed significant differences among the three groups, but a considerable overlap occurred in the size distribution of cell nuclei. At present, therefore, planimetric measurements of cell nuclei in fine needle aspirates do not improve the accuracy of standard cytologic examination in the differential diagnosis of follicular thyroid lesions.

Adenocarcinoma↗
PubMed1990

Determination of low-energy beta-emitter radionuclides deposited on surfaces by attapulgite treatment.

A method for the determination of surface contamination of various materials by 3H and 99Tc is reported. Both 3H and 99Tcm are widely used in chemical and clinical applications. The isotopes 99Tc, the decay product of 99Tcm, and 3H are soft beta-emitter radionuclides and the use of unsealed sources can frequently produce contamination and excessive internal dosing for workers. The removal of radionuclides from surfaces was effected with attapulgite, a clay with a high absorption capacity for many organic and inorganic substances. The determination was carried out by extracting the absorbed radionuclide from the clay and then measuring it in a beta-scintillation counter. The determination limits of the method, 20 Bq cm-2 for 3H and 100 Bq cm-2 for 99Tc, are below the "derived working limits" for these radionuclides.

Magnesium↗
PubMed1990

Elevated insulin receptor content in human breast cancer.

The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors.

Binding, Competitive↗
PubMed1990

Increased aggressiveness of thyroid cancer in patients with Graves' disease.

To evaluate whether coexistence of Graves' disease affects the prognosis of thyroid cancer we examined the clinical and pathological characteristics of 22 differentiated thyroid carcinomas concomitant with hyperthyroidism; 13 were associated with Graves' disease, and 9 with autonomous thyroid nodules. Carcinomas were identified in a consecutive series of 359 hyperthyroid patients (132 with Graves' disease and 227 with autonomous thyroid nodules) who underwent surgery during a 6-yr period. One hundred and thirty-seven thyroid carcinomas were found in the 582 euthyroid patients operated on in the same period. In Graves' patients, carcinomas were more often multifocal (46.1% vs. 0%), locally invasive (61.5% vs. 11.1%), and metastatic to lymph nodes (61.5% vs. 11.1%) or to distant sites (23.0% vs. 0%) than in patients with autonomous thyroid nodules. In addition, carcinomas concomitant with Graves' disease were larger (3.3 +/- 1.8 vs. 1.0 +/- 0.7 cm) than the ones associated with autonomous thyroid nodules and showed a high recurrence rate. In euthyroid patients, aggressiveness of thyroid cancer was intermediate. Serum TSH levels were suppressed in all hyperthyroid patients with thyroid cancer. However, circulating thyroid-stimulating antibodies were present in 12 of 13 cancer patients with Graves' disease, but were absent in patients with autonomous thyroid nodules. Our study suggests, therefore, that TSAb may play a role in determining the high aggressiveness of thyroid cancer in Graves' disease patients and indicates that a vigorous treatment should be pursued in this subgroup of patients.

Graves Disease↗
PubMed1989

Purification and characterization of a calf thymus protein active on lipid metabolism.

1. This work concerns the purification of a calf thymus protein that increases the binding of human 125I-labeled low density lipoprotein (LDL) on both human skin fibroblasts and a special line of rat liver cells, BRL 3A. 2. It was found that the thymus gland affects cholesterol metabolism via an activation of the LDL receptor pathway. 3. Moreover, the thymus protein active on the LDL receptor pathway has a different amino acid composition and molecular weight from other well-characterized thymic peptides.

Amino Acids↗
PubMed1989

Thymus fraction (FIII) effect on cholesterol metabolism: modulation of the low density lipoprotein receptor pathway.

1. A heat stable protein fraction from calf thymus is able to determine a marked drop of total serum cholesterol and B apoproteins in rats fed a cholesterol enriched diet. 2. It is known that the catabolism of low density lipoprotein (LDL) cholesterol is mediated by the existence of high affinity surface receptor on membrane cells. 3. The purpose of the present paper is to verify if the heat stable thymus protein fraction is able to affect the LDL receptor pathway in vitro. 4. The results obtained show that the protein calf thymus is able to increase human and rat LDL catabolism.

Adult↗
PubMed1989

High frequency of cancer in cold thyroid nodules occurring at young age.

In order to evaluate the risk of malignancy of cold thyroid nodules occurring in young as compared with adult patients, we studied a consecutive series of 2327 patients with a solitary cold thyroid nodule over a 6-year period. None of these patients had been previously irradiated in the neck or head. Fine needle aspiration of the nodule and cytologic examination were carried out in all patients and, on the basis of this evaluation and clinical examination 391 patients were selected for surgery; 109 patients were 4-20 years old and 2218 patients were older than 20 years. Malignancy was found in 11 (10.1%) and in 112 (5.0%) of cold thyroid nodules occurring in young and adult patients, respectively. The annual incidence of cold thyroid nodules in the population of the area studied was 5.2 vs 55.9 (per 10(5) inhabitants) in the young and in the adult group, respectively, and the annual incidence of thyroid cancer was 0.53 vs 2.82 (per 10(5) inhabitants) in the young and in the adult patients, respectively. The present study indicates, therefore, that in the absence of head or neck irradiation, cold thyroid nodules are much less frequent in young age, but that the malignancy rate of cold nodules occurring in young patients is 2-fold higher than in adults patients.

Adolescent↗
PubMed1988

The effect of L-carnitine on the apolipoprotein pattern of rats fed a cholesterol-rich diet.

1. L-Carnitine was administered to hypercholesterolemic rats for eight days, after which the blood was collected by intracardiac puncture and lipoproteins were collected by preparative ultracentrifuge. 2. The chemical composition of lipoproteins of normal rats and hypercholesterolemic rats before and after L-carnitine treatment was determined. 3. The total serum B and E apoproteins were assayed by rocket electrophoresis, while apoproteins in VLDL, IDL, LDL and HDL were determined by densitometric scanning of SDS and TMU polyacrylamide disc gel electrophoresis. 4. The results obtained showed that the L-carnitine treatment tends to restore to normal values both the chemical composition of lipoproteins and the apoproteins pattern of rats fed on a diet enriched with cholesterol.

Animals↗
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

The serum lipoprotein pattern of water buffalo (Bubalus bubalis).

1. The serum lipoprotein pattern of water buffalo was studied by means of electrophoresis and the lipoproteins were isolated by ultracentrifugation on the basis of their hydrated density. 2. High density lipoproteins (HDL) showed a higher level of cholesterol than did the other lipoproteins. Moreover, the level of phospholipids was higher in HDL than in very low density lipoproteins (VLDL). 3. The buffalo B100 apoprotein was similar to that of man and rat. Three apoproteins similar to human apo E, apo AI and AII were found in buffalo HDL, buffalo VLDL contained essentially apo B protein.

Animals↗
PubMed1987

The serum apo B and apo E in rats following cholesterol diet and thymus treatment.

The serum levels of apo B and apo E in rats fed on a diet rich in cholesterol before and after thymus treatment were determined by the authors. The diet enriched with cholesterol increases the serum levels of apo E and of the large and small species of apo B. After treatment the large apo B and the small one strongly decrease, while apo E increases further. These data support the hypothesis that the dropping of total cholesterol, after thymus treatment, cannot be ascribed to apo E decrease but possibly to B-apoproteins.

Animals↗
PubMed1987

Thyrocyte HLA class II expression and regulation in relation to thyroid autoimmunity.

The occurrence of HLA Class II expression by thyroid (and other endocrine) epithelia in autoimmune diseases suggests that these cells may facilitate their own destruction by immunogenically presenting autoantigens. This is supported by the findings that Class II+ thyrocytes can specifically stimulate virus-specific and autoreactive T cell clones, and that Class II expression by thyrocytes correlates with the occurrence of thyroid autoantibodies. A variety of factors may contribute to the regulation of Class II expression by thyrocytes: this is induced by interferon (IFN-gamma), and is enhanced by thyroid stimulating hormone (TSH) and by tumour necrosis factor (TNF). Conversely, epidermal growth factor (EGF) suppresses the induction of Class II in thyrocytes. This complex regulation is reflected in differences in HLA-D subregion expression between patients (DR greater than DP greater than DQ). The immune-based mechanisms of thyrocyte Class II regulation are clearly applicable to the on-going disease in an infiltrated thyroid, but the possibility of nonimmune Class II induction deserves attention, particularly in identifying factors which might contribute to the initial autoimmune attack. The possible involvement of such mechanisms in autoimmunity is supported by findings in Type I diabetes in which Class II+ islet beta cells can be found in the absence of infiltration. Further evidence is provided by the observation that a proportion of thyrocytes transformed with SV40 DNA constitutively express Class II molecules. Finally, the 'activated' state of capillary endothelial cells in organs subject to autoimmune attack suggests that they may play an important role in facilitating the autoreactive infiltration of the tissues.

Epithelium↗
PubMed1986

Organ-specific autoimmunity: a 1986 overview.

The normally functioning immune system is subject to intricate networks of regulatory mechanisms: it is therefore not surprising to find that autoimmune diseases present a complex pathogenic picture in which the relative contributions of various factors probably determine the precise nature and course of disease. This is particularly evident in the effector mechanisms of organ-specific autoimmunity which are described in this chapter. These ultimately give rise to the disease symptoms, and can be directly cytotoxic, or may either stimulate or block functional activity or growth of the target cells. Their various contributions to human diseases are becoming more firmly established, as in Type I diabetes, or are only now being described, as in the case of EC-Ab in protracted diarrhea of infancy and as evidenced by the growing lists of receptor-stimulating or -blocking antibodies. The nature and precise location of relevant autoantigens is also coming under closer scrutiny. The answers to the question of why these diseases arise in the first place remain more elusive. However, it is again likely that a variety of factors can contribute. The attractive possibility of a role for idiotypic interactions is gaining ground, particularly within the context of antibodies to hormones and their receptors. Another potential mechanism which we believe may be of central importance, particularly in the development of organ-specific destructive autoimmunity, and which we have discussed here in detail, is the aberrant expression of HLA Class II molecules by target cells. Whether this is actually an initiating factor is presently not known, but its potential for promoting pathogenesis both early and late in the process is clear. Furthermore, the complex nature of the regulation of epithelial Class II expression may help to explain the heterogeneity of features and course of disease in different patients with the same underlying pathology. All these advances in our basic understanding of the disease processes should ultimately lead to more effective and specific means of therapeutic intervention.

Animals↗