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F. Monaco and M. Andreoli

ABSTRACT

Thyroglobulins (TG) from a "hot" human thyroid nodule and from Fisher rats have been purified and the effects of progressive removal of sialic acid and galactose on the immunoreactive properties of the proteins were studied. Terminal sialic acid and galactose were released by stepwise hydrolysis with neuraminidase and beta-galactosidase.

Agalacto-TG shows a slower electrophoretic mobility than native TG, but in polyacrylamide gel electrophoresis and immunoelectrophoresis it migrates in the same position as asialo-TG.

In immunodiffusion agalacto-TG forms a spur with native TG and asialo-TG when tested against anti 19S native TG or anti-asialo-TG sera.

It is thus shown that galactose in the terminal environment of the oligosaccharide chains of thyroglobulin is essential for the structural groups involved in the antigenic properties of thyroglobulin.

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F. Monaco, C. Santolamazza, I. De Ros, and A. Andreoli

Abstract.

The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI. analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds.

It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit.

In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as wellas in carbohydrate chains addition.

Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.

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F. Monaco, S. Grimaldi, G. Scuncio, and M. Andreoli

ABSTRACT

In an experimental rat thyroid tumour (Wollman line 1-1C2) thyroglobulin (TG) was isolated from soluble iodoproteins by ammonium sulphate fractionation and density gradient ultracentrifugation. The isolated TG was characterized by polyacrylamide gel electrophoresis, microimmunodiffusion, immunoelectrophoresis, analytical ultracentrifugation and by chemical determination of sialic acid and iodine content.

Tumour thyroglobulin has a sedimentation coefficient of 17.7S, which is similar to that of enzymatically desialylated thyroglobulin (18.4S) in the normal rat; tumour TG shows a slower electrophoretic mobility than native TG and similar to rat desialylated TG.

In double immunodiffusion tumour TG is shown to precipitate with an identity reaction with both native and desialylated rat TG; in immunoelectrophoresis it has a slower migration than native TG and is very close to that of enzymatically desialylated TG. Tumour TG has an iodine content of 0.02 % and a sialic content of 0.15 %. Chromatography of the 125I-labelled tumour TG revealed the presence of mono- and diiodothyrosines, a very small amount of triiodothyronine but no thyroxine.

These results suggest that tumour TG, isolated in the experimental rat thyroid tumour, previously shown not to incorporate sialic acid into thyroglobulin, has a different electrophoretic mobility from native TG but is very similar to desialylated rat TG and has a very low sialic acid and iodine content as well as a striking decrease in thyroxine.

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F Basolo, E Molinaro, L Agate, A Pinchera, L Pollina, G Chiappetta, C Monaco, M Santoro, A Fusco, P Miccoli, R Elisei, M Capezzone, and F Pacini

BACKGROUND: RET proto-oncogene rearrangements (RET/PTC) are causative events in the pathogenesis of a subset of papillary thyroid cancer (PTC). The prevalence of RET/PTC varies in different countries and according to specific clinical features: it is higher after radiation exposure and it is claimed to be higher in young patients. Conflicting results are reported regarding the prognostic role of RET/PTC activation. OBJECTIVE: To investigate the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC. METHODS: We have studied the expression of the RET encoded protein in 127 papillary thyroid carcinomas by immunohistochemistry using a polyclonal antibody against the tyrosine-kinase domain of the RET protein. These cases have been collected during 1970-1985, and have a mean (+/-S.D.) period of follow-up of 18.6+/-3.7 years (range 12-27 years). The results have been compared with the patients' outcome. RESULTS: The tyrosine-kinase domain of RET was expressed in 82 (64.6%) papillary carcinomas. Among them, RET was highly expressed in 65 (51.2%) cases and moderately expressed in 17 (13.4%). RET expression was absent in 45 (35.4%) cases. No correlation was found between RET expression and other parameters such as sex, age at diagnosis, tumor class and histological variant. Follow-up analysis showed no influence of RET expression on patients' outcome. By multivariate analysis, age (>45 years) and tumor class IV, but not sex and RET expression were adverse prognostic indicators of death. CONCLUSION: In conclusion, our analysis indicates that RET expression is frequently found in PTC, and has no influence on tumor outcome.