Biomedical subjects

J C Utrilla

Publications and source records attributed to J C Utrilla.

7 recordsLinked to original sources

PubMed2000

Expression of a neu/c-erbB-2-like product in neuroendocrine cells of mammals.

The neu/c-erbB-2 oncogene encodes a 185 kDa protein closely homologous to the epidermal growth factor receptor. The protein product (p185) is a glycoprotein with an external domain and an internal domain with tyrosine kinase activity. Amplification and/or overexpression of p185 is related to several human adenocarcinomas. Subsequent studies demonstrated its presence in certain neuroendocrine (NE) neoplasms, including phaeochromocytomas, insulinomas and medullary thyroid carcinomas. However, relatively little is known about its role in normal cell growth regulation and development. Therefore, our objective was to determine whether neu/c-erbB-2 was expressed in normal NE tissues of different mammals, specially in humans, as it was in their neoplasms. We have examined by immunohistochemistry different endocrine glands (thyroid, pancreas, suprarrenal and hypophysis) and the small intestine of human beings, rats and guinea pigs, using two polyclonal antibodies raised against the intracytoplasmic part of the protein, and specific antigen absorption controls. We have found that a neu/c-erbB-2-like product occurs in all normal NE tissues examined: C cells of the thyroid gland, chromaffin cells of the adrenal medulla, pancreatic islets, enteroendocrine cells of the small intestine and, finally, scattered cells of the adenohypophysis, according to a typical granular immunohistochemical pattern. Our results indicate that normal NE cells share a new common antigen in their cytoplasms, a neu/c-erbB-2-like product, with a similar immunostaining pattern to that presented by the neoplasms derived from them.

Animals↗

PubMed1999

Expression of c-erbB-2 oncoprotein in human thyroid tumours.

AIMS: c-erbB-2 expression has been found to be a potential marker of aggressive biological behaviour in some tumours, but the role played by this oncoprotein in the development and maintenance of thyroid tumours is still controversial. Therefore our objective was to determine whether c-erbB-2 was overexpressed in a large retrospective series of human thyroid tumours, including both from follicular and C-cell differentiation. METHODS AND RESULTS: We have studied 67 thyroid tumours (10 follicular adenomas, 11 follicular carcinomas, three anaplastic carcinomas, 25 papillary carcinomas and 18 medullary carcinomas and 16 metastases) by immunohistochemistry using an antigen retrieval method for paraffin-embedded material and a specific polyclonal antibody against the intracytoplasmic part of c-erbB-2 oncoprotein. There are marked differences in the pattern of c-erbB-2 immunoreactivity depending on the type of thyroid tumour. Thus, no expression of the oncoprotein has been found in follicular adenomas, follicular carcinomas and anaplastic carcinomas, but 52% of papillary carcinomas (membranous and diffuse cytoplasmic patterns) and all medullary carcinomas (granular cytoplasmic pattern) are immunopositive. CONCLUSIONS: Our results indicate that overexpression of c-erbB-2 oncoprotein is easily identifiable by immunohistochemistry in paraffin sections of certain thyroid tumours after applying an antigen retrieval method. This study suggests that c-erbB-2 oncoprotein may play some role in disease progression in papillary and medullary thyroid carcinomas, but the significance of the different immunohistochemical patterns merits further investigations.

Adenoma↗

PubMed1998

Chronic hypervitaminosis D3 determines a decrease in C-cell numbers and calcitonin levels in rats.

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

Animals↗

PubMed1997

Expression and prognostic value of c-erbB-2 oncogene product in human phaeochromocytomas.

AIMS: Amplification of c-erbB-2 proto-oncogene has been reported in endocrine tumours, but the results were unclear and no predictive prognostic value has been established in the case of phaeochromocytoma. We investigated the immunohistochemical expression of c-erbB-2 oncogene in 34 cases of human phaeochromocytoma (27 sporadic, seven familial type MEN (multiple endocrine neoplasm)) in order to find out if it could be used to differentiate sporadic and familial forms and whether c-erbB-2 expression is related to tumour biological behaviour. METHODS AND RESULTS: All the cases showed diffuse, generally heterogeneous, intracytoplasmic granular c-erbB-2 staining. The percentage of tumour cells expressing c-erbB-2 was used as the comparative variable. The percentage of c-erbB-2 positive cells had a statistically significant (P < 0.001) relationship with tumour aggressiveness, as manifested by the presence of distant metastasis or association with other malignant neoplasms. We also found significantly higher levels (P = 0.007) of c-erbB-2 overexpression in MEN phaeochromocytoma than in sporadic cases. CONCLUSIONS: These results clarify the important role of c-erbB-2 proto-oncogene in the pathogenesis of human phaeochromocytoma and confirm the unfavourable prognostic significance of c-erbB-2 expression.

Adrenal Gland Neoplasms↗

PubMed1995

Postnatal variations in the number and size of C-cells in the rat thyroid gland.

The heterogeneous distribution of thyroid C-cells has until now hindered an objective evaluation of changes caused by age or experimental stimuli. To overcome this, a rigorous methodology has been designed to detect variations in shape, size, and number of C-cells throughout development. Using this methodology, we have demonstrated that C-cells do not significantly alter their shape with age. However, their volume increases gradually from 472 microns3 in newborn rats to 1653 microns3 in 120-day-old animals. Over the same time period, the mean number of C-cells within the thyroid gland increased 9-fold (from 1.6 x 10(4) to 1.5 x 10(5), and the number of C-cells per unit area decreased (from 6.15 x 10(4)/mm3 to 2.6 x 10(4)/mm3). We conclude that there are marked variations in size, total number, and number of C-cells per unit area in the rat thyroid gland after birth.

Aging↗

PubMed1992

Evidence of the occurrence of calcitonin cells in the ultimobranchial follicle of the rat postnatal thyroid.

A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.

Aging↗

PubMed1992

Mitotic activity of the endocrine cells in rat thyroid glands during postnatal life.

This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells.

Aging↗