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P Bastiani

Publications and source records attributed to P Bastiani.

At least 19 recordsLinked to original sources
PubMed1993

Intracellular routing of GLcNAc-bearing molecules in thyrocytes: selective recycling through the Golgi apparatus.

Previous experiments led us to speculate that thyrocytes contain a recycling system for GlcNAc-bearing immature thyroglobulin molecules which prevents these molecules from lysosomal degradation (Miquelis, R., C. Alquier, and M. Monsigny. 1987. J. Biol. Chem. 262:15291-15298). To confirm this hypothesis, the fate of GlcNAc-bearing proteins after internalization by thyrocytes was monitored and compared to that of fluid phase markers. Kinetic internalization studies were performed using 125I-GlcNAc-BSA and 131I-Man-BSA. We observed that the apparent intake rate as well as the amount of hydrolyzed GlcNAc-BSA are smaller than the corresponding values for Man-BSA. These differences were reduced by GlcNAc competitors (thyroglobulin and ovomucoid) or a weak base (chloroquine). Part of the internalized GlcNAc-BSA was released into the extracellular milieu at a higher rate and shorter half life (t1/2 = approximately 30 min) than the Man-BSA (t1/2 = approximately 8 h). Subcellular homing was first studied by cell fractionation after internalization using 125I-ovomucoid and 131I-BSA. During Percoll density gradient fractionation, endogenous thyroperoxidase was used to separate subsets of organelles involved in the biosynthetic exocytotic pathway. Incubation of the cell homogenate in the presence of DAB and H2O2 before cell fractionation give rise to a shift in the density of organelles containing 3.5 times more ovomucoid than BSA. Discontinuous sucrose gradient showed that: (a) thyroperoxidase was colocalized with galactosyltransferase-contraining organelles in Golgi-rich subfractions; and (b) that at every time studied from 10 to 100 min, the ovomucoid/BSA ratio was higher in these organelles than in other subfractions. Finally we also observed that: (a) ovomucoid sequestered in the Golgi-rich subfraction incorporated [3H]galactose; and (b) that part of internalized ovomucoid was localized on the Golgi stacks as well as elements of the trans-Golgi, as revealed by immunogold labeling on ultrathin cryosections. These data prove that in thyrocytes GlcNAc accessible sugar moieties on soluble internalized molecules are sufficient to trigger their recycling via the Golgi apparatus.

Acetylglucosamine↗
PubMed1989

Down regulation of hypertrophied follicular cell volume in thyroid hyperplastic gland.

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.

Animals↗
PubMed1988

Glycosylphosphatidylinositol is involved in the membrane attachment of proteins in granules of chromaffin cells.

Incubation at 37 degrees C or treatment of granule membranes of chromaffin cells with Staphylococcus aureus phosphatidylinositol-specific phospholipase C converted from an amphiphilic to a hydrophilic form two proteins with molecular masses of 82 and 68 kDa respectively. Their release is time- and enzyme-concentration-dependent. We showed that they were immunoreactive with an anti-(cross-reacting determinant) antibody known to be revealed only after removal of a diacylglycerol anchor. Furthermore, the action of HNO2 suggests the presence of a non-acetylated glucosamine residue in the determinant. This is one of the first reports suggesting that a glycosylphosphatidylinositol anchor might exist in membranes other than the plasma membrane. We showed that the 68 kDa protein is probably not the subunit of dopamine (3,4-dihydroxyphenethylamine) beta-hydroxylase, an enzyme present in granules in both soluble and membrane-associated forms.

Animals↗
PubMed1988

Monoiodotyrosine formation during thyroglobulin processing in Golgi vesicles.

A golgi-enriched subfraction was obtained from porcine thyroid glands by differential centrifugation. When incubated in a suitable medium, these vesicles were able to concentrate iodide from the medium and bind it to protein. The iodination process was inhibited by methylmercapto-imidazole and was increased by the addition of an H2O2 generating system to the medium. Analysis of the protein content of the vesicles revealed the presence of 18 and 12-13 S thyroglobulin molecules, lacking mannose residues, and containing only monoiodotyrosine. It is concluded that in vitro, iodination can begin before exocytosis, in the smooth-surfaced vesicles derived from the golgi apparatus, as soon as N-acetylglucosamine is incorporated onto the pre-thyroglobulin molecule.

Animals↗
PubMed1987

Involution of hyperplastic goitre in the adult male rat. Tissue compartment process with early iodide effect: a stereological and biochemical study.

The morphological and functional changes during involution of hyperplastic goitre have been investigated in the adult male rat. Male wistar rats received an iodine-deficient diet for 6 months and during the last 2 months received propylthiouracil (PTU, 0.15%). By the end of this treatment (day 0), a hyperplastic goitre was obtained. A normal iodine supply was then given and PTU withdrawn. During the first 8 days of iodine refeeding, the plasma thyrotropin (TSH) remained at a high level (ten times the control value), whereas the thyroid iodide content was low on day 0, markedly increased on day 1 and decreased on day 4. Plasma T3 and T4 levels remained unchanged for 4 days and only increased on day 8. The total thyroid protein concentration was low on day 0 and then increased rapidly on day 8 (by 34%). The volume density of colloid remained low and unchanged until day 8, when it started to increase. However, the thyroid epithelial cell volume and the volume density of capillaries were raised on day 0, decreased rapidly in the next 8 days and more slowly later on. The total number of thyroid epithelial cells was considerably raised in the hyperplastic gland. It did not vary until day 16, when it decreased slowly, reaching a plateau on day 45 above the control value. The present data show that involution of hyperplastic goitre in the rat is due essentially to a decrease in thyroid epithelial cell volume and to a reduction of the increased number of capillary blood vessels present. The decrease in the number of epithelial cells is only 16.5%, suggesting that the death of thyroid epithelial cells contributes little. Half the process of involution, which occurs from days 0 to 8, is controlled by the thyroid iodide concentration rather than TSH, indicating the involvement of a thyroid autoregulatory mechanism. It must be emphasized, however, that the discontinuous pattern of epithelial cell number during involution may indicate that some cells with larger nuclei and more rapid turnover disappear more quickly after iodine refeeding.

Animals↗
PubMed1987

Intralysosomal hydrolysis of thyroglobulin: specific and cAMP-mediated activation by TSH.

Pig thyroid slices, pre-labelled with [125I]iodide, were incubated with or without thyrotropin (TSH), dibutyryl cyclic AMP (dbcAMP) or forskolin. After lysosome isolation, intralysosomal thyroglobulin (Tg) hydrolysis was determined by the increment in trichloroacetic acid (TCA)-soluble radioactivity. TSH stimulated the intralysosomal Tg hydrolysis. This stimulation was time and concentration dependent and was mimicked by forskolin or dbcAMP. When endocytosis and protein synthesis were blocked by inhibitors (nocodazole and puromycin) the stimulatory effect was still maintained. We conclude that TSH increases quickly and specifically, via a cAMP-mediated process, intralysosomal Tg hydrolysis, independent of its effects on endocytosis of Tg and lysosomal protease synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Thyroid autoregulation: impact on thyroid structure and function in rats.

Global response of the thyroid to a 10-fold increase in plasma iodide concentration results only in modifications of basolateral transfer for iodide where, by a balance phenomenon between influx and efflux, a net thyroid intake of 1.2 micrograms I/day is constantly maintained. The other main steps of thyroid iodine metabolism, thyroglobulin (Tg) iodination, endocytosis, and hydrolysis, remain constant. A stationary hormone secretion delivery results. This constant state is not found at a cellular level, where structural changes are observed in correlation with functional regulation of the cell dynamic state. Thus, an increase in plasma iodide concentration results in an increase of the apical membrane area (40%), whereas the basolateral membrane area decreases (18%). The volume of the follicle lumen increases (76%). Nevertheless, neither epithelial cell volume nor the structure of microvilli are modified. Comparison of iodine fluxes through the apical and basolateral membrane of the epithelial cell shows that an increase in plasma iodide concentration is correlated to a decrease of the Tg iodination and endocytotic fluxes (45%). A regulation also appears for basolateral transfer of iodide, whereas the lysosome system does not modulate the hormone secretion mechanism.

Animals↗
PubMed1985

Iodide accumulation into thyroid Golgi vesicles.

Pig thyroid Golgi vesicles incubated in a suitable medium were able to concentrate iodide from the medium. This trapping required the integrity of the vesicles, was time- and temperature-dependent, and was inhibited by a competitive inhibitor of iodide active transport (perchlorate), suggesting a facilitated transport mechanism.

Animals↗
PubMed1985

Waldeyer's ring (WR) involvement in Hodgkin's disease.

Of 750 patients with stage I, II or III Hodgkin's disease, admitted to the University and Hospital Radiotherapy Divisions, Florence, between 1960 and 1981, 28 (3.7%) had involvement of Waldeyer's ring (WR). In 25 patients there was associated involvement of upper cervical nodes. Other factors associated with WR involvement were age over 55 years, lymphocyte predominant histological sub-type, uninvolved mediastinum, and size of involved upper cervical nodes greater than that of involved lower cervical nodes. These factors help to define indications for prophylactic irradiation of WR.

Adolescent↗
PubMed1985

Thyroid morphological and functional heterogeneity: impact on iodine secretion.

Thyroid iodine turnover heterogeneity includes morphological (cellular and colloidal distribution space for iodide) and functional heterogeneity (hormone synthesis in the colloid). In 'normal' rats, both iodide actively trapped by the epithelial cell and that coming from deiodination of iodotyrosines present the same probability for thyroglobulin (Tg) iodination (Tg iodination flux: 4.0 +/- 0.3 micrograms I/day). A portion of the thyroid iodide is sequestered in the colloid lumen and is inoperative in the Tg iodination mechanisms. The masses of cell and colloid compartments are equivalent (0.018 +/- 0.002 micrograms I) while colloid iodide concentration is twice that of the cell (0.11 and 0.06, respectively). The turnover of about 3 micrograms I of colloid iodine (Tg) is follicle diameter-dependent (inter-follicular heterogeneity) and it is mainly characterized by 2 different half lives of 8 and 16 hours, respectively. Ninety percent of the thyroid iodine (hormone) secretion (1.10 +/- 0.11 micrograms I/day) is provided by this compartment rich in iodotyrosine residues (70%). The remaining 10% of iodine secretion is provided by a Tg pool (7 micrograms I) characterized by 2 compartments (intra-follicular heterogeneity) with slow and very slow turnovers. The longer the transit time of Tg molecules in the colloid, the higher their iodothyronine content.

Animals↗
PubMed1984

Early detection of local recurrences in the follow-up of primary breast cancer.

The results of physical examination (PE) in the detection of local recurrences (LR) from breast cancer are reviewed in the follow-up experience of 1139 breast cancer patients. A minimum follow-up time of 5 years was considered. LR accounted for 40% of total first relapses and isolated (without distant metastases) LR represented about 1/3 of total relapses. The chest wall was the most frequent site of LR. The extent of LR was correlated with the probability of associated distant metastases detectable at the time of LR diagnosis, whereas no correlations were found with the presence or absence of subjective symptoms at diagnosis. The mean free interval from primary surgery was 3 months shorter for LR detected in asymptomatic phase than in the symptomatic phase. This difference increased to 5 months for recurrences detected in the first 2 years, when PE controls were repeated every 6 months whereas a smaller difference of 2 months was observed over 2 years with yearly controls. The mean and 5-year actuarial survival was better (75.5 vs. 64.9 months and 54% vs. 40%) for cases detected in the asymptomatic phase than in the symptomatic phase; however, the difference was not statistically significant for the small sample considered and could be even partially due to length biased sampling. On the basis of the reported results, PE should still be recommended as a follow-up test, although further studies are needed to assess its real impact on prognosis.

Breast Neoplasms↗
PubMed1984

Hydrolysis of thyroglobulin inside isolated rat thyroid and liver lysosomes.

In vitro, poorly iodinated thyroglobulin (Tg) is hydrolysed at the same rate whether it is enclosed in thyroid or in liver lysosomes, while fully iodinated Tg is degraded faster inside liver lysosomes. After in vivo TSH administration, thyroid lysosomes hydrolyse fully iodinated Tg as fast as do liver lysosomes.

Animals↗
PubMed1982

Correlation between thyroid-follicle fusion and structural modifications of the epithelial cells. A quantitative study in the adult rat.

Changes in thyroid structure induced by a decrease in TSH or iodide-dependent stimulation were quantified by stereological analysis of light micrographs. Studies were carried out on intact (R5) and hypophysectomized (R5H) rats receiving 5 micrograms iodide, and on intact rats (R5O) receiving 50 micrograms iodide daily. For R5H- and R5O-thyroids, the mean parameters of the epithelial cells, height, volume and lateral membrane area, were smaller than those of R5-thyroids. An inverse shift was observed for the apical membrane area, whereas the peripheral membrane area was unchanged. The number of epithelial cells was similar in each of the three groups; however, the number of follicles was greater in R5-thyroids, suggesting that follicular fusion occurs in R5O- and R5H-thyroids. This was confirmed by direct observation. The present results demonstrate that in adult rats a lack of TSH or an increased iodide diet (insufficient to produce a physiopathological state) induce follicle fusion probably by means of cellular reorganization. This increase in follicle size could be involved in the regulation of thyroid iodine turnover.

Animals↗
PubMed1982

Thyroid iodide compartments and their implication in the rat thyroid iodine organification.

To estimate the relative participation of transported and intrathyroidally generated iodide (internal iodide) in the iodination of newly synthesized and preexisting thyroglobulin (Tg) in the rat thyroid, the specific radioactivities (SRAs) of thyroid iodide, Tg, lysosomal iodine, and plasma hormones were followed for 92 h after radioactive iodide injection in intact or hypophysectomized rats. In control rats, the SRA of Tg and lysosomal iodine reached a maximum at 12 h. However, the SRA of lysosomal iodide was always smaller than that of Tg. In contrast, the SRA of hormonal iodide attained a maximum at 48 h. Thus, newly labeled iodine is endocytosed and mixed inside the lysosomes with older previously iodinated molecules; hormone secretion is mainly due to old labeled iodine (i.e. iodine with a high SRA from 48-96 h). These results are consistent with the presence of least two Tg compartments, with different turnover rates and hormone contents. On the other hand, in hypophysectomized rats, the SRA of Tg, lysosomes, and hormones showed only one maximum, at 24 h. Furthermore, the SRAs of Tg and lysosomes were similar at each time interval. It is inferred that in such rats, the old labeled iodine compartment is strongly reduced, and that inside the lysosomes, newly labeled iodine is predominant. Since in hypophysectomized rats, the recycling of iodide is abolished, it is concluded that in normal rats: 1) transported iodide is organified mainly by direct iodination of newly synthesized Tg, independently of TSH, and 2) internal iodide is organified mainly by delayed iodination of preexisting Tg, this process being TSH dependent.

Animals↗
PubMed1980

Intrafollicular re-cycling of organic iodine in the hypophysectomized rat as observed by a long-term kinetic study.

A long-term kinetic study was started 8 days after hypophysectomy in rats previously adapted to receive 5 micrograms iodide daily, and maintained on the same diet after surgery. At each time, the renewed fraction for thyroglobulin (Tg) and lysosomes in the gland, and hormones in the plasma was calculated by the method of isotropic equilibrium. All the pools studied are renewed very slowly, but with different kinetics. Between time zero and the 25th day of the experiment, the renewed fraction in plasma hormones always exceeds that of Tg. Thus, in hypophysectomized rats, Tg pool is composed of at least two compartments with different turn-over rates. Tg molecules of both compartments are endocytosed, but that of the faster compartment participate in secretion in a preferential way. Peeling of the data for the 60-day period of experiment confirms these results. In addition, peeling demonstrates a 15-day delay in the turn-over of the second compartment. Such a delay was not found in the turn-over of this compartment in lysosomes. Thus, we may again postulate, in hypophysectomized rats, a recycling of iodine in organic form from the lysosomes back to the luminal colloid, as previously porposed for control rats.

Animals↗
PubMed1980

Impairment of the mental status of patients on regular dialysis treatment.

The purpose of this study was to assess the mental status of 42 patients on regular dialysis treatment (RDT) by using the Wechsler Adult Intelligence Scale (WAIS) and Wechsler Memory Scale (WMS). Findings were correlated with serum aluminium levels, PTH levels, residual renal function (RRF) and duration of RDT. An impairment of neuropsychological performance related to the duration of RDT was found. However, a possible role of PTH and of absence of RRF could not be excluded. These observations suggest that standard haemodialysis strategies are not able to prevent pathological changes in the brain of uraemic patients.

Adolescent↗
PubMed1979

The follicular iodide pool as a two-compartment system: evidence from the unstimulated thyroid gland.

The isotopic equilibrium method was used for a 60-day period to follow iodine turnover in control and hypophysectomized rats. After the suppression of TSH by hypophysectomy, only the captured iodide is used for iodination of thyroglobulin, the iodide recycling being abolished. In unstimulated gland, two metabolically distinct iodide compartments do exist which differ either in their chemical form or in their morphological distribution, or both.

Animals↗