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A Radulescu

Publications and source records attributed to A Radulescu.

9 recordsLinked to original sources
PubMed2000

Spin accumulation and domain wall magnetoresistance in 35 nm Co wires

An enhancement of the resistance due to the presence of only one or two isolated domain walls is clearly evidenced by transport measurements in 35 nm epitaxial Co wires, 20 &mgr;m long. The deduced relative change in the resistivity is at least 1 order of magnitude larger than the one predicted from a model based on the mixing of spin channels occurring over the length scale of the domain wall width [P. M. Levy and S. Zhang, Phys. Rev. Lett. 79, 5110 (1997)]. This inconsistency can be resolved by taking the effect of spin accumulation into account, which scales in the case of Co over the much larger distance of the spin diffusion length.

Journal Article↗
PubMed2000

Characterization of autonomous thyroid adenoma: metabolism, gene expression, and pathology.

Fifty-one in vivo characterized autonomous single adenomas have been studied for functional parameters in vitro, for gene and protein expression and for pathology, and have been systematically compared to the corresponding extratumoral quiescent tissue. The adenomas were characterized by a high level of iodide trapping that corresponds to a high level of Na+ /iodide symporter gene expression, a high thyroperoxidase mRNA and protein content, and a low H2O2 generation. This explains the iodide metabolism characteristics demonstrated before, ie, the main cause of the "hot" character of the adenomas is their increased iodide transport. The adenomas spontaneously secreted higher amounts of thyroid hormone than the quiescent tissue and in agreement with previous in vivo data, this secretion could be further enhanced by thyrotropin (TSH). Inositol uptake was also increased but there was no spontaneous increase of the generation of inositol phosphates and this metabolism could be further activated by TSH. These positive responses to TSH are in agreement with the properties of TSH-stimulated thyroid cells in vitro and in vivo. They are compatible with the characteristics of mutated TSH receptors whose constitutive activation accounts for the majority of autonomous thyroid adenomas in Europe. The number of cycling cells, as evaluated by MIB-1 immunolabeling was low but increased in comparison with the corresponding quiescent tissue or normal tissue. The cycling cells are observed mainly at the periphery; there was very little apoptosis. Both findings account for the slow growth of these established adenomas. On the other hand, by thyroperoxidase immunohistochemistry, the whole lesion appeared hyperfunctional, which demonstrates a dissociation of mitogenic and functional stimulations. Thyroglobulin, TSH receptor, and E-cadherin mRNA accumulations were not modified in a consistent way, which confirms the near-constitutive expression of the corresponding genes in normal differentiated tissue. On the contrary, early immediate genes expressions (c-myc, NGF1B, egr 1, genes of the fos and jun families) were decreased. This may be explained by the proliferative heterogeneity of the lesion and the previously described short, biphasic expression of these genes when induced by mitogenic agents. All the characteristics of the autonomous adenomas can therefore be explained by the effect of the known activating mutations of genes coding for proteins of the TSH cyclic adenosine monophosphate (cAMP) cascade, all cells being functionally activated while only those at the periphery multiply. The reason of this heterogeneity is unknown.

Adenoma↗
PubMed1997

Cloning and sequence analysis of human calcyphosine complementary DNA.

Calcyphosine, initially identified as thyroid protein p24, is a calcium-binding protein containing four EF-hand domains. It was first cloned and characterized in the dog and corresponds to R2D5 antigen in rabbit. Using the canine calcyphosine cDNA sequence as a probe, we have isolated its human counterpart from a thyroid cDNA library. The two sequences display a high degree of conservation, both at nucleotide and deduced amino acid levels. Sequence comparison with other proteins showed that the closest homologue of calcyphosine is the crustacean CCBP-23 protein. Northern blot analysis revealed that calcyphosine messenger RNA is much less abundant in human than in canine thyrocytes. Western blot experiments indicated that the amount of protein is also dramatically reduced in man compared to dog.

Amino Acid Sequence↗
PubMed1996

Identification and characterization of novel genes modulated in the thyroid of dogs treated with methimazole and propylthiouracil.

Induction of cell proliferation by mitogen or growth factor stimulation leads to the specific stimulation or repression of a large number of genes. To better understand differentiated epithelial cell growth regulation, we have initiated a study to identify genes which are regulated by the thyrotropin-dependent mitogenic pathway in dog thyroid cells. A thyroid cDNA library was prepared from a methimazole and propylthiouracil-treated dog and differentially screened with probes derived from control or stimulated thyroids. Among 19 clones isolated, 6 encode known proteins (inwardly rectifying potassium channel, nucleosome assembly protein, ribosomal protein L7, elongation factor 1alpha, non-muscle myosin light chain, and heat shock protein 90beta). The 13 others correspond to proteins whose function is unknown. Among them, 5 correspond to mRNAs whose expression was modulated by mitogenic stimulation of thyrocytes in primary culture. A preliminary characterization of two of these cDNAs is reported: clone 5, which might represent a novel, atypical protein kinase, and clone 3, which contains ankyrin-like repeats, suggesting that it might interact with other proteins.

Animals↗
PubMed1995

Expression of mutant p21ras induces insulin-like growth factor 1 secretion in thyroid epithelial cells.

There is substantial evidence supporting the existence of insulin-like growth factor 1 (IGF-1) autocrine circuits in many tumor types, although the underlying inducing event has remained undefined. In order to address this matter, we have generated several immortalized human thyroid epithelial cell lines containing a zinc-inducible mutant H-ras gene and used these to investigate the relationship between expression of mutant p21ras and secretion of IGF-1. Induction of the transgene in the presence of zinc ions (Zn2+) was confirmed by Northern blot analysis and immunocytochemistry. IGF-1 levels in serum-free medium, stripped of binding proteins, were monitored using a sensitive radioimmunoassay. Expression of mutant p21ras in these cells, induced by Zn2+, resulted in an approximate 30-fold increase in the IGF-1 production rate, reaching a level exceeding that of human embryo fibroblasts. The data presented here suggest that an activating mutation of a ras oncogene may directly account for IGF-1 secretion in some human tumor cells.

Base Sequence↗
PubMed1994

Evidence against involvement of APC mutation in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is one of several tumours associated with familial adenomatous polyposis (FAP), an inherited tumour syndrome which appears to result from germ-line mutation of the APC tumour suppressor gene. Here we investigate the possibility that somatic mutation of APC might play a role in sporadic PTC. 16 cases of PTC together with matched normal tissue were examined by single-strand conformation polymorphism (SSCP) analysis, concentrating on the mutation cluster region (MCR) of the APC gene (codons 1286-1513). No evidence of mutation was observed in any sample. We conclude that APC mutation, at least in the MCR, is not a significant causal mechanism in sporadic PTC.

Adolescent↗
PubMed1994

In vitro reconstruction of tumour initiation in a human epithelium.

Knowledge of tumour initiation in human epithelia is limited by sample availability and difficulty in experimental manipulation of human cells. The thyroid is a useful model since, in addition to multiple tumour stages, it presents two distinct 'pathways' of tumorigenesis: 'follicular' tumours, in which ras oncogene mutations occur at high frequency and 'papillary' tumours, associated with ret (or trk) activation. We have used these observations to reconstruct early thyroid tumorigenesis, using amphotropic retroviral vectors. When introduced into normal thyroid epithelial cells, mutant ras induces self-limiting growth of well-demarcated, differentiated colonies--a phenotype consistent with follicular adenoma. Activated ret on the other hand induces smaller, poorly-demarcated colonies with a morphology consistent with early papillary tumours. Mutant p53--which occurs only in the latest stages of thyroid cancer--was without effect. Our results provide the first direct experimental evidence in a human epithelium for alternative initiating oncogenes and their determination of the subsequent 'direction' of tumour development.

Base Sequence↗