[Hepatic angiosarcoma in a patient with autoimmune hepatitis].
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Biomedical subjects
Publications and source records attributed to J Boniver.
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We have used in situ hybridization to investigate the expression of TNF-alpha genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-alpha mRNA. A second phase of cytokine gene expression starts on day 16. The density of positive cells progressively increases up to day 20. Thymuses at 15 days of gestation and after birth do not express detectable cytokine mRNA. In an attempt to identify the nature of the TNF-alpha mRNA-producing cells, acid phosphatase activity, which is characteristic of the macrophage lineage, was studied in the same thymuses. Acid phosphatase-positive cells only appear on day 15. Their frequency increases up to birth. However, no correlation can be established between acid phosphatase--and TNF alpha mRNA--positive cells. The results indicate that a small subset of thymic cells is responsible for TNF-alpha mRNA production during ontogeny: These cells are not yet identified. The possible role of TNF-alpha in thymic ontogeny is discussed.
Thymic epithelial cell physiology is known to be under neuroendocrine control. In particular, thyroid hormones modulate thymic hormone secretion by thymic epithelial cells in vivo and in vitro, thus suggesting the existence of specific receptors for those hormones in this component of the thymic microenvironment. Yet, thyroid hormone-binding sites have previously been detected only in crude thymus fractions and lymphocytes. We, thus, decided to search for T3 receptors in the thymic epithelium, by using an antinuclear T3 receptor monoclonal antibody. In situ immunohistochemical analysis of thymic frozen sections showed nuclear labeling of both lymphoid and nonlymphoid cells in the cortex and medulla. Moreover, in vitro studies using thymic epithelial cell lines and the so-called thymic nurse cells revealed a positive reaction in the chromatin, with nucleoli remaining negative. Immunoblot data clearly showed a single protein band of 57K reactive with the antinuclear T3 receptor antibody in murine thymus extracts as well as in the thymic epithelial cell lines. Lastly, in vitro treatment of these cells with T3 resulted in a transient, yet profound, down-modulation of the receptor. In conclusion, our findings provide molecular evidence that the action of thyroid hormones on thymic epithelium occurs via the typical 57K nuclear T3 receptors.
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The CUBIC program displays three-dimensional colored dot plots of flow cytometric trivariate data collected by unmodified commercial instruments (FACScan flow cytometer, FACS 440 cell sorter). Assuming a bimodal distribution of the fluorescence intensity of the cells, the eight theoretical subpopulations involved in a three-color fluorescence histogram are clearly localized in the 3-D space by colored dots that are clustered near each corner of a cubic frame. Rotation, tilting, and zoom functions are available. Table look-up is not needed. CUBIC was illustrated by two experiments: 1) three-color immunofluorescence of antigens on human lymphocytes using monoclonal antibodies conjugated either to fluorescein (FITC), to R-phycoerythrin (PE), or to biotin revealed by a streptavidin coupled to a PE-Texas red tandem conjugate (TC); 2) two-color immunofluorescence of CD4 and CD8 antigens on thymocytes of healthy or preleukemic mice correlated to the DNA content quantified by 7-amino-actinomycin D (7-AAD). The three fluorescences were excited by a single argon-ion laser emitting at 488 nm.
The thymic stroma plays a critical role in the generation of T lymphocytes by direct cell-to-cell contacts as well as by secreting growth factors or hormones. The thymic epithelial cells, responsible for thymic hormone secretion, include morphologically and antigenically distinct subpopulations that may exert different roles in thymocyte maturation. The recent development of thymic epithelial cell lines provided an interesting model for studying thymic epithelial influences on T cell differentiation. Treating mouse thymocytes by supernatants from one of TEC line (IT-76M1), we observed an induction of thymocyte proliferation and an increase in the percentages of CD4-/CD8- thymocytes. This proliferation was largely inhibited when thymocytes were incubated with IT-76M1 supernatants together with an anti-thymulin monoclonal antibody, but could be enhanced by pretreating growing epithelial cells by triiodothyronine. We suggest that among the target cells for thymulin within the thymus, some putative precursors of early phenotype might be included.
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The insulin-like growth factor II (IGF-II) is a small protein implicated in fetal growth and development. It may play a role in the neoplastic process. The IGF-II gene is located on the short arm of chromosome II near insulin and c-Ha-ras I genes. Three distinct promoters control the transcription of this gene, leading to different IGF-II mRNA species. We have analyzed 21 human colorectal tumors and found overexpression of IGF-II in 6 of them (30%). When compared with expression in normal adjacent tissues, IGF-II mRNA increase in these tumors was either moderate (2- to 15-fold) or very marked (200- to 800-fold). In situ hybridization experiments confirmed that high IGF-II mRNA amounts were localized in cancer cells of the tumors overexpressing the IGF-II gene. In addition, DNA analysis revealed a structural modification of one IGF-II locus in one tumor characterized by very high IGF-II mRNA.
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Isolated thymic nurse cells (TNC) represent a specialized microenvironment in vivo where thymocytes interact specifically with subcapsular epithelial cells. They are thought to play a critical role in the process of T cell differentiation. We demonstrate that recombinant murine interferon-gamma and recombinant human tumor necrosis factor-alpha can act on these interactions: they stimulate TNC-derived epithelial cells to establish interactions with thymocytes in vitro and to form new lymphoepithelial complexes. This phenomenon is partially inhibited by anti-Ia monoclonal antibodies. Implications of these findings for normal intrathymic differentiation are discussed.