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Shuji Toda - One of the best experts on this subject based on the ideXlab platform.
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effects of various types of extracellular matrices on adhesion proliferation differentiation and c fos protein expression of porcine Thyroid Follicle cells
Cell Structure and Function, 1995Co-Authors: Shuji Toda, Sueo Matsumura, Nobuhisa Yonemitsu, Noboru Fujitani, Kiyomi Terayama, Sadayuki Funatsumaru, Hajime SugiharaAbstract:Thyroid Follicles in vivo are embedded in extracellular matrix (ECM). The composing epithelial cells are in close contact with ECM at the basal side. To examine cell-to-ECM interactions, we studied adhesion, proliferation and differentiation of porcine Follicle cells monolayer-cultured on type I and IV collagen, fibronectin or laminin. At 3 h in culture, laminin had the lowest rate of cell adhesion. In proliferation, type IV collagen induced the highest level of nuclear bromodeoxyuridine intake. In a functional differentiation, laminin had about 3 times as much triiodothyronine production as the other ECM molecules. In confluent, culture cells, we also examined an expression of c-fos protein, a transcription factor that plays crucial roles in signal transduction. Immunocytochemistry detected the protein mainly in the nuclei. Western blot showed that laminin induced the highest level of its expression. Thyrotropin (TSH, 10 mU/ml) did not affect adhesion of the cells on any of the substrata or proliferation of the cells on fibronectin ; nor did TSH affect c-fos protein expression of the cells on the substrata except for fibronectin. Our results suggest that type IV collagen and laminin, major components of basement membrane, play positive roles in proliferation and differentiation of Follicle cells, respectively, while laminin has no positive effect on adhesion of the cells at early culture ; that the cells express c-fos protein even in contact inhibition of growth and its expression is regulated in part by ECM ; and that ECM controls some behaviors of the cells in a TSH-dependent or TSH-independent manner.
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differentiation of human Thyroid Follicle cells from normal subjects and basedow s disease in three dimensional collagen gel culture
Pathology Research and Practice, 1992Co-Authors: Shuji Toda, N Yonernitsu, Y Hikichi, Hajime Sugihara, Norimasa KoikeAbstract:Thyroid Follicles, an essential functional unit of the Thyroid, exist in the extracellular matrix of the tissue in vivo. Therefore, in any monolayer culture system, the Follicles cannot be reconstructed. Our previous study adopting three-dimensional collagen gel culture showed that isolated porcine Follicle cells reconstructed Thyroid Follicles specific for the Thyroid gland in vivo. To elucidate whether this culture system is also applicable to human Follicle cells, and furthermore to provide a culture system for investigations of the pathogenesis of human Thyroid diseases, we tried to culture isolated human Follicle cells of normal Thyroid tissue and of Basedow's disease in three-dimensional collagen gel. In this culture system, they apparently reconstructed Thyroid Follicles. The component cells of the reconstructed Follicles exhibited structural polarity specific for human Thyroid Follicle cells and produced Thyroid hormones. In addition, the cells responded to a TSH-stimulation in terms of morphological and functional differentiation, and they presented HLA-DR antigen with an interferon-gamma-stimulation. This report is a first instance of reconstruction of human Thyroid Follicles and HLA-DR antigen induction in three-dimensional Follicle structures in vitro. This culture system provides a more physiological environment in vitro for biological and pathogenetic investigations of human Thyroid Follicle cells than the monolayer culture system. Further experiments using this method will probably provide new clues to the pathogenetic mechanisms of human Thyroid diseases.
Bengt Westermark - One of the best experts on this subject based on the ideXlab platform.
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expression of transforming growth factor beta1 activin a and their receptors in Thyroid Follicle cells negative regulation of thyrocyte growth and function
Endocrinology, 1999Co-Authors: Asa Franzen, Bengt Westermark, Ester Piek, Peter Ten Dijke, Nilserik HeldinAbstract:Expression of transforming growth factor-beta1, activin A, and their receptors in Thyroid Follicle cells: negative regulation of thyrocyte growth and function.
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epidermal growth factor stimulates Thyroid Follicle neogenesis in collagen gel culture
Thyroid, 1991Co-Authors: Kerstin Westermark, Mikael Nilsson, Bengt WestermarkAbstract:The mechanism involved in the neoformation of Thyroid Follicles is poorly understood. In the present study, whole porcine Thyroid Follicles were cultured as "miniorgans", embedded within collagen gels. Incubation was performed up to 4 days with or without EGF (10 ng/ml) and TSH (2 mU/ml). A single dose of 3H-thymidine was added at the start of the experiments in some cases. Light microscopy and autoradiography was performed. EGF induced a dramatic migration of Follicles cells; these were seen to back out from the mother Follicle and formed microFollicles with normal polarity including microvilli at the apical border. As evident from the analysis of 3H-thymidine incorporation, most microFollicles were comprised of newly divided cells. The results infer a new mechanism for the neoformation of Follicles in the Thyroid.
Terry F Davies - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Follicle formation and thyroglobulin expression in multipotent endodermal stem cells
Thyroid, 2013Co-Authors: Rauf Latif, Terry F DaviesAbstract:Objective: The aim of this study was to assess the impact of transcriptional induction on Thyroid follicular cell (TFC) differentiation from endodermally matured embryonic stem (ES) cells. The Thyroid transcription factors—NKx2 homeobox 1 (NKx2-1, formerly called TTF-1) and Paired box gene 8 (Pax8)—are known to associate biochemically and synergistically in the activation of Thyroid functional genes including the sodium/iodide symporter (NIS), thyrotropin (TSH) receptor (TSHR), thyroglobulin (Tg), and Thyroid peroxidase (TPO) genes. In this study, we investigated the ability of ectopically expressed Pax8 and NKx2-1 to further the induction and differentiation of murine ES cells into potential TFCs. Methods: ES cells were stably transfected with either the Pax8 gene, the NKx2-1 gene, or both genes to study the induction of NIS, TSHR, Tg, and TPO genes as assessed using both quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and protein expression. The derived cells were cultured with or...
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preservation of functioning human Thyroid organoids in the severe combined immunodeficient mouse iii thyrotropin independence of Thyroid Follicle formation
Endocrinology, 1994Co-Authors: M Valentine, A Martin, Pamela D Unger, N Katz, L D Shultz, Terry F DaviesAbstract:The severe combined immunodeficient (scid) mouse allows the in vivo reconstitution of Thyroid Follicles from Thyroid monolayer cells when transplanted sc within an extracellular basement membrane matrix. After 2-3 weeks, these human Thyroid organoids show an active microfollicular histology and secrete human thyroglobulin into the murine serum in response to the administration of recombinant human TSH. Furthermore, such organoids survive for more than 3 months in this functional state. To assess whether Thyroid follicular reconstitution was TSH dependent, we examined organoid follicular reconstruction in T3-induced hyperThyroid scid mice, in which endogenous murine TSH was presumed to be totally suppressed. By providing water with 12 micrograms/ml T3, we increased the murine serum T3 levels from a mean of 1.9 nmol/liter in controls to greater than 12.0 nmol/liter. After 3 weeks, Thyroid cells derived from normal human Thyroid monolayers were suspended in an extracellular basement membrane matrix, and the suspension was transplanted sc into scid mice (with or without T3-induced hyperThyroidism) and allowed to reconstitute. Histological examination 4 weeks later showed a similar degree of Thyroid Follicle formation in mice treated with or without T3, indicating that the hyperThyroid state had caused no interference with Thyroid Follicle reconstitution. This was further confirmed by transmission electron microscopy, which demonstrated normal human Thyroid Follicle cell polarity in the organoids of both euThyroid and hyperThyroid mice. In addition, using an extracellular basement membrane preparation with reduced growth factor (epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor) levels also allowed normal Thyroid Follicle formation in T3-fed mice. These data demonstrate that in vivo Thyroid Follicle formation is TSH independent and that extraThyroidal epidermal growth factor, insulin-like growth factor-I, and platelet-derived growth factor may be relatively unimportant. The factors and molecular mechanisms leading to follicular reorganization of adult human Thyroid cells remain to be determined, but are likely to depend largely on intraThyroidal growth factor secretion and cell-cell interaction.
Norimasa Koike - One of the best experts on this subject based on the ideXlab platform.
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differentiation of human Thyroid Follicle cells from normal subjects and basedow s disease in three dimensional collagen gel culture
Pathology Research and Practice, 1992Co-Authors: Shuji Toda, N Yonernitsu, Y Hikichi, Hajime Sugihara, Norimasa KoikeAbstract:Thyroid Follicles, an essential functional unit of the Thyroid, exist in the extracellular matrix of the tissue in vivo. Therefore, in any monolayer culture system, the Follicles cannot be reconstructed. Our previous study adopting three-dimensional collagen gel culture showed that isolated porcine Follicle cells reconstructed Thyroid Follicles specific for the Thyroid gland in vivo. To elucidate whether this culture system is also applicable to human Follicle cells, and furthermore to provide a culture system for investigations of the pathogenesis of human Thyroid diseases, we tried to culture isolated human Follicle cells of normal Thyroid tissue and of Basedow's disease in three-dimensional collagen gel. In this culture system, they apparently reconstructed Thyroid Follicles. The component cells of the reconstructed Follicles exhibited structural polarity specific for human Thyroid Follicle cells and produced Thyroid hormones. In addition, the cells responded to a TSH-stimulation in terms of morphological and functional differentiation, and they presented HLA-DR antigen with an interferon-gamma-stimulation. This report is a first instance of reconstruction of human Thyroid Follicles and HLA-DR antigen induction in three-dimensional Follicle structures in vitro. This culture system provides a more physiological environment in vitro for biological and pathogenetic investigations of human Thyroid Follicle cells than the monolayer culture system. Further experiments using this method will probably provide new clues to the pathogenetic mechanisms of human Thyroid diseases.
A Desbree - One of the best experts on this subject based on the ideXlab platform.
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dosimetry at the sub cellular scale of auger electron emitter 99mtc in a mouse single Thyroid Follicle
Applied Radiation and Isotopes, 2016Co-Authors: A Taborda, Nadia Benabdallah, A DesbreeAbstract:The Auger-electrons emitted by (99m)Tc have been recently associated with the induction of Thyroid stunning in in vivo experiments in mice, making the dosimetry at the sub-cellular level of (99m)Tc a pertinent and pressing subject. The S-values for (99m)Tc were calculated using MCNP6, which was first validated for studies at the sub-cellular scale and for low energies electrons. The calculation was then performed for (99m)Tc within different cellular compartments in a single mouse Thyroid Follicle model, considering the radiative and non-radiative transitions of the (99m)Tc radiation spectrum. It was shown that the contribution of the (99m)Tc Auger and low energy electrons to the absorbed dose to the follicular cells' nucleus is important, being at least of the same order of magnitude compared to the emitted photons' contribution and cannot be neglected. The results suggest that Auger-electrons emitted by (99m)Tc play a significant role in the occurrence of the Thyroid stunning effect in mice.
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we ab 204 12 dosimetry at the sub cellular scale of auger electron emitter 99m tc in a mouse single Thyroid Follicle model
Medical Physics, 2015Co-Authors: A Taborda, Nadia Benabdallah, A DesbreeAbstract:Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single Thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the Thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres of unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single Thyroid Follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse Thyroid Follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.