19 research outputs found

    A Novel Role for Niemann-Pick Disease Type 2C Protein in Papillae Formation

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    BACKGROUND: Despite the presence of papillary structures and papillary tumors in humans, the mechanism of papillae formation is unknown. We describe herein a novel role for Niemann-Pick disease type 2C (NPC2) protein, a cholesterol binding protein in the lysosome, in papillae formation. METHODOLOGY/PRINCIPAL FINDING: We examined NPC2 protein expression in surgical samples of papillary tissues by immunohistochemical stain, and all papillary tissues expressed NPC2 protein in the epithelium. To examine our hypothesis of NPC2 protein-mediated papillae formation, we carried out xenograft experiments using wild H460 cells (large cell lung carcinoma cell line) that constitutively expressed abundant NPC2 protein and NPC2 protein-depleted H460 cells by NPC2 shRNA. The xenografts of wild H460 cells and empty shRNA vector cells showed distinct papillae formation, whereas NPC2 protein-depleted H460 cells displayed markedly reduced or no papillae. Since all papillary tissues have open spaces we examined whether NPC2 protein might also contribute to the creation of open spaces. The TUNEL assay in the xenografts of wild and empty shRNA vector H460 cells showed massive cell death, and NPC2 protein-depleted cells displayed minimal cell death. Measurement of caspase 3/7 activities in cultured H460 cells supported NPC2 protein-mediated apoptotic cell death. The presence of excess NPC2 protein, however, did not always produce papillae as seen in the xenografts of CHO cells that were stably transfected with NPC2. CONCLUSIONS/SIGNIFICANCE: The NPC2 protein of certain cells forms papillae coupled with apoptosis that creates open space. This protein may have future applications to modulate papillae formation and papillary growth in tumor tissues

    Clinical Study Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy

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    The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves' disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low

    Guidelines for the treatment of childhood-onset Graves’ disease in Japan, 2016

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    NPC2 protein expression in cultured H460 cells.

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    <p>Immunohistochemical staining showed abundant NPC2 protein in wild and empty vector cells and markedly reduced NPC2 protein in <i>NPC2-shRNA</i>-containing cells.</p

    Papillae formation in xenografts of three types of H460 cells.

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    <p>A: Hematoxylin-eosin stain. B: Immunohistochemical stain for NPC2 protein. Distinct papillae formation was seen in wild and empty vector cells. No papilla was seen in <i>NPC2-shRNA</i> containing cells (A). NPC2 protein was localized in the epithelium of papillae (B).</p

    NPC2 protein expression in human papillary tissues.

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    <p>Immunohistochemical stain showed the presence of cytoplasmic NPC2 protein (brown color) in surgical samples of human papillary tissues. All papillary tissues have open spaces outside of papillary projections. The numbers indicate the degree of the magnification.</p

    NPC2 protein expression in CHO cells.

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    <p>Immunohistochemical stain of NPC2 protein in wild CHO cell (a), CHO cells stably transfected with <i>NPC2</i> (b) and xenograft of CHO cells transfected with <i>NPC2</i> (c). No papilla was seen in the xenograft, despite abundant NPC2 protein expression.</p

    Presence of apoptotic cells in human papillary tissues.

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    <p>TUNEL assay showed the presence of apoptotic cells in representative samples of human papillary tissues; arrows indicate examples of apoptotic cells.</p

    Characterization of three types of cultured H460 cells.

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    <p>Cell morphology: Wild and empty vector cells showed the same cell morphology, whereas cells containing <i>NPC2-shRNA</i> displayed clearly separated individual cells. Cell proliferation activity in NPC2-rich and-depleted H460 cells: Cells (1000 cells/well) were plated into a 96-well plate. Cell proliferation activity on each day was measured by incubating cells with the reagents for 2 hours in a CO2 incubator. The results are mean ± SD of quadruplicate samples of one of the three experiments. *<i>p</i><0.01 when compared with the empty vector cells.</p
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