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2.
Diagn Cytopathol ; 42(8): 694-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23729380

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is a rare but aggressive form of undifferentiated thyroid carcinoma which arises from previously well-differentiated thyroid carcinomas, such as papillary carcinoma or follicular carcinoma. We report on an interesting case of ATC found in an enlarging neck mass with metastatic papillary carcinoma found in mediastinal lymph nodes sampled by endoscopic bronchial-ultrasound guided- fine-needle aspiration, due to the incidental finding of a lung mass by CT scan. Divergent morphologies on cytology preparations were resolved by immunohistochemistry, which aided in the identification of both sites of malignancy and the common thread between them. The eventual palliative resection demonstrated the various components including undifferentiated thyroid carcinoma, papillary carcinoma, and background lymphocytic thyroiditis.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Mediastinum/pathology , Thyroid Carcinoma, Anaplastic/pathology , Aged, 80 and over , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Mediastinum/diagnostic imaging , Neck/diagnostic imaging , Neck/pathology , Tomography, X-Ray Computed
3.
Proc Natl Acad Sci U S A ; 99(5): 3117-22, 2002 Mar 05.
Article in English | MEDLINE | ID: mdl-11867720

ABSTRACT

The protein defective in hereditary hemochromatosis, called HFE, is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). Its association with beta2M was previously shown to be necessary for its stability, normal intracellular processing, and cell surface expression in transfected COS cells. Here we use stably transfected Chinese hamster ovary cell lines expressing both HFE and beta2M or HFE alone to study the effects of beta2M on the stability and maturation of the HFE protein and on the role of HFE in transferrin receptor 1 (TfR1)-mediated iron uptake. In agreement with prior studies on other cell lines, we found that overexpression of HFE, without overexpressing beta2M, resulted in a decrease in TfR1dependent iron uptake and in lower iron levels in the cells, as evidenced by ferritin and TfR1 levels measured at steady state. However, overexpression of both HFE and beta2M had the reverse effect and resulted in an increase in TfR1-dependent iron uptake and increased iron levels in the cells. The HFE-beta2M complex did not affect the affinity of TfR1 for transferrin or the internalization rate of transferrin-bound TfR1. Instead, HFE-beta2M enhanced the rate of recycling of TfR1 and resulted in an increase in the steady-state level of TfR1 at the cell surface of stably transfected cells. We propose that Chinese hamster ovary cells provide a model to explain the effect of the HFE-beta2M complex in duodenal crypt cells, where the HFE-beta2M complex appears to facilitate the uptake of transferrin-bound iron to sense the level of body iron stores. Impairment of this process in duodenal crypt cells leads them to be iron poor and to signal the differentiating enterocytes to take up iron excessively after they mature into villus cells in the duodenum of hereditary hemochromatosis patients.


Subject(s)
HLA Antigens/metabolism , Hemochromatosis/metabolism , Histocompatibility Antigens Class I/metabolism , Iron/metabolism , Major Histocompatibility Complex , Membrane Proteins , Transferrin/metabolism , Animals , CHO Cells , Cell Membrane/metabolism , Cricetinae , Endocytosis , Genetic Diseases, Inborn , HLA Antigens/physiology , Hemochromatosis Protein , Histocompatibility Antigens Class I/physiology , Humans , Mice , Receptors, Transferrin/genetics , Receptors, Transferrin/metabolism , Receptors, Transferrin/physiology , beta 2-Microglobulin/metabolism , beta 2-Microglobulin/physiology
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