{"_buckets": {"deposit": "09441669-4430-4c17-97a8-b8814c4c3026"}, "_deposit": {"id": "3721", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "3721"}, "status": "published"}, "_oai": {"id": "oai:soar-ir.repo.nii.ac.jp:00003721", "sets": ["462"]}, "author_link": ["6571", "6572", "6573", "6574", "6575", "6576", "6577"], "item_1628147817048": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_ab4af688f83e57aa", "subitem_version_type": "AM"}]}, "item_6_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2014-01", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "1", "bibliographicPageEnd": "107", "bibliographicPageStart": "101", "bibliographicVolumeNumber": "133", "bibliographic_titles": [{"bibliographic_title": "THROMBOSIS RESEARCH"}]}]}, "item_6_description_20": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Background: Hepatic endoplasmic reticulum (ER) storage disease (HERSD) associated with hypofibrinogenemia has been reported in patients with four types of heterozygous gamma-chain variant fibrinogen in the C terminal region. Of interest, substitution of gamma R375W induced hypofibrinogenemia and HERSD, whereas gamma R375G induced dysfibrinogenemia. Objectives: To analyze the synthesis of variant fibrinogen and morphological characteristics, we established variant fibrinogen-producing cells and compared them with wild-type fibrinogen-synthesizing cells. Methods: The fibrinogen gamma-chain expression vectors coding gamma 375W and gamma 375G were altered by oligonucleotide-directed mutagenesis and transfected into Chinese hamster ovary (CHO) cells. Synthesis of fibrinogen (media and cell lysates) was measured by ELISA for each cloned cell line and morphological characteristics were observed by immunofluorescence and transmission electron microscopy. Results: The medium/cell lysate fibrinogen ratio of gamma 375W-CHO cells was markedly lower than that of the normal cells and gamma 375G-CHO cells. Immunostaining with anti-fibrinogen antibody showed only gamma 375W-CHO cells, but revealed two types of cells containing cytoplasmic inclusion bodies, scattered large-granular bodies and fibrous forms. Observation by confocal microscopy indicated that both inclusion bodies were colocalized with fibrinogen and ER-membrane protein; furthermore, transmission electron microscopic observation demonstrated dilatation of the ER by large-granular inclusion bodies and fibrous forms filled with regularly structured fibular materials within the dilated ER. Conclusion: These results demonstrated that assembled and non-secreted gamma 375W fibrinogen was accumulated in the dilated ER and aggregated variant fibrinogen was seen as regularly structured fibular materials, which was similar to the fingerprint-like pattern observed at inclusion bodies in patients\u0027 hepatocytes affected with HERSD.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "THROMBOSIS RESEARCH. 133(1):101-107 (2014)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Okumura, Nobuo", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.OVnmgCkh.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000328911900018"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "PERGAMON-ELSEVIER SCIENCE LTD"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "24210681"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/24210681", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1016/j.thromres.2013.10.033"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1016/j.thromres.2013.10.033", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "Copyright© 2013 Elsevier Ltd."}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "author"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0049-3848", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0049-3848", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA00863148", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Endoplasmic reticulum; Fibrinogen storage disease; Fibrinogen gamma-chain mutation; Hepatic endoplasmic reticulum storage disease; Hypofibrinogenemia"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "STORAGE DISEASE; LIVER-DISEASE; ALPHA(1)-ANTITRYPSIN DEFICIENCY; HYPOFIBRINOGENEMIA; MUTATION; DEGRADATION; BIOSYNTHESIS; SECRETION; AUTOPHAGY; MODEL"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Background: Hepatic endoplasmic reticulum (ER) storage disease (HERSD) associated with hypofibrinogenemia has been reported in patients with four types of heterozygous gamma-chain variant fibrinogen in the C terminal region. Of interest, substitution of gamma R375W induced hypofibrinogenemia and HERSD, whereas gamma R375G induced dysfibrinogenemia. Objectives: To analyze the synthesis of variant fibrinogen and morphological characteristics, we established variant fibrinogen-producing cells and compared them with wild-type fibrinogen-synthesizing cells. Methods: The fibrinogen gamma-chain expression vectors coding gamma 375W and gamma 375G were altered by oligonucleotide-directed mutagenesis and transfected into Chinese hamster ovary (CHO) cells. Synthesis of fibrinogen (media and cell lysates) was measured by ELISA for each cloned cell line and morphological characteristics were observed by immunofluorescence and transmission electron microscopy. Results: The medium/cell lysate fibrinogen ratio of gamma 375W-CHO cells was markedly lower than that of the normal cells and gamma 375G-CHO cells. Immunostaining with anti-fibrinogen antibody showed only gamma 375W-CHO cells, but revealed two types of cells containing cytoplasmic inclusion bodies, scattered large-granular bodies and fibrous forms. Observation by confocal microscopy indicated that both inclusion bodies were colocalized with fibrinogen and ER-membrane protein; furthermore, transmission electron microscopic observation demonstrated dilatation of the ER by large-granular inclusion bodies and fibrous forms filled with regularly structured fibular materials within the dilated ER. Conclusion: These results demonstrated that assembled and non-secreted gamma 375W fibrinogen was accumulated in the dilated ER and aggregated variant fibrinogen was seen as regularly structured fibular materials, which was similar to the fingerprint-like pattern observed at inclusion bodies in patients\u0027 hepatocytes affected with HERSD. (C) 2013 Elsevier Ltd. All rights reserved."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Kobayashi,  Tamaki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6571", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Arai,  Shinpei", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6572", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ogiwara,  Naoko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6573", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takezawa,  Yuka", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6574", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nanya,  Mai", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6575", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Terasawa,  Fumiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6576", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Okumura,  Nobuo", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "6577", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "gamma_375W_fibrinogen-synthesizing_CHO_cells.pdf", "filesize": [{"value": "884.1 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 884100.0, "url": {"label": "gamma_375W_fibrinogen-synthesizing_CHO_cells.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3721/files/gamma_375W_fibrinogen-synthesizing_CHO_cells.pdf"}, "version_id": "69f55d14-d403-419c-bc20-dffdb1a9340a"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Endoplasmic reticulum", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Fibrinogen storage disease", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Fibrinogen gamma-chain mutation", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Hepatic endoplasmic reticulum storage disease", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Hypofibrinogenemia", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "gamma 375W fibrinogen-synthesizing CHO cells indicate the accumulation of variant fibrinogen within endoplasmic reticulum", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "gamma 375W fibrinogen-synthesizing CHO cells indicate the accumulation of variant fibrinogen within endoplasmic reticulum", "subitem_title_language": "en"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/17618", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2014-06-20"}, "publish_date": "2014-06-20", "publish_status": "0", "recid": "3721", "relation": {}, "relation_version_is_last": true, "title": ["gamma 375W fibrinogen-synthesizing CHO cells indicate the accumulation of variant fibrinogen within endoplasmic reticulum"], "weko_shared_id": -1}