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Although the affected residue(s) in Okayama II and Otsu I overlapped, functionally determined fibrinogen levels and the ratio of functionally to immunologically determined plasma fibrinogen levels were markedly different.\u003cbr/\u003eMethods: DNA sequence and functional analyses were performed for purified plasma fibrinogen. A recombinant protein was synthesized in Chinese hamster ovary (CHO) cells to determine the secretion of variant fibrinogens.\u003cbr/\u003eResults: A heterozygous A\u003eG in FGG, resulting in gamma 320Asp\u003eGly for Okayama II, and a heterozygous deletion of AATGAT in FGG, resulting in the deletion of gamma Asn319 and gamma Asp320 (gamma Delta N319-Delta D320) for Otsu I, were obtained. SDS-PAGE and Coomassie staining revealed that the variant gamma-chain was not clear in Okayama II, but was clearly present in Otsu I. The lag period for the fibrin polymerization of Okayama II was slightly slower than that of the normal control, whereas Otsu I fibrinogen indicated no polymerization within 30 min. Both variant gamma-chains were synthesized in CHO cells and assembled into fibrinogen; however, the fibrinogen concentration ratio of the medium/cell lysate of gamma 320Gly was six-fold lower than that of gamma Delta N319-Delta D320.\u003cbr/\u003eConclusions: We concluded that the plasma fibrinogen of Okayama II, constituted by a lower ratio of the variant gamma-chain, led to the almost normal functioning of fibrin polymerization. However, the plasma fibrinogen of Otsu I, with a higher ratio of the variant gamma-chain, led to marked reductions in fibrin polymerization. (C) 2015 Elsevier Ltd. All rights reserved. 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Although the affected residue(s) in Okayama II and Otsu I overlapped, functionally determined fibrinogen levels and the ratio of functionally to immunologically determined plasma fibrinogen levels were markedly different.\u003cbr/\u003eMethods: DNA sequence and functional analyses were performed for purified plasma fibrinogen. A recombinant protein was synthesized in Chinese hamster ovary (CHO) cells to determine the secretion of variant fibrinogens.\u003cbr/\u003eResults: A heterozygous A\u003eG in FGG, resulting in gamma 320Asp\u003eGly for Okayama II, and a heterozygous deletion of AATGAT in FGG, resulting in the deletion of gamma Asn319 and gamma Asp320 (gamma Delta N319-Delta D320) for Otsu I, were obtained. SDS-PAGE and Coomassie staining revealed that the variant gamma-chain was not clear in Okayama II, but was clearly present in Otsu I. The lag period for the fibrin polymerization of Okayama II was slightly slower than that of the normal control, whereas Otsu I fibrinogen indicated no polymerization within 30 min. Both variant gamma-chains were synthesized in CHO cells and assembled into fibrinogen; however, the fibrinogen concentration ratio of the medium/cell lysate of gamma 320Gly was six-fold lower than that of gamma Delta N319-Delta D320.\u003cbr/\u003eConclusions: We concluded that the plasma fibrinogen of Okayama II, constituted by a lower ratio of the variant gamma-chain, led to the almost normal functioning of fibrin polymerization. However, the plasma fibrinogen of Otsu I, with a higher ratio of the variant gamma-chain, led to marked reductions in fibrin polymerization. (C) 2015 Elsevier Ltd. All rights reserved. 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Differences in the function and secretion of congenital aberrant fibrinogenemia between heterozygous gamma D320G (Okayama II) and gamma Delta N319-Delta D320 (Otsu I)
http://hdl.handle.net/10091/00018853
http://hdl.handle.net/10091/00018853d35de185-52fd-4ab9-920a-2515046bfc0a
名前 / ファイル | ライセンス | アクション |
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Differences_in_the_function_and_secretion (627.0 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2016-05-17 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Differences in the function and secretion of congenital aberrant fibrinogenemia between heterozygous gamma D320G (Okayama II) and gamma Delta N319-Delta D320 (Otsu I) | |||||
言語 | ||||||
言語 | eng | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.thromres.2015.11.011 | |||||
関連名称 | 10.1016/j.thromres.2015.11.011 | |||||
キーワード | ||||||
主題 | Fibrinogen, gamma-Chain, Dysfibrinogenemia, Hypofibrinogenemia, Secretion | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Mukai, Saki
× Mukai, Saki× Ikeda, Minami× Takezawa, Yuka× Sugano, Mitsutoshi× Honda, Takayuki× Okumura, Nobuo |
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信州大学研究者総覧へのリンク | ||||||
氏名 | Honda, Takayuki | |||||
URL | http://soar-rd.shinshu-u.ac.jp/profile/ja.WeDUHFkh.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Okumura, Nobuo | |||||
URL | http://soar-rd.shinshu-u.ac.jp/profile/ja.OVnmgCkh.html | |||||
出版者 | ||||||
出版者 | PERGAMON-ELSEVIER SCIENCE LTD | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | THROMBOSIS RESEARCH. 136(6):1318-1324 (2015) | |||||
書誌情報 |
THROMBOSIS RESEARCH 巻 136, 号 6, p. 1318-1324, 発行日 2015-12 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: We encountered two patients with hypodysfibrinogenemia and designated them as Okayama II and Otsu I. Although the affected residue(s) in Okayama II and Otsu I overlapped, functionally determined fibrinogen levels and the ratio of functionally to immunologically determined plasma fibrinogen levels were markedly different.<br/>Methods: DNA sequence and functional analyses were performed for purified plasma fibrinogen. A recombinant protein was synthesized in Chinese hamster ovary (CHO) cells to determine the secretion of variant fibrinogens.<br/>Results: A heterozygous A>G in FGG, resulting in gamma 320Asp>Gly for Okayama II, and a heterozygous deletion of AATGAT in FGG, resulting in the deletion of gamma Asn319 and gamma Asp320 (gamma Delta N319-Delta D320) for Otsu I, were obtained. SDS-PAGE and Coomassie staining revealed that the variant gamma-chain was not clear in Okayama II, but was clearly present in Otsu I. The lag period for the fibrin polymerization of Okayama II was slightly slower than that of the normal control, whereas Otsu I fibrinogen indicated no polymerization within 30 min. Both variant gamma-chains were synthesized in CHO cells and assembled into fibrinogen; however, the fibrinogen concentration ratio of the medium/cell lysate of gamma 320Gly was six-fold lower than that of gamma Delta N319-Delta D320.<br/>Conclusions: We concluded that the plasma fibrinogen of Okayama II, constituted by a lower ratio of the variant gamma-chain, led to the almost normal functioning of fibrin polymerization. However, the plasma fibrinogen of Otsu I, with a higher ratio of the variant gamma-chain, led to marked reductions in fibrin polymerization. (C) 2015 Elsevier Ltd. All rights reserved. | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0049-3848 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00863148 | |||||
権利 | ||||||
権利情報 | © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
WoS | ||||||
表示名 | Web of Science | |||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000366712800048 |