JP5589000B2 - 脳卒中のinvitro診断方法 - Google Patents
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4712—Muscle proteins, e.g. myosin, actin, protein
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- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
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- G01N2333/4737—C-reactive protein
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- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/58—Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
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Description
(a)患者の生物学的サンプルにおいて、プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片の濃度を測定する工程;
(b)前記患者の生物学的サンプルにおいて、ヌクレオシド二リン酸キナーゼA(NDKA)の濃度を測定する工程;
(c)プロBNP(1−108)またはプロBNP(1−108)の断片の濃度及びNDKAの濃度を、一つまたはいくつかのカットオフ値と比較する工程;
(d)そこから脳卒中または一過性虚血性発作(TIA)を前記患者が発症しているかを決定する工程
を含む、患者における脳卒中及び一過性虚血性発作(TIA)のin vitro診断のための方法に関する。
−プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片を検出するのに適した少なくとも一つの抗体;及び
−場合により、少なくとも1pg/mlの濃度での、プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片を含む少なくとも一つの較正物質;及び
−NDKAを検出するのに適した少なくとも一つの抗体;及び
−場合により、少なくとも7ng/mlの濃度での、NDKAを含む少なくとも一つの較正物質
を含む、脳卒中を診断するためのキットに関する。
−プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片;及び
−NDKA
の使用に関する。
1. 方法
a.サンプル
プロBNP(1−108)及びNDKAの濃度を、開始後3時間未満で脳卒中を発症している患者から得た70の血清サンプル(15の出血性脳卒中サンプル(HM)及び55の虚血性脳卒中サンプル(IM))と、見かけ上健康な患者から得た148のコントロール血清サンプルで測定した。
プロBNP(1−108)濃度を、BioPlex(登録商標)2200プロBNP(1−108)アッセイ(Bio-Rad)を使用して測定した。
患者の状態に従ったバイオマーカーの分布をボックスプロット表記によって表し、それは5の数値の要約を通じた数字データの図式的な表記群の従来法である(最小の観察、より低い四分位数(Q1)、中間(Q2)、より高い四分位数(Q3)、及び最大の観察)。
ROCを最大化するために(Staack等, BMC Urology 2006; 6: 1-12)直線状の組み合わせを計算する専用のプログラムである(Su等, Journal of the American Statistical Association 1993; 88: 1350-1355)。それぞれの組み合わせについての等式が提供され、新たなバーチャルマーカーとして使用できる。マーカーの組み合わせについて、及び選択されたサンプルについて、カットオフは、mROCプログラムに対応し、それによって計算される直線状の等式の結果値である。
[式中、a及びbは計算された係数であり、マーカー1及びマーカー2は個々のマーカーカットオフ値である]。
a)示差的分析
脳卒中サンプルとコントロールサンプルの間のNDKAとプロBNP(1−108)濃度の差の統計学的有意性を測定した:
・NDKAマーカー
・コントロール対脳卒中(Ctrl Vs Stroke)
Claims (14)
- (a)患者の生物学的サンプルにおいて、プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片の濃度を測定する工程;
(b)前記患者の生物学的サンプルにおいて、ヌクレオシド二リン酸キナーゼA(NDKA)の濃度を測定する工程;
(c)プロBNP(1−108)またはプロBNP(1−108)の断片の濃度及びNDKAの濃度を、一つまたはいくつかのカットオフ値と比較する工程;
(d)そこから脳卒中または一過性虚血性発作(TIA)を前記患者が発症しているかを決定する工程
を含み、前記プロBNP(1−108)またはプロBNP(1−108)の断片の濃度が、RAPRSP配列(配列番号1)を含むエピトープを標的とする抗体を含むイムノアッセイを使用して測定される、患者における脳卒中及び一過性虚血性発作(TIA)のin vitro診断のための方法。 - 前記プロBNP(1−108)の断片が、FGRKMDR配列(配列番号2)を更に含む、請求項1に記載の方法。
- 前記プロBNP(1−108)の断片が、BNP(32)の配列(配列番号3)を含む、請求項1または2に記載の方法。
- 前記の脳卒中が、虚血性脳卒中及び出血性脳卒中からなる群から選択される、請求項1から3のいずれか一項に記載の方法。
- 前記工程(a)が、前記患者における脳卒中の指標となる少なくとも一つの症状の開始後6時間以内で実施される、請求項1から4のいずれか一項に記載の方法。
- 前記抗体が、受託番号I−3073の下で2005年4月29日にブタペスト条約の下でCNCM(パリ、フランス)に寄託されたハイブリドーマによって分泌される、請求項1に記載の方法。
- 前記イムノアッセイが、FGRKMDR配列(配列番号2)を含むエピトープを標的とする抗体を含む、請求項1から6のいずれか一項に記載の方法。
- 前記抗体が、受託番号I−3746の下で2007年4月13日にブタペスト条約の下でCNCM(パリ、フランス)に寄託されたハイブリドーマによって分泌される、請求項7に記載の方法。
- 前記NDKA濃度が、イムノアッセイを使用して測定される、請求項1から8のいずれか一項に記載の方法。
- 前記NDKAの濃度が、前記プロBNP(1−108)またはプロBNP(1−108)の断片の濃度を測定するのと同じ生物学的サンプルで測定される、請求項1から9のいずれか一項に記載の方法。
- 前記生物学的サンプルが、血液サンプル、血清サンプル、血漿サンプル、脳脊髄液サンプル、尿サンプル、及び唾液サンプルから構成される群から選択される、請求項1から10のいずれか一項に記載の方法。
- 少なくとも一つの心臓血管疾患のマーカーの濃度を測定する工程を更に含む、請求項1から11のいずれか一項に記載の方法。
- 前記少なくとも一つの心臓血管疾患のマーカーが、CRP及びcTnIからなる群から選択される、請求項12に記載の方法。
- −プロBNP(1−108)またはRAPRSP配列(配列番号1)を含むプロBNP(1−108)の断片を検出する少なくとも一つの抗体;及び
−NDKAを検出する少なくとも一つの抗体
を含む、脳卒中またはTIAを診断するためのキット。
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CN104094121B (zh) | 2011-12-01 | 2016-10-26 | 霍夫曼-拉罗奇有限公司 | 用于诊断中风的nt-原anp和nt-原bnp |
GB2497138A (en) | 2011-12-02 | 2013-06-05 | Randox Lab Ltd | Biomarkers for stroke and stroke subtype diagnosis. |
US9366678B2 (en) | 2012-10-25 | 2016-06-14 | Wisconsin Alumni Research Foundation | Neutron encoded mass tags for analyte quantification |
US10265012B2 (en) | 2013-05-20 | 2019-04-23 | Beyond Verbal Communication Ltd. | Method and system for determining a pre-multisystem failure condition using time integrated voice analysis |
GB201309928D0 (en) | 2013-06-04 | 2013-07-17 | Randox Lab Ltd | Method |
JP2015137272A (ja) * | 2014-01-24 | 2015-07-30 | 東ソー株式会社 | 新規のペプチド及び疾患の検出方法 |
US10670611B2 (en) | 2014-09-26 | 2020-06-02 | Somalogic, Inc. | Cardiovascular risk event prediction and uses thereof |
US10456059B2 (en) | 2015-04-06 | 2019-10-29 | Forest Devices, Inc. | Neuorological condition detection unit and method of using the same |
GB201619823D0 (en) | 2016-11-23 | 2017-01-04 | Randox Laboratories Ltd And Teoranta Randox | GFAP accumulating stroke |
WO2019028602A1 (zh) * | 2017-08-07 | 2019-02-14 | 深圳市汇顶科技股份有限公司 | 应用于超取样转换器的向量量化数模转换电路 |
US11446009B2 (en) | 2018-12-11 | 2022-09-20 | Eko.Ai Pte. Ltd. | Clinical workflow to diagnose heart disease based on cardiac biomarker measurements and AI recognition of 2D and doppler modality echocardiogram images |
US11931207B2 (en) | 2018-12-11 | 2024-03-19 | Eko.Ai Pte. Ltd. | Artificial intelligence (AI) recognition of echocardiogram images to enhance a mobile ultrasound device |
US12001939B2 (en) | 2018-12-11 | 2024-06-04 | Eko.Ai Pte. Ltd. | Artificial intelligence (AI)-based guidance for an ultrasound device to improve capture of echo image views |
CN112808550B (zh) * | 2020-12-28 | 2021-10-01 | 青岛理工大学 | 用于海洋工程的劣化免疫仿生防护界面及制备方法 |
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US7608406B2 (en) * | 2001-08-20 | 2009-10-27 | Biosite, Inc. | Diagnostic markers of stroke and cerebral injury and methods of use thereof |
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US20040219509A1 (en) * | 2001-08-20 | 2004-11-04 | Biosite, Inc. | Diagnostic markers of stroke and cerebral injury and methods of use thereof |
FR2843396B1 (fr) * | 2002-08-07 | 2005-04-15 | Bio Rad Pasteur | Anticorps specifiques pour le diagnostic de l'insuffisance cardiaque |
CA2522709A1 (en) * | 2003-04-17 | 2004-11-04 | Ciphergen Biosystems, Inc. | Polypeptides related to natriuretic peptides and methods of their identification and use |
JP5019878B2 (ja) | 2003-09-20 | 2012-09-05 | エレクトロフォレティックス リミテッド | 脳障害関連疾患の診断のためのマーカーの検出に関する方法 |
GB2428240A (en) * | 2005-07-14 | 2007-01-24 | Univ Gen Ve | Diagnostic method for brain damage-related disorders |
KR101582321B1 (ko) * | 2006-12-05 | 2016-01-05 | 디코드 제네틱스 이에이치에프 | 심장성 부정맥의 위험 관리를 위한 유전적 마커 |
WO2010012509A1 (en) * | 2008-08-01 | 2010-02-04 | Bio-Rad Pasteur | Method for the in vitro diagnosis of stroke |
EP2356450B1 (en) * | 2008-10-24 | 2019-02-06 | B.R.A.H.M.S GmbH | Prognosis and risk assessment in stroke patients by determining the level of marker peptides |
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