JP4307250B2 - 炎症性疾患及び敗血症の診断及び治療のための、カルシニューリンb様タンパク質(chp)の使用 - Google Patents
炎症性疾患及び敗血症の診断及び治療のための、カルシニューリンb様タンパク質(chp)の使用 Download PDFInfo
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- JP4307250B2 JP4307250B2 JP2003510960A JP2003510960A JP4307250B2 JP 4307250 B2 JP4307250 B2 JP 4307250B2 JP 2003510960 A JP2003510960 A JP 2003510960A JP 2003510960 A JP2003510960 A JP 2003510960A JP 4307250 B2 JP4307250 B2 JP 4307250B2
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- G—PHYSICS
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1738—Calcium binding proteins, e.g. calmodulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
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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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/26—Infectious diseases, e.g. generalised sepsis
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/105831—Protein or peptide standard or control [e.g., hemoglobin, etc.]
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
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Description
A. Beishuizen等, "Endogenous Mediators in Sepsis and Septic Shock", Advances in Clinical Chemistry, vol. 33, 1999, 55-131 C. Gabay等, "Acute Phase Proteins and Other Systemic Responses to Inflammation", The New England Journal of Medicine, vol. 340, No. 6, 1999, 448-454 K. Reinhart等, "Sepsis und septischer Schock" [Sepsis and septic shock], Intensivmedizin, Georg Thieme Verlag, Stuttgart, New York, 2001, 756-760 M. Assicot等, "High serum procalsitonin concentrations in patients with sepsis and infection", The Lancet, Vol. 341, No. 8844, 1993, 515-518
エンドトキシン注射によるプロカルシトニン分泌の刺激のためのヒヒで実施された実験に基づいて(H. Redl等, "Procalcitonin release patterns in a baboon model of trauma and sepsis: Relationship to cytokines and neopterin", Crit Care Med 2000, Vol. 28, No. 11, 3659-3663;H. Redl等, "Non-Human Primate Models of Sepsis", in : Sepsis 1998; 2: 243-253参照)、ヒヒ(オス、約2年齢、27−29kgの体重)を、体重のkg当たり100μgのLPS(Salmonella Typhimurium由来のリポ多糖、Sigma供給)をそれぞれ静脈内に投与した。注射後5から5.5時間後、10mlのドレタールの静脈内投与によって動物を殺傷した。死から60分以内で、全ての器官/組織を切除し、液体窒素中での凍結によって安定化した。
個々の組織のサンプルを、一方でポリスチレンチューブに固定化されたヒヒカルシトニンに対する抗体で、他方でアクリジニウムエステルでマークされ、ヒヒプロカルシトニンのN末端に対して向けられたモノクローナル抗体で実施する免疫蛍光試験(ヒトプロカルシトニンの測定のために開発された、本出願人のLU-MItest(登録商標)PCTと類似する)の補助の下で調査した。この試験の目的では、個々のサンプル中のヒヒプロカルシトニンの含量を、組換えヒトプロカルシトニンを使用する試験の較正の後に測定した。
一方で健康なヒヒ(コントロール)の、他方でLPSで注射されているヒヒの細胞質肝細胞タンパク質抽出物が、プロテオーム分析で使用された。最初の分析的2次元ゲル電気泳動では、100μgのタンパク質を含む肝抽出物が、9Mウレア、70mM DTT、2%アンフォライト、pH2−4に安定化され、次いでJ. Klose等, "Two-dimensional electrophoresis of proteins: An updated protocol and implications for a functional analysis of the genome", Electrophoresis 1995, 16, 1034-1059に記載されたような分析的2次元ゲル電気泳動によって分離された。2次元電気泳動ゲルにおけるタンパク質の視覚化は、銀染色によって実施された(J. Heukeshoven等, "Improved silver staining procedure for fast staining in Phast-System Development Unit. I. Staining of sodium dodecyl gels", Electrophoresis 1988, 9, 28-32参照)。
図1(A)及び1(B)に示されているように、LPS注射を投与されているヒヒの肝細胞抽出物はとりわけ、約22,900±700ドルトンの分子量が、既知の分子量のマーカー物質と比較してゲル電気泳動に基づいて見積もられ、第一次元のタンパク質の相対的位置から、6.1から6.3の等電点が測定されるタンパク質のスポットを含んだ。
Claims (3)
- 敗血症の疑いがある患者からの組織サンプルをカルシニューリンB様タンパク質(CHP)の存在について試験する工程を含む前記患者における敗血症を検出するための方法であって、コントロール群と比較して前記サンプル中の前記CHPのより高い量が敗血症を示す方法。
- 前記CHPの存在を免疫診断的測定方法によって測定する、請求項1に記載の方法。
- 配列番号1、配列番号2、配列番号4、または配列番号5の配列を含むCHP断片に特異的に結合する抗体を用いてCHPを測定する、請求項2に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10131922A DE10131922A1 (de) | 2001-07-02 | 2001-07-02 | Verwendung des Calcineurin B Homologen Proteins (CHP) für die Diagnose und Therapie von Entzündungserkrankungen und Sepsis |
PCT/EP2002/006660 WO2003005035A1 (de) | 2001-07-02 | 2002-06-17 | Chp als marker für sepsisähnliche entzündungskrankheiten |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2005500044A JP2005500044A (ja) | 2005-01-06 |
JP4307250B2 true JP4307250B2 (ja) | 2009-08-05 |
Family
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Family Applications (1)
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JP2003510960A Expired - Fee Related JP4307250B2 (ja) | 2001-07-02 | 2002-06-17 | 炎症性疾患及び敗血症の診断及び治療のための、カルシニューリンb様タンパク質(chp)の使用 |
Country Status (6)
Country | Link |
---|---|
US (1) | US7235368B2 (ja) |
EP (1) | EP1402267B1 (ja) |
JP (1) | JP4307250B2 (ja) |
AT (1) | ATE313801T1 (ja) |
DE (2) | DE10131922A1 (ja) |
WO (1) | WO2003005035A1 (ja) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1318404B1 (de) | 2001-12-04 | 2004-07-28 | B.R.A.H.M.S Aktiengesellschaft | Verfahren zur Diagnose von Sepsis unter Bestimmung von CA 19-9 |
ATE282831T1 (de) | 2001-12-04 | 2004-12-15 | Brahms Ag | Verfahren zur diagnose von sepsis unter bestimmung löslicher cytokeratinfragmente |
DE50103030D1 (de) | 2001-12-04 | 2004-09-02 | Brahms Ag | Verfahren zur Diagnose von Sepsis unter Bestimmung von S100B |
ATE278194T1 (de) | 2001-12-07 | 2004-10-15 | Brahms Ag | Verwendungen der aldose-1-epimerase (mutarotase) für die diagnose von entzündungserkrankungen und sepsis |
US20050196817A1 (en) * | 2004-01-20 | 2005-09-08 | Molecular Staging Inc. | Biomarkers for sepsis |
US20100160171A1 (en) * | 2008-12-22 | 2010-06-24 | The Children's Research Institute | Methods For Detection Of Sepsis |
US20110217301A1 (en) * | 2009-12-22 | 2011-09-08 | The Children's Research Instute | Methods for treating or screening for compounds for the treatment of sepsis |
US10260111B1 (en) | 2014-01-20 | 2019-04-16 | Brett Eric Etchebarne | Method of detecting sepsis-related microorganisms and detecting antibiotic-resistant sepsis-related microorganisms in a fluid sample |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US5660994A (en) * | 1986-11-10 | 1997-08-26 | Progen Biotechnik Gmbh | Method of detecting tissue-specific, insoluble cytoskeletal proteins |
DE4227454C1 (de) * | 1992-08-19 | 1994-02-03 | Henning Berlin Gmbh | Verfahren zur Früherkennung, zur Erkennung des Schweregrads sowie zur therapiebegleitenden Verlaufsbeurteilung einer Sepsis sowie Mittel zur Durchführung des Verfahrens |
US5969102A (en) * | 1997-03-03 | 1999-10-19 | St. Jude Children's Research Hospital | Lymphocyte surface receptor that binds CAML, nucleic acids encoding the same and methods of use thereof |
AU2326099A (en) | 1998-01-21 | 1999-08-09 | Incyte Pharmaceuticals, Inc. | Human calcineurin b-like protein |
CN1100566C (zh) * | 1998-08-26 | 2003-02-05 | 北京师范大学 | 含有钙调神经磷酸酶b亚基的药物组合物 |
DE19847690A1 (de) | 1998-10-15 | 2000-04-20 | Brahms Diagnostica Gmbh | Verfahren und Substanzen für die Diagnose und Therapie von Sepsis und sepsisähnlichen systemischen Infektionen |
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2001
- 2001-07-02 DE DE10131922A patent/DE10131922A1/de not_active Ceased
-
2002
- 2002-06-17 EP EP02735421A patent/EP1402267B1/de not_active Expired - Lifetime
- 2002-06-17 US US10/480,847 patent/US7235368B2/en not_active Expired - Fee Related
- 2002-06-17 WO PCT/EP2002/006660 patent/WO2003005035A1/de active IP Right Grant
- 2002-06-17 AT AT02735421T patent/ATE313801T1/de not_active IP Right Cessation
- 2002-06-17 DE DE50205358T patent/DE50205358D1/de not_active Expired - Lifetime
- 2002-06-17 JP JP2003510960A patent/JP4307250B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
WO2003005035A1 (de) | 2003-01-16 |
EP1402267B1 (de) | 2005-12-21 |
DE10131922A1 (de) | 2003-01-30 |
ATE313801T1 (de) | 2006-01-15 |
JP2005500044A (ja) | 2005-01-06 |
US20050064409A1 (en) | 2005-03-24 |
EP1402267A1 (de) | 2004-03-31 |
US7235368B2 (en) | 2007-06-26 |
DE50205358D1 (en) | 2006-01-26 |
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