JP4927825B2 - 初期段階の心機能異常を診断または予測するための装置および方法 - Google Patents
初期段階の心機能異常を診断または予測するための装置および方法 Download PDFInfo
- Publication number
- JP4927825B2 JP4927825B2 JP2008510547A JP2008510547A JP4927825B2 JP 4927825 B2 JP4927825 B2 JP 4927825B2 JP 2008510547 A JP2008510547 A JP 2008510547A JP 2008510547 A JP2008510547 A JP 2008510547A JP 4927825 B2 JP4927825 B2 JP 4927825B2
- Authority
- JP
- Japan
- Prior art keywords
- subject
- bnp
- amount
- heart failure
- nyha class
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 66
- 230000000747 cardiac effect Effects 0.000 title description 7
- 230000004064 dysfunction Effects 0.000 title description 2
- 210000002700 urine Anatomy 0.000 claims abstract description 50
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 claims description 121
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 claims description 120
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 claims description 120
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 claims description 117
- 206010019280 Heart failures Diseases 0.000 claims description 89
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 23
- 150000001413 amino acids Chemical class 0.000 claims description 20
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 52
- 208000019267 mild heart failure Diseases 0.000 abstract description 11
- 208000019266 moderate heart failure Diseases 0.000 abstract description 11
- 102100036836 Natriuretic peptides B Human genes 0.000 abstract description 3
- 101710187802 Natriuretic peptides B Proteins 0.000 abstract description 3
- 230000007211 cardiovascular event Effects 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 38
- 239000003446 ligand Substances 0.000 description 37
- 229920001184 polypeptide Polymers 0.000 description 32
- 239000000523 sample Substances 0.000 description 26
- 208000024891 symptom Diseases 0.000 description 22
- 238000003745 diagnosis Methods 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 238000003556 assay Methods 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 239000000758 substrate Substances 0.000 description 9
- 101500026735 Homo sapiens Brain natriuretic peptide 32 Proteins 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 230000037081 physical activity Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000027455 binding Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000036755 cellular response Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000002526 effect on cardiovascular system Effects 0.000 description 6
- 238000003018 immunoassay Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 206010013975 Dyspnoeas Diseases 0.000 description 5
- 238000003491 array Methods 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 230000002485 urinary effect Effects 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000006911 enzymatic reaction Methods 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 239000004816 latex Substances 0.000 description 4
- 229920000126 latex Polymers 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 108091023037 Aptamer Proteins 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108020001621 Natriuretic Peptide Proteins 0.000 description 3
- 102000004571 Natriuretic peptide Human genes 0.000 description 3
- 206010033557 Palpitations Diseases 0.000 description 3
- -1 antibodies Proteins 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000000692 natriuretic peptide Substances 0.000 description 3
- 238000004848 nephelometry Methods 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 201000003695 Alexia Diseases 0.000 description 2
- 241000752021 Alexia Species 0.000 description 2
- 206010049993 Cardiac death Diseases 0.000 description 2
- 206010011906 Death Diseases 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 238000007675 cardiac surgery Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 206010013932 dyslexia Diseases 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000002821 scintillation proximity assay Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- QRXMUCSWCMTJGU-UHFFFAOYSA-L (5-bromo-4-chloro-1h-indol-3-yl) phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP([O-])(=O)[O-])=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-L 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- HJCUTNIGJHJGCF-UHFFFAOYSA-N 9,10-dihydroacridine Chemical class C1=CC=C2CC3=CC=CC=C3NC2=C1 HJCUTNIGJHJGCF-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 101900159346 Influenza A virus Hemagglutinin Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101800001904 NT-proBNP Proteins 0.000 description 1
- 102400001263 NT-proBNP Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010079855 Peptide Aptamers Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000035965 Postoperative Complications Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000007818 agglutination assay Methods 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- UKWLRLAKGMZXJC-QIECWBMSSA-L disodium;[4-chloro-3-[(3r,5s)-1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl]phenyl] phosphate Chemical compound [Na+].[Na+].O1OC2([C@@H]3CC4C[C@H]2CC(Cl)(C4)C3)C1(OC)C1=CC(OP([O-])([O-])=O)=CC=C1Cl UKWLRLAKGMZXJC-QIECWBMSSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011337 individualized treatment Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
-
- 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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/325—Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- External Artificial Organs (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Electrotherapy Devices (AREA)
Description
a)被験体の尿サンプル中の脳性ナトリウム利尿ペプチド (BNP)の量を測定すること;および
b)ステップa)にて測定されたBNP量に基づいて、被験体が心不全に罹患しているか否か診断すること
を含む、上記方法に関する。
a)被験体の尿サンプル中のBNP量を測定するための手段;および
b)BNP量に基づいて被験体が心不全に罹患しているか否か診断するための手段、
を備える、被験体の心不全を診断するための装置を含む。
a)被験体の尿サンプル中のBNP量を測定すること;および
b)ステップa)にて測定されたBNPの量に基づいて、被験体が心不全を伴う心血管系疾患発症の危険にあるか否かを予測すること、
を含む、上記方法に関する。
a)被験体の尿サンプル中のBNP量を測定するための手段;および
b)BNP量に基づいて被験体が心不全を伴う心血管系疾患発症の危険にあるか否かを予測するための手段、
を備える上記装置を含む。
a)ヒトBNP;
b)ヒトBNPと少なくとも60%同一であるポリペプチド;ならびに
c)ヒトBNPと比較して、アミノ酸の欠失、置換、および/または付加を有し、BNP特性を有するポリペプチド、
からなる群から選択されるものが好ましい。
今回の調査は、ヒト尿中のBNPの存在を分析するため、対象および疾患群にて見出されたBNPレベルを比較するため、ならびに尿中BNPの診断値および予後値を調べるためのものであった。尿中のBNPレベルは、15人の健全なボランティアと91人の心不全 (HF) 患者にて測定した。HF群中、8人はNYHAクラスIの状態にあり、63人はNYHAクラスIIの状態にあり、20人はNYHAクラスIIIの状態であった。
Claims (13)
- ニューヨーク心臓協会(New York Heart Association、NYHA)クラスI, II, IIIまたはIVに被験体の心不全を分類するための方法であって、
a)被験体の尿サンプル中の32個のアミノ酸からなる成熟脳性ナトリウム利尿ペプチド (BNP)の量を測定すること;および
b)ステップa)にて測定された該32個のアミノ酸からなる成熟BNP量に基いて被験体がNYHAクラスI, II, IIIまたはIVによるところのいずれの心不全に罹患しているかを分類すること、
を含み、BNP量が0.8 pg/ml〜2.4 pg/mlである場合、被験体はNYHAクラスIに属し、BNP量が2.5 pg/ml〜3.9 pg/mlである場合、被験体はNYHAクラスIIに属し、BNP量が4.0 pg/ml〜12.0 pg/mlである場合、被験体はNYHAクラスIIIに属し、BNP量が12.0 pg/mlよりも高い量である場合、被験体はNYHAクラスIVに属すると分類する、上記方法。 - 被験体が心不全を伴う心血管系疾患発症の危険にあるか否かを予測するための方法であって、
a)被験体の尿サンプル中の32個のアミノ酸からなる成熟BNP量を測定すること;および
b)ステップa)にて測定された該32個のアミノ酸からなる成熟BNP量に基づいて被験体が心不全を伴う心血管系疾患発症の危険にあるか否か予測すること、
を含み、BNP量が少なくとも2.5 pg/mlである場合、被験体は心血管系疾患の発症および/または将来的な死亡の高いリスクを有すると予測する、上記方法。 - 32個のアミノ酸からなる成熟BNP量に基づく予測が、被験体の尿サンプル中の該32個のアミノ酸からなる成熟BNP量と心不全を発症していないこと、または心不全を発症していることが知られている被験体の尿サンプル中の該32個のアミノ酸からなる成熟BNP量とを比較することを含む、請求項2に記載の方法。
- 心不全を伴う心血管系疾患を発症する危険が12ヶ月の予後期間に関する、請求項2または3に記載の方法。
- 心不全が、ニューヨーク心臓協会(New York Heart Association、NYHA)クラスI, IIまたはIIIによるところの心不全である、請求項2〜4のいずれか1項に記載の方法。
- 心不全が慢性心不全である、請求項1〜5のいずれか1項に記載の方法。
- 被験体がヒトである、請求項1〜6のいずれか1項に記載の方法。
- 被験体の心不全をニューヨーク心臓協会(New York Heart Association、NYHA)クラスI, II, IIIまたはIVに分類するための装置であって、
a)被験体の尿サンプル中の32個のアミノ酸からなる成熟BNPの量を測定する手段;および
b)該成熟BNP量に基いて被験体の心不全をニューヨーク心臓協会(New York Heart Association、NYHA)クラスI, II, IIIまたはIVに分類する手段、
を備え、BNP量が0.8 pg/ml〜2.4 pg/mlである場合、被験体はNYHAクラスIに属し、BNP量が2.5 pg/ml〜3.9 pg/mlである場合、被験体はNYHAクラスIIに属し、BNP量が4.0 pg/ml〜12.0 pg/mlである場合、被験体はNYHAクラスIIIに属し、BNP量が12.0 pg/mlよりも高い量である場合、被験体はNYHAクラスIVに属すると分類する、上記装置。 - 被験体が心不全を伴う心血管系疾患発症の危険にあるか否かを予測するための装置であって、
a)被験体の尿サンプル中の32個のアミノ酸からなる成熟BNP量を測定する手段;および
b)該32個のアミノ酸からなる成熟BNPの量に基いて被験体が心不全を伴う心血管系疾患発症の危険にあるか否かを予測する手段、
を備え、BNP量が少なくとも2.5 pg/mlである場合、被験体は心血管系疾患の発症および/または将来的な死亡の高いリスクを有すると予測する、上記装置。 - 心不全をNYHAクラス I, II, III または IVに分類するための、被験体の尿サンプル中の32個のアミノ酸からなる成熟BNPの使用であって、BNP量が0.8 pg/ml〜2.4 pg/mlである場合、被験体はNYHAクラスIに属し、BNP量が2.5 pg/ml〜3.9 pg/mlである場合、被験体はNYHAクラスIIに属し、BNP量が4.0 pg/ml〜12.0 pg/mlである場合、被験体はNYHAクラスIIIに属し、BNP量が12.0 pg/mlよりも高い量である場合、被験体はNYHAクラスIVに属すると分類する、上記使用。
- 被験体の心不全をNYHAクラスI, II, IIIまたはIVに分類するための、被験体の尿サンプル中の32個のアミノ酸からなる成熟BNP量を測定する手段および心不全をNYHAクラスI, II, IIIまたはIVに分類するための診断手段を備える装置の使用であって、BNP量が0.8 pg/ml〜2.4 pg/mlである場合、被験体はNYHAクラスIに属し、BNP量が2.5 pg/ml〜3.9 pg/mlである場合、被験体はNYHAクラスIIに属し、BNP量が4.0 pg/ml〜12.0 pg/mlである場合、被験体はNYHAクラスIIIに属し、BNP量が12.0 pg/mlよりも高い量である場合、被験体はNYHAクラスIVに属すると分類する、上記使用。
- 被験体が心不全発症の危険にあるか否かを予測するための、被験体の尿サンプル中の32個のアミノ酸からなる成熟BNPの使用であって、BNP量が少なくとも2.5 pg/mlである場合、被験体は心血管系疾患の発症および/または将来的な死亡の高いリスクを有すると予測する、上記使用。
- 被験体が心不全発症の危険にあるか否かを予測するための、被験体の尿サンプル中の32個のアミノ酸からなる成熟BNPの量を測定する手段および被験体が心不全発症の危険にあるか否かを予測する手段を備える装置の使用であって、BNP量が少なくとも2.5 pg/mlである場合、被験体は心血管系疾患の発症および/または将来的な死亡の高いリスクを有すると予測する、上記使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP05010043.7 | 2005-05-09 | ||
EP05010043A EP1722232A1 (en) | 2005-05-09 | 2005-05-09 | Devices and methods for diagnosing or predicting early stage cardiac dysfunctions |
PCT/EP2006/062031 WO2006120152A1 (en) | 2005-05-09 | 2006-05-03 | Devices and methods for diagnosing or predicting early stage cardiac dysfunctions |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008541078A JP2008541078A (ja) | 2008-11-20 |
JP4927825B2 true JP4927825B2 (ja) | 2012-05-09 |
Family
ID=34936290
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008510547A Active JP4927825B2 (ja) | 2005-05-09 | 2006-05-03 | 初期段階の心機能異常を診断または予測するための装置および方法 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20110104813A1 (ja) |
EP (2) | EP1722232A1 (ja) |
JP (1) | JP4927825B2 (ja) |
CN (2) | CN103091497A (ja) |
AT (1) | ATE482398T1 (ja) |
CA (1) | CA2605247A1 (ja) |
DE (1) | DE602006017058D1 (ja) |
ES (1) | ES2352351T3 (ja) |
HK (1) | HK1119771A1 (ja) |
WO (1) | WO2006120152A1 (ja) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1722232A1 (en) * | 2005-05-09 | 2006-11-15 | F.Hoffmann-La Roche Ag | Devices and methods for diagnosing or predicting early stage cardiac dysfunctions |
JP2010517023A (ja) * | 2007-01-25 | 2010-05-20 | エフ.ホフマン−ラ ロシュ アーゲー | 心不全の評価におけるigfbp−7の使用 |
US20120115929A1 (en) | 2009-04-29 | 2012-05-10 | Esther Elisa Johanna Maria Creemers | Means And Methods For Counteracting, Preventing And/Or Determining Heart Failure, Or A Risk Of Heart Failure |
EP2646822B1 (en) * | 2010-11-29 | 2017-11-01 | Alere San Diego, Inc. | Methods for diagnosis and risk prediction in heart failure |
WO2014023820A1 (en) | 2012-08-09 | 2014-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Diagnostic of heart failure |
SG11201702490PA (en) * | 2014-10-10 | 2017-04-27 | Akira Matsumori | Method for detecting cardiac failure patient, method for discrimination of cardiac disease, test reagent for cardiac failure, test kit for cardiac failure, device for detecting cardiac failure, and program for detecting cardiac failure |
US11193947B2 (en) | 2016-06-03 | 2021-12-07 | Cedars-Sinai Medical Center | B-type natriuretic peptide proteolytic assay for cardiovascular disease risk assessment |
WO2017210488A1 (en) * | 2016-06-03 | 2017-12-07 | Cedars-Sinai Medical Center | B-type natriuretic peptide proteolytic assay for cardiovascular disease risk assessment |
US20190257842A1 (en) * | 2016-08-09 | 2019-08-22 | Otsuka Pharmaceutical Co., Ltd. | Method for assisting diagnosis of alzheimer's disease using urine biomarker |
JP7414281B2 (ja) * | 2017-08-08 | 2024-01-16 | クイーンズランド ユニバーシティ オブ テクノロジー | 初期心不全の診断方法 |
US11255844B2 (en) * | 2018-03-06 | 2022-02-22 | Fresenius Medical Care Holdings, Inc. | Peritoneal dialysis systems and related methods |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03297392A (ja) * | 1990-04-16 | 1991-12-27 | Shionogi & Co Ltd | hBNPを認識するモノクローナル抗体および該抗体を用いるhBNPの免疫測定法 |
JP2004037455A (ja) * | 2002-05-14 | 2004-02-05 | F Hoffmann La Roche Ag | マーカーの組み合わせを用いた心臓疾患症例の予後判定 |
WO2004046729A2 (en) * | 2002-11-21 | 2004-06-03 | The University Of Leicester | Bodily fluid markers of tissue hypoxia |
JP2004519688A (ja) * | 2001-04-13 | 2004-07-02 | バイオサイト インコーポレイテッド | 急性冠状症候群の予後指標としてのb型ナトリウム排泄促進ペプチドの使用 |
WO2005011803A2 (en) * | 2003-07-30 | 2005-02-10 | Medtronic, Inc. | Method of optimizing cardiac resynchronization therapy using sensor signals of septal wall motion |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5744101A (en) * | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
DE50015291D1 (de) * | 1999-01-29 | 2008-09-11 | Roche Diagnostics Gmbh | Verfahren zum Nachweis von N-terminalem proBNP |
AUPS169202A0 (en) * | 2002-04-11 | 2002-05-16 | Goetze, Jens Peter | Neuropeptide assay |
GB0216191D0 (en) * | 2002-07-11 | 2002-08-21 | Univ Leicester | Plasma urotensin in human heart failure |
US8263325B2 (en) * | 2002-11-15 | 2012-09-11 | Ottawa Heart Institute Research Corporation | Predicting, detecting and monitoring treatment of cardiomyopathies and myocarditis |
US7109023B2 (en) * | 2002-11-18 | 2006-09-19 | Princeton Biomeditech Corporation | Immunossay device for diagnosing congestive heart failure and predicting mortality in congestive heart failure patients |
US7887750B2 (en) * | 2004-05-05 | 2011-02-15 | Bayer Healthcare Llc | Analytical systems, devices, and cartridges therefor |
EP1722232A1 (en) * | 2005-05-09 | 2006-11-15 | F.Hoffmann-La Roche Ag | Devices and methods for diagnosing or predicting early stage cardiac dysfunctions |
-
2005
- 2005-05-09 EP EP05010043A patent/EP1722232A1/en not_active Withdrawn
-
2006
- 2006-05-03 CA CA002605247A patent/CA2605247A1/en not_active Abandoned
- 2006-05-03 JP JP2008510547A patent/JP4927825B2/ja active Active
- 2006-05-03 WO PCT/EP2006/062031 patent/WO2006120152A1/en not_active Application Discontinuation
- 2006-05-03 AT AT06754992T patent/ATE482398T1/de active
- 2006-05-03 CN CN2013100056784A patent/CN103091497A/zh active Pending
- 2006-05-03 DE DE602006017058T patent/DE602006017058D1/de active Active
- 2006-05-03 EP EP06754992A patent/EP1880221B1/en active Active
- 2006-05-03 ES ES06754992T patent/ES2352351T3/es active Active
- 2006-05-03 CN CN2006800158682A patent/CN101171517B/zh active Active
-
2007
- 2007-11-07 US US11/936,169 patent/US20110104813A1/en not_active Abandoned
-
2008
- 2008-10-17 HK HK08111542.2A patent/HK1119771A1/xx unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03297392A (ja) * | 1990-04-16 | 1991-12-27 | Shionogi & Co Ltd | hBNPを認識するモノクローナル抗体および該抗体を用いるhBNPの免疫測定法 |
JP2004519688A (ja) * | 2001-04-13 | 2004-07-02 | バイオサイト インコーポレイテッド | 急性冠状症候群の予後指標としてのb型ナトリウム排泄促進ペプチドの使用 |
JP2004037455A (ja) * | 2002-05-14 | 2004-02-05 | F Hoffmann La Roche Ag | マーカーの組み合わせを用いた心臓疾患症例の予後判定 |
WO2004046729A2 (en) * | 2002-11-21 | 2004-06-03 | The University Of Leicester | Bodily fluid markers of tissue hypoxia |
WO2005011803A2 (en) * | 2003-07-30 | 2005-02-10 | Medtronic, Inc. | Method of optimizing cardiac resynchronization therapy using sensor signals of septal wall motion |
Also Published As
Publication number | Publication date |
---|---|
CA2605247A1 (en) | 2006-11-16 |
EP1880221A1 (en) | 2008-01-23 |
ATE482398T1 (de) | 2010-10-15 |
JP2008541078A (ja) | 2008-11-20 |
EP1722232A1 (en) | 2006-11-15 |
CN103091497A (zh) | 2013-05-08 |
ES2352351T3 (es) | 2011-02-17 |
CN101171517B (zh) | 2013-10-09 |
DE602006017058D1 (de) | 2010-11-04 |
EP1880221B1 (en) | 2010-09-22 |
WO2006120152A1 (en) | 2006-11-16 |
US20110104813A1 (en) | 2011-05-05 |
CN101171517A (zh) | 2008-04-30 |
HK1119771A1 (en) | 2009-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4927825B2 (ja) | 初期段階の心機能異常を診断または予測するための装置および方法 | |
JP4823170B2 (ja) | 進行型冠動脈疾患およびその合併症のインジケーターとしての心筋トロポニン | |
JP4731525B2 (ja) | 心因性と肺因性の急性呼吸窮迫を鑑別する手段と方法 | |
JP2011523051A (ja) | 1型糖尿病におけるバイオマーカーとしてのgdf−15 | |
JP4944185B2 (ja) | 症状のある患者における急性および慢性の心筋壊死の区別のための手段と方法 | |
JP6034394B2 (ja) | 切迫妊娠高血圧腎症および/またはHELLP症候群の指標としてのsFlt−1またはエンドグリン/PlGF比の動態 | |
JP2011509403A (ja) | Gdf−15に基づいて救急室を受診する患者のリスクを評価するための手段及び方法 | |
JP2011501112A (ja) | 心筋梗塞のモニタリング及びその治療のための手段及び方法 | |
JP2014532887A5 (ja) | ||
JP2020034564A (ja) | 心不全リスクの予測改善のためのバイオマーカー | |
JP4689651B2 (ja) | 急性肺塞栓症用生化学マーカー | |
JP5306218B2 (ja) | トロポニンTおよびNT−proBNPの検出に基づく慢性動脈疾患での診断および治療的アプローチの最適化のための手段および方法 | |
JP2010537212A (ja) | 息切れの原因の鑑別におけるサーファクタントプロテインb及びd | |
JP4664939B2 (ja) | 息切れの心臓原因および肺原因を鑑別するための手段および方法 | |
JP5369118B2 (ja) | バイオマーカーplgfを用いてアテローム性動脈硬化負荷を決定する手段及び方法 | |
JP2011524533A (ja) | 炎症バイオマーカーを用いて動脈硬化性狭窄を決定する手段及び方法 | |
CN105960593B (zh) | 用于慢性肾病进展预测的生物标记物和方法 | |
JP5307141B2 (ja) | 心筋梗塞の早期予測因子としてのミオグロビン | |
US8440463B2 (en) | Predicting renal failure in diabetes patients based on placental growth factor and soluble FLT-1 | |
JP2010528306A (ja) | 心筋梗塞の早期予測因子としてのh−fabp | |
JP2011523072A (ja) | 1型糖尿病を有する患者の合併症の評価 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100615 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20100617 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110308 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110608 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110705 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110929 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111006 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111213 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120117 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120209 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150217 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4927825 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |