JP2010538252A - 器官損傷の同定方法 - Google Patents
器官損傷の同定方法 Download PDFInfo
- Publication number
- JP2010538252A JP2010538252A JP2010522447A JP2010522447A JP2010538252A JP 2010538252 A JP2010538252 A JP 2010538252A JP 2010522447 A JP2010522447 A JP 2010522447A JP 2010522447 A JP2010522447 A JP 2010522447A JP 2010538252 A JP2010538252 A JP 2010538252A
- Authority
- JP
- Japan
- Prior art keywords
- sample
- protein
- identification method
- patient
- induced
- 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.)
- Pending
Links
- 230000008816 organ damage Effects 0.000 title claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 103
- 229940079593 drug Drugs 0.000 claims abstract description 73
- 239000003814 drug Substances 0.000 claims abstract description 73
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 72
- 229960005489 paracetamol Drugs 0.000 claims abstract description 47
- 206010067125 Liver injury Diseases 0.000 claims abstract description 35
- 231100000234 hepatic damage Toxicity 0.000 claims abstract description 33
- 230000008818 liver damage Effects 0.000 claims abstract description 33
- 108090000623 proteins and genes Proteins 0.000 claims description 162
- 102000004169 proteins and genes Human genes 0.000 claims description 158
- 239000000523 sample Substances 0.000 claims description 131
- 210000002700 urine Anatomy 0.000 claims description 63
- 210000001808 exosome Anatomy 0.000 claims description 50
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 claims description 41
- 239000011859 microparticle Substances 0.000 claims description 36
- 150000007523 nucleic acids Chemical class 0.000 claims description 22
- 239000013074 reference sample Substances 0.000 claims description 21
- 210000004369 blood Anatomy 0.000 claims description 20
- 239000008280 blood Substances 0.000 claims description 20
- 108091023040 Transcription factor Proteins 0.000 claims description 17
- 102000040945 Transcription factor Human genes 0.000 claims description 17
- 102000039446 nucleic acids Human genes 0.000 claims description 16
- 108020004707 nucleic acids Proteins 0.000 claims description 16
- 210000000056 organ Anatomy 0.000 claims description 15
- 230000003834 intracellular effect Effects 0.000 claims description 13
- 210000004185 liver Anatomy 0.000 claims description 13
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims description 10
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 claims description 8
- 210000002966 serum Anatomy 0.000 claims description 8
- 108010072220 Cyclophilin A Proteins 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 5
- 210000001519 tissue Anatomy 0.000 claims description 5
- 230000001900 immune effect Effects 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 230000001754 anti-pyretic effect Effects 0.000 claims description 3
- 239000002221 antipyretic Substances 0.000 claims description 3
- 210000000805 cytoplasm Anatomy 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 238000001574 biopsy Methods 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 230000000762 glandular Effects 0.000 claims description 2
- 210000002751 lymph Anatomy 0.000 claims description 2
- 210000003296 saliva Anatomy 0.000 claims description 2
- 230000028327 secretion Effects 0.000 claims description 2
- 210000004243 sweat Anatomy 0.000 claims description 2
- 239000013068 control sample Substances 0.000 claims 2
- 235000018102 proteins Nutrition 0.000 description 144
- 241001044073 Cypa Species 0.000 description 45
- 239000000126 substance Substances 0.000 description 37
- 230000027455 binding Effects 0.000 description 31
- 102100023132 Transcription factor Jun Human genes 0.000 description 29
- 239000000758 substrate Substances 0.000 description 26
- 102000005741 Metalloproteases Human genes 0.000 description 25
- 102100021758 E3 ubiquitin-protein transferase MAEA Human genes 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- 208000006930 Pseudomyxoma Peritonei Diseases 0.000 description 20
- 208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 description 20
- 229920000306 polymethylpentene Polymers 0.000 description 20
- 239000006228 supernatant Substances 0.000 description 17
- 230000006378 damage Effects 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 101710082961 GATA-binding factor 2 Proteins 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- 238000001262 western blot Methods 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000090 biomarker Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 108020004999 messenger RNA Proteins 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000001124 body fluid Anatomy 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 230000002485 urinary effect Effects 0.000 description 9
- 108010004729 Phycoerythrin Proteins 0.000 description 8
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 8
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 8
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 8
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 6
- 108010082126 Alanine transaminase Proteins 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 6
- 101001070790 Homo sapiens Platelet glycoprotein Ib alpha chain Proteins 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 102100034173 Platelet glycoprotein Ib alpha chain Human genes 0.000 description 6
- 102000018614 Uromodulin Human genes 0.000 description 6
- 108010027007 Uromodulin Proteins 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- 239000010839 body fluid Substances 0.000 description 6
- 238000010804 cDNA synthesis Methods 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000005199 ultracentrifugation Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229940109239 creatinine Drugs 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 201000001474 proteinuria Diseases 0.000 description 4
- 229920002477 rna polymer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 102000004195 Isomerases Human genes 0.000 description 3
- 108090000769 Isomerases Proteins 0.000 description 3
- 102000007999 Nuclear Proteins Human genes 0.000 description 3
- 108010089610 Nuclear Proteins Proteins 0.000 description 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
- 108010071390 Serum Albumin Proteins 0.000 description 3
- 102000007562 Serum Albumin Human genes 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000091 biomarker candidate Substances 0.000 description 3
- 230000004637 cellular stress Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000002853 nucleic acid probe Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 238000002731 protein assay Methods 0.000 description 3
- 238000000575 proteomic method Methods 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 102000015936 AP-1 transcription factor Human genes 0.000 description 2
- 108050004195 AP-1 transcription factor Proteins 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 208000003870 Drug Overdose Diseases 0.000 description 2
- 108010075641 GATA2 Transcription Factor Proteins 0.000 description 2
- 102000011852 GATA2 Transcription Factor Human genes 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 208000034486 Multi-organ failure Diseases 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 206010033296 Overdoses Diseases 0.000 description 2
- 208000005374 Poisoning Diseases 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 108010026552 Proteome Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000000729 antidote Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 231100000725 drug overdose Toxicity 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000010419 fine particle Substances 0.000 description 2
- -1 for example Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 230000008383 multiple organ dysfunction Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- AQQSXKSWTNWXKR-UHFFFAOYSA-N 2-(2-phenylphenanthro[9,10-d]imidazol-3-yl)acetic acid Chemical compound C1(=CC=CC=C1)C1=NC2=C(N1CC(=O)O)C1=CC=CC=C1C=1C=CC=CC=12 AQQSXKSWTNWXKR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 208000032529 Accidental overdose Diseases 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 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
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 102100031785 Endothelial transcription factor GATA-2 Human genes 0.000 description 1
- 101150005295 GATA2 gene Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001066265 Homo sapiens Endothelial transcription factor GATA-2 Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 1
- 101001067833 Homo sapiens Peptidyl-prolyl cis-trans isomerase A Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 102000000521 Immunophilins Human genes 0.000 description 1
- 108010016648 Immunophilins Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 1
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108010016131 Proto-Oncogene Proteins c-jun Proteins 0.000 description 1
- 102000000427 Proto-Oncogene Proteins c-jun Human genes 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 102000046661 human PECAM1 Human genes 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000002977 intracellular fluid Anatomy 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008775 paternal effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012959 renal replacement therapy Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000009885 systemic effect Effects 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 230000006492 vascular dysfunction Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000003519 ventilatory effect Effects 0.000 description 1
- 238000005406 washing 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
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
- G01N2333/9121—Phosphotransferases in general with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
- G01N2333/91215—Phosphotransferases in general with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases with a definite EC number (2.7.1.-)
-
- 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
- G01N2333/99—Isomerases (5.)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/08—Hepato-biliairy disorders other than hepatitis
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0716804.0A GB0716804D0 (en) | 2007-08-29 | 2007-08-29 | Identifying organ damage |
| PCT/GB2008/002947 WO2009027703A2 (en) | 2007-08-29 | 2008-08-29 | Identifying organ damage |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010538252A true JP2010538252A (ja) | 2010-12-09 |
| JP2010538252A5 JP2010538252A5 (enExample) | 2011-10-13 |
Family
ID=38616940
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010522447A Pending JP2010538252A (ja) | 2007-08-29 | 2008-08-29 | 器官損傷の同定方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8110371B2 (enExample) |
| EP (1) | EP2183601A2 (enExample) |
| JP (1) | JP2010538252A (enExample) |
| GB (1) | GB0716804D0 (enExample) |
| WO (1) | WO2009027703A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019215342A (ja) * | 2018-06-07 | 2019-12-19 | 株式会社Ｌｓｉメディエンス | ヒト尿からのマイクロベシクルの分離方法及び分析方法 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3181705A1 (en) | 2008-11-12 | 2017-06-21 | Caris Life Sciences Switzerland Holdings GmbH | Methods and systems of using exosomes for determining phenotypes |
| EP2449384B1 (en) * | 2009-07-01 | 2016-04-20 | INSERM - Institut National de la Santé et de la Recherche Médicale | Methods for predicting cardiovascular mortality risk |
| CN103237901B (zh) | 2010-03-01 | 2016-08-03 | 卡里斯生命科学瑞士控股有限责任公司 | 用于治疗诊断的生物标志物 |
| CA2795776A1 (en) | 2010-04-06 | 2011-10-13 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Circulating biomarkers for disease |
| ITNA20110012A1 (it) * | 2011-03-14 | 2012-09-15 | Amal Raj Delfin Albert | Procedura di isolamento e di purificazione degli esosomi urinari per la ricerca di biomarcatori proteici |
| CN105606811A (zh) * | 2016-02-01 | 2016-05-25 | 中南大学 | 一种鼻咽癌诊断试剂盒 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10507184A (ja) * | 1994-10-12 | 1998-07-14 | ペーアーツェト アルツナイミッテル−エントヴィックルングスゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒトにおけるショック状態の診断評価法及び経過コントロール法及び治療用薬剤 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6719969B1 (en) * | 1999-08-09 | 2004-04-13 | The Regents Of The University Of Michigan | Treatment of liver disease and injury with CXC chemokines |
| EP1405072A2 (en) * | 2000-12-29 | 2004-04-07 | Oxford GlycoSciences (UK) Limited | Proteins, genes and their use for diagnosis and treatment of kidney response |
| US7469185B2 (en) * | 2002-02-04 | 2008-12-23 | Ocimum Biosolutions, Inc. | Primary rat hepatocyte toxicity modeling |
| US8758991B2 (en) * | 2006-04-26 | 2014-06-24 | University Of Louisville Research Foundation, Inc. | Isolation of membrane vesicles from biological fluids and methods of using same |
-
2007
- 2007-08-29 GB GBGB0716804.0A patent/GB0716804D0/en not_active Ceased
-
2008
- 2008-08-29 US US12/675,479 patent/US8110371B2/en not_active Expired - Fee Related
- 2008-08-29 WO PCT/GB2008/002947 patent/WO2009027703A2/en not_active Ceased
- 2008-08-29 EP EP08788492A patent/EP2183601A2/en not_active Withdrawn
- 2008-08-29 JP JP2010522447A patent/JP2010538252A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10507184A (ja) * | 1994-10-12 | 1998-07-14 | ペーアーツェト アルツナイミッテル−エントヴィックルングスゲゼルシャフト ミット ベシュレンクテル ハフツング | ヒトにおけるショック状態の診断評価法及び経過コントロール法及び治療用薬剤 |
Non-Patent Citations (1)
| Title |
|---|
| JPN6012037899; Ｇｕｔ Ｖｏｌ．５６, 2006, ｐ９８２-９９０ * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019215342A (ja) * | 2018-06-07 | 2019-12-19 | 株式会社Ｌｓｉメディエンス | ヒト尿からのマイクロベシクルの分離方法及び分析方法 |
| JP7444386B2 (ja) | 2018-06-07 | 2024-03-06 | 株式会社Ｌｓｉメディエンス | ヒト尿からのマイクロベシクルの分離方法及び分析方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20110039276A1 (en) | 2011-02-17 |
| US8110371B2 (en) | 2012-02-07 |
| WO2009027703A3 (en) | 2009-06-25 |
| GB0716804D0 (en) | 2007-10-10 |
| EP2183601A2 (en) | 2010-05-12 |
| WO2009027703A2 (en) | 2009-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8021895B2 (en) | Markers of renal transplant rejection and renal damage | |
| CN102105794B (zh) | 移植物衰竭和死亡的标志物 | |
| Jung et al. | Quantification of ATP7B protein in dried blood spots by peptide immuno-SRM as a potential screen for Wilson’s disease | |
| JP6841765B2 (ja) | 慢性腎疾患の発症のリスクを予測するための方法 | |
| US8110371B2 (en) | Identifying organ damage | |
| JP2012524883A (ja) | 腎臓障害生物マーカとしてのｗｎｔ１ | |
| Khan et al. | Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers | |
| JPWO2008056480A1 (ja) | 脂肪性肝疾患の診断方法、診断装置、診断プログラム、診断薬及び脂肪性肝疾患用治療薬のスクリーニング方法 | |
| Brown et al. | Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea | |
| CN108414765A (zh) | 用G72蛋白质与SLC7A11mRNA作为生物标记来诊断与治疗阿兹海默氏症的方法 | |
| US8969015B2 (en) | Methods and kits for diagnosing Sjögren's syndrome | |
| US20160244835A1 (en) | Urinary neuropilin-1 (nrp-1) as a prognostic marker for nephritis and lupus nephritis | |
| CN105510592A (zh) | 梗阻性肾病的蛋白标志物 | |
| CN110678757A (zh) | 诊断或监测肾功能或诊断肾功能障碍的方法 | |
| JPWO2017126514A1 (ja) | 非アルコール性脂肪肝炎検出方法 | |
| TW202104900A (zh) | 定量功能性ｃ１酯酶抑制子（ｆｃ１—ｉｎｈ）之方法 | |
| WO2022178407A1 (en) | Compositions and methods for characterizing and treating diseases and disorders associated with multiple organ failure | |
| US20170030929A1 (en) | Diagnosis of chronic kidney disease by quantitative analysis of post-translational modifications of plasma proteins | |
| EP3730942A1 (en) | Diagnosis markers for atrial fibrillation | |
| JP2020020755A (ja) | 肝硬変の診断方法、非アルコール性脂肪肝炎及び肝細胞がんの合併症の診断方法並びに非アルコール性脂肪肝炎及び食道胃静脈瘤の合併症の診断方法 | |
| JP5010220B2 (ja) | 造血幹細胞移植療法の施行患者の病態把握方法 | |
| WO2021245413A1 (en) | Methods of determining cancer | |
| Donia et al. | Study for the relationship between lupus nephritis and Anti-C1q antibodies | |
| WO2024130093A2 (en) | Assays and methods for detection of biomarkers associated with neurological diseases | |
| Dissayabutra et al. | Increased protein excretion, including albumin by children of patients with urolithiasis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20101228 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20101228 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110202 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20110202 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110826 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110826 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120718 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120724 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121024 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121031 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121126 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121203 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130312 |