JP2009235090A - 敗血症及び敗血症様全身性感染の検出のための方法及び物質 - Google Patents
敗血症及び敗血症様全身性感染の検出のための方法及び物質 Download PDFInfo
- Publication number
- JP2009235090A JP2009235090A JP2009152844A JP2009152844A JP2009235090A JP 2009235090 A JP2009235090 A JP 2009235090A JP 2009152844 A JP2009152844 A JP 2009152844A JP 2009152844 A JP2009152844 A JP 2009152844A JP 2009235090 A JP2009235090 A JP 2009235090A
- Authority
- JP
- Japan
- Prior art keywords
- procalcitonin
- sepsis
- pro
- serum
- peptide
- 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.)
- Granted
Links
- 206010040047 Sepsis Diseases 0.000 title claims abstract description 65
- 208000015181 infectious disease Diseases 0.000 title claims description 21
- 238000000034 method Methods 0.000 title claims description 15
- 230000009885 systemic effect Effects 0.000 title claims description 14
- 239000000463 material Substances 0.000 title description 5
- 108010048233 Procalcitonin Proteins 0.000 claims abstract description 110
- CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 claims abstract description 109
- 150000001413 amino acids Chemical class 0.000 claims abstract description 16
- 238000003556 assay Methods 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000010353 genetic engineering Methods 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 239000002299 complementary DNA Substances 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 238000011097 chromatography purification Methods 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 24
- 229960004015 calcitonin Drugs 0.000 abstract description 8
- 102000055006 Calcitonin Human genes 0.000 abstract description 7
- 108060001064 Calcitonin Proteins 0.000 abstract description 7
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 abstract description 7
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 239000002243 precursor Substances 0.000 abstract description 5
- 239000003550 marker Substances 0.000 abstract description 2
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 abstract 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 abstract 1
- 238000004458 analytical method Methods 0.000 abstract 1
- 210000002966 serum Anatomy 0.000 description 36
- 238000005259 measurement Methods 0.000 description 28
- 101000886298 Pseudoxanthomonas mexicana Dipeptidyl aminopeptidase 4 Proteins 0.000 description 20
- 230000000694 effects Effects 0.000 description 16
- 108010016626 Dipeptides Proteins 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 7
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 7
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 210000001685 thyroid gland Anatomy 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000002723 Atrial Natriuretic Factor Human genes 0.000 description 6
- 102100026651 Pro-adrenomedullin Human genes 0.000 description 6
- 238000004949 mass spectrometry Methods 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000002955 immunomodulating agent Substances 0.000 description 4
- 229940121354 immunomodulator Drugs 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 101800000285 Big gastrin Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 102000004862 Gastrin releasing peptide Human genes 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- RZIMNEGTIDYAGZ-HNSJZBNRSA-N pro-gastrin Chemical compound N([C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C(=O)[C@@H]1CCC(=O)N1 RZIMNEGTIDYAGZ-HNSJZBNRSA-N 0.000 description 3
- 102000034567 proadrenomedullin Human genes 0.000 description 3
- 108010012004 proadrenomedullin Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 description 2
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 2
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 101150040383 pel2 gene Proteins 0.000 description 2
- 101150050446 pelB gene Proteins 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JVMUPDOMGALPOW-UHFFFAOYSA-N 4-methoxynaphthalen-1-amine Chemical compound C1=CC=C2C(OC)=CC=C(N)C2=C1 JVMUPDOMGALPOW-UHFFFAOYSA-N 0.000 description 1
- YSMPVONNIWLJML-FXQIFTODSA-N Ala-Asp-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(O)=O YSMPVONNIWLJML-FXQIFTODSA-N 0.000 description 1
- CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 1
- WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical group C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 210000003771 C cell Anatomy 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- JEGFCFLCRSJCMA-IHRRRGAJSA-N Phe-Arg-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N JEGFCFLCRSJCMA-IHRRRGAJSA-N 0.000 description 1
- CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 108010052590 amastatin Proteins 0.000 description 1
- QFAADIRHLBXJJS-ZAZJUGBXSA-N amastatin Chemical compound CC(C)C[C@@H](N)[C@H](O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O QFAADIRHLBXJJS-ZAZJUGBXSA-N 0.000 description 1
- 238000012801 analytical assay Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)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(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)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)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 101150047356 dec-1 gene Proteins 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
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 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 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 108010080850 prepro-brain natriuretic peptide Proteins 0.000 description 1
- 108010061031 pro-gastrin-releasing peptide (31-98) Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000013214 routine measurement Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000000352 storage cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000002366 time-of-flight method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 239000003643 water by type Substances 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
- G01N33/74—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
-
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/585—Calcitonins
-
- 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
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/585—Calcitonins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Peptides Or Proteins (AREA)
Abstract
【解決手段】敗血症疾患の診断及び治療、及び、プロカルシトニン以外のプロホルモン並びにジペプチジルペプチダーゼIVの測定における、並びに、敗血症の診断でのバイオマーカーとしての、組み換えプロカルシトニン3−116の使用が可能である。
【選択図】なし
Description
図2は、高いプロカルシトニン免疫反応性を有する、図1からのプール血清の各フラクションの質量分光分析結果を示す。
図3は、敗血症血清及び正常な血清中のジペプチジル−アミノペプチダーゼIVの酵素活性の測定結果を示す。
図4は、敗血症血清及び正常な血清中のプロカルシトニンの測定結果を、同じ血清中のさらなるプロホルモン、すなわちプロ−ガストリン放出ペプチド(proGRP)の測定結果と比較して示す。
図5は、健常者20人のグループと敗血症患者20人のグループの血清中のプロカルシトニンの測定結果を示す。
図6は、図5と同じ健常者と敗血症患者の各グループにおける、pro-ANFの測定結果(pg/チューブ)を示す。
図7は、図5と同じ健常者と敗血症患者の各グループにおける、pro-ADMの測定結果(pg/チューブ)を示す。
図8は、図5と同じ健常者と敗血症患者の各グループにおける、pro-ENDの測定結果(pg/チューブ)を示す。
図9は、図5と同じ健常者と敗血症患者の各グループにおける、pro-BNPの測定結果(pg/チューブ)を示す。
A. 敗血症患者の血清からの内因性プロカルシトニンペプチドの単離と確認
重度の敗血症に苦しむ複数の患者からの血清サンプルを混合することによって、総容量68mlの混合血清が調製された。得られたプール血清中のプロカルシトニン濃度は、市販のプロカルシトニンアッセイ(LUMItest PCT, B.R.A.H.M.S. Diagnostica)を用いて測定したところ、280ng/ml(総量19μg)であった。前記プール血清は、同量のバッファー(68ml;10mM EDTA、1mg/mlマウス−IgG、2mg/ml ヒツジ−IgG、2mg/mlウシ−IgG、0.1mmolロイペプチン、PBS中50μMアマスタチン)と混合し、そのサンプル中に含まれるプロカルシトニンを、アフィニティークロマトグラフィーによって単離及び精製した。
1.クローニング
プロカルシトニン3−116(以下、PCT 114と略す)をコードするDNAフラグメントを、適当なオリゴヌクレオチドプライマーを用いたPCR増幅によって、ヒト甲状腺cDNAプールから単離した。望ましいフラグメントが通常の手法(Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA及びStruhl K (1991), Current Protocols in Molecular Biology, John Wiley & Sons, New York)によってクローニングされ、その正確なヌクレオチド配列がDNA塩基配列決定と、プロカルシトニンをコードする既知のDNA配列との比較とによって確かめられた。
健常者から、及び、敗血症患者からの、それぞれ20の血清サンプルを、それらのジペプチジル−アミノペプチダーゼIV特異的酵素活性について調べた。このDAP IV酵素活性は、Lys−Pro−4−メトキシ−ベータ−ナフチルアミドを用いるそれ自身は既知の方法で、フルオロメトリーによって測定した。このために、各ケース、2μlの血清が3mlの基質(50μg/ml Lys−Pro−4−メトキシ−ベータ−ナフチルアミド、50mM Tris/HCl、pH7.5)を用いてテストされ、340nmの波長を有する光による励起で生じた蛍光は、410nmの放射波長で持続的に測定された。その蛍光シグナルは、4−メトキシナフチルアミン溶液を用いて校正された。この方法で決定された酵素活性は、nmol/minで記載される。
敗血症のケースで放出されるのが完全なプロホルモンのプロカルシトニンではなく、Xaa-Proジペプチドの分短くなった変性プロホルモンであるという事実は、敗血症のケースで放出されるのはプロカルシトニン3−116だけではなく、プロカルシトニン3−116は単に、例えば、免疫調節能を有するものであり、敗血症のケースではおそらく変換形態で高度に遊離されるプロホルモン又は同様のペプチド全体の中の代表的な1つにすぎないという仮説を導く。
アッセイは、proGRP決定用のものが市販されている。近年の出版物に、proGRPが気管支の小細胞癌の腫瘍マーカーとして記載されている(Petra Stieber et al., J Lab Med 1997, 21 (6): 336-344)。proGRPの決定用アッセイは、トーネンコーポレーションのProGRP ELISA KITTMの名称のものが市販されている。
プレホルモンであるpro-ANF、pro-ADM、pro-END及びpro-BNPの決定については、アッセイは、DRG(DRG Instruments GmbH, D-35018 Marburg, ドイツ)からキットの形態で市販されており、製造者の指示に従って次の測定に用いられた。
Claims (4)
- 遺伝子工学によって調製されたプロカルシトニン3−116。
- 遺伝子工学によるプロカルシトニン3−116の調製方法であって、
−プロカルシトニン3−116の114のアミノ酸をコードしているcDNA配列を適当なベクターに挿入し、
−形成した該ベクターを用いて、適当なホスト細胞を形質転換させ、プロカルシトニン3−116を発現させ、
−前記ホスト細胞を刺激し、
−発現したプロカルシトニン3−116を含むフラクションを回収し、そして、
−前記フラクションから、遺伝子工学によって調製された生成物として、クロマトグラフィーによる精製によって、少なくとも90%の純度で前記プロカルシトニン3−116を得ること
を含む方法。 - プロカルシトニンアッセイにおける標準物質として、又は、敗血症及び敗血症様全身性感染の予防及び処置のための治療の準備のための、組み換えプロカルシトニン3−116の使用。
- 症状とは無関係な診断上のパラメーターとしてのプロカルシトニン3−116の測定方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19847690.6 | 1998-10-15 | ||
DE19847690A DE19847690A1 (de) | 1998-10-15 | 1998-10-15 | Verfahren und Substanzen für die Diagnose und Therapie von Sepsis und sepsisähnlichen systemischen Infektionen |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000576286A Division JP4444507B2 (ja) | 1998-10-15 | 1999-10-13 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009235090A true JP2009235090A (ja) | 2009-10-15 |
JP5215250B2 JP5215250B2 (ja) | 2013-06-19 |
Family
ID=7884648
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000576286A Expired - Lifetime JP4444507B2 (ja) | 1998-10-15 | 1999-10-13 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
JP2009152845A Expired - Lifetime JP5219939B2 (ja) | 1998-10-15 | 2009-06-26 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
JP2009152844A Expired - Lifetime JP5215250B2 (ja) | 1998-10-15 | 2009-06-26 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
JP2009152843A Expired - Lifetime JP4510920B2 (ja) | 1998-10-15 | 2009-06-26 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000576286A Expired - Lifetime JP4444507B2 (ja) | 1998-10-15 | 1999-10-13 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
JP2009152845A Expired - Lifetime JP5219939B2 (ja) | 1998-10-15 | 2009-06-26 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009152843A Expired - Lifetime JP4510920B2 (ja) | 1998-10-15 | 2009-06-26 | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 |
Country Status (6)
Country | Link |
---|---|
US (6) | US6756483B1 (ja) |
EP (4) | EP1408334B1 (ja) |
JP (4) | JP4444507B2 (ja) |
AT (4) | ATE475889T1 (ja) |
DE (5) | DE19847690A1 (ja) |
WO (1) | WO2000022439A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010519322A (ja) * | 2007-02-28 | 2010-06-03 | ベー・エル・アー・ハー・エム・エス・アクティエンゲゼルシャフト | 診断のためのプロカルシトニン1−116の選択的測定法、ならびにそのような方法を実行するための抗体およびキット |
Families Citing this family (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
EP1110970B1 (de) | 1999-12-22 | 2008-05-14 | Dade Behring Marburg GmbH | Gegen Procalcitonin gerichtete Antikörper, ihre Herstellung und Verwendung |
ATE356874T1 (de) | 1999-12-22 | 2007-04-15 | Dade Behring Marburg Gmbh | Lösungen von humanem procalcitonin |
PT1311269E (pt) | 2000-08-04 | 2012-05-10 | Dmi Biosciences Inc | Método de utilização de dicetopiperazinas e composição que contém as mesmas |
US9053222B2 (en) | 2002-05-17 | 2015-06-09 | Lawrence A. Lynn | Patient safety processor |
US7632647B2 (en) * | 2001-04-13 | 2009-12-15 | Biosite Incorporated | Use of B-type natriuretic peptide as a prognostic indicator in acute coronary syndromes |
US7524635B2 (en) * | 2003-04-17 | 2009-04-28 | Biosite Incorporated | Methods and compositions for measuring natriuretic peptides and uses thereof |
US20030219734A1 (en) * | 2001-04-13 | 2003-11-27 | Biosite Incorporated | Polypeptides related to natriuretic peptides and methods of their identification and use |
US20040176914A1 (en) * | 2001-04-13 | 2004-09-09 | Biosite Incorporated | Methods and compositions for measuring biologically active natriuretic peptides and for improving their therapeutic potential |
DE10119804A1 (de) | 2001-04-23 | 2002-10-24 | Brahms Ag | Entzündungsspezifische Peptide und deren Verwendungen |
DE10130985B4 (de) | 2001-06-27 | 2004-03-18 | B.R.A.H.M.S Ag | Verfahren zur Diagnose von Sepsis und schweren Infektionen unter Bestimmung löslicher Cytokeratin-1-Fragmente |
DE10131922A1 (de) * | 2001-07-02 | 2003-01-30 | Brahms Ag | Verwendung des Calcineurin B Homologen Proteins (CHP) für die Diagnose und Therapie von Entzündungserkrankungen und Sepsis |
EP1318403B1 (de) | 2001-12-04 | 2004-07-28 | B.R.A.H.M.S Aktiengesellschaft | Verfahren zur Diagnose von Sepsis unter Bestimmung von S100B |
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 |
DE50104561D1 (de) | 2001-12-04 | 2004-12-23 | Brahms Ag | Verfahren zur Diagnose von Sepsis unter Bestimmung löslicher Cytokeratinfragmente |
DE50103907D1 (de) | 2001-12-07 | 2004-11-04 | Brahms Ag | Verwendungen der Aldose-1-Epimerase (Mutarotase) für die Diagnose von Entzündungserkrankungen und Sepsis |
EP1355159A1 (de) * | 2002-04-19 | 2003-10-22 | B.R.A.H.M.S Aktiengesellschaft | Verwendungen von Fragmenten der Carbamoylphosphat Synthetase 1 (CPS 1) für die Diagnose von Entzündungserkrankungen und Sepsis |
EP1355158A1 (de) * | 2002-04-19 | 2003-10-22 | B.R.A.H.M.S Aktiengesellschaft | Verfahren zur Diagnose von Entzündungserkrankungen und Infektionen unter Bestimmung des Phosphoproteins LASP-1 als Inflammationsmarker |
EP1367395A1 (de) | 2002-05-02 | 2003-12-03 | B.R.A.H.M.S Aktiengesellschaft | Diagnose von Neoplasmen mit Hilfe von anti-Gangliosid-Antikörpern |
EP1369693A1 (de) * | 2002-06-04 | 2003-12-10 | B.R.A.H.M.S Aktiengesellschaft | Verfahren zur Sepsisdiagnose und zur Kontrolle von Spenderblut durch Bestimmung von anti-Asialo-Gangliosid-Antikörpern |
EP1369118A1 (de) * | 2002-06-04 | 2003-12-10 | B.R.A.H.M.S Aktiengesellschaft | Verfahren und Mittel zur Prävention, Hemmung und Therapie von Sepsis |
EP1571970B1 (en) * | 2002-10-02 | 2011-08-17 | DMI Biosciences, Inc. | Diagnosis and monitoring of diseases |
MXPA05005031A (es) * | 2002-11-12 | 2005-11-17 | Becton Dickinson Co | Diagnostico de la sepsis o sirs usando perfiles de biomarcadores. |
JP4656493B2 (ja) * | 2002-11-20 | 2011-03-23 | ベー・エル・アー・ハー・エム・エス・ゲーエムベーハー | 部分的proANPペプチドを同定するためのサンドイッチイムノアッセイ |
DE10316583A1 (de) * | 2003-04-10 | 2004-10-28 | B.R.A.H.M.S Aktiengesellschaft | Bestimmung eines midregionalen Proadrenomedullin-Teilpeptids in biologischen Flüssigkeiten zu diagnostischen Zwecken, sowie Immunoassays für die Durchführung einer solchen Bestimmung |
CA2522709A1 (en) * | 2003-04-17 | 2004-11-04 | Ciphergen Biosystems, Inc. | Polypeptides related to natriuretic peptides and methods of their identification and use |
KR20060022659A (ko) | 2003-05-15 | 2006-03-10 | 디엠아이 바이오사이언시스, 인크 | T-세포 매개성 질환의 치료 방법 |
US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
JP2007518062A (ja) * | 2003-09-29 | 2007-07-05 | バイオサイト インコーポレイテッド | 敗血症を診断する方法および診断するための組成物 |
ES2255003T3 (es) | 2004-02-13 | 2006-06-16 | B.R.A.H.M.S Aktiengesellschaft | Procedimiento para determinar la formacion de endotelinas con fines diagnostico medico, y anticuerpos y kits para realizar un procedimiento de este tipo. |
US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
EP1753730A1 (en) | 2004-06-04 | 2007-02-21 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
ATE392623T1 (de) * | 2004-07-22 | 2008-05-15 | Brahms Ag | Verfahren für die diagnose von schwerkranken patienten |
DE102004045705A1 (de) * | 2004-09-21 | 2006-04-06 | B.R.A.H.M.S Ag | Verwendungen der Carbamoylphosphat Synthetase 1(CPS) als humoraler Biomarker für die Diagnose von Tumorerkrankungen und chronisch entzündlichen Darmerkrankungen |
DE102004047968A1 (de) * | 2004-10-01 | 2006-04-06 | B.R.A.H.M.S Ag | Bestimmung von Gastrokine 1 (GKN1) als Biomarker für Entzündungen und Infektionen |
DE102005003687A1 (de) * | 2005-01-26 | 2006-07-27 | Sphingo Tec Gmbh | Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation |
US7731965B2 (en) * | 2005-02-17 | 2010-06-08 | Abbott Lab | Human ring specific BNP antibodies |
CA2605143A1 (en) | 2005-04-15 | 2006-10-26 | Becton, Dickinson And Company | Diagnosis of sepsis |
US7939069B2 (en) | 2005-11-09 | 2011-05-10 | Abbott Laboratories | Human BNP immunospecific antibodies |
US20070207152A1 (en) * | 2005-11-09 | 2007-09-06 | Brophy Susan E | Human BNP immunospecific antibodies |
US8906857B2 (en) | 2005-12-01 | 2014-12-09 | B.R.A.H.M.S. Gmbh | Methods for the diagnosis and treatment of critically ill patients with endothelin, endothelin agonists and adrenomedullin antagonists |
WO2007062676A1 (en) * | 2005-12-01 | 2007-06-07 | B.R.A.H.M.S. Aktiengesellschaft | Methods for the diagnosis and treatment of critically ill patients with endothelin, endothelin agonists and adrenomedullin antagonists |
WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
US7838250B1 (en) | 2006-04-04 | 2010-11-23 | Singulex, Inc. | Highly sensitive system and methods for analysis of troponin |
ES2550004T3 (es) | 2006-04-04 | 2015-11-03 | Singulex, Inc. | Sistema de alta sensibilidad y métodos de análisis de la troponina |
US20080064045A1 (en) * | 2006-09-07 | 2008-03-13 | Huaiqin Wu | Biomarker fragments for the detection of human BNP |
DE102006046996A1 (de) | 2006-10-01 | 2008-04-03 | Brahms Aktiengesellschaft | Diagnose von Infektionen oder Entzündungserkrankungen der Atemwege und Lunge assoziiert mit Herzinsuffizienz |
DE102006052916A1 (de) * | 2006-11-08 | 2008-05-15 | Brahms Aktiengesellschaft | Diagnose und Risikostratifizierung von Diabetes mellitus mittels MR-proADM |
DE102006053442A1 (de) | 2006-11-12 | 2008-05-15 | Brahms Aktiengesellschaft | Diagnose und Risikostratifizierung von Infektionen und chronischen Erkrankungen der Atemwege und Lunge mittels proVasopressin, insbesondere Copeptin oder Neurophysin II |
DE102006060112A1 (de) * | 2006-12-20 | 2008-06-26 | Brahms Aktiengesellschaft | Diagnose und Risikostratifizierung mittels dem neuen Marker CT-proADM |
DE102007021443A1 (de) | 2007-05-08 | 2008-11-13 | Brahms Aktiengesellschaft | Diagnose und Risikostratifizierung mittels NT-proET-1 |
WO2009123737A2 (en) | 2008-04-03 | 2009-10-08 | Becton, Dickinson And Company | Advanced detection of sepsis |
US7776522B2 (en) * | 2008-04-24 | 2010-08-17 | Becton, Dickinson And Company | Methods for diagnosing oncogenic human papillomavirus (HPV) |
JP5474937B2 (ja) | 2008-05-07 | 2014-04-16 | ローレンス エー. リン, | 医療障害パターン検索エンジン |
WO2009146320A1 (en) | 2008-05-27 | 2009-12-03 | Dmi Life Sciences, Inc. | Therapeutic methods and compounds |
CA2745189A1 (en) * | 2008-12-22 | 2010-07-01 | The Children's Research Institute | Methods for detection of sepsis |
AU2010259022B2 (en) | 2009-06-08 | 2016-05-12 | Singulex, Inc. | Highly sensitive biomarker panels |
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 |
US9709565B2 (en) | 2010-04-21 | 2017-07-18 | Memed Diagnostics Ltd. | Signatures and determinants for distinguishing between a bacterial and viral infection and methods of use thereof |
JP2013537195A (ja) | 2010-09-07 | 2013-09-30 | ディエムアイ アクイジション コーポレイション | 疾患の治療 |
EP2533052A1 (en) | 2011-06-07 | 2012-12-12 | B.R.A.H.M.S GmbH | Diagnostic use of proSomatostatin |
US9925300B2 (en) | 2011-10-10 | 2018-03-27 | Ampio Pharmaceuticals, Inc. | Implantable medical devices with increased immune tolerance, and methods for making and implanting |
US8980834B2 (en) | 2011-10-10 | 2015-03-17 | Ampio Pharmaceuticals, Inc. | Treatment of degenerative joint disease |
WO2013063413A1 (en) | 2011-10-28 | 2013-05-02 | Ampio Pharmaceuticals, Inc. | Treatment of rhinitis |
SG11201402358RA (en) | 2011-11-16 | 2014-06-27 | Adrenomed Ag | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for use in therapy of an acute disease or acute condition of a patient for stabilizing the circulation |
EP2780717B1 (en) | 2011-11-16 | 2016-12-21 | sphingotec GmbH | Adrenomedullin assays and methods for determining mature adrenomedullin |
SG11201402366PA (en) | 2011-11-16 | 2014-06-27 | Adrenomed Ag | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for prevention or reduction of organ dysfunction or organ failure in a patient having a chronic or acute disease or acute condition |
JP6193872B2 (ja) | 2011-11-16 | 2017-09-06 | アドレノメト アクチェンゲゼルシャフト | 慢性又は急性疾患に罹患している患者の体液平衡を調整するための抗アドレノメデュリン(ADM)抗体、抗ADM抗体フラグメント又は抗ADM非Ig足場 |
US9726668B2 (en) | 2012-02-09 | 2017-08-08 | Memed Diagnostics Ltd. | Signatures and determinants for diagnosing infections and methods of use thereof |
JP5945063B2 (ja) | 2012-04-12 | 2016-07-05 | ベー.エル.アー.ハー.エム.エス ゲゼルシャフト ミット ベシュレンクテル ハフツング | 慢性心不全が疑われる患者における有害事象の予後 |
US9953453B2 (en) | 2012-11-14 | 2018-04-24 | Lawrence A. Lynn | System for converting biologic particle density data into dynamic images |
US10354429B2 (en) | 2012-11-14 | 2019-07-16 | Lawrence A. Lynn | Patient storm tracker and visualization processor |
US20140241602A1 (en) | 2013-02-28 | 2014-08-28 | Lawrence A. Lynn | System for Presentation of Sequential Blood Laboratory Measurements to Image Recognition Systems |
MX2015010937A (es) | 2013-03-15 | 2015-10-29 | Ampio Pharmaceuticals Inc | Composiciones para la movilizacion, autodireccion, expansion y diferenciacion de celulas madre y metodos para usar las mismas. |
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 |
CN104792997B (zh) * | 2014-01-22 | 2017-07-11 | 天津汇滨生物科技有限公司 | 一种人降钙素原免疫检测试剂盒及其制备方法与应用 |
EP3180621B1 (en) | 2014-08-14 | 2020-04-01 | Memed Diagnostics Ltd. | Computational analysis of biological data using manifold and a hyperplane |
RU2020136589A (ru) | 2014-08-18 | 2020-12-24 | Ампио Фармасьютикалз, Инк. | Лечение дегенеративных заболеваний суставов |
WO2016059636A1 (en) | 2014-10-14 | 2016-04-21 | Memed Diagnostics Ltd. | Signatures and determinants for diagnosing infections in non-human subjects and methods of use thereof |
EP3310375A4 (en) | 2015-06-22 | 2019-02-20 | Ampio Pharmaceuticals, Inc. | USE OF LOW MOLECULAR WEIGHT HUMAN SERUM ALBUMIN FRACTIONS FOR TREATING DISEASES |
EP3423590A4 (en) | 2016-03-03 | 2020-02-26 | Memed Diagnostics Ltd. | DETERMINANTS OF RNA TO DIFFERENTIATE BACTERIAL VIRAL INFECTIONS |
EP4184167A1 (en) | 2016-07-10 | 2023-05-24 | MeMed Diagnostics Ltd. | Early diagnosis of infections |
WO2018011795A1 (en) | 2016-07-10 | 2018-01-18 | Memed Diagnostics Ltd. | Protein signatures for distinguishing between bacterial and viral infections |
JP7138326B2 (ja) | 2016-08-16 | 2022-09-16 | 株式会社タカギ | 水栓 |
US11385241B2 (en) | 2016-09-29 | 2022-07-12 | Memed Diagnostics Ltd. | Methods of prognosis and treatment |
US11353456B2 (en) | 2016-09-29 | 2022-06-07 | Memed Diagnostics Ltd. | Methods of risk assessment and disease classification for appendicitis |
US10209260B2 (en) | 2017-07-05 | 2019-02-19 | Memed Diagnostics Ltd. | Signatures and determinants for diagnosing infections and methods of use thereof |
EP3438668A1 (en) | 2017-08-04 | 2019-02-06 | B.R.A.H.M.S GmbH | Diagnosis and risk stratification of fungal infections |
EP3971572A1 (en) | 2017-09-13 | 2022-03-23 | B.R.A.H.M.S GmbH | Proadrenomedullin as a marker for abnormal platelet levels |
US20210109118A1 (en) * | 2017-12-20 | 2021-04-15 | B.R.A.H.M.S Gmbh | Antibiotic therapy guidance based on pro-adm |
EP3502706A1 (en) | 2017-12-20 | 2019-06-26 | B.R.A.H.M.S GmbH | Workflow for risk assessment and patient management using procalcitonin and midregional-proadrenomedullin |
CN113348368A (zh) | 2019-03-29 | 2021-09-03 | B.R.A.H.M.S有限公司 | 基于生物标志物开具远程患者管理处方 |
EP3715851A1 (en) | 2019-03-29 | 2020-09-30 | B.R.A.H.M.S GmbH | Prescription of remote patient management based on biomarkers |
EP4133281A1 (en) | 2020-04-09 | 2023-02-15 | B.R.A.H.M.S GmbH | Biomarkers for the diagnosis of respiratory tract infections |
EP4357778A1 (en) | 2022-10-20 | 2024-04-24 | Heraeus Medical GmbH | Treatment of microbial infections diagnosed using the biomarker d-lactate |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08501151A (ja) * | 1992-08-19 | 1996-02-06 | ヘニング ベルリン ゲーエムベーハー | 敗血症の早期検出、重篤度測定、および治療に伴なう敗血症経過の評価のための方法、ならびにその方法の実施手段 |
WO1998033524A1 (en) * | 1997-02-03 | 1998-08-06 | Endocrinology Associates-Australia Llc | Method and compositions for preventing and treating the systemic inflammatory response syndrome including sepsis |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0115459A3 (en) | 1983-01-26 | 1986-11-20 | University Of Medicine And Dentistry Of New Jersey | Hematological prediction of sepsis and other disease states |
US5298605A (en) * | 1986-10-08 | 1994-03-29 | Regents Of The University Of Minnesota | Antibodies to islet amyloid polypeptide (IAPP) and subunits thereof |
WO1994000555A2 (en) * | 1992-06-25 | 1994-01-06 | Cetus Oncology Corporation | Compositions for the inhibition of protein hormone formation and uses thereof |
JP3578787B2 (ja) * | 1993-05-14 | 2004-10-20 | ラホヤ インスティチュート フォア アレルギー アンド イムノロジー | 生物学的に活性なポリペプチドの組換え製造方法 |
WO1995030012A1 (en) * | 1994-04-26 | 1995-11-09 | Cadus Pharmaceutical Corporation | Functional expression of mammalian adenylyl cyclase in yeast |
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 |
DE60235416D1 (de) | 2001-05-04 | 2010-04-01 | Biosite Inc | Diagnostische Marker der akuten koronaren Syndrome und ihre Verwendungen |
-
1998
- 1998-10-15 DE DE19847690A patent/DE19847690A1/de not_active Withdrawn
-
1999
- 1999-10-13 EP EP03028136A patent/EP1408334B1/de not_active Expired - Lifetime
- 1999-10-13 DE DE59914934T patent/DE59914934D1/de not_active Expired - Lifetime
- 1999-10-13 JP JP2000576286A patent/JP4444507B2/ja not_active Expired - Lifetime
- 1999-10-13 DE DE59914077T patent/DE59914077D1/de not_active Expired - Lifetime
- 1999-10-13 EP EP99953805.1A patent/EP1121600B2/de not_active Expired - Lifetime
- 1999-10-13 WO PCT/EP1999/007692 patent/WO2000022439A2/de active IP Right Grant
- 1999-10-13 US US09/806,437 patent/US6756483B1/en not_active Expired - Lifetime
- 1999-10-13 DE DE59915190T patent/DE59915190D1/de not_active Expired - Lifetime
- 1999-10-13 AT AT08075749T patent/ATE475889T1/de active
- 1999-10-13 EP EP08075749A patent/EP2028493B1/de not_active Expired - Lifetime
- 1999-10-13 EP EP06026319A patent/EP1770397B1/de not_active Expired - Lifetime
- 1999-10-13 AT AT03028136T patent/ATE349013T1/de active
- 1999-10-13 AT AT99953805T patent/ATE320607T1/de active
- 1999-10-13 AT AT06026319T patent/ATE417860T1/de active
- 1999-10-13 DE DE59913233T patent/DE59913233D1/de not_active Expired - Lifetime
-
2004
- 2004-03-25 US US10/808,368 patent/US7498139B2/en not_active Expired - Fee Related
-
2008
- 2008-09-29 US US12/240,485 patent/US7998686B2/en not_active Expired - Fee Related
- 2008-09-29 US US12/240,500 patent/US7723492B2/en not_active Expired - Fee Related
-
2009
- 2009-02-18 US US12/388,029 patent/US7972799B2/en not_active Expired - Fee Related
- 2009-06-26 JP JP2009152845A patent/JP5219939B2/ja not_active Expired - Lifetime
- 2009-06-26 JP JP2009152844A patent/JP5215250B2/ja not_active Expired - Lifetime
- 2009-06-26 JP JP2009152843A patent/JP4510920B2/ja not_active Expired - Lifetime
-
2010
- 2010-04-08 US US12/756,235 patent/US8691512B2/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08501151A (ja) * | 1992-08-19 | 1996-02-06 | ヘニング ベルリン ゲーエムベーハー | 敗血症の早期検出、重篤度測定、および治療に伴なう敗血症経過の評価のための方法、ならびにその方法の実施手段 |
WO1998033524A1 (en) * | 1997-02-03 | 1998-08-06 | Endocrinology Associates-Australia Llc | Method and compositions for preventing and treating the systemic inflammatory response syndrome including sepsis |
Non-Patent Citations (5)
Title |
---|
JPN6011061864; J. Invest. Med., 1997, Vol.45, No.9, p.552-560 * |
JPN6011061866; Proc. Nalt. Acad. Sci. USA, 1989, Vol.86, p.9519-9523 * |
JPN6012053852; J.Clin.Endocrinol.Metab.,Vol.79,No.6(1994)p.1605-1608 * |
JPN6012053853; FEBS Lett.,Vol.198,No.1(1986)p.71-79 * |
JPN6012053854; Biochem.Biophys.Res.Commun.,Vol.226,No.2(1996)p.420-425 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010519322A (ja) * | 2007-02-28 | 2010-06-03 | ベー・エル・アー・ハー・エム・エス・アクティエンゲゼルシャフト | 診断のためのプロカルシトニン1−116の選択的測定法、ならびにそのような方法を実行するための抗体およびキット |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5215250B2 (ja) | 敗血症及び敗血症様全身性感染の検出のための方法及び物質 | |
JP4932714B2 (ja) | コペプチンを使用する疾患の診断方法 | |
US9541549B2 (en) | Determination of a midregional proadrenomedullin partial peptide in biological fluids for diagnostic purposes, and immunoassays for carrying out such a determination | |
US8124366B2 (en) | Method for the determination of the formation of endothelins for medical diagnostic purposes, and antibodies and kits for carrying out such a method | |
WO1999013331A1 (fr) | Procede de dosage immunologique pour bnp | |
JP4656493B2 (ja) | 部分的proANPペプチドを同定するためのサンドイッチイムノアッセイ | |
Drǎguşanu et al. | Epitope motif of an anti‐nitrotyrosine antibody specific for tyrosine‐nitrated peptides revealed by a combination of affinity approaches and mass spectrometry | |
FR3001805A1 (fr) | Procede de detection d'un cancer colorectal | |
CA2721936A1 (en) | Novel polypeptides related to b-type natriuretic peptides and methods of their identification and use | |
Matikainen et al. | Demonstration of the Predominant Urine Osteocalcin Fragments Detectable by Two‐Site Immunoassays | |
JPH09229933A (ja) | p53蛋白質に対する自己抗体検出法 | |
Rehfeld et al. | The expression of peptide hormones in normal cells and tumour cells | |
CN115280148A (zh) | 测定肽酰甘氨酸α-酰胺化单加氧酶(PAM)的方法及其用于诊断目的的用途 | |
JP2001281257A (ja) | 化学発光標識剤及びそれを用いたアミノ酸標識方法、アミノ酸配列決定方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111129 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120224 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20120224 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121016 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130111 |
|
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: 20130205 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130228 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5215250 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160308 Year of fee payment: 3 |
|
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 |
|
EXPY | Cancellation because of completion of term |