JP2001524809A - 神経系疾患の治療に使用するための遺伝薬理学的方法 - Google Patents
神経系疾患の治療に使用するための遺伝薬理学的方法Info
- Publication number
- JP2001524809A JP2001524809A JP52750798A JP52750798A JP2001524809A JP 2001524809 A JP2001524809 A JP 2001524809A JP 52750798 A JP52750798 A JP 52750798A JP 52750798 A JP52750798 A JP 52750798A JP 2001524809 A JP2001524809 A JP 2001524809A
- Authority
- JP
- Japan
- Prior art keywords
- patient
- disease
- patients
- diagnosed
- apoe4
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 99
- 208000012902 Nervous system disease Diseases 0.000 title claims abstract description 27
- 230000002974 pharmacogenomic effect Effects 0.000 title claims description 10
- 239000003814 drug Substances 0.000 claims abstract description 88
- 229940079593 drug Drugs 0.000 claims abstract description 84
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 23
- 238000004393 prognosis Methods 0.000 claims abstract description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims description 133
- 108700028369 Alleles Proteins 0.000 claims description 132
- 101150037123 APOE gene Proteins 0.000 claims description 65
- 101100216294 Danio rerio apoeb gene Proteins 0.000 claims description 63
- 208000006011 Stroke Diseases 0.000 claims description 56
- 230000000694 effects Effects 0.000 claims description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 201000010099 disease Diseases 0.000 claims description 37
- 238000004458 analytical method Methods 0.000 claims description 26
- 208000018737 Parkinson disease Diseases 0.000 claims description 19
- 201000006417 multiple sclerosis Diseases 0.000 claims description 17
- 229940127243 cholinergic drug Drugs 0.000 claims description 10
- 208000005736 Nervous System Malformations Diseases 0.000 claims description 7
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 201000004931 neurofibromatosis Diseases 0.000 claims description 7
- 208000024777 Prion disease Diseases 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 5
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 5
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 206010010071 Coma Diseases 0.000 claims description 4
- 208000032170 Congenital Abnormalities Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 206010020575 Hyperammonaemia Diseases 0.000 claims description 4
- 206010061216 Infarction Diseases 0.000 claims description 4
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 4
- 201000002832 Lewy body dementia Diseases 0.000 claims description 4
- 208000002720 Malnutrition Diseases 0.000 claims description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
- 210000001766 X chromosome Anatomy 0.000 claims description 4
- 230000037354 amino acid metabolism Effects 0.000 claims description 4
- 239000003623 enhancer Substances 0.000 claims description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 4
- 230000007574 infarction Effects 0.000 claims description 4
- 210000000653 nervous system Anatomy 0.000 claims description 4
- 230000002536 noncholinergic effect Effects 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 206010020365 Homocystinuria Diseases 0.000 claims description 3
- 206010021888 Nervous system infections Diseases 0.000 claims description 3
- 201000011252 Phenylketonuria Diseases 0.000 claims description 3
- 102000015499 Presenilins Human genes 0.000 claims description 3
- 108010050254 Presenilins Proteins 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 230000007547 defect Effects 0.000 claims description 3
- 238000002474 experimental method Methods 0.000 claims description 3
- 235000018343 nutrient deficiency Nutrition 0.000 claims description 3
- 102000011772 Apolipoprotein C-I Human genes 0.000 claims description 2
- 108010076807 Apolipoprotein C-I Proteins 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 230000001131 transforming effect Effects 0.000 claims 3
- 241000282412 Homo Species 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- 208000024571 Pick disease Diseases 0.000 claims 1
- 238000010422 painting Methods 0.000 claims 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 74
- 238000012360 testing method Methods 0.000 abstract description 15
- 108010060159 Apolipoprotein E4 Proteins 0.000 description 45
- 210000004556 brain Anatomy 0.000 description 43
- 101710095339 Apolipoprotein E Proteins 0.000 description 40
- 102100029470 Apolipoprotein E Human genes 0.000 description 39
- 229960001685 tacrine Drugs 0.000 description 28
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 28
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 26
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 26
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 26
- 108090000623 proteins and genes Proteins 0.000 description 26
- 230000004044 response Effects 0.000 description 23
- 239000000969 carrier Substances 0.000 description 21
- 210000001320 hippocampus Anatomy 0.000 description 19
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 18
- 230000027455 binding Effects 0.000 description 16
- 230000006870 function Effects 0.000 description 16
- 230000002123 temporal effect Effects 0.000 description 16
- 229960004373 acetylcholine Drugs 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 230000001713 cholinergic effect Effects 0.000 description 13
- 230000002068 genetic effect Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 108010060215 Apolipoprotein E3 Proteins 0.000 description 12
- 102000008128 Apolipoprotein E3 Human genes 0.000 description 12
- 210000002569 neuron Anatomy 0.000 description 12
- 208000037259 Amyloid Plaque Diseases 0.000 description 11
- 102100032404 Cholinesterase Human genes 0.000 description 11
- 238000011888 autopsy Methods 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 229960001231 choline Drugs 0.000 description 11
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 11
- 230000007423 decrease Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 206010010904 Convulsion Diseases 0.000 description 9
- 210000005013 brain tissue Anatomy 0.000 description 9
- 230000000971 hippocampal effect Effects 0.000 description 9
- 229960002715 nicotine Drugs 0.000 description 9
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 235000012000 cholesterol Nutrition 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000003205 genotyping method Methods 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 7
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 6
- 210000002932 cholinergic neuron Anatomy 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000003551 muscarinic effect Effects 0.000 description 6
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 6
- 239000011574 phosphorus Substances 0.000 description 6
- 229910052698 phosphorus Inorganic materials 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- ZAOCCYZFRAVVGT-WFASDCNBSA-N (1r,3s)-1-(furan-2-yl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indol-2-ium-3-carboxylate Chemical compound C1([C@H]2C3=C(C4=CC=CC=C4N3)C[C@H](N2)C(=O)O)=CC=CO1 ZAOCCYZFRAVVGT-WFASDCNBSA-N 0.000 description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000007619 statistical method Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 102000017926 CHRM2 Human genes 0.000 description 4
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 4
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000943274 Homo sapiens Cholinesterase Proteins 0.000 description 4
- 108010005714 Interferon beta-1b Proteins 0.000 description 4
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000006727 cell loss Effects 0.000 description 4
- 230000006949 cholinergic function Effects 0.000 description 4
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 4
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- -1 phosphatidylethanol Phospholipids Chemical class 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 101150012960 Chrm2 gene Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 3
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 3
- 238000011887 Necropsy Methods 0.000 description 3
- 206010044565 Tremor Diseases 0.000 description 3
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 229960002028 atropine sulfate Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000010256 biochemical assay Methods 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 description 3
- 230000001149 cognitive effect Effects 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000002664 nootropic agent Substances 0.000 description 3
- 210000001009 nucleus accumben Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 230000001242 postsynaptic effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- MTKNGOHFNXIVOS-UHFFFAOYSA-N ticlopidine hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 MTKNGOHFNXIVOS-UHFFFAOYSA-N 0.000 description 3
- 201000011296 tyrosinemia Diseases 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
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 2
- 108010060219 Apolipoprotein E2 Proteins 0.000 description 2
- 102000013918 Apolipoproteins E Human genes 0.000 description 2
- 108010025628 Apolipoproteins E Proteins 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 108090000426 Caspase-1 Proteins 0.000 description 2
- 102100035904 Caspase-1 Human genes 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 2
- 102000000853 LDL receptors Human genes 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 201000003554 argininosuccinic aciduria Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229940021459 betaseron Drugs 0.000 description 2
- 230000005821 brain abnormality Effects 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000000064 cholinergic agonist Substances 0.000 description 2
- 208000030251 communication disease Diseases 0.000 description 2
- 210000005257 cortical tissue Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- NGAZZOYFWWSOGK-UHFFFAOYSA-N heptan-3-one Chemical compound CCCCC(=O)CC NGAZZOYFWWSOGK-UHFFFAOYSA-N 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000030214 innervation Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960003161 interferon beta-1b Drugs 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- 230000007334 memory performance Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 230000003518 presynaptic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000032817 regulation of phospholipid transport Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 230000002739 subcortical effect Effects 0.000 description 2
- 230000003956 synaptic plasticity Effects 0.000 description 2
- 229940028869 ticlid Drugs 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 101100029765 Arabidopsis thaliana PIA2 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 102000009660 Cholinergic Receptors Human genes 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 206010011906 Death Diseases 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
- 101710204837 Envelope small membrane protein Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101000771674 Homo sapiens Apolipoprotein E Proteins 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010023388 Ketonuria Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000001851 Low Density Lipoprotein Receptor-Related Protein-1 Human genes 0.000 description 1
- 108010015340 Low Density Lipoprotein Receptor-Related Protein-1 Proteins 0.000 description 1
- 101710145006 Lysis protein Proteins 0.000 description 1
- 206010027145 Melanocytic naevus Diseases 0.000 description 1
- 102000007207 Muscarinic M1 Receptor Human genes 0.000 description 1
- 108010008406 Muscarinic M1 Receptor Proteins 0.000 description 1
- 102000007205 Muscarinic M2 Receptor Human genes 0.000 description 1
- 108010008407 Muscarinic M2 Receptor Proteins 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 102000004659 Presynaptic Receptors Human genes 0.000 description 1
- 108010003717 Presynaptic Receptors Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241001655798 Taku Species 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000002027 Tuberin Human genes 0.000 description 1
- 108050009309 Tuberin Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- HCCBNDDJPKNSLM-WOQKIVQTSA-N [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-4-[[3-(2-hexadecylsulfanylethylamino)-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSCCCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 HCCBNDDJPKNSLM-WOQKIVQTSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 229940005524 anti-dementia drug Drugs 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 201000004051 cystathioninuria Diseases 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-N dCTP Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 230000004055 genetic distribution Effects 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 102000053020 human ApoE Human genes 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000003562 morphometric effect Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 239000000359 muscarinic M1 receptor agonist Substances 0.000 description 1
- 210000003365 myofibril Anatomy 0.000 description 1
- LUPAFPUKESJDMZ-UHFFFAOYSA-N n-[3-[1-[2-(8-chloro-6-oxo-5h-pyrido[2,3-b][1,4]benzodiazepin-11-yl)-2-oxoethyl]piperidin-4-yl]propyl]-n-ethyl-2,2-dimethylpentanamide Chemical compound C1CC(CCCN(CC)C(=O)C(C)(C)CCC)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC(Cl)=CC=C21 LUPAFPUKESJDMZ-UHFFFAOYSA-N 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940053504 other anti-dementia drug in atc Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000012006 phospholipid homeostasis Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- ZSLZBFCDCINBPY-YHBLMJDYSA-N s-[2-[3-[[(2r)-4-[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] ethanethioate Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS[14C](=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-YHBLMJDYSA-N 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 229940001089 sinemet Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960002961 ticlopidine hydrochloride Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
- SZCZSKMCTGEJKI-UHFFFAOYSA-N tuberin Natural products COC1=CC=C(C=CNC=O)C=C1 SZCZSKMCTGEJKI-UHFFFAOYSA-N 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/172—Haplotypes
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- Neurology (AREA)
- General Physics & Mathematics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Electrotherapy Devices (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/766,975 | 1996-12-16 | ||
| US08/766,975 US6022683A (en) | 1996-12-16 | 1996-12-16 | Methods for assessing the prognosis of a patient with a neurodegenerative disease |
| PCT/IB1997/001648 WO1998027227A2 (en) | 1996-12-16 | 1997-12-16 | Pharmacogenetic methods for use in the treatment of nervous system diseases |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009113073A Division JP5202429B2 (ja) | 1996-12-16 | 2009-05-07 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001524809A true JP2001524809A (ja) | 2001-12-04 |
| JP2001524809A5 JP2001524809A5 (https=) | 2005-08-11 |
Family
ID=25078098
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52750798A Withdrawn JP2001524809A (ja) | 1996-12-16 | 1997-12-16 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
| JP2009113073A Expired - Fee Related JP5202429B2 (ja) | 1996-12-16 | 2009-05-07 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
| JP2012117411A Pending JP2012152229A (ja) | 1996-12-16 | 2012-05-23 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
| JP2012274378A Pending JP2013059347A (ja) | 1996-12-16 | 2012-12-17 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009113073A Expired - Fee Related JP5202429B2 (ja) | 1996-12-16 | 2009-05-07 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
| JP2012117411A Pending JP2012152229A (ja) | 1996-12-16 | 2012-05-23 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
| JP2012274378A Pending JP2013059347A (ja) | 1996-12-16 | 2012-12-17 | 神経系疾患の治療に使用するための遺伝薬理学的方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US6022683A (https=) |
| EP (2) | EP0948647B1 (https=) |
| JP (4) | JP2001524809A (https=) |
| AT (1) | ATE269978T1 (https=) |
| AU (2) | AU5571798A (https=) |
| CA (2) | CA2275504C (https=) |
| DE (2) | DE69729473T2 (https=) |
| WO (2) | WO1998027227A2 (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014519076A (ja) * | 2011-04-28 | 2014-08-07 | ゼネラル・エレクトリック・カンパニイ | 薬理データの全体論的分析および可視化を用いて薬効を評価するための装置、システム、および方法 |
| US10658073B2 (en) | 2014-08-15 | 2020-05-19 | QIAGEN Redwood City, Inc. | Methods and systems for interpretation and reporting of sequence-based genetic tests using pooled allele statistics |
| US10665328B2 (en) | 2014-06-30 | 2020-05-26 | QIAGEN Redwood City, Inc. | Methods and systems for interpretation and reporting of sequence-based genetic tests |
| WO2020091375A3 (ko) * | 2018-10-29 | 2020-06-25 | 고려대학교 산학협력단 | 항우울제 추천 방법 및 시스템 |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6022683A (en) * | 1996-12-16 | 2000-02-08 | Nova Molecular Inc. | Methods for assessing the prognosis of a patient with a neurodegenerative disease |
| US6441149B1 (en) | 1998-06-15 | 2002-08-27 | Mitokor | Diagnostic method based on quantification of extramitochondrial DNA |
| US6489095B2 (en) | 1998-06-15 | 2002-12-03 | Mitokor | Diagnostic method based on quantification of extramitochondrial DNA |
| US6218117B1 (en) | 1998-06-15 | 2001-04-17 | Mitokor | Compositions and methods for identifying agents that quantitatively alter detectable extramitochondrial DNA:mitochondrial DNA ratios |
| CA2330829C (en) | 1998-06-16 | 2011-08-02 | Variagenics, Inc. | Methods for treating a neurological disease by determining bche genotype |
| JP2002526124A (ja) | 1998-10-01 | 2002-08-20 | ノヴァ モレキュラー インク. | 変異型gpiiia対立遺伝子および/または変異型gpiib対立遺伝子の存在を決定することにより、神経系疾患のリスクを有する対象を治療又は同定する方法 |
| AU773329B2 (en) * | 1999-05-14 | 2004-05-20 | Proteomedica Ab | Materials and methods relating to disease diagnosis |
| JP2003521024A (ja) * | 1999-06-25 | 2003-07-08 | ジェネサンス・ファーマシューティカルズ・インコーポレーテッド | ハプロタイプデータの入手および使用のための方法 |
| US7058517B1 (en) | 1999-06-25 | 2006-06-06 | Genaissance Pharmaceuticals, Inc. | Methods for obtaining and using haplotype data |
| US6692916B2 (en) * | 1999-06-28 | 2004-02-17 | Source Precision Medicine, Inc. | Systems and methods for characterizing a biological condition or agent using precision gene expression profiles |
| US6960439B2 (en) * | 1999-06-28 | 2005-11-01 | Source Precision Medicine, Inc. | Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles |
| US6573049B1 (en) | 1999-07-26 | 2003-06-03 | Nuvelo, Inc. | Genotyping of the paraoxonase 1 gene for prognosing, diagnosing, and treating a disease |
| US6896881B1 (en) | 1999-09-24 | 2005-05-24 | Mayo Foundation For Medical Education And Research | Therapeutic methods and compositions using viruses of the recombinant paramyxoviridae family |
| AU2001240820A1 (en) * | 2000-03-15 | 2001-09-24 | Oxford Glycosciences (Uk) Ltd. | Proteins, genes and their use for diagnosis and treatment of vascular dementia |
| US20070179197A1 (en) * | 2000-05-01 | 2007-08-02 | Accera, Inc. | Compositions and methods for improving or preserving brain function |
| WO2007115282A2 (en) * | 2006-04-03 | 2007-10-11 | Accera, Inc. | Use of ketogenic compounds for treatment of age-associated memory impairment |
| AU2001257451A1 (en) | 2000-05-01 | 2001-11-12 | Accera, Inc. | Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism |
| US6835750B1 (en) | 2000-05-01 | 2004-12-28 | Accera, Inc. | Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II |
| US20080009467A1 (en) * | 2000-05-01 | 2008-01-10 | Accera, Inc. | Combinations of medium chain triglycerides and therapeutic agents for the treatment and prevention of alzheimers disease and other diseases resulting from reduced neuronal metabolism |
| US6931326B1 (en) | 2000-06-26 | 2005-08-16 | Genaissance Pharmaceuticals, Inc. | Methods for obtaining and using haplotype data |
| US20030105082A1 (en) * | 2001-12-03 | 2003-06-05 | Murphy Greer Marechal | Methods for improving the therapeutic response of humans having major depression and carrying the gene for apolipoprotein E4 |
| US20040106124A1 (en) * | 2001-02-12 | 2004-06-03 | Murphy Greer M. | Methods for improving the treatment of major depression by genotyping for the gene for apolipoproteine e4 and for improving the terapeutic response of humans having major depression and carrying the gene for apolipoprotein e4 |
| US6399310B1 (en) | 2001-02-12 | 2002-06-04 | Akzo Nobel N.V. | Methods for improving the therapeutic response of humans having major depression and carrying the gene for apolipoprotein E4 |
| GB0106051D0 (en) * | 2001-03-12 | 2001-05-02 | Isis Innovation | Diagnostic screens for alzheimer's disease |
| US20030104453A1 (en) * | 2001-11-06 | 2003-06-05 | David Pickar | System for pharmacogenetics of adverse drug events |
| CN1612936A (zh) * | 2001-11-09 | 2005-05-04 | 苏尔斯精细医药公司 | 利用基因表达分布图识别、监控和治疗疾病以及鉴定生物学状态 |
| US20030224446A1 (en) * | 2001-12-20 | 2003-12-04 | Harry G. Jean | Method of predicting cytokine response to tissue injury |
| US20040267458A1 (en) * | 2001-12-21 | 2004-12-30 | Judson Richard S. | Methods for obtaining and using haplotype data |
| WO2003069431A2 (en) * | 2002-02-14 | 2003-08-21 | Medavante, Inc. | System and method for facilitating candidate and subject participation in clinical trial studies |
| US7432355B2 (en) * | 2002-08-09 | 2008-10-07 | The J. David Gladstone Institutes | Apolipoprotein E stable folding intermediate and methods of use thereof |
| US8688385B2 (en) | 2003-02-20 | 2014-04-01 | Mayo Foundation For Medical Education And Research | Methods for selecting initial doses of psychotropic medications based on a CYP2D6 genotype |
| CA2525517C (en) * | 2003-06-19 | 2016-05-31 | Applied Research Systems Ars Holding N.V. | Use of prion conversion modulating agents |
| US20050038692A1 (en) * | 2003-08-14 | 2005-02-17 | Kane John Michael | System and method for facilitating centralized candidate selection and monitoring subject participation in clinical trial studies |
| WO2005073892A2 (en) * | 2004-01-16 | 2005-08-11 | Disease Management Services, Plc | Disease management system |
| WO2006008119A1 (en) | 2004-07-16 | 2006-01-26 | Proteosys Ag | Muscarinic antagonists with parp and sir modulatng activity as agents for inflammatory diseases |
| US20060252775A1 (en) * | 2005-05-03 | 2006-11-09 | Henderson Samuel T | Methods for reducing levels of disease associated proteins |
| WO2007001883A2 (en) * | 2005-06-20 | 2007-01-04 | Accera, Inc. | Method to reduce oxidative damage and improve mitochondrial efficiency |
| EP3703058A1 (en) * | 2005-11-29 | 2020-09-02 | Children's Hospital Medical Center | A method of selecting a medication for a patient |
| US20080126118A1 (en) * | 2006-11-24 | 2008-05-29 | General Electric Company, A New York Corporation | Systems, methods and apparatus for a network application framework system |
| TWI362012B (en) * | 2007-07-23 | 2012-04-11 | System of providing hygienic education information and method thereof | |
| CA2853992C (en) | 2007-07-31 | 2020-06-23 | Cerecin Inc. | Use of genomic testing and ketogenic compounds for treatment of reduced cognitive function |
| US20090198504A1 (en) * | 2008-02-05 | 2009-08-06 | Medavante, Inc. | Rater resource allocation systems and methods |
| US8105809B2 (en) * | 2008-07-03 | 2012-01-31 | Accera, Inc. | Enzymatic synthesis of acetoacetate esters and derivatives |
| AU2009266869B2 (en) * | 2008-07-03 | 2016-07-07 | Cerecin Inc. | Monoglyceride of acetoacetate and derivatives for the treatment of neurological disorders |
| WO2010081825A2 (en) | 2009-01-13 | 2010-07-22 | Proteosys Ag | Pirenzepine as an agent in cancer treatment |
| EP2360280A1 (en) * | 2010-02-24 | 2011-08-24 | Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol | Genetic marker for the diagnosis of dementia with Lewy bodies |
| US20130080182A1 (en) * | 2011-09-26 | 2013-03-28 | Athleticode Inc. | Methods For Using DNA Testing To Screen For Genotypes Relevant To Athleticism, Health And Risk Of Injury |
| RU2467680C1 (ru) * | 2011-10-04 | 2012-11-27 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Воронежская государственная медицинская академия им. Н.Н. Бурденко" Министерства здравоохранения и социального развития Российской Федерации | Способ прогнозирования эффективности лечения больных ишемическим инсультом |
| EP3628315A1 (en) | 2018-09-28 | 2020-04-01 | Université de Caen Normandie | Combination of acetylcholinesterase inhibitor and 5-ht4 receptor agonist as neuroprotective agent in the treatment of neurodegenerative diseases |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3265577B2 (ja) * | 1992-10-13 | 2002-03-11 | デューク・ユニバーシティ | アポリポ蛋白eの4型イソ型の測定法 |
| CA2111503A1 (en) * | 1993-12-15 | 1995-06-16 | Mcgill University | Apolipoprotein e polymorphism and alzheimer's disease |
| FR2716894B1 (fr) * | 1994-03-07 | 1996-05-24 | Pasteur Institut | Marqueurs génétiques utilisés conjointement pour le diagnostic de la maladie d'Alzheimer, méthode et kit de diagnostic. |
| GB9408465D0 (en) * | 1994-04-27 | 1994-06-22 | Univ Mcgill | Apolipoprotein e polymorphism & treatment of alzheimer's disease |
| GB9415073D0 (en) * | 1994-06-27 | 1994-09-14 | Smithkline Beecham Plc | Novel method |
| GB9414624D0 (en) * | 1994-07-20 | 1994-09-07 | Smithkline Beecham Plc | Novel method |
| US6022683A (en) * | 1996-12-16 | 2000-02-08 | Nova Molecular Inc. | Methods for assessing the prognosis of a patient with a neurodegenerative disease |
-
1996
- 1996-12-16 US US08/766,975 patent/US6022683A/en not_active Expired - Lifetime
-
1997
- 1997-12-16 JP JP52750798A patent/JP2001524809A/ja not_active Withdrawn
- 1997-12-16 AU AU55717/98A patent/AU5571798A/en not_active Withdrawn
- 1997-12-16 WO PCT/IB1997/001648 patent/WO1998027227A2/en not_active Ceased
- 1997-12-16 EP EP97952129A patent/EP0948647B1/en not_active Expired - Lifetime
- 1997-12-16 WO PCT/IB1997/001641 patent/WO1998027226A2/en not_active Ceased
- 1997-12-16 AT AT97952129T patent/ATE269978T1/de not_active IP Right Cessation
- 1997-12-16 CA CA002275504A patent/CA2275504C/en not_active Expired - Fee Related
- 1997-12-16 CA CA2275404A patent/CA2275404C/en not_active Expired - Fee Related
- 1997-12-16 DE DE69729473T patent/DE69729473T2/de not_active Expired - Lifetime
- 1997-12-16 AU AU56757/98A patent/AU745073B2/en not_active Ceased
- 1997-12-16 EP EP97953011A patent/EP0946753B1/en not_active Expired - Lifetime
- 1997-12-16 DE DE69729654T patent/DE69729654T2/de not_active Expired - Lifetime
-
2000
- 2000-02-08 US US09/500,162 patent/US7001736B1/en not_active Expired - Fee Related
-
2009
- 2009-05-07 JP JP2009113073A patent/JP5202429B2/ja not_active Expired - Fee Related
-
2012
- 2012-05-23 JP JP2012117411A patent/JP2012152229A/ja active Pending
- 2012-12-17 JP JP2012274378A patent/JP2013059347A/ja active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014519076A (ja) * | 2011-04-28 | 2014-08-07 | ゼネラル・エレクトリック・カンパニイ | 薬理データの全体論的分析および可視化を用いて薬効を評価するための装置、システム、および方法 |
| US10665328B2 (en) | 2014-06-30 | 2020-05-26 | QIAGEN Redwood City, Inc. | Methods and systems for interpretation and reporting of sequence-based genetic tests |
| US10658073B2 (en) | 2014-08-15 | 2020-05-19 | QIAGEN Redwood City, Inc. | Methods and systems for interpretation and reporting of sequence-based genetic tests using pooled allele statistics |
| WO2020091375A3 (ko) * | 2018-10-29 | 2020-06-25 | 고려대학교 산학협력단 | 항우울제 추천 방법 및 시스템 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998027227A2 (en) | 1998-06-25 |
| US6022683A (en) | 2000-02-08 |
| JP2013059347A (ja) | 2013-04-04 |
| WO1998027226A3 (en) | 1998-08-20 |
| EP0946753B1 (en) | 2004-06-09 |
| AU5675798A (en) | 1998-07-15 |
| ATE269978T1 (de) | 2004-07-15 |
| EP0948647A1 (en) | 1999-10-13 |
| CA2275504C (en) | 2009-09-22 |
| JP5202429B2 (ja) | 2013-06-05 |
| CA2275404A1 (en) | 1998-06-25 |
| AU745073B2 (en) | 2002-03-14 |
| EP0948647B1 (en) | 2004-06-23 |
| US7001736B1 (en) | 2006-02-21 |
| CA2275404C (en) | 2011-02-08 |
| WO1998027227A3 (en) | 1998-08-27 |
| DE69729473D1 (de) | 2004-07-15 |
| DE69729654D1 (de) | 2004-07-29 |
| AU5571798A (en) | 1998-07-15 |
| EP0946753A2 (en) | 1999-10-06 |
| CA2275504A1 (en) | 1998-06-25 |
| JP2009213482A (ja) | 2009-09-24 |
| DE69729473T2 (de) | 2005-06-09 |
| DE69729654T2 (de) | 2005-07-21 |
| JP2012152229A (ja) | 2012-08-16 |
| WO1998027226A2 (en) | 1998-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5202429B2 (ja) | 神経系疾患の治療に使用するための遺伝薬理学的方法 | |
| JP3285585B2 (ja) | アポリポ蛋白質eの多形性およびアルツハイマー病の治療 | |
| Tsai et al. | Apolipoprotein E: risk factor for Alzheimer disease | |
| Blacker et al. | ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative | |
| Wilkins et al. | Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients | |
| Corbo et al. | Association of estrogen receptor α (ESR1) Pvu II and Xba I polymorphisms with sporadic Alzheimer’s disease and their effect on apolipoprotein E concentrations | |
| US20100240744A1 (en) | Methods for the treatment of dementia based on apo e genotype | |
| US7049078B2 (en) | Apolipoprotein E polymorphism and treatment of alzheimer's disease | |
| EP1074634B1 (en) | Method for the diagnosis or the prognosis of Alzheimer disease therapeutical composition for preventing or treating Alzheimer disease | |
| Kazukauskiene et al. | Importance of thyroid hormone level and genetic variations in deiodinases for patients after acute myocardial infarction: a longitudinal observational study | |
| US20140088035A1 (en) | Treating schizophrenia | |
| Helisalmi et al. | The leucine (7)-to-proline (7) polymorphism in the signal peptide of neuropeptide Y is not associated with Alzheimer's disease or the link apolipoprotein E | |
| Padilla et al. | Genetics of dementia | |
| AU733237B2 (en) | Use of Apolipoprotein polymorphism E in the treatment of Alzheimer's disease | |
| US20140142150A1 (en) | Treating neuropsychiatric disorders | |
| Miller | Genetic Susceptibility in Alzheimer’s Disease and the Role of Lipid Metabolism | |
| NZ500375A (en) | A genotyping survey for characterising the presence of E2 and E3 allele or the absence of apolipoprotein E4 allele for determining the level of treatment medication for Alzheimer's patients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041215 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20041215 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080325 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20080613 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080625 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080804 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080723 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080901 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080822 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080929 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080929 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090106 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090408 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20090630 |