AU2007238533C1 - Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung - Google Patents
Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung Download PDFInfo
- Publication number
- AU2007238533C1 AU2007238533C1 AU2007238533A AU2007238533A AU2007238533C1 AU 2007238533 C1 AU2007238533 C1 AU 2007238533C1 AU 2007238533 A AU2007238533 A AU 2007238533A AU 2007238533 A AU2007238533 A AU 2007238533A AU 2007238533 C1 AU2007238533 C1 AU 2007238533C1
- Authority
- AU
- Australia
- Prior art keywords
- collagen
- col
- type
- lung
- transplantation
- 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.)
- Ceased
Links
- 210000004072 lung Anatomy 0.000 title claims abstract description 345
- 238000011282 treatment Methods 0.000 title claims description 21
- 208000019693 Lung disease Diseases 0.000 title abstract description 39
- 210000002808 connective tissue Anatomy 0.000 title abstract description 17
- 230000008105 immune reaction Effects 0.000 title 1
- 102000012432 Collagen Type V Human genes 0.000 claims abstract description 127
- 108010022514 Collagen Type V Proteins 0.000 claims abstract description 127
- 108010035532 Collagen Proteins 0.000 claims abstract description 91
- 102000008186 Collagen Human genes 0.000 claims abstract description 90
- 229920001436 collagen Polymers 0.000 claims abstract description 90
- 238000000034 method Methods 0.000 claims abstract description 77
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims abstract description 48
- 210000001519 tissue Anatomy 0.000 claims abstract description 45
- 239000012530 fluid Substances 0.000 claims abstract description 41
- 239000000203 mixture Substances 0.000 claims abstract description 15
- 208000027930 type IV hypersensitivity disease Diseases 0.000 claims description 147
- 230000004044 response Effects 0.000 claims description 132
- 230000000890 antigenic effect Effects 0.000 claims description 34
- 230000028993 immune response Effects 0.000 claims description 30
- 238000002347 injection Methods 0.000 claims description 23
- 239000007924 injection Substances 0.000 claims description 23
- 230000005784 autoimmunity Effects 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 21
- 239000011324 bead Substances 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- -1 plates Substances 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 6
- 230000005867 T cell response Effects 0.000 claims description 5
- 239000000872 buffer Substances 0.000 claims description 5
- 230000006058 immune tolerance Effects 0.000 claims description 4
- 206010036790 Productive cough Diseases 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 210000003802 sputum Anatomy 0.000 claims description 3
- 208000024794 sputum Diseases 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 239000004599 antimicrobial Substances 0.000 claims description 2
- 210000003097 mucus Anatomy 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 239000000427 antigen Substances 0.000 abstract description 105
- 102000036639 antigens Human genes 0.000 abstract description 98
- 108091007433 antigens Proteins 0.000 abstract description 98
- 230000006472 autoimmune response Effects 0.000 abstract description 47
- 208000036971 interstitial lung disease 2 Diseases 0.000 abstract description 42
- 238000003556 assay Methods 0.000 abstract description 38
- 210000000056 organ Anatomy 0.000 abstract description 28
- 241000486679 Antitype Species 0.000 abstract description 15
- 238000012544 monitoring process Methods 0.000 abstract description 15
- 238000002054 transplantation Methods 0.000 description 166
- 230000005951 type IV hypersensitivity Effects 0.000 description 143
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 142
- 238000011706 wistar kyoto rat Methods 0.000 description 96
- 241000700159 Rattus Species 0.000 description 86
- 210000004988 splenocyte Anatomy 0.000 description 58
- 239000000523 sample Substances 0.000 description 57
- 210000004027 cell Anatomy 0.000 description 56
- 230000001154 acute effect Effects 0.000 description 49
- 230000035611 feeding Effects 0.000 description 44
- 230000007170 pathology Effects 0.000 description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 41
- 230000000961 alloantigen Effects 0.000 description 35
- 201000010099 disease Diseases 0.000 description 35
- 210000002966 serum Anatomy 0.000 description 35
- 210000004698 lymphocyte Anatomy 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 32
- 238000012360 testing method Methods 0.000 description 32
- 230000020192 tolerance induction in gut-associated lymphoid tissue Effects 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 30
- 239000003085 diluting agent Substances 0.000 description 29
- 206010029888 Obliterative bronchiolitis Diseases 0.000 description 27
- 201000003848 bronchiolitis obliterans Diseases 0.000 description 27
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 description 27
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 26
- 238000011161 development Methods 0.000 description 26
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 26
- 206010014025 Ear swelling Diseases 0.000 description 24
- 210000001744 T-lymphocyte Anatomy 0.000 description 24
- 108090000978 Interleukin-4 Proteins 0.000 description 20
- 102000004388 Interleukin-4 Human genes 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 210000000038 chest Anatomy 0.000 description 15
- 230000000735 allogeneic effect Effects 0.000 description 14
- 230000001363 autoimmune Effects 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 230000006698 induction Effects 0.000 description 14
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 13
- 108060003951 Immunoglobulin Proteins 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 230000001684 chronic effect Effects 0.000 description 13
- 102000018358 immunoglobulin Human genes 0.000 description 13
- 230000004083 survival effect Effects 0.000 description 13
- 229940098773 bovine serum albumin Drugs 0.000 description 12
- 230000003292 diminished effect Effects 0.000 description 12
- 210000001165 lymph node Anatomy 0.000 description 12
- 210000005087 mononuclear cell Anatomy 0.000 description 12
- 239000002158 endotoxin Substances 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 238000010171 animal model Methods 0.000 description 10
- 210000000621 bronchi Anatomy 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 229940072221 immunoglobulins Drugs 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 208000011580 syndromic disease Diseases 0.000 description 10
- 230000002792 vascular Effects 0.000 description 10
- 206010048748 Graft loss Diseases 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 210000003484 anatomy Anatomy 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 210000000987 immune system Anatomy 0.000 description 9
- 238000003018 immunoassay Methods 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 229920006008 lipopolysaccharide Polymers 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 230000001629 suppression Effects 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 208000024869 Goodpasture syndrome Diseases 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 230000001900 immune effect Effects 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 230000009257 reactivity Effects 0.000 description 8
- 238000010254 subcutaneous injection Methods 0.000 description 8
- 102000000503 Collagen Type II Human genes 0.000 description 7
- 108010041390 Collagen Type II Proteins 0.000 description 7
- 102000004266 Collagen Type IV Human genes 0.000 description 7
- 108010042086 Collagen Type IV Proteins 0.000 description 7
- 230000005875 antibody response Effects 0.000 description 7
- 230000000747 cardiac effect Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000009885 systemic effect Effects 0.000 description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 6
- 102000009736 Collagen Type XI Human genes 0.000 description 6
- 108010034789 Collagen Type XI Proteins 0.000 description 6
- 241000287828 Gallus gallus Species 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 6
- 230000024932 T cell mediated immunity Effects 0.000 description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 6
- 230000003367 anti-collagen effect Effects 0.000 description 6
- 230000006907 apoptotic process Effects 0.000 description 6
- 230000007969 cellular immunity Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 108010021083 hen egg lysozyme Proteins 0.000 description 6
- 230000002962 histologic effect Effects 0.000 description 6
- 230000004046 hyporesponsiveness Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000012453 sprague-dawley rat model Methods 0.000 description 6
- 206010051604 Lung transplant rejection Diseases 0.000 description 5
- 238000000585 Mann–Whitney U test Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 238000003304 gavage Methods 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 230000001771 impaired effect Effects 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000000386 microscopy Methods 0.000 description 5
- 230000008506 pathogenesis Effects 0.000 description 5
- 230000008807 pathological lesion Effects 0.000 description 5
- 230000002685 pulmonary effect Effects 0.000 description 5
- 238000011552 rat model Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000008961 swelling Effects 0.000 description 5
- 230000024664 tolerance induction Effects 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 4
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 102000001187 Collagen Type III Human genes 0.000 description 4
- 108010069502 Collagen Type III Proteins 0.000 description 4
- 102000002734 Collagen Type VI Human genes 0.000 description 4
- 108010043741 Collagen Type VI Proteins 0.000 description 4
- 241000701022 Cytomegalovirus Species 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
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 210000000845 cartilage Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 4
- 230000004727 humoral immunity Effects 0.000 description 4
- 229960002591 hydroxyproline Drugs 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000007108 local immune response Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 238000013105 post hoc analysis Methods 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 102100031168 CCN family member 2 Human genes 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- 201000003883 Cystic fibrosis Diseases 0.000 description 3
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 3
- 102000006354 HLA-DR Antigens Human genes 0.000 description 3
- 108010058597 HLA-DR Antigens Proteins 0.000 description 3
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 3
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 3
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 3
- 238000012313 Kruskal-Wallis test Methods 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 206010069351 acute lung injury Diseases 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 230000003176 fibrotic effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 229940124589 immunosuppressive drug Drugs 0.000 description 3
- 238000002650 immunosuppressive therapy Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000004199 lung function Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 210000002826 placenta Anatomy 0.000 description 3
- 230000009696 proliferative response Effects 0.000 description 3
- 210000001147 pulmonary artery Anatomy 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 238000011808 rodent model Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 210000000115 thoracic cavity Anatomy 0.000 description 3
- 230000002992 thymic effect Effects 0.000 description 3
- 238000007492 two-way ANOVA Methods 0.000 description 3
- 229930003347 Atropine Natural products 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 208000029147 Collagen-vascular disease Diseases 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 208000029464 Pulmonary infiltrates Diseases 0.000 description 2
- 241000219061 Rheum Species 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 238000010161 Student-Newman-Keuls test Methods 0.000 description 2
- 206010042618 Surgical procedure repeated Diseases 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 208000037883 airway inflammation Diseases 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 230000003872 anastomosis Effects 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 230000005889 cellular cytotoxicity Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000009699 differential effect Effects 0.000 description 2
- 238000002845 discoloration Methods 0.000 description 2
- 230000002222 downregulating effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 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 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 229960003132 halothane Drugs 0.000 description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 230000003832 immune regulation Effects 0.000 description 2
- 230000008629 immune suppression Effects 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000004224 pleura Anatomy 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 208000018299 prostration Diseases 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 230000008458 response to injury Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Chemical group 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- LVXLCZPTUBQNHH-UHFFFAOYSA-N 2-amino-5-[[1-(carboxymethylamino)-3-(2-chloro-1,1,2-trifluoroethyl)sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound OC(=O)C(N)CCC(=O)NC(CSC(F)(F)C(F)Cl)C(=O)NCC(O)=O LVXLCZPTUBQNHH-UHFFFAOYSA-N 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- QWVRTSZDKPRPDF-UHFFFAOYSA-N 5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine Chemical compound C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 QWVRTSZDKPRPDF-UHFFFAOYSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000024985 Alport syndrome Diseases 0.000 description 1
- 108090000672 Annexin A5 Proteins 0.000 description 1
- 102000004121 Annexin A5 Human genes 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 102000013602 Cardiac Myosins Human genes 0.000 description 1
- 108010051609 Cardiac Myosins Proteins 0.000 description 1
- 206010068051 Chimerism Diseases 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- 208000002197 Ehlers-Danlos syndrome Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 206010035588 Pleural adhesion Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004792 Prolene Substances 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 101000960939 Rattus norvegicus Interleukin-4 Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 108700008242 S-(2-chloro-1,1,2-trifluoroethyl)glutathione Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000013276 bronchoscopy Methods 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000009795 fibrotic process Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 208000003215 hereditary nephritis Diseases 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000017555 immunoglobulin mediated immune response Effects 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000011293 immunotherapeutic strategy Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 210000005059 placental tissue Anatomy 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000012859 tissue stain Substances 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/12—Pulmonary diseases
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Rehabilitation Therapy (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75919506P | 2006-01-13 | 2006-01-13 | |
| US60/759,195 | 2006-01-13 | ||
| PCT/US2007/060533 WO2007120947A1 (en) | 2006-01-13 | 2007-01-13 | Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2007238533A1 AU2007238533A1 (en) | 2007-10-25 |
| AU2007238533B2 AU2007238533B2 (en) | 2012-09-20 |
| AU2007238533C1 true AU2007238533C1 (en) | 2013-08-15 |
Family
ID=38609836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007238533A Ceased AU2007238533C1 (en) | 2006-01-13 | 2007-01-13 | Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US7759075B2 (enExample) |
| EP (2) | EP2672266B1 (enExample) |
| JP (2) | JP5030973B2 (enExample) |
| CN (1) | CN101375157B (enExample) |
| AU (1) | AU2007238533C1 (enExample) |
| BR (1) | BRPI0706575B8 (enExample) |
| CA (2) | CA2965211C (enExample) |
| WO (1) | WO2007120947A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2672266B1 (en) * | 2006-01-13 | 2018-08-01 | Indiana University Research & Technology Corporation | Method for screening a lung transplant candidate for an elevated risk of rejection |
| WO2008082821A1 (en) * | 2006-11-28 | 2008-07-10 | University Of Southern California | Method for promoting wound healing |
| JP2012518001A (ja) * | 2009-02-13 | 2012-08-09 | インディアナ ユニバーシティ リサーチ アンド テクノロジー コーポレイション | Ｍｍｐ２およびｍｍｐ９を阻害する化合物および方法 |
| CA2759611C (en) * | 2009-04-22 | 2018-11-13 | Indiana University Research And Technology Corporation | Compositions and methods for the treatment of chronic obstructive pulmonary disease and asthma |
| GB2488289A (en) | 2009-11-06 | 2012-08-22 | Univ Leland Stanford Junior | Non-invasive diagnosis of graft rejection in organ transplant patients |
| AU2012262154B2 (en) * | 2011-05-31 | 2016-08-04 | Idexx Laboratories, Inc. | Detection of degradation products of feline NT-proBNP |
| SG11201405830VA (en) * | 2012-03-27 | 2014-10-30 | Genentech Inc | Methods of prognosing, diagnosing and treating idiopathic pulmonary fibrosis |
| JP6058354B2 (ja) * | 2012-11-02 | 2017-01-11 | 東芝メディカルシステムズ株式会社 | 画像処理装置及び画像処理方法 |
| JP6312054B2 (ja) * | 2013-11-06 | 2018-04-18 | 学校法人日本大学 | 間質性肺炎のバイオマーカー |
| US20170082619A1 (en) | 2015-09-23 | 2017-03-23 | One Lambda, Inc. | Methods of Detecting Alloantibodies Using HLA and Non-HLA Antigens |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444879A (en) * | 1981-01-29 | 1984-04-24 | Science Research Center, Inc. | Immunoassay with article having support film and immunological counterpart of analyte |
| EP0487289B1 (en) * | 1990-11-20 | 1996-09-04 | BEHRINGWERKE Aktiengesellschaft | Cyclosporin immunoassay |
| US6911220B1 (en) * | 1992-02-19 | 2005-06-28 | The General Hospital Corporation | Allogeneic and xenogeneic transplantation |
| JP2702354B2 (ja) * | 1992-05-11 | 1998-01-21 | 帝人株式会社 | 血中の肺組織障害マーカー |
| US5778875A (en) * | 1996-05-06 | 1998-07-14 | U.S. Divers Co., Inc. | First stage regulator and rotatable in-line valve |
| AUPO026596A0 (en) * | 1996-06-05 | 1996-06-27 | Biomolecular Research Institute Limited | Viral peptide |
| US5962025A (en) | 1996-07-16 | 1999-10-05 | The University Of Tennessee Research Corporation | Method for treatment of systemic sclerosis and related fibrotic diseases |
| US5990274A (en) * | 1997-11-25 | 1999-11-23 | Dade Behring Inc. | Cyclosporine derivatives and uses thereof |
| UA74141C2 (uk) * | 1998-12-09 | 2005-11-15 | Дж.Д. Сірл Енд Ко. | Фармацевтична композиція на основі тонкоподрібненого еплеренону (варіанти), спосіб її одержання та спосіб лікування розладів, опосередкованих альдостероном (варіанти) |
| KR100734994B1 (ko) * | 2000-01-31 | 2007-07-04 | 아사히 가세이 가부시키가이샤 | 클라미디아 뉴모니아 검출용 항체 |
| US7348005B2 (en) * | 2000-03-15 | 2008-03-25 | Advanced Research And Technology Institute | Oral tolerance induction by collagen to prevent allograft rejection |
| EP1267907A1 (en) * | 2000-03-23 | 2003-01-02 | Akzo Nobel N.V. | Use of mia in immunotherapy |
| JP2002220343A (ja) * | 2001-01-26 | 2002-08-09 | Toray Ind Inc | びまん性肺疾患延命剤 |
| AU2005234006A1 (en) * | 2004-04-08 | 2005-10-27 | Janssen Pharmaceutica N.V. | Immunohistochemical detection method of collagen in a tissue sample |
| CA2627974A1 (en) | 2005-11-16 | 2007-05-24 | The University Of Tennessee Research Foundation | Methods of treating fibrosing diseases by induction of immune tolerance |
| EP2672266B1 (en) * | 2006-01-13 | 2018-08-01 | Indiana University Research & Technology Corporation | Method for screening a lung transplant candidate for an elevated risk of rejection |
-
2007
- 2007-01-13 EP EP13175642.1A patent/EP2672266B1/en not_active Not-in-force
- 2007-01-13 EP EP07756361.7A patent/EP1977234B1/en not_active Not-in-force
- 2007-01-13 BR BRPI0706575A patent/BRPI0706575B8/pt not_active IP Right Cessation
- 2007-01-13 WO PCT/US2007/060533 patent/WO2007120947A1/en not_active Ceased
- 2007-01-13 CA CA2965211A patent/CA2965211C/en active Active
- 2007-01-13 CA CA2641318A patent/CA2641318C/en active Active
- 2007-01-13 AU AU2007238533A patent/AU2007238533C1/en not_active Ceased
- 2007-01-13 CN CN200780003133.2A patent/CN101375157B/zh not_active Expired - Fee Related
- 2007-01-13 JP JP2008550549A patent/JP5030973B2/ja not_active Expired - Fee Related
-
2008
- 2008-07-11 US US12/171,661 patent/US7759075B2/en active Active
-
2010
- 2010-06-25 US US12/823,570 patent/US7939281B2/en active Active
-
2011
- 2011-04-07 US US13/082,203 patent/US8039225B2/en active Active
- 2011-12-27 JP JP2011285617A patent/JP5936349B2/ja not_active Expired - Fee Related
Non-Patent Citations (5)
| Title |
|---|
| FERNANDEZ-MADRID, F. et al., Cancer research, 1996, vol. 56, pages 121-126 * |
| SUMPTER, T.L. and WILKES, D.S., American Journal of Physiology - Lung Cellular and Molecular Physiology, 2004, vol. 286, pages L1129-L1139 * |
| WILKES, D. S., Graft, 2003, vol. 6, pages 42-49 * |
| YASUFUKU, K. et al., American Journal of Respiratory cell molecular biology, 2001, pages 26-34 * |
| YASUFUKU, K. et al., Transplantation, 2002, vol. 73, no. 4, pages 500-505 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007238533B2 (en) | 2012-09-20 |
| CN101375157A (zh) | 2009-02-25 |
| US8039225B2 (en) | 2011-10-18 |
| CN101375157B (zh) | 2015-06-17 |
| AU2007238533A1 (en) | 2007-10-25 |
| CA2641318C (en) | 2017-06-20 |
| BRPI0706575B8 (pt) | 2021-05-25 |
| BRPI0706575A2 (pt) | 2011-04-05 |
| HK1126861A1 (en) | 2009-09-11 |
| BRPI0706575B1 (pt) | 2018-12-11 |
| US20110020838A1 (en) | 2011-01-27 |
| EP2672266B1 (en) | 2018-08-01 |
| EP1977234B1 (en) | 2015-11-04 |
| JP2012108137A (ja) | 2012-06-07 |
| JP5936349B2 (ja) | 2016-06-22 |
| WO2007120947A1 (en) | 2007-10-25 |
| CA2641318A1 (en) | 2007-10-25 |
| CA2965211A1 (en) | 2007-10-25 |
| JP2009524023A (ja) | 2009-06-25 |
| US20110183356A1 (en) | 2011-07-28 |
| US20090017013A1 (en) | 2009-01-15 |
| US7939281B2 (en) | 2011-05-10 |
| EP2672266A3 (en) | 2014-02-05 |
| US7759075B2 (en) | 2010-07-20 |
| EP1977234A1 (en) | 2008-10-08 |
| EP1977234A4 (en) | 2009-06-03 |
| EP2672266A2 (en) | 2013-12-11 |
| JP5030973B2 (ja) | 2012-09-19 |
| CA2965211C (en) | 2020-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8039225B2 (en) | Method to identify patients at risk for lung transplant rejection | |
| Yasufuku et al. | Oral tolerance induction by type V collagen downregulates lung allograft rejection | |
| CN101801402B (zh) | 炎性疾病和自身免疫疾病的治疗和预防 | |
| Behairy et al. | Assessment of intrahepatic regulatory T cells in children with autoimmune hepatitis | |
| Wall et al. | Autoimmune thyroid disease: immunological, pathological, and clinical aspects | |
| US9005982B2 (en) | Biomarkers associated with autoimmune diseases of the lung | |
| US20170340716A1 (en) | Compositions and methods for the treatment of chronic obstructive pulmonary disease and asthma | |
| HK1126861B (en) | Molecules for the treatment of lung disease involving an immune reaction to connective tissue found in the lung | |
| Latorre-Rodríguez et al. | Noninvasive biomarkers for the detection of GERD-induced pulmonary injury | |
| US7348005B2 (en) | Oral tolerance induction by collagen to prevent allograft rejection | |
| WO2019077143A1 (en) | METHODS AND COMPOSITIONS FOR PREDICTING AND PRECOCUALLY DIAGNOSING A CHRONIC ACTIVE FORM OF ABMR WITH GRAFT GLOMERULOPATHY AND RENAL TRANSPLANT LOSS | |
| Aziz et al. | Immunobiology, Diagnosis, and Treatment of Rejection | |
| Okon et al. | Đcheck for updates | |
| Beber | Analysis of the T Cell Composition of Clinically Stable ISHLT Grade A1 Rejection Lesions | |
| Ratkay | Investigation of an adjuvant-enhanced model of murine arthritis and its therapeutic application | |
| Garioch | Dermatitis herpetiformis: clinical and immunological aspects |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| DA2 | Applications for amendment section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 14 JAN 2013 . |
|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 14 JAN 2013 |
|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |