WO1996017249A1 - Procedes de detection de l'encephalopathie spongiforme - Google Patents
Procedes de detection de l'encephalopathie spongiforme Download PDFInfo
- Publication number
- WO1996017249A1 WO1996017249A1 PCT/GB1995/002766 GB9502766W WO9617249A1 WO 1996017249 A1 WO1996017249 A1 WO 1996017249A1 GB 9502766 W GB9502766 W GB 9502766W WO 9617249 A1 WO9617249 A1 WO 9617249A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- agent
- animal
- spongiform encephalopathy
- body fluid
- amount
- Prior art date
Links
- 208000024777 Prion disease Diseases 0.000 title claims abstract description 15
- 238000001514 detection method Methods 0.000 title description 6
- 241001465754 Metazoa Species 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 34
- 210000001124 body fluid Anatomy 0.000 claims abstract description 12
- 239000010839 body fluid Substances 0.000 claims abstract description 12
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims abstract description 11
- 238000010186 staining Methods 0.000 claims abstract description 5
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 claims description 14
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 claims description 14
- 101710095339 Apolipoprotein E Proteins 0.000 claims description 7
- 102100029470 Apolipoprotein E Human genes 0.000 claims description 7
- 230000002163 immunogen Effects 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 230000002596 correlated effect Effects 0.000 claims description 3
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 claims description 2
- 238000001419 two-dimensional polyacrylamide gel electrophoresis Methods 0.000 claims description 2
- 238000001502 gel electrophoresis Methods 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 8
- 238000000326 densiometry Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 description 25
- 239000000499 gel Substances 0.000 description 10
- 241000283690 Bos taurus Species 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 3
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 2
- 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 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 244000144980 herd Species 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000003307 slaughter Methods 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108700021402 PrP 27-30 Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 208000012936 Sheep disease Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000003703 cisterna magna Anatomy 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000009313 farming Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
-
- 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2828—Prion diseases
Definitions
- the present invention relates to methods for the detection of spongiform encephalopathies in animals, and in particular for the detection of bovine spongiform encephalopathy (BSE) in cattle.
- BSE bovine spongiform encephalopathy
- Spongiform encephalopathies are a group of diseases which include scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans.
- BSE is a notifiable fatal neurodegenerative disease found in cattle. BSE is of major importance to the British farming industry.
- Cases of BSE are identified by clinical manifestations in the animal. Cases are confirmed by post-mortem analysis of brain tissue, for instance by histopathology, by detection of scrapie associated fibrils or proteinase K resistant protein.
- the present invention has now provided a method for detecting spongiform encephalopathies in animals which addresses some, and in preferred forms all, of these problems.
- a method for detecting the presence of spongiform encephalopathy in an animal comprising determining the presence and/or amount of agent in a body fluid of the animal which cross-reacts with antibody raised against apoliprotein E, and relating the result of this determination to the infection status of the animal.
- the result of the determination is compared with a control value, and the relationship between the two is correlated with the infection status of the animal.
- the method is used to detect BSE.
- Apolipoprotein E is a cholesterol transporting protein produced in the peripheral and central nervous system. Its presence in either multiple- or single-forms has been categorised in cerebrospinal fluid (CSF) and serum.
- CSF cerebrospinal fluid
- agent or agents are cross reactive with anti-apolipoprotein E, have a molecular weight of around 34-38 kDa, and have a pi of around 5-4 - 5-7- This is consistent with their identification as apolipoprotein E, and the term 'Apo E agent' as used hereinafter is intended to embrace any agent which has these properties (including apolipoprotein E itself and isoforms or multiple-forms thereof).
- the control value may be derived from the Apo E agent concentration in a different animal (for which the infection status is known) and which is analysed in parallel with the test animal.
- the control value may come from the same animal, or be a known standard.
- the control value may be determined using the same method used for the test animal, or may be derived by a different analytical method.
- the results from the 'control' animal may be used to derive a standard positive- or negative-control value, or to calibrate the test animal result.
- the body fluid analysed in the method is CSF since authentic apolipoprotein E is the major apolipoprotein found in this fluid.
- the proximity of the CSF to brain means that neurological disorders which produce alterations in the protein composition of the brain may be manifested in the CSF.
- Methods for extracting samples of CSF are well known to those skilled in the art.
- the invention embraces any method for analysing the concentration of Apo E agent in a body fluid of an animal which is currently comprised in the art, and any methods which may later become available.
- the presence and/or amount of Apo E agent in a body fluid of the animal is derived by the use of PAGE or 2DPAGE to separate out the Apo E agent from other agents in the body fluid, and then staining the gel and making densitometry measurements in the region of the gel of interest in order to determine the presence and/or amount of the Apo E agent.
- the identity of the Apo E agent is confirmed by use of immunogenic material, for instance antibody raised against Apo E agent or a synthetic peptide based on a sequence thereof.
- immunogenic material for instance antibody raised against Apo E agent or a synthetic peptide based on a sequence thereof.
- Suitable immunogen-based techniques for identifying the presence of cross-reactive agents are well known to those skilled in the art eg. ELISA or Western Blotting.
- these immunogenic techniques may be used both to identify the Apo E agent, and also to estimate its concentration.
- the invention makes available methods for detecting the presence of spongiform encephalopathy in a test animal which address many, and in preferred forms all, of the problems of the prior art.
- the balance between test certainty and ease of use will be dependent on the precise method of Apo E agent analysis chosen for use in the methods of the current invention.
- the pre-mortem diagnosis of BSE in cattle opens up the possibility of mass-testing in herds, thereby reducing the likelihood of slaughtering uninfected animals or 'missing' infected ones.
- Sample preparation CSF samples were collected from BSE-positive cattle and BSE-negative cattle. In each case the diagnosis was confirmed by post-mortem histopathology and electron microscopy. CSF samples were taken by cisternamagna puncture after death and concentrated 10-15 fold. Volumes of CSF containing 40 ⁇ g total protein were mixed in a 4:1 ratio with denaturing solution (lg sodium dodecyl sulphate (SDS) and 0.232g dithiothreitol in 10ml water) and heated at 95°C for 5 minutes. Samples were then pulse centrifuged.
- denaturing solution lg sodium dodecyl sulphate (SDS) and 0.232g dithiothreitol in 10ml water
- Electrophoresis The prepared samples were 2D electrophoresed using a Millipore Investigator 2D electrophoresis system according to the method in the instruction manual. First dimensional iso-electric-focussing was carried out in 26 cm threaded glass tubes with 1 mm inner diameter in a pH gradient of 3 _ 10 for 18000 volt hours after pre-focussing the gels for 1 hour to 1500 V. Second dimension SDS-PAGE was carried out using 1 mm thick large format gels (23 cm x 23 cm) with 12 .5% acrylamide and no stacking gel. Staining and Image analysis: The 2D gels were silver stained according to the Millipore manual. Gels were scanned with an O ⁇ -nimedia scanner XRS and analysed using Bioimage software and Investigator Database programme (Millipore) using a sunSPARC station computer.
- Comparison of BSE-negative and BSE-positive cattle A comparison of the stained gels from typical BSE-positive and -negative samples is shown in Fig 1(a) and Fig 1(b). As can be seen the number and intensity of the silver stained spots in the region corresponding to agents having an approximate molecular weight of 34-38 kDa, and a pi of around 5.4 - 5-7 (labelled 'Apo E' ) is higher in the BSE-positive sample.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
Abstract
Ce procédé de détection de la présence d'une encéphalopathie spongiforme, chez un animal, comprend les étapes consistant à déterminer la présence et/ou la quantité d'un agent (par exemple par électrophorèse bidimensionnelle sur gel polyacrylamide, suivie d'une coloration et de lectures densitométriques de l'agent coloré), dans un fluide organique (par exemple le fluide cérébro-spinal) de l'animal examiné, lequel agent réagit de façon croisée avec l'anticorps dirigé contre l'apoliprotéine E et possède un poids moléculaire compris entre 34 et 38 kDa ainsi qu'un pI compris entre 5,4 et 5,7, puis à comparer la concentration avec une valeur témoin, et enfin à déduire du rapport entre ces deux valeurs la présence probable chez l'animal de l'encéphalopathie spongiforme.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95937124A EP0795132A1 (fr) | 1994-11-29 | 1995-11-28 | Procedes de detection de l'encephalopathie spongiforme |
| AU39328/95A AU3932895A (en) | 1994-11-29 | 1995-11-28 | Spongiform encephalopathy detection methods |
| GB9708663A GB2308659B (en) | 1994-11-29 | 1995-11-28 | Spongiform encephalopathy detection methods |
| SK678-97A SK67897A3 (en) | 1994-11-29 | 1995-11-28 | Spongiform encephalopathy detection methods |
| NZ295721A NZ295721A (en) | 1994-11-29 | 1995-11-28 | Detection of antibodies to spongiform encephalopathy |
| CZ971642A CZ164297A3 (en) | 1994-11-29 | 1995-11-28 | Method of detecting spongy-like encephalopathy |
| NO972339A NO972339D0 (no) | 1994-11-29 | 1997-05-22 | Fremgangsmåter for påvisning av spongiform encefalopati |
| FI972253A FI972253L (fi) | 1994-11-29 | 1997-05-28 | Sienimuotoisen aivosairauden defektiomenetelmät |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9424015.7 | 1994-11-29 | ||
| GB9424015A GB9424015D0 (en) | 1994-11-29 | 1994-11-29 | Spongiform encepmalopathy detection methods |
| GB9424769.9 | 1994-12-07 | ||
| GBGB9424769.9A GB9424769D0 (en) | 1994-11-29 | 1994-12-07 | Spongiform encephalopathy detection methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996017249A1 true WO1996017249A1 (fr) | 1996-06-06 |
Family
ID=26306057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1995/002766 WO1996017249A1 (fr) | 1994-11-29 | 1995-11-28 | Procedes de detection de l'encephalopathie spongiforme |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0795132A1 (fr) |
| AU (1) | AU3932895A (fr) |
| CA (1) | CA2205179A1 (fr) |
| CZ (1) | CZ164297A3 (fr) |
| FI (1) | FI972253L (fr) |
| GB (1) | GB2308659B (fr) |
| HU (1) | HUT77340A (fr) |
| NO (1) | NO972339D0 (fr) |
| NZ (1) | NZ295721A (fr) |
| SK (1) | SK67897A3 (fr) |
| WO (1) | WO1996017249A1 (fr) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998016834A1 (fr) | 1996-10-15 | 1998-04-23 | Imperial College Of Science, Technology And Medicine | Diagnostic de l'encephalopathie spongiforme |
| EP0854364A1 (fr) * | 1997-01-18 | 1998-07-22 | Harash Kumar Narang | Diagnostique de troubles neurodégénérescents |
| GB2333362A (en) * | 1996-10-15 | 1999-07-21 | Imperial College | Diagnosis of spongiform encephalopathy |
| WO1999040439A1 (fr) * | 1998-02-06 | 1999-08-12 | Harash Kumar Narang | Diagnostic de troubles neurodegeneratifs |
| FR2827047A1 (fr) * | 2001-07-03 | 2003-01-10 | Apoh Technollgies Sa | Procede de separation et/ou detection et/ou identification et/ou quantification de proteines prions |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4892814A (en) * | 1987-06-22 | 1990-01-09 | The United States Of America As Represented By The Department Of Health And Human Services | Method for distinguishing Creutzfeldt-Jakob disease from other dementias |
-
1995
- 1995-11-28 EP EP95937124A patent/EP0795132A1/fr not_active Withdrawn
- 1995-11-28 GB GB9708663A patent/GB2308659B/en not_active Expired - Fee Related
- 1995-11-28 HU HU9702327A patent/HUT77340A/hu unknown
- 1995-11-28 SK SK678-97A patent/SK67897A3/sk unknown
- 1995-11-28 AU AU39328/95A patent/AU3932895A/en not_active Abandoned
- 1995-11-28 NZ NZ295721A patent/NZ295721A/xx unknown
- 1995-11-28 WO PCT/GB1995/002766 patent/WO1996017249A1/fr not_active Application Discontinuation
- 1995-11-28 CA CA002205179A patent/CA2205179A1/fr not_active Abandoned
- 1995-11-28 CZ CZ971642A patent/CZ164297A3/cs unknown
-
1997
- 1997-05-22 NO NO972339A patent/NO972339D0/no unknown
- 1997-05-28 FI FI972253A patent/FI972253L/fi unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4892814A (en) * | 1987-06-22 | 1990-01-09 | The United States Of America As Represented By The Department Of Health And Human Services | Method for distinguishing Creutzfeldt-Jakob disease from other dementias |
Non-Patent Citations (5)
| Title |
|---|
| CHEMICAL ABSTRACTS, vol. 120, no. 25, 20 June 1994, Columbus, Ohio, US; abstract no. 320660v, page 634; column 2; * |
| J.F. DIEDRICH ET AL.: "Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of Apolipoprotein E and cathepsin in astrocytes.", JOURNAL OF VIROLOGY, vol. 65, no. 9, 1 September 1991 (1991-09-01), WASHINGTON DC USA, pages 4759 - 4768, XP000567293 * |
| M.G. HARRINGTON ET AL.: "Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jacob disease.", NEW ENGLAND JOURNAL OF MEDICINE, vol. 315, no. 2, 31 July 1986 (1986-07-31), BOSTON MA USA, pages 279 - 283, XP000567332 * |
| See also references of EP0795132A1 * |
| Y. NAMBA: "Immunochemical demonstration of apolipoprotein E in cerebral amyloid deposits in Alzheimer's disease and kuru plaque amyloids in Creutzfeldt-Jacob disease.", SHINKEI KENKYU NO SHINPO, vol. 37, no. 6, TOKYO, pages 1039 - 1051 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998016834A1 (fr) | 1996-10-15 | 1998-04-23 | Imperial College Of Science, Technology And Medicine | Diagnostic de l'encephalopathie spongiforme |
| GB2333362A (en) * | 1996-10-15 | 1999-07-21 | Imperial College | Diagnosis of spongiform encephalopathy |
| GB2333362B (en) * | 1996-10-15 | 2001-05-16 | Imperial College | Typing and diagnosis of spongiform encephalopathy |
| US6998231B2 (en) | 1996-10-15 | 2006-02-14 | D-Gen Limited | Typing and diagnosis of spongiform encephalopathy |
| EP0854364A1 (fr) * | 1997-01-18 | 1998-07-22 | Harash Kumar Narang | Diagnostique de troubles neurodégénérescents |
| WO1999040439A1 (fr) * | 1998-02-06 | 1999-08-12 | Harash Kumar Narang | Diagnostic de troubles neurodegeneratifs |
| FR2827047A1 (fr) * | 2001-07-03 | 2003-01-10 | Apoh Technollgies Sa | Procede de separation et/ou detection et/ou identification et/ou quantification de proteines prions |
| WO2003005037A1 (fr) * | 2001-07-03 | 2003-01-16 | Apoh Technologies Sa | Procede de separation et/ou detection et/ou identification et/ou quantification de proteines prions |
Also Published As
| Publication number | Publication date |
|---|---|
| AU3932895A (en) | 1996-06-19 |
| EP0795132A1 (fr) | 1997-09-17 |
| CZ164297A3 (en) | 1997-11-12 |
| GB2308659B (en) | 1998-11-18 |
| NO972339L (no) | 1997-05-22 |
| HUT77340A (hu) | 1998-03-30 |
| CA2205179A1 (fr) | 1996-06-06 |
| SK67897A3 (en) | 2000-02-14 |
| NO972339D0 (no) | 1997-05-22 |
| FI972253A0 (fi) | 1997-05-28 |
| FI972253L (fi) | 1997-07-28 |
| GB2308659A (en) | 1997-07-02 |
| NZ295721A (en) | 1999-03-29 |
| GB9708663D0 (en) | 1997-06-18 |
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