CA2205228A1 - Spongiform encephalopathy detection methods - Google Patents
Spongiform encephalopathy detection methodsInfo
- Publication number
- CA2205228A1 CA2205228A1 CA002205228A CA2205228A CA2205228A1 CA 2205228 A1 CA2205228 A1 CA 2205228A1 CA 002205228 A CA002205228 A CA 002205228A CA 2205228 A CA2205228 A CA 2205228A CA 2205228 A1 CA2205228 A1 CA 2205228A1
- Authority
- CA
- Canada
- Prior art keywords
- animal
- agent
- spongiform encephalopathy
- infection status
- body fluid
- 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.)
- Abandoned
Links
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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
A method for detecting the presence of a spongiform encephalopathy (e.g. Bovine Spongiform Encephalopathy) in an animal comprising determining the presence and/or amount of agent (e.g. by 2D-polyacrylamide gel electrophoresis and staining) in a body fluid (e.g. cerebrospinal fluid) of the animal which has a molecular weight of between 35-39 kDa, and a pI of 5.3 and which does not cross-react with antibody raised against apoliprotein E and relating the result of this determination to a control value (e.g. from a known uninfected animal) so as to be able to detect the likely presence of spongiform encephalopathy in the animal.
Description
-CA 0220~228 1997-0~-13 W O96/172S0 ~CT/GB95/02767 ~d~Gl~O.~1 ENCEPHALOPATHY D~ LlON METHODS
The present invention relates to methods for the detection of spongiform encephalopathies in An;~ls, and in particular to the detection of bovine spongiform encephalopathy (BSE) in cattle.
Spongiform encephalopathies are a class of diseases which inC~ P
scrapie in sheep and Creutzfeldt-Jakob disease in humans. BSE is a notifiable fatal neurodegenerative disease found in cattle. BSE is of major importance to the British farming industry.
Currently 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.
These methods have the disadvantage that they necessitate the slaughter of potentially-infected Ani ~l s which may turn out to be disease-free. Alternatively, clinical signs may be absent or go undetected, thus leaving infected Ani ~1~ in the herd.
Thus there exists a need for a pre-mortem test for BSE which can be used when diagnosing potentially-infected ~n; ~
The present invention has now provided a method for detecting spongiform encephalopathy in an animal which addresses some, and in preferred forms all, of these problems.
According to one aspect of the present invention there is provided a method for detecting the presence of a spongiform PncephAlopathy in an animal comprising determining the presence and/or amount of agent -~, in a body fluid of the animal which has a molecular weight of between 35-39 kDa, a pI of approximately 5.3, and which does not cross-react with antibody raised against apoliprotein E and relating the result of this determination to the infection status of the animal.
Preferably the result of the determination is compared with a control CA 0220~228 lss7-0~-l3 value and the relationship between the two is correlated with the infection status of the animal.
.., Preferably the method is used to detect BSE.
Thus the discovery that the spongiform ~ncephAlopathy infection in an animal may be correlated with the presence of, or an increase in the concentration of, an agent or agents in the body fluids of that animal forms the basis for the methods of the current invention.
Apolipoprotein E is 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. Its molecular weight (37 kDa) and pI (around 5.4 to 5.7) are similar to those of the agent described above. However the agent which is determined in the methods of the present invention does not cross-react with anti-apolipoprotein E antibody.
It should be noted that there is no requirement to accurately determine the agent concentration because the spongiform encephalopathy infection status of the animal may be detected by comparison with a control.
The control value may be derived from the agent concentration in a different animal (for which the infection status is known) and which is analysed in parallel with the test animal. Alternatively, the control value may come from the same animal, or be a known standard.
In either case the control value may be determined using the same method used for the test animal or using a different analytical method.
The results from the 'control' animal may be used to derive a standard control value, or to calibrate the test animal result.
Preferably the body fluid analysed in the method is CSF since the proximity of the CSF to brain means that neurological disorders which CA 0220~228 1997-0~-13 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 Sk; 11 ed in the art.
t The invention embraces any method for determining the presence and/or amount of agent in a body fluid of an animal which is currently comprised in the art, and any methods which may later become available.
Preferably the presence and/or amount of agent in a body fluid of the animal is derived by the use of polyacrylamide gel electrophoresis (PAGE) to separate out the agents having both a molecular weight of between 35-39 kDa and a pI of approximately 5.3 from other materials in the body fluid, and then st~;ning the gel and making densitometry measurements in the region of the gel cont~in;ng the agent so as to determine the presence and/or amount of the agent present.
Preferably the PAGE is two ~; ?n~;onal polyacrylamide gel electrophoresis (2DPAGE) and the stain is silver stain.
Preferably the lack of cross reactivity between the agent and anti-apolipoprotein E antibody agent is confirmed by the use of antibody raised against apolipoprotein E. Immunogen-based techniques for measuring cross-reactivity are well known to those sk;lled in the art eg. ELISA or Western Blotting.
In alternative embodiments of the invention, these immunogenic techniques may be used both to identify the agent and to estimate its concentration. This can be achieved by raising antibodies against the agent, or a synthetic peptide derived from the sequence thereof.
t Thus 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 agent analysis chosen for use in the methods of the current invention. However, the pre-mortem diagnosis of BSE in CA 0220~228 lgg7-0~-l3 W 096tl72SO PCT/GB9~102767 cattle opens up the possibility of mass-testing in herds, thereby re~uc~ng the likelih~od of slaughtering uninfected An;rol.~ or t mi .CS; ng' infected ones.
The methods of the present invention will now be described, by way of illustration only, through reference to the following example and figures. Other embodiments falling within the scope of the invention will occur to those skilled in the art in the light of this.
EXAMPLE - IDENTIFICATION OF BSE IN CATTLE
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 cisternAm~gnfl puncture after death and concentrated 10-15 fold. Volumes of CSF contAining 40 ug total protein were mixed in a 4:1 ratio with denaturing solution (lg sodium dodecyl sulphate (SDS) and 0.232g dithiothreitol in lOml water) and heated at 95C for 5 minutes. Samples were then pulse centrifuged.
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 stArking gel.
StAining and Image analysis: The 2D gels were silver stained according to the Millipore manual. Gels were scanned with an Omnime~ia scanner XRS and analysed using Bioimage software and Investigator Database programme (Millipore) using a sunSPARC station computer.
Confirmation of the identity of the agent: The 2D gels were electroblotted onto Immobilon-P membranes overnight at 30V using a CA 0220~228 1997-0~-13 W 096/172S0 P~l/~b5'/~2767 Bio-Rad Trans-Blot cell. The blots were blocked using Tween 80 for l hour and then incubated for 90 minutes with sheep antiserum contAin;ng polyclonal antibody raised against Aroliroprotein E.
Bound sheep antibodies were detected using rabbit anti-sheep IgG and a horseradish peroxidase detection system.
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 l(a) and Fig l(b). As can be seen the number and intensity of the silver stained spots in the region correspnn~inE 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. Those spots in the region labelled 'Apo E' were found to cross react with anti-apolipoprotein E antibody. However, the 2-3 spots, molecular weight 35-39 kDa and pI 5.3 (arrowed in each gel), correspon~;nE to one or more agents which did not cross react with this antibody, are undetectable in the BSE-negative sample but are present in clearly detectable amounts in the BSE-positive sample Using a number of samples of body fluid from different cattle samples it was found that the agent was consistently present in detectable amounts in BSE-positive Anim~l~ but was undetectable in BSE-negative An; ~1~, thus indicating that the presence and/or amount of this agent may be used to detect the likely presence of BSE in potentially infected An; m~
~ . ~
The present invention relates to methods for the detection of spongiform encephalopathies in An;~ls, and in particular to the detection of bovine spongiform encephalopathy (BSE) in cattle.
Spongiform encephalopathies are a class of diseases which inC~ P
scrapie in sheep and Creutzfeldt-Jakob disease in humans. BSE is a notifiable fatal neurodegenerative disease found in cattle. BSE is of major importance to the British farming industry.
Currently 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.
These methods have the disadvantage that they necessitate the slaughter of potentially-infected Ani ~l s which may turn out to be disease-free. Alternatively, clinical signs may be absent or go undetected, thus leaving infected Ani ~1~ in the herd.
Thus there exists a need for a pre-mortem test for BSE which can be used when diagnosing potentially-infected ~n; ~
The present invention has now provided a method for detecting spongiform encephalopathy in an animal which addresses some, and in preferred forms all, of these problems.
According to one aspect of the present invention there is provided a method for detecting the presence of a spongiform PncephAlopathy in an animal comprising determining the presence and/or amount of agent -~, in a body fluid of the animal which has a molecular weight of between 35-39 kDa, a pI of approximately 5.3, and which does not cross-react with antibody raised against apoliprotein E and relating the result of this determination to the infection status of the animal.
Preferably the result of the determination is compared with a control CA 0220~228 lss7-0~-l3 value and the relationship between the two is correlated with the infection status of the animal.
.., Preferably the method is used to detect BSE.
Thus the discovery that the spongiform ~ncephAlopathy infection in an animal may be correlated with the presence of, or an increase in the concentration of, an agent or agents in the body fluids of that animal forms the basis for the methods of the current invention.
Apolipoprotein E is 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. Its molecular weight (37 kDa) and pI (around 5.4 to 5.7) are similar to those of the agent described above. However the agent which is determined in the methods of the present invention does not cross-react with anti-apolipoprotein E antibody.
It should be noted that there is no requirement to accurately determine the agent concentration because the spongiform encephalopathy infection status of the animal may be detected by comparison with a control.
The control value may be derived from the agent concentration in a different animal (for which the infection status is known) and which is analysed in parallel with the test animal. Alternatively, the control value may come from the same animal, or be a known standard.
In either case the control value may be determined using the same method used for the test animal or using a different analytical method.
The results from the 'control' animal may be used to derive a standard control value, or to calibrate the test animal result.
Preferably the body fluid analysed in the method is CSF since the proximity of the CSF to brain means that neurological disorders which CA 0220~228 1997-0~-13 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 Sk; 11 ed in the art.
t The invention embraces any method for determining the presence and/or amount of agent in a body fluid of an animal which is currently comprised in the art, and any methods which may later become available.
Preferably the presence and/or amount of agent in a body fluid of the animal is derived by the use of polyacrylamide gel electrophoresis (PAGE) to separate out the agents having both a molecular weight of between 35-39 kDa and a pI of approximately 5.3 from other materials in the body fluid, and then st~;ning the gel and making densitometry measurements in the region of the gel cont~in;ng the agent so as to determine the presence and/or amount of the agent present.
Preferably the PAGE is two ~; ?n~;onal polyacrylamide gel electrophoresis (2DPAGE) and the stain is silver stain.
Preferably the lack of cross reactivity between the agent and anti-apolipoprotein E antibody agent is confirmed by the use of antibody raised against apolipoprotein E. Immunogen-based techniques for measuring cross-reactivity are well known to those sk;lled in the art eg. ELISA or Western Blotting.
In alternative embodiments of the invention, these immunogenic techniques may be used both to identify the agent and to estimate its concentration. This can be achieved by raising antibodies against the agent, or a synthetic peptide derived from the sequence thereof.
t Thus 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 agent analysis chosen for use in the methods of the current invention. However, the pre-mortem diagnosis of BSE in CA 0220~228 lgg7-0~-l3 W 096tl72SO PCT/GB9~102767 cattle opens up the possibility of mass-testing in herds, thereby re~uc~ng the likelih~od of slaughtering uninfected An;rol.~ or t mi .CS; ng' infected ones.
The methods of the present invention will now be described, by way of illustration only, through reference to the following example and figures. Other embodiments falling within the scope of the invention will occur to those skilled in the art in the light of this.
EXAMPLE - IDENTIFICATION OF BSE IN CATTLE
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 cisternAm~gnfl puncture after death and concentrated 10-15 fold. Volumes of CSF contAining 40 ug total protein were mixed in a 4:1 ratio with denaturing solution (lg sodium dodecyl sulphate (SDS) and 0.232g dithiothreitol in lOml water) and heated at 95C for 5 minutes. Samples were then pulse centrifuged.
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 stArking gel.
StAining and Image analysis: The 2D gels were silver stained according to the Millipore manual. Gels were scanned with an Omnime~ia scanner XRS and analysed using Bioimage software and Investigator Database programme (Millipore) using a sunSPARC station computer.
Confirmation of the identity of the agent: The 2D gels were electroblotted onto Immobilon-P membranes overnight at 30V using a CA 0220~228 1997-0~-13 W 096/172S0 P~l/~b5'/~2767 Bio-Rad Trans-Blot cell. The blots were blocked using Tween 80 for l hour and then incubated for 90 minutes with sheep antiserum contAin;ng polyclonal antibody raised against Aroliroprotein E.
Bound sheep antibodies were detected using rabbit anti-sheep IgG and a horseradish peroxidase detection system.
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 l(a) and Fig l(b). As can be seen the number and intensity of the silver stained spots in the region correspnn~inE 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. Those spots in the region labelled 'Apo E' were found to cross react with anti-apolipoprotein E antibody. However, the 2-3 spots, molecular weight 35-39 kDa and pI 5.3 (arrowed in each gel), correspon~;nE to one or more agents which did not cross react with this antibody, are undetectable in the BSE-negative sample but are present in clearly detectable amounts in the BSE-positive sample Using a number of samples of body fluid from different cattle samples it was found that the agent was consistently present in detectable amounts in BSE-positive Anim~l~ but was undetectable in BSE-negative An; ~1~, thus indicating that the presence and/or amount of this agent may be used to detect the likely presence of BSE in potentially infected An; m~
~ . ~
Claims (14)
1. A method for determining the spongiform encephalopathy infection status of an animal comprising determining the presence and/or amount of agent in a body fluid of the animal which:
(a) is obtainable from the cerebrospinal fluid of an animal with a positive infection status, (b) has a molecular weight of between 35 and 39 kDa, (c) has a pI of approximately 5.3, (d) does not cross-react with antibody raised against apolipoprotein E, and relating the result of this determination to the infection status of the animal.
(a) is obtainable from the cerebrospinal fluid of an animal with a positive infection status, (b) has a molecular weight of between 35 and 39 kDa, (c) has a pI of approximately 5.3, (d) does not cross-react with antibody raised against apolipoprotein E, and relating the result of this determination to the infection status of the animal.
2. A method as claimed in claim 1 wherein 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.
3. A method as claimed in claim 1 or claim 2 wherein the spongiform encephalopathy is bovine spongiform encephalopathy.
4. A method as claimed in any one of the preceding claims wherein the body fluid analysed in the method is cerebrospinal fluid.
5. A method as claimed in any one of the preceding claims wherein the presence and/or amount of agent in a body fluid of the animal is derived by the use polyacrylamide gel electrophoresis (PAGE) to separate out the agents having both a molecular weight of between 35 and 39 kDa and a pI of 5.3 from other materials in the body fluid, and then staining the gel and making densitometry measurements in the region of the gel containing the agent so as to determine the presence and/or amount of the agent present.
6. A method as claimed in claim 5 wherein the PAGE is two dimensional polyacrylamide gel electrophoresis.
7. A method as claimed in claim 5 or claim 6 wherein the stain is silver stain.
8. A method as claimed in any preceding claim wherein the lack of cross reactivity between the agent and anti-apolipoprotein E
antibody is confirmed by the use of antibody raised against apolipoprotein E.
antibody is confirmed by the use of antibody raised against apolipoprotein E.
9. A method as claimed in any of claims 1 to 4 wherein antibodies are raised against the agent, or a synthetic peptide derived generated from the sequence thereof, and the presence and/or amount of agent in a body fluid of the animal is determined by use of these antibodies.
10. A method as claimed in any one of claims 2 to 9 wherein the control value is derived by the same method as that used with the animal but using a further animal for which the infection status is known.
11. A method for detecting the presence of spongiform encephalopathy in an animal substantially as described hereinbefore with reference to the Example.
12. An agent which:
(a) is obtainable from the cerebrospinal fluid of an animal with a positive spongiform encephalopathy infection status, (b) has a molecular weight of between 35 and 39 kDa, (c) has a pI of approximately 5.3, and (d) does not cross-react with antibody raised against apolipoprotein E.
(a) is obtainable from the cerebrospinal fluid of an animal with a positive spongiform encephalopathy infection status, (b) has a molecular weight of between 35 and 39 kDa, (c) has a pI of approximately 5.3, and (d) does not cross-react with antibody raised against apolipoprotein E.
13. An agent as claimed in claim 12 for use in a method of determining the spongiform encephalopathy infection status of an animal.
14. An antibody raised against the agent of claim 12, or a synthetic peptide derived generated from the sequence thereof.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9424068.6 | 1994-11-29 | ||
| GB9424068A GB9424068D0 (en) | 1994-11-29 | 1994-11-29 | Spongiform encephalopathy detection methods |
| GBGB9424768.1A GB9424768D0 (en) | 1994-11-29 | 1994-12-07 | Spongiform encephalopathy detection methods |
| GB9424768.1 | 1994-12-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2205228A1 true CA2205228A1 (en) | 1996-06-06 |
Family
ID=26306060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002205228A Abandoned CA2205228A1 (en) | 1994-11-29 | 1995-11-28 | Spongiform encephalopathy detection methods |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0795133A1 (en) |
| AU (1) | AU3932995A (en) |
| CA (1) | CA2205228A1 (en) |
| CZ (1) | CZ164197A3 (en) |
| FI (1) | FI972254A (en) |
| GB (1) | GB2308658B (en) |
| HU (1) | HUT77339A (en) |
| NO (1) | NO972340L (en) |
| NZ (1) | NZ295722A (en) |
| SK (1) | SK67797A3 (en) |
| WO (1) | WO1996017250A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2319607A (en) * | 1996-11-23 | 1998-05-27 | Electrophoretics International | Detection of prion proteins in mononuclear cells |
| GB9701045D0 (en) * | 1997-01-18 | 1997-03-05 | Narang Harash K | Diagnosis of neuro-degenerative disorders |
| CA2286279C (en) * | 1998-02-06 | 2009-05-12 | Harash Kumar Narang | Diagnosis of neuro-degenerative disorders |
Family Cites Families (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 GB GB9708654A patent/GB2308658B/en not_active Expired - Fee Related
- 1995-11-28 CZ CZ971641A patent/CZ164197A3/en unknown
- 1995-11-28 EP EP95937125A patent/EP0795133A1/en not_active Withdrawn
- 1995-11-28 HU HU9702330A patent/HUT77339A/en unknown
- 1995-11-28 AU AU39329/95A patent/AU3932995A/en not_active Abandoned
- 1995-11-28 WO PCT/GB1995/002767 patent/WO1996017250A1/en not_active Application Discontinuation
- 1995-11-28 CA CA002205228A patent/CA2205228A1/en not_active Abandoned
- 1995-11-28 SK SK677-97A patent/SK67797A3/en unknown
- 1995-11-28 NZ NZ295722A patent/NZ295722A/en unknown
-
1997
- 1997-05-22 NO NO972340A patent/NO972340L/en unknown
- 1997-05-28 FI FI972254A patent/FI972254A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO972340D0 (en) | 1997-05-22 |
| FI972254A0 (en) | 1997-05-28 |
| CZ164197A3 (en) | 1997-11-12 |
| GB2308658A (en) | 1997-07-02 |
| NO972340L (en) | 1997-05-22 |
| WO1996017250A1 (en) | 1996-06-06 |
| HUT77339A (en) | 1998-03-30 |
| AU3932995A (en) | 1996-06-19 |
| FI972254A (en) | 1997-07-28 |
| NZ295722A (en) | 1999-03-29 |
| SK67797A3 (en) | 2000-02-14 |
| GB2308658B (en) | 1998-11-18 |
| EP0795133A1 (en) | 1997-09-17 |
| GB9708654D0 (en) | 1997-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| de Graaff et al. | Identification of delta/notch‐like epidermal growth factor‐related receptor as the Tr antigen in paraneoplastic cerebellar degeneration | |
| US11933792B2 (en) | Markers for renal disease | |
| US20050176078A1 (en) | Detection and/or monitoring of synuclein-related diseases | |
| EA004953B1 (en) | Method for detecting and separating abnormal prion protein and kit therefor | |
| Nonno et al. | Molecular analysis of cases of Italian sheep scrapie and comparison with cases of bovine spongiform encephalopathy (BSE) and experimental BSE in sheep | |
| US4892814A (en) | Method for distinguishing Creutzfeldt-Jakob disease from other dementias | |
| US20230221337A1 (en) | Method for testing aggravation risk of person infected with novel coronavirus, test kit therefor, companion diagnostic drug and aggravation risk marker thereof | |
| CA2205228A1 (en) | Spongiform encephalopathy detection methods | |
| CA2205179A1 (en) | Spongiform encephalopathy detection methods | |
| AU2013285362B2 (en) | Tropomyosin isoforms related to Alzheimers disease and Mild Cognitive Impairment | |
| Narang et al. | Sensitive detection of prion protein in human urine | |
| Russell et al. | Fibrinogen heterogeneity in horses | |
| US20030044868A1 (en) | Method for detecting prion proteins in tissue samples | |
| US20040175775A1 (en) | Method of detecting PrPsc in eye fluid | |
| AU2017204520B2 (en) | Markers for renal disease | |
| Gaunitz et al. | Suitability of antigens PGP 9.5 and Neurofilament light as marker proteins for detection of neuronal tissue in processed meat products | |
| Koyama et al. | Novel method for classification of prion diseases by detecting PrPres signal patterns from formalin-fixed paraffin-embedded samples | |
| WO2009145478A2 (en) | Kit for the diagnosis of glaucoma | |
| WO2018094221A1 (en) | Assessing and treating fibrillary glomerulonephritis | |
| Mousseau et al. | Western blot analysis | |
| BG64291B1 (en) | Method and kit for extracting prion protein | |
| Khalil et al. | SERUM SECRETOGRANIN III AS A MARKER FOR CLINICAL SUBTYPING IN MULTIPLE SCLEROSIS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |