Research
The identification of disease-induced biomarkers in the urine of BSE infected cattle
Sharon LR Simon , Lise Lamoureux , Margot Plews , Micheal Stobart , Jillian LeMaistre , Ute Ziegler , Catherine Graham , Stefanie Czub , Martin Groschup and J. David Knox
Proteome Science 2008, 6:23doi:10.1186/1477-5956-6-23
Published: 5 September 2008
Abstract (provisional)
Background
The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrPd, in brain tissue and consequently are only suitable for post-mortem diagnosis.
Objectives:
In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements.
Results
Two dimensional differential gel eletrophoresis (2D-DIGE) and mass spectrometry analyses were used to identify proteins exhibiting differential abundance in the urine of BSE infected cattle and age matched controls over the course of the disease. Multivariate analyses of protein expression data identified a single protein able to discriminate, with 100% accuracy, control from infected samples. In addition, a subset of proteins were able to predict with 85% +/- 13.2 accuracy the time post infection that the samples were collected.
Conclusions These results suggest that in principle it is possible to identify biomarkers in urine useful in the diagnosis, prognosis and monitoring of disease progression of transmissible spongiform encephalopathy diseases (TSEs).
http://www.proteomesci.com/content/6/1/23/abstract
BUT, will the USDA et al let any test be used to detect BSE or any TSE in the USA bovine ???
i doubt it $$$
Sunday, September 07, 2008 CWD LIVE TEST, and the political aspects or fallout of live testing for BSE in cattle in the USA http://chronic-wasting-disease.blogspot.com/2008/09/cwd-live-test-and-political-aspects-or.html
Friday, August 29, 2008
CREEKSTONE VS USDA COURT OF APPEALS, BUSH SAYS, NO WAY, NO HOW
http://madcowtesting.blogspot.com/2008/08/creekstone-vs-usda-court-of-appeals.html
1996 NARANG URINE TEST
http://www.bseinquiry.gov.uk/files/yb/1996/02/09003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1996/02/21004001.pdf
http://www.bseinquiry.gov.uk/files/yb/1996/02/21005001.pdf
http://www.bseinquiry.gov.uk/files/ws/s113.pdf
http://www.bseinquiry.gov.uk/report/volume11/chaptec3.htm
5.289 We have concluded, for the reasons given above, that Dr Narang's work received fair consideration by MAFF scientists. While we would pay tribute to Dr Narang's dedication to research into TSEs, we feel that he had a fair opportunity to demonstrate the validity of his work but did not succeed in doing so.
http://www.bseinquiry.gov.uk/report/volume11/chaptec4.htm
No way to treat a pioneer Apr 20 2003 By Phil Doherty
A leading charity has called for a public inquiry into the way a top mad cow disease expert has been treated by the establishment. Harash Narang was the first scientist to make the link between the illness and its human equivalent- variant Creutzfeldt-Jakob disease - in 1990. Dr Narang says he was made redundant from his job at Newcastle's Public Health Laboratory Services after making his findings known. He claims that he lost his post after the then Health Minister Stephen Dorrell ordered all the lab's work on the killer disease to cease. Since he became a whistle-blower, he says, he has not been able to get lab time in the UK to continue his work.
Dr Narang has since moved to the United States. He is now working at the CJD surveillance unit based at Case Western Reserve University in Cleveland, Ohio.
CJD Foundation head Noel Baldwin, who lost his son Patrick to the killer disease, said: "There is more and more information coming out that proves Dr Narang was right all along.
Medical
"He said years ago that CJD could be found in blood and passed on by transfusions and medical instruments. This has now been accepted.
"He argued that BSE could cause both sporadic as well as vCJD, and recent research has shown this to be correct. He also invented a urine test which shows if someone is harbouring the disease."
Mr Baldwin also rued the Government's decision to pull Medical Research Council funding from Dr Narang.
He said: "Now it looks as if the US will benefit financially from this ground-breaking research. "The UK establishment has ignored him for more than 10 years. We believe those responsible should be made accountable for this because if they had listened to Dr Narang maybe some of those poor people wouldn't have died from this terrible disease.
Scandal
"This is a national scandal that needs to be fully addressed by a public inquiry. "We are planning to launch this campaign in the next few months and will be involving sympathetic MPs to get this issue aired in the House of Commons."
http://icnewcastle.icnetwork.co.uk/0100news/0100local/page.cfm?objectid=12871105&method=full&siteid=50081&headline=No%20way%20to%20treat%20a%20pioneer
2005 NARANG URINE TEST USA CWRU
CJD doc jets off
Mar 9 2003
By Phil Doherty, Sunday Sun
The North scientist who first established a link between mad cow disease and its human form is quitting Britain.
Harash Narang has been head-hunted by a top US university to continue his research into variant Creutzfeldt-Jakob disease.
He was working for the Government's Public Health Laboratory Service in Newcastle when he revealed the link and later lost his job.
Dr Narang claimed he was made redundant because he went public with his findings, an allegation which has always been denied. He said: "I now have a job at the United States CJD Surveillance Centre based in Case Western Reserve University, Cleveland, Ohio.
"I'm very excited because it has excellent facilities and is one of the best CJD surveillance centres in the world.
The university is examining a urine test pioneered by Dr Narang which can show whether someone has CJD.
Currently only a post-mortem diagnosis can be made.
Dr Narang said: "Early indications show that my test has performed even better than anticipated. It is expected to be validated very shortly."
And he revealed: "I do not regret telling the truth all those years ago. If I had to do it again then I would."
Ken Bell, a financial backer of Dr Narang's work, claimed he had been forced to go abroad because he cannot get laboratory time in the UK.
He said: "Harash has been blackballed in the UK because he told the public the truth. "The establishment will try anything to stop him working here. It's a disgrace."
Noel Baldwin, of the CJD Foundation charity, said: "He has been proved right about so many things . . . that CJD can be transmitted through blood, that BSE can cause both variant and sporadic CJD and that you can test for the disease through urine samples."
Dr Narang starts work at Case University later this month. Shu Chen, one of his future colleagues, said: "He will be a great asset to our CJD research."
http://icnewcastle.icnetwork.co.uk/0100news/0100local/page.cfm?objectid=12716797&method=full&siteid=50081
Edmonton company boasts cheap BSE test Duncan Thorne , CanWest News Service; Edmonton Journal Published: Friday, July 21, 2006 EDMONTON -- An Edmonton company is confident it has a cheap, ground-breaking test for mad cow disease, but the test's British inventor who claims to have first made the link between BSE and the disease's human form insists he still holds the rights.
Despite their differences, inventor Harash Narang and BSE Prion Solutions Inc. agree the test holds amazing potential to quickly and inexpensively test live cattle for bovine spongiform encephalopathy better known as mad-cow disease. The only approved tests so far for mad cow and its human equivalent depend on removing brain samples after death. A test on live animals would open the way to guaranteeing disease-free herds.
"We have a test that not only works, but works each and every time," said Ron Arnold of BSE Prion Solutions Inc., adding formal validation may take up to two years and regulatory approval. Narang, a former British government scientist who went public about human risks from BSE in 1990, started developing tests for detecting the disease in the late 1980s while at a public health laboratory. He had been studying cases of a fatal but rare human brain illness, Creutzfeldt-Jakob disease (CJD), when he started noticing some cases were different. He has said he was well on the way to establishing a link between BSE and the unusual CJD cases when he was ordered to stop his research. He has also claimed officials rejected his calls for increased testing for BSE and the new form of CJD, now known as variant CJD.
Narang developed three diagnostic tests, including an early version of the urine test that BSE Prion intends to bring to market.
A wide-ranging 1998 inquiry into Britain's response to the mad cow crisis found problems with Narang's claims. It cited evidence that fellow scientists could not get his test to work. Even so, Narang continued development of the urine test. A British company, Biotec Global, sponsored much of his work. He is no longer part of the research, but work on it continues at the United States National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland. Narang and Case Western researchers reported in 2005 that the urine test could reliably detect a harmless form of the prion protein that is blamed for BSE and variant CJD. It could also detect the bad form if the prion was first added directly to the urine.
They said their findings "may lay the foundation for a future technique," if in fact the bad prion can turn up naturally in urine.
"It needs a lot of work still," Ayuna Dagdanova, one of the test's researchers at the U.S. prion surveillance centre, said from Cleveland.
Without solid data it's not possible to say if they are close to detecting BSE in urine, she said. "No one actually knows, but preliminary experiments show the possibility."
Arnold, a partner in Biotec, said Narang gave Biotec the patent rights in 2003 and it in turn gave BSE Prion the licence for the Americas and Europe.
"We've talked with patent attorneys in London and also in Newcastle. Everyone agrees that the documents and the transfer of ownership of the patents was done judiciously and was extremely well put together by the solicitors," said Arnold.
Edmonton company boasts cheap BSE test Duncan Thorne , CanWest News Service; Edmonton Journal Published: Friday, July 21, 2006 Narang, speaking from Newcastle, acknowledged signing papers, but said it was not clear what he was signing. He said he continues to pay the patent renewal fees.
Biotec has sunk more than $2 million into the research, but BSE Prion has not had to pay a licence fee, Arnold said. That's because the project is humanitarian, with plans to hand over any earnings for research purposes, in the form of grants and scholarships.
Narang, who holds shares in Biotec despite the ownership dispute, also said he also wants any profits to go into further research. Meanwhile, he said he's owed back pay and expenses for work he did over the past five years a claim Arnold rejects.
[email protected]
Edmonton Journal © CanWest News Service 2006
http://www.canada.com/topics/news/national/story.html?id=e0300291-19dd-48a8-8e88-963a06087ce2&k=6995
http://www.canada.com/topics/news/national/story.html?id=e0300291-19dd-48a8-8e88-963a06087ce2&k=6995&p=2
Experimental Biology and Medicine 230:343-349 (2005) © 2005 Society for Experimental Biology and Medicine
----------------------------------------------------------
ORIGINAL RESEARCH ARTICLE
Sensitive Detection of Prion Protein in Human Urine
Harash K. Narang*,2, Ayuna Dagdanova, Zhiliang Xie, Qiwei Yang and Shu G. Chen,1 * BioTech Global, 22-40 Brentwood Avenue, Newcastle Upon Tyne, NE2 3DH, UK; and Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106 1To whom requests for reprints should be addressed at Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106. E-mail: [email protected].
ABSTRACT
Transmissible spongiform encephalopathies are a group of infectious diseases typically associated with the accumulation of a protease-resistant and ß-sheet-rich prion protein, PrPSc, in affected brains. PrPSc is an altered isoform derived from the host-encoded glycoprotein, PrPC. The expression of PrPC is the highest in brain tissue, but it can also be detected at low levels in peripheral tissue. However, it is unclear whether a significant amount of PrPC is released into body fluid and excreted into urine. We have developed a simple, rapid method for the reliable detection of PrPC in urine from normal subjects by Western blotting. Our method can easily and reliably detect PrPC in apparently healthy individuals using less than 1 ml of urine in which the amount of urinary PrPC is estimated to be in the range of low micrograms/liter.
http://www.ebmonline.org/cgi/content/full/230/5/343
SIMPLE FACT, if you don't test, you don't find.
WHERE might we have been if Narang's research (and others that were not 'in the round'), would have been supported from the start ???
WHY were there just these 'chosen few' that recieved funding and got into the 'peer review round' ???
(please note, i have heard through the grapevine that Narang has recently past away, i have not confirmed this, (came from a good source though), and i never saw this in the news, but i hope that i am wrong. if true, this would be a great loss to the TSE science). ...TSS
http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html
TSS
The identification of disease-induced biomarkers in the urine of BSE infected cattle
Sharon LR Simon , Lise Lamoureux , Margot Plews , Micheal Stobart , Jillian LeMaistre , Ute Ziegler , Catherine Graham , Stefanie Czub , Martin Groschup and J. David Knox
Proteome Science 2008, 6:23doi:10.1186/1477-5956-6-23
Published: 5 September 2008
Abstract (provisional)
Background
The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrPd, in brain tissue and consequently are only suitable for post-mortem diagnosis.
Objectives:
In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements.
Results
Two dimensional differential gel eletrophoresis (2D-DIGE) and mass spectrometry analyses were used to identify proteins exhibiting differential abundance in the urine of BSE infected cattle and age matched controls over the course of the disease. Multivariate analyses of protein expression data identified a single protein able to discriminate, with 100% accuracy, control from infected samples. In addition, a subset of proteins were able to predict with 85% +/- 13.2 accuracy the time post infection that the samples were collected.
Conclusions These results suggest that in principle it is possible to identify biomarkers in urine useful in the diagnosis, prognosis and monitoring of disease progression of transmissible spongiform encephalopathy diseases (TSEs).
http://www.proteomesci.com/content/6/1/23/abstract
BUT, will the USDA et al let any test be used to detect BSE or any TSE in the USA bovine ???
i doubt it $$$
Sunday, September 07, 2008 CWD LIVE TEST, and the political aspects or fallout of live testing for BSE in cattle in the USA http://chronic-wasting-disease.blogspot.com/2008/09/cwd-live-test-and-political-aspects-or.html
Friday, August 29, 2008
CREEKSTONE VS USDA COURT OF APPEALS, BUSH SAYS, NO WAY, NO HOW
http://madcowtesting.blogspot.com/2008/08/creekstone-vs-usda-court-of-appeals.html
1996 NARANG URINE TEST
http://www.bseinquiry.gov.uk/files/yb/1996/02/09003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1996/02/21004001.pdf
http://www.bseinquiry.gov.uk/files/yb/1996/02/21005001.pdf
http://www.bseinquiry.gov.uk/files/ws/s113.pdf
http://www.bseinquiry.gov.uk/report/volume11/chaptec3.htm
5.289 We have concluded, for the reasons given above, that Dr Narang's work received fair consideration by MAFF scientists. While we would pay tribute to Dr Narang's dedication to research into TSEs, we feel that he had a fair opportunity to demonstrate the validity of his work but did not succeed in doing so.
http://www.bseinquiry.gov.uk/report/volume11/chaptec4.htm
No way to treat a pioneer Apr 20 2003 By Phil Doherty
A leading charity has called for a public inquiry into the way a top mad cow disease expert has been treated by the establishment. Harash Narang was the first scientist to make the link between the illness and its human equivalent- variant Creutzfeldt-Jakob disease - in 1990. Dr Narang says he was made redundant from his job at Newcastle's Public Health Laboratory Services after making his findings known. He claims that he lost his post after the then Health Minister Stephen Dorrell ordered all the lab's work on the killer disease to cease. Since he became a whistle-blower, he says, he has not been able to get lab time in the UK to continue his work.
Dr Narang has since moved to the United States. He is now working at the CJD surveillance unit based at Case Western Reserve University in Cleveland, Ohio.
CJD Foundation head Noel Baldwin, who lost his son Patrick to the killer disease, said: "There is more and more information coming out that proves Dr Narang was right all along.
Medical
"He said years ago that CJD could be found in blood and passed on by transfusions and medical instruments. This has now been accepted.
"He argued that BSE could cause both sporadic as well as vCJD, and recent research has shown this to be correct. He also invented a urine test which shows if someone is harbouring the disease."
Mr Baldwin also rued the Government's decision to pull Medical Research Council funding from Dr Narang.
He said: "Now it looks as if the US will benefit financially from this ground-breaking research. "The UK establishment has ignored him for more than 10 years. We believe those responsible should be made accountable for this because if they had listened to Dr Narang maybe some of those poor people wouldn't have died from this terrible disease.
Scandal
"This is a national scandal that needs to be fully addressed by a public inquiry. "We are planning to launch this campaign in the next few months and will be involving sympathetic MPs to get this issue aired in the House of Commons."
http://icnewcastle.icnetwork.co.uk/0100news/0100local/page.cfm?objectid=12871105&method=full&siteid=50081&headline=No%20way%20to%20treat%20a%20pioneer
2005 NARANG URINE TEST USA CWRU
CJD doc jets off
Mar 9 2003
By Phil Doherty, Sunday Sun
The North scientist who first established a link between mad cow disease and its human form is quitting Britain.
Harash Narang has been head-hunted by a top US university to continue his research into variant Creutzfeldt-Jakob disease.
He was working for the Government's Public Health Laboratory Service in Newcastle when he revealed the link and later lost his job.
Dr Narang claimed he was made redundant because he went public with his findings, an allegation which has always been denied. He said: "I now have a job at the United States CJD Surveillance Centre based in Case Western Reserve University, Cleveland, Ohio.
"I'm very excited because it has excellent facilities and is one of the best CJD surveillance centres in the world.
The university is examining a urine test pioneered by Dr Narang which can show whether someone has CJD.
Currently only a post-mortem diagnosis can be made.
Dr Narang said: "Early indications show that my test has performed even better than anticipated. It is expected to be validated very shortly."
And he revealed: "I do not regret telling the truth all those years ago. If I had to do it again then I would."
Ken Bell, a financial backer of Dr Narang's work, claimed he had been forced to go abroad because he cannot get laboratory time in the UK.
He said: "Harash has been blackballed in the UK because he told the public the truth. "The establishment will try anything to stop him working here. It's a disgrace."
Noel Baldwin, of the CJD Foundation charity, said: "He has been proved right about so many things . . . that CJD can be transmitted through blood, that BSE can cause both variant and sporadic CJD and that you can test for the disease through urine samples."
Dr Narang starts work at Case University later this month. Shu Chen, one of his future colleagues, said: "He will be a great asset to our CJD research."
http://icnewcastle.icnetwork.co.uk/0100news/0100local/page.cfm?objectid=12716797&method=full&siteid=50081
Edmonton company boasts cheap BSE test Duncan Thorne , CanWest News Service; Edmonton Journal Published: Friday, July 21, 2006 EDMONTON -- An Edmonton company is confident it has a cheap, ground-breaking test for mad cow disease, but the test's British inventor who claims to have first made the link between BSE and the disease's human form insists he still holds the rights.
Despite their differences, inventor Harash Narang and BSE Prion Solutions Inc. agree the test holds amazing potential to quickly and inexpensively test live cattle for bovine spongiform encephalopathy better known as mad-cow disease. The only approved tests so far for mad cow and its human equivalent depend on removing brain samples after death. A test on live animals would open the way to guaranteeing disease-free herds.
"We have a test that not only works, but works each and every time," said Ron Arnold of BSE Prion Solutions Inc., adding formal validation may take up to two years and regulatory approval. Narang, a former British government scientist who went public about human risks from BSE in 1990, started developing tests for detecting the disease in the late 1980s while at a public health laboratory. He had been studying cases of a fatal but rare human brain illness, Creutzfeldt-Jakob disease (CJD), when he started noticing some cases were different. He has said he was well on the way to establishing a link between BSE and the unusual CJD cases when he was ordered to stop his research. He has also claimed officials rejected his calls for increased testing for BSE and the new form of CJD, now known as variant CJD.
Narang developed three diagnostic tests, including an early version of the urine test that BSE Prion intends to bring to market.
A wide-ranging 1998 inquiry into Britain's response to the mad cow crisis found problems with Narang's claims. It cited evidence that fellow scientists could not get his test to work. Even so, Narang continued development of the urine test. A British company, Biotec Global, sponsored much of his work. He is no longer part of the research, but work on it continues at the United States National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland. Narang and Case Western researchers reported in 2005 that the urine test could reliably detect a harmless form of the prion protein that is blamed for BSE and variant CJD. It could also detect the bad form if the prion was first added directly to the urine.
They said their findings "may lay the foundation for a future technique," if in fact the bad prion can turn up naturally in urine.
"It needs a lot of work still," Ayuna Dagdanova, one of the test's researchers at the U.S. prion surveillance centre, said from Cleveland.
Without solid data it's not possible to say if they are close to detecting BSE in urine, she said. "No one actually knows, but preliminary experiments show the possibility."
Arnold, a partner in Biotec, said Narang gave Biotec the patent rights in 2003 and it in turn gave BSE Prion the licence for the Americas and Europe.
"We've talked with patent attorneys in London and also in Newcastle. Everyone agrees that the documents and the transfer of ownership of the patents was done judiciously and was extremely well put together by the solicitors," said Arnold.
Edmonton company boasts cheap BSE test Duncan Thorne , CanWest News Service; Edmonton Journal Published: Friday, July 21, 2006 Narang, speaking from Newcastle, acknowledged signing papers, but said it was not clear what he was signing. He said he continues to pay the patent renewal fees.
Biotec has sunk more than $2 million into the research, but BSE Prion has not had to pay a licence fee, Arnold said. That's because the project is humanitarian, with plans to hand over any earnings for research purposes, in the form of grants and scholarships.
Narang, who holds shares in Biotec despite the ownership dispute, also said he also wants any profits to go into further research. Meanwhile, he said he's owed back pay and expenses for work he did over the past five years a claim Arnold rejects.
[email protected]
Edmonton Journal © CanWest News Service 2006
http://www.canada.com/topics/news/national/story.html?id=e0300291-19dd-48a8-8e88-963a06087ce2&k=6995
http://www.canada.com/topics/news/national/story.html?id=e0300291-19dd-48a8-8e88-963a06087ce2&k=6995&p=2
Experimental Biology and Medicine 230:343-349 (2005) © 2005 Society for Experimental Biology and Medicine
----------------------------------------------------------
ORIGINAL RESEARCH ARTICLE
Sensitive Detection of Prion Protein in Human Urine
Harash K. Narang*,2, Ayuna Dagdanova, Zhiliang Xie, Qiwei Yang and Shu G. Chen,1 * BioTech Global, 22-40 Brentwood Avenue, Newcastle Upon Tyne, NE2 3DH, UK; and Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106 1To whom requests for reprints should be addressed at Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106. E-mail: [email protected].
ABSTRACT
Transmissible spongiform encephalopathies are a group of infectious diseases typically associated with the accumulation of a protease-resistant and ß-sheet-rich prion protein, PrPSc, in affected brains. PrPSc is an altered isoform derived from the host-encoded glycoprotein, PrPC. The expression of PrPC is the highest in brain tissue, but it can also be detected at low levels in peripheral tissue. However, it is unclear whether a significant amount of PrPC is released into body fluid and excreted into urine. We have developed a simple, rapid method for the reliable detection of PrPC in urine from normal subjects by Western blotting. Our method can easily and reliably detect PrPC in apparently healthy individuals using less than 1 ml of urine in which the amount of urinary PrPC is estimated to be in the range of low micrograms/liter.
http://www.ebmonline.org/cgi/content/full/230/5/343
SIMPLE FACT, if you don't test, you don't find.
WHERE might we have been if Narang's research (and others that were not 'in the round'), would have been supported from the start ???
WHY were there just these 'chosen few' that recieved funding and got into the 'peer review round' ???
(please note, i have heard through the grapevine that Narang has recently past away, i have not confirmed this, (came from a good source though), and i never saw this in the news, but i hope that i am wrong. if true, this would be a great loss to the TSE science). ...TSS
http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html
TSS
