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Britain may 'never be rid of vCJD threat'

A

Anonymous

Guest
Britain may 'never be rid of vCJD threat' without screening
LYNDSAY MOSS
HEALTH CORRESPONDENT ([email protected])
VARIANT CJD - the human form of mad cow disease - may never disappear from the UK due to the risks from blood transfusions and surgical equipment, a leading expert in the disease has warned.

Professor James Ironside, of the National CJD Surveillance Unit at Edinburgh University, said that unless a rapid screening test for vCJD is developed soon, the fatal infection could become endemic in the UK.
Prof Ironside will issue the warning at a major conference in Edinburgh this week on vCJD.

Concerns have been raised that the disease - caused by humans eating meat infected with the cattle disease BSE in the 1980s and 1990s - could be lying dormant in thousands of people.

While many will never develop the disease, they could pass it on to others by donating blood or through contaminated surgical instruments if they have an operation.

Prof Ironside said the National Blood Transfusion Service had already gone to great lengths to protect the blood supply, screening and filtering donations to try to reduce the risks from vCJD.

Also, after the first case of vCJD through blood transfusion was identified, people who had previously received blood were banned from donating.

But he said that the nature of the infection, which is not destroyed by heat treatment or decontamination of surgical equipment, meant it continued to be a significant issue.

"If you make certain assumptions about the number of people who might be infected with vCJD, because we know that with BSE many of us were exposed, and what the incubation periods might be, it is possible to arrive at a scenario where vCJD will never completely disappear.

"It will remain at a low level, an endemic level, maintained by secondary transmission. That is something that is very undesirable and should be avoided."

Graham Steel, co-founder of the CJD Alliance and the information resource manager of the CJD International Support Alliance, said: "We are closer than ever before to actually implementing new screening technologies to prevent further secondary infection of these diseases. The latest published research that I am aware of clearly demonstrates this.

"The time has almost come for screening to become a reality."

Marc Turner, of the Scottish National Blood Transfusion Service, said:

"We believe that the risk of transmission of vCJD by blood transfusion is low but that a highly precautionary approach is justified."

SPREAD OF THE DISEASE

VARIANT Creutzfeldt-Jakob Disease (vCJD) was first identified in 1996.

Patients with vCJD develop brain damage which eventually leads to death.

It was passed to humans through the food chain in meat infected with BSE. The disease spreads to the brain in tiny proteins called prions, which are extremely difficult to destroy using normal methods.

So far, 166 cases of vCJD have been diagnosed in the UK, but it is impossible to know how many more people could be affected but are not showing symptoms.

Scotland and the north of England have been worst hit by the disease.

Scotland has seen 4.12 cases per million people, compared with 2.03 in Wales and 2.8 cases per million in the south-east of England.

http://news.scotsman.com/uk.cfm?id=1524202007
 

Kathy

Well-known member
vCJD - may never disappear from the UK due to the risks from blood transfusions and surgical equipment, a leading expert in the disease has warned
.

This is not the human form of mad cow disease. It is contamination from nuclear industry/reactors/reprocessors/disposal/ and uranium weapons. As long as this nuclear entourage exists, there will be diseases associated with the misfolding, polymerization and aggregation of proteins, including TSEs, vCJD, CJD, Alzheimer's, Parkinson, ALS, cancer, etc.

The Atomic Commissions have successfully deceived the world into believing that nuclear energy is safe and green. Radiation is invisible; but the biological effects of internal ionizing radiation are staring us in the face every day.

While many will never develop the disease, they could pass it on to others...

And how is this possible, how can they have the disease but never develop the clinical manifestations of the disease?? According to Ironside, Matthews, Wells, Terry et al. (VLA), the causative agent of TSEs are prions (PrPSc) - how can you have the so-called infectious prions and never develop the disease.... this is completely contrary to everything they have espoused for the last 25 years.

It will remain at a low level, an endemic level, maintained by secondary transmission.

Yes, as long as depleted uranium, cesium 137, strontium 90 and the hundreds of other radiological isotopes are continually released into the environment, the threat of contamination of the brain with these deadly metals will continue to exist - therefore the diseases they cause will continue to exist. Once the cat was let out of the bag, by atmospheric testing and more recent military use (in war zones and on practice ranges) of DU weapons, there is no going back to the pre1945 background radiation levels.

VARIANT Creutzfeldt-Jakob Disease (vCJD) was first identified in 1996.
- four years after the USA bombed the sh*$ out of Iraq and Kuwait with depleted uranium (DU) missiles and bunker busters.

Patients with vCJD develop brain damage which eventually leads to death.
- according to Ironside (stated above) "many will never develop the disease" but can pass it on?????

What about the fact that when PrPSc was heated to temperatures over 660C, thus destroying all protein material and leaving only the basic elements making up proteins ie: sulfur, metals, carbon.... when injected into the brains of genetically modified mice - still developed the disease. Therefore the transmissible agent is not a protein, but a element making up the protien.

As for poor Scotland's higher rates of vCJD, look no further than the radioactive fallout of Chernobyl, and the nuclear waste washing up onto Scotland's shores from the nuclear reprocessing facility in Sellafield, UK.
"Low Level Radiation Campaign" has a DVD which shows where the radiation levels are higher nearest to the shorelines of rivers connected to the ocean and on the coast lines. See link: http://www.llrc.org/

Scotland doesn't just have higher rates of vCJD, they have high rates of leukemia. The blood borne radionuclides are destroying the immune system, destroying the ability of the body to create new stem cells which migrate to where they are needed and become the specific cells required.

www.llrc.org/ [excerpt]:

"Leukaemia risk covered up by Scottish Cancer Registry

The Scottish Cancer Registry, desperate to keep leukaemia data secret, is going to the House of Lords to try overturning orders by the Information Commissioner and the Court of Session to release it.
In an earlier move they published a fudged analysis of the data. It seems obvious that they fear the data will eventually be dragged into the light and that people will see higher risks near the coast of the Solway Firth, which is contaminated by Sellafield and by the testing of depleted Uranium weapons at the Dundrennan firing range."

I suggest you order Mark Purdey's new book, Animal Pharm, and read it. Before the next shoe drops; you better understand how the nuclear industry and military industrial complex are pulling the wool over your eyes.
 

bse-tester

Well-known member
Kathy wrote/quoted:

Quote:
While many will never develop the disease, they could pass it on to others...


And how is this possible, how can they have the disease but never develop the clinical manifestations of the disease?? According to Ironside, Matthews, Wells, Terry et al. (VLA), the causative agent of TSEs are prions (PrPSc) - how can you have the so-called infectious prions and never develop the disease.... this is completely contrary to everything they have espoused for the last 25 years.
 

bse-tester

Well-known member
Kathy wrote/quoted:

Quote:
While many will never develop the disease, they could pass it on to others...


And how is this possible, how can they have the disease but never develop the clinical manifestations of the disease?? According to Ironside, Matthews, Wells, Terry et al. (VLA), the causative agent of TSEs are prions (PrPSc) - how can you have the so-called infectious prions and never develop the disease.... this is completely contrary to everything they have espoused for the last 25 years.

The obvious reason for non-development of clinical symptoms or even the so-called non-transference of the disease from one human "positive vCJD carrier" to a non-carrier human is the incubation period of the disease and how it varies from one human to another as it does in animals. The important fact to remember is that although we may have all been created equal in the eyes of God - depending on what God one relies upon - , Orwell summed it up nicely in his book, Animal Farm, [no pun intended Kathy] by stating that not all animals/humans are created equal but some are more equal than others. Of course, I am twisting it a little out of context but the saying holds when the discussion relates to Prion disease and the transmissable abilities/effects of the disease.

A person who carrys the misfolded prion can be considered a positive and yet still not fall into the infectious catagory due to the incredibly low numbers of PrPsc being carried within them. (Having said that, I sure as heck would not want their blood in me) It is not until they replicate into such numbers as to be virtually present throughout the body inclusive of all fluids such as blood for example and creating inhibitors within the neuro-network of the host brain, that the transference will most occur with 100% certainty. Even when it is transmitted from one human to another, from one who is already clinically assigned, it may take longer to manifest itself with clinical symptoms in the new (host) than it did in the original carrier. Why is that? Simply put, we are not all equal when it comes to development of a human disease or one that is acquired from an outside source. Therefore, we can safely state that evidence has already shown that many people who carried many different types of diseases never actually died of them due to the long and unual length of the incubation period within that individual. But they were still able to play a vital role in contaminating many others through their participation with blood donor clinics while showing no obvious symptoms.

Lastly, consider how many people who unknowingly carry or carried the deadly PrPsc and gave blood to thousands of others and literally handed them a death sentence? Also consider how many cattle walked down the shute into the plant without showing any sign or clinical symptoms of carrying the disease??

Consider how many still do it each and every day and consider the fact that the governments tell us that all is well in Paradise because they test only a few thousand out of many millions of cattle. Most comforting wouldn't you say??
 

flounder

Well-known member
Oldtimer said:
Britain may 'never be rid of vCJD threat' without screening
LYNDSAY MOSS
HEALTH CORRESPONDENT ([email protected])
VARIANT CJD - the human form of mad cow disease - may never disappear from the UK due to the risks from blood transfusions and surgical equipment, a leading expert in the disease has warned.

Professor James Ironside, of the National CJD Surveillance Unit at Edinburgh University, said that unless a rapid screening test for vCJD is developed soon, the fatal infection could become endemic in the UK.
Prof Ironside will issue the warning at a major conference in Edinburgh this week on vCJD.

Concerns have been raised that the disease - caused by humans eating meat infected with the cattle disease BSE in the 1980s and 1990s - could be lying dormant in thousands of people.

While many will never develop the disease, they could pass it on to others by donating blood or through contaminated surgical instruments if they have an operation.

Prof Ironside said the National Blood Transfusion Service had already gone to great lengths to protect the blood supply, screening and filtering donations to try to reduce the risks from vCJD.

Also, after the first case of vCJD through blood transfusion was identified, people who had previously received blood were banned from donating.

But he said that the nature of the infection, which is not destroyed by heat treatment or decontamination of surgical equipment, meant it continued to be a significant issue.

"If you make certain assumptions about the number of people who might be infected with vCJD, because we know that with BSE many of us were exposed, and what the incubation periods might be, it is possible to arrive at a scenario where vCJD will never completely disappear.

"It will remain at a low level, an endemic level, maintained by secondary transmission. That is something that is very undesirable and should be avoided."

Graham Steel, co-founder of the CJD Alliance and the information resource manager of the CJD International Support Alliance, said: "We are closer than ever before to actually implementing new screening technologies to prevent further secondary infection of these diseases. The latest published research that I am aware of clearly demonstrates this.

"The time has almost come for screening to become a reality."

Marc Turner, of the Scottish National Blood Transfusion Service, said:

"We believe that the risk of transmission of vCJD by blood transfusion is low but that a highly precautionary approach is justified."

SPREAD OF THE DISEASE

VARIANT Creutzfeldt-Jakob Disease (vCJD) was first identified in 1996.

Patients with vCJD develop brain damage which eventually leads to death.

It was passed to humans through the food chain in meat infected with BSE. The disease spreads to the brain in tiny proteins called prions, which are extremely difficult to destroy using normal methods.

So far, 166 cases of vCJD have been diagnosed in the UK, but it is impossible to know how many more people could be affected but are not showing symptoms.

Scotland and the north of England have been worst hit by the disease.

Scotland has seen 4.12 cases per million people, compared with 2.03 in Wales and 2.8 cases per million in the south-east of England.

http://news.scotsman.com/uk.cfm?id=1524202007


:shock: :?


kathy's been in the therapeutic weed again :lol: :lol: :cboy:



PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS
SEPTEMBER 2007

Date: Mon, 24 Sep 2007 21:31:55 -0500

I suggest that you all read the data out about h-BASE and sporadic CJD, GSS,
blood, and some of the other abstracts from the PRION2007. ...


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744



TSS
 

flounder

Well-known member
Subject: Nonpsychoactive Cannabidiol Prevents Prion Accumulation and
Protects Neurons against Prion Toxicity
Date: September 14, 2007 at 2:52 pm PST

Neurobiology of Disease
Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons
against Prion Toxicity

Sevda Dirikoc,1 Suzette A. Priola,2 Mathieu Marella,3 Nicole Zsürger,1 and
Joëlle Chabry1

1Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de
Recherche 6097, Centre National de la Recherche Scientifique, 06560
Valbonne, France, 2Laboratory of Persistent Viral Diseases, National
Institutes of Health, National Institute of Allergy and Infectious Diseases,
Rocky Mountain Laboratories, Hamilton, Montana 59840, and 3Scripps Research
Institute, La Jolla, California 92037

Correspondence should be addressed to Dr. Joëlle Chabry, Institut de
Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097,
Université de Nice-Sophia Antipolis, Centre National de la Recherche
Scientifique, 660, route des lucioles, 06560 Valbonne, France. Email:
[email protected]

Prion diseases are transmissible neurodegenerative disorders characterized
by the accumulation in the CNS of the protease-resistant prion protein
(PrPres), a structurally misfolded isoform of its physiological counterpart
PrPsen. Both neuropathogenesis and prion infectivity are related to PrPres
formation. Here, we report that the nonpsychoactive cannabis constituent
cannabidiol (CBD) inhibited PrPres accumulation in both mouse and sheep
scrapie-infected cells, whereas other structurally related cannabinoid
analogs were either weak inhibitors or noninhibitory. Moreover, after
intraperitoneal infection with murine scrapie, peripheral injection of CBD
limited cerebral accumulation of PrPres and significantly increased the
survival time of infected mice. Mechanistically, CBD did not appear to
inhibit PrPres accumulation via direct interactions with PrP,
destabilization of PrPres aggregates, or alteration of the expression level
or subcellular localization of PrPsen. However, CBD did inhibit the
neurotoxic effects of PrPres and affected PrPres-induced microglial cell
migration in a concentration-dependent manner. Our results suggest that CBD
may protect neurons against the multiple molecular and cellular factors
involved in the different steps of the neurodegenerative process, which
takes place during prion infection. When combined with its ability to target
the brain and its lack of toxic side effects, CBD may represent a promising
new anti-prion drug.


Key words: prion; cannabinoid; neuroprotection; scrapie-infected mice;
cell-free conversion; microglia


----------------------------------------------------------------------------
----
Received Feb. 20, 2006; revised May 24, 2007; accepted June 13, 2007.

Correspondence should be addressed to Dr. Joëlle Chabry, Institut de
Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097,
Université de Nice-Sophia Antipolis, Centre National de la Recherche
Scientifique, 660, route des lucioles, 06560 Valbonne, France. Email:
[email protected]


http://www.jneurosci.org/cgi/content/abstract/27/36/9537?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=27&issue=36&resourcetype=HWCIT


I'll Never Smoke Weed With Willie Again Lyrics
Artist(Band):Toby Keith Review The Song (2) Print the Lyrics



Artist/Band: Keith Toby
Lyrics for Song: Weed With Willie
Lyrics for Album: Shock'n Y'all
(Toby Keith/Scotty Emerick)

I always heard that his herb was top shelf
I just could not wait to find out for myself
Don't knock it til' you tried it, Well I tried it my friend
And I'll never smoke weed with Willie again

I learned a hard lesson in a small Texas town
He fired up a fat boy and passed him around
The last words that I spoke before they tucked me in
Was I'll never smoke weed with Willie again

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

I hopped on his old bus, the Honey Suckle Rose
The party was Vegas it was after the show.
Alone in the front lounge with just me and him,
With one parting puff grim creeper set in.

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

Now we're passing the guitar and telling good jokes
I know ones a-comin' cause I'm smelling smoke
No I do not partake, I just let it pass by
With a smile on my face and a great contact high

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

In the fetal position with drool on my chin
I messed up and smoked weed with Willie again


There's a funny story about Willie and my mom I should tell you about some
times. I remember (partially) his Gonzales 3 day picnic in 1976 on a 2000
acre ranch somewhere. what a picnic it was. remind me to tell you that too,
we had backstage passes, old Leon and Marry Russel was there too, what a
space in time it was ;-), maybe some of us are more well protected from
those prions than we thought, or can remember ...TSS
 

Kathy

Well-known member
bse tester,

The agent, in my opinion, that is translocating from a blood transfusion to the brain, thus contaminating the brain IS not PrPSc protein, but the metal uranium, for example, that slips into the bloodstream via many methods: ie: inhalation, injection, ingestion, absorption via skin.

The difference between cases that go onto develop Gulf War Syndrome, and those that have other symptoms of DU contamination are just as broad as the scenario you discuss with vCJD.

The problem is that in what form do these metals get to the brain and cause neurological disorders. The prion protein acts as an antioxidant protecting the brain cells from the ROS produced by the low levels of radiation afflicting the cell. When the PrPC protein becomes malformed due to the wrong metals attaching to it (an excess of manganese due to the ionizing radiation effect) the ability of the PrPC to protect the cell membrane from ROS is removed. More PrPC is produced to protect the cell, and this is where people/animals differ. Some are more fortunate and have access to the appropriate minerals, ie: copper zinc. Many researchers are working on antioxidant cocktails to alleviate the cellular damage caused by unchecked ROS.

Prusiner's papers clearly show that uranium allows the formation of prion fibrils. Not molybdenum or other metal stains commonly used in labs. The uranium nanoparticles that can be found in blood, may be present without evidence of prions, or the prions present may be a convenient hidding place for the uranium, either way.... the "transmissible agent" is not a protein. It is a radioactive metal.

Since most tests done by governments to detect "depleted uranium" in war vets and their spouses, are set to levels too high to detect the trace amounts necessary for disease.... soldiers go home with the Negative Test, and still spread these toxic particles.

In the future, Americans and Canadians will be more at risk from an injection of morphine (manufactured with Afgani and Iraqi poppies) than a blood transfusion. The bioavailability of the DU nanoparticles from a plant sourced, injectible medication, are much higher than from ingesting meat.

Everyone wants to blame the first epidemiological connection, but they need to re-examine the facts with information that has come to light recently. Dr. Chris Busby has proven that DU travelled from Iraq/Afganastan/Kosovo/Bosnia et al. (DU targets). Twice during bombing raids in Iraq and Afganastan the levels of DU in the air in the UK were at levels requiring an alarm - an alarm which indicates a severe radiation leak from the Sellafield nuclear facilities - EXCEPT IT WASN'T ONLY FROM SELLAFIELD ON THOSE OCCASSIONS, the spikes in background radiation were the direct effect of WAR thousands of miles away. For weeks, people in the UK inhaled this toxic air. The nanoparticles go deep in the lungs and quickly translocate from lungs, eyes, nasal passages to the brain and other organs. The brain is a target organ for uranium.

Eur J Mass Spectrom (Chichester, Eng). 2007;13(1):1-6.Links
New developments in laser ablation inductively coupled plasma mass spectrometry for brain research and life sciences.
Becker JS, Becker JS, Zoriy MV, Dobrowolska J, Matucsh A.
Central Division of Analytical Chemistry, Research Centre Jülich, D-52425 Jülich, Germany.

Of all the inorganic mass spectrometric techniques, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) plays a key role as a powerful and sensitive microanalytical technique enabling multi- element trace analysis and isotope ratio measurements at trace and ultratrace level. LA-ICP-MS was used to produce images of detailed regionally-specific element distribution in 20 microm thin sections of different parts of the human brain. The quantitative determination of copper, zinc, lead and uranium distribution in thin slices of human brain samples was performed using matrix-matched laboratory standards via external calibration procedures. Imaging mass spectrometry provides new information on the spatially inhomogeneous element distribution in thin sections of human tissues, for example, of different brain regions (the insular region) or brain tumor tissues. The detection limits obtained for Cu, Zn, Pb and U were in the ng g(1) range. Possible strategies of LA-ICP-MS in brain research and life sciences include the elemental imaging of thin slices of brain tissue or applications in proteome analysis by combination with matrix-assisted laser desorption/ionization MS to study phospho- and metal- containing proteins will be discussed.

PMID: 17885277


It is imparative to find the best available methods to discover the uranium nanoparticles in the body/brain.

As in the Peyer's Patch study by Wells, et al. their mass spectrometry tests over-looked uranium, yet is was clearly there.

Some tests are better at finding, or hiding, what you are looking for.
 

Kathy

Well-known member
Jpn J Infect Dis. 2007 Sep;60(5):317-20. Links
Experimental Transmission of Two Young and One Suspended Bovine Spongiform Encephalopathy (BSE) Cases to Bovinized Transgenic Mice.
Yokoyama T, Masujin K, Yamakawa Y, Sata T, Murayama Y, Shu Y, Okada H, Mohri S, Shinagawa M.
Prion Disease Research Center, National Institute of Animal Health, Ibaraki 305-0856, Japan. [email protected]

Bovine spongiform encephalopathy (BSE) is caused by a prion that primarily consists of an abnormal isoform of the prion protein (PrP(Sc)). Since PrP(Sc) is partially resistant to proteolytic digestion, the routine diagnosis of BSE is based on the immunological detection of the proteinase K (PK)-resistant moiety of PrP(Sc) (PrP(core)). However, transmission studies are indispensable in order to demonstrate prion infectivity and to analyze prion characteristics. Transmission experiments were accordingly performed on 2 young BSE cases (BSE/JP8, BSE/JP9) and 1 suspected BSE case (Suspended-1) that were detected by the BSE screening program in Japan. In this study, we attempted to transmit the prion from these 3 animals by using transgenic mice overexpressing bovine PrP (TgBoPrP). In spite of the use of BSE-sensitive transgenic mice, none of the mice developed neurological signs nor accumulated PrP(Sc) in their brains for more than 600 days post-inoculation, even with subsequent blind passages. The results of a dilution experiment using the classical BSE prion indicated that prion infectivity in these 3 cattle was below the detection limit of 10(3.0) LD(50)/g.

PMID: 17881878
 

flounder

Well-known member
Kathy said:
Jpn J Infect Dis. 2007 Sep;60(5):317-20. Links
Experimental Transmission of Two Young and One Suspended Bovine Spongiform Encephalopathy (BSE) Cases to Bovinized Transgenic Mice.
Yokoyama T, Masujin K, Yamakawa Y, Sata T, Murayama Y, Shu Y, Okada H, Mohri S, Shinagawa M.
Prion Disease Research Center, National Institute of Animal Health, Ibaraki 305-0856, Japan. [email protected]

Bovine spongiform encephalopathy (BSE) is caused by a prion that primarily consists of an abnormal isoform of the prion protein (PrP(Sc)). Since PrP(Sc) is partially resistant to proteolytic digestion, the routine diagnosis of BSE is based on the immunological detection of the proteinase K (PK)-resistant moiety of PrP(Sc) (PrP(core)). However, transmission studies are indispensable in order to demonstrate prion infectivity and to analyze prion characteristics. Transmission experiments were accordingly performed on 2 young BSE cases (BSE/JP8, BSE/JP9) and 1 suspected BSE case (Suspended-1) that were detected by the BSE screening program in Japan. In this study, we attempted to transmit the prion from these 3 animals by using transgenic mice overexpressing bovine PrP (TgBoPrP). In spite of the use of BSE-sensitive transgenic mice, none of the mice developed neurological signs nor accumulated PrP(Sc) in their brains for more than 600 days post-inoculation, even with subsequent blind passages. The results of a dilution experiment using the classical BSE prion indicated that prion infectivity in these 3 cattle was below the detection limit of 10(3.0) LD(50)/g.

PMID: 17881878



Jpn. J. Infect. Dis., 60 (5), 305-308, 2007


Short Communication

Accumulation of Mono-Glycosylated Form-Rich, Plaque-Forming PrPSc in the
Second Atypical Bovine Spongiform Encephalopathy Case in Japan

Ken'ichi Hagiwara1,3*, Yoshio Yamakawa1,3, Yuko Sato2, Yuko Nakamura1,
Minoru Tobiume2, Morikazu Shinagawa3 and Tetsutaro Sata2,3

1Department of Biochemistry and Cell Biology and 2Department of Pathology,
National Institute of Infectious Diseases, Tokyo 162-8640, and 3The Expert
Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare, Tokyo
100-8916, Japan

(Received March 23, 2007. Accepted June 1, 2007)



----------------------------------------------------------------------------
----


*Corresponding author: Mailing address: Department of Biochemistry and Cell
Biology, National Institute of Infectious Diseases, Toyama 1-23-1,
Shinjuku-ku, Tokyo 162-8640, Japan. Tel: +81-3-5285-1111, Fax:
+81-3-5285-1157, E-mail: [email protected]



----------------------------------------------------------------------------
----


SUMMARY: The recent identification of several atypical cases of bovine
spongiform encephalopathy (BSE) has raised the possibility of the existence
of distinct strains of BSE agents, arguing against the previous notion that
BSE is caused by a single strain. To date, at least, two atypical types (L
and H) of agent have been reported based on the molecular sizes of the
proteinase K-resistant forms of prion protein (PrPSc). These atypical agents
were identified first in Japan, Italy, France, and Germany, and later in
other European countries. Here, we have identified a case of BSE in a
169-month-old cow (designated as BSE/JP24), in which predominant deposition
of the mono-glycosylated form of PrPSc was observed by Western-blot
analysis, and plaques of PrPSc were detected in the brain by
immunohistochemical analysis. The glycoform ratio of PrPSc was different
from that of the typical BSE agent, in which the di-glycosylated form is
dominant; instead, the ratio resembled that of type-2 human sporadic
Creutzfeldt-Jakob disease and that reported for the L-type BSE. The
characteristic glycoform ratio and plaques of PrPSc suggested that the agent
in BSE/JP24 was relevant, if not identical, to the agent in bovine
amyloidotic spongiform encephalopathy (BASE), an L-type BSE identified in
Italy. It was of interest that at the level of the obex, the medulla
oblongata was devoid of plaques of PrPSc, and a pathological phenotype
similar to that of typical BSE specimens with vacuolations and coarse
granular/linear deposition of PrPSc were observed.


http://www.nih.go.jp/JJID/60/305.html


FULL TEXT ;

http://www.nih.go.jp/JJID/60/305.pdf



P02.35
Molecular Features of the Protease-resistant Prion Protein (PrPres) in
H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2;
Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden


Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have
demonstrated 3 different molecular phenotypes regarding to the apparent molecular
masses and glycoform ratios of PrPres bands. We initially described isolates (H-type
BSE) essentially characterized by higher PrPres molecular mass and decreased
levels of the diglycosylated PrPres band, in contrast to the classical type of BSE.
This type is also distinct from another BSE phenotype named L-type BSE, or also BASE
(for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low
representation of the diglycosylated PrPres band as well as a lower PrPres
molecular mass. Retrospective molecular studies in France of all available BSE cases
older than 8 years old and of part of the other cases identified since the beginning of the
exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases,
among 594 BSE cases that could be classified as classical, L- or H-type BSE.
By Western blot analysis of H-type PrPres, we described a remarkable
specific feature with antibodies raised against the C-terminal region of PrP that
demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in
addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2
migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the
PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another
PK–resistant fragment at about 7 kDa was detected by some more N-terminal
antibodies and presumed to be the result of cleavages of both N- and C-terminal parts
of PrP. These singular features were maintained after transmission of the disease to
C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and
7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease
and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.


FC5.5.1
BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc
C-terminal Truncated Fragments

Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,
MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;
Monaco, S3 1University of Verona, of Neurological and Visual Sciences,
Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological and Visual
Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA


The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human
prion disease, remains still unknown. The marked disease phenotype heterogeneity
observed in sCJD is thought to be influenced by the type of proteinase K-resistant
prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of
the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V)
codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE)
and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type,
distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD
subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three
PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;

(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V-
2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD
subtype M/V-2 shared molecular and pathological features with an atypical form of
BSE, named BASE, thus suggesting a potential link between the two conditions. This
connection was further confirmed after 2D-PAGE analysis, which showed an
identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this
issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally
inoculated with brain homogenates from BASE. Samples were separated by using
a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here
show that the PrPSc pattern obtained in infected primates is identical to BASE
and sCJD MV-2 subtype. These data strongly support the link, or at least a common
ancestry, between a sCJD subtype and BASE. This work was supported by Neuroprion
(FOOD-CT-2004-506579)


*******************************************************


USA MAD COW CASES IN ALABAMA AND TEXAS


***PLEASE NOTE***


USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it
today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were
''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007
11:52 PM. ...TSS


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779


*******************************************************


FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into
a
Typical BSE Phenotype and a Muscle Wasting Disease


Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2; Torcoli, G2;
Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3;
Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2
1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA,
Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy


The clinical phenotype of bovine spongiform encephalopathy has been extensively
reported in early accounts of the disorder. Following the introduction of statutory active
surveillance, almost all BSE cases have been diagnosed on a pathological/molecular
basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance
system has uncovered atypical BSE cases, which are characterized by distinct
conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose
clinicopathological phenotypes remain unknown. We recently reported two
Italian atypical cases with a PrPSc type similar to BSE-L, pathologically
characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently
disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A
major limitation of transmission studies to mice is the lack of reliable information on
clinical phenotype of BASE in its natural host. In the present study, we experimentally
infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates
by i.c. route. BASE infected cattle showed survival times significantly
shorter than BSE, a finding more readily evident in Fresian/Holstein, and in keeping with
previous observations in TgBov mice. Clinically, BSE-infected cattle developed a
disease phenotype highly comparable with that described in field BSE cases
and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle
developed an amyotrophic disorder accompanied by mental dullness.
The molecular and neuropathological profiles, including PrP deposition
pattern, closely matched those observed in the original cases. This study further confirms
that BASE is caused by a distinct prion isolate and discloses a novel disease
phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated
cattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.
Oral Abstracts
14


FC5.1.1
Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,
and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;
Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA;
3University of Texas MD Anderson Cancer Center, USA; 4Western General
Hospital, UK; 5Baxter BioSience, Austria


Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy
(TSE) have documented blood infectivity in both the pre-clinical and clinical phases of
disease. Results in a (presumably more appropriate) non-human primate model have not been reported.
Objective: To determine if blood components (red cells, white cells, platelets, and
plasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and
intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic
Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease
(vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from
chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker
disease (GSS). Animals were monitored for a period of 5 years, and all dying
or sacrificed animals had post-mortem neuropathological examinations and
Western blots to determine the presence or absence of the misfolded ‘prion’ protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated with
blood components from patients with sporadic or variant CJD. All donor
chimpanzees
(sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase
plasmapheresis, several months earlier than the expected onset of illness.
One monkey inoculated with purified leukocytes from a pre-clinical GSS
chimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood components
from 4 patients with sporadic CJD and 3 patients with variant CJD.


***However, a single transmission from a chimpanzee-passaged strain of GSS
shows that infectivity may be present in leukocytes, and the ‘shock’ of
general anaesthesia and plasmspheresis appears to have triggered the onset of illness in
pre-clinical donor chimpanzees.



FC5.1.2
Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and

vCJD Blood Specimens


Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus,
D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7; Will,
R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI,
Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden; 7CJD
Surveillance Unit, UK


BSE and vCJD transmitted to cynomolgus macaques reproduce many features of
human vCJD, including clinical symptoms, neuropathological hallmarks of vCJD,
PrPres electrophoretical pattern and, most importantly, the wide distribution of
infectivity in peripheral organs. The latter characteristic distinguishes vCJD from sCJD
in both humans and cynomolgus macaques, and prompted us to use this non-human
primate model for further investigations of vCJD and its risk for human health. The
occurrence of four vCJD infections in humans transfused with blood from patients who
later developed vCJD has raised concern about blood transfusion safety in countries
with vCJD.
In this collaborative European study, we investigated the infectivity of
blood components and whole blood administered by intracerebral (ic) and
intravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic and
iv route, respectively, from two vCJD patients and from two clinical vCJD-inoculated
macaques. Transfusions were also performed from whole blood and blood leucodepleted
according to hospital practice standards from two clinical BSE inoculated
macaques. Blood infectivity during the preclinical phase is being examined in orally
infected macaques. Whole blood was collected and transfused from one such animal two
years after oral challenge, whereas buffy-coat and plasma from two animals
at 2 and 4.5 years post-challenge, respectively, have been inoculated by the ic
route.
This is an ongoing study in which recipient animals continue to be observed
at various times post-inoculation. So far, we have had one positive transmission in one
animal transfused 65 months earlier with 40 ml of whole blood from a vCJD macaque
(the characteristics of the disease in this animal will be shown in a separate poster by E.
Comoy). This positive transmission reproduces transfusion transmission of vCJD in
humans, with an incubation of 5.5 years compatible with incubation periods
observed in humans.


FC5.3
Assessing the Risk of vCJD Transmission by Dentistry; Distribution of
Infectivity in Oral Tissues of VM Mice after Simulated Oral Feeding of
BSE-301V

Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,
MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH1
1Health Protection Agency, Centre for Emergency Preparedness and Response,,
TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3Health
Protection Agency, Centre for Emergency Preparedness and Response,, UK


Background: Ongoing concerns about the prevalence of variant Creutzfeldt Jakob
Disease (vCJD) in the UK population has heightened concerns about the risks
of iatrogenic transmission of the disease. Although there have been no cases
to date of transmission by surgery there have been 4 cases involving blood
transfusion. This study aims to assess the potential of transmission of the disease by
dental procedures. Whilst the risks are undoubtably low the very large numbers of
procedures carried out annually have the potential to amplify the risks considerably
and there is very little data in this area to form the basis for accurate risk
assessments. Aim(s)/Objective(s): To assess the relative levels of infectivity in oral
tissues from a murine model following exposure to BSE-301V through the small intestine.
Methods. The study uses a BSE-301V, VM mouse model as a clinically relevant model for
assessing iatrogenic vCJD transmission between humans. Infectious mouse
brain homogenate was prepared and inoculated into a loop of the duodenum, to
prevent direct contamination of the oral tissues. Mice were sacrificed at 3-weekly
intervals and at appearance of clinical symptoms. A range of oral tissues,
including dental pulp, gingival margin, salivary gland, saliva, lingual tonsil and
trigeminal ganglia, together with brain and spleen tissues were removed, processed as
homogenates and reinoculated intracranially (ic.) into indicator mice.
Results: The primary challenge proved to be a very efficient route of
infection with a 100% attack rate and a mean incubation to clinical disease
of 157 ± 17 days (compared to 120 days for the same titre inoculum ic.). Infectivity was
observed in all oral and control tissues with varying time-courses and titres estimated from
incubation period.
Discussion: The results throw new light on the potential routes of
dissemination and spread of infectivity from the small intestine to the oral cavity and its
implications for possible iatrogenic transmission of vCJD via dental, endoscopic or other
forms of surgery.
Conclusion: The data generated from the study provides support for ongoing
risk assessments to look at the potential for vCJD transmission via dental
procedures alongside other elements of studies looking at effectiveness of
decontamination and re-use of dental instruments.


P02.15
Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease

Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5;
Ironside, J6; Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8; Stressenberger, N9;
Langeveld, J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13; Andreoletti, O1
1Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’Anatomie Pathologique
and INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France;
5 Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular &
Clinical Medicine (Pathology),, National Creutzfeldt-Jakob Disease Surveillance Un,
UK; 7Pitié Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière, Service de
Biochimie et Biologie Moléculaire,, France; 9Hôpital Neurologique -Service de
Neurochimie, France; 10CIDC-Lelystad, Netherlands; 11University of Edinburgh, Western General
Hospital, UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire de Neuropathologie, France;
13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France


Creutzfeldt-Jakob disease (CJD) cases are currently classified according to
established diagnostic criteria and by the genotype at codon 129 of the PRNP
gene and the Western blotting of the proteinase K digested abnormal prion protein
that distinguishes a type 1 and a type 2 profile. These biochemically distinct
PrPres types have been proposed to represent distinct prion strains. However, since the
cooccurence of type 1 and type 2 PrPres in the same patient is common, the rationale of
this classification and strain concept as applied to CJD are currently under discussion.
Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD (both dura
matter-, and growth hormone-associated) cases, originating from UK and France, were
systematically investigated, using Western blotting typing, and by two others
biochemical assays that depend on the behaviour of PrPSc in variable PK digestion
conditions. As described previously, co-occurrence of type 1 and type 2 PrPres was
found in 30% of the CJD patients examined. However, our novel PK concentration
dependent assays identified a single uniform PrP type in cases where both type 1 and
type 2 were present. Moreover, in sCJD four distinct biochemical PrPSc
signatures were identified by the PK concentration dependent assays and these
correlated to the current genotype/clinico-pathological sCJD groups. In iCJD the four similar
biochemical signatures were observed, but were not correlated to particular PRNP 129
polymorphism or Western Blot PrPres patterns. Moreover notable differences were
observed between PrPSc biochemical properties of French and UK GH-CJD cases,
which could reflect, as already suspected, differences in the causative agents.
Identification, in sCJD and iCJD, of four different PrPSc phenotypes
irrespective of patients PRNP polymorphism at codon 129 and Western blot profile provides
new insights into human prion disease aetiology and could reflects an unsuspected
diversity of TSE agents in human disease. Further investigations are currently
underway using animal transmission to correlate agent strain with our new
discriminant biochemical assays.


see full text 143 pages ;


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


TSS
 

TimH

Well-known member
bse-tester said:
Kathy wrote/quoted:

Quote:
While many will never develop the disease, they could pass it on to others...


And how is this possible, how can they have the disease but never develop the clinical manifestations of the disease?? According to Ironside, Matthews, Wells, Terry et al. (VLA), the causative agent of TSEs are prions (PrPSc) - how can you have the so-called infectious prions and never develop the disease.... this is completely contrary to everything they have espoused for the last 25 years.

The obvious reason for non-development of clinical symptoms or even the so-called non-transference of the disease from one human "positive vCJD carrier" to a non-carrier human is the incubation period of the disease and how it varies from one human to another as it does in animals. The important fact to remember is that although we may have all been created equal in the eyes of God - depending on what God one relies upon - , Orwell summed it up nicely in his book, Animal Farm, [no pun intended Kathy] by stating that not all animals/humans are created equal but some are more equal than others. Of course, I am twisting it a little out of context but the saying holds when the discussion relates to Prion disease and the transmissable abilities/effects of the disease.

A person who carrys the misfolded prion can be considered a positive and yet still not fall into the infectious catagory due to the incredibly low numbers of PrPsc being carried within them. (Having said that, I sure as heck would not want their blood in me) It is not until they replicate into such numbers as to be virtually present throughout the body inclusive of all fluids such as blood for example and creating inhibitors within the neuro-network of the host brain, that the transference will most occur with 100% certainty. Even when it is transmitted from one human to another, from one who is already clinically assigned, it may take longer to manifest itself with clinical symptoms in the new (host) than it did in the original carrier. Why is that? Simply put, we are not all equal when it comes to development of a human disease or one that is acquired from an outside source. Therefore, we can safely state that evidence has already shown that many people who carried many different types of diseases never actually died of them due to the long and unual length of the incubation period within that individual. But they were still able to play a vital role in contaminating many others through their participation with blood donor clinics while showing no obvious symptoms.

Lastly, consider how many people who unknowingly carry or carried the deadly PrPsc and gave blood to thousands of others and literally handed them a death sentence? Also consider how many cattle walked down the shute into the plant without showing any sign or clinical symptoms of carrying the disease??

Consider how many still do it each and every day and consider the fact that the governments tell us that all is well in Paradise because they test only a few thousand out of many millions of cattle. Most comforting wouldn't you say??

TRANSLATION---

"If you'll only buy my patented wonder BSE test kit for only $39.95(plus shipping and handling), you won't have to be scared $hitless anymore.
Call now... operators are standing by... 1-888-BSE-KILL or 1-888-RON-BANK!!!!!

:D :D :D :D :D
 

flounder

Well-known member
Kathy said:
Quote:
While many will never develop the disease, they could pass it on to others...


And how is this possible, how can they have the disease but never develop the clinical manifestations of the disease?? According to Ironside, Matthews, Wells, Terry et al. (VLA), the causative agent of TSEs are prions (PrPSc) - how can you have the so-called infectious prions and never develop the disease.... this is completely contrary to everything they have espoused for the last 25 years.

************************

kathy, you should really pay attention. this is old news ;



Docket

No. 04-047-l

No. 04-021ANPR

No. 2004N-0264

NEW BSE SAFEGUARDS

Federal Measures to Mitigate BSE Risks: Considerations for Further Action

http://www.fda.gov/cvm/index/updates/bseanprm.htm

Greetings FDA, USDA and APHIS et al,


https://web01.aphis.usda.gov/regpublic.nsf/168556f5aa7a82ba85256ed00044eb1f/eff9eff1f7c5cf2b87256ecf000df08d


http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf


From: Terry S. Singeltary Sr. [[email protected]]
Sent: Thursday, September 08, 2005 6:17 PM
To: [email protected]
Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle


Greetings FSIS,


I would kindly like to submit the following to [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle THE BSE/TSE SUB CLINICAL Non-Ambulatory Disabled Cattle Broken bones and such may be the first signs of a sub clinical BSE/TSE Non-Ambulatory Disabled Cattle ;


SUB CLINICAL PRION INFECTION MRC-43-00

Issued: Monday, 28 August 2000


NEW EVIDENCE OF SUB-CLINICAL PRION INFECTION: IMPORTANT RESEARCH FINDINGS RELEVANT TO CJD AND BSE



A team of researchers led by Professor John Collinge at the Medical Research Council Prion Unit1 report today in the Proceedings of the National Academy of Sciences, on new evidence for the existence of a 'sub-clinical' form of BSE in mice which was unknown until now. The scientists took a closer look at what is known as the 'species barrier' - the main protective factor which limits the ability of prions2 to jump from one species to infect another. They found the mice had a 'sub-clinical' form of disease where they carried high levels of infectivity but did not develop the clinical disease during their normal lifespan. The idea that individuals can carry a disease and show no clinical symptoms is not new. It is commonly seen in conventional infectious diseases. Researchers tried to infect laboratory mice with hamster prions3 called Sc237 and found that the mice showed no apparent signs of disease. However, on closer inspection they found that the mice had high levels of mouse prions in their brains. This was surprising because it has always been assumed that hamster prions could not cause the disease in mice, even when injected directly into the brain. In addition the researchers showed that this new sub-clinical infection could be easily passed on when injected into healthy mice and hamsters. The height of the species barrier varies widely between different combinations of animals and also varies with the type or strain of prions. While some barriers are quite small (for instance BSE easily infects mice), other combinations of strain and species show a seemingly impenetrable barrier. Traditionally, the particular barrier studied here was assumed to be robust. Professor John Collinge said: "These results have a number of important implications. They suggest that we should re-think how we measure species barriers in the laboratory, and that we should not assume that just because one species appears resistant to a strain of prions they have been exposed to, that they do not silently carry the infection. 9/13/2005

03-025IFA
03-025IFA-2
Terry S. Singeltary 2

Page 2 of 17

This research raises the possibility, which has been mentioned before, that apparently healthy cattle could harbour, but never show signs of, BSE. "This is a timely and unexpected result, increasing what we know about prion disease. These new findings have important implications for those researching prion disease, those responsible for preventing infected material getting into the food chain and for those considering how best to safeguard health and reduce the risk that theoretically, prion disease could be contracted through medical and surgical procedures."


ISSUED FRIDAY 25 AUGUST UNDER EMBARGO. PLEASE NOTE THAT THE EMBARGO IS SET BY THE JOURNAL. FOR FURTHER INFORMATION CONTACT THE MRC PRESS OFFICE ON 020 7637 6011 (OFFICE HOURS) OR 07818 428297 OR 0385 774357 (OUT-OF-OFFICE-HOURS) OR PROFESSOR JOHN COLLINGE ON 020 7594 3760. PLEASE NOTE THAT OWING TO TRAVEL COMMITMENTS PROFESSOR COLLINGE WILL ONLY BE AVAILABLE UNTIL 16.30 ON FRIDAY 25 AUGUST AND CONTACTABLE AGAIN ON MONDAY 28 AUGUST VIA THE MRC PRESS OFFICE. DR ANDREW HILL (A CO-AUTHOR ON THE PAPER) FROM THE DEPARTMENT OF PATHOLOGY AT THE UNIVERSITY OF MELBOURNE WILL BE AVAILABLE ON 00 61 3 8344 3995 (DURING OFFICE HOURS) OR 00 61 3 9443 0009 (OUT-OF-OFFICE HOURS). PLEASE NOTE THAT AUSTRALIA IS TEN HOURS AHEAD OF UK TIME. NOTES FOR EDITORS


Professor Collinge is a consultant neurologist and Director of the newly formed MRC Prion Unit based at The Imperial College School of Medicine at St Mary's Hospital. He is also a member of the UK Government's Spongiform Encephalopathy Advisory Committee (SEAC). The MRC prion unit is was set up in 1999, and its work includes molecular genetic studies of human prion disease and transgenic modelling of human prion diseases. Prions are unique infectious agents that cause fatal brain diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and BSE (mad cow disease) in animals. In some circumstances prions from one species of animals can infect another and it is clear that BSE has done this to cause the disease variant CJD in the UK and France. It remains unclear how large an epidemic of variant CJD will occur over the years ahead. The strain of prion used here to infect the mice is the Sc237 strain (also known as 263K) which infects hamsters, and until now was assumed not to infect mice. This research was funded by the Medical Research Council and Wellcome Trust. The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC's expenditure of £345 million is invested in over 50 of its Institutes and Units, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools. The Wellcome Trust is the world's largest medical research charity with a spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 5,000 researchers, at 400 locations, in 42 different countries to promote and foster research with the aim of improving human and animal health. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country's leading supporter of research into the history of medicine.


http://www.mrc.ac.uk/index/public_interest/public-press_office/public-press_releases_2000/public-mrc-43-00.htm


SNIP...FULL TEXT; 9/13/2005


Page 3 of 17


https://web01.aphis.usda.gov/regpublic.nsf/0/eff9eff1f7c5cf2b87256ecf000df08d?OpenDocument


http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf



GOING BACK FURTHER ;


British Medical Bulletin 66:161-170 (2003)
© 2003 The British Council


Subclinical prion infection in humans and animals
Andrew F Hill and John Collinge
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK

ABSTRACT


Transmission of prion diseases between mammalian species is limited by a so-called ‘species’ or ‘transmission’ barrier. Recognition of prion transmission usually relies on the appearance of clinical symptoms in inoculated animals and the interval between inoculation and appearance of clinical disease is designated incubation period. At some point during this clinically silent period, neuropathological and biochemical changes as well as accumulation of prions in the brain can be detected and this stage can be called preclinical prion disease. Recently, several lines of evidence have suggested that subclinical forms of prion disease exist, in which high levels of infectivity and PrPSc are found in animals that do not develop clinically apparent disease during a normal life-span. Such asymptomatic prion ‘carrier’ states challenge our current understanding of pathogenesis as well as of the molecular basis of barriers to transmission. Subclinical as well as preclinical/clinical prion disease may be relevant when analysing the risk to public health of potential sources of prion exposure.


snip...


CONCLUSIONS


The demonstration of PrPSc and infectivity in mice thought to be resistant to prions from a different species as well as clinically silent prion infection after same-species passage questions our current understanding of prion ‘species barriers’ and mechanisms of pathogenicity15. Assessment of ‘species barriers’ have relied on the failure of inoculated animals to develop clinical symptoms. From the studies discussed above, it now appears prudent to include molecular and neuropathological assessment of clinically healthy inoculated animals to exclude the possibility of subclinical prion infection. The possibility of iatrogenic transmission of vCJD is of obvious concern in public health issues and, given the results obtained from the experimental studies discussed above, warrants appropriate infection control guidelines to be considered when using surgical instruments and ‘at-risk’ tissues from apparently healthy humans for medical procedures. Further research into developing early, non-invasive diagnostic tests and defining molecular pathways involved in the long, clinically silent period of these diseases will be of great importance. Resulting insights could lead to early therapeutic strategies for these diseases and perhaps help solve the most enigmatic problem in the prion field at present – defining the neurotoxic and infectious entity at the molecular level.


http://bmb.oxfordjournals.org/cgi/content/full/66/1/161



I suggest you order Mark Purdey's new book, Animal Pharm, and read it. Before the next shoe drops; you better understand how the nuclear industry and military industrial complex are pulling the wool over your eyes.


purdey's shoe has done dropped, and fell, and he was wrong, OPs and Metals do not _cause_ TSE. once again ;


24. The project also generated information concerning the relation of
TSEs to environmental factors:
• __Potentially no role for organophosphates in TSEs.__
• Increased Mn in the diet results in higher PrP levels in the
brain.
• No conclusion is yet possible in terms of the relationship
between environmental trace element concentrations and the
geographical occurrence of TSEs (classical scrapie or BSE).
• Some confirmation was provided that in some specific farms
occurrence of classical scrapie correlates with high Mn levels.


http://www.seac.gov.uk/papers/97-4.pdf



a) As regards the involvement of organophosphates in the origin of BSE, no
new scientific
information providing evidence or supporting the hypothesis by valid data
became
available after the adoption of the last opinion of the SSC on this issue.
Consequently
there is no reason for modifying the existing opinions.
b) Regarding the possibility of OP poisoning, the European legislation for
registration of
plant protection products and veterinary medicines – addressed in the
enquiries – provide
the basis for safe use of registered compounds and their formulations.
Regarding the
alleged intoxication cases reported and OP exposure it must be concluded
that safety
measures may not have been strictly followed.
References
Brown, D.R., Qin, K., Herms, J.W., Madlung, A., Manson, J., Strome, R.,
Fraser, P.E., Kruck, T., von
Bohlen, A., Schulz- Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar,
H. (1997) The Cellular
Prion Protein Binds Copper In Vivo, Nature, 390, 684-7.
Purdey, M. (2000) Ecosystems Supporting Clusters of Sporadic TSEs
Demonstrate Excesses of the Radical-
Generating Divalent Cation Manganese and Deficiencies of Antioxidant
Co-Factors Cu, Se, Fe, Zn Medical
Hypotheses, 54, 278-306.
Scientific Steering Committee, 1998. Opinion on possible links between BSE
and Organophosphates. Adopted
on 25-26 June 1998
Scientific Steering Committee, 2001. Opinion on Hypotheses on the origin and
transmission of BSE. Adopted
on 29-30 November 2001.

http://europa.eu.int/comm/food/fs/sc/ssc/out356_en.pdf



OP'S MEETING WITH PURDEY

http://www.bseinquiry.gov.uk/files/yb/1994/02/09001001.pdf



transmission studies do not lie, amplification and transmission!


1: J Infect Dis 1980 Aug;142(2):205-8


Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of
sheep and goats were transmitted to squirrel monkeys (Saimiri
sciureus) that were exposed to the infectious agents only by their
nonforced consumption of known infectious tissues. The asymptomatic
incubation period in the one monkey exposed to the virus of kuru was
36 months; that in the two monkeys exposed to the virus of
Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and
that in the two monkeys exposed to the virus of scrapie was 25 and
32 months, respectively. Careful physical examination of the buccal
cavities of all of the monkeys failed to reveal signs or oral
lesions. One additional monkey similarly exposed to kuru has
remained asymptomatic during the 39 months that it has been under
observation.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract



look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused
7% (1 of 14) of the cows to come down with BSE;

Risk of oral infection with bovine spongiform encephalopathy agent in
primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie
Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe
Deslys
Summary The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease
(vCJD)--is compounded by incomplete knowledge about the efficiency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to
non-human primates. We gave two macaques a 5 g oral dose of brain homogenate
from a BSE-infected cow. One macaque developed vCJD-like neurological
disease 60 months after exposure, whereas the other remained free of disease
at 76 months. On the basis of these findings and data from other studies, we
made a preliminary estimate of the food exposure risk for man, which
provides additional assurance that existing public health measures can
prevent transmission of BSE to man.


snip...


BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%)
1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum
used in our study with primates against a bovine brain inoculum with a
similar PrPres concentration that was

inoculated into mice and cattle.8 *Data are number of animals
positive/number of animals surviving at the time of clinical onset of
disease in the first positive animal (%). The accuracy of

bioassays is generally judged to be about plus or minus 1 log. ic
ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected
orally with similar BSE brain inocula


Published online January 27, 2005

http://www.thelancet.com/journal/journal.isa


It is clear that the designing scientists must also have shared Mr Bradley’s
surprise at the results because all the dose levels right down to 1 gram
triggered infection.


http://www.bseinquiry.gov.uk/files/ws/s145d.pdf



and for Gods sake, if someone is smearing this [email protected] all over there kids
heads for lice and did not come up with a TSE, i would say this is good case
study;


UK FARMER WITH BSE


1) None of our animals that contracted BSE were treated with OP's, even
in utero.
2) My kids were treated with OP's as infants to control head lice. This
seems to be endemic as infection waves in UK primary schools (and
possibly elsewhere).
3) One might argue if the continued use of british beef in the UK was
ethical, none the less it happened. We have a duty to learn from it, not
least a duty to learn on behalf of those people who died so horribly....


However, i have never dusputed the remote possibility that ;


Phosmet induces up-regulation of surface levels of the cellular prion
protein.
Neuroreport. 9(7):1391-1395, May 11, 1998.
Gordon, Irit 1; Abdulla, Elizabeth M. 1; Campbell, Iain C. 1; Whatley,
Stephen A. 1,2
Abstract:
CHRONIC (2 day) exposure of human neuroblastoma cells to the organophosphate
pesticide phosmet induced a marked concentration-dependent increase in the
levels of PrP present on the cell surface as assessed by biotin labelling
and immunoprecipitation. Levels of both phospholipase C (PIPLC)-releasable
and non-releasable forms of PrP were increased on the plasma membrane. These
increases appear to be due to post-transcriptional mechanisms, since PrP
mRNA levels as assessed by Northern blotting were unaffected by phosmet
treatment. These data raise the possibility that phosmet exposure could
increase the _susceptibility to the prion agent by altering the levels of
accessible PrP_.

(C) Lippincott-Raven Publishers.


http://www.neuroreport.com/

http://www.ranchers.net/forum/about15704-0-asc-60.html


PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS
SEPTEMBER 2007

Date: Mon, 24 Sep 2007 21:31:55 -0500

I suggest that you all read the data out about h-BASE and sporadic CJD, GSS,
blood, and some of the other abstracts from the PRION2007. ...


please note transmission studies.......

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744


TSS
 
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