----- Original Message -----
From: Senator Kay Bailey Hutchison
To: flounder9@verizon.net
Sent: Monday, October 25, 2010 11:32 AM
Subject: Constituent Response From Senator Kay Bailey Hutchison
Dear Friend:
Thank you for contacting me regarding funding for Alzheimer’s disease. I welcome your thoughts and comments.
On July 22, 2009, Senator Barbara Mikulski (D-MD) introduced S. 1492, the Alzheimer’s Breakthrough Act. This bill would increase Alzheimer’s research funding through the National Institutes of Health (NIH) from $400 million to $2 billion in 2010. The legislation would also establish a National Summit on Alzheimer’s disease to coordinate researchers, policymakers and public health professionals. Additionally, it would expand the Alzheimer’s State Matching Grant Program as well as the Alzheimer’s 24/7 call center to provide updated resources and tools for caregivers, family members and those affected in a multilingual capacity.
The Alzheimer’s Breakthrough Act has been referred to the Senate Committee on Health, Education, Labor and Pensions, on which I do not serve. Should this legislation come before the full Senate for a vote, you may be certain I will keep your views in mind.
I am a strong proponent of biomedical research to help discover the causes of and cures for diseases like Alzheimer’s. I recently supported an amendment introduced by Senator Tom Harkin (D-IA) to H.R. 1, America’s Recovery and Reinvestment Act, which appropriated $6.5 billion to the NIH.
As a member of the Senate Appropriations Committee, I worked to include more than $945 million for chronic disease prevention, health promotion and genomics in the FY 2010 Labor, Health and Human Services, Education, and Related Agencies Appropriations Bill (H.R. 3293). This funding is almost a $65 million increase from FY 2009 and includes $2 million specifically for Alzheimer's disease. I also worked with the Committee to include approximately $1.1 billion for the National Institute on Aging (NIA) and strongly urged the NIA to devote more funding to clinical studies and the renewal of the Alzheimer's Disease Neuroimaging Initiative. H.R. 3293 was passed by the Senate Appropriations Committee on July 30, 2009, and is now ready to be considered by the full Senate.
I appreciate hearing from you, and I hope that you will not hesitate to contact me on any issue that is important to you.
Sincerely,
Kay Bailey Hutchison
United States Senator
284 Russell Senate Office Building
Washington, DC 20510
202-224-5922 (tel)
202-224-0776 (fax)
http://hutchison.senate.gov
PLEASE DO NOT REPLY to this message as this mailbox is only for the delivery of outbound messages, and is not monitored for replies. Due to the volume of mail Senator Hutchison receives, she requests that all email messages be sent through the contact form found on her website at http://hutchison.senate.gov/contact.cfm .
If you would like more information about issues pending before the Senate, please visit the Senator's website at http://hutchison.senate.gov . You will find articles, floor statements, and press releases, along with her weekly column and monthly television show on current events. You can also sign up to receive Senator Hutchison's weekly e-newsletter.
Thank you.
end
========================
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
http://betaamyloidcjd.blogspot.com/
2010 PRION UPDATE
Thursday, August 12, 2010
Seven main threats for the future linked to prions
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
TSS
Friday, October 22, 2010
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
http://betaamyloidcjd.blogspot.com/2010/10/peripherally-applied-containing.html
Showing posts with label CJD. Show all posts
Showing posts with label CJD. Show all posts
Thursday, October 28, 2010
Friday, October 22, 2010
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
Yvonne S. Eisele,1,2 Ulrike Obermüller,1,2 Götz Heilbronner,1,2,3 Frank Baumann,1,2 Stephan A. Kaeser,1,2
Hartwig Wolburg,4 Lary C. Walker,5 Matthias Staufenbiel,6 Mathias Heikenwalder,7 Mathias Jucker1,2*
1Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen,
Germany. 2DZNE - German Center for Neurodegenerative Diseases, Tübingen, Germany. 3Graduate School for Cellular and
Molecular Neuroscience, University of Tübingen, Tübingen, Germany. 4Department of Pathology, University of Tübingen,
Tübingen, Germany. 5Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA,
USA. 6Novartis Institutes for Biomedical Research, Neuroscience Discovery, Basel, Switzerland. 7Department of Pathology,
Institute for Neuropathology, University Hospital, Zürich, Switzerland.
*To whom correspondence should be addressed. E-mail: mathias.jucker@uni-tuebingen.de
The intracerebral injection of â-amyloid–containing brain extracts can induce cerebral â-amyloidosis and associated pathologies in susceptible hosts. Here, we found that intraperitoneal inoculation with â-amyloid–rich extracts induced â-amyloidosis in the brains of â-amyloid precursor protein transgenic mice after prolonged incubation times.
Intracerebral (i.c.) inoculation with minute amounts of brain extract containing misfolded ß-amyloid (Aß) from patients with Alzheimer’s Disease or from amyloid-bearing ß-amyloid precursor protein (APP) transgenic (tg) mice induces cerebral ß-amyloidosis and related pathologies in APP tg mice in a time- and concentration-dependent manner (1). However, oral, intravenous, intraocular, or intranasal inoculations have failed to induce cerebral ß-amyloidosis in APP tg hosts (2). These findings suggest that Aß-containing brain material in direct contact with the brain can induce cerebral ß-amyloidosis, but that, unlike prions, either the inducing agent is not readily conveyed from peripheral sites to the brain, or a higher concentration or longer incubation period is required for peripherally delivered Aß seeds.
Intraperitoneal (i.p.) administration of prion-rich material is more efficient at transmitting prion disease than is oral administration (3, 4). To test whether i.p. inoculation of Aß- rich material might similarly trigger Aß misfolding and deposition in the brain, we administered two i.p. injections (100 µl each, 1 week apart) of Aß-laden (10-20 ng/µl) brain extract from aged APP23 tg mice (Tg extract) to a cohort of young (2-month-old) female APP23 tg mice (5). After a 7-month incubation period, cerebral ß-amyloidosis was robustly induced in all i.p. inoculated mice compared to untreated littermate controls (Fig. 1). To confirm this finding, we inoculated a second cohort of 2-month-old female APP23 mice with a different batch of Tg brain extract in another laboratory (cohort 2: Tübingen, vs. cohort 1: Basel). After 6–7 months, mice injected i.p. with the Tg extract exhibited robust cerebral ß-amyloidosis, whereas i.p. inoculation with phosphate-buffered saline (PBS) or brain extract from agematched, non-tg wildtype mice (Wt extract) was ineffective (Fig. 1).
Induced ß-amyloidosis was strongest in the anterior and entorhinal cortices with additional deposition in the hippocampus, resembling the regional development of endogenous ß-amyloidosis in aged APP23 mice (6). However, whereas normal aged APP23 mice manifest mostly parenchymal deposits, the induced ß-amyloid in i.p. seeded mice was predominantly associated with blood vessels (cerebral ß-amyloid angiopathy [Aß-CAA]), often with massive spreading into the neighboring brain parenchyma (Fig. 1). The presence of Aß was confirmed by immunoblotting, and amyloid fibrils were evident ultrastructurally; in addition, the induced ß-amyloidosis was linked to gliosis, hyperphosphorylated tau, and other associated pathologies (Fig. 2), reminiscent of the cerebral ß-amyloid deposition in aged APP23 mice (6, 7).
To compare the efficiency and time course of i.p. versus i.c. inoculation, 2-month-old female APP23 mice were inoculated either i.p. (2 x 100 µl) or i.c. (2.5 µl into the hippocampus) with Tg extract, and then analyzed 4 months later. No cerebral ß-amyloid induction was found in any of the 4 i.p. inoculated mice, while all 6 i.c. inoculated mice revealed ß-amyloid induction identical to that previously reported (1, 2). From this observation, together with previous time course and 1:20 dilution experiments for i.c. inoculations (1), we estimate that i.p. inoculations with 103-fold more Aß take 2–5 months longer to induce cerebral ß-amyloidosis than do i.c. inoculations.
The replication of peripherally applied prions and their translocation into the central nervous system depend on hematopoietic and stromal immune cells, in combination with sympathetic innervation of abdominal lymphoid organs (8). Both activation of the immune system and chronic inflammation promote prion replication (9, 10). To assess the immune response to Aß-rich brain extracts, additional APP23 mice were given single i.p. injections of 200 µl Tg or Wt extract and sacrificed 1 hour, 1 week, or 1 month postinjection (5). An acute immune activation to the injected brain material was indicated by transient increases in plasma chemokines and cytokines (IL6, IL10, TNF-a, MCP-1, MIP-1ß) in both Tg and Wt extract-inoculated mice after 1 hour, with IL-6 still mildly elevated in Tg extract-injected mice 1 week post-inoculation (fig. S1). However, no signs of chronic inflammation in various peripheral organs (e.g. liver,pancreas, kidney, lung) or serum anti-Aß antibody titers were found in any mice investigated at 1 or 7 months postseeding (5). Moreover, no ß-amyloid deposition was found in any of the peripheral tissues at any time point studied.
Thus, like prion disease, cerebral ß-amyloidosis can be seeded in the brain by homologous protein aggregates delivered into the peritoneal cavity, although the i.p. route required more time and was less efficient than was direct injection into the brain (1, 2). The amyloid-inducing factor in the Tg extract is probably a species of misfolded Aß that is generated in its most effective form or composition in vivo (1). Because the expression of tg (human) APP is restricted to the nervous system in APP23 mice (7), in this model it is likely that the seed carried to the brain was the injected material itself, rather than Aß aggregates that were first amplified in peripheral tissues.
There is now persuasive evidence that the aggregation of Aß is a key pathogenic feature of AD and Aß-CAA (11–14), although the majority of these cases are initiated by unknown causes. The possibility that mechanisms exist allowing for the transport of Aß aggregates (and possibly other seeds) from the periphery to the brain justifies further studies to better understand the cellular and molecular origin of these diseases and to clarify the basis of infectious vs. non-infectious proteopathies (15, 16).
References and Notes
References and Notes
1. M. Meyer-Lühmann et al., Science 131, 1781 (2006).
2. Y. S. Eisele et al., Proc Natl Acad Sci USA 106, 12926
(2009).
3. S.B. Prusiner, Prion Biology and Diseases (Cold Spring
Harbor Laboratory Press), 2nd Ed pp. 1050 (2004).
4. R.H. Kimberlin, C.A. Walker, J Comp Path 88, 39 (1978).
5. For methods, see Supporting Online Material.
6. C. Sturchler-Pierrat et al., Proc Natl Acad Sci USA 94,
13287 (1997).
7. M.E. Calhoun et al., Proc Natl Acad Sci USA 96, 14088
(1999).
8. A. Aguzzi, C. Sigurdson, M. Heikenwälder, Ann Rev
Pathol Mech Dis 3, 11 (2008).
9. M. Heikenwalder et al., Science 307, 1107 (2005).
10. J. Bremer et al., PloS One 4, e7160 (2009).
11. J. Hardy, D. J. Selkoe, Science 297, 353 (2002).
12. M. Sorandt, M. A. Mintun, D. Head, J. C. Morris, Arch
Neurol 66, 1476 (2009).
13. J. C. Morris et al., Arch Neurol 66, 1469 (2009).
14. S. X. Zhang-Nunes et al., Brain Pathology 16, 30 (2006).
15. L. C. Walker, H. LeVine, M. P. Mattson, M. Jucker,
Trends Neurosci 29, 438 (2006).
16. A. Aguzzi, L. Rajendran, Neuron 64, 783 (2009).
17. We thank M.-J. Runser, L. Jacobson (Basel), F. Langer, J.
Coomaraswamy, S. Grathwohl, N. Varvel, T. Hamaguchi,
C. Schäfer, A. Bosch, G. Frommer-Kästle, U. Scheurlen
(Tübingen) for experimental help and A. Aguzzi (Zürich)
for insightful comments. Supported by the Competence
Network on Degenerative Dementias (BMBF-01GI0705),
the BMBF in the frame of ERA-Net NEURON
(MIPROTRAN), the CIN (DFG), and NIH RR-00165.
Supporting Online Material
www.sciencemag.org/cgi/content/full/science.1194516/DC1
Materials and Methods
Fig. S1
References
1 July 2010; accepted 24 September 2010
Published online 21 October 2010; 10.1126/science.1194516
Fig. 1. Induced Aß deposition. (A and B) Aß-immunostained frontal cortex of Tg extract- (A) and Wt extract- (B) i.p. inoculated APP23 mice. (C and D) Most induced ß-amyloid was vascular (Aß-CAA), with Aß-immunoreactivity extending into the brain parenchyma (arrows). Amyloid-laden vessels were congophilic (red in D; birefringent under crosspolarized light, insert) and often were surrounded by diffuse, Congo red-negative Aß deposits (arrowheads). (E and F) Analysis of the entire neocortex for Aß-CAA frequency (indicated are all three [I-III] CAA severity grades [5]), and for total Aß load in Tg extract-inoculated mice compared to control (Ctr) mice. Cohort 1 consisted of 6 Tg extractinoculated mice vs. 7 untreated control mice. Aß-CAA: t(11) = 6.78 (all severity grades combined), ***P < 0.0001; Aß load: t(11) = 8.79, ***P < 0.0001. Cohort 2 consisted of 5 Tg extract-inoculated mice vs. 5 Wt extract-inoculated mice and 4 PBS-injected mice. These latter 2 (control) groups did not differ significantly, and were combined for analysis. Aß-CAA: t(12) = 7.79, ***P < 0.0001; Aß load t(12) = 2.71, *P < 0.05. The occasional parenchymal Aß-deposits in control mice are normal for 9-month-old APP23 mice. Indicated are means ±SEM. Scale bars: 200 µm (A,B); 50 µm (C,D).
Fig. 2. Induced Aß deposition was linked to multiple associated pathologies. (A) Ultrastructural analysis showed amyloid deposition within the vascular basal lamina (BL), with typical amyloid fibrils (arrowheads) extending into the brain parenchyma. Insets are low- and high-magnification views of the examined vessel (L = lumen) and the typical non-branching amyloid fibrils. (B to E) Vascular amyloid(stained by Congo Red in B and C) and parenchymal plaques were surrounded by hypertrophic, Iba1-positive microglia (B), GFAP-positive astrocytes (C), hyperphosphorylated taupositive neurites (D; asterisk indicates amyloid core), but a paucity of proximate neurons (cresyl-violet stain, E). (F and G) Vessels with CAA types II and III showed smooth muscle cell loss at the site of amyloid deposition (arrowheads; confocal image, maximum projection of 5 µm z-stack: red, Aß; green, smooth muscle actin). A normal vessel (G) has a complete ring of smooth muscle cells. (H) Immunoblotting of micropunches of Aß-immunoreactive material revealed the expected Aß band. Synthetic Aß40/42 is shown as control. Markers = 3 and 6 kD. Scale bars: 1 µm (A; insets 5 and 0.5 µm); 50 µm (B-E); 10 µm (F, G).
end...see ;
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
http://www.sciencemag.org/cgi/content/abstract/science.1194516
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
http://betaamyloidcjd.blogspot.com/
2010 PRION UPDATE
Thursday, August 12, 2010
Seven main threats for the future linked to prions
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
TSS
Yvonne S. Eisele,1,2 Ulrike Obermüller,1,2 Götz Heilbronner,1,2,3 Frank Baumann,1,2 Stephan A. Kaeser,1,2
Hartwig Wolburg,4 Lary C. Walker,5 Matthias Staufenbiel,6 Mathias Heikenwalder,7 Mathias Jucker1,2*
1Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen,
Germany. 2DZNE - German Center for Neurodegenerative Diseases, Tübingen, Germany. 3Graduate School for Cellular and
Molecular Neuroscience, University of Tübingen, Tübingen, Germany. 4Department of Pathology, University of Tübingen,
Tübingen, Germany. 5Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, GA,
USA. 6Novartis Institutes for Biomedical Research, Neuroscience Discovery, Basel, Switzerland. 7Department of Pathology,
Institute for Neuropathology, University Hospital, Zürich, Switzerland.
*To whom correspondence should be addressed. E-mail: mathias.jucker@uni-tuebingen.de
The intracerebral injection of â-amyloid–containing brain extracts can induce cerebral â-amyloidosis and associated pathologies in susceptible hosts. Here, we found that intraperitoneal inoculation with â-amyloid–rich extracts induced â-amyloidosis in the brains of â-amyloid precursor protein transgenic mice after prolonged incubation times.
Intracerebral (i.c.) inoculation with minute amounts of brain extract containing misfolded ß-amyloid (Aß) from patients with Alzheimer’s Disease or from amyloid-bearing ß-amyloid precursor protein (APP) transgenic (tg) mice induces cerebral ß-amyloidosis and related pathologies in APP tg mice in a time- and concentration-dependent manner (1). However, oral, intravenous, intraocular, or intranasal inoculations have failed to induce cerebral ß-amyloidosis in APP tg hosts (2). These findings suggest that Aß-containing brain material in direct contact with the brain can induce cerebral ß-amyloidosis, but that, unlike prions, either the inducing agent is not readily conveyed from peripheral sites to the brain, or a higher concentration or longer incubation period is required for peripherally delivered Aß seeds.
Intraperitoneal (i.p.) administration of prion-rich material is more efficient at transmitting prion disease than is oral administration (3, 4). To test whether i.p. inoculation of Aß- rich material might similarly trigger Aß misfolding and deposition in the brain, we administered two i.p. injections (100 µl each, 1 week apart) of Aß-laden (10-20 ng/µl) brain extract from aged APP23 tg mice (Tg extract) to a cohort of young (2-month-old) female APP23 tg mice (5). After a 7-month incubation period, cerebral ß-amyloidosis was robustly induced in all i.p. inoculated mice compared to untreated littermate controls (Fig. 1). To confirm this finding, we inoculated a second cohort of 2-month-old female APP23 mice with a different batch of Tg brain extract in another laboratory (cohort 2: Tübingen, vs. cohort 1: Basel). After 6–7 months, mice injected i.p. with the Tg extract exhibited robust cerebral ß-amyloidosis, whereas i.p. inoculation with phosphate-buffered saline (PBS) or brain extract from agematched, non-tg wildtype mice (Wt extract) was ineffective (Fig. 1).
Induced ß-amyloidosis was strongest in the anterior and entorhinal cortices with additional deposition in the hippocampus, resembling the regional development of endogenous ß-amyloidosis in aged APP23 mice (6). However, whereas normal aged APP23 mice manifest mostly parenchymal deposits, the induced ß-amyloid in i.p. seeded mice was predominantly associated with blood vessels (cerebral ß-amyloid angiopathy [Aß-CAA]), often with massive spreading into the neighboring brain parenchyma (Fig. 1). The presence of Aß was confirmed by immunoblotting, and amyloid fibrils were evident ultrastructurally; in addition, the induced ß-amyloidosis was linked to gliosis, hyperphosphorylated tau, and other associated pathologies (Fig. 2), reminiscent of the cerebral ß-amyloid deposition in aged APP23 mice (6, 7).
To compare the efficiency and time course of i.p. versus i.c. inoculation, 2-month-old female APP23 mice were inoculated either i.p. (2 x 100 µl) or i.c. (2.5 µl into the hippocampus) with Tg extract, and then analyzed 4 months later. No cerebral ß-amyloid induction was found in any of the 4 i.p. inoculated mice, while all 6 i.c. inoculated mice revealed ß-amyloid induction identical to that previously reported (1, 2). From this observation, together with previous time course and 1:20 dilution experiments for i.c. inoculations (1), we estimate that i.p. inoculations with 103-fold more Aß take 2–5 months longer to induce cerebral ß-amyloidosis than do i.c. inoculations.
The replication of peripherally applied prions and their translocation into the central nervous system depend on hematopoietic and stromal immune cells, in combination with sympathetic innervation of abdominal lymphoid organs (8). Both activation of the immune system and chronic inflammation promote prion replication (9, 10). To assess the immune response to Aß-rich brain extracts, additional APP23 mice were given single i.p. injections of 200 µl Tg or Wt extract and sacrificed 1 hour, 1 week, or 1 month postinjection (5). An acute immune activation to the injected brain material was indicated by transient increases in plasma chemokines and cytokines (IL6, IL10, TNF-a, MCP-1, MIP-1ß) in both Tg and Wt extract-inoculated mice after 1 hour, with IL-6 still mildly elevated in Tg extract-injected mice 1 week post-inoculation (fig. S1). However, no signs of chronic inflammation in various peripheral organs (e.g. liver,pancreas, kidney, lung) or serum anti-Aß antibody titers were found in any mice investigated at 1 or 7 months postseeding (5). Moreover, no ß-amyloid deposition was found in any of the peripheral tissues at any time point studied.
Thus, like prion disease, cerebral ß-amyloidosis can be seeded in the brain by homologous protein aggregates delivered into the peritoneal cavity, although the i.p. route required more time and was less efficient than was direct injection into the brain (1, 2). The amyloid-inducing factor in the Tg extract is probably a species of misfolded Aß that is generated in its most effective form or composition in vivo (1). Because the expression of tg (human) APP is restricted to the nervous system in APP23 mice (7), in this model it is likely that the seed carried to the brain was the injected material itself, rather than Aß aggregates that were first amplified in peripheral tissues.
There is now persuasive evidence that the aggregation of Aß is a key pathogenic feature of AD and Aß-CAA (11–14), although the majority of these cases are initiated by unknown causes. The possibility that mechanisms exist allowing for the transport of Aß aggregates (and possibly other seeds) from the periphery to the brain justifies further studies to better understand the cellular and molecular origin of these diseases and to clarify the basis of infectious vs. non-infectious proteopathies (15, 16).
References and Notes
References and Notes
1. M. Meyer-Lühmann et al., Science 131, 1781 (2006).
2. Y. S. Eisele et al., Proc Natl Acad Sci USA 106, 12926
(2009).
3. S.B. Prusiner, Prion Biology and Diseases (Cold Spring
Harbor Laboratory Press), 2nd Ed pp. 1050 (2004).
4. R.H. Kimberlin, C.A. Walker, J Comp Path 88, 39 (1978).
5. For methods, see Supporting Online Material.
6. C. Sturchler-Pierrat et al., Proc Natl Acad Sci USA 94,
13287 (1997).
7. M.E. Calhoun et al., Proc Natl Acad Sci USA 96, 14088
(1999).
8. A. Aguzzi, C. Sigurdson, M. Heikenwälder, Ann Rev
Pathol Mech Dis 3, 11 (2008).
9. M. Heikenwalder et al., Science 307, 1107 (2005).
10. J. Bremer et al., PloS One 4, e7160 (2009).
11. J. Hardy, D. J. Selkoe, Science 297, 353 (2002).
12. M. Sorandt, M. A. Mintun, D. Head, J. C. Morris, Arch
Neurol 66, 1476 (2009).
13. J. C. Morris et al., Arch Neurol 66, 1469 (2009).
14. S. X. Zhang-Nunes et al., Brain Pathology 16, 30 (2006).
15. L. C. Walker, H. LeVine, M. P. Mattson, M. Jucker,
Trends Neurosci 29, 438 (2006).
16. A. Aguzzi, L. Rajendran, Neuron 64, 783 (2009).
17. We thank M.-J. Runser, L. Jacobson (Basel), F. Langer, J.
Coomaraswamy, S. Grathwohl, N. Varvel, T. Hamaguchi,
C. Schäfer, A. Bosch, G. Frommer-Kästle, U. Scheurlen
(Tübingen) for experimental help and A. Aguzzi (Zürich)
for insightful comments. Supported by the Competence
Network on Degenerative Dementias (BMBF-01GI0705),
the BMBF in the frame of ERA-Net NEURON
(MIPROTRAN), the CIN (DFG), and NIH RR-00165.
Supporting Online Material
www.sciencemag.org/cgi/content/full/science.1194516/DC1
Materials and Methods
Fig. S1
References
1 July 2010; accepted 24 September 2010
Published online 21 October 2010; 10.1126/science.1194516
Fig. 1. Induced Aß deposition. (A and B) Aß-immunostained frontal cortex of Tg extract- (A) and Wt extract- (B) i.p. inoculated APP23 mice. (C and D) Most induced ß-amyloid was vascular (Aß-CAA), with Aß-immunoreactivity extending into the brain parenchyma (arrows). Amyloid-laden vessels were congophilic (red in D; birefringent under crosspolarized light, insert) and often were surrounded by diffuse, Congo red-negative Aß deposits (arrowheads). (E and F) Analysis of the entire neocortex for Aß-CAA frequency (indicated are all three [I-III] CAA severity grades [5]), and for total Aß load in Tg extract-inoculated mice compared to control (Ctr) mice. Cohort 1 consisted of 6 Tg extractinoculated mice vs. 7 untreated control mice. Aß-CAA: t(11) = 6.78 (all severity grades combined), ***P < 0.0001; Aß load: t(11) = 8.79, ***P < 0.0001. Cohort 2 consisted of 5 Tg extract-inoculated mice vs. 5 Wt extract-inoculated mice and 4 PBS-injected mice. These latter 2 (control) groups did not differ significantly, and were combined for analysis. Aß-CAA: t(12) = 7.79, ***P < 0.0001; Aß load t(12) = 2.71, *P < 0.05. The occasional parenchymal Aß-deposits in control mice are normal for 9-month-old APP23 mice. Indicated are means ±SEM. Scale bars: 200 µm (A,B); 50 µm (C,D).
Fig. 2. Induced Aß deposition was linked to multiple associated pathologies. (A) Ultrastructural analysis showed amyloid deposition within the vascular basal lamina (BL), with typical amyloid fibrils (arrowheads) extending into the brain parenchyma. Insets are low- and high-magnification views of the examined vessel (L = lumen) and the typical non-branching amyloid fibrils. (B to E) Vascular amyloid(stained by Congo Red in B and C) and parenchymal plaques were surrounded by hypertrophic, Iba1-positive microglia (B), GFAP-positive astrocytes (C), hyperphosphorylated taupositive neurites (D; asterisk indicates amyloid core), but a paucity of proximate neurons (cresyl-violet stain, E). (F and G) Vessels with CAA types II and III showed smooth muscle cell loss at the site of amyloid deposition (arrowheads; confocal image, maximum projection of 5 µm z-stack: red, Aß; green, smooth muscle actin). A normal vessel (G) has a complete ring of smooth muscle cells. (H) Immunoblotting of micropunches of Aß-immunoreactive material revealed the expected Aß band. Synthetic Aß40/42 is shown as control. Markers = 3 and 6 kD. Scale bars: 1 µm (A; insets 5 and 0.5 µm); 50 µm (B-E); 10 µm (F, G).
end...see ;
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
http://www.sciencemag.org/cgi/content/abstract/science.1194516
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
http://betaamyloidcjd.blogspot.com/
2010 PRION UPDATE
Thursday, August 12, 2010
Seven main threats for the future linked to prions
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
TSS
Tuesday, July 27, 2010
Commons Hansard for The United Kingdom Parliament Written Answers for 26 July 2010 Alzheimer's and CJD
Commons Hansard for The United Kingdom Parliament Written Answers for 26 July 2010 Alzheimer's and CJD
CJD
Mr Weir: To ask the Secretary of State for Health what testing of the relatives of individuals affected by variant Creutzfeldt-Jakob disease his Department undertakes. [10942]
Anne Milton: The Department does not undertake any such testing.
There is no blood or other test currently available for routine variant Creutzfeldt-Jakob disease testing of asymptomatic individuals.
26 July 2010 : Column 823W
Mr Weir: To ask the Secretary of State for Health what recent estimate his Department has made of the time taken for variant Creutzfeldt-Jakob disease to incubate. [10945]
Anne Milton: The incubation period for variant Creutzfeldt-Jakob disease (vCJD) is unknown and may vary due to factors such as route of transmission and genotype of patient. For the majority of cases where consumption of meat or meat products is presumed to be the route of infection the minimum incubation period is likely to be five years, with a mean period of around 10-12 years and the maximum, as in other human transmissible spongiform encephalopathies, may extend over decades. Of the three clinical cases of vCJD presumed to be associated with blood transfusion the incubation periods are estimated to be between six and nine years.
Mr Weir: To ask the Secretary of State for Health (1) how many cases of variant Creutzfeldt-Jakob disease affecting the MV gene type have been reported in (a) Scotland, (b) Wales, (c) England and (d) Northern Ireland since 1996; [11005]
(2) how many cases of (a) definite, (b) probable and (c) possible variant Creutzfeldt-Jakob disease of the MV gene type have been recorded since 1996; [11006]
(3) how many deaths from variant Creutzfeldt-Jakob disease among people with (a) MM variations, (b) MV variations and (c) VV variations there have been since 1996. [11008]
Anne Milton: There have been no definite or probable cases of variant Creutzfeldt-Jakob disease (vCJD) in patients with a MV genotype. A single possible case of vCJD in a patient with a MV genotype was reported in 2008 in Scotland. This case is recorded in the 17th Annual Report of the National Creutzfeldt-Jakob disease Surveillance Unit published in November 2009 and publicly available at:
www.cjd.ed.ac.uk/report17.htm
The 17th Annual Report records that of the four patients with a final classification of possible vCJD, three were of the MM genotype and only one of MV genotype.
The MV case has also been described in a publication: "Variant CJD in an individual heterozygous for PRNP codon 129 Kaski D, Mead S, Hyare H, Cooper S, Jampana R, Overell J, Knight R, Collinge J, Rudge Lancet 2009. 374:212.
The National Creutzfeldt-Jakob disease Surveillance Unit has provided the following information about deaths from vCJD:
United Kingdom definite and probable vCJD deaths 1995 to 2010
Number deaths Genotype known Genotype unknown MM MV VV
1995 3 0 3 0
1996 10 0 10 0
1997 10 0 10 0
1998 18 0 18 0
1999 15 0 15 0
2000 28 25 3 25 0
2001 20 18 2 18 0
2002 17 15 2 15 0
2003 18 8 10 8 0
2004 9 8 1 8 0
26 July 2010 : Column 824W 2005 5 0 5 0
2006 5 0 5 0
2007 5 0 5 0
2008 1 0 1 0
2009 3 0 3 0
2010 2 0 2 0
Total 169 151 18 151 0
Mr Weir: To ask the Secretary of State for Health what definition of (a) probable and (b) possible his Department uses in the identification of variant Creutzfeldt-Jakob disease cases. [11007]
Anne Milton: The Department uses the internationally recognised World Health Organisation diagnostic criteria for case classification, research protocols and official statistics. These are publicly available at:
www.who.int/entity/zoonoses/diseases/Creutzfeldt.pdf
http://www.publications.parliament.uk/pa/cm201011/cmhansrd/cm100726/text/100726w0008.htm#10072719000041
Alzheimer's Disease: Cumbria John Stevenson: To ask the Secretary of State for Health (1) how much funding has been allocated to caring for people with Alzheimer's disease in (a) Cumbria and (b) Carlisle constituency for the next 12 months. [10759]
(2) how many people in (a) Cumbria and (b) Carlisle constituency have been diagnosed with Alzheimer's disease. [10760]
Mr Burstow: The Department currently allocates funding directly to primary care trusts (PCTs). PCT allocations are not broken down by policy area. PCTs make decisions on investment in health care for their communities, taking into account both local and national priorities.
In 2010-11, Cumbria Teaching PCT received a revenue allocation of £826.9 million. Data on the number of people diagnosed with Alzheimer's disease is not collected centrally. However, the Quality and Outcomes Framework includes a disease register for patients who have been diagnosed with any form of dementia (including Alzheimer's disease). The latest available figures are for 2008-09.
There were .3,114 patients on the dementia register in Cumbria PCT in 2008-09. The figures are organised by practice and aggregated into PCT and strategic health authority. It is therefore not possible to give figures for Carlisle constituency.
Notes:
1. QOF: QOF is the national Quality and Outcomes Framework, introduced as part of the new General Medical Services (GMS) contract on 1 April 2004. Participation by practices in the QOF is voluntary, though participation rates are very high, with most Personal Medical Services (PMS) practices also taking part.
2. The published QOF information was derived from the Quality Management Analysis System (QMAS), a national system developed by NHS Connecting for Health.
3. QMAS uses data from general practices to calculate individual practices' QOF achievement. QMAS is a national IT system developed by NHS Connecting for Health to support the QOF. The Quality Management Analysis System captures the number of patients on the various disease registers for each practice.
http://www.publications.parliament.uk/pa/cm201011/cmhansrd/cm100726/text/100726w0008.htm#10072719000040
Greetings,
For anyone that cares, from 1993 to 2005, a steady increase of sporadic CJD from 27 in 1993, to 104 in 2005, tapering off to 94 in 2006, and 88 in 2007, which seems to correlate to other BSE countries, which to me shows a relationship with human Sporadic CJD rising and falling along the same lines as the BSE cases. Course, nobody cares about that factor because of the UKBSEnvCJD only theory. nobody cares that in fact what Collinge, Asante et al showed, that BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein, but who cares about sound science anymore $
2002
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: j.collinge@prion.ucl.ac.ukReceived August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002. This article has been cited by other articles in PMC. Other Sections?
Abstract
Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Keywords: BSE/Creutzfeldt-Jakob disease/prion/transgenic
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC136957/?tool=pubmed
2004
Originally published in Science Express on 11 November 2004 Science 3 December 2004: Vol. 306. no. 5702, pp. 1793 - 1796 DOI: 10.1126/science.1103932
Reports Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype Jonathan D. F. Wadsworth, Emmanuel A. Asante, Melanie Desbruslais, Jacqueline M. Linehan, Susan Joiner, Ian Gowland, Julie Welch, Lisa Stone, Sarah E. Lloyd, Andrew F. Hill,* Sebastian Brandner, John Collinge
Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.
Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
* Present address: Department of Biochemistry and Molecular Biology and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.
To whom correspondence should be addressed. E-mail: j.collinge@prion.ucl.ac.uk
http://www.sciencemag.org/cgi/content/abstract/306/5702/1793
2008
Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD
The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.
Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.
Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission.
snip...
Discussion Top In this study we used tg650 mice, a newly developed transgenic line expressing human PrPC, to investigate some aspects of the pathogenesis of vCJD infection. As main findings, we demonstrate that prion strain divergence can occur upon transmission of human, primary vCJD to such mice, and that peripheral challenge leads to an asymptomatic, life-long infection of the lymphoid compartment. A feature of tg650 mice is that following primary intracerebral vCJD challenge they developed a neurological disease with typically 100% attack rate, unlike for previously established PrP129Met, including overexpressing lines [16], [19]. The mean survival time - typically around 500 days in homozygous mice - did not change notably on subpassaging, implying that vCJD agent might clinically infect the tg650 mice with little or no transmission barrier. This discrepant result may reflect the use of different constructs and genetic backgrounds (Text S1), and the transgene expression levels, although the latter does not seem to greatly differ as far as the tg650+/- and tg45 mice [16] are concerned.
A surprising result of these studies is the alternate pattern of disease that was induced by one of the inoculated vCJD cases, a WHO reference case here designated vCJD no. 4. Indeed, while vCJD strain features were faithfully propagated in the majority of tg650 mice, almost half of the vCJD 4-inoculated mice were found to propagate a prion replicating faster than vCJD agent, and exhibiting sCJD-like PrPres and neuropathological features. Although strain divergence upon transmission of BSE/vCJD agent to mice was reported to occur in earlier studies [16], [24], it was unprecedented within a context of homotypic transmission, i.e. full matching between the donor and receiver PrP sequences. To address the issue of a possible contamination, we performed independent transmission experiments, involving separate inoculum batches of the incriminated case, which all produced consistent results. Therefore, we consider the data inconsistent with contamination of the VCJD no. 4 material by a sCJD infectious source within our laboratory. An alternate possibility, i.e. a cross-contamination of the source material, was judged highly improbable owing to the procedures applied during the collect of the specimen and the preparation of the homogenates ([25] and P. Minor, personal communication). On the other hand, our observation intriguingly parallels the phenotypic disjunction observed upon transmission of BSE agent to human PrP129Met mice (tg35 line [16]). Together, these findings lend support to the hypothesis that a minor strain component might be created upon cattle-to-human transmission of BSE agent and could emerge upon subsequent human-to-human transmission. It is also worth mentioning that, while the probability to detect such a variant through mouse bioassay would be expected to depend on the amount - and possibly the regions - of brain tissue taken to establish the source material, the vCJD-4 homogenate was prepared using a larger amount of tissue from the same brain than for the other homogenates analyzed in this study (i.e. 100 mg instead of 1 mg of frontal cortex [25]).
The above finding has obvious implications in terms of public health as it raises the concern that some humans iatrogenically infected by vCJD agent may develop a clinical disease that would not be recognized as of vCJD origin [17], [26]. Strikingly however, all vCJD-4-inoculated mice, notwithstanding the strain phenotype divergence propagated bona fide vCJD agent in their spleen, based on the PrPres pattern and the disease phenotype produced by secondary transmission to tg650 mice. This result is of direct relevance to the diagnosis of variant and sporadic CJD. Indeed, looking for peripheral lymphoreticular deposition of abnormal PrP on cases diagnosed as sporadic CJD might reveal a vCJD infection resulting from human-to-human, or cattle-to-human transmission. In this respect, it would be of interest to examine whether BSE-inoculated tg35 mice showing discordant PrPres signatures [16], or vCJD-challenged PrP129Val transgenic mice producing 'type 5' prion in their brain [17] do accumulate PrPvCJD in their spleens. In any case, our findings provide clear evidence that, as a consequence of strain-related tropism disparities, the same mouse can propagate different prions in different tissues following a single infection event.
Another salient finding emerging from this study was the remarkable ability of vCJD agent to establish asymptomatic infection despite sustained, life-long propagation in extraneural tissues. When challenged peripherally, tg650 mice remained asymptomatic over the whole observation period, and did not accumulate PrPres at detectable levels in their brain before 750 days pi, near the life end-stage. In the spleen of these mice however, PrPres accumulation reached its maximum at an early stage of infection, and remained at stable and substantial levels until death. Plateauing of prion infection in the spleen is consistent with earlier observations, and has been suggested to reflect an exhaustion of target cells (for review [22]) Importantly, the spleen tissue was highly infectious as it killed 100% of intracerebrally challenged mice within the minimal mean incubation time (~500 days). Altogether these data support the view that the sustained multiplication of the vCJD prion in lymphoid tissues was not accompanied by an efficient neuroinvasion in tg650 mice. Such an extremely delayed neuroinvasion appears to be rare in TSE rodent models, and to our knowledge was only reported for the mouse-adapted strain 87V on IM mice infected intraperitoneally with diluted inoculum [27]. Clearly, while early accumulation of prions in lymphoid tissues may be essential for efficient neuroinvasion [22], efficient lymphoinvasion does not inevitably lead to rapid neuroinvasion. This finding strengthens the notion that humans infected by vCJD from a human source - including individuals of the MM genotype - might remain clinically asymptomatic for a very prolonged period of time while harboring relatively high levels of prion infectivity in their lymphoid tissues from an early stage of infection on, thereby amplifying the risk of iatrogenic transmission. It also supports the view that the large-scale survey of lymphoreticular tissues [28] may lead to a reliable assessment of the actual prevalence of vCJD infection in the UK population.
Finally, the human PrP transgenic model described in this study may help to further our understanding of peripheral vCJD pathogenesis, for instance in trying to identify factors that might enhance neuroinvasion efficiency, or modulate the shedding of prion infectivity from the lymphoreticular to the blood compartment. Moreover, preliminary results indicate that the search for abnormal PrP in the spleen of such mice culled at time intervals post infection [29], [30] could allow the detection of low levels of vCJD infectivity within a reasonably short time scale.
Citation: Béringue V, Le Dur A, Tixador P, Reine F, Lepourry L, et al. (2008) Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD. PLoS ONE 3(1): e1419. doi:10.1371/journal.pone.0001419
Academic Editor: Adam Ratner, Columbia University, United States of America
Received: September 20, 2007; Accepted: December 17, 2007; Published: January 9, 2008
Copyright: © 2008 Beringue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by INRA, Institut de Veille Sanitaire (InVS) and the Ministry of Research, France. The sponsors of this study had no role in study conduct, collection analysis, interpretation of the data, writing of the report or approval of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* To whom correspondence should be addressed. E-mail: hubert.laude@jouy.inra.fr (HL); vincent.beringue@jouy.inra.fr (VB)
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001419
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html
Thursday, July 08, 2010
Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/nosocomial-transmission-of-sporadic.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
please see full text ;
Wednesday, March 31, 2010
Atypical BSE in Cattle
http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
Monday, October 19, 2009
Atypical BSE, BSE, and other human and animal TSE in North America Update October 2009
http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER
>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas. She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-
Physician Discharge Summary, Parkland Hospital, Dallas Texas
Admit Date: 12/29/2009 Discharge Date: 1/20/2010
Attending Provider: Greenberg, Benjamin Morris;
General Neurology Team: General Neurology Team Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence. She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers. The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.
http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8
>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<
please see full text ;
Monday, March 29, 2010
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
http://creutzfeldt-jakob-disease.blogspot.com/2010/03/irma-linda-andablo-cjd-victim-she-died.html
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER
http://cjdtexas.blogspot.com/2010/03/cjd-texas-38-year-old-female-worked.html
USA sporadic CJD cases rising ;
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection. He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Friday, February 05, 2010
New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review
http://vcjd.blogspot.com/2010/02/new-variant-creutzfelt-jakob-disease.html
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Archive Number 20100405.1091 Published Date 05-APR-2010 Subject PRO/AH/EDR> Prion disease update 1010 (04)
snip...
[Terry S. Singeltary Sr. has added the following comment:
"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.
The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"
http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101
Saturday, July 17, 2010
Variant Creutzfeldt-Jakob disease Ironside JW., Haemophilia. 2010 Jul;16 Suppl 5:175-80
REVIEW ARTICLE
http://vcjdtransfusion.blogspot.com/2010/07/variant-creutzfeldtjakob-disease.html
Sunday, July 18, 2010
Alzheimer's Assocition International Conference on Alzheimer's Disease (updated diagnostic criteria) 2010 July 10 - 15 Honolulu, Hawaii
snip...
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, March 31, 2010
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
snip...
see full text ;
http://betaamyloidcjd.blogspot.com/2010/07/alzheimers-assocition-international.html
http://betaamyloidcjd.blogspot.com/
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
CJD
Mr Weir: To ask the Secretary of State for Health what testing of the relatives of individuals affected by variant Creutzfeldt-Jakob disease his Department undertakes. [10942]
Anne Milton: The Department does not undertake any such testing.
There is no blood or other test currently available for routine variant Creutzfeldt-Jakob disease testing of asymptomatic individuals.
26 July 2010 : Column 823W
Mr Weir: To ask the Secretary of State for Health what recent estimate his Department has made of the time taken for variant Creutzfeldt-Jakob disease to incubate. [10945]
Anne Milton: The incubation period for variant Creutzfeldt-Jakob disease (vCJD) is unknown and may vary due to factors such as route of transmission and genotype of patient. For the majority of cases where consumption of meat or meat products is presumed to be the route of infection the minimum incubation period is likely to be five years, with a mean period of around 10-12 years and the maximum, as in other human transmissible spongiform encephalopathies, may extend over decades. Of the three clinical cases of vCJD presumed to be associated with blood transfusion the incubation periods are estimated to be between six and nine years.
Mr Weir: To ask the Secretary of State for Health (1) how many cases of variant Creutzfeldt-Jakob disease affecting the MV gene type have been reported in (a) Scotland, (b) Wales, (c) England and (d) Northern Ireland since 1996; [11005]
(2) how many cases of (a) definite, (b) probable and (c) possible variant Creutzfeldt-Jakob disease of the MV gene type have been recorded since 1996; [11006]
(3) how many deaths from variant Creutzfeldt-Jakob disease among people with (a) MM variations, (b) MV variations and (c) VV variations there have been since 1996. [11008]
Anne Milton: There have been no definite or probable cases of variant Creutzfeldt-Jakob disease (vCJD) in patients with a MV genotype. A single possible case of vCJD in a patient with a MV genotype was reported in 2008 in Scotland. This case is recorded in the 17th Annual Report of the National Creutzfeldt-Jakob disease Surveillance Unit published in November 2009 and publicly available at:
www.cjd.ed.ac.uk/report17.htm
The 17th Annual Report records that of the four patients with a final classification of possible vCJD, three were of the MM genotype and only one of MV genotype.
The MV case has also been described in a publication: "Variant CJD in an individual heterozygous for PRNP codon 129 Kaski D, Mead S, Hyare H, Cooper S, Jampana R, Overell J, Knight R, Collinge J, Rudge Lancet 2009. 374:212.
The National Creutzfeldt-Jakob disease Surveillance Unit has provided the following information about deaths from vCJD:
United Kingdom definite and probable vCJD deaths 1995 to 2010
Number deaths Genotype known Genotype unknown MM MV VV
1995 3 0 3 0
1996 10 0 10 0
1997 10 0 10 0
1998 18 0 18 0
1999 15 0 15 0
2000 28 25 3 25 0
2001 20 18 2 18 0
2002 17 15 2 15 0
2003 18 8 10 8 0
2004 9 8 1 8 0
26 July 2010 : Column 824W 2005 5 0 5 0
2006 5 0 5 0
2007 5 0 5 0
2008 1 0 1 0
2009 3 0 3 0
2010 2 0 2 0
Total 169 151 18 151 0
Mr Weir: To ask the Secretary of State for Health what definition of (a) probable and (b) possible his Department uses in the identification of variant Creutzfeldt-Jakob disease cases. [11007]
Anne Milton: The Department uses the internationally recognised World Health Organisation diagnostic criteria for case classification, research protocols and official statistics. These are publicly available at:
www.who.int/entity/zoonoses/diseases/Creutzfeldt.pdf
http://www.publications.parliament.uk/pa/cm201011/cmhansrd/cm100726/text/100726w0008.htm#10072719000041
Alzheimer's Disease: Cumbria John Stevenson: To ask the Secretary of State for Health (1) how much funding has been allocated to caring for people with Alzheimer's disease in (a) Cumbria and (b) Carlisle constituency for the next 12 months. [10759]
(2) how many people in (a) Cumbria and (b) Carlisle constituency have been diagnosed with Alzheimer's disease. [10760]
Mr Burstow: The Department currently allocates funding directly to primary care trusts (PCTs). PCT allocations are not broken down by policy area. PCTs make decisions on investment in health care for their communities, taking into account both local and national priorities.
In 2010-11, Cumbria Teaching PCT received a revenue allocation of £826.9 million. Data on the number of people diagnosed with Alzheimer's disease is not collected centrally. However, the Quality and Outcomes Framework includes a disease register for patients who have been diagnosed with any form of dementia (including Alzheimer's disease). The latest available figures are for 2008-09.
There were .3,114 patients on the dementia register in Cumbria PCT in 2008-09. The figures are organised by practice and aggregated into PCT and strategic health authority. It is therefore not possible to give figures for Carlisle constituency.
Notes:
1. QOF: QOF is the national Quality and Outcomes Framework, introduced as part of the new General Medical Services (GMS) contract on 1 April 2004. Participation by practices in the QOF is voluntary, though participation rates are very high, with most Personal Medical Services (PMS) practices also taking part.
2. The published QOF information was derived from the Quality Management Analysis System (QMAS), a national system developed by NHS Connecting for Health.
3. QMAS uses data from general practices to calculate individual practices' QOF achievement. QMAS is a national IT system developed by NHS Connecting for Health to support the QOF. The Quality Management Analysis System captures the number of patients on the various disease registers for each practice.
http://www.publications.parliament.uk/pa/cm201011/cmhansrd/cm100726/text/100726w0008.htm#10072719000040
Greetings,
For anyone that cares, from 1993 to 2005, a steady increase of sporadic CJD from 27 in 1993, to 104 in 2005, tapering off to 94 in 2006, and 88 in 2007, which seems to correlate to other BSE countries, which to me shows a relationship with human Sporadic CJD rising and falling along the same lines as the BSE cases. Course, nobody cares about that factor because of the UKBSEnvCJD only theory. nobody cares that in fact what Collinge, Asante et al showed, that BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein, but who cares about sound science anymore $
2002
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: j.collinge@prion.ucl.ac.ukReceived August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002. This article has been cited by other articles in PMC. Other Sections?
Abstract
Variant Creutzfeldt-Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Keywords: BSE/Creutzfeldt-Jakob disease/prion/transgenic
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC136957/?tool=pubmed
2004
Originally published in Science Express on 11 November 2004 Science 3 December 2004: Vol. 306. no. 5702, pp. 1793 - 1796 DOI: 10.1126/science.1103932
Reports Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype Jonathan D. F. Wadsworth, Emmanuel A. Asante, Melanie Desbruslais, Jacqueline M. Linehan, Susan Joiner, Ian Gowland, Julie Welch, Lisa Stone, Sarah E. Lloyd, Andrew F. Hill,* Sebastian Brandner, John Collinge
Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.
Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
* Present address: Department of Biochemistry and Molecular Biology and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.
To whom correspondence should be addressed. E-mail: j.collinge@prion.ucl.ac.uk
http://www.sciencemag.org/cgi/content/abstract/306/5702/1793
2008
Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD
The evolution of the variant Creutzfeldt-Jakob disease (vCJD) epidemic is hazardous to predict due to uncertainty in ascertaining the prevalence of infection and because the disease might remain asymptomatic or produce an alternate, sporadic-like phenotype.
Transgenic mice were produced that overexpress human prion protein with methionine at codon 129, the only allele found so far in vCJD-affected patients. These mice were infected with prions derived from variant and sporadic CJD (sCJD) cases by intracerebral or intraperitoneal route, and transmission efficiency and strain phenotype were analyzed in brain and spleen. We showed that i) the main features of vCJD infection in humans, including a prominent involvement of the lymphoid tissues compared to that in sCJD infection were faithfully reproduced in such mice; ii) transmission of vCJD agent by intracerebral route could lead to the propagation of either vCJD or sCJD-like prion in the brain, whereas vCJD prion was invariably propagated in the spleen, iii) after peripheral exposure, inefficient neuroinvasion was observed, resulting in an asymptomatic infection with life-long persistence of vCJD prion in the spleen at stable and elevated levels.
Our findings emphasize the possibility that human-to-human transmission of vCJD might produce alternative neuropathogical phenotypes and that lymphoid tissue examination of CJD cases classified as sporadic might reveal an infection by vCJD-type prions. They also provide evidence for the strong propensity of this agent to establish long-lasting, subclinical vCJD infection of lymphoreticular tissues, thus amplifying the risk for iatrogenic transmission.
snip...
Discussion Top In this study we used tg650 mice, a newly developed transgenic line expressing human PrPC, to investigate some aspects of the pathogenesis of vCJD infection. As main findings, we demonstrate that prion strain divergence can occur upon transmission of human, primary vCJD to such mice, and that peripheral challenge leads to an asymptomatic, life-long infection of the lymphoid compartment. A feature of tg650 mice is that following primary intracerebral vCJD challenge they developed a neurological disease with typically 100% attack rate, unlike for previously established PrP129Met, including overexpressing lines [16], [19]. The mean survival time - typically around 500 days in homozygous mice - did not change notably on subpassaging, implying that vCJD agent might clinically infect the tg650 mice with little or no transmission barrier. This discrepant result may reflect the use of different constructs and genetic backgrounds (Text S1), and the transgene expression levels, although the latter does not seem to greatly differ as far as the tg650+/- and tg45 mice [16] are concerned.
A surprising result of these studies is the alternate pattern of disease that was induced by one of the inoculated vCJD cases, a WHO reference case here designated vCJD no. 4. Indeed, while vCJD strain features were faithfully propagated in the majority of tg650 mice, almost half of the vCJD 4-inoculated mice were found to propagate a prion replicating faster than vCJD agent, and exhibiting sCJD-like PrPres and neuropathological features. Although strain divergence upon transmission of BSE/vCJD agent to mice was reported to occur in earlier studies [16], [24], it was unprecedented within a context of homotypic transmission, i.e. full matching between the donor and receiver PrP sequences. To address the issue of a possible contamination, we performed independent transmission experiments, involving separate inoculum batches of the incriminated case, which all produced consistent results. Therefore, we consider the data inconsistent with contamination of the VCJD no. 4 material by a sCJD infectious source within our laboratory. An alternate possibility, i.e. a cross-contamination of the source material, was judged highly improbable owing to the procedures applied during the collect of the specimen and the preparation of the homogenates ([25] and P. Minor, personal communication). On the other hand, our observation intriguingly parallels the phenotypic disjunction observed upon transmission of BSE agent to human PrP129Met mice (tg35 line [16]). Together, these findings lend support to the hypothesis that a minor strain component might be created upon cattle-to-human transmission of BSE agent and could emerge upon subsequent human-to-human transmission. It is also worth mentioning that, while the probability to detect such a variant through mouse bioassay would be expected to depend on the amount - and possibly the regions - of brain tissue taken to establish the source material, the vCJD-4 homogenate was prepared using a larger amount of tissue from the same brain than for the other homogenates analyzed in this study (i.e. 100 mg instead of 1 mg of frontal cortex [25]).
The above finding has obvious implications in terms of public health as it raises the concern that some humans iatrogenically infected by vCJD agent may develop a clinical disease that would not be recognized as of vCJD origin [17], [26]. Strikingly however, all vCJD-4-inoculated mice, notwithstanding the strain phenotype divergence propagated bona fide vCJD agent in their spleen, based on the PrPres pattern and the disease phenotype produced by secondary transmission to tg650 mice. This result is of direct relevance to the diagnosis of variant and sporadic CJD. Indeed, looking for peripheral lymphoreticular deposition of abnormal PrP on cases diagnosed as sporadic CJD might reveal a vCJD infection resulting from human-to-human, or cattle-to-human transmission. In this respect, it would be of interest to examine whether BSE-inoculated tg35 mice showing discordant PrPres signatures [16], or vCJD-challenged PrP129Val transgenic mice producing 'type 5' prion in their brain [17] do accumulate PrPvCJD in their spleens. In any case, our findings provide clear evidence that, as a consequence of strain-related tropism disparities, the same mouse can propagate different prions in different tissues following a single infection event.
Another salient finding emerging from this study was the remarkable ability of vCJD agent to establish asymptomatic infection despite sustained, life-long propagation in extraneural tissues. When challenged peripherally, tg650 mice remained asymptomatic over the whole observation period, and did not accumulate PrPres at detectable levels in their brain before 750 days pi, near the life end-stage. In the spleen of these mice however, PrPres accumulation reached its maximum at an early stage of infection, and remained at stable and substantial levels until death. Plateauing of prion infection in the spleen is consistent with earlier observations, and has been suggested to reflect an exhaustion of target cells (for review [22]) Importantly, the spleen tissue was highly infectious as it killed 100% of intracerebrally challenged mice within the minimal mean incubation time (~500 days). Altogether these data support the view that the sustained multiplication of the vCJD prion in lymphoid tissues was not accompanied by an efficient neuroinvasion in tg650 mice. Such an extremely delayed neuroinvasion appears to be rare in TSE rodent models, and to our knowledge was only reported for the mouse-adapted strain 87V on IM mice infected intraperitoneally with diluted inoculum [27]. Clearly, while early accumulation of prions in lymphoid tissues may be essential for efficient neuroinvasion [22], efficient lymphoinvasion does not inevitably lead to rapid neuroinvasion. This finding strengthens the notion that humans infected by vCJD from a human source - including individuals of the MM genotype - might remain clinically asymptomatic for a very prolonged period of time while harboring relatively high levels of prion infectivity in their lymphoid tissues from an early stage of infection on, thereby amplifying the risk of iatrogenic transmission. It also supports the view that the large-scale survey of lymphoreticular tissues [28] may lead to a reliable assessment of the actual prevalence of vCJD infection in the UK population.
Finally, the human PrP transgenic model described in this study may help to further our understanding of peripheral vCJD pathogenesis, for instance in trying to identify factors that might enhance neuroinvasion efficiency, or modulate the shedding of prion infectivity from the lymphoreticular to the blood compartment. Moreover, preliminary results indicate that the search for abnormal PrP in the spleen of such mice culled at time intervals post infection [29], [30] could allow the detection of low levels of vCJD infectivity within a reasonably short time scale.
Citation: Béringue V, Le Dur A, Tixador P, Reine F, Lepourry L, et al. (2008) Prominent and Persistent Extraneural Infection in Human PrP Transgenic Mice Infected with Variant CJD. PLoS ONE 3(1): e1419. doi:10.1371/journal.pone.0001419
Academic Editor: Adam Ratner, Columbia University, United States of America
Received: September 20, 2007; Accepted: December 17, 2007; Published: January 9, 2008
Copyright: © 2008 Beringue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by INRA, Institut de Veille Sanitaire (InVS) and the Ministry of Research, France. The sponsors of this study had no role in study conduct, collection analysis, interpretation of the data, writing of the report or approval of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* To whom correspondence should be addressed. E-mail: hubert.laude@jouy.inra.fr (HL); vincent.beringue@jouy.inra.fr (VB)
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001419
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html
Thursday, July 08, 2010
Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/nosocomial-transmission-of-sporadic.html
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
page 114 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
please see full text ;
Wednesday, March 31, 2010
Atypical BSE in Cattle
http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
Monday, October 19, 2009
Atypical BSE, BSE, and other human and animal TSE in North America Update October 2009
http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER
>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas. She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-
Physician Discharge Summary, Parkland Hospital, Dallas Texas
Admit Date: 12/29/2009 Discharge Date: 1/20/2010
Attending Provider: Greenberg, Benjamin Morris;
General Neurology Team: General Neurology Team Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence. She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers. The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.
http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8
>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<
please see full text ;
Monday, March 29, 2010
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
http://creutzfeldt-jakob-disease.blogspot.com/2010/03/irma-linda-andablo-cjd-victim-she-died.html
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER
http://cjdtexas.blogspot.com/2010/03/cjd-texas-38-year-old-female-worked.html
USA sporadic CJD cases rising ;
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection. He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
Friday, February 05, 2010
New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review
http://vcjd.blogspot.com/2010/02/new-variant-creutzfelt-jakob-disease.html
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Archive Number 20100405.1091 Published Date 05-APR-2010 Subject PRO/AH/EDR> Prion disease update 1010 (04)
snip...
[Terry S. Singeltary Sr. has added the following comment:
"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.
The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"
http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101
Saturday, July 17, 2010
Variant Creutzfeldt-Jakob disease Ironside JW., Haemophilia. 2010 Jul;16 Suppl 5:175-80
REVIEW ARTICLE
http://vcjdtransfusion.blogspot.com/2010/07/variant-creutzfeldtjakob-disease.html
Sunday, July 18, 2010
Alzheimer's Assocition International Conference on Alzheimer's Disease (updated diagnostic criteria) 2010 July 10 - 15 Honolulu, Hawaii
snip...
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, March 31, 2010
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
snip...
see full text ;
http://betaamyloidcjd.blogspot.com/2010/07/alzheimers-assocition-international.html
http://betaamyloidcjd.blogspot.com/
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Friday, May 7, 2010
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset:
Husbands Appear at Higher Risk Than Wives
April 30th, 2010
Strictly Embargoed Until 00.01 Hours (EST) Wednesday, May 5, 2010
Contact: Jennifer Beal +44 (0) 1243 770633 Medicalnews@wiley.com
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Husbands Appear at Higher Risk Than Wives Older married adults whose spouse has dementia are at significantly higher risk for developing dementia themselves, compared to similar older married adults whose spouse never develops dementia. This is the key finding of a study published today in the Journal of the American Geriatrics Society.
Informal dementia caregiving for a spouse is a natural marital obligation, and spousal caregivers often report positive feelings toward caregiving, yet it is difficult, requiring time, energy and usually physical exertion. Dementia caregivers have been shown to provide more assistance, and to report more personal sacrifices and stress, than those who care for physically-impaired elderly without dementia. While there are many published studies showing that dementia caregivers are at higher risk for health problems and depression, none have examined risk for dementia in the caregiver.
2,442 subjects (1,221 married couples) aged 65 and older from Northern Utah, USA, without dementia at onset were studied for up to 12 years to monitor for onset of dementia in husbands, wives or both. During this time, 125 cases of dementia only in the husband were diagnosed, 70 only in the wife, and 30 where both spouses were diagnosed (60 people).
The researchers, led by Dr. Maria Norton of Utah State University, USA, adjusted for socioeconomic status, a significant predictor of many health-related outcomes including dementia to control for shared environmental exposures that might influence risk for dementia in both spouses.
The results showed that incident dementia was significantly associated with older age, and having a spouse with dementia. Participants with a spouse who developed dementia were at a six times increased risk of developing dementia, net of the effect of age, gender, APOE genotype, and socioeconomic status, with higher risk in men (11.9) than women (3.7).
“Future studies are needed to determine how much of this association is due to caregiver stress compared to a shared environment,” said Norton. “On the positive side, the majority of these individuals, with spouses who develop dementia, did not themselves develop dementia, therefore more research is needed to explore which factors distinguish those who are more vulnerable.”
“Given the significant public health concern of Alzheimer’s disease and other dementias, and the upcoming shift in population age composition, continued research into the causes of dementia is urgent,” concluded Norton. __________________________________________________________________
This study is published in the issue of the Journal of the American Geriatrics Society. Media wishing to receive a PDF of this article may contact medicalnews@wiley.com
Full citation: Norton et al; Increased Risk of Dementia When Spouse Has Dementia? The Cache County Study; The Journal of the American Geriatrics Society, May 2010
About the Author: Dr. Maria Norton is based at Utah State University, USA. To arrange an interview with Dr. Norton, please contact Tim Vitale at Utah State University’s Public Relations office on tim.vitale@usu.edu or +1 435-797-1356.
About the Journal: The Journal of the American Geriatrics Society is a comprehensive and reliable source of monthly research and information about common diseases and disorders of older adults. The journal is published by Wiley-Blackwell on behalf of the American Geriatrics Society. For more information, please visit www.blackwellpublishing.com/jgs.
About Wiley-Blackwell: Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
Modified On: May 5th, 2010
http://www.americangeriatrics.org/press/id:665
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
76 pages on hound study;
http://web.archive.org/web/20030327022236/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf
I thought that in Britain dogs had contracted BSE, but perhaps not.
not so fast here;
The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.
38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
http://www.bseinquiry.gov.uk/witness/htm/stat067.htm
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
NEW URL ;
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
SEE LETTER FROM MAFF TO ME IN 2005 ABOUT THE HOUND STUDY ;
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================END...TSS
WHAT ABOUT THOSE STUMBLING, STAGGERING, AND BLIND DOGS, the old dog syndrome, just another spontaneous event ???
The signs of canine cognitive dysfunction syndrome or "old dog syndrome" commonly seen in dogs are: lose of house training increased barking or whining increased anxiety or fear signs disorientation-appearing lost or confused,getting stuck behind furniture or in corners, walking in circles, becoming forgetful,walking aimlessly,staring into space, repetitious or compulsive behavior change in sleep patterns-up at night, sleep all day
lack of responsiveness other changes,may not recognize you, their name,may become more docile, more aggressive.. You can liken it to human senility. An article at the petcenter says "CDS is not "normal aging". A number of pathophysiological changes are suspected to play a role in its development. These include: * deposition of amyloid plaques in the cerebral cortex and hippocampal part of the brain * alterations in neurotransmitters, including dopamine * increased levels of monoamine oxidase B (MAOB) in the brain * increased levels of free radicals L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE,BRAND NAME: ANIPRYL OR ELDEPRYL is used to help treat canine cognitive dysfunction by increasing brain concentrations of the neurotransmitter dopamine. Hopefully you can see a difference in a month or so. If you don't see a difference in the first month, your vet might tell you to try two pills a day for the next month. ANIPRYL doesn't work for all dogs. A great writeup on L-DEPRENYL can be found at
http://www.petsinfo.org/elderlydogs1.html
"One third of canine CD patients respond extremely well to treatment with deprenyl by regaining their youthful vigor; another one third respond reasonably well; and one third do not respond at all (perhaps there is a variant of CD with different neuropathology). The bottom line is that for any dog that is slowing down to the point that problems become apparent, treatment with deprenyl is the logical route once other organic causes for reduced mental function have been ruled out. Here is a write up on selegline " Selegiline has immune-system-boosting and anti-neurodegenerative effects. ....
Taken consistently in low doses, selegiline tends to extend the life-expectancy of rats by some 20%; enhances drive, libido and endurance; and independently improves cognitive performance in Alzheimer's patients and in some healthy normals. It is used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs...Selegiline protects the brain's dopamine cells from oxidative stress. " Some also use alpha lipoic acid and r-lipoic acid. powerful antioxidants to help slow down canine cognitive dysfunction. There is a dog food that is rich in antioxidants for CDS but I am assuming if you supplement with your own antioxidants you don't have to worry if your dog likes the food or not. I know my dog Hammy has become very picky and at least if I pill him, I know he is getting his antioxidants.
http://www.thensome.com/cds.htm
Doggie Dementia
Does 14-year-old Fido get lost in his own back yard?
Does he not respond when you call his name?
Does he generally seem confused?
According to Pulse, the official magazine of the Southern California Veterinary Medical Association, just as humans in the 21st Century are living longer, so is man’s best friends—more than 7.3 million dogs in the United States are age 10 or older. And with age dogs become prone to the same age-related diseases as their human companions, including dementia.
A disease of old age affects dogs and humans alike
Kazzy, a 17-year-old Lhasa Apso, is one of the 60 percent of dogs aged 11 to 15 who suffer from one or more symptoms of canine cognitive dysfunction syndrome (CDS), also known to veterinarians as doggie dementia. "He used to be the most incredible watchdog," says his owner, Olivia Feldman-Rich. "But he’s not like that anymore. He’s quite bewildered."
Experts like Dr. Maritza Perez, a veterinarian at West Orange (NJ) Animal Hospital, say that confusion is one of the four major signs of CDS (see sidebar). Dr. Perez says dogs may "pace around in circles, get stuck behind furniture, or they don’t know where the back door is anymore."
Often the most distressing sign of CDS is that, like human patients with Alzheimer’s disease, your pet seems to forget you and your family. "A lot of people notice that when you walk in the door, and this dog that was happy to see you doesn’t get up off the couch or off the floor to greet you," says Dr. Perez. "And he doesn’t come anymore when you call him."
These symptoms, coupled with others debilitating diseases affecting older dogs, such as arthritis, all add up to a serious loss in quality of life for your canine friend. The American Veterinary Medical Association reports that some 500,000 dogs are put to sleep each year because of CDS.
Researchers say that deposits of beta-amyloid plaques in brain tissues are likely to play a role in CDS. These plaques build up and eventually inhibit transmission of the brain’s neural signals. Still, the recognized symptoms of CDS are behavioral, so a diagnosis is exclusionary, meaning it is arrived at only after all other physical and neurological causes are ruled out.
No cure yet, but relief for some dogs
Dr. Perez with a 14 year-old beagle who is on Anipryl.
While scientists search for a permanent cure for CDS, there is one treatment currently FDA-approved for CDS. Selegiline hydrochloride, whose brand name is Anipryl, may give some dogs relief from its symptoms. Researchers speculate that Anipryl works by increasing levels of dopamine, a neurotransmitter. Other treatments are currently being investigated, including diets high in anti-oxidants as well as a new drug, Adrafinil, in one Canadian study.
Dr. Perez says that Anipryl does cause an improvement in many dogs with CDS, meaning relief from at least one of the common symptoms. "We have lots of animals on it and it does work," she says. But it’s not a sure thing—Dr. Perez tried it on her own dog with no effect.
Feldman-Rich is debating putting Kazzy on Anipryl. "I’m hoping that it will give a little more balance to his life and make him a little more aware that he’s still here and we’re still here for him," she says. "I always told him that he couldn’t leave me too soon, and he’s definitely kept up his end of it, but I’d definitely like for him to feel a little more like he’s part of the family."
by Debra Utacia Krol
http://www.sciencentral.com/articles/view.php3?article_id=218391360&cat=1_6
SEE CJD IN MAN AND HIS CAT ;
[Image] Research letters Volume 352, Number 9134 [Image] 3 October 1998 [Previous] [Next]
[Image][Image]
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
[Image]
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited, acquired, and sporadic mammalian neurological disorders, and are characterised by the conversion of the cellular prion protein (PrP) in an insoluble and protease-resistant isoform (PrPres). In human TSE, four types of PrPres have been identified according to size and glycoform ratios, which may represent different prion strains. Type-1 and type-2 PrPres are associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence that variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion strain.2-4 The BSE strain has been identified in three cats with feline spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in the UK.5 We report the simultaneous occurrence of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta activity. A brain magnetic resonance imaging scan was unremarkable. 10 days later, he was speechless and able to follow only simple commands. Repeat EEGs showed periodic triphasic complexes. 2 weeks after admission, he was mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November, 1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The cat was usually fed on canned food and slept on its owner's bed. No bites from the cat were recalled. In the next few days, the cat became ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient and the cat were methionine homozygous at codon 129. Histology of the patient's brain showed neocortical and cerebellar neuronal loss, astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed a punctate pattern and paralleled spongiform changes (figure B). The cat's brain showed mild and focal spongiosis in deeper cortical layers of all four lobes (figure C), vacuolated cortical neurons (figure D), and mild astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and caudate nucleus (figure E). Western blot analysis of control and affected human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After digestion with proteinase K and deglycosylation, only samples from the affected patient and cat showed type-1 PrPres, with PrP glycoform ratios comparable to those observed in sporadic CJD1 (details available from author).
[Image]
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform degeneration and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration (haematoxylin and eosin).D: vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline prion diseases. The clinical features of the cat were different from previously reported cases of FSE which were characterised by gradual onset of behavioural changes preceding locomotor dysfunction and ataxia.5 Neuropathological changes were also at variance with the diffuse spongiosis and vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern of PrP deposition, similar in the cat and in the patient, was atypical for a BSE-related condition. Evidence of a new type of FSE was further provided by the detection of a type-1 PrPres, other than the BSE-associated type 4.2 Taken together, our data suggest that the same agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal transmission in either direction, infection from an unknown common source, or the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78 [PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501 [PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform encephalopathy: a review. Vet Annual 1993; 33: 1-10.
------------------------------------------------------------------------ Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia
=======================================
Terry S. Singeltary Sr. wrote:
######## Bovine Spongiform Encephalopathy #########
Greetings list members,
ODD that some FELINE in Italy seem to have this same or maybe very similar phenotype of TSE;
In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition.
http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html
-------- Original Message --------
Subject: FDA BSE Update - Pet Food from Canadian Manufacturer & MAD DOG DATA
Date: Tue, 27 May 2003 08:07:58 -0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
Statement
FOR IMMEDIATE RELEASE Statement May 26, 2003
Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA BSE Update - Pet Food from Canadian Manufacturer
The Food and Drug Administration (FDA) has learned from the government of Canada that rendered material from a Canadian cow that last week tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease ) may have been used to manufacture pet food, specifically dry dog food, some of which was reported to have been shipped to the United States. The Canadian government prevented the BSE positive cow from being processed for human food. Therefore, consumers can be assured that their food does not contain any remnants of the BSE positive cow.
It is also important to stress that there is no scientific evidence to date that dogs can contract BSE or any similar disease. In addition there is no evidence that dogs can transmit the disease to humans.
FDA notified the U.S. pet food firm, The Pet Pantry International, of Carson City, Nevada, when FDA learned that the pet food that the firm received may have included rendered material from the BSE positive cow. The manufacturer of the pet food is Champion Pet Food, Morinville, Alberta. Even though there is no known risk to dogs from eating this dog food, as a prudent measure to help assure that the U.S. stays BSE free The Pet Pantry International is asking its customers who may have purchased the suspect product to hold it for pickup by the distributor so that the dog food will not mistakenly be mixed into cattle or other feeds if any of the dog food is discarded or otherwise not used to feed dogs. The suspect dog food was produced by Champion Pet Food between February 4, 2003, and March 12, 2003.
The Pet Pantry products were packaged in 50 lb bags, distributed to franchises around the country, and sold by home delivery only. There was no retail distribution of the product. Consumers purchase Pet Pantry products by phone or email orders. The product is then delivered by the nearest franchisee directly to the consumer s home.
The product subject to this notification includes Maintenance Diet labeled with a use by date of 17FEB04 and Beef with Barley with a use by date of 05MAR04 . Consumers who have purchased dog food from The Pet Pantry since February of this year are asked to check their present supplies and see if any match the description of the product being removed. If so, consumers are asked to contact The Pet Pantry at 1-800-381-7387 for further information on how to return the product to The Pet Pantry for proper disposal. Consumers are asked not to destroy or discard the product themselves. The Pet Pantry will also use its sales records to contact consumers who purchased the affected product.
FDA is working closely with the Pet Pantry International to assure for proper disposal of the recovered product.
FDA will continue to provide updates on this case of BSE in Canada as additional information becomes available.
http://www.fda.gov/bbs/topics/NEWS/2003/NEW0910.html
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994)
Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier.
Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
cases have been reported in domestic cats), are characterised by long asymptomatic incubation periods followed by progressive symptoms and signs of degeneration of the brain, leading eventually to death.
http://www.bsereview.org.uk/download/draft_2.pdf
PET FOODS MAD CATS AND MAD DOGS BSE/TSEs
worse still, there is serious risk the media could get to hear of such a meeting...
snip...
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer...
http://collections.europarchive.org/tna/20080102163540/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf
2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture...
snip...
YOU explained that imported crushed heads were extensively used in the petfood industry...
http://collections.europarchive.org/tna/20080102154438/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed...
http://collections.europarchive.org/tna/20081105230259/http://www.bseinquiry.gov.uk/files/yb/1989/04/24003001.pdf
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
http://collections.europarchive.org/tna/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf
Meldrum's notes on pet foods and materials used
http://collections.europarchive.org/tna/20081105230323/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf
http://collections.europarchive.org/tna/20080102200123/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
http://collections.europarchive.org/tna/20080103005226/http://www.bseinquiry.gov.uk/files/yb/1989/05/18002001.pdf
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
http://web.archive.org/web/20030509205351/http://www.bseinquiry.gov.uk/files/yb/1989/05/22012001.pdf
full text ;
http://caninespongiformencephalopathy.blogspot.com/
http://betaamyloidcjd.blogspot.com/
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
Transmissible Spongiform Encephalopathy
http://transmissiblespongiformencephalopathy.blogspot.com/
Monday, April 5, 2010
Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010
http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html
TSS
Husbands Appear at Higher Risk Than Wives
April 30th, 2010
Strictly Embargoed Until 00.01 Hours (EST) Wednesday, May 5, 2010
Contact: Jennifer Beal +44 (0) 1243 770633 Medicalnews@wiley.com
Spouses of Dementia Sufferers Have a Six-Fold Increased Risk of Dementia Onset
Husbands Appear at Higher Risk Than Wives Older married adults whose spouse has dementia are at significantly higher risk for developing dementia themselves, compared to similar older married adults whose spouse never develops dementia. This is the key finding of a study published today in the Journal of the American Geriatrics Society.
Informal dementia caregiving for a spouse is a natural marital obligation, and spousal caregivers often report positive feelings toward caregiving, yet it is difficult, requiring time, energy and usually physical exertion. Dementia caregivers have been shown to provide more assistance, and to report more personal sacrifices and stress, than those who care for physically-impaired elderly without dementia. While there are many published studies showing that dementia caregivers are at higher risk for health problems and depression, none have examined risk for dementia in the caregiver.
2,442 subjects (1,221 married couples) aged 65 and older from Northern Utah, USA, without dementia at onset were studied for up to 12 years to monitor for onset of dementia in husbands, wives or both. During this time, 125 cases of dementia only in the husband were diagnosed, 70 only in the wife, and 30 where both spouses were diagnosed (60 people).
The researchers, led by Dr. Maria Norton of Utah State University, USA, adjusted for socioeconomic status, a significant predictor of many health-related outcomes including dementia to control for shared environmental exposures that might influence risk for dementia in both spouses.
The results showed that incident dementia was significantly associated with older age, and having a spouse with dementia. Participants with a spouse who developed dementia were at a six times increased risk of developing dementia, net of the effect of age, gender, APOE genotype, and socioeconomic status, with higher risk in men (11.9) than women (3.7).
“Future studies are needed to determine how much of this association is due to caregiver stress compared to a shared environment,” said Norton. “On the positive side, the majority of these individuals, with spouses who develop dementia, did not themselves develop dementia, therefore more research is needed to explore which factors distinguish those who are more vulnerable.”
“Given the significant public health concern of Alzheimer’s disease and other dementias, and the upcoming shift in population age composition, continued research into the causes of dementia is urgent,” concluded Norton. __________________________________________________________________
This study is published in the issue of the Journal of the American Geriatrics Society. Media wishing to receive a PDF of this article may contact medicalnews@wiley.com
Full citation: Norton et al; Increased Risk of Dementia When Spouse Has Dementia? The Cache County Study; The Journal of the American Geriatrics Society, May 2010
About the Author: Dr. Maria Norton is based at Utah State University, USA. To arrange an interview with Dr. Norton, please contact Tim Vitale at Utah State University’s Public Relations office on tim.vitale@usu.edu or +1 435-797-1356.
About the Journal: The Journal of the American Geriatrics Society is a comprehensive and reliable source of monthly research and information about common diseases and disorders of older adults. The journal is published by Wiley-Blackwell on behalf of the American Geriatrics Society. For more information, please visit www.blackwellpublishing.com/jgs.
About Wiley-Blackwell: Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
Modified On: May 5th, 2010
http://www.americangeriatrics.org/press/id:665
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
Wednesday, April 14, 2010
Food Combination and Alzheimer Disease Risk A Protective Diet
http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
76 pages on hound study;
http://web.archive.org/web/20030327022236/http://www.bseinquiry.gov.uk/files/sc/seac16/tab04.pdf
I thought that in Britain dogs had contracted BSE, but perhaps not.
not so fast here;
The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.
38.I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on 'hound ataxia' mirrored those in material from Robert Higgins' hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in 'blind' examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.
39.Hound ataxia had reportedly been occurring since the 1930's, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.
40.The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.
41.The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.
Histopathological support to various other published MAFF experiments
42.These included neuropathological examination of material from experiments studying the attempted transmission of BSE to chickens and pigs (CVL 1991) and to mice (RVC 1994).
http://www.bseinquiry.gov.uk/witness/htm/stat067.htm
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
NEW URL ;
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
SEE LETTER FROM MAFF TO ME IN 2005 ABOUT THE HOUND STUDY ;
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less
critical. For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================END...TSS
WHAT ABOUT THOSE STUMBLING, STAGGERING, AND BLIND DOGS, the old dog syndrome, just another spontaneous event ???
The signs of canine cognitive dysfunction syndrome or "old dog syndrome" commonly seen in dogs are: lose of house training increased barking or whining increased anxiety or fear signs disorientation-appearing lost or confused,getting stuck behind furniture or in corners, walking in circles, becoming forgetful,walking aimlessly,staring into space, repetitious or compulsive behavior change in sleep patterns-up at night, sleep all day
lack of responsiveness other changes,may not recognize you, their name,may become more docile, more aggressive.. You can liken it to human senility. An article at the petcenter says "CDS is not "normal aging". A number of pathophysiological changes are suspected to play a role in its development. These include: * deposition of amyloid plaques in the cerebral cortex and hippocampal part of the brain * alterations in neurotransmitters, including dopamine * increased levels of monoamine oxidase B (MAOB) in the brain * increased levels of free radicals L-DEPRENYL HYDROCHLORIDE SELEGILINE HYDROCHLORIDE,BRAND NAME: ANIPRYL OR ELDEPRYL is used to help treat canine cognitive dysfunction by increasing brain concentrations of the neurotransmitter dopamine. Hopefully you can see a difference in a month or so. If you don't see a difference in the first month, your vet might tell you to try two pills a day for the next month. ANIPRYL doesn't work for all dogs. A great writeup on L-DEPRENYL can be found at
http://www.petsinfo.org/elderlydogs1.html
"One third of canine CD patients respond extremely well to treatment with deprenyl by regaining their youthful vigor; another one third respond reasonably well; and one third do not respond at all (perhaps there is a variant of CD with different neuropathology). The bottom line is that for any dog that is slowing down to the point that problems become apparent, treatment with deprenyl is the logical route once other organic causes for reduced mental function have been ruled out. Here is a write up on selegline " Selegiline has immune-system-boosting and anti-neurodegenerative effects. ....
Taken consistently in low doses, selegiline tends to extend the life-expectancy of rats by some 20%; enhances drive, libido and endurance; and independently improves cognitive performance in Alzheimer's patients and in some healthy normals. It is used successfully to treat canine cognitive dysfunction syndrome (CDS) in dogs...Selegiline protects the brain's dopamine cells from oxidative stress. " Some also use alpha lipoic acid and r-lipoic acid. powerful antioxidants to help slow down canine cognitive dysfunction. There is a dog food that is rich in antioxidants for CDS but I am assuming if you supplement with your own antioxidants you don't have to worry if your dog likes the food or not. I know my dog Hammy has become very picky and at least if I pill him, I know he is getting his antioxidants.
http://www.thensome.com/cds.htm
Doggie Dementia
Does 14-year-old Fido get lost in his own back yard?
Does he not respond when you call his name?
Does he generally seem confused?
According to Pulse, the official magazine of the Southern California Veterinary Medical Association, just as humans in the 21st Century are living longer, so is man’s best friends—more than 7.3 million dogs in the United States are age 10 or older. And with age dogs become prone to the same age-related diseases as their human companions, including dementia.
A disease of old age affects dogs and humans alike
Kazzy, a 17-year-old Lhasa Apso, is one of the 60 percent of dogs aged 11 to 15 who suffer from one or more symptoms of canine cognitive dysfunction syndrome (CDS), also known to veterinarians as doggie dementia. "He used to be the most incredible watchdog," says his owner, Olivia Feldman-Rich. "But he’s not like that anymore. He’s quite bewildered."
Experts like Dr. Maritza Perez, a veterinarian at West Orange (NJ) Animal Hospital, say that confusion is one of the four major signs of CDS (see sidebar). Dr. Perez says dogs may "pace around in circles, get stuck behind furniture, or they don’t know where the back door is anymore."
Often the most distressing sign of CDS is that, like human patients with Alzheimer’s disease, your pet seems to forget you and your family. "A lot of people notice that when you walk in the door, and this dog that was happy to see you doesn’t get up off the couch or off the floor to greet you," says Dr. Perez. "And he doesn’t come anymore when you call him."
These symptoms, coupled with others debilitating diseases affecting older dogs, such as arthritis, all add up to a serious loss in quality of life for your canine friend. The American Veterinary Medical Association reports that some 500,000 dogs are put to sleep each year because of CDS.
Researchers say that deposits of beta-amyloid plaques in brain tissues are likely to play a role in CDS. These plaques build up and eventually inhibit transmission of the brain’s neural signals. Still, the recognized symptoms of CDS are behavioral, so a diagnosis is exclusionary, meaning it is arrived at only after all other physical and neurological causes are ruled out.
No cure yet, but relief for some dogs
Dr. Perez with a 14 year-old beagle who is on Anipryl.
While scientists search for a permanent cure for CDS, there is one treatment currently FDA-approved for CDS. Selegiline hydrochloride, whose brand name is Anipryl, may give some dogs relief from its symptoms. Researchers speculate that Anipryl works by increasing levels of dopamine, a neurotransmitter. Other treatments are currently being investigated, including diets high in anti-oxidants as well as a new drug, Adrafinil, in one Canadian study.
Dr. Perez says that Anipryl does cause an improvement in many dogs with CDS, meaning relief from at least one of the common symptoms. "We have lots of animals on it and it does work," she says. But it’s not a sure thing—Dr. Perez tried it on her own dog with no effect.
Feldman-Rich is debating putting Kazzy on Anipryl. "I’m hoping that it will give a little more balance to his life and make him a little more aware that he’s still here and we’re still here for him," she says. "I always told him that he couldn’t leave me too soon, and he’s definitely kept up his end of it, but I’d definitely like for him to feel a little more like he’s part of the family."
by Debra Utacia Krol
http://www.sciencentral.com/articles/view.php3?article_id=218391360&cat=1_6
SEE CJD IN MAN AND HIS CAT ;
[Image] Research letters Volume 352, Number 9134 [Image] 3 October 1998 [Previous] [Next]
[Image][Image]
Simultaneous occurrence of spongiform encephalopathy in a man and his cat in Italy
[Image]
Gianluigi Zanusso, Ettore Nardelli, Anna Rosati, GianMaria Fabrizi, Sergio Ferrari, Antonella Carteri, Franco De Simone, Nicola Rizzuto, Salvatore Monaco
Transmissible spongiform encephalopathies (TSE) encompass inherited, acquired, and sporadic mammalian neurological disorders, and are characterised by the conversion of the cellular prion protein (PrP) in an insoluble and protease-resistant isoform (PrPres). In human TSE, four types of PrPres have been identified according to size and glycoform ratios, which may represent different prion strains. Type-1 and type-2 PrPres are associated with sporadic Creutzfeldt-Jakob disease (CJD), type 3 with iatrogenic CJD, and type 4 with variant CJD.1,2 There is evidence that variant CJD is caused by the bovine spongiform encephalopathy (BSE)-prion strain.2-4 The BSE strain has been identified in three cats with feline spongiform encephalopathy (FSE), a prion disease which appeared in 1990 in the UK.5 We report the simultaneous occurrence of sporadic CJD in a man and a new variety of FSE in his cat.
A 60-year-old man, with no unusual dietary habits, was admitted in November, 1993, because of dysarthria, cerebellar ataxic gait, visual agnosia, and myoclonus. An electroencephalogram (EEG) showed diffuse theta-delta activity. A brain magnetic resonance imaging scan was unremarkable. 10 days later, he was speechless and able to follow only simple commands. Repeat EEGs showed periodic triphasic complexes. 2 weeks after admission, he was mute, akinetic, and unable to swallow. He died in early January, 1994.
His 7-year-old, neutered, female shorthaired cat presented in November, 1993, with episodes of frenzy, twitching of its body, and hyperaesthesia. The cat was usually fed on canned food and slept on its owner's bed. No bites from the cat were recalled. In the next few days, the cat became ataxic, with hindquarter locomotor dysfunction; the ataxia got worse and there was diffuse myoclonus. The cat was killed in mid-January, 1994.
No pathogenic mutations in the patient's PrP gene were found. The patient and the cat were methionine homozygous at codon 129. Histology of the patient's brain showed neocortical and cerebellar neuronal loss, astrocytosis, and spongiosis (figure A). PrP immunoreactivity showed a punctate pattern and paralleled spongiform changes (figure B). The cat's brain showed mild and focal spongiosis in deeper cortical layers of all four lobes (figure C), vacuolated cortical neurons (figure D), and mild astrogliosis. The cerebellar cortex and the dentate nucleus were gliosed. Immunoreactive PrP showed a punctate pattern in neocortex, allocortex, and caudate nucleus (figure E). Western blot analysis of control and affected human and cat brain homogenates showed 3 PrP bands of 27-35 kDa. After digestion with proteinase K and deglycosylation, only samples from the affected patient and cat showed type-1 PrPres, with PrP glycoform ratios comparable to those observed in sporadic CJD1 (details available from author).
[Image]
Microscopic sections of patient and cat brains
A: Occipital cortex of the patient showing moderate spongiform degeneration and neuronal loss (haematoxylin and eosin) and B: punctate perineuronal pattern of PrP immunoreactivity; peroxidase immunohistochemistry with monoclonal antibody 3F4. C: cat parietal cortex showing mild spongiform degeneration (haematoxylin and eosin).D: vacuolated neurons (arrow, haematoxylin and eosin), E: peroxidase immunohistochemistry with antibody 3F4 shows punctate perineuronal deposition of PrP in temporal cortex.
This study shows a spatio-temporal association between human and feline prion diseases. The clinical features of the cat were different from previously reported cases of FSE which were characterised by gradual onset of behavioural changes preceding locomotor dysfunction and ataxia.5 Neuropathological changes were also at variance with the diffuse spongiosis and vacuolation of brainstem neurons, seen in FSE.5 The synaptic pattern of PrP deposition, similar in the cat and in the patient, was atypical for a BSE-related condition. Evidence of a new type of FSE was further provided by the detection of a type-1 PrPres, other than the BSE-associated type 4.2 Taken together, our data suggest that the same agent strain of sporadic CJD was involved in the patient and in his cat.
It is unknown whether these TSE occurred as the result of horizontal transmission in either direction, infection from an unknown common source, or the chance occurrence of two sporadic forms.
1 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variablity in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39: 767-78 [PubMed].
2 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90 [PubMed].
3 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501 [PubMed].
4 Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50 [PubMed].
5 Pearson GR, Wyatt JM, Henderson JP, Gruffydd-Jones TJ. Feline spongiform encephalopathy: a review. Vet Annual 1993; 33: 1-10.
------------------------------------------------------------------------ Sezione di Neurologie Clinica, Dipartimento di Scienze Neurologiche e della Visione, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy (S Monaco; e mail rizzuto@Gorgorna.univr.it); and Istituto Zooprofilattico Sperimentale della Lombardia e dell' Emilia, Brescia
=======================================
Terry S. Singeltary Sr. wrote:
######## Bovine Spongiform Encephalopathy #########
Greetings list members,
ODD that some FELINE in Italy seem to have this same or maybe very similar phenotype of TSE;
In October 1998 the simultaneous occurrence of spongiform encephalopathy in a man and his pet cat was reported. The report from Italy noted that the cat did not display the same clinical features as FSE cases previously seen. Indeed, the presence of a new type of FSE was suggested. The man was diagnosed as having sporadic CJD, and neither case (man nor cat) appeared to be affected by a BSE-related condition.
http://www.defra.gov.uk/animalh/bse/bse-science/level-4-othertses.html
-------- Original Message --------
Subject: FDA BSE Update - Pet Food from Canadian Manufacturer & MAD DOG DATA
Date: Tue, 27 May 2003 08:07:58 -0500
From: "Terry S. Singeltary Sr."
To: Bovine Spongiform Encephalopathy
Statement
FOR IMMEDIATE RELEASE Statement May 26, 2003
Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA BSE Update - Pet Food from Canadian Manufacturer
The Food and Drug Administration (FDA) has learned from the government of Canada that rendered material from a Canadian cow that last week tested positive for bovine spongiform encephalopathy (BSE, also known as mad cow disease ) may have been used to manufacture pet food, specifically dry dog food, some of which was reported to have been shipped to the United States. The Canadian government prevented the BSE positive cow from being processed for human food. Therefore, consumers can be assured that their food does not contain any remnants of the BSE positive cow.
It is also important to stress that there is no scientific evidence to date that dogs can contract BSE or any similar disease. In addition there is no evidence that dogs can transmit the disease to humans.
FDA notified the U.S. pet food firm, The Pet Pantry International, of Carson City, Nevada, when FDA learned that the pet food that the firm received may have included rendered material from the BSE positive cow. The manufacturer of the pet food is Champion Pet Food, Morinville, Alberta. Even though there is no known risk to dogs from eating this dog food, as a prudent measure to help assure that the U.S. stays BSE free The Pet Pantry International is asking its customers who may have purchased the suspect product to hold it for pickup by the distributor so that the dog food will not mistakenly be mixed into cattle or other feeds if any of the dog food is discarded or otherwise not used to feed dogs. The suspect dog food was produced by Champion Pet Food between February 4, 2003, and March 12, 2003.
The Pet Pantry products were packaged in 50 lb bags, distributed to franchises around the country, and sold by home delivery only. There was no retail distribution of the product. Consumers purchase Pet Pantry products by phone or email orders. The product is then delivered by the nearest franchisee directly to the consumer s home.
The product subject to this notification includes Maintenance Diet labeled with a use by date of 17FEB04 and Beef with Barley with a use by date of 05MAR04 . Consumers who have purchased dog food from The Pet Pantry since February of this year are asked to check their present supplies and see if any match the description of the product being removed. If so, consumers are asked to contact The Pet Pantry at 1-800-381-7387 for further information on how to return the product to The Pet Pantry for proper disposal. Consumers are asked not to destroy or discard the product themselves. The Pet Pantry will also use its sales records to contact consumers who purchased the affected product.
FDA is working closely with the Pet Pantry International to assure for proper disposal of the recovered product.
FDA will continue to provide updates on this case of BSE in Canada as additional information becomes available.
http://www.fda.gov/bbs/topics/NEWS/2003/NEW0910.html
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994)
Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier.
Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
http://collections.europarchive.org/tna/20080102174910/http://www.bseinquiry.gov.uk/files/ws/s324.pdf
cases have been reported in domestic cats), are characterised by long asymptomatic incubation periods followed by progressive symptoms and signs of degeneration of the brain, leading eventually to death.
http://www.bsereview.org.uk/download/draft_2.pdf
PET FOODS MAD CATS AND MAD DOGS BSE/TSEs
worse still, there is serious risk the media could get to hear of such a meeting...
snip...
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer...
http://collections.europarchive.org/tna/20080102163540/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf
2. The Parliamentary Secretary said that he was concerned about the possibility that countries in which BSE had not yet been detected could be exporting raw meat materials (in particular crushed heads) contaminated with the disease to the UK for use in petfood manufacture...
snip...
YOU explained that imported crushed heads were extensively used in the petfood industry...
http://collections.europarchive.org/tna/20080102154438/http://www.bseinquiry.gov.uk/files/yb/1989/04/14001001.pdf
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed...
http://collections.europarchive.org/tna/20081105230259/http://www.bseinquiry.gov.uk/files/yb/1989/04/24003001.pdf
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
http://collections.europarchive.org/tna/20090505233052/http://www.bseinquiry.gov.uk/files/yb/1989/05/03007001.pdf
Meldrum's notes on pet foods and materials used
http://collections.europarchive.org/tna/20081105230323/http://www.bseinquiry.gov.uk/files/yb/1989/05/16001001.pdf
http://collections.europarchive.org/tna/20080102200123/http://www.bseinquiry.gov.uk/files/yb/1989/05/16002001.pdf
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
http://collections.europarchive.org/tna/20080103005226/http://www.bseinquiry.gov.uk/files/yb/1989/05/18002001.pdf
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
http://web.archive.org/web/20030509205351/http://www.bseinquiry.gov.uk/files/yb/1989/05/22012001.pdf
full text ;
http://caninespongiformencephalopathy.blogspot.com/
http://betaamyloidcjd.blogspot.com/
Wednesday, February 24, 2010
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th
ICID International Scientific Exchange Brochure -
http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html
Transmissible Spongiform Encephalopathy
http://transmissiblespongiformencephalopathy.blogspot.com/
Monday, April 5, 2010
Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010
http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html
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