Alzheimer's Dementia U.S. News Man, 88, kills wife in Calif. nursing home

U.S. News Man, 88, kills wife in Calif. nursing home

Published: Nov. 22, 2010 at 9:57 AM

SEAL BEACH, Calif., Nov. 22 (UPI) -- A man who had long cared for his ailing wife, whose "mind was gone," ended 70 years of marriage by shooting her in a nursing home, their daughter said.

Roy Charles Laird, 88, killed his wife Clara, 86, Sunday with a single gunshot to the head at the Country Villa Health Care Center in Seal Beach, police told the Los Angeles Times.

"It was a mercy killing," said their daughter, Kathy Palmateer, 68. "Her mind was gone."

As Clara Laird declined steadily from dementia over five years, her husband cared for her himself at home until three months ago. He would visit her at the nursing home three times a day, spoon-feeding her at each meal, friends and family said.

Around noon Sunday, a single gunshot was heard at the nursing home. Within minutes, police surrounded it and called in backup.

"We didn't know if we had a shooter or not," said Seal Beach police Sgt. Steve Bowles.

Police found Clara Laird dead in her bed and her husband in the hallway. He followed them into her room, took a .38-caliber revolver out of his pocket and calmly set it on a table, Bowles said.

Laird was arrested on suspicion of murder.

http://www.upi.com/Top_News/US/2010/11/22/Man-88-kills-wife-in-Calif-nursing-home/UPI-65541290437876/


God bless his soul, and may they both rest in peace. he will not last long now, because his soul died too. Alzheimer's, Prion disease, Dementia, and all neurological disease are truly a nightmare. If you have never witnessed the demise and death of a person from this, long term, or short, then you really should not persecute this man.

AS a layperson, and as someone that has witnessed the demise and death of a close loved one to hvCJD and Alzheimer's, it is a cruel, brutal death, and the loved ones and friends that care for them, a part of them die as well, and you never forget.

I do not condone, or approve of this man choice to end the brutal clutches of Alzheimer's that had a hold of his wife, but i have been there before. ...

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


Saturday, March 22, 2008

10 Million Baby Boomers to have Alzheimer's in the coming decades


http://betaamyloidcjd.blogspot.com/2008/03/10-million-baby-boomers-to-have.html


see full text Alzheimer's and CJD i.e. TSE, aka mad cow disease


http://betaamyloidcjd.blogspot.com/



Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html



Tuesday, November 02, 2010

IN CONFIDENCE

The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992


http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html



with saddest regards, terry

Alzheimer's Disease Constituent Response From Senator Kay Bailey Hutchison

----- 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

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

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE



Sunday, August 8, 2010

The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids

http://betaamyloidcjd.blogspot.com/2010/08/transcellular-spread-of-cytosolic.html



Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility

Monday, October 12, 2009

SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009

http://www.seac.gov.uk/pdf/hol-response091008.pdf



see full text and more science on this topic here ;


http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html



13

Simultaneous Onset of Alzheimer's Disease in a Husband and Wife in Their Mid Fifties: What do We Really Know?


Jonathan Heath1, Lindsay Goicochea2, Mark Smith3, Rudy Castellani4. 1Department of Pathology, University of Maryland; 2University; 3Case Western Reserve University; 4University of Maryland, Baltimore, Maryland

Whereas the genetic factors influencing the development and expression of Alzheimer's disease are well characterized, environmental factors are currently thought to play a marginal role. Such factors as prior closed head injury, post-menopausal estrogen deficiency, aluminum exposure, smoking, diabetes, atherosclerotic cardiovascular disease, and diet, among others, confer only a modest increased risk if any, and are only tangentially considered in the major pathogenic cascades that are presently hypothesized. We present the simultaneous onset of Alzheimer's disease in a husband and wife, with both subjects experiencing cognitive dysfunction within the same month. Both subjects were in their mid-fifties at the time of presentation, both subjects showed progressively neurological decline with prominent memory loss, both subjects experienced myoclonus late in their disease course prompting referral to the National Prion Disease Pathology Surveillance Center, and both subjects expired 12 years after onset, within two months of each other. Review of the family pedigree revealed no family history of dementia or other neurologic illnesses in multiple first degree relatives. The only historical finding of note was that both subjects had moved out of their home briefly while it was being remodeled, and both became symptomatic shortly after moving back in. At autopsy, the subjects had classic advanced Alzheimer's disease, with Braak stage VI pathology that was otherwise identiical in quantity and distribution of amyloid-beta, cerebral amyloid angiopathy, and neurofibrillary degeneration. While no specific toxin or other environmental cause was discerned, these two cases raise the issue of epigenetic factors in Alzheimer's disease that may be more robust than current literature indicates.

http://journals.lww.com/jneuropath/Fulltext/2010/05000/American_Association_of_Neuropathologists,_Inc__.9.aspx



NEUROLOGY 1998;50:684-688 © 1998 American Academy of Neurology

Creutzfeldt-Jakob disease in a husband and wife

P. Brown, MD, L. Cervenáková, MD, L. McShane, PhD, L. G. Goldfarb, MD, K. Bishop, BS, F. Bastian, MD, J. Kirkpatrick, MD, P. Piccardo, MD, B. Ghetti, MD and D. C. Gajdusek, MD From the Laboratory of CNS Studies (Drs. Brown, Cervenáková, Goldfarb, and Gajdusek), NINDS, and Biometric Research Branch (Dr. McShane), NCI, National Institutes of Health, Bethesda, MD; the Department of Obstetrics (K. Bishop), Gynecology and Reproductive Sciences, University of Texas Houston Health Science Center, Houston, TX; the Department of Pathology (Dr. Bastian), University of South Alabama Medical Center, Mobile, AL; the Department of Pathology (Dr. Kirkpatrick), The Methodist Hospital, Houston, TX; and the Department of Pathology (Drs. Piccardo and Ghetti), Indiana University School of Medicine, Indianapolis, IN.

Address correspondence and reprint requests to Dr. Paul Brown, Building 36, Room 5B21, National Institutes of Health, Bethesda, MD 20892.

A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.

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

Received May 5, 1997. Accepted in final form September 10, 1997.

http://www.neurology.org/cgi/content/abstract/50/3/684



Research Lead: Dr. David Westaway, University of Alberta

Project: "Extending the spectrum of Prionopathies to Amyotrophic Lateral Sclerosis and Autism"

This project proposes to link the chemistry of the prion protein to the new territory of other nervous system diseases, such as ALS (Lou Gehrig's disease) and the socialization disorder autism-diseases which are at least one thousand times more common than prion diseases. It is believed that a different type or prion protein may operate in other types of brain diseases, which could lead to new ways of thinking about incurable disorders. The project will create changes in the amounts of the various forms of the new membrane protein, and then perform an array of analyses on the behavior and nervous system transmission of laboratory mice. Nervous transmission by electrical impulse can be measured in isolated brain cells, a system that is also convenient to study the effect of stress by adding small amounts of toxins to the fluids bathing the cultures. By these means, the project aims to extend the boundaries of what is considered "prion disease."

Funding: $520,500

http://www.prioninstitute.ca/index.php?page=webpages&menucat=42&id=26&action=displaypage&side=1



Unfolding the Prion Mystery Building and Growing Research Expertise in Alberta Year 4 2008-2009 Annual Report

Dr. David Westaway, University of Alberta Extending the spectrum of prionopathies to amyotrophic lateral sclerosis (ALS) and autism Dr. Westaway’s study aims to extend the boundaries of what is considered prion disease. His project takes the chemistry of the prion protein into the territory of nervous system diseases such as ALS (Lou Gehrig’s disease) and socialization disorder diseases such as autism. These brain diseases are at least 1,000 times more common than diseases currently accepted as prion related. Dr. Westaway hypothesizes that a different type of protein misfolding may operate in brain diseases such as Lou Gehrig’s and autism. This type of protein misfolding may occur in response to stresses in the brain. Unlike misfolded prions, other misfolded proteins may be noninfectious and not viable outside of the affected animal. Dr. Westaway’s research team will investigate these hypotheses by inducing changes in the brain cells of laboratory mice, measuring the resulting electrical impulses in the animals’ nervous systems and analyzing the effect on behaviour. Because nervous transmission by electrical impulse can be measured in isolated brain cells, adding small amounts of toxins to the fluids bathing the cell cultures will make it possible to study the effect of stress. The results could lead to new ways of thinking about nervous system disorders.

http://www.prioninstitute.ca/forms/WEBSITE%20AR.pdf



Sunday, May 18, 2008

MAD COW DISEASE BSE CJD CHILDREN VACCINES

TWA LITTLE STATEMENT 331


http://collections.europarchive.org/tna/20080102163939/http://www.bseinquiry.gov.uk/files/ws/s331.pdf


http://collections.europarchive.org/tna/20080103032631/http://www.bseinquiry.gov.uk/files/yb/1988/11/04003001.pdf


8. The Secretary of State has a number of licences. We understand that the inactivated polio vaccine is no longer being used. There is a stock of smallpox vaccine. We have not been able to determine the source material. (Made in sheep very unlikely to contain bovine ingredients).

CONFIDENTIAL

http://collections.europarchive.org/tna/20080102164642/http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf


see full text ;

http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html


Terry S. Singeltary Sr. [flounder@wt.net]
Monday, January 08,200l 3:03 PM
freas@CBS5055530.CBER.FDA.GOV CJD/BSE (aka madcow) Human/Animal TSE’s --U.S.-- Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

Greetings again Dr. Freas and Committee Members,

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf



BELOW, PAGE 1 ACTUALLY STARTS ON PAGE 13, then when you get to the bottom, part 3 starts at the top.........TSS


From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION

snip...

ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bear with me)

THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone.

These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

snip... 48 pages...


http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8



Subject: Louping-ill vaccine documents from November 23rd, 1946


Date: Sat, 9 Sep 2000 17:44:57 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de


http://www.whale.to/v/singeltary.html



Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein


http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html



Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?


http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html



Wednesday, August 18, 2010

Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010


http://creutzfeldt-jakob-disease.blogspot.com/2010/08/incidence-of-cjd-deaths-reported-by-cjd.html


Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)


(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)


http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html




TSS

The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids

Neuron

Perspective

The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids

Adriano Aguzzi1,* and Lawrence Rajendran2,* 1Institute of Neuropathology, University Hospital of Zu¨ rich, Schmelzbergstrasse 12, CH-8091 Zu¨ rich, Switzerland 2Systems and Cell Biology of Neurodegeneration, Psychiatry Research, University of Zurich, CH-8008 Zu¨ rich, Switzerland *Correspondence: adriano.aguzzi@usz.ch (A.A.), rajendran@bli.uzh.ch (L.R.) DOI 10.1016/j.neuron.2009.12.016

Recent reports indicate that a growing number of intracellular proteins are not only prone to pathological aggregation but can also be released and ‘‘infect’’ neighboring cells. Therefore, many complex diseases may obey a simple model of propagation where the penetration of seeds into hosts determines spatial spread and disease progression. We term these proteins prionoids, as they appear to infect their neighbors just like prions—but how can bulky protein aggregates be released from cells and how do they access other cells? The widespread existence of such prionoids raises unexpected issues that question our understanding of basic cell biology.

Imagine that you are a neuroscientist vacationing on Mars. One day you encounter a colony of Martians that, as it happens, look similar to water bottles. The Martians are highly distressed and seek your advice, as their community is plagued by an enigmatic transmissible disease. Intrigued, you agree to help. It turns out that the bodies of your exobiotic friends consist of bottles filled with a supersaturated salt solution. At some point crystals have started forming in one individual, and then crystallization has somehow been transferred to other community members. Lacking molecular insight, you would initially conclude that the Martians are affected by an infectious agent. Through ingenuity and technology, you may then discover that the infectious agent is exceedingly simple and homogeneous, that it lacks informational nucleic acids, and that it is generated both by ordered aggregation of an intrinsic precursor and by appositional growth of extrinsically added seeds. Your discovery will earn you the Intergalactic Nobel Prize, yet two crucial questions remain unanswered: how do the crystals transfer between individuals, and what can be done to prevent this from happening?

Middle-aged readers may feel reminded of the plot for Andromeda Strain, a stunningly prescient novel published in 1969 by the late Michael Crichton. But the sci-fi scenario described above is also the blueprint of Prusiner’s hypothesis of prion propagation. Over time, we have learned that prions consist of PrPSc, higher-order aggregates of a physiological protein termed PrPC. Accordingly, prions propagate through elongation and breakage of PrPSc aggregates (Aguzzi and Polymenidou, 2004)—not unlike the crystals vexing our extraterrestrial friends.

There is mounting evidence (Clavaguera et al., 2009; Frost et al., 2009; Ren et al., 2009; Desplats et al., 2009; Luk et al., 2009) suggesting that the events sketched above, far from being confined to science-fiction and prion diseases (whose incidence in humans is just z1/106/year), may underlie highly prevalent human diseases of the brain and many other organs. The unifying characteristics of all these diseases is the aggregation of proteins into highly ordered stacks, henceforth termed ‘‘amyloids’’ irrespective of their size. Since PrPSc undoubtedly fulfills the latter definition of amyloid, one is led to wonder whether the prion principle may be much more pervasive than previously appreciated and whether many more diseases of unknown cause may eventually turn out to rely on prion-like propagation (Table 1, upper panel). Even more intriguingly, a number of proteins appear to exert normal functions when arranged in highly ordered stacks that are similar to amyloids and to prionoids (Table 1, lower panel).

Prions and Prionoids

There is one crucial difference between bona fide prion diseases and all other amyloids and prion-like phenomena hitherto described in uni- and pluricellular organisms (Table 1). Prions are infectious agents, transmissible between individuals, and tractable with microbiological techniques—including, e.g., titer determinations. Even if certain amyloids of yeast and mammals appear to infect neighboring molecules and sometimes neighboring cells, they do not propagate within communities, and none of them were found to cause macroepidemics such as Kuru and bovine spongiform encephalopathy. We have therefore termed these self-aggregating proteins ‘‘prionoids’’ (Aguzzi, 2009), since the lack of microbiological transmissibility precludes their classification as true prions.

Some prionoids may soon qualify for an upgrade to prion status. At least in select settings, amyloid A (AA) amyloidosis may exist as a truly infectious disease based on a self-propagating protein. AA amyloid consists of orderly aggregated fragments of SAA protein, whose deposition can damage many organs of the body. Somewhat bizarrely, AA aggregation is also present in the liver of force-fed geese, hence contributing to the pathophysiology of foie gras (Solomon et al., 2007). AA seeds can induce amyloidosis upon transfer of white blood cells (Sponarova et al., 2008). Furthermore, AA seeds are excreted with the feces, and AA amyloidosis is endemic in populations of cheetah (Zhang et al., 2008). It is therefore tantalizing to suspect that amyloid may entertain the complete life cycle of an infectious agent, including transmission by the orofecal and hematogenous route—similarly to enteroviruses and, perhaps, scrapie prions. While there may be many other good reasons to avoid foie gras, including, e.g., animal welfare concerns, gourmets may not need to panic: under experimental conditions, AA amyloidosis is only transmitted to AgNO3-pretreated mice that display elevated levels of the SAA precursor protein.

Alzheimer’s disease (AD) has long been suspected to be a transmissible disease, but these suspicions have never materialized in epidemiological studies. On the other hand, Mathias Jucker and Lary Walker observed that injection of the Ab peptide from human AD brains induced robust and convincing aggregation of Ab in transgenic mice overexpressing the Ab precursor protein, APP (Kane et al., 2000; Meyer-Luehmann et al., 2006). Jucker’s finding raises an epistemologically significant question: if aggregation depends on the introduction of seeds and on the availability of the monomeric precursor, and if amyloid represents the primordial state of all proteins (Chiti and Dobson, 2006), wouldn’t all proteins—under appropriate conditions— give rise to prionoids in the presence of sufficient precursor?

The issues sketched above go well beyond AD and prions. There are many other diseases—not necessarily involving the nervous system—whose pathogenesis involves ordered aggregation of proteins, but for which there is no evidence of transmission between individuals. The best-studied of these are the systemic amyloidoses, which come about through the nucleation of some aggregation-prone proteins such as transthyretin and immunoglobulin light chains. Yet ordered protein aggregation is by no means confined to the ‘‘classical’’ amyloidoses and extends to a number of conditions, some of which have been rather unexpected.

Type II diabetes is yet another disease whose pathogenesis may involve ordered protein aggregation. Evidence to support this idea was discovered over a century ago (Opie, 1901) but was largely forgotten until recently. It is now evident that aggregation of islet amyloid polypeptide (IAPP) is an exceedingly frequent feature of type II diabetes. IAPP amyloids damage the insulin-producing b cells within pancreatic islets and may crucially contribute to the pathogenesis of diabetes (Hull et al., 2004). It is unknown, however, whether IAPP deposition simply accrues linearly with IAPP production or whether it spreads prion-like from one pancreatic islet to the next.

A body of recent work supports the idea that many aggregation proteinopathies are, in one way or another, transmissible. A recent report showed that a-synuclein is released from neurons and is then taken up by the neighboring cells, thereby aiding in a progressive spread of the protein (Desplats et al., 2009; Lee et al., 2005). When exogenously added to cultured cells, fluorescently labeled, recombinant a-synuclein was internalized from the extracellular milieu into the cytosol. Furthermore, injection of GFP-labeled mouse cortical neuronal stem cells into the hippocampus of a-synuclein-transgenic mice led to the efficient uptake of the host a-synuclein into the grafted cells after just 4 weeks. These findings are reminiscent of the observation that healthy fetal tissue, grafted into the brains of Parkinson’s disease patients, acquired intracellular Lewy bodies. The latter phenomenon is somewhat anecdotal and has been disputed (Mendez et al., 2008), yet it would be entirely compatible with the hypothesis that a-synuclein aggregates are prionoids (Li et al., 2008). A similar study conclusively demonstrated that exogenous a-synuclein fibrils induced the formation of Lewy body-like intracellular inclusions in vitro (Luk et al., 2009). This study also showed that the conversion of the host cell a-synuclein was accompanied by dramatic changes, including hyperphosphorylation and ubiquitination of a-synuclein aggregates—thus recapitulating some key features of the human pathology.

In experiments conceptually analogous to those discussed above, polyglutamine-containing protein aggregates similar to those present in Huntington’s disease and in spinocerebellar ataxias exhibited prion-like propagation (Ren et al., 2009). There, aggregation of huntingtin progressed from the extracellular space to the cytosol and eventually to the nucleus. What is more, similar phenomena occurred upon exposure of cells to Sup35 aggregates, which consist of a yeast protein for which there are no known mammalian paralogs. This suggests that the prionoid properties are intrinsic to amyloids and are not tied to the origin or function of their monomeric precursor protein.

In another work, Tolnay and colleagues report a similar phenomenon in a mouse model of ‘‘tauopathy,’’ a neurodegenerative disease due to intraneuronal aggregation of the microtubule- associated tau protein (Clavaguera et al., 2009). Aggregation- prone mutant tau, when extracted from the brain of transgenic mice, induced tauopathy in mice overexpressing wild-type tau. Assuming that tau pathology wasn’t elicited by some indirect pathway (tau-overexpressing mice develop tangles when exposed to Ab aggregates [Go¨ tz et al., 2001]), these transgenic mice appear to behave like the Martian bottles, since tauopathy was not induced in mice expressing normal levels of tau. In yet another study, the microtubule binding part of the full-length tau was found to attack and penetrate cells when added exogenously, and this again induced host tau misfolding (Frost et al., 2009). This study also showed that aggregated intracellular Tau spontaneously transferred between two cocultured cell populations (Frost et al., 2009). In the case of both tau and polyglutamines, the protein aggregates appear to gain access to the cytosol and to cause further aggregation of their host counterparts—presumably by nucleation.

The unifying characteristics of all these diseases is the aggregation of proteins into highly ordered stacks, termed amyloids irrespective of their size; the growth of these structures also exhibits generic features (Knowles et al., 2009) shared with a wide class of self-assembly phenomena characterized by elongation and fragmentation, such as the formation of analogous aggregates in micro-organisms and in vitro. Two conclusions can be drawn from the recent studies: (1) an unexpected number of amyloidogenic proteins can be released from affected cells in the form of extracellular amyloid seeds, and (2) even more surprisingly, these seeds can then re-enter other cells and nucleate the aggregation of their intracellular counterparts—in the cytosol or even in the nucleus. The biological and practical implications are far-reaching. On the one hand, cell therapies of aggregation diseases may be more difficult than anticipated, as the transplanted cells may undergo infection. A possible remedy could consist in the removal of the genes encoding the precursor of the offending proteins from the cells utilized for therapy—e.g., using the zinc-finger nuclease strategy (Hockemeyer et al., 2009). On the other hand, a novel paradigm of amyloid pathogenesis is emerging from these data, whereby each prionoid behaves as a self-assembling and self-replicating nanomachine.

Conversely, these findings raise a number of enigmas for which we are lacking any satisfactory answer. Whereas PrPC and the Ab are luminally exposed, a-synuclein and tau are cytoplasmic— and huntingtin is even nuclear. Aggregates of both Ab and PrPSc, as well as their monomeric precursors, are found in the extracellular space; it is hence intuitive that the nucleation process can propagate spatially across large distances. Instead, the propagation of cytoplasmic prionoids challenges our basic cell-biological understanding, since it posits that protein aggregates are released into the extracellular space and can subsequently reenter—and wreak havoc—in the cytosol of other cells. The release of cytosolic amyloids is supported by the amelioration of Lewy body pathology in a-synuclein transgenic mice immunized with human a-synuclein (Masliah et al., 2005). Similarly, anti-tau oligomer immunotherapy reduced brain pathology (Asuni et al., 2007), and immunization with mutant SOD1 led to clearance of SOD1 and delayed the onset of the disease in mice (Urushitani et al., 2007). All of these results indicate that cytosolic amyloids are somehow accessible to extracellular antibodies. This raises the question of how these proteins are released into the extracellular space (‘‘cytosol to lumen’’) and how they subsequently re-enter cellular cytosol (‘‘lumen to cytosol’’). Both events require trespassing lipid bilayer barriers—by no means a trivial feat for proteins, let alone highmolecular- weight aggregates.

snip...

Conclusion

The wave of these recent reports on the prion-like behavior of disparate pathogenic proteins raises many more questions than it answers. Here we have highlighted a number of open issues related to mechanisms of cell-to-cell spread of prionoids. The resolution of such issues may constitute the first step toward the development of rational strategies aimed at blocking transcellular propagation. There is justified hope that the latter may decelerate the progression of pathology and, consequently, help toward fighting the devastating outcome of aggregation proteinopathies.

http://www.cell.com/neuron/abstract/S0896-6273(09)01006-X



Sunday, July 18, 2010

Alzheimer's Assocition International Conference on Alzheimer's Disease (updated diagnostic criteria) 2010 July 10 - 15 Honolulu, Hawaii

http://betaamyloidcjd.blogspot.com/2010/07/alzheimers-assocition-international.html



Saturday, April 24, 2010

New connection between Alzheimer’s and prionic illnesses discovered

http://betaamyloidcjd.blogspot.com/2010/04/new-connection-between-alzheimers-and.html



Sunday, June 7, 2009

ALZHEIMER'S DISEASE IS TRANSMISSIBLE

http://betaamyloidcjd.blogspot.com/2009/06/alzheimers-disease-is-transmissible.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



Alzheimer's and CJD


http://betaamyloidcjd.blogspot.com/




Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

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