Chapter 14: The Pathological Protein

Is Sporadic CJD really sporadic or does it have a defined source?-environmental? …BSE? Insufficient testing?

- …. odds ratio = frequency of factor in patient divided by control- Health profession: 1.5- Contact with cows: 1.7- Contact with sheep: 1.6- Family history: 19.1- Psychotic disease: 9.9- Eating meat or brains: 0.6

- Problems with low statistics…with the presence of carriers?

Undercounting- Misdiagnosed as Alzheimer’s…raising incidence of Alzheimer’s

Fig. 2 AD incidence rates from a systematic review <ce:cross-ref refid="bib10"> [10]</ce:cross-ref> and the Chicago Health and Aging Project (CHAP) <ce:cross-ref refid="bib13"> [13]</ce:cross-ref> . For interpretation of the references to color in this fi...

Ron Brookmeyer , Denis A. Evans , Liesi Hebert , Kenneth M. Langa , Steven G. Heeringa , Brenda L. Plassman , Walt...

National estimates of the prevalence of Alzheimer’s disease in the United States

Alzheimer's &amp; Dementia, Volume 7, Issue 1, 2011, 61 - 73

http://dx.doi.org/10.1016/j.jalz.2010.11.007

Alzheimers Dement. Jan 2011; 7(1): 80–93.

But rise seems to be due to aging of the population

http://www.cjdsurveillance.com/abouthpd-acquired.html

Director Dr. Pierluigi Gambetti

- underreporting-they now charge for testing.-blood and urine test are not diagnostic of the disease

AlabamaIowa

IndianaKentucky

NevadaNew MexicoWashington

West Virginia

States Where CJD Diagnosis is Reportable by LawInformation on all US Individual State requirements for doctors who make a diagnosis of  CJD.  Mandatory reporting of CJD diagnosis to State Health Department in all states except the following:

CJD Voice

Cats….

http://www.cdc.gov/ncidod/dvrd/cjd/

CJD in the USA

CJD Foundation…

Menu choices…low risk

Man-Made Madness….risks of innovation….unintended consequences…asbestos, Freon, wind turbines

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998

My son received Albumin. in 1990. I was notified of the recall in 1996, It went as follows: to date there has been virtually no evidence that your child will develop CJD. Therefore, there is little reason for concern. But we also know that the more informed you are about this situation, the more assured you will feel. How can anyone get any reassurance from that letter..

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998

My initial reaction was that I was glad I was told, I felt it was my right to now......now I don't think I should of been told. It causes me much pain and worry. Especially the unknowns of the disease. Upon asking questions as to whether my son would be allowed to donate blood the response was one I had not expected it was then that I changed my opinion and thought.

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998

When speaking with a representative from RED CROSS she said not to worry because by the time your son has become of age to donate blood we will have some answers. My response to her was what about the teenagers that got these letters and would be eligible to donate this year. are we re-infecting with infectious blood by doing nothing preventative with recipients of tainted blood.

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998

I have spoken to a woman who has received some 30 recalls there are many of these people and they would of succumbed to CJD if it was possible. I do believe that recalls of tainted blood should continue but as we know the blood could of already been used these Recipients of this blood should be kept in a registry .

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998 Other thoughts I have gone thru are how do I tell my son about this, if something was to happen to me, would he really need to know just because someone felt we needed to know. I have also felt do I need to stop him from donating blood or organs until research proves to me that it is alright for him to do so. It was important enough for me to be notified but not enough for him to be considered a risk factor. As long as I am alive he will NOT be told it would be too much for him as I am sure it is too much for a lot of people.

Speeches Concerning CJDConference on CJD - Recall, Withdrawal, Notification and Recipient Notification, Ontario, Canada June 1 & 2, 1998

JIFSAN TSE Workshop-Baltimore, MD June 1998 At some point I have also believed the only reason we were told was because of the legal aspect when I rationalize the history it is the only reason I can come up with. No one can be held responsible for the unknowns of any disease, it would be a greater benefit to have more knowledge, not have hundreds of people feel like they are lepers in society.

There is much confusion when you receive this letter of notification and when you are done researching all that is available you become frustrated, angry and many tears are shed.

Protein Only or Virus???

What did you learn that provided strong evidence of the protein only hypothesis?

- mutations in the prion protein cause different outcomes

- filtration should have removed the virus- lack of sensitivity to radiation- lack of immune response, inflammation- protease resistance associated with activated form

Nature Review Genetics

Infectious particles, stress, and induced prion amyloids: a unifying perspective.Manuelidis L.Virulence. 2013 Jul 1;4(5):373-83. doi: 10.4161/viru.24838. Epub 2013 Apr 30. Review.Continuous production of prions after infectious particles are eliminated: implications for Alzheimer's disease.Miyazawa K, Kipkorir T, Tittman S, Manuelidis L.PLoS One. 2012;7(4):e35471. doi: 10.1371/journal.pone.0035471. Epub 2012 Apr 11.High CJD infectivity remains after prion protein is destroyed.Miyazawa K, Emmerling K, Manuelidis L.J Cell Biochem. 2011 Dec;112(12):3630-7. doi: 10.1002/jcb.23286.Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture.Miyazawa K, Emmerling K, Manuelidis L.Virulence. 2011 May-Jun;2(3):188-99. Epub 2011 May 1.Transmissible encephalopathy agents: virulence, geography and clockwork.Manuelidis L.Virulence. 2010 Mar-Apr;1(2):101-4. doi: 10.4161/viru.1.2.10822.Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD.Manuelidis L.J Neurovirol. 2011 Apr;17(2):131-45. doi: 10.1007/s13365-010-0007-0. Epub 2010 Dec 7.Proliferative arrest of neural cells induces prion protein synthesis, nanotube formation, and cell-to-cell contacts.Miyazawa K, Emmerling K, Manuelidis L.J Cell Biochem. 2010 Sep 1;111(1):239-47. doi: 10.1002/jcb.22723.Agent-specific Shadoo responses in transmissible encephalopathies.Miyazawa K, Manuelidis L.J Neuroimmune Pharmacol. 2010 Mar;5(1):155-63. doi: 10.1007/s11481-010-9191-1. Epub 2010 Jan 30.

More publication in Pubmed….

That Which Must Not, Can Not BeCharles Weissmann, Professor and ChairmanScripps Florida, Jupiter, FL 33458, USAConsidering that it took the Vatican 359 years to admit that the earth revolves around the sun (1), we should accept with equanimity that Igor V. Zaitsev and Laura Manuelidis are unwilling to relinquish their belief that the TSE agent is a virus……….But, as Max Planck observed (7), “a scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die…”. No malice intended; we look forward to jousting with our adversaries for many years to come.

…………………………………In summary, the would-be polemical letters fail to weaken our conclusions; rather, they reflect Palmstroem’s ruminations (10) which conclude with the lines: “For, he reasons pointedly, that which must not, can not be“.

Could Prion Protein Assumptions Engender Misleading Sensational Conclusions?Igor V. Zaitsev

The Backwards Evolution of PrionsLaura Manuelidis, Professor and Head of Neuropathology