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Transcript
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
But rise seems to be due to aging of the population
Alzheimers Dement. Jan 2011; 7(1): 80–93.
Director Dr. Pierluigi Gambetti
- underreporting
-they now charge for testing.
-blood and urine test are not
diagnostic of the disease
http://www.cjdsurveillance.com/abouthpdacquired.html
States Where CJD Diagnosis is Reportable by Law
Information 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:
Alabama
Nevada
Iowa
New Mexico
Indiana
Washington
Kentucky
West Virginia
CJD Voice
Cats….
CJD in the USA
http://www.cdc.gov/ncidod/dvrd/cjd/
CJD Foundation…
Menu choices…low risk
Man-Made Madness
….risks of innovation
….unintended consequences…asbestos, Freon, wind turbines
Speeches Concerning CJD
Conference 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 CJD
Conference 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 CJD
Conference 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 CJD
Conference 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 CJD
Conference 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 CJD
Conference 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
More publication in Pubmed….
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.
Could Prion Protein Assumptions Engender
Misleading Sensational Conclusions?
Igor V. Zaitsev
The Backwards Evolution of Prions
That Which Must Not, Can Not Be
Laura Manuelidis, Professor and Head of
Charles Weissmann, Professor and Chairman Neuropathology
Scripps Florida, Jupiter, FL 33458, USA
Considering 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“.