r-kaiser wrote ;
ust think about what a waste of time your life will have been flounder, when the feed transmission thing turns out to be nothing but fear monguering and government employment.
All of that time reading and writing and proving and showing ---- for what, 5 or six cows in all of North America with no actual proof of infection, and not one human being other than a few suicides being actually affected.
Geez Terry, could you at least cut your posts down a bit. I am sure that most simply scroll down due to the shear length. I actually try to read most, but time is a factor for most here on ranchers.
+++++++++++++++++++++++++++++++++++++
i agree, it has been a waste of time, but i tried. rest assured, you will see less postings from me in the future. i have wasted 8 years of my life, and a great deal of it recently here. but i will leave you with one last thought, something i never forget, you only have to see it once ;
DIVISION OF NEUROPATHOLOGY
University of Texas Medical Branch
114 McCullough Bldg.
Galveston, Texas 77555-0785
FAX COVER SHEET
DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell
FAX: (409) 772-5315 PHONE: (409) 772-2881
Number of Pages (including cover sheet):
Message:
*CONFIDENTIALITY NOTICE*
This document accompanying this transmission contains
confidential information belonging to the sender that is legally
privileged. This information is intended only for the use of the
individual or entry names above. If you are not the intended recipient,
you are hereby notified that any disclosure, copying distribution, or
the taking of any action in reliances on the contents of this telefaxed
information is strictly prohibited. If you received this telefax in
error, please notify us by tlephone immediately to arrange for return
of the original documents.
--------------------------
Patient Account: 90000014-518
Med. Rec. No.: (0160)118511Q
Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34
Sex: F Admitting Race: C
Attending Dr.:
Date / Time Admitted : 12/14/97 1228
Copies to:
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report
FINAL AUTOPSY DIAGNOSIS
Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435
AUTOPSY INFORMATION:
Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach
Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00
Pathologist/Resident: Pencil/Fernandez Service: Private
Restriction: Brain only
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
***TYPE: Anatomic(A) or Clinical(C) Diagnosis.
IMPORTANCE: 1-immediate cause of death (COD); 2.ureterlying COD;
3-contributory COD: 4.concomitant, significant; 5-incidental ***
Patient Name: POULTER, BARBARA
Patlenttc~'ation: AUTOPSY
Room/Bed:
Printed Date; Time: 01/30/98 - 0832
Page: 1
Continued ....
--------------
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report
Autopsy NO,: AU-97-00435
MICROSCOPIC DESCRIPTION:
The spongiform change is evident in all areas of neocortex, varying
from mild to moderate in severity with only very mild neuronal loss and
gliosis. In the bilateral occipital lobes, there is severe loss
cortical neurons and gliosis, with a corresondinq pallor of the
underlying white matter. There is only minimal, focal spongiform change
in corpus striatum, lentiform nuclei, thalamus, hippocampus, brainstem
and cerebellum. There is no significant loss of neurons from the lateral
geniculate nucleus, and the optic chiasm and tracts are well-myelinated.
SECTIONS TAKEN:
N-l) Pituitary, N-2) Right frontal, N-3) Right inferior frontal, N-4)
Right caudate putamen. N-5) Right lentiform nuclei, N-6) Right
hippocampus, N-7) optic chiasm. N-8) Left inferior temporal lobe, N-9)
Right inferior occipital, N-10} Cerabellum. N-l1) Midbrain, N-12) Pons,
N-13) Medulla.
FINAL DIAGNOSES:
BRAIN:
1. Clinical history of rapidly progressive dementia, clinically
consistent with Creutzfeldt-Jakob Disease.
a. spongiform encephalopathy, most Severe in occipital lobes, consistent
with Heidenhain variant of Creutzfeldt-Jakob disease.
b. Ventriculer enlargement, moderate, consistent with atrophy.
1. Communicating spherical enlargement of occipital horn of left
lateral ventricle (possible incidental congenital anomaly.
DURA; Left subdural hemorrhage, recent, minimal.
PITUITARY: Severe capillary congestion.
COMMENTS; See also western blot report from Dr. Gambetti's lab
Amyloid stains are not completed for this case as of this date. The
results, which are not essential for the diagnosis, will be reported
separately in an addendum.
(this was hand written notes)
no anyloid evident in the special stains.
no evidence of paques.
Gerald A. Campbell, M.D., Pathologist
Division of Neuropathology
(Electronic Signature}.
(Gross: 01/16/98
Final: 02/08/98
Patient Name: POULTER, BARBARA
Patient Location: AUTOPSY
Room/Bed:
Printed Date: Time: 02/09/98 - 1120
Page 2
END OF REPORT
-------
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238
fax (409) 772-5683
Pathology Report
Date/Time of Death: 12/14/97
Autopsy No.: AU-97-00435
NEUROPATHOLOGY CONSULTATION
CLINICAL HISTORY
This patient was a 63-year-old white female with recent onset of
progressive dementia. She was well until September of this year, when
she noted a decrease in her visual activity and was found to have visual
field defets as well. MRI revealed no lesions in the orbits or optic
pathways. She was admitted to the hospital with the working diagnosis
of bilateral optic neuropathy for a course of intravenous
methylprednisolone, but her vision continued to deteriorate. She
developed increasing memory and speech impairment, weakness and
myoclonus. She died on 12/14/97, approximately three and one-half
months after her symptoms started.
Date/Time of Death: 12/14/97 13:30 Date/Time Autopsy: 12/15/97 15:00
Pathologist Resident: PENCIL/FERNANDEZ
GROSS DESCRIPTION:
Submitted are the brain, convexity dura and pituitary gland.
The pituitary gland is very dark and almost hemorrhagic in appearance,
but has no obvious hematoma. It is submitted totally for histology.
The right convexity dura has diffuse but minimal subdura hemorrhage,
and the dura is otherwize unremarkable.
The brain is normally developed with normal size for an adult and is
symmetric externally. It does not have apparent sulcal widening. There
is mild congestion of thc leptomeninges, which are transparent. There is
no evidence of inflammatory exudete. There is no evidence of internal
softenings or other lesions externally. The cerebral arteries have focal
atherosclerosis, but are without significant compromise of the vessels
lumens. There im no evidence of aneurysms or malformations.
The hemispheres are sliced coronally revealing, a ventricular system
which is mildly enlarged. The cortical ribbon is normal in thickness
throuqhout most of the brain, except for the inferior amd medial
occipital lobes bilaterally, where the cortex is firm, thin and has a
brownish discoloration, more severely so on the left than the right. In
addition there is a spherical enlargement of the left occipital horn of
the lateral ventricle which communicates with the remainder of the
lateral ventricle. Tho tissue of the white matter around this
enlargement is somewhat softer then in other areas. Other areas of the
brain are grossly unremarkable. The brainstem and cerebellum are sliced
transversely, revealing normal development and no evidence of gross
changes or lesions.
DICTATED BY: GERALD A. CAMPBELL, M.D., PATHOLOGIST
01/16/98
Page 1
Continued ....
---------------
Patient Account: 90000014-518
Med. Rec. No,: (0160)118511Q
Patient Name: POULTER, BARBARA
Age: 63 YRS DOB: 10/17/34 Sex:F Race:C
Admitting Dr.:
Attending Dr:
Date/Time Admitted: 12/14/97 1228
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report
FINAL AUTOPSY REPORT
Autopsy Office (409)772-2858
Autopsy No.: AU-97-00435
CLINICAL SUMMARY:
This is a 63-year-old white female with a recent onset of progressive
dementia. Her past medical history is significant for hypothyroidism.
She was well until September of this year, when she noted visual
difficulty. By mid-October, she could not read the newspaper. She was
found to have a decrease in visual acuity and visual field defects. One
week after her initial evaluation, a panel of blood tests showed no
significant abnormalities and a MRI revealed some periventricular white
matter "plaque-like" areas but no lesions in the orbits or optic
pathways.
The patient had continued deterioration and distortion of her vision.
The visual field defects increased, and she was found to have
paracentral scotomas which were thought to be consistent with bilateral
optic neuropathy. Early in November, she was admitted to the hospital
for a course of intravenous methyl prednisolone.
During her hospital stay, she was noted to have short term memory and
speech impairment; her vision did not improve. She was discharged with
the diagnosis of Creutzfeldt-Jakob disease.
Later, the patient developed progressive dementia with marked
impairment of speech and memory. She had complete visual loss,
increased weakness and myoclonus. She died on December 14, 1997.
MF /AV
12/16/97
Patient Name: POULTER, BARBARA
Patient Location: AUTOPSY
Room/Bed:
Printed Date / Time: 01//30/98 - 0832
Page: 2
Continued ....
--------------
Patient Account: 90000014-518
Med. Rec. No.: (0160)118511Q
Patient Name: POULTER, BARBARA
Age: 63 YRS DOB: 10/17/34 Sex: F Race: C
Admitting Dr.:
Attending Dr.:
Date / Time Admitted : 12/14/97 1228
UTMB
University of Texas Medical Branch
Galveston. Texas 77555-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report
AU-97-00435
GROSS DESCRIPTION:
EXTERNAL EXAMINATION: The body is that of a 63-year-old well-nourished,
well-developed white female. There is no rigor mortis present, and there
is unfixed dependent lividity on the posterior surface. The head is
normocephalic with a moderate amount of gray, medium length scalp hair.
The irides are blue with equal pupils measuring 0.4 mm in diameter. The
nares are patent with no exudate. Dentition is fair. Buccal membranes
are normal. There is normal female hair distribution. The chest does not
have increased anterior-posterior diameter. The abdomen is slightly
protuberant. Lymph node enlargement is not present. The extremities are
unremarkable. The genitalia are those of a normal female. Two
well-healed remote scars are identified in the abdomen: one in the right
upper quadrant and another in the superpubic area.
BRAIN: The brain weighs 1450 gm. The gyri and sulci display a normal
pattern without edema or atrophy. The meninges show no abnormalities.
The circle of Willis, basilar and vertebral arteries show no significant
atherosclerosis. The brain is fixed in formalin for later examination by
a neuropathologist (see neuropathology report). No indentation of the
cingulate gyri, unci or molding of the cerebellar tonsils are noted.
SPINAL CORD: The spinal cord is not removed.
PITUITARY GLAND: The pituitary gland is removed and is fixed in formalin
for subsequent examination by a neuropathologist.
MF /AV
12/16/97
Patient Name: POULTER, BARBARA
Patient Location: AUTOPSY
Room/Bed:
Printed Date / Time: 01/30/98 - 0832
Page 3
Continued ....
--------------
Patient Account : 90000014-518
Med. Rec. No.: (0160)118511Q
patient Name: POULTER, BARBARA
Age: 63 YRS DOB: 10/17/34 Sex: F Race: C
Admitting Dr.:
Attending Dr,:
Date/Time Admitted: 12/14/97 1228
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report AU-97-00435
MICROSCOPIC DESCRIPTION:
BRAIN: Histologic examination of multiple sampled areas of the brain
showed the characteristic features of Creutzfetdt-Jakob disease. These
were present in most sections, but were particularly prominent in the
occipital cortex. The spongiform degeneration was seen in the neuropil
of the gray matter as multiple vacuoles amoung numerous reactive
astrocytes and occasional neuronal cell bodies. These changes were most
notable in the basal layer of the cortex. PAS and amyloid stains will be
performed on selected sections to asses the presence of plaques.
MF /MF
01/28/98
patient Name: POULTER, BARBARA
Patient Location: AUTOPSY
Room/Bed:
Printed Date / Time: 01/30/98 - 0832
Page: 4
Continued ....
--------------
Patient Account: 90000014-518
Med. Rec. No.: (0160}118511Q
Patient Name: POULTER, BARBARA
Age: 63 YRS DOB: 10/17/34 Sex: F Race: C
Admitting Dr.:
Attending Dr.:
Date / Time Admitted : 12/14/97 1228
UTMB
University of Texas Medical Branch
Galveston, Toxas 775550-0543
(409) 772-1238 Fax (409) 772-5683
Pathology Report
Autopsy office (409)772-2858
Autopsy No.: AU-97-00435
FINAL AUTOPSY REPORT
CLINICOPATHOLOGIC CORRELATION:
The clinical findings in this case strongly suggest the diagnosis of
Creutzfeldt-Jakob disease: progressive dementia, typical EEG changes,
visual disturbances and myoclonus. These characteristics indicate this
is a "probable case of CJD", according the criteria set by the EC
Surveillance Group of Creutzfeldt-Jakob Disease in Europe (1).
The definitive diagnosis of Creutzfeldt-Jakob disease, however, is
established by neuropathologic findings. There are three changes that
are classically described and considered diagnoseic: spongiform change,
neuronal loss and astrocytic gliosis. The presence of these can vary
significantly in proportion and distribution and often correlate with
clinical symptoms. This permits classification of the disease into
several variants.
Three variants of Creutzfeldt-Jakob disease have been proposed by Roos
and Gajdusek (2): frontopyramidal, with pyramidal or lower motor neuron
involvement; occipitoparietal {Heidenhain), characterized by disorders
in higher cortical function and vision; and diffuse, with cerebral,
cortical, basal ganglia, thalamic, cerebellar, midbrain and spinal cord
involvement.
Histological examination from multiple samples of the brain in this case
revealed astrocytic gliosis, spongiform degeneration and neuronal loss.
Although these changes were seen in most sections, they were most
prominent in the occipital cortex. This correlates very well with the
clinical history of visual disturbances. Based on this finding, the
present case corresponds to the Heidenhain variant. It is not uncommon
for Creutzfeldt-Jakob disease to present with visual symptoms as the
initial manifestation of the disease. Vargas et al (3) has reported
three cases with these characteristics.
There have been numerous and significant advances in our understanding
of Creutzfeldt-Jakob disease and prion diseases in general. These have
been reviewed in several papers written recently, including one by
Horowich and Weissman (4).
In summary, this 63 year old female with a history of visual
disturbances and dementia of rapid progression was found to have the
neuropathologic changes characteristic of Creutzfeldt-Jakob disease,
predominantly in the occipital cortex. The occipital tropism and
consequent visual symptoms indicate this case corresponds to the
Heidenhain variant.
REFERENCES:
Patient Name: POULTER, BARBARA
Patient location: AUTOPSY
Room/Bed:
Printed Date / Time: 01/30/98 * 0832
Page: 5
Continued ....
--------------
Patient Account: 90000014-518
Med. Rec. No.: (0160)118511Q
Patient Name: POULTER, BARBARA
Age: 63 YRS DOB: 10/17/34 Sex: F Race: C
Admitting Dr.:
Attending Dr.:
Date l Time Admitted : 12/14/97 1228
UTMB
University of Texas Medical Branch
Galveston, Texas 77555-0543
(409) 772-1238 Fax (409} 772-5683
Pathology Report
Autopsy No.: AU-97-00435
FINAL AUTOPSY REPORT
CLINICOPATHOLOGIC CORRELATION:
1. Budka H, et al: Tissue handling in suspected Creutzfeldt-Jakob
disease (CJD) and other human spongiform encephalopathies
(prion diseases), Brain Pathology. 5:319-322,1995.
2. Roos R, Gajdusek DC, Gibbs CJ Jr: The clinical characteristics of
transmissible Creutzfeldt-Jakob disease. Brain 96: 1-20, 1973.
3. Vargas ME, et al: Homonymous field defect as the first
Manifestation of Creutzfeldt-Jakob disease. American Journal of
Ophthalmology. 119:497-504, 1995.
4. Horowich AL, Weissman JS: Deadly conformations - protein misfolding
in prion disease. Cell Vol.89, 499-510, 1997.
MF /MF
01/28/98
SCOT D. PENCIL, M.D., PATHOLOGIST
MARTIN FERNANDEZ, M.D.
01/29/98
(Electronic Signature)
Patient Name: POULTER, BARBARA
Patient Location: AUTOPSY
Room/Bed:
Printed Date / Time: 01/30/98 - 0832
Page: 6
END OF REPORT
--------------
The University of Texas Medical Branch at Galveston
Gerald A, Campbell, Ph.D., M.D,
Associate Professor and Director
Division of Neuropathology
Department of Pathology
February 26, 1998
Pieduigi Gambetti, M.D.
Professor
Institute of Pathology
Case Western Reserve University
2085 Adelbert Road
Cleveland Ohio 44106
Dear Dr, Gambetti:
Enclosed please find the microscopic slides and autopsy report from our
patient, Barbara Poulter (Hosp.# 11851lQ, Autopsy # AU97-435). These
slides are being sent for consultation at the request of Mr. Singletary,
Ms. Poulter's son and next of kin. We will also send frozen tissue from
the brain on dry ice next week, and someone will call you on the day
the tissue is shipped. Please return the slides when you have finished
with your examination. If you need any further information, please do
not hesitate to call me. Thanks for your assistance with this case.
Sincerely,
Gerald A. Campbell
------------------
CASE WESTERN RESERVE UNIVERSITY
February 26, 1988
Gerald Campbell, M.D,, PhD.
Division of Neuropathology, G85
University TX Medical Branch
Galveston, TX 77555-0785
Dear Dr. Campbell,
As per our telephone conversation concerning a recent case of CJD, I
Will be willing to examine slides and the frozen tissue on western
blotting, I will issue a report to you about our conclusions. Below is
my address, Our Fed Ex number is XXXXXXXXXXXXXXX.
Thank your for your assistance in this matter,
Best personal regards,
Pierluigi Gambetti, M.D.
PG:In
Division of Neuropathology
Pierluigi Gambetti, M.D. Director
Institute Of Neuropathology
2085 Adelbert Road
Cleveland, Ohio 44106
Phone 216-368-0587
Fax 216-368-2546
------------------
CASE WESTERN RESERVE UNIVERSITY
February 27, 1998
Dr. Gerald A. Campbell
The University of Texas
Medical Branch at Galveston
Division of Neuropathology, G85
Galveston. TX 77555-0785
Dear Dr. Campbell,
We are in receipt of the slides you sent on Mrs. Barbara Poulter (your
#: AU97-435;our#098-28).
Best personal regards,
Pierluigi Gambetti, M.D.
PG:sb
Division of Neuropathology
Pierluigi Gambetti, M.D., Director
-----------------------------------
CASE WESTERN RESERVE UNIVERSITY
March 30, 1998
Dr. Gerald A, Campbell
The University of Texas
Medical Branch at Galveston
Division of Neuropathology
Department of Pathology
Galveston, Texas
Dear Dr Campbell,
We performed Western immunoblot analysis on the frozen tissue from your
case #AU97-435 (our #098-28). The Immunoblot reveals the presence of
protease-resistant prion probein (PrPres) confirming the diagnosis of
prion disease. The immunoblot pattern of PrPres is consistent with the
diagnosis of Creutzfeldt-Jakob disease.
Thank you for referring to us this interesting case.
Sincerely,
Piero Parchi, M.D.
Pierluigi Gambetti, M.D.
PP:sb
Division of Neuropathology
Pierluigi Gambetti, M.D., Director
Case Western Reserve University
This Autopsy report is for the use of anyone, who is trying to
understand this hideous disease CJD. I hope it can be benificial for
some in researching human TSE. Please remember, this was my Mom, and
to use this with great respect.
thank you,
kind regards,
Terry S. Singeltary Sr., Bacliff, Texas USA
-------------------------------
From: Jeff (webwizard.vegsource.org)
Subject: Very interesting letter from son of CJD victim -- and
alleged connection to cows
Date: April 22, 1998 at 19:53:42 EST
This was sent to Oprah Winfrey, reprinted here by permission:
I am the madson of a deadmom who died of madcow.(heidenhain variant
creutzfeldt-jacob disease.) I sat with her for 10 weeks and watched
as this hidious disease ate her brain up. She wrote in her journal
that she started to see brown spots on sept. 27, 1997. These were her
first symptoms -- apprx.10 days later she was blind, about 2 weeks
later she had lost control of her coordination, walking, and speech.
She would get these uncontrolable jerks that at
times would take 3 of us to hold her down. Around the
8th week she was totally bedridden. She died in the
10th week on 12-14-97. THANK GOD!
If you ever see this disease, as I did with my mom,
you will truly believe that madcow is here. I truely
believe that is what my mom died of. They can call it
what ever they want to.
Now, I will take this a step further. My neighbor's
mother also died of c.j.d. She died on 12-14-96, they
had diagnosed it as Alzheimers, until the autopsy he demanded
ruled out alzheimers and ruled in c.j.d.
About a month ago my neighbor called me over, he had
been going through some old boxes of his mom's
and came across some pills he thought I should see.
When I read the ingredients I just about sh*t!
INGREDIENTS: vacuum dried bovine brain, bone meal,
bovine eye, veal bone, bovine liver powder,
bovine adrenal, vacuum dried bovine kidney, and
vacuum dried porcine stomach. It was a cow in a pill!
This woman taking these pills died of c.j.d. Could
it be madcow in a pill?
I called the texas dept. of health (T.D.H.) the
next day, and the following day they were out here and
got the pills. I had located the manufacture and
called with a bogus story and a list of doctors that
would prescribe them in houston. The T.D.H. called a
few days later, asking for the list of doctors, their
phone numbers, and told me they would take it from there.
I need not persue it any further!
Not to long ago, 4 or 5 weeks, a girl showed up at
my door. She had called crying a week earlier and
could not talk. She had seen a story on T.V. about
my mother. Anyway, when I first saw her I knew she
had seen it too (madcow). Her mother had died of
c.j.d. on 2-14-97.
This disease is here and you can call it what ever you
want, c.j.d., n.v.c.j.d., hvCJD, b.s.e. or madcow, for
what it is. But, that young man who died of n.v.c.j.d.
in England, Steve Churchhill, had the exact same
symptoms as my mother. There is also a girl in Ft. Worth
Texas who called me. She had seen an article
about my mom in the dallas morning news. Her dad had died
of c.j.d. so far we have come up with about
18 people who has died of c.j.d. in texas, 15 confirmed.
I have heard from other people its up to 32.
I am tired of hearing this crap about nv-cjd being
in just young people. That same old line about how
nv-cjd victims are much younger and their clinical
course from first sign of symtoms to death is much
longer. Any diseases clinical course is going to be
longer in younger people, because their body and
organs are much younger and healthier. But, in the
end, their brains are full of spongiform holes, just like
the older folks. Just because the plaques are more
extreme, does not mean its a different disease. Could
it not be just a more extreme case of typical c.j.d.????
Greed is what it is all about. They banned feeding
cattle to cattle. But, are still allowed to feed those
downer cows to pork and poultry. Then they are still
allowed to feed the pork and poultry byproducts
back to the cows. Now Dr. Gibbs writes that the
prion-protien can survive the digestinal track and
composting process. So the prion-protein goes right
back to the cow. We must ban feeding all animals to
animals. Its just an endless cycle of greed thats
killing people.
I have requested that further test be done on my moms
brain.(frozen tissue, paraffeine sections and
serum) be sent to case western reserve university in
Cleveland, Ohio. Dr. Pierre Lugi Gambetti.
I hope you find some interest in this. I just don't
believe we are being told everything. The gov. lied
about asbestos for 75 years.
P.S.-- the results from Case Western Reserve Universitiy,
on my Mothers Brain, came back positive for
the prion protein PrPres, confirming the prion disease.........
kind regards,
Terry S. Singelary Sr.
Bacliff, Texas USA
=============
2006
HUMAN and ANIMAL TSE Classifications i.e. mad cow
disease and the UKBSEnvCJD only theory
TSEs have been rampant in the USA for decades in many
species, and they all have been rendered and fed back
to animals for human/animal consumption. 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 2005.
With all the science to date refuting it, to continue
to validate this myth, will only spread this TSE agent
through a multitude of potential routes and sources
i.e. consumption, surgical, blood, medical, cosmetics
etc. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Ironside, Manuelidis,
Marsh, et al and many more, that the world of TSE
Tranmissible 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. This would further have to be broken down to
strain of species and then the route of transmission
would further have to be broken down. Accumulation and
Transmission are key to the threshold from subclinical
to clinical disease, and of that, I even believe that
physical and or blunt trauma may play a role of onset
of clinical symptoms in some cases, but key to all
this, is to stop the amplification and transmission of
this agent, the spreading of, no matter what strain.
BUT, to continue with this myth that the U.K. strain of
BSE one strain in cows, and the nv/v CJD, one strain in
humans, and that all the rest of human TSE is one
single strain i.e. sporadic CJD (when to date there are
6 different phenotypes of sCJD), and that no other
animal TSE transmits to humans, to continue with this
masquerade will only continue to spread, expose, and
kill, who knows how many more in the years and decades
to come. ONE was enough for me, My Mom, hvCJD, DOD
12/14/97 confirmed, which is nothing more than another
mans name added to CJD, like CJD itself, Jakob and
Creutzfeldt, or Gerstmann-Straussler-Scheinker
syndrome, just another CJD or human TSE, named after
another human. WE are only kidding ourselves with the
current diagnostic criteria for human and animal TSE,
especially differentiating between the nvCJD vs the
sporadic CJD strains and then the GSS strains and also
the FFI fatal familial insomnia strains or the ones
that mimics one or the other of those TSE? Tissue
infectivity and strain typing of the many variants of
the human and animal TSEs are paramount in all variants
of all TSE. There must be a proper classification that
will differentiate between all these human TSE in order
to do this. With the CDI and other more sensitive
testing coming about, I only hope that my proposal will
some day be taken seriously.
My name is Terry S. Singeltary Sr. and I am no
scientist, no doctor and have no PhDs, but have been
independently researching human and animal TSEs since
the death of my Mother to the Heidenhain Variant of
Creutzfeldt Jakob Disease on December 14, 1997
'confirmed'. ...TSS
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
SOURCES
Full Text
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al.
JAMA.2001; 285: 733-734
http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama
Coexistence of multiple PrPSc types in individuals with
Creutzfeldt-Jakob disease
Magdalini Polymenidou, Katharina Stoeck, Markus
Glatzel, Martin Vey, Anne Bellon, and Adriano Aguzzi
Summary
Background The molecular typing of sporadic
Creutzfeldt-Jakob disease (CJD) is based on the size
and glycoform
ratio of protease-resistant prion protein (PrPSc), and
on PRNP haplotype. On digestion with proteinase K, type
1 and
type 2 PrPSc display unglycosylated core fragments of
21 kDa and 19 kDa, resulting from cleavage around amino
acids 82 and 97, respectively.
Methods We generated anti-PrP monoclonal antibodies to
epitopes immediately preceding the differential proteinase
K cleavage sites. These antibodies, which were
designated POM2 and POM12, recognise type 1, but not
type 2, PrPSc.
Findings We studied 114 brain samples from 70 patients
with sporadic CJD and three patients with variant CJD.
Every patient classified as CJD type 2, and all variant
CJD patients, showed POM2/POM12 reactivity in the
cerebellum and other PrPSc-rich brain areas, with a
typical PrPSc type 1 migration pattern.
Interpretation The regular coexistence of multiple
PrPSc types in patients with CJD casts doubts on the
validity of
electrophoretic PrPSc mobilities as surrogates for
prion strains, and questions the rational basis of
current CJD
classifications.
snip...
The above results set the existing CJD classifications
into debate and introduce interesting questions about
human CJD types. For example, do human prion types
exist in a dynamic equilibrium in the brains of affected
individuals? Do they coexist in most or even all CJD
cases? Is the biochemically identified PrPSc type simply
the dominant type, and not the only PrPSc species?
Published online October 31, 2005
http://neurology.thelancet.com
Detection of Type 1 Prion Protein in Variant
Creutzfeldt-Jakob Disease
Helen M. Yull,* Diane L. Ritchie,*
Jan P.M. Langeveld,? Fred G. van Zijderveld,?
Moira E. Bruce,? James W. Ironside,* and
Mark W. Head*
From the National CJD Surveillance Unit,* School of
Molecular
and Clinical Medicine, University of Edinburgh, Edinburgh,
United Kingdom; Central Institute for Animal Disease
Control
(CIDC)-Lelystad, ? Lelystad, The Netherlands; Institute
for Animal
Health, Neuropathogenesis Unit, ? Edinburgh, United Kingdom
Molecular typing of the abnormal form of the prion
protein (PrPSc) has come to be regarded as a powerful
tool in the investigation of the prion diseases. All
evidence
thus far presented indicates a single PrPSc molecular
type in variant Creutzfeldt-Jakob disease (termed
type 2B), presumably resulting from infection with a
single strain of the agent (bovine spongiform
encephalopathy).
Here we show for the first time that the PrPSc
that accumulates in the brain in variant Creutzfeldt-
Jakob disease also contains a minority type 1 component.
This minority type 1 PrPSc was found in all 21
cases of variant Creutzfeldt-Jakob disease tested,
irrespective
of brain region examined, and was also
present in the variant Creutzfeldt-Jakob disease tonsil.
The quantitative balance between PrPSc types was maintained
when variant Creutzfeldt-Jakob disease was
transmitted to wild-type mice and was also found in
bovine spongiform encephalopathy cattle brain, indicating
that the agent rather than the host specifies their
relative representation. These results indicate that PrPSc
molecular typing is based on quantitative rather than
qualitative phenomena and point to a complex relationship
between prion protein biochemistry, disease phenotype
and agent strain. (Am J Pathol 2006, 168:151-157;
DOI: 10.2353/ajpath.2006.050766)
snip...
Discussion
In the apparent absence of a foreign nucleic acid genome
associated with the agents responsible for transmissible
spongiform encephalopathies or prion diseases,
efforts to provide a molecular definition of agent strain
have focused on biochemical differences in the abnormal,
disease-associated form of the prion protein, termed
PrPSc. Differences in PrPSc conformation and glycosylation
have been proposed to underlie disease phenotype
and form the biochemical basis of agent strain. This
proposal has found support in the observation that the
major phenotypic subtypes of sCJD appear to correlate
with the presence of either type 1 or type 2 PrPSc in
combination with the presence of either methionine or
valine at codon 129 of the prion protein gene.2 Similarly,
the PrPSc type associated with vCJD correlates with the
presence of type 2 PrPSc and is distinct from that found in
sCJD because of a characteristically high occupancy of
both N-linked glycosylation sites (type 2B).6,11 The
means by which such conformational difference is detected
is somewhat indirect; relying on the action of proteases,
primarily proteinase K, to degrade the normal
Figure 6. Type 1 PrPSc is a stable minority component
of PrPSc from the vCJD
brain. Western blot analysis of PrP in a sample of
cerebral cortex from a
case
of vCJD during digestion with proteinase K is shown.
Time points assayed
are indicated in minutes (T0, 5, 10, 30, 60, 120, 180).
Duplicate blots were
probed with 3F4, which detects both type 1 and type 2
PrPSc, and with 12B2,
which detects type 1. The insert shows a shorter
exposure of the same time
course study from a separate experiment also probed
with 3F4. Both blots
included samples of cerebral cortex from a case of
sporadic CJD MM1 (Type
1) and molecular weight markers (Markers) indicate
weights in kd.
Figure 7. A minority type 1-like PrPSc is found in vCJD
tonsil, vCJD
transmitted
to mice and in BSE. Western blot analysis of PrPSc in a
concentrated
sample of tonsil from a case of vCJD (Tonsil), in a
concentrated brain
sample
of a wild-type mouse (C57BL) infected with vCJD and in
a sample of cattle
BSE brain (BSE) is shown. Tissue extracts were digested
with proteinase K.
Duplicate blots were probed with either 3F4 or 6H4,
both of which detect
type 1 and type 2 PrPSc, and with 12B2, which detects
type 1. The blots
included samples of cerebral cortex from a case of
sporadic CJD MM1 (Type
1) and molecular weight markers (Markers) indicate
weights in kd.
Type 1 PrPSc in Variant Creutzfeldt-Jakob Disease 155
AJP January 2006, Vol. 168, No. 1
cellular form of PrP and produce a protease-resistant
core fragment of PrPSc that differs in the extent of its
N-terminal truncation according to the original
conformation.
A complication has recently arisen with the finding that
both type 1 and type 2 can co-exist in the brains of
patients with sCJD.2,5-8 More recently this same phenomenon
has been demonstrated in patients with iatrogenically
acquired and familial forms of human prion disease.
9,10 The existence of this phenomenon is now
beyond doubt but its prevalence and its biological
significance
remain a matter of debate.
Conventional Western blot analysis using antibodies
that detect type 1 and type 2 PrPSc has severe quantitative
limitations for the co-detection of type 1 and type 2
PrPSc in individual samples, suggesting that the prevalence
of co-occurrence of the two types might be underestimated.
We have sought to circumvent this problem by
using an antibody that is type 1-specific and applied this
to the sole remaining human prion disease where the
phenomenon of mixed PrPSc types has not yet been
shown, namely vCJD.
These results show that even in vCJD where susceptible
individuals have been infected supposedly by a
single strain of agent, both PrPSc types co-exist: a
situation
reminiscent of that seen when similarly discriminant
antibodies were used to analyze experimental BSE in
sheep.14,17 In sporadic and familial CJD, individual
brains can show a wide range of relative amounts of the
two types in samples from different regions, but where
brains have been thoroughly investigated a predominant
type is usually evident.2,6,10 This differs from this
report
on vCJD, where type 1 is present in all samples
investigated
but always as a minor component that never
reaches a level at which it is detectable without a type
1-specific antibody. It would appear that the relative
balance
between type 1 and type 2 is controlled within
certain limits in the vCJD brain. A minority type-1-like
band is also detected by 12B2 in vCJD tonsil, in BSE
brain and in the brains of mice experimentally infected
with vCJD, suggesting that this balance of types is agent,
rather than host or tissue, specific. Interestingly the
"glycoform
signature" of the type 2 PrPSc found in vCJD (type
2B) is also seen in the type 1 PrPSc components, suggesting
that it could legitimately be termed type 1B.
PrPSc isotype analysis has proven to be extremely
useful in the differential diagnosis of CJD and is
likely to
continue to have a major role in the investigation of human
prion diseases. However, it is clear, on the basis of
these findings, that molecular typing has quantitative
limitations
and that any mechanistic explanation of prion
replication and the molecular basis of agent strain
variation
must accommodate the co-existence of multiple
prion protein conformers. Whether or not the different
conformers we describe here correlate in a simple and
direct way with agent strain remains to be determined. In
principle two interpretations present themselves: either
the two conformers can be produced by a single strain of
agent or vCJD (and, therefore, presumably BSE) results
from a mixture of strains, one of which generally
predominates.
Evidence for the isolation in mice of more than one
strain from individual isolates of BSE has been presented
previously.18,19
One practical consequence of our findings is that the
correct interpretation of transmission studies will depend
on a full examination of the balance of molecular types
present in the inoculum used to transmit disease, in
addition
to a thorough analysis of the molecular types that
arise in the recipients. Another consequence relates to
the diagnostic certainty of relying on PrPSc molecular
type alone when considering the possibility of BSE
infection
or secondary transmission in humans who have a
genotype other than methionine at codon 129 of the
PRNP gene. In this context it is interesting to note
that this
minority type 1B component resembles the type 5 PrPSc
described previously to characterize vCJD transmission
into certain humanized PRNP129VV transgenic mouse
models.12,20 This apparently abrupt change in molecular
phenotype might represent a selection process imposed
by this particular transgenic mouse model. Irrespective of
whether this proves to be the case, the results shown
here point to further complexities in the relationship
between
the physico-chemical properties of the prion protein,
human disease phenotype, and prion agent strain.
Acknowledgments
snip...
Type 1 PrPSc in Variant Creutzfeldt-Jakob Disease 157
AJP January 2006, Vol. 168, No. 1 ...TSS
http://ajp.amjpathol.org/cgi/content/abstract/168/1/151maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1136646133963_237&FIRSTINDEX=0&volume=168&issue=1&journalcode=amjpathol
Neuropathology and Applied Neurobiology
(2005),
31
, 565-579 doi: 10.1111/j.1365-2990.2005.00697.x
© 2005 Blackwell Publishing Ltd
565
Blackwell Science, LtdOxford, UKNANNeuropathology and
Applied Neurobiology0305-1846Blackwell Publishing Ltd, 2005
316565579
Review article
Phenotypic variability in human prion diseases
J. W. Ironside, D. L. Ritchie and M. W. Head
National Creutzfeldt-Jakob Disease Surveillance Unit,
Division of Pathology, University of Edinburgh,
Edinburgh, UK
J. W. Ironside, D. L. Ritchie and M. W. Head (2005)
Neuropathology and Applied Neurobiology
31,
565-579
Phenotypic variability in human prion diseases
Human prion diseases are rare neurodegenerative disorders
that can occur as sporadic, familial or acquired disorders.
Within each of these categories there is a wide range
of phenotypic variation that is not encountered in other
neurodegenerative disorders. The identification of the
prion protein and its key role in the pathogenesis of this
diverse group of diseases has allowed a fuller
understanding
of factors that influence disease phenotype. In particular,
the naturally occurring polymorphism at codon 129
in the prion protein gene has a major influence on the
disease
phenotype in sporadic, familial and acquired prion
diseases, although the underlying mechanisms remain
unclear. Recent technical advances have improved our
ability to study the isoforms of the abnormal prion protein
in the brain and in other tissues. This has lead to the
concept
of molecular strain typing, in which different isoforms
of the prion protein are proposed to correspond to
individual strains of the transmissible agent, each with
specific biological properties. In sporadic
Creutzfeldt-Jakob
disease there are at least six major combinations of codon
129 genotype and prion protein isotype, which appear to
relate to distinctive clinical subgroups of this disease.
However, these relationships are proving to be more complex
than first considered, particularly in cases with more
than a single prion protein isotype in the brain. Further
work is required to clarify these relationships and to
explain the mechanism of neuropathological targeting of
specific brain regions, which accounts for the diversity of
clinical features within human prion diseases.
© 2005 Blackwell Publishing Ltd, Neuropathology and
Applied Neurobiology, 31, 565-579
BSE prions propagate as either variant CJD-like or
sporadic CJD-like prion strains in transgenic mice
expressing human prion protein
The EMBO Journal Vol. 21 No. 23 pp. 6358±6366, 2002
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:
[email protected].
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 BSEderived
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.
snip...
These studies further strengthen the evidence that vCJD
is caused by a BSE-like prion strain. Also, remarkably, the
key neuropathological hallmark of vCJD, the presence of
abundant ¯orid PrP plaques, can be recapitulated on BSE
or vCJD transmission to these mice. However, the most
surprising aspect of the studies was the ®nding that an
alternate pattern of disease can be induced in 129MM
Tg35 mice from primary transmission of BSE, with a
molecular phenotype indistinguishable from that of a
subtype
of sporadic CJD. This ®nding has important potential
implications as it raises the possibility that some humans
infected with BSE prions may develop a clinical disease
indistinguishable from classical CJD associated with type 2
PrPSc. This is, in our experience, the commonest molecular
sub-type of sporadic CJD. In this regard, it is of interest
that the reported incidence of sporadic CJD has risen
in the
UK since the 1970s (Cousens et al., 1997). This has been
attributed to improved case ascertainment, particularly as
much of the rise is reported from elderly patients and
similar rises in incidence were noted in other European
countries without reported BSE (Will et al., 1998).
However, it is now clear that BSE is present in many
European countries, albeit at a much lower incidence than
was seen in the UK. While improved ascertainment is
likely to be a major factor in this rise, that some of
these
additional cases may be related to BSE exposure cannot be
ruled out. It is of interest in this regard that a 2-fold
increase in the reported incidence of sporadic CJD in 2001
has recently been reported for Switzerland, a country that
had the highest incidence of cattle BSE in continental
Europe between 1990 and 2002 (Glatzel et al., 2002). No
epidemiological case±control studies with strati®cation of
CJD cases by molecular sub-type have yet been reported.
It will be important to review the incidence of sporadic
CJD associated with PrPSc type 2 and other molecular
subtypes
in both BSE-affected and unaffected countries in the
light of these ®ndings. If human BSE prion infection can
result in propagation of type 2 PrPSc, it would be expected
that such cases would be indistinguishable on clinical,
pathological and molecular criteria from classical CJD. It
may also be expected that such prions would behave
biologically like those isolated from humans with sporadic
CJD with type 2 PrPSc. The transmission properties of
prions associated with type 2 PrPSc from BSE-inoculated
129MM Tg35 mice are being investigated by serial
passage.
We consider these data inconsistent with contamination
of some of the 129MM Tg35 mice with sporadic CJD
prions. These transmission studies were performed according
to rigorous biosafety protocols for preparation of
inocula and both the inoculation and care of mice, which
are all uniquely identi®ed by sub-cutaneous transponders.
However, crucially, the same BSE inocula have been used
on 129VV Tg152 and 129MM Tg45 mice, which are
highly sensitive to sporadic CJD but in which such
transmissions producing type 2 PrPSc were not observed.
Furthermore, in an independent experiment, separate
inbred lines of wild-type mice, which are highly resistant
to sporadic CJD prions, also propagated two distinctive
PrPSc types on challenge with either BSE or vCJD. No
evidence of spontaneous prion disease or PrPSc has been
seen in groups of uninoculated or mock-inoculated aged
129MM Tg35 mice.
While distinctive prion isolates have been derived from
BSE passage in mice previously (designated 301C and
301V), these, in contrast to the data presented here, are
propagated in mice expressing different prion proteins
(Bruce et al., 1994). It is unclear whether our ®ndings
indicate the existence of more than one prion strain in
individual cattle with BSE, with selection and preferential
replication of distinct strains by different hosts, or that
`mutation' of a unitary BSE strain occurs in some types of
host. Western blot analysis of single BSE isolates has not
shown evidence of the presence of a proportion of
monoglycosylated dominant PrPSc type in addition to the
diglycosylated dominant pattern (data not shown).
Extensive strain typing of large numbers of individual
BSE-infected cattle either by biological or molecular
methods has not been reported.
Presumably, the different genetic background of the
different inbred mouse lines is crucial in determining
which prion strain propagates on BSE inoculation. The
transgenic mice described here have a mixed genetic
background with contributions from FVB/N, C57BL/6 and
129Sv inbred lines; each mouse will therefore have a
different genetic background. This may explain the
differing response of individual 129MM Tg35 mice, and
the difference between 129MM Tg35 and 129MM Tg45
mice, which are, like all transgenic lines, populations
derived from single founders. Indeed, the consistent
distinctive strain propagation in FVB and C57BL/6 versus
SJL and RIIIS lines may allow mapping of genes relevant
to strain selection and propagation, and these studies
are in
progress.
That different prion strains can be consistently isolated
in different inbred mouse lines challenged with BSE
prions argues that other species exposed to BSE may
develop prion diseases that are not recognizable as being
caused by the BSE strain by either biological or molecular
strain typing methods. As with 129MM Tg35 mice, the
prions replicating in such transmissions may be
indistinguishable
from naturally occurring prion strains. It
remains of considerable concern whether BSE has transmitted
to, and is being maintained in, European sheep
¯ocks. Given the diversity of sheep breeds affected by
scrapie, it has to be considered that some sheep might have
become infected with BSE, but propagated a distinctive
strain type indistinguishable from those of natural sheep
scrapie. ...
The EMBO Journal Vol. 21 No. 23 pp. 6358±6366, 2002
6358 ãEuropean Molecular Biology Organization
http://embojournal.npgjournals.com/cgi/reprint/21/23/6358
J Neuropsychiatry Clin Neurosci 17:489-495, November 2005
doi: 10.1176/appi.neuropsych.17.4.489
© 2005 American Psychiatric Publishing, Inc.
Psychiatric Manifestations of Creutzfeldt-Jakob
Disease: A 25-Year Analysis
Christopher A. Wall, M.D., Teresa A. Rummans, M.D.,
Allen J. Aksamit, M.D.,
Lois E. Krahn, M.D. and V. Shane Pankratz, Ph.D.
Received April 20, 2004; revised September 9, 2004;
accepted September 13,
2004. From the Mayo Clinic, Department of Psychiatry
and Psychology,
Rochester, Minnesota; Mayo Clinic, Department of
Neurology, Rochester,
Minnesota. Address correspondence to Dr. Wall, Mayo
Clinic, Department of
Psychiatry and Psychology, Mayo Building-W11A, 200
First St., SW, Rochester,
MN 55905;
[email protected]. (E-mail).
This study characterizes the type and timing of
psychiatric manifestations
in sporadic Creutzfeldt-Jakob disease (sCJD).
Historically, sCJD has been
characterized by prominent neurological symptoms, while
the variant form
(vCJD) is described as primarily psychiatric in
presentation and course: A
retrospective review of 126 sCJD patients evaluated at
the Mayo Clinic from
1976-2001 was conducted. Cases were reviewed for
symptoms of depression,
anxiety, psychosis, behavior dyscontrol, sleep
disturbances, and
neurological signs during the disease course. Eighty
percent of the cases
demonstrated psychiatric symptoms within the first 100
days of illness, with
26% occurring at presentation. The most commonly
reported symptoms in this
population included sleep disturbances, psychotic
symptoms, and depression.
Psychiatric manifestations are an early and prominent
feature of sporadic
CJD, often occurring prior to formal diagnosis.
snip...
CONCLUSIONS
Historically, psychiatric manifestations have been
described as a relatively
infrequent occurrence in the sporadic form of
creutzfeldt-Jakob disease.
However, our findings suggest otherwise. In this study,
a vast majority of
the cases were noted to have at least one psychiatric
symptom during the
course of illness, with nearly one-quarter occurring in
the prodromal or
presenting phase of the illness. After comparing the
frequency of
neuropsychiatric symptoms in sporadic CJD to studies
describing the variant
form of CJD, we found that there are fewer clinical
differences than
previously reported.5-7 While the age of patients
with vCJD presentation
is significantly younger and the course of illness is
longer, the type and
timing of psychiatric manifestations appear similar
between these two
diseases. ...snip...
http://neuro.psychiatryonline.org/cgi/content/abstract/17/4/489
Personal Communication
-------- Original Message --------
Subject: re-BSE prions propagate as
either variant CJD-like or sporadic CJD Date: Thu, 28
Nov 2002 10:23:43
-0000 From: "Asante, Emmanuel A" To:
"'
[email protected]'"
Dear Terry,
I have been asked by Professor Collinge to respond to
your request. I am
a Senior Scientist in the MRC Prion Unit and the lead
author on the
paper. I have attached a pdf copy of the paper for your
attention. Thank
you for your interest in the paper.
In respect of your first question, the simple answer
is, yes. As you
will find in the paper, we have managed to associate
the alternate
phenotype to type 2 PrPSc, the commonest sporadic CJD.
It is too early to be able to claim any further
sub-classification in
respect of Heidenhain variant CJD or Vicky Rimmer's
version. It will
take further studies, which are on-going, to establish
if there are
sub-types to our initial finding which we are now
reporting. The main
point of the paper is that, as well as leading to the
expected new
variant CJD phenotype, BSE transmission to the
129-methionine genotype
can lead to an alternate phenotype which is
indistinguishable from type
2 PrPSc.
I hope reading the paper will enlighten you more on the
subject. If I
can be of any further assistance please to not hesitate
to ask. Best wishes.
Emmanuel Asante
<> ____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics
Dept. Imperial
College School of Medicine (St. Mary's) Norfolk Place,
LONDON W2 1PG
Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email:
[email protected]. (until 9/12/02)
New e-mail:
[email protected]. (active from now)
____________________________________
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.
snip...end...TSS
that's all folks...............TSS
