Prions
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Husband-to-wife CJD
3 cases now of unconfirmed nvCJD in Florida
Americans' love affair with hamburgers
Update on UK nv-CJD victims
Flowery plaques reported in Japanese dura mater case
U.S. Takes Steps to Avoid Mad Cow Disease

24-nucleotide deletions in the prion gene: analysis of associated phenotypes

Cervenakova, L, Brown, P,Piccardo, P,  ... Gajdushek, DC, Goldfarb, LG
in Transmisablle Subacute Spongiform Encephalopathies: Prion Diseases  pp 433-444
L Court, B Dodet, editors.  Elsevier, Paris 1996
Article notes by webmaster 20 Sept 1997
This is an interesting case where clinical, pathological, and immunocytochemical data strongly support the diagnosis of CJD in both husband and wife. The wife was the only caregiver during the husband's illness.

The husband had died at age 54, after a 9 month illness of progressive mental and physical decline five years before the onset of clinical symptoms in his wife, who died at age 54, after subacute onset of agitation, confusion and mental slowness progressing to ataxic gait and myoclonic jerks, with severe gliosis and punctate prion imunoreactivity.

Genetically, the husband's prion gene was normal: no changes and homozygous methionine at codon 129. The wife had an R3/R4 deletion in one repeat region (a common polymorphism) and was also met/met. This allele may provide genetically determined susceptibility to environmentally CJD but is not normally causative.

The couple evidently lived in the US. The case record is consistent with horizontal transfer from husband to wife. There is no information provided as to occupation, dietary preferences, or travel history. Strain-typing was not reported -- however, this would not be expected to distinguish between horizontal transfer and common dietary exposure. Two unrelated cases of sporadic CJD at such early ages seems unlikely if the incidence is 250 cases per year in the entire US.

3 cases now of unconfirmed nvCJD in Florida

Listeserve postings 18 Sept 97
Events are still unfolding in the [unconfirmed] Florida nvCJD story. It seems now that a second and third patient are under discusssion. An elderly woman and a 67 year-old male are affected in addition to the original 51 year-old. Both doctor and family want anonymity. A paper is said to be in press in the New England Journal of Medicine.

Florid plaques reported in Japanese dura mater case

20 Sept 97 Lancet
[View color slide].
Shutaro Takashima, Jun Tateishi, Yoshiharu Taguchi, Hiroshi Inoue
The Japanese National Committee for Creutzfeldt-Jakob disease (CJD) reported there are 43 patients with CJD in Japan after implantation of cadaveric dura mater, and that no case of new-variant CJD (nvCJD) has been detected. We report a case with similar features to nvCJD.

At the age of 38 years, a Japanese woman received a cadaveric dural graft (Lyodura, B Braun Melsungen AG, Germany) after a clipping procedure of the right middle cerebral artery aneurysm in September, 1985. In November, 1994, 110 months after the procedure, she became unsteady and had blurred vision. She was admitted to hospital because of progressing ataxia. Examination disclosed dementia, visual disturbance, hyperreflexia, and cerebellar ataxia. Blood chemistry and cerebrospinal fluid were normal. Brain computed tomography (CT) showed no abnormal lesions. There was slow activities without periodic discharge on her electroencephalogram (EEG). After admission, she successively developed dementia and myoclonus, and became akinetic and mute. Serial brain CT scans revealed no abnormal findings, and serial EEGs showed diffuse slow activity without periodic discharge. She died in March 1995, 17 months after the first symptoms.

The prion protein immunohistochemical staining of temporal cortex showed unicentric PrP plaque surrounded by a zone of spongiform change, the same appearance as florid plaque.

The PrP gene analysis of her blood and brain tissue showed no mutations with homozygosity, Met/Met, at codon 129. Because she had received a dural graft and had a normal PrP gene, she was thought to have iatrogenic CJD although there were numerous PrP plaques including typical florid plaques. There have been two previous cases of CJD with PrP plaques who had received a dural graft. These three cases had a relatively long latency, no periodic discharge on EEG, and no gross brain atrophy. The unusual features of this case are similar to the features of nvCJD.

Different patterns of immunoblotting have been reported between cases with nvCJD and dura-graft cases. No western blotting was done in this present case because the whole brain had been fixed by formalin. This and the other two cases suggest that florid plaques are not specific to nvCJD.

1 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25.

2 Lane KL, Brown P, Howell DN, et al. Creutzfeldt-Jakob disease in a pregnant woman with an implanted dura mater graft. Neurosurgery 1994; 34: 737-40.

3 Kopp N, Streichenberger N, Deslys JP, et al. Creutzfeldt-Jakob disease in a 52-year-old woman with florid plaques. Lancet 1996; 348: 1239-40.

4 Collinge J, Sidle KCL, Meads J, et al. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90.

5 Parchi P, Capellari S, Chen G, et al. Typing prion isoforms. Nature 1997; 386: 232-33.

Creutzfeldt-Jakob-disease in a 52-year-old woman with florid plaques

Kopp,N.; Streichenberger,N.; Deslys,J.P.; Laplanche,J.L.; Chazot,G.
Lancet 1996; 348(N9036): 1239-40
Sir--A new variant of Creutzfeldt-Jakob disease (nvCJD) has been recently described.1,2 CJD has been reported in recipients of cadaveric human dura mater grafts. We report a case which may be related to both conditions. A 52-year-old woman from Savoie was referred to a neurology department in March, 1995, with progressively evolving impairment of walking. She had a left sylvian artery aneurism operated on in 1984....

Charles Arthur:

"The CJDSU says that this case was examined and determined not to be nv-CJD. The count of cases remains one in France; this would have been the second if confirmed, but it wasn't. The point about florid plaques is interesting as it seems to imply something about both the route and form of infection."

Commentary: the trouble with dura mater and florid plaques is that we have no idea what form of the disease the donor(s) had, whether it was familial, sporadic, itself iatrogenic, or even nvCJD. No patient records or DNA was kept by the German company for the dura mater donors, leaving us with only strain-typing as a way to move forward, but that has not been done for any of the florid plaque cases. It might make some sense to pursue this in the Japanese situation, to investigate whether the contamination of their donor mater was heterogeneous, what exactly it was contaminated with. I am not sure if they have saved any tainted dura mater itself or passaged it directly to animals. There is potential distant relevence to therapy. -- webmaster

Update on nv-CJD victims

Charles Arthur The Independent newspaper
"The London Times report quoting the CJDSU saying that those developing (the paper said "catching", which is a clue to how well-informed this wasn't) CJD appeared to have eaten beef and other meat products three times more than those who didn't.

I spoke today to James Ironside who said that (i) these results are ONLY for sporadic CJD victims - no nv-CJD cases were included in the study; (ii) though some of the results might appear to be statistically significant, realistically it's very hard to be sure what people actually ate, because you're interviewing their relatives; (iii) effect does not imply cause. He wasn't too impressed by the squirrel brain stuff either, but that's by the way.

Now, on to the list of nv-CJD victims. I am reliably informed by two sources that Vicky Rimmer is NOT a case of nv-CJD. Refer to the original Lancet article for age, sex, geographic details about the person who was in a long coma (but died earlier this year). The person who is still alive with nv-CJD according to the official figures is, I think, Donna Mellowship.

So here's my list of 23, though I suspect a couple may be missing. I've put question marks against those which I wasn't certain about."

Peter Hall
Stephen Churchill
Michelle Bowen
Jean Wake
Maurice Callaghan
Ann Richardson
Leonard Franklin
Alison Williams
Anna Pearson
Ken Sharp
Andrew Haig [denied??]
Barry Baker
Janice Stuart
Vicky Lowther
Donna Mellowship [alive?]
?Adrian Hodgkinson
Matthew Parker
Susan Carey
Keith Humphrey
Donnamarie McGivern (alive)
Mandy Minto (alive)
Clare Tomkins (alive)
Chris Warne (alive)

Americans' love of hamburgers seems endless

September 21, 1997 By SCOTT BAUER, Associated Press Writer
LINCOLN, Neb. (10:15 p.m. EDT) -- So a hamburger can kill you. So what? This, fellow Americans, is One Nation, Under God, Indivisible, with burgers and ketchup for all. And if you think that some itty bitty bacteria are going to change all that, well, you're a Quarter Pounder short of a full load.
"There's something about eating a big bite of hamburger," said Sam Ross, former manager of King's Drive In, a Lincoln, Neb., fast food restaurant dating back to the 1960s. "It's something you can chow down on."
There's the "Sunshine Burger" in San Francisco, served with sprouts, scallions and avocado; the "Jiffy Burger" in Lincoln, Neb., with peanut butter and bacon; the five-pound "Family Burger" in Sault St. Marie, Mich., designed to serve 10 to 12 people. Since the 1940s, hamburgers have been America's favorite food, according to Nation's Restaurant News. There were 5.4 billion hamburgers/cheeseburgers served in commercial restaurants in 1996, that is up 3.8 percent from the previous year.

Ross said burger sales make up 75 percent of King's business -- about 300 burgers a day. He said business did not slow even with the E. coli contamination scare that led to the recall of 25 million pounds of ground beef from a Columbus, Neb., plant -- the largest meat recall in the nation's history. No lag in beef sales was reported across the country, even though the contaminated hamburger sickened more than a dozen people in Colorado. Of course, many years of warnings about cholesterol haven't pushed McDonald's or Burger King out of business, either.

"All Americans grew up with hamburgers," said Alisa Harrison with the National Cattlemen's Beef Association -- a group that, admittedly, has a steak in the burger's popularity. "Especially when you're a teen-ager. What do you do when you get your driver's license? You get a burger."
The hamburger's roots can be traced back to the tribes of Tartary living in the Baltic provinces in the Middle Ages. German trading partners developed the Hamburg steak -- fried beef seasoned with onions -- and brought it to America in the 1700s and 1800s.

Stories vary on just how the Hamburg steak evolved into the present-day hamburger. Some credit Charlie Nagreen of Seymour, Wis., with inventing it in 1885 and selling it at the Outagamie County Fair. Others say Louis Lassen of New Haven, Conn., created the hamburger steak in 1900 as a means for using the trimmings from the steak sandwich he featured at his lunch wagon.

In any case, the hamburger as we know it today gained widespread attention at the 1904 World's Fair in St. Louis, Mo., where it was said to be all the rage. In 1921, White Castle became the world's first hamburger chain, and eventually billions and billions and billions were served. ...

Brian Lewis, 24, of Lincoln, Neb., said he doesn't think about why he likes hamburgers so much.

"I don't really know," he said, eyeing his bacon double cheeseburger at Wendy's in downtown Lincoln. "It's just something that's not too difficult."
Bingo. Ross, the man who managed the Lincoln drive-in, says burgers are relaxing food. Is that special sauce dripping down your arm? Who cares?
"You don't have to worry about silverware," he said.

U.S. Takes Steps to Avoid Mad Cow Disease

JAMA Tuesday September 23 (Reuters)
NEW YORK -- A handful of young adults in the U.K. have died of a fatal neurological disease that may have been caused by eating beef from cattle infected with "mad cow disease," or bovine spongiform encephalopathy (BSE). Could it happen in the U.S.? It's possible, although steps are being taken to help prevent such an outbreak, according to Dr. Paul Brown, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

Both countries used ground-up animal carcasses to make cattle feed and nutritional supplements, a step that probably helped a neurological disease in sheep, scrapie, to be passed to cows. In the late 1970s, both the U.K. and the U.S. changed the way it processed sheep carcasses, increasing the likelihood that scrapie could be passed to cattle. And both countries have scrapie-infected sheep -- a disease known for centuries that has never caused illness in humans. The U.S. has had an annual incidence of 30 to 50 cases of scrapie in 8 million sheep and the U.K. has 200 to 300 cases in 42 million sheep.

"Why then have we not seen a BSE epidemic in the United States?" Brown wrote in the current issue of The Journal of the American Medical Association. There may be a couple of reasons, he said. For example, the strains of scrapie in the U.S. may not be capable of causing illness in cattle. And in the U.S. only about 0.6% of rendered animal protein is derived from sheep tissue compared with 14% in the U.K.

"A third explanation is that we do have an epidemic, but have simply not recognized it," he said. Cattle injected with U.S. strains of scrapie do develop a neurological disorder, but do not show the spongy holes in the brain that are characteristic of BSE-cows in Europe. And there have been outbreaks of spongiform encephalopathy in U.S. mink that were fed meat from "downer cows," so-called because they lie down from an unknown illness before dying.

However, analysis of more than 6,000 cows in the U.S. with neurological disorders or considered "downer cows" have not yet turned up a single case of BSE.

"This is reassuring, and will be increasingly persuasive as additional
thousands of animals are examined in coming years," Brown wrote.
It could take several years to conclusively determine that the 21 people in the U.K. and 1 in France who died of the neurodegenerative disorder Creutzfeldt-Jakob disease, in fact contracted the illness from eating contaminated beef. In the meantime, the British government has made a number of changes to reduce the possible spread of BSE, including slaughter of sick animals, eliminating bovine brain, spleen and thymus from human food, and banning mechanically recovered meat -- meat recovered from a carcass using high-powered hoses -- from the spinal column.

In the U.S., cattle and cattle products from Great Britain have been banned and tighter controls on sheep have been instituted, including a ban on transferring sheep from scrapie-infected flocks to uninfected flocks. In June 1997, the Food and Drug Administration banned the use of most mammal carcasses in cattle feed, and at some point in the future, the use of any animal tissue in livestock feed may also be banned.

It's possible that high-risk tissues, such as the cow brain, could be banned as food for humans in the U.S., despite the lack of evidence that it is a problem in this country. And other cow-derived products are under scrutiny, including gelatin, which is in multiple products including drug capsules and cosmetics.

"Altogether, a full plate for government regulatory agencies," Brown concluded.

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