Post by malxscfc on Sept 14, 2006 22:29:52 GMT
Have you ever noticed that on most mass-public websites the FAQs are NEVER EVER of any use to the particular problem you wish to find an answer to? Even though the company has spent about £3.2M developing said website?!
They answer all the stuff EVERYBODY knows, (even your deceased Great Aunt), but never anything useful.
On the other hand, just occasionally you come across some spectacularly intriguing FAQs.
To whit:Uh-Huh!!
It's so obvious once you know!
I've asked myself that question every day for... oooooh.... ages!!
So nice to get that particular conundrum cleared up at last!
So, esteemed, friends, does that make FAQs a Hero or Villain? Or is this issue so mundane as to be a...... FAQ?
They answer all the stuff EVERYBODY knows, (even your deceased Great Aunt), but never anything useful.
On the other hand, just occasionally you come across some spectacularly intriguing FAQs.
To whit:
QUESTION 1.
The pathology of the copper deficient brain is completely different from the pathology of TSE diseased brain, so how can you claim that copper deficiency is linked to the cause of TSE ?
ANSWER
People get me wrong - my thesis promotes a multifactorial aetiology involving a combination of factors. I am saying that sporadic TSEs are essentially trivalent manganese toxicity on top of subclinical copper deficiency, so you would get an entirely different pathological profile than what you would observe in straight Cu deficiency. For instance, the classic Mn toxicity hallmarks such as amyloid fibrils, neuronal loss, astrogliosis and shrunken basal ganglia (caudate nucleii, putamina). are precisely present in TSE neuropathology.
Most normal prion proteins bond onto five copper atoms per molecule in the healthy individual; but the different strains of scrapie are largely dictated by the number of copper atoms that bond to prion protein. Some TSE susceptible genes only encode for synthesis of prion proteins that will bond 3 copper atoms; thus predisposing that mammal to scrapie susceptibility which will take some time to incubate, etc, etc.
On the other hand, the copper deficit in the more aggressive, short lived BSE and variant CJD syndromes is not caused by primary copper deficiency due to environmental deficiencies , but is caused by certain organo pollutants such as systemic insecticides (eg OP warble fly chemicals , which actually directly modify the histidine ligands (via generation of singlet oxygen) which bond copper to the prion protein. So basically, no copper can bond to prion protein any longer; whether copper is abundant in the brain or not! This is why vCJD/BSE is so much more rapid than traditional scrapie, simply because no copper can bond at all; whereas the more protracted incubation period in sporadic TSEs, such as scrapie, is genetically mediated by a maximum of only one, two or three copper atoms being able to bond to the prion protein - thereby creating the scrapie susceptible genotypes where susceptibility is activated once environmental copper becomes deficient
(From www.markpurdey.com/faqs_1.htm )
The pathology of the copper deficient brain is completely different from the pathology of TSE diseased brain, so how can you claim that copper deficiency is linked to the cause of TSE ?
ANSWER
People get me wrong - my thesis promotes a multifactorial aetiology involving a combination of factors. I am saying that sporadic TSEs are essentially trivalent manganese toxicity on top of subclinical copper deficiency, so you would get an entirely different pathological profile than what you would observe in straight Cu deficiency. For instance, the classic Mn toxicity hallmarks such as amyloid fibrils, neuronal loss, astrogliosis and shrunken basal ganglia (caudate nucleii, putamina). are precisely present in TSE neuropathology.
Most normal prion proteins bond onto five copper atoms per molecule in the healthy individual; but the different strains of scrapie are largely dictated by the number of copper atoms that bond to prion protein. Some TSE susceptible genes only encode for synthesis of prion proteins that will bond 3 copper atoms; thus predisposing that mammal to scrapie susceptibility which will take some time to incubate, etc, etc.
On the other hand, the copper deficit in the more aggressive, short lived BSE and variant CJD syndromes is not caused by primary copper deficiency due to environmental deficiencies , but is caused by certain organo pollutants such as systemic insecticides (eg OP warble fly chemicals , which actually directly modify the histidine ligands (via generation of singlet oxygen) which bond copper to the prion protein. So basically, no copper can bond to prion protein any longer; whether copper is abundant in the brain or not! This is why vCJD/BSE is so much more rapid than traditional scrapie, simply because no copper can bond at all; whereas the more protracted incubation period in sporadic TSEs, such as scrapie, is genetically mediated by a maximum of only one, two or three copper atoms being able to bond to the prion protein - thereby creating the scrapie susceptible genotypes where susceptibility is activated once environmental copper becomes deficient
(From www.markpurdey.com/faqs_1.htm )
It's so obvious once you know!
I've asked myself that question every day for... oooooh.... ages!!
So nice to get that particular conundrum cleared up at last!
So, esteemed, friends, does that make FAQs a Hero or Villain? Or is this issue so mundane as to be a...... FAQ?