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Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

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Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#161

Post by arkades »

travisoneill1 wrote: post #109
nonbel wrote: post #100

Earlier quoted context omitted.

How is this at all a "twist"? The reason you cannot deactivate prions using these methods is that they are meant to denature protein. Prions are "amyloids"/beta-sheets, which means they are already in the lowest-energy state. This lowest-energy-state is exactly why the presence of prion can serve as a nucleation point for other proteins to denature into beta-sheets.

I don't care whether or not it's a "twist". I care that there is an entire class of pathogen that we don't know how to sterilize a surface of.

It’s been said a few times in this thread that that is a misrepresentation by the article. Allow me to quote at length from an article on the topic by Brown and Lee:

One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature, or modify proteins do have activity against prions [7]. The PrP purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 hours), or immersion in 1N NaOH (for 30 minutes, repeat three times), or immersion in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat-resistant subpopulations that fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13].

Newer decontamination techniques are being investigated. There has been some success in sterilization using a combination of sodium dodecyl sulfate (SDS), proteinase K, and pronase [14]. A radio-frequency gas-plasma treatment has been shown to effectively decontaminate surgical instruments [15]. Another group has tested a decontamination formula combining copper metal ions with hydrogen peroxide [16].

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#162

Post by chc4 »

stef25 wrote: post #147
chc4 wrote: post #141

A few months ago I was talking at a family gathering and learned that one of my distant relatives has CJD. They're a high-ranking company executive, but their cognition is rapidly wasting away and will be dead within a few years. Another family member that was a nurse in Kentucky(?) said they have a high rate of prion disease due to farmers inhaling contaminated dirt for years. There are a few comments here about how…

> A few months ago I was talking at a family gathering and learned that one of my distant relatives has CJD. They're a high-ranking company executive, but their cognition is rapidly wasting away and will be dead within a few years Are you sure it's CJD? Article says 95% of CJD patients won't live 12 months after diagnosis. > Another family member that was a nurse in Kentucky(?) said they have a high rate of prion dis…

I was told mad cow disease and CJD interchangably, which looking it up seems to be slightly different. I don't know the difference between CJD and vCJD and Wikipedia isn't helping much. Honestly, I don't know how fast it's progressing, so it may in fact be months. They may already be dead for all I know, but it sounded like they were diagnosed several months before - they don't know how long ago she got it though, due to the long incubation. The family member mentioned mood swings, improper outbursts in conversation, and memory degeneration and how they're nearly bedbound now due to loss of balance.

The nurse family member said cow farmers, so I assume cow feces contaminated dirt, and that their brains looked "like Swiss cheese". This was also in the context of mad cow disease. I checked my notes from the day and it was North Carolina, not Kentucky.

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#163

Post by Terr_ »

arkades wrote: post #10

Prion disease is exceedingly rare. CJD is the most common, with an incidence of 1 per 1,000,000 person-years worldwide, inclusive of all transmission vectors (including medical procedures). Iatrogenic transmission is a rarer subset still: the riskiest transplants (with respect to CJD) are in the central nervous system. The UK tracked their transmission rates from 1970 to 2003 (a long period is needed because surgical…

> Prion disease is exceedingly rare.

Isn't that begging the question? I mean, the author's concern seems to be that the prevailing belief hasn't been well-tested compared to the potential impact of it being wrong.

It's already happened before: There was a period of time when most medical practitioners were adamant that their actions could possibly be transferring disease, and it was an uphill fight to get regular disinfectants and hand-washing.

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#164

Post by Terr_ »

OldFatCactus wrote: post #24

I had project in college on Prions. Some interesting things I remember: * Kuru (laughing disease) was transmitted from cannibalism. Women and children of the tribe were more likely to contract it because they were more often given the less palatable parts of the bodies, which included brains * Some countries do not trust American cattle because our standards for Prion screening are too low * Kentucky has issues with…

I wonder if the correlation between prion diseases and brains indicates either:

1. Symptoms show up soonest in brains and so can be distinguished from other causes of impairment or death.

2. Humans already some immune mechanism that helps protect against prions, but brain tissue is particularly susceptible because of it's less-usual immune-system setup.

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#165

Post by subroutine »

nwallin wrote: post #145
arkades wrote: post #21

Earlier quoted context omitted.

We take measures now, for tissues where prions are a possible transmission risk. The article mis-represented that. But: (1) there are only so many resources to go around. Should we be devoting them to vanishingly rare things rather than things that might actually affect you? (2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. One step up…

> (2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. Chronic wasting disease (CWD) (affects deer) can be transmitted by infected saliva. One of the symptoms of symptoms of CWD is excessive saliva production. It is very transmissible, and is devastating captive populations of deer, although it is relatively rare in the wild. I think if a…

Is there any mammalian prion disease not linked to the PRNP gene (which is fairly conserved across mammals)?

At first I assumed that 'prions' came in many flavors, like virus. However from my brief lit search, it seems like people are talking about (p)rion proteins as if they were't all (P)rion proteins (PRNP). If all mammalian 'prion' disease can be traced to a single conserved gene, I think the risk of another 'prion-like' disease cropping up is pretty low.

But then again, who knows? Prion disease still seems shrouded mystery, which I find odd given (1) how inherently interesting this topic seems, and (2) we've gotten really, really good at molecular biology.

I feel like we are missing a key piece of the puzzle when it comes to understanding prion disease. The literature seems to want people to conceptualize the disease etiology as such: an alternately folded (disease causing) variant of PRNP protein (PrPs) bumps into a normal version of PRNP (PrPc), causing a normal copy of PrPc to also misfold into PrPs. Rinse, repeat. So you can basically think of it like an enzyme that catalyzes a conformational change on versions of itself, in a feed-forward cascade. I feel like an alternative hypothesis however, could be one of an autoimmune response. The mammalian immune system, particularly the antibody system, is mind blowing. This system can recognize virtually any foreign protein -- it can even recognize specific sub-moieties and conformations of proteins (antigens). It must, do this while never mistaking an endogenous protein to be foreign; if it does, you get an autoimmune disease. My idea is basically that PrPs is just slightly different enough from PrPc to get tagged as foreign by the antibody system (which it absolutely can do, given that we can perform western blots to detect the PrPs variant), but also just similar enough for the antibody system to mistake some endogenous PRNP for the foreign version.

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#166

Post by fao_ »

arkades wrote: post #21
fallingknife wrote: post #18

Earlier quoted context omitted.

Infectious disease is one area where fear of the unknown is rational. We don't just need to defend against existing diseases, but also diseases yet to emerge. Just because CJD is rare doesn't mean that the next prion disease will be, so it would make sense to take measures to prevent transmission of prions now.

We take measures now, for tissues where prions are a possible transmission risk. The article mis-represented that. But: (1) there are only so many resources to go around. Should we be devoting them to vanishingly rare things rather than things that might actually affect you? (2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. One step up…

> (2) prions will never be a wildfire plague. They have little or no tranmissive ability

Mad Cow Disease was caused by a prion[0].

[0]:https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#167

Post by davemp »

davemp wrote: post #87
arkades wrote: post #10

Prion disease is exceedingly rare. CJD is the most common, with an incidence of 1 per 1,000,000 person-years worldwide, inclusive of all transmission vectors (including medical procedures). Iatrogenic transmission is a rarer subset still: the riskiest transplants (with respect to CJD) are in the central nervous system. The UK tracked their transmission rates from 1970 to 2003 (a long period is needed because surgical…

> This article is one good step above scare-mongering, but only one. I agree. Could a moderator please change the title at the least? "Prions, A Rare and Lethal Infection, ..." would be slightly better.

In lue of the downvotes, would anyone like to defend the efficacy of the article's title?

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#168

Post by Nasrudith »

gumby wrote: post #91
folli wrote: post #76

Earlier quoted context omitted.

Passive immunization might indeed be a feasible option, but of course requires timely detection.

Couldn't we immunize before exposure as we do with, say polio, TB, influenza et al? Then no detection would be needed. Or are the abnormal prions in CJD and the like not uniform enough for general prophylaxis? I really have a naive understanding of immunotherapy, so sorry if my question is dumb.

Whatever it is isn't that simple given that CJD is just a standard of care. I'm more an enthusiastic dabbler who occasionally checks if I could have been capable technically than an expert admittedly.

I did some more cursory research. Interestingly I was half-wrong about the immune system - while I was right about it not being equipped to stop it can do something. Monoclonal antibody treatments delay it. However another problem is that the body's own proteins which are deformed into prions aren't recognized as foreign bodies. Given that notes mention that mice vaccines only delay the onset along with monoclonal antibody treatments. Some sources seem to indicate that it only blocks prions from deforming as opposed to eliminating combined with the fact that native proteins will keep on cascading.

I wonder how much processing power would be required just to get a candidate 'prion grabber' - never mind going through ones which won't turn out to be horrifyingly toxic in other ways.

Here are a few sources I skimmed I would be glad to know where I went wrong.

https://www.researchgate.net/publication/233941323_Immunothe...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063508/

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#169

Post by mirimir »

arkades wrote: post #161
travisoneill1 wrote: post #109

Earlier quoted context omitted.

I don't care whether or not it's a "twist". I care that there is an entire class of pathogen that we don't know how to sterilize a surface of.

It’s been said a few times in this thread that that is a misrepresentation by the article. Allow me to quote at length from an article on the topic by Brown and Lee: One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denatu…

OK, but how do ophthalmologists typically decontaminate their instruments?

Re: Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims

#170

Post by mirimir »

fao_ wrote: post #166
arkades wrote: post #21

Earlier quoted context omitted.

We take measures now, for tissues where prions are a possible transmission risk. The article mis-represented that. But: (1) there are only so many resources to go around. Should we be devoting them to vanishingly rare things rather than things that might actually affect you? (2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. One step up…

> (2) prions will never be a wildfire plague. They have little or no tranmissive ability Mad Cow Disease was caused by a prion[0]. [0]: https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...

And it was spread by the livestock industry.
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