Discussion in 'XMRV Research and Replication Studies' started by richvank, Sep 10, 2010.
I was at the river
"As for activation of more or less low level or quiescent but persistent infectious virus, there seem to be several mechanisms. The virus has both a glucocorticoid response element (GRE) and an androgen response element (ARE) in its promotor region. It also has binding regions for NK Kappa B proteins in its response elements. In any organ with high levels of local androgenic stimulation such as the prostate and perhaps during puberty, the virus could activate. No mention was made of the effect of the predominant female sex hormones but estrogen is the equivalent androgen-like hormone in females. As for the NF Kappa B sites, any strong immune response with an associated cytokine storm would also be a strong. As for the GRE in the promotor region, severe stress will activate the virus or the use of glucocortocoid hormones and perhaps any precursor steroid hormone such as pregnenolone stimulant and such stimulation certainly occurs in the bronchial tree which is frequently stimulated with antigen, especially during allergy season
well, it matches what I have been experiencing but......Yikes! We all new this about hormones activating xmrv, but again....Yikes! Certainly explains how onset and progression of the disease is highly influenced by stress. It also explains how my last relapse followed a course of (low dose) Prednisone. But this also begins to illuminate ideas for treatment.
I'm sure that "allergy season" hypothetically could cause pressure on the system and make it more likely that the virus will reactivate.
But I wonder if the actual effect that they see during "allergy season" might not really be due to the increased presence of outdoor biotoxins during that time.
It's hard to know for sure, without hearing exactly when and where they observed the effect.
However, I don't have any allergies at all. I just have toxicity reactions to biotoxins.
And the seasons of the year really affect how I'm feeling.
The worst relapse I had in 20+ years was after a course of low dose Prednisone. Damn near killed me. It was given to me after an anaphylactic reaction. I got on the stuff and couldn't get off. Every time I tried my throat would swell, and I couldn't breathe. Thank god for epipens. I slowly weaned myself off over four torturous months, but was completely bedridden and terribly ill the entire time. It felt like some pathogen had taken over my body, maybe several. Lost over 40 pounds throughout the ordeal. Surprisingly once the Predisone was out of my system, I bounced back fairly well and quickly gained back the weight (and more, of course). That's one drug I won't be taking again.
So McClure is claiming that the heparin tubes are not only contaminated, but keeping the virus alive? (otherwise there would not be positives for virus culture and serology since there would only be viral DNA contaminants)
puberty; grief; childbirth; surgery; exercise; sleep deprivation; allergies; ear infections;pneumonia;any parasitic, bacterial, viral or yeast infection----even panic attacks!
Where did she say that? If the heparin was the cause of the contaminant, wouldn't it have caused positive results in the controls as well? Their blood was drawn into heparin tubes as well, no? I don't get it.
If heparin is the cause of the contamination, and it can produce viable virus that can infect cells, we are in big trouble. Heparin is used in all kinds of medical procedures. Almost every person who undergoes bypass surgery gets heparin in the OR.
I really want to know what the incidence of cervix-cancer is within the CFS population. As we all know, we've been told that some strains of HPV is causing these kind of cancers. But, there appears also a very agressive form of cancer of the cervix, so I was wondering whether a kind of XMRV could be the puppet master making HPV more virulance, same as with EBV, CMV and all other viruses. It would render HPV not the direct cause...
Altho' this may be off topic - as it is the Paul Cheney thread, I was wondering where I may access the Cheney XMRV conference poster presentation, the data of which was touted as being something extraordinary.
I guess there could be all kinds of reasons why the monkeys in that study didn't get sick:
- Monkeys aren't 100% identical to humans, obviously.
- It might take a long time, before actual symptoms appear (we might have been virus ridden for years, before we displayed symptoms).
- It might need a specific trigger, like suggested multiple times in this thread.
- Monkeys are still wild animals. Wild animals don't tend to display symptoms of sickness, unless they are really, really sick or handicapped. Predators recognize sick animals and target them as easy prey. So most wild animals are very good at hiding symptoms.
- Would we even recogznize a monkey that has mild CFS? Animals tend to rest and sleep a lot, anyways.
I feel like a trainwreck most days, but I am still able to work about 28 hours a week, and I look healthy. If I wasn't able to speak, people might consider me healthy as well.
Two-Strike Alzheimer's Theory, B12, methylation blocks and ME/CFS
Writing, as always, as an enthusiastic amateur...
ETA: These thoughts seem to be rather off-topic now but arose from thoughts around discussions earlier in the thread and from further thoughts after reading Dr Cheny's comments - do let me know if I should take them elsewhere...
I agree Elisabeth, that a picture seems to emerge...
I find a number of further confirmations in Dr Cheney's comments that seem very consistent not only with a model of XMRV latent and reactivated infection, but also with the rather broader proposed models of both ME/CFS and neuro-immune pathophysiology. As I explore around this I even begin to wonder about some aspects of neuro-psychiatric disease also.
It might or might not help if I broaden the picture considerably in considering the first model above. I came across the following "2-strike" model from the Institute of Psychiatric Research, Indiana University, which seems to me to be similar to one of the "3-strike" models, in that the two strikes may only hit home at those with specific vulnerabilities, but note that this model allows that they need not take place within a short space of time.
The proposed vulnerabilities, in the case of ME/CFS at least, that enable the two-strike process are that (eg) APOBEC3 and RNAsel mutations may mean that some of the DNA methylation defence mechanisms are unable to "tidy up" certain types of infected cells - they can no longer mutate the infected DNA so as to render rogue sequences harmless.
So here's the '2-strike' theory affecting those with genetic vulnerabilities...in Alzheimer's...extracts from the abstract...
The model seems to be quite similar:
1. In early life, environmental stress (in the broadest sense) can affect the regulation of relevant genes through the DNA methylation process. In effect, certain genes become 'tagged' in what amounts to a long-term memory mechanism. Hypo-methylation, or a block in the methylation process, maintains this process.
2. Later in life, under extreme stress (perhaps repeating the same or similar environmental conditions and/or with the same or similar deficiencies of SAM, B6, B9, B12?) a second hit occurs and reactivates the latent learned environmental damage.
This only seems to make sense to me by imagining the situation as an invasion which is sufficiently severe as to 'breach the inner walls' and infect the system itself - the situation can be brought under control, but whenever the same type of invader is encountered again, there are enemies lurking inside the walls...and the immune vulnerabilities are essentially weaknesses in the process for identifying and rooting out those intruders.
Thinking more generally there are several connections which the above-mentioned paper highlights which overlap with ME/CFS - the hypo-methylation, the B12 deficiency, the role of genetic vulnerabilities, the 2-strike hypothesis: the combination of early environmental risk factors and later severe stress and trauma; perhaps most importantly the result being neurological symptoms...I find myself particularly struck by the involvement in this story of two more connections which I've saved to last in this list: psychiatric symptoms and trauma in early childhood - because at this point we may risk wandering into the territory of neuropsychiatry...
And yet perhaps we must: As I peruse the exclusionary conditions for a Fukuda diagnosis I'm struck by the thought that the following Fukuda exclusionary conditions lie in the range of ideopathic psychiatric conditions, and that these too presumably ultimately involve neuropathology: major depressive disorder with psychotic or melancholic features; bipolar affective disorders; schizophrenia of any subtype; delusional disorders of any subtype; dementias of any subtype; anorexia nervosa; or bulimia nervosa.
These conditions are, presumably, specifically exclusionary because they may otherwise present with the same or similar symptomology to ME/CFS - and if so, then might there be aspects of the pathophysiology in common also? It seems possible, at least. Perhaps a clue lies in the role of B12 deficiency in both of the above proposed models of the pathophysiology: a recent study in Alzheimer's adds to the evidence associating B12 and B6 deficiency with an increased rate of loss of neural tissue.
Here are some papers on B12 deficiencies in Alzheimer's and in CFS:
And also if the gut is dysfunctional and unable to absorb B12 and/or B6, perhaps even due to a deficient enzyme produced by a messed-up gene...then neural degeneration and further breakdown of the methylation process might be expected and there is the potential for a vicious cycle of inability to cope with DNA degradation.
Moreover that vicious cycle is only maintained in the case of XMRV by cortisol and hormones - which will eventually be depleted causing the replication process to subside, whereupon XMRV can be seen as parasite (as indeed can any such "corruption sequence" that thrives on the body's stress responses be seen as parasite), replicating only when the host is able to mount a "fight" mode, as soon as the host becomes energetic, and otherwise lying dormant in or around the regulator genes - potentially still causing deficiencies such as selected vitamin uptake inhibition, and thus impairing neurological maintenance and other fuctions.
This whole pattern seems to fit the strange patterns of ME/CFS symptomology very well. We seem to be describing an immune deficiency syndrome in which the pathogen is somewhat synergistic with the host, via its dependence on the host's stress responses.
Finally, what's also striking to me is the way that these emerging theories seem so consistent with anecdotal observations about both the common patterns of personal histories of ME/CFS illness progression, and also accounts of family histories. There is quite a bit of interest already, of course, in sporadic ME/CFS/XMRV connections to early-onset and childhood Alzheimer's, which I've most recently seen discussed in this thread of Gerwyn's:
Of course what would be needed to confirm all of the above, is more evidence - and so as we know only too well, of one thing we can be confident: more research is required...
This post is connected to mark's post, which is too long to quote conveniently. If that is moved, this should be moved as well.
First, there is recent evidence that vitamin D can delay progression of Alzheimer's. Vitamin D deficiency is also present in CFS/ME.
Second, in response to a number of comments on hypotheses requiring multiple 'hits'. This is more a change in the way researchers talk about disease than a difference in diseases. Polio was a devastating common disease only 60 years ago. While thorough population studies were not run before vaccination put an end to epidemics, the general consensus was that 90% of people infected with polio virus did not go on to develop the paralytic illness. If you go even further back, you could say much the same about tuberculosis. Diseases like rabies, where infection generally leads to disaster, are comparatively rare.
Most diseases involve multiple factors even if the first 'hits' take place at the time your genes are formed. Polio virus was practically endemic in urban populations. Bad luck in not inheriting genes which gave you innate immunity would be one 'hit'. Not being first exposed to a weak form of the virus, to provide acquired immunity, would be a second 'hit'. Today, because of vaccination programs using live virus, we have acquired immunity, even if we are not all lucky enough to inherit innate immunity.
Third, those primary psychiatric conditions treated as exclusionary generally lack known etiology. Major depressive disorders secondary to physical illness are very well known. Idiopathic depression is the 'common cold' of psychiatry. When an illness like MS is diagnosed, many patients may be moved from a primary psychiatric diagnosis to a secondary psychiatric illness diagnosis. Depression is very common in MS, and fatigue is often the earliest symptom. Dementia may also be present.
There is even more to this connection. A significant number of MS patients develop bipolar mood swings. When you include those MS patients initially classified as delusional, or having a somatization disorder, but reclassified after signs become clear, you cover a broad spectrum of psychiatric conditions. There will be substantial overlap between people with physical illnesses and those with undeniable psychiatric disorders.
Until all the overlap is sorted out, it behooves those of us lucky enough to be able present ourselves as rational sufferers from a physical illness to behave like we are rational. We wake up to the reality of this illness ever morning (even if we sleep well at night). Physicians don't experience this direct confirmation of hypotheses unless they come down with the disease.
I had precancerous changes in my cervix. I must have gotten HPV around the same time I got sick. To make etiology even more complex, I also got sick during pregnancy when, according to Cheney's website the same TH1 shift happens that's required for ERVs like XMRV.
What is very interesting about ERVs and likely true for XMRV is that they are TH1 immunosuppressive which is believed to be critical in the ability to get pregnant as the mother needs to be Th1 immunosuppressed to avoid rejection of the implanted fetus.
Thanks for asking about HPV. My sister who has CFS and I have both had repeat abnormal smears and treatment on our cervixes. It keeps coming back.
My first abnormal smear was in my late teens and a couple of years before the acute viral onset of this disease.
Like others, I've had problems in that area. Within the first 4 years or so of becoming ill, I had cervical dysplasia twice - both times treated. Shortly after, I went into menopause very early - late thirties. Haven't had an abnormal pap since.
I should have included that I do not know my XMRV status, so it's pure conjecture on my part!
OMG there is so much amazing information here I think my head is going to explode! I really wish we could get further comment from some of the researchers and doctors in the ME/CFS field (not to dis the brilliance that is expressed in this and other threads) so that we could really start to
pull all the puzzle-pieces together. I feel we're at such a brink, but the areas of research are so diverse, and acting so separately; it is in a forum-style discussion like this that the inter-disciplinary thinking that is needed can bear fruit. As we saw in the NIH Q&A, there is still so much in-fighting and political posturing, that true, swift progress is inhibited. Can we not get some of the brilliant hypotheses suggested here published editorially in some medical review
to get the appropriate people/agencies back on their toes?
Yeah, Cort wrote something in regards to this I believe, there was also an article in the NY Times on the UnPrecedented cooperation that is/has occurred for Alzheimer's, if I recall correctly?!
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