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XMRV: Necessary but not sufficient?

garcia

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> Lowering glutathione produces oxidative stress, and the virus apparently needs oxidizing conditions to form disulfide bonds in its protein coat.

True, the redox conditions they need are certainly oxidizing compared to /something/. But one has to wonder whether the human body could ever in fact be reducing enough to inactivate a significant fraction of the virions via a non-catalyzed redox reaction. After all, while I'm sure different disulfide bonds vary in their proclivity for being reduced, depending on context (the amount of bond strain, etc)... the human body has many of them, and many "kinds" of them (that is, has em in many different contexts). A priori, why should we imagine that XMRV's disulfides are any more easily reduced than the thousands of "kinds" of disulfide bonds whose stability we depend on?

I have to wonder the same thing about claims that N-acetyl cysteine can damage a significant number of chlamydial elementary bodies.
Hi Eric, I'm surprised at you saying this coming as you do (like me) from a Chlamydia pneumoniae background. NAC can and does damage a significant number of chlamydial elemetary bodies, as witnessed by the intense reactions people get to it. In my case an increase in dosage feels like someone has poured gasoline down my oesophagus. There is also the distinct endotoxin reaction one gets - a sudden drop in body temperature that is quite unnatural. These brisk reactions are repeated with other disulphide-bond reducers such as DMPS.

I don't know anything about XMRV disulphide bonds, but I do know that when I first saw a picture of the virions being released it reminded me of only one thing, namely Chlamydial elementary bodies.

How well a chlamydia infection spreads and propagates will depend on how oxidizing the body is, since at the least it will determine how long the elementary bodies survive.

I can only imagine that the same is true for XMRV. If so it provides a natural docking point for Rich's Methylation block theory.
 

Jenny

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Hi Eric, I'm surprised at you saying this coming as you do (like me) from a Chlamydia pneumoniae background. NAC can and does damage a significant number of chlamydial elemetary bodies, as witnessed by the intense reactions people get to it. In my case an increase in dosage feels like someone has poured gasoline down my oesophagus. There is also the distinct endotoxin reaction one gets - a sudden drop in body temperature that is quite unnatural. These brisk reactions are repeated with other disulphide-bond reducers such as DMPS.

Hi Garcia

Can you tell me - what is the evidence that NAC (or anything else for that matter) damages CpN elementary bodies? Why do intense reactions mean that this has happened? I've always wondered this when people discuss this on the CpN board. Surely there's a whole range of possibilities when we get strong reactions to something?

Jenny
 

serg1942

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Disagreement with XMVRV being Necesary to develope CFS...

Dear Rich,

Sorry to everybody for answering only alter having reading the Richs post. I have no energies to read all the other messages, so maybe some of my ideas are already exposed.

Well, Rich, as you as for comments, Id like to tell you my point of view on this regard. I dont think it is Necessary to have XMRV, or at least, many thinks doesnt fit yet to assert that. Let me explain my rationale:

- It is supposed (not yet published I think) that, in fact, XMRV has being found almost in all the PWCs samples taken in the WPI. This of course would lead to think of causality. But it is also said that XMRV has being found ONLY in 60% of people with FM (if this data has not changed). So, what happens?, now CFS in different to FM? XMRV is the source of CFS, but an opportunistic infection on FM? Given the high comorbidity of both conditions, and the almost identical abnormalities found in both diseases, my guess is that is the immune system has much to do here. We know that immune system (IS) in people with FM sometimes tend to be over hyperactive (yet still dysfunctional), while in CFS the IS use to be completed exhausted. Well, maybe is the weakening of the IS what determines the XMRV incidence. Well, this reasoning also could give to think that XMRV can still be necessary to develop CFS, if some people would first develop FM and afterwards CFS. As far as I know this is not the case. The order of developing both illnesses is random.

- My second reasoning is based on my own case: I developed CFS at my 21 years old (I am 27 right now). But I developed my first idiopathic symptoms ate the age of 14-15, just after having been intoxicated seriously with Hg. At this age, I still had not had intimate relationships (sex), so if the XMRV is finally shown to be transmitted the same way VIH does, and if I was then infected by XMRV, the only way of transmission would had been my mother. If this is the case, I am so lucky that all my closer family (fathers, 4 grandfather, 7 uncles, 6 cousins) are ALL very healthy, so if the virus would be needed to develop my CFS, its virulence would be very mild (my family also has been exposed to many stressors, but not to the huge amount of Hg I was exposed to). Well, if in the other hand, it is finally shown that the XMRV transmission ways are also saliva or air, controls would have more prevalence of the virus. Anyway, thinking in that possibility, the virulence of the virus would be almost meaningless!!

Finally, and think this has being brought already up to the discussion, autism shows a 40% of XMRV prevalence. Well, again, what happens? XMRV is only the origin for CFS, but oportinistic in autism?. Remember here that Autims is very similar to CFS if we study the basic metabolic, cellular, and systemic abnormities in both conditionsAnd again, the same that with FM, their immune system tend to be a bit strong than in PWCsSo again, this leads me to the same conclusion.

I would appreciate if anyone could give some explanation to the questions I am raising, as so far nobody I have ask for, has convinced me. I am aware of the relevance of the almost 100% PWCs infected with XMRV, but maybe the results could be different if they had look for PWCs having developed the disease after a toxic exposure instead of after an infectionJust my thoughts, probably wrong!

Regards,
Sergio
 

garcia

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Hi Garcia
Can you tell me - what is the evidence that NAC (or anything else for that matter) damages CpN elementary bodies? Why do intense reactions mean that this has happened? I've always wondered this when people discuss this on the CpN board. Surely there's a whole range of possibilities when we get strong reactions to something?
Jenny
Hi Jenny,
according to Dr Stratton's patent:

[0003] EBs are small (300-400 nm) infectious, spore-like
forms which are metabolically inactive, non-replicating, and
found most often in the acellular milieu. EBs are resistant to
a variety of physical insults such as enzyme degradation,
sonication and osmotic pressure. This physical stability is
thought to be a result of extensive disulfide cross-linking of
the cysteine-rich major outer membrane protein
(MOMP)
(Bavoil et al., Infection and Immunity, 44:479-485 (1984);
Hackstadt et al., Journal of Bacteriology, 161:25-31 (1985);
Hatch et al., Journal of Bacteriology, 165:379-385 (1986);
Peeling et al., Infection and Immunity, 57:3338-3344 (1989);
J. C. A. Bardwell, Molecular Microbiology, 14:199-205
(1994); and T. P. Hatch, Journal of Bacteriology, 178:1-5
(1993)). Under oxidizing conditions in the acellular milieu
of the host, the outer membrane of EBs is relatively impermeable
as well as resistant to inactivation. EBs are thus well
suited to survive long enough outside of their hosts to be
transmitted to a new host in the form of a droplet nuclei
(Theunissen et al., Applied Environmental Microbiology,
59:2589-2593 (1993)) or a fomite (Fasley et al., The Journal
of Infectious Diseases, 168:493-496 (1993)).
[0087] Physiochemical agents have been identified that
can inactivate chlamydial EBs in their respective hosts by
reducing disulfide bonds
which maintain the integrity of the
outer membrane proteins of the EBs. For Chlamydia, disruption
of the outer membrane proteins of EBs thereby
initiates the transition of the EB form to the RB form. When
this occurs in the acellular milieu where there is no available
energy source, the nascent RB perishes or falls victim to the
immune system. Thus, disulfide reducing agents that can
interfere with this process are suitable as compounds for
eliminating EBs
.
[0088] One such class of disulfide reducing agents are
thiol-disulfide exchange agents. Examples of these include,
but are not limited to, 2,3-dimercaptosuccinic acid (DMSA;
also referred to herein as "succimer"); D,L,-β,β-dimethylcysteine
(also known as penicillamine); β-lactam agents
(e.g., penicillins, penicillin G, ampicillin and amoxicillin,
which produce penicillamine as a degradation product),
cycloserine, dithiotreitol, mercaptoethylamine (e.g., mesna,
cysteiamine, dimercaptol), N-acetylcysteine, tiopronin, and
glutathione. A particularly effective extracellular antichlamydial
agent within this class is DMSA which is a
chelating agent having four ionizable hydrogens and two
highly charged carboxyl groups which prevent its relative
passage through human cell membranes. DMSA thus
remains in the extracellular fluid where it can readily
encounter extracellular EBs. The two thiol (sulfhydryl)
groups on the succimer molecule (DMSA) are able to reduce
disulfide bonds in the MOMP of EBs located in the extracellular
milieu.
Table 8 from the Stratton Patent lists various disulfide-reducing agents and their efficacy at reducing EBs.

According to Dr David Wheldon's webpage:

NAC is a thiol-containing amino acid; it is readily absorbed and is non-toxic. It has many beneficial effects; perhaps the most surprising is the likely ability of this molecule to destroy chlamydial elementary bodies.
It is reasonable to think that, were the EB coat to be opened up before achieving attachment to a nutrient-rich host cell, the unprotected EB would perish through starvation.

Destruction of EBs may be very important, as there is evidence that they may accumulate in extracellular spaces awaiting their chance to enter host cells - this may be analogous to the 'acellular (or extracellular) load' seen in HIV infections [Chuck Stratton, personal communication.]

Penicillamine (dimethyl cysteine), which reduces disulphide bonds, inactivates EBs in vitro and prevents the initiation of infection in vivo. Amoxycillin, an inexpensive b-lactam antibiotic, is also effective in inactivating EBs in vivo; penicillamine is one of its major metabolites. [Chuck Stratton, personal communication.]

N-acetyl cysteine, which, being a thiol antioxidant, is a good candidate for the reduction of disulphide bonds in EB coating proteins. It is readily available as a health supplement without the need for prescription.

The NAC Test

One indirect indicator of chronic infection with this organism is the N-acetyl cysteine test. This relies on the ability of NAC to rupture the extracellular Elementary Body by opening up surface disulphide bonds in the organisms geodesic coat, as described above. The EB opens and perishes. The release of naked bacterial components causes local inflammatory symptoms. Because EBs are more numerous in primary respiratory infections, the acellular load of EBs is likely to be highest around respiratory structures. In a positive NAC test the daily administration of 2.4 G of NAC will cause, after a few days, sinusitis-like symptoms, with watery mucous; also a cough productive of a clear, moderately viscous sputum. Systemic symptoms 'NAC flu' may also occur. If symptoms are severe, the dose of NAC may be cut down to 600mg and slowly built up as may be tolerated. Symptoms wane, sometimes quickly, after a few days if the chlamydial load is small; if the load is large they may continue for a month or more as the EBs are destroyed and their remains removed by the immune system. As far as I am aware, NAC is unlikely to produce die-off reactions with any other genus.
 

Jenny

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NAC CpN

Hi again garcia

Thanks very much for taking the trouble to post details of these studies. I actually phrased my question wrongly though!

What I meant to say was - how do YOU know that the reaction you are getting from NAC is from the killing of CpN?

As I understand it,tests for CpN are unreliable, so how can anyone be sure they do or don't have it?

If one does have it, how do you know that the reaction you get from NAC means it's being killed? There may be evidence that NAC CAN kill CpN, but that doesn't mean that the reaction one gets after taking it is from the bacteria being killed. Perhaps it's doing something else to the body, or killing something else? It seems likely that we all have lots of pathogens, as well as toxicities from heavy metals and other things.

I have a similar situation in trying to treat borrelia. I'm told my test results show I have this. So I've taken a whole range of abx to get rid of it. Sometimes I get a bad reaction. However I'm not sure I trust the test - too many people come up positive it seems and I've never been exposed to ticks. I know that these abx attack many pathogens, not just borrelia, and after years of abx treatment I'm no better. So I don't think there's much evidence that what I'm taking is killing the borrelia, even if I have it.

Not feeling very articulate this afternoon. Ignore all this if it makes no sense!

Jenny
 

richvank

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I didn't have severe stress before getting sick, just a tickbite on a lovely June day, with something very virulent in it. I'd like to know if XMRV can be transmitted by ticks. A few of us have speculated it may be the reason for chronic abx refractory lyme.
Hi, Jenbooks.

I'd like to know that, too!

Rich
 
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xmvr levels

is there a difference at levels of xmrv in %4 healty controls and pwc ?

maybe it ( xmrv) has to be above a certain amount to make someone sick ..
 

richvank

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To sergio re: objections

Hi, Sergio.

Thanks for your response. I think you make some good points. We do need more data on broader groups of people who have these various disorders. I think this is the main type of objection people have made to what I suggested. What I suggested may still be true, if additional data support the currently available data in CFS, but time will tell. The fuzzy diagnostic categories that we currently have probably obscure the picture some, too. Until we have better case definitions, that will probably continue to be true. Using the XMRV tests as a diagnostic may help us to define these illnesses better in the future.

Best regards,

Rich

Dear Rich,

Sorry to everybody for answering only alter having reading the Richs post. I have no energies to read all the other messages, so maybe some of my ideas are already exposed.

Well, Rich, as you as for comments, Id like to tell you my point of view on this regard. I dont think it is Necessary to have XMRV, or at least, many thinks doesnt fit yet to assert that. Let me explain my rationale:

- It is supposed (not yet published I think) that, in fact, XMRV has being found almost in all the PWCs samples taken in the WPI. This of course would lead to think of causality. But it is also said that XMRV has being found ONLY in 60% of people with FM (if this data has not changed). So, what happens?, now CFS in different to FM? XMRV is the source of CFS, but an opportunistic infection on FM? Given the high comorbidity of both conditions, and the almost identical abnormalities found in both diseases, my guess is that is the immune system has much to do here. We know that immune system (IS) in people with FM sometimes tend to be over hyperactive (yet still dysfunctional), while in CFS the IS use to be completed exhausted. Well, maybe is the weakening of the IS what determines the XMRV incidence. Well, this reasoning also could give to think that XMRV can still be necessary to develop CFS, if some people would first develop FM and afterwards CFS. As far as I know this is not the case. The order of developing both illnesses is random.

- My second reasoning is based on my own case: I developed CFS at my 21 years old (I am 27 right now). But I developed my first idiopathic symptoms ate the age of 14-15, just after having been intoxicated seriously with Hg. At this age, I still had not had intimate relationships (sex), so if the XMRV is finally shown to be transmitted the same way VIH does, and if I was then infected by XMRV, the only way of transmission would had been my mother. If this is the case, I am so lucky that all my closer family (fathers, 4 grandfather, 7 uncles, 6 cousins) are ALL very healthy, so if the virus would be needed to develop my CFS, its virulence would be very mild (my family also has been exposed to many stressors, but not to the huge amount of Hg I was exposed to). Well, if in the other hand, it is finally shown that the XMRV transmission ways are also saliva or air, controls would have more prevalence of the virus. Anyway, thinking in that possibility, the virulence of the virus would be almost meaningless!!

Finally, and think this has being brought already up to the discussion, autism shows a 40% of XMRV prevalence. Well, again, what happens? XMRV is only the origin for CFS, but oportinistic in autism?. Remember here that Autims is very similar to CFS if we study the basic metabolic, cellular, and systemic abnormities in both conditionsAnd again, the same that with FM, their immune system tend to be a bit strong than in PWCsSo again, this leads me to the same conclusion.

I would appreciate if anyone could give some explanation to the questions I am raising, as so far nobody I have ask for, has convinced me. I am aware of the relevance of the almost 100% PWCs infected with XMRV, but maybe the results could be different if they had look for PWCs having developed the disease after a toxic exposure instead of after an infectionJust my thoughts, probably wrong!

Regards,
Sergio
 

richvank

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To Lebowski re: level of XMRV

Hi, lebowski.

is there a difference at levels of xmrv in %4 healty controls and pwc ?

maybe it ( xmrv) has to be above a certain amount to make someone sick ..
What may differ is whether they are serum PCR positive or not. If they are serum PCR positive, that means that there are viruses outside the cells, which means it's an active infection. Maybe the PWCs will be found to have active infections, while the healthy controls will be found to have latent infections.

Rich
 
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slow replicating

hi rich vank ,

thanks for the answer .. when i think of ppl with aids , it takes a while for them to develop disease after they got the hiv , maybe it is a similar thing with xmrv .. u get the virus then passes some time and some critical places r invaded and damaged by the virus and this may take some long time because xmrv replicates very slow ?..
 

richvank

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To Lebowski

Hi, Lebowski.

Maybe. I don't know enough to say whether it could work that way with this retrovirus or not.

Rich
 

kurt

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toxins, sufficient or necessary?

I've always felt the rise of Autistic Spectrum Disorders, and perhaps many other modern epiemic illnesses, is due in part to an increasing "burden" of toxicity passed on from mothers to their infants. For example heavy metals accumulate and can pass via the placenta. I'm not sure what else....some medications maybe? Organophosphates? A whole host of things that in isolation may not cause great harm, but as part of a cumulative burden may do so.
I've long suspected a link between many of the modern epidemic illnesses and figured that somewhere in the mid-eighties when they did in fact become epidemic it was, in simple terms, because for many the cumulative level of toxic burden began to overtake our detoxification capacity.
It's been easy for me to think and feel this way because when I first became very unwell I personally felt 'poisoned' rather than virus-struck.
Your view is very consistent with Gary Gordon's that we are all being poisoned. Have you seen his theory that everyone should be compensating for toxins, particularly sick people? He has what he calls the F.I.G.H.T. approach that includes much emphasis on toxins, methylation support, working on infections, etc.

see www.gordonresearch.com

And Dr Gordon claims there is mercury in the air we breathe, even in high fructose corn syrup which is now such a popular ingredient. Toxins are ubiquitous at this point in time. The mother-child transmission is just one possible vector, everyone gets exposed. Dr. Gordon also focuses on toxins from plastics, which disrupt hormone systems.

I have always felt that same way, poisoned. But also I sensed right off that some bug or bugs were involved, perhaps partly increasing the toxin load.

So toxins are probably a necessary part of all this, from the scientific viewpoint anyway.
 

kurt

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neither sufficient nor necessary - overreaching about XMRV?

XMRV may be neither sufficient nor necessary. I agree with an earlier poster here about that. I think there is too much hype right now about XMRV. There is too much overreaching.

Aren't we transferring some pent-up frustration about CFS into the idea that maybe an explanation has been found? Is that warping people's judgment? There is so much vulnerability in PWC. I have been taken in several times before myself by explanations and treatments that I should have been able to see were improbable.

Maybe some CFS co-infections have psychotropic effects, I think sometimes judgment is impaired with CFS. I was such a clear-minded and logical person before CFS, that is almost hard for me to remember, my brain worked like a well-oiled machine, like a computer. My brain may be slower now so I have to be careful to go through all the steps I used to. But finally it is kicking in to gear about XMRV.

OK, here are the facts, and I am going to reach a conclusion that I believe is supportable. Speculating about XMRV is fun, but it is not reality. Here is what is real... we only have one small study of XMRV and CFS right now. It is from a lab with no particular expertise in retroviral testing, and they are using older methods that are proven, but have known risks. This is not a good basis for drawing any grand conclusions. The WPI study could have any number of problems that have not been revealed yet, at this point all we can say is that XMRV and CFS are a hypothesis.

Remember Cold Fusion in the late 80s/early 90s? I believe one of the research teams even got an article published in Science. The mindset of the world shifted those first few months after the initial announcement, finally an answer to our energy problems. It was a game changer, and the researchers insisted they had measured many ways and this was solid. Nobody could reproduce their work, and over a few years the subtle measurement errors were identified.

There is NO WAY we as a CFS community should be running so fast with this conclusion that XMRV is important to CFS. It has not even been proven important to prostate cancer yet.

At this point XMRV may be neither sufficient nor necessary for CFS pathology. But clearly it is useful for dealing with CFS frustration, and has helped produce good PR for CFS. THIS IS A BIG PROBLEM. What are we going to do if this is just another cold fusion finding?

How can we get people here to realize that this is science and that the process is always two steps forward and one step backwards? That one study is not a trend? That there is not yet scientifically acceptable proof?

I think the best thing that has come from the Science article so far is an increased awareness of CFS, maybe even the birth of CFS activism. The yellow T-shirts at CFSAC were a start, Wanda even realized what that meant, that there was now CFS activism. I'm not sure the CFS community realized what Wanda's comments really mean for us. Some gears shifted and we need to take advantage of that. But the gears shifted for CFS, not for XMRV.

If something looks too good to be true, it is probably not true. My memory of having a strong, rational brain is bothering me, something inside me says to be more rational here, cut through the hype. CFS will not be solved so easily. I hope WPI can survive if XMRV turns into a bust, which is a very real possibility based on what some people are saying backchannel. The search for a retrovirus for CFS is a very good and reasonable mission, but hanging one's hat on the first candidate found is a big gamble.
 

gracenote

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infected by hope

There is NO WAY we as a CFS community should be running so fast with this conclusion that XMRV is important to CFS.
Kurt, you might be right. You're probably right in a logical, reasonable, cautious way.

But . . . this isn't just about the facts, as much as we need to be reminded of them. And we do, and you are very articulate and your thoughts are very welcome. But . . . and now I'm going to sound like the desperate, anxious, unexpectedly hopeful sick person that I am. There is something else going on in this community of ignored, disbelieved, mistreated, and devalued sick-for-too-long individuals. We are finding our voice. We are being heard. AND we are being believed that WE ARE VERY ILL.

Maybe logic can only get us so far. Maybe our passionate response to this news is the impetus that has been needed to finally energize not only those of us who are suffering, but those who could not see our suffering before at all.

As you said so well yourself
I think the best thing that has come from the Science article so far is an increased awareness of CFS, maybe even the birth of CFS activism.
I think you are still "clear-minded and logical" but maybe now you've been infected by hope. Hope can be a very good thing if it is hope for a better future, rather than hope for this one thing.

I've been infected by hope, and I'm happy about it!
 
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A gammaretrovirus is a nasty thing. It could easily be responsible for the neurological damage, CFS symptoms, and cancers we're seeing. I don't think it's hype at all.
 

kurt

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Kurt, you might be right. You're probably right in a logical, reasonable, cautious way.

...

I think you are still "clear-minded and logical" but maybe now you've been infected by hope. Hope can be a very good thing if it is hope for a better future, rather than hope for this one thing.

I have been infected by hope.
Good point, and you are right. What I am saying is that my rational brain says to be infected by a rational hope, hope that this is a turning point for CFS funding, research, and maybe eventually treatment. And not a high-risk hope that XMRV is the cause and toxic ART will be the primary solution. Thomas Edison may have gotten excited working on the light bulb the first time a filament lasted a few hours. But how many more did he have to try before he found a combination that really was workable... We may have a retrovirus, Mikovitz has connected our symptoms to classic retroviral problems in a new and more profound way, but the actual culpret may or may not be XMRV. There is a LOT of work left, many more 'filaments to try-out.'

The science is not very strong yet for XMRV in CFS. People with prostate cancer and XMRV do not get CFS. Think about that. My father has prostate cancer, a serious heart condition, two artificial knees, and is in his late 70s, and he can run circles around me. He still goes golfing and walks the course, in fact he recently had a heart attack while golfing, and his pacemaker/defibrillator implant stopped the attack instantly. My father did not even fall down, he borrowed a golf cart and went home, down-loaded the data to his doctor, and is fine. That is nothing like CFS, I can hardly walk to the mailbox three houses away some days.

What worries me is if there is a collective loss of hope from the CFS community if XMRV turns out to not be involved in CFS. And what I read here is so much excitement and expectation, placing too much load on WPI and Mikovitz to solve our problems. Too much anticipation and not enough caution. That is all I am trying to say.
 

gracenote

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a tidal wave of action

What worries me is if there is a collective loss of hope from the CFS community if XMRV turns out to not be involved in CFS. And what I read here is so much excitement and expectation, placing too much load on WPI and Mikovitz to solve our problems. Too much anticipation and not enough caution. That is all I am trying to say.
Well said, Kurt. And I actually completely agree with you.

But I haven't come down off this high yet and I don't want to. I'm enjoying this while it lasts. There is way too much somber realism in my life (and I'll speak for myself), that a little bit of giddy, perhaps unwarranted, ecstasy feels mighty fine. There will be time for sober reality soon enough. And then maybe we'll be able to turn all our "excitement and expectation" into a "collective" forward tidal wave of action that obliterates all the previous categories and makes way for something new and better.

Even after all these years of struggle with my own confounding health issues, I think I'm still an idealist at heart. But don't let me stop you, Kurt. I value your clarity of thought and cautionary reminders.
 
A

anne

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While "the lab" may not have experience in retroviruses, the person actually at the lab has plenty.

Dr. Mikovits spent more than 20 years at the National Cancer Institute in Frederick MD during which time she received her PhD in Biochemistry and Molecular Biology, investigating mechanisms by which retroviruses dysregulate the delicate balance of cytokines in the immune response. This work led to the discovery of the role aberrant DNA methylation plays in the pathogenesis of HIV. Later in her career at the NCI, Dr. Mikovits directed the Lab of Antiviral Drug Mechanisms (LADM) a section of the NCI's Screening Technologies Branch in the Developmental Therapeutics Program. The LADM's mission was to identify, characterize and validate molecular targets and to develop high-throughput cell-based, genomic and epigenomic screens for the development of novel therapeutic agents for AIDS and AIDS-associated malignancies (Kaposi's sarcoma). Formally trained as a cell biologist, molecular biologist and virologist, Dr. Mikovits has studied the immune response to retroviruses and herpes viruses including HIV, SIV, HTLVI, HERV, HHV6 and HHV8 with a special emphasis on virus host cell interactions in cells of the hematopoietic system including hematopoietic stem cells (HSC). Dr. Mikovits' commercial experience includes serving as a senior scientist and group leader at Biosource International, where she led the development of proteomic assays for the Luminex platform that is used extensively for cytokine activity assessment in therapy development. She also served as Chief Scientific Officer and VP of Drug Discovery at Epigenx Biosciences, where she led the development and commercialization of cell and array-based methylation assays for drug discovery and diagnostic development. Dr. Mikovits has co-authored more than 40 peer-reviewed publications that address fundamental issues of viral pathogenesis, hematopoiesis and cytokine biology.
 
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Kurt

Kurt, when I was first told the news, I thought, Well, another opportunistic virus.

But another CFSer said this virus is different. So I looked into it. And so it is. This virus logically explains all the other studies on viruses. Not saying it is the cause, genetics, other viruses, and many other things, including stress may contribute to the ultimate abyss of illness we experience.

But this is more likely to be the key player.

Addressing your points one by one:
Thomas Edison. Yes, his first lightbulb was not such a great thing, unless of course except it was the first of its kind. Crude in its infancy, it still was a beginning that ultimately changed the world. The WPI study may be just as baby-like, but it is a birth that may just change our world.

I absolutely agree that hope based on hype will likely lead to disappointment. We must use our reasoning abilities and set aside the emotional desires.

As to your reference to prostate cancer patients not having CFS... Well, I don't know if that is true. First off, the prostate cancer patients showing positive were a subgroup with very aggressive cancer and the Rnase dysfunction in the immune system. Could these men have CFS, but their cancer doctors attributed their symptoms to the immune system problem or the cancer, or the cancer treatment? So not all people with prostate cancer have the virus. In fact, the study showed only 27% of the cancer patients tested did. So they certainly couldn't put a cause link reasoning to that study. But in CFS, we are talking 98% CFSers compared to 4% of controls. Completely different results. So just because prostate cancer patients don't seem to have CFS, doesn't mean XMRV is not a key player in developing CFS. Now, if 98% of prostate cancer patients had XMRV, then maybe the reasoning would be different. But even then, the prostate cancer patients could have CFS (mild, medium or severe) and it not be diagnosed. There may be many possible causes of prostate cancer. If your father does not have the very aggressive form of prostate cancer and the RNase abnormality, then I wouldn't expect he would show any signs of having XMRV or XAND or CFS. He is not in that 27%. It is possible, likely and supported by evidence that XMRV is a lot more important factor in CFS than in prostate cancer.

I understand your point about too much hope and not enough caution. I have been reading Osler's Web. And I am at the point of HHV-6 discovery. I see that they thought it was the answer. And the disappointment came later. For those patients who experienced that, I understand your hesitation. I did not experience that. I got sick in 2006, plummeted, although likely had been gradually getting sick for years before that. But I don't blame the veterans for holding off on the excitement. By the same token, though, could those veterans also be blinded by their previous disappointments that they can't see the evidence is stronger in this case? The boy who cried wolf so many times made it so the towns people never believed him. But remember, one time the boy cried wolf and there actually was a wolf. Also, Thomas Edison had many failures. But eventually he did succeed. How many dismissed Thomas Edison when he came up with his new invention after so many failures? I just read he did 10,000 experiments on a possible lightbulb until he found the one that worked. Each failure brought him closer to success. So whereas you believe the need for a hope is influencing people's ability to see the evidence clearly, I say that possibly past disappointments may be influencing some to not see the evidence clearly.
I think we need to look at XMRV finding on its own evidence and use reasoning on what we already know about CFS to draw conclusions, if we even want to draw conclusions. Of course, no matter our conclusions, more studies will show what is true and false, in time. With the discoveries in the last two decades, which many put hope in but led to disappointment, we were in fact coming to understand CFS more and it was leading us to success, eventually. I don't know if there are more filaments to try out. WPI may have just turned on the first lightbulb. We don't know yet.

We do not have just one small study. WPI study was verified by tests at NCI and Cleveland Clinic. I doubt it would have been published in the Science Journal had it been just one study by WPI. Also, the study involved a comparitively high number of individuals for it to be a first study. Usually first studies are 40-80 patients. This had 101 and 218 controls. Dr. Coffin, the retrovirus expert, commented that as a first study goes, it is very impressive. When he was asked what other explanations could explain the study results, Coffin listed off a few but said each was unlikely.

As for Mikovitz, while it is true she is not a retrovirus expert, her research experience is in viruses. She was one of the doctors in a published study of Kaposi's sarcoma-associated herpesvirus. This is what she says of her experience: My background is in virus caused cancers. My training for over 22 years at the NCI was in how viruses dysregulate the immune system and cause disease cancer."

I do agree that science is two steps forward and one step back. But I do believe we can say XMRV is important to CFS, given the nature of the virus and the prevalence in patients in the first study. But there is no certainty of any other conclusions.

I am not as much excited about the activity and hope of the patients as a result of this discovery. But I am excited at the response of the research community. I read that Mikovitz gave a talk in Portugal on October 19 to a cytokeine conference. She said she got an applause before she said a word. Quest and Labcorps is interested. 75 researchers met last week to form collaborations. The interest went from 4% to 95% (I couldn't resist.). Retrovirus specialists are interested. When Mikovitz met with the doctors privately before the study publication, she said mouths fell open. So my excitement is that this has turned the page in putting us on the map in the scientific / research world. Whatever the answer is, it will come faster now.

Tina
 

hvs

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Here is what is real... we only have one small study of XMRV and CFS right now. It is from a lab with no particular expertise in retroviral testing, and they are using older methods that are proven, but have known risks.
Hey, Kurt. By all means, be skeptical. That's your prerogative. Indeed, as you say, if the Science thesis collapses, there will be a lot of hurt.

I, however, have not heard a convincing argument undermining it. ...Not a one.

And while I encourage you to be skeptical, I have an obligation to my neighbors on these fora to correct misstatements.

To address what you state in the quote above:
1. We do have one study showing a link between XMRV and CFS, but it is relatively large by the standards of the field.
2. Judy Mikovits is one of the most experienced retrovirologists in the country.
3. The WPI was joined by the NCI and Cleveland Clinic in their testing. That Cleveland Clinic department is, beyond any possible doubt, the most experienced in the world when it comes to XMRV.