XMRV and chronic fatigue syndrome: British cohort

Oh yes the government and some of their scientists and doctors always do the right thing and should always be believed. Just see below. No conspiracy theory here. Just the bold faced truth coming out years later. What other experiments were carried out on various populations. I can think of a few.

Secretary Clinton & Secretary Sibelius Release Joint Statement on the Horrific Medical Experiments Carried Out in Guatemala

Joint Statement by Secretaries Clinton and Sebelius on a 1946-1948 Study

Following is a joint statement by Secretary of State Hillary Rodham Clinton and Secretary of Health and Human Services Kathleen Sebelius on the U.S. Public Health Service Sexually Transmitted Disease Inoculation Study of 1946-1948:

The sexually transmitted disease inoculation study conducted from 1946-1948 in Guatemala was clearly unethical. Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health. We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices. The conduct exhibited during the study does not represent the values of the United States, or our commitment to human dignity and great respect for the people of Guatemala. The study is a sad reminder that adequate human subject safeguards did not exist a half-century ago.

Today, the regulations that govern U.S.-funded human medical research prohibit these kinds of appalling violations. The United States is unwavering in our commitment to ensure that all human medical studies conducted today meet exacting U.S. and international legal and ethical standards. In the spirit of this commitment to ethical research, we are launching a thorough investigation into the specifics of this case from 1946. In addition, through the Presidential Commission for the Study of Bioethical Issues we are also convening a body of international experts to review and report on the most effective methods to ensure that all human medical research conducted around the globe today meets rigorous ethical standards.

The people of Guatemala are our close friends and neighbors in the Americas. Our countries partner together on a range of issues, and our people are bound together by shared values, commerce, and by the many Guatemalan Americans who enrich our country. As we move forward to better understand this appalling event, we reaffirm the importance of our relationship with Guatemala, and our respect for the Guatemalan people, as well as our commitment to the highest standards of ethics in medical research.

Your blog still makes me laugh.
Thanks. :-)

Mind Hacks had a nice post on this the other day - I was hoping someone else would pick it up and have a go at the science, since I'm not a virologist or an epidemiologist so I can't really interpret it properly.

Still, I remember one bitchy comment listing all the differences (different reagents, different genomic template concentrations, different primer combinations...) and snarking about how this meant it wasn't surprising that it didn't replicate the results.

This struck me as entirely missing the point. If a well designed, properly controlled and appropriately powered experiment can't replicate the findings of another lab, that's exactly the kind of info that should be raising questions about the original work. If the results depend on you using the right tubes, surely it's not a particularily robust or reliable result to start with?

Whatever.

Confused, what you're missing here is the fact the "patients" chosen for this study were chosen for the express purpose of NOT finding any organic cause for ME/CFS. Simon Wesseley is a psychiatrist who continues to push his idea that ME/CFS is somatic,despite decades of evidence to the contrary. In UK he and his fellow psychiatrists have claimed this illness as their own and have an Orwellian control over the medical system there. People who are unable to go to ME "treatment centers" for forced excercise have been "sectioned", that is committed against their will to mental institutions as "a danger to themselves". One who died because of this has been found to have extreme abnormalities of her spinal nerves, indicating infection of some sort. The paper claims he has no conflicts of interest, but I don't believe it. In the past he has co-written hundreds of "studies" purportedly proving that ME is just depression, studies which have been paid for by companies that sell drugs for depression - surprise, surprise - such as Novartis. The authors of this paper are not dedicated to getting out the "truth", but are simply continuing Wesseley's campaign to prove this illness to be overblown depression, no matter what the real science shows.

Please read:
http://www.wpinstitute.org/news/docs/WPI_Erlwein_010610.pdf
http://www.economist.com/sciencetechnology/displaystory.cfm?story_id=15…

Confused-- Bingo. Its irrelevant whether this group used the exact same PCR reagents as the first paper. The very first thing you do with any PCR reaction is optimize it to determine your sensitivity. The gold standard is "These reagents can positively identify one copy/ul, but are still negative at zero copies/ul." Seeing one copy of a gene in a mix of a ton of DNA might seem impossible, but it is whats expected with todays technology :)

Now, the 'optimal' PCR reaction recipe using one primer/probe set might be different than another primer/probe set.

Mentioning their optimal concentrations are different is, frankly, stupid. No one who has performed PCR in Genetics 101 would think that fact is significant. No one would ever have to optimize their reactions if primers were interchangeable like that. *weird look*

All that matters is that the primers sensitivity is down to one copy, and they were in this paper.

My explanation for this data is XMRV is endemic in the US. It is not the cause of CFS, but it could be an effect that perpetuates the disease.

oregano-- Your reply doesnt answer Confuseds question in the slightest. You used him as an excuse to bitch about how everyone is out to get you. Dont use my commentors, fruit loop.

To respond to your comment, the patients used in this paper met the CDC requirements for CFS. If XMRV causes CFS, you shouldnt have to know in advance who the 'right' CFS patients are to test. That doesnt make any sense.

How, EXACTLY, did these authors 'know' all of their samples were going to be negative?

Simon Wessely, the man orengo mentioned, has in past papers argued that even if CFS is caused by a virus patients should be encouraged not to believe this as it reduces their chance of recovery. While I can't imagine that he'd therefore deliberatly distort this study, I do understand why CFS patients may be sceptical of his involvement.

XMRV never made sense to me as the sold cause for all cases of CFS, but CFS is such a dustbin diagnosis I'd be surprised if any single cause could ever be found. It would be like looking for one single cause for headaches.

I don't understand the science behind PCR, but is it really impossible for these varying result to not be explainable by a problem with these tests? Given the level of international mobility we've seen over the last fifty years, it just seems strange that a virus could be endemic in America and not Britain or Germany. The prostate cancer XMRV researchers seemed to alos think it was likely that the failure to find XMRV in Germany was based on different testing methods used.

ERV- Do we have to go through what a ranting raving psychotic obnoxious calcified twit you can be AGAIN?

"oregano-- Your reply doesnt answer Confuseds question in the slightest. You used him as an excuse to bitch about how everyone is out to get you. Dont use my commentors, fruit loop.

To respond to your comment, the patients used in this paper met the CDC requirements for CFS. If XMRV causes CFS, you shouldnt have to know in advance who the 'right' CFS patients are to test. That doesnt make any sense."

Good science is all about cohorts. Stick to the virology. Educate yourself on the cohorts. The science paper carefully selected for patients that had immune dysfunction. The UK paper screened out all patients with any sign of immune dysfunction.

Go take your meds and then read the WPI link posted by Gonzales (#5).

"ranting raving psychotic obnoxious calcified twit"

AND

Doer of "Fruitless Deeds of Darkness"

Wheeeeeeee!

Erv, I will buy shots for all of tequila bend when you knock P.Z. off the front page.

C'mon, this xmrv hypothesis is just as sad as Gallo's hypothesis. Finding some partial correlation doesn't prove anything. You have to find the microbe in abundance in the affected tissues, have a clear paper where it's isolated and inject low doses into animals. These XMRV virus hunters seem just as clueless as Gallo and Levy.

gf1-- There are lots of diseases that are still endemic :) HHV-8, HTLV, ebola, polio, lots more viruses, lots bacterial... when humans arent THE target of the virus, or if its really hard to be transmitted human-to-human, or even local animals/insects can keep a disease more 'localized'.

If XMRV is really in these folks, it could be a particular species of mouse here, maybe a species of flea, maybe the MLV variant-- something is unique, allowing a zoonotic event that didnt happen when we were living with mice/rats in the Dark Ages in Europe, possible in the US.

Ive done the procedures described in both papers a million times-- to blame the lack of XMRV in the British cohort on 'how the DNA was isolated' or 'they used a different polymerase' is like me saying the reason why Im not Rembrandt is because I dont have his exact paint brushes. :-/

SC-- The phrase 'immune dysfunction' is never used in the PLOS paper, so Im not sure where you got the idea they eliminated those patients, whatever that vague phrase means.

If you think 'All patients had undergone medical screening to exclude detectable organic illness' means they just so happened to eliminate all the patients you just KNOW were infected with XMRV, youre an idiot.

That phrase means that they eliminated patients that had chronic fatigue symptoms because they have an obvious explanation for those patients symptoms like HIV/AIDS or Lupus or cancer. For example, hypothyroidism can cause CFS-like symptoms-- fatigue, depression, muscle pain. So they screened everyone for normal thyroid function before they could be included in the study.

Why is that odd?

Why is that 'cheating'?

Or do you not understand what youre talking about, while trying to lecture *me* on this topic?

And why do you think I want to read a PR release when I have the scientific papers at my disposal, and I understand them?

Cooler, Which XMRV hypothesis are you referring to? Correct me if I am wrong but wasn't Gallo's hypothesis that HIV caused AIDS all by itself? I don't know that I have seen anyone hypothesize that XMRV is responsible for a subset of CFS all on its own.

If the association of XMRV and a CFS subset holds up, the Gallo comparison is actually quite appropriate according to Dr. Nancy Klimas, U Miami, HIV and CFS specialist. XMRV - suppressed immune response - chronic viral activation. As she said, "You don't have to believe in CFS like you do Santa Claus. There are immune markers all over the place in CFS patients."

There's a long way to go from where we are today and knowing that this is actually what is or isn't going on but studies that screen out everyone with any immune abnormalities don't make any sense.

Imagine you're back in 1980 looking for the cause of the 'gay flu.' Best of luck trying to find the cause by eliminating EVERYONE with any immune abnormalities from your study. You'd have all sorts of fatigued/depressed people you could test (caring for your dying friends has got to be both tiring and a downer) but you'd have a tough time finding HIV, especially with the early tests.

That said, lots of questions remain for people who are serious about investigating this issue.

@ ERV: Thanks. I'm still not really clear on the PCR stuff as it seems the American researchers for CFS and prostate cancer did seem to think differences in testing methods were important, but I expect it will be cleared up with the further replication studies being done.

re the British study excluding patients: they do mention some funny things, like 9 a.m. cortisol measures as part of the screening out of organic illnesses. I really don't think they would have excluded those patients with abnormal cortisol results, as apparently these are common for CFS patients, but for those who already think the worst of Wessely it's not really water-tight.

It sounds like there are a number of other replication studies coming though, including ones from collaborators with the WPI, and I'm sure things will be clearer soon.

No PCR expert here. But I have a question. At one point, all of the samples analyzed by this team were in the possession of one man before they were passed to the scientific team for testing.

Whether deserved or not, this particular man is considered by most CFS advocates to be the "Darth Vader" of the academic CFS cadre. So my question is hypothetical; if this man deliberately wanted to confound the testing, what measures could he have taken to eliminate any finding of XMRV in the samples? None of which were found to be positive.

Microwaving? Bleach? Substition of labrador retriever blood? Could the scientific team detect if the samples had been tampered with? If your life depended on it, how would YOU go about invalidating the PCR test results without being caught?

Well, the samples were intact enough to always recognize the cellular control, beta-globin (the same cellular control I use), so, no bleach or anything else that would damage the DNA.

Maybe if you used blood from another mammal, but not mice... but you would still have to be pretty damn certain they werent infected with a gamma retrovirus, but a beta-globin close enough that your primers will still work perfectly and not raise any suspicions, um, if I had to bet my life on 186 samples not testing positive, off the top of my head, right now-- maybe cow blood?

Maybe?

Maybe dogs would work.

Actually one of those sterile pigs theyre using for xenotransplants in Australia would be perfect :P

Probably not cats (cats have a pretty prominent gamma).

But, let me be clear, if he did send out sterile ERV-free pig blood instead of the human samples, thats federal fraud (at least in the US), and you will spend time in a federal prison when youre found out. You are also forbidden from ever receiving money from the government for research ever again. And, he would be found out when other researchers went to get more samples from the patients... sooooo... not much of a point in faking samples.

@sc
Yes, but only looking for retroviruses can be a quandry. I was referring to Gallo's experiment were he could only isolate with great difficulty in 26/72 AIDS patients and find antibodies in 88%. This correlation is like the XMRV correlation, is not convincing at all. Like is said in the previous post you should find the microbe in abundance in the affected tissues with a microscope/electron microscope (That is what Robert Koch did) and inject low doses into animals.

Many scientists have pointed out for years that other factors in AIDS and CFS have been ignored, like the enormous stress people with AIDS and CFS have, AZT chemotherapy, the enormous amount of drug use in certain risk groups and other microbes like mycoplasma. Google an article called "is HIV guilty" from the Miami Herald, good article on dissenting views.

Left out of the timeline in this blog posting were the occasions on which you posted that you 'don't give a shit' about CFS. Rheumatoid arthritis, yes, because of a concern that you might actually come down with it. How nice.

It's amazing how sometimes some of the smartest people say some of the dumbest things, especially about things they don't know anything about.

I don't know anything about retroviruses, lab protocols, or whether or not the technical aspects of the McClure/Wessely study makes sense. So I'll keep my mouth shut on that (Dusty Miller has opened a line of inquiry directly with McClure, though).

I do know that if someone doesn't give a shit about CFS, then it's not exactly likely they're going to know much about why Wessely's name on a study like this should be a reason for anyone interested enough to blog about it should recognize that it's cause for red flags regardless of their position on the WPI study.

I also know that in your zeal to pat yourself on the back for your prior stated hunch, you overlooked a detail I would've thought might've managed to catch the fine eye of a scientist. Guess not.

>the patients used in this paper met the CDC requirements for CFS.

Which requirements would those be? Holmes? Fukuda? Empirical?

Fukuda. You know what they didn't meet? A standard specifically used by the WPI, something known as the Canadian Criteria. You didn't even notice this on the WPI paper? I would suggest that theirs was a cohort far too ill to attend a clinic, such as at King's Hospital, which the 186 Wessely supplied apparently can.

>If XMRV causes CFS, you shouldnt have to know in advance who the 'right' CFS patients are to test. That doesnt make any sense.

In a perfect world, perhaps. However, by screening out anyone with 'organic illness,' they have reduced this cohort to a collection of patients where, I would suggest, you are not likely to find any of the biological abnormalities that were found in the patients of Cheney and Peterson in Incline Village--the ones that the term "CFS" was created to represent.

I don't believe that anyone who knows anything about Wessely is shocked by the conclusions drawn in this paper, and you, you 'don't give a shit.' That is your prerogative.

>How, EXACTLY, did these authors 'know' all of their samples were going to be negative?

I don't think they did, save Wessely. I believe there was a cohort available at Imperial College, yet Wessely hand-picked the samples himself. Hmmm. The WPI specifically chose some of the most ill people they could find, and Wessely did pretty much the exact opposite.

Since you enjoy waltzing with creationists so much, you might take just a second to think about the possibility that on this issue, you're on a side that's analogous with theirs. That the 'Wessely School' is the Discovery Institute combined with Answers In Genesis, cubed.

And you're one of their Ben Steins.

But don't let any of this distract you from not giving a shit. Willful ignorance is great when you know everything.

"And, he would be found out when other researchers went to get more samples from the patients... sooooo... not much of a point in faking samples."

Thanks so much for your insights. Since this research was done in the UK, our hypothetical Darth Vader need not worry about Federal Prison. And his career would have certainly been finished had the scientific team found XMRV. So future funding was at risk in any case.

Also, the patient blood used was stored for years, and in some cases, decades. Most of these patients are no loonger available for study. All of the stored blood was/is under Darth's control, and will remain that way. I was just wondering if their was some way to globally inhibit the PCR signal in the samples without being detected by the scientfic team. Apparently not.

Although the blinded PCR operator was not supposed to know the difference between the blood samples, and negative samples which were water. Or am I missing something? Maybe that was only to screen for contaminants. News sources state that there were healthy controls, but for some reason, there was no mention of them in the actual report. Are water controls typical and sufficient?

If you were on the scientific team, is there some reason that you would go to the most mistrusted figure by CFS patients in all existence to get stored blood from and outside source,when your very own College runs a world class CFS clinic and fresh blood from diagnosed CFS patients was available?

Sterile pig blood. Hmmm. I wonder if that has ever been actually done. Could be a large black market will be created by your post.

I've been reading the comments posted at this blog for the past few weeks, and it has really driven home the difference between science and politics. Scientists are very far from perfect, but they are pretty much constrained by the rules of the game to stay fairly close to observed data and experimental results. In politics, on the other hand, there are no facts -- just symbols to be manipulated -- and the ultimate goal is persuasion, rather than analysis.

And it's clear that creationism, HIV denial, and global warming denial are all political, rather than scientific, positions -- attempts to persuade, rather than analyze. And as such, they are all fundamentally Lysenkoist in character.

So I'm sitting here wondering how CFS got to be so politicised, and what point there is -- even in political terms -- in turning XMRV-as-the-cause-of-CFS into The Position To Be Defended.

Look, my sister has CFS, and I would very much like to see someone identify its cause (or causes) and come up with an effective treatment. I don't have any strong opinions about what causes CFS, other than the suspicion that it is physical, rather than psychological.

It looks to me as if the research on CFS is still in the stage where scientists are following up any interesting lead in the search for a cause -- which means that most of the leads that they investigate will turn out to be duds. That's normal science, and it's a necessary way of doing things. The more politics that people bring into the situation -- particularily at this stage -- the more they're likely to make it difficult to discuss (or even do) basic research.

And is there something particularily wonderful or important about turning XMRV, or EBV, or tobacco mosaic virus, or whatever, into the political position to be defended? Is there some political reason why it would be better for CFS to be caused by XMRV, rather than some other agent? I can't see any scientific reason for preferring XMRV to another virus, for example. It's much more important to do the research and find out what's going on, rather than dig in and take a position in favor of a particular virus.

@ Cooler â First, thanks for pointing me to the Burkett article. I think that part of what is going on here is a matter of measuring importance from a patients view compared with a scientists view. At least I think thatâs the constructive part.
I think itâs a pretty safe argument that HIV patients are better off today than they were in 1984, even if the theory of HIV as the retroviral cause has more holes than a block of Swiss cheese. Many that were very ill improved greatly with the introduction of retoviral meds, even AZT which is hell on the body but now retroviral cocktails greatly increase the quality of life for a large majority of âHIVâ patients.
I would not be the least surprised if it were found that a combination of infectious agents were all required to cause CFS. I think there are pieces of this that may already be in place. Many CFS patients have elevated levels across the range of HH viruses. Enterovirus infections that no one has ever given much thought are also quite common. Add to that, the occasional parasitic infections.
The Burkett article quoted John Coffin â âWe do not yet know how HIV causes AIDS," Dr. John Coffin of Tufts University, a member of the international committee that named the virus, told the delegates to the Sixth International Conference on AIDS last June (1990).â
The same John Coffin testified in front of the HHS CFS Advisory Committee in late October, 2009 on the importance of the recent XMRV association with CFS. Dr. Coffin also wrote an opinion paper accompanying the original WPI article in Science (http://www.sciencemag.org/cgi/content/short/326/5952/530) entitled: Virology: A New Virus for Old Diseases? Coffin states: âBoth laboratory and epidemiological studies are now needed to determine whether this virus has a causative role, not only in this disease, but perhaps in others as well.â
In January 6th, 2010edition of Science Now, Dr. Coffin writes in response to the UK article and the WPI response: âOne distinct possibility, is that both papers are right. He called the PLoS ONE paper too "preliminary" to settle the debate and said XMRV could show more genetic variety, and thus be harder to detect, than anyone assumed. It's also possible that distinct strains of XMRV appear in different parts of the world, like the retroviruses HIV and HTLV (a leukemia virus).â

Coffin says âone more possibility, raised by many different scientists, is that CFS is actually a suite of diseases that presents the same symptoms and so might have many causes.â Lombardi (of the WPI) seconds this point. "It's naive to think that everyone with chronic fatigue has the same etiology. There's probably going to be a subset of people with CFS that have XMRV, and it will probably end up being classified as XMRV-related CFS."
From the Burkett article to explain the absence of HIV in all AIDS patients: âThe virus or its antibodies are not being found in all cases of AIDS because tests for it are not yet sensitive enough, the CDC argues.â
The irony of the CDC claiming that a for a group of AIDS patients âthe virus or its antibodies are not being found because tests for it are not yet sensitive enough, is quite rich given the CDCâs campaign to deny the existence of CFS right out of the lab and on to the therapists couch or into the psych ward. Keep in mind that being âsectionedâ â committed against your will is not uncommon for CFS patients in the UK that insist there is an organic cause for their illness. This is Wessleyâs policy

Another comment from the Burket article that stood out âBut there is another glitch in AIDS epidemiology that Root-Bernstein finds even more disturbing: An increasing number of people coming down with infections typical of AIDS patients are turning out not to have HIV.â

This does not surprise me in the least. I have been tested for HIV approx. 15 times. My infectious disease docs keep coming back to HIV as the easiest explanation for all of the infections I keep coming down with. I am not alone. As I mentioned earlier, one of the leading CFS doctors in the country is Nancy Klimas, an HIV specialist. According to Dr. Klimas, her âHIV patients are hale and hearty while her CFS patients are really sick and not doing well at all.â

So is XMRV the answer for even a sub-set of CFS cases? It is probably not The Answer. But it may be something and if so it would definitely be a start. And that start is something that CFS patients have not had in over 20 years while doctors like Wessley have written polices that block access for those using the NHS to even look for the abnormalities that Dr. Klimas have consistently found such as âPlasma cytokines in women with chronic fatigue syndromeâ - http://www.translationalemedicine.com/content/7/1/96â

So would CFS patients be better off than they are today with the kind of misguided, wrong headed treatment that the Burkett article claims that HIV/AIDS patients are still receiving? The purpose of a scientific theory is to describe and predict. Even thought current theories may fail to adequately explain many anomalies, they get it right enough to provided relief to a large number of people who would otherwise be quite ill. Are some exceptional patients harmed by the inadequacies of the HIV causes AIDS theory (assuming from inconsistent data that those inadequacies exist), I would assume that unfortunately, harm is done. Will theories on HIV/AIDS evolve, of course and perhaps radically.

Now compare the plight of todayâs HIV patientâs to that of todays CFS patient. Drs. like Wessley and Reeves are fighting for their professional lives with every thing they have to stop serious inquiry into the possibility of an XMRV association with CFS - Patients and morality be damned. Do you honestly believe Dr. McClure when she says"We take no pleasure in finding colleagues wrong or dashing the hopes of patients, but it's imperative the truth gets out." Are you kidding, they waited an entire three days and then did everything they could to discredit the WPI article and all âfor the good of the patients.â Please, McClure and Wessley, (and Reeves), CFS patients are pleading with you â Stop Trying to Help!

âOpinionated but ignorant doctors and scientists who wouldnât spend 10 minutes reading Hillary Johnsonâs Oslerâs Web, mindlessly adopt the CDC position (âthe patients met the CDC diagnostic criteriaâ) that CFS is nothing more than depression, malingering and âerroneous illness beliefs.â Does anyone outside of the CFS field even know about the Canadian Consensus criteria, the WHO ME criteria, the Fukoda criteria, the CDC and CDC revised criteria. Can any retrovirologist reading this give me a coherent list of the primary differences and why they are thought to be important?

For CFS patients today, itâs not about getting it perfect. Itâs about getting it STARTED. The glib manner that many otherwise educated people use to dismiss CFS does nothing to assist the patient with CFS, instead it displays an appalling ignorance while some of the most afflicted are dying and all because of what was stated so eloquently in the 1990 Burkett article:

"What epidemiologist or federal official wants to admit that the entire thrust of research and education might be misguided?" asks Robin Haueter, an AIDS activist in New York City. "What person with AIDS wants to consider the horrendous thought that we have wasted five years of research, that the end might not be anywhere in sight?"

The irony here is that people with CFS know is that the last 20 years have been wasted and that signs of an end might be in sight and those standing in the way are the very same epidemiologists and federal officials claiming to an imperative to get the âtruthâ out.

As for digging in and rooting for a particular cause. Not happening. Digging in and insisting that all avenues be explored with an open mind. Damn right I am!

^A letter-perfect example of politics in action.

It's been nothing but politics for the last 20 years. Before the first dime is allocated, it's all about who can most effectively get their point across and who controls the dialog. Wish it wasn't so, but as long as resources have to be allocated, that's the world we live in.

Best of luck to your sister.

More politics.

http://report.nih.gov/rcdc/categories/

Abbie isn't the only one who doesn't give a shit about CFS.

Yeah, Imagine how this is gong to be interpreted if there really is a 3-4% rate of XMRV infection in asymptomatic controls.

Regardless, that will all change over night once drugs are identified for treatment of if a treatment is found.

Left out of the timeline in this blog posting were the occasions on which you posted that you 'don't give a shit' about CFS.
Dear Emotional Train Wreck-- I dont care about CFS. The only reason I write about it is that the disease has been associated with a retrovirus. Technically, Im one of the *best* advocates the XMRV-->CFS advocates could hope for. Ask anyone who reads this blog and doesnt just drive-by shit on it like you/SC/cooler, Im obsessed with retroviruses in their exogenous and endogenous forms, and I freak the hell out when they are connected to yet another disease, whether theyre directly causal, or just a marker for disease (eg, MS). On personal level, my lab also works on a different mouse virus that may/may not be associated with a different disease in humans.

But I dont believe the XMRV-->CFS connection yet.

It doesnt make sense.

I dont care about the real/perceived political 'war!' against CFS.

I dont care who/what/which scientists or MDs think its all in your head.

I dont care about hearing CFS patients medical history since they were 2 years old in comments on my blog. Im not an MD, dont care.

I care about whether a retrovirus is a cause of, or at least a useful diagnostic marker for, CFS.

At this point, its not.

John-- Awesome Qs!

1-- Darth simply has nothing to gain by faking samples, though. At best, he delayed his scientific death by a few months. I mean, everyone else is looking for this virus-- if his study is the only one that comes up negative, then hes going to be outed. If it then comes up that he 'cheated', he will be lynched. I just dont see what he would have to gain in the long run.

2-- We found HIV-1 sequences in tissue kept at room temperature, soaked in formaldehyde, for 50 years ;) 'Old' doesnt mean the DNA is damaged/gone.

3-- However, random people online seem to have lots of extemporaneous information about these samples/how they were collected/from whom they were collected. Their 'information' is not in the paper, and directly contradicts the methods in the paper. For instance, how were the thyroid tests, interviews, etc performed if these patients are no longer available? I dont think #2 is necessary justification.

4-- The main reason people cant get their PCR detection down to one copy number is background. Nonspecific bands, or noise in the case of real-time PCR. You do always do water to see what kind of noise you get, and, whether you contaminated a reagent. Healthy controls were necessary in the first paper, because if all their CFS are positive, and all their healthy were positive, somethings up. In the case of this second paper, healthy controls would have been useful, but since all the CFS are negative, theyre not really *necessary*. Its just humorous the PCR techs thought there were healthy controls in the mix :)

5-- If I had a controversial publication, the first person I would go to for validation is my arch enemy in the field. If they can make it work, no one would question us (ie me).

6-- Moar about the piggies :)

TotallyUncool-- That was probably the most rational comment in the history of my blog.

*bow*

re not giving a shit about CFS.

I'm sure that you understand that there are lots of people who are severely disabled by CFS, often bed bound and totally unable to continue with their old lives. XMRV is the first hint in a long time that 'real' science might be able to get in gear for them, rather than the highly theoretical quackery they've been stuck with so far. A lot of them are going to be highly strung about the way their condition is talked about, because their has been such prejudice and nonsense over the last thirty years. I think that their intemperate outbursts are more justifiable than your own.

re Wesseley: It really makes no sense for him to be fraudulently selecting patients according to a new understanding of CFS which now excludes biological markers like unusual cortisol results. Other replication studies are coming. It is funny that he's a co-author of the first paper which fails to replicate the XMRV work, but even if, as expected, he used a much looser definition of CFS than the WPI, it still should have picked up some instances of XMRV if the XMRV/CFS link was to hold up.

The WPI did mention using the 'sickest of the sick' though, and the British study only used those who were well enough to attend a clinic in London, so it's possible that the XMRV link could hold up for a very small section of those with the most serious cases of CFS? CFS is a bitch to study though, which is probably why most decent scientists leave well alone. I can't imagine being inspired by a recent medical paper on CFS if I was deciding my specialism.

re politics: This is a problem I have with Wessely. He really does approach his medical research from a political and philosophical perspective, rather than attempting a purely scientific one. His early papers were quite open about this. He think CFS is part of a wider problem of people 'medicalising' symptoms, rather than managing with them themselves; this pushes ever greater responsibility away from individuals and towards society and the medical community. He's recently written that the fatigue of MS and Cancer patients should also be treated as a psychological problem. He could be right - but I can't help but feel that he's been given such authority within CFS only because it is a disease no-one else is terribly interested in. If he were writing his papers as part of a Philosophy department, that would be one thing. Imposing his treatments upon patients seems a little premature at this point.

It seems widely thought that until a clear biological cause for CFS is found, it should be assumed to be a psychological problem even if no psychological cause can be found either. I understand CFS patients resenting that.

gf1, I'm not a CFS sufferer so I doubtless don't get it, but I find it refreshing that Abbie said she didn't care about CFS patients. She's not a clinician or even a medical doctor, she's a virologist. So she cares about viruses.

I know there are people out there who are such great humanitarians that any human suffering whatsoever causes them pain, but the vast majority of people are more or less indifferent to the non-life threatening suffering of strangers beyond a "Gee, that must kind of suck". They just pretend to. One of the things I like about Abbie is that she doesn't pretend to be nicer than she is (and I mean that in the nicest possible way), and her natural personality shines through in her writing.

That should be "They just pretend to care" not "They just pretend to".

Sure - it's fine to be honestly callous, but I don't think you should be surprised if people are upset by that, especially if they're already struggling to manage in an extremely difficult situation.

If during the fifties you'd told people that 'I don't give a shit about segregation' that could well have been an honest expression of how most White Americans felt at the time, but it would still be legitimate for African-Americans to be angered by such an assertion. Indeed, such anger was then used to try to undermine the push to civil rights - it's often easy to see those enduring hardships as unreasonable, especially if you have no interest in understanding their hardships.

I'm fine with Abbie not giving shit about CFS (well - of course I wish that people we more driven by moral and humanitarian concerns - but I understand this is often not the case), but she sometimes seems to be surprised or upset by the bitterness and anger her comments can prompt from CFS patients and I think this shows that she may not have thought about what they are going through and how it would feel to have such a difficult affliction be so dismissed by another.

Whether or not you have CFS has nothing to do with the issue of causation.

Anecdote is an attempt to manipulate an evidence based discussion to give sympathetic credence to a less credible position.

Ham handed emotionally manipulative behavior is to be regarded with scorn if not disregarded entirely.

It isn't mean because it isn't personal, it's the uniform pragmatism that is supposed to drive science.

P.S. You should also know that I am an orphan and am typing this with my flipper.

@TotallyUncool

CFS research is so politicized because so much rides on it. I was denied state disability help when I was ill. If I had a blood test showing infection, it might have made the difference between worrying about rent and worrying about health. Schools, jobs, tons of things depend on the results of the CFS science.

I feel sorry for the scientists caught up in the middle of this whirlpool when they just wanted to answer an interesting technical question. But don't be shocked. Life sucks when you have CFS; first you feel sick, then people question your sanity and your work ethic.

You should also know that I am an orphan and am typing this with my flipper.

Prometheus, I adore you.

@gf1

The WPI did mention using the 'sickest of the sick' though, and the British study only used those who were well enough to attend a clinic in London, so it's possible that the XMRV link could hold up for a very small section of those with the most serious cases of CFS? CFS is a bitch to study though, which is probably why most decent scientists leave well alone.

If the WPI study truly did use the "sickest of the sick", the issue of infering causation from association becomes a little more complex. If you're comparing these patients to healthy controls, you cannot rule out increased susceptibility to XMRV due to being "sicker". And if XMRV is truly only endemic to the United States, this would explain why the British cohort did not have any evidence of XMRV infection.

@ Prometheus: If you were replying to me, then you have misunderstood something.

@ NP: Yeah sure. Especially as I think these patients were selected partly due to immune abnormalities.

Just to clear one thing up: could our immune system 'cure' us of a retrovirus like XMRV? The 4% XMRV rate in healthy people seems low if it is just coincidental that immune compromised CFS patients have a really high rate of infection, especially if PCR is meant to be able to pick up any level of infection.

Ta.

#36 gf1

"@ Prometheus: If you were replying to me, then you have misunderstood something."

I wasn't, but with your Marie Antoinette sense of moral equivalence I suspect you think you are the subject of most conversations.

Segregation?? Really?

Wow.

*slaps forehead with flipper*

Who were you replying to? I had a quick look through, and could find no-one arguing that their personal experiences or diagnosis are evidence of any particular causation. I could well have missed it though, in which case I apologise.

It's best to stick to simple moral examples like racism when talking to people who may have no particular interest in moral philosophy. I didn't say I saw them as morally equaivalent.

#38 gf1

SC in the context of past and present rounds on this topic.

Racism isn't a simple moral example.

Equivalence is a corollary of comparison.

I suspect you are being slippery but I will give you the benefit of the doubt and just reiterate that interjecting identity politics into considerations of causation is distracting, counterproductive and renders the opinions of the commenter at the very least fishy.

When commenters feel it is germane to identify as having or not having CFS the discussion degenerates into the Lourdes bulletin board.

So did SC actually argue that because he has CFS this has some significant importance with regards to causation?

Racism works well as a simple moral example because it is so widely viewed as 'bad'.

If you meant equivalence as in 'equal to' then I did not make such a claim. If you meant equivalence as in 'comparable to' then your initial complaint makes no sense.

I've made no appeals to identity politics.

The topic was widened out, beyond the purely scientific matter as to the the likely etiology of CFS, and into the reasonable moral and emotional responses to the condition and attitudes that surround it. This is nothing to be afraid of.

The gold standard is "These reagents can positively identify one copy/ul, but are still negative at zero copies/ul."

ul = µL?

There are at least 3 official definitions of CFS used in the US and about a dozen more around the world. The name Chronic Fatigue Syndrome is analogous to "Smurf". Thus if you want to know whether a retrovirus causes or is diagnostic for CFS, you do have to care enough to learn something about which "CFS" is being studied.

Is it Smurf (Canadian Consensus), Smurf (Fukuda), Smurf (Reeves), Smurf (Oxford), or which Smurf are we talking about?

It does matter because Chronic Fatigue Syndrome was a name originally used to investigate an infectious outbreak at Incline Village, NV. The psychiatrists coopted the name for their own purposes to study psychiatric patients with fatigue. Imagine if they coopted the name AIDS or MS and there were 15 different official definitions and what a mess that would make of research.

Smurf--call off the dogs. She doesn't care. Read the thread. She doesn't know, or want to, about any of the particulars--why would she? If the samples were hand-picked to fail, then Wessely would be outed, she says.

She obviously knows everything about how things work.

Her mind's made up.

Just a quickie about the 'sickest of the sick' comment-

When Dr. Mikovits mentioned that XMRV was found in the 'sickest of the sick' of patients, I believe she was referring to the patients who Dr. Peterson has been following who went on to develop lymphoma. See- http://www.scivee.tv/node/7030 'Antiviral treatment of patients with HHV-6, EBV & Enterovirus: case reports' International Symposium on Viruses in CFS & Post-viral Fatigue A satellite meeting of the 6th International Conference on HHV-6 & 7 in Baltimore, Maryland, USA Day 4 - June 23, 2008

Anyways, my understanding is that it was these patients who they initially tested with their microarrays to see what, if anything, might come up positive.

When they started finding XMRV in these patient's blood which was stored in Dr. Peterson's personal repository, they then randomly selected samples from the WPI sample repository and which is seperate from Dr. Peterson's personal repository. The WPI repository contains samples from CFS patients around the country which were obtained by CFS clinicians which I would guess Dr. Peterson is especially comfortable with their diagnosis such as Dr. Cheney, Peterson's old colleague from Incline Village.

I'm not positive, but I think that's how the Science paper was done.

WPI has offered their samples to the UK group for them to study. If they refuse to do this they should shut up about their arrogantly saying that their study proves anything other than their own incompetence.

As a non scientist I wish to add something to this topic. I cannot comment on which study is or is not valid, though it appears that they are studying different things (due to looking at patients with diseases which are different although lumped into the nearly meaningless descriptor "CFS").

There is clearly a group of people who have a very serious organic disease; at a minimum those included in the WPI study. There is quite likely a slightly broader group with similar symptoms but without cancers who have either the same or a related disease. This disease is not characterized simply by feeling tired, it has a number of symptoms of which exhaustion, different from normal fatigue, is the most visible. It clearly includes immune system dysfunction; additionally, low blood volume and improper pressure regulation are frequently seen. Considering how little is known, it is possible that there are several diseases which cause similar, overlapping sets of symptoms.

Little has been done to describe and investigate these disease(s), much less their cause. There are palliative measures which reduce symptoms for some people but no known means to remove or inactivate the underlying disease. I think its reasonable to believe that with a concerted effort more progress would be made.

But there has been no such effort. A few physicians are doing what they can, but that is not enough to find answers. I do not personally know if the WPI result is correct nor if XMRV is a cause, co-factor, result or irrelevant to this disease. What is clear that WPI is making an effort to improve the health of their patients.

What matters is not a particular virus or a disputed research result. What matters is finding the cause(s) of this disease and effective treatments, much as was done with other formerly mysterious diseases such as AIDS.

Where are the other scientists targeting this beast?

Racism works well as a simple moral example because it is so widely viewed as 'bad'.

What if this hypothetical '50s person had said instead: "I don't give a shit about racism, I'm only interested in the law, and if we find that segregation is unconstitutional I'm prepared to argue it all the way to the supreme court."

Do you a) realize how such a person could be very useful to your cause even if you think he's being an asshole, or
b) shout "Go away you big meany head!!"

CFS/ME is most probably going to be a "Neurodegenerative Conformational (Misfolded) Protein Disease" resulting in :

"Chronic Retrovirus-Induced Neurodegeneration",
"Chronic Retrovirus-Induced Encephalomyelitis",
"Chronic Retrovirus-Induced Myalgic Encephalomyelitis".

SERPINA1 (Z-A1AT) and HFE (C282Y) gene mutations may be the cause of XMRV-related CFS/ME.

Molecular analysis of A1AT (S and Z) and HFE (C282Y and H63D) gene mutations may be the answer in the search for the cause of CFS/ME.

Conformational (Misfolded) Protein Diseases :

- Alpha-1 Antitrypsin Deficiency (Z-A1AT/Z-A1AT)
- Hereditary Hemochromatosis (C282Y/C282Y)
- CFS/ME (Z-A1AT/C282Y)

Comparison 1 : car + motor + key = driving
Comparison 2 : XMRV + Z-A1AT + C282Y = CFS/ME
Comparison 3 : ER Stress Induced by a Neurovirulent Retrovirus + ER stress induced by a (first) Conformational (Misfolded) Protein Disease + ER stress induced by a (second) Conformational (Misfolded) Protein Disease = too severe and prolonged Endoplasmic Reticulum (ER) Stress => Blood-Brain Barrier Breached => Chronic Brainstem Inflammation

Three must-read articles for those looking for a causal association between CFS/ME and Z-A1AT/C282Y, and between CFS/ME and XMRV, and between Neurodegenerative Disease and Neurovirulent Retroviruses, saying :

- Z-A1AT associated with CNS disorders and neurodegenerative illness
- Endoplasmic Reticulum (ER) Stress Induced by a Neurovirulent Mouse Retrovirus
- C282Y HFE protein & ER stress => Co-existence of both C282Y HFE and Z-A1AT protein expression on ER Stress Responses => potential disease modifiers with respect to each other.

[1]
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Z-A1AT associated with CNS disorders and neurodegenerative illness
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Neurotoxicology. 2007 Sep;28(5):899-914. Epub 2007 Jun 14.
Art, alpha-1-antitrypsin polymorphisms and intense creative energy: blessing or curse? Schmechel DE.

http://www.ncbi.nlm.nih.gov/pubmed/17659342

==> heterozygous for Z ... alpha-1-antitrypsin (AAT, SERPIN1A) polymorphisms ... AAT polymorphisms ... CNS disorders. Z polymorphism ... associated with ... neurodegenerative illness
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[2]
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Endoplasmic Reticulum (ER) Stress
Induced by a Neurovirulent Mouse Retrovirus
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Endoplasmic Reticulum (ER) Stress Induced by a Neurovirulent Mouse Retrovirus Is Associated with Prolonged BiP Binding and Retention of a Viral Protein in the ER*

http://www.jbc.org/content/279/32/33782.full

August 6, 2004 The Journal of Biological Chemistry
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[3]
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Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses

BMC Cell Biology 2007

http://www.biomedcentral.com/1471-2121/8/30

==> C282Y HFE protein induced apoptotic responses associated with activation of ER stress.

==> co-existence of both C282Y HFE and Z alpha 1-antitrypsin protein ... expression on ER stress responses acted as potential disease modifiers with respect to each other.

------------------------------------------------------------

Causal link between XMRV and CFS/ME is expected to be established sooner than later :

- Retrovirus-Induced Spongiform Neurodegeneration
- protein-folding disease : accumulation of unfolded proteins in the endoplasmic reticulum (ER) => Endoplasmic Reticulum Stress

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Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration

Journal of Virology, December 2003, p. 12617-12629, Vol. 77, No. 23

Derek E. Dimcheff

=> mouse retrovirus

=> Neurovirulence

=> the accumulation of unfolded proteins in the endoplasmic reticulum (ER)

=> retrovirus-induced spongiform neurodegeneration represents a protein-folding disease

http://jvi.asm.org/cgi/content/abstract/77/23/12617

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IMPORTANT EVIDENCE-BASED CONCLUSIONS
DIRECTLY OR INDIRECTLY RELATED TO CFS/ME & XMRV :

CFS/ME has been associated with XMRV.

"Increased neutrophil apoptosis" has been associated with CFS/ME.

"Increased neutrophil apoptosis" has been associated with SIV.

SIV is related to HIV.

SIV, HIV and XMRV are retroviruses.

Z-A1AT is a potent neutrophil chemoattractant.

Z-A1AT has been associated with recruitment of neutrophils.

Recruitment of neutrophils into the brain has been associated with chemoattractants within the brain.

Z-A1AT is a potent neutrophil chemoattractant.

Polymers of Z-A1AT Co-Localize with Neutrophils.

Z-A1AT has been associated with neurodegeneration.

Neutrophils have been associated with blood-brain barrier (BBB) disruption.

Blood-brain barrier (BBB) disruption has been associated with neurodegeneration.

HFE C282Y gene mutation has been associated with ER stress.

C282Y has been associated with ER stress.

Alpha 1 antitrypsin Z allele = Z-A1AT

Z-A1AT has been associated with ER stress.

MuLV has been associated with ER stress.

Endoplasmic Reticulum Stress = ER stress

XMRV has been associated with MuLV.

XMRV has been associated with ER stress.

The pathogenic Z alpha-1 antitrypsin => Z-A1AT

The normal M alpha-1 antitrypsin => M-A1AT

PATHOGENIC => Z-A1AT

NORMAL => M-A1AT

5% of the general population has => Z-A1AT

95% of the general population has => M-A1AT

5% of the general population has => XMRV

95% of the general population has => NO XMRV

Z-A1AT has been associated with promoting HIV infection.

M-A1AT has been associated with preventing HIV infection.

CONCLUSION - CONCLUSION - CONCLUSION - CONCLUSION
CONCLUSION - CONCLUSION - CONCLUSION - CONCLUSION

Z-A1AT should be considered as promoting XMRV infection.

M-A1AT should be considered as preventing XMRV infection.

M-A1AT should be considered as alleviating the effects of XMRV infection.

Z-A1AT should be considered as being a co-factor in causing CFS/ME.

M-A1AT should be considered as a possible cure for CFS/ME.

M-A1AT should be considered as alleviating or preventing CFS/ME.

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Z-A1AT has been associated with liver disease (1969/1985)

Z-A1AT has been associated with lung disease (1969/1985)

Z-A1AT has been associated with brain disease (2007)
http://cat.inist.fr/?aModele=afficheN&cpsidt=19690474

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M-A1AT inhibits HIV-1 (LELAND SHAPIRO - 2001)

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Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1
LELAND SHAPIRO - University of Colorado
http://www.fasebj.org/cgi/reprint/15/1/115.pdf

FASEB J. 15, 115â122 (2001)
Key Words:
alpha-1-proteinase inhibitor
serine proteinase inhibitors
HIV-1

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ONE VERY IMPORTANT QUESTION HAS BEEN LEFT UNANSWERED REGARDING HUMAN RETROVIRUSES HIV-1 and XMRV :

AND THAT QUESTION IS :

Is the prevalence of the HFE C282Y gene mutation and alpha 1 antitrypsin Z allele increased in patients with retroviruses such as HIV-1 and XMRV ? And is the answer a nearly one hundred procent (±100%) yes ?

If the answer is a nearly one hundred procent (±100%) yes, then the real cause of AIDS and CFS/ME has been found, meaning that the Z-A1AT gene mutation is the most important bad guy in both HIV-1 and XMRV, and the normal M-A1AT gene variant is the most important good guy in both HIV-1 and XMRV. What we already know is : M-A1AT inhibits HIV-1 (LELAND SHAPIRO - 2001). Is this also true for XMRV ? Most probably yes ! Is M-A1AT going to be a possible cure for both AIDS and CFS/ME ? Most probably yes. Research should be done on this. As soon as possible ! Starting with giving an answer to the above-mentioned question.

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HIV infection in a patient with alpha-1 antitrypsin deficiency: a detrimental combination?

AIDS. 2007 Oct 1;21(15):2115-6.

Potthoff AV, Münch J, Kirchhoff F, Brockmeyer NH.

http://www.ncbi.nlm.nih.gov/pubmed/17885308

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THE RIGHT QUESTION SHOULD BE :

HIV infection in a patient with alpha-1 antitrypsin deficiency :
is there a causal link between HIV-1 infection and alpha-1 antitrypsin deficiency ? Does Z-A1AT (or other SERPINA1 gene mutations) cause AIDS in HIV-1 infected individuals, perhaps with the help of the HFE C282Y gene mutation (or other HFE gene mutations) ?

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is there a causal link between HIV-1 infection and alpha-1 antitrypsin deficiency ? Does Z-A1AT (or other SERPINA1 gene mutations) cause AIDS in HIV-1 infected individuals, perhaps with the help of the HFE C282Y gene mutation (or other HFE gene mutations) ?

is there a causal link between HIV-1 infection and alpha-1 antitrypsin deficiency ? Does Z-A1AT (or other SERPINA1 gene mutations) cause AIDS in HIV-1 infected individuals, perhaps with the help of the HFE C282Y gene mutation (or other HFE gene mutations) ?

Posted by: sikiÅ | January 23, 2010 11:35 AM

YAY FOR PORNSPAM!
(In Turkish, no less, in case anyone wants a free language lesson.)

XMRV/CFS/ME : conclusion based on relevant medical/scientific literature - January 25, 2010

Endoplasmic Reticulum Stress Is a Determinant of XMRV-Induced Neurodegeneration in CFS/ME : A1AT (Z and S) and HFE (C282Y and H63D) heterozygous gene mutations, and especially the co-existence of both C282Y HFE and Z A1AT protein expression are main determinants of the neuropathogenicity of XMRV in patients with CFS/ME, with the major target of XMRV toxicity aimed at the oligodendrocytes, first in the spinal cord and brainstem and subsequently in the cerebellum.

Conclusion based on relevant medical/scientific literature :

[VC Lombardi - 2009]
[MW Lawless - 2007]
[DE Schmechel - 2007]
[AC Clase - DE Dimcheff 2006]
[DE Dimcheff - 2003]
[JC Coffey - 1997]
[RM NAGRA - 1994]

============================================================
XMRV-induced CFS/ME & Co-existence of both R462Q and Z-A1AT
============================================================

================================================================================
Co-existence of both R462Q RNASEL and Z A1AT protein expression : the most important hitherto overlooked risk factor for XMRV-induced CFS/ME ?
================================================================================

CONCLUSION :

Endoplasmic reticulum (ER) stress plays a critical role in prostate cancer and CFS/ME. Homozygosity for the R462Q RNASEL gene mutation variant may be a risk factor for XMRV-related retrovirus-induced prostate cancer, and it should be hypothesized that heterozygosity for the R462Q RNASEL gene mutation variant, especially co-existence of both R462Q RNASEL and Z A1AT protein expression, drastically reducing not only ribonuclease but also alpha 1-antitrypsin antiretroviral protein activity, and furthermore, promoting accumulation of misfolded proteins, ER stress and apoptosis, may be the most important hitherto overlooked risk factor for XMRV-induced CFS/ME.

KEYWORDS:

XMRV; retrovirus-induced neurodegeneration; neurodegenerative disease; cancer; accumulation of misfolded proteins; ER stress; endoplasmic reticulum (ER) stress; apoptosis; ER stress and cancer; ER homeostasis; Myalgic Encephalomyelitis; Chronic Fatigue Syndrome; Xenotropic MuLV-Related Virus; RQ alleles in RNASEL R462Q; QQ alleles in RNASEL R462Q; RQ genotypes; QQ genotypes; RNASEL Q allele; RR, RQ, QQ; heterozygous and homozygous; RNASEL QQ genotype; RNASEL RQ genotype; QQ allele at R462Q in the RNaseL gene; RQ allele at R462Q in the RNaseL gene; a mutation in one allele of RNASEL; RNASEL genotypes : QQ, homozygous R462Q variant; RQ, heterozygous variant; RR, homozygous wild-type variant; retrovirus-induced cancer.

LITERATURE :

[VC Lombardi - 2009]
[X Li - 2009]
[R Schlaberg - 2009]
[DE Schmechel - 2007]
[MW Lawless - 2007]
[A Urisman - 2006]
[DE Dimcheff - 2003]
[HM Temin - 1988]

Remarkable Things what Cats & Humans have in Common !

Remarkable resemblance between XMRV & FeLV

FeLV is part of the same family of retroviruses, of which XMRV is also being a part of.

MuLV and FeLV are like brothers and sisters :

- MuLV is what you find in mice.
- FeLV is what you find in cats.
- XMRV is what you find in humans.

MuLV, FeLV and XMRV are belonging to one and the same familiy of retroviruses, the gammaretroviruses, formerly called oncoretroviruses, meaning oncogenic retroviruses.

Approximately 0.5% of pet cats have been found to be persistently infected with FeLV, which is exactly the same percentage found in XMRV-induced CFS/ME, where the prevalence is also 0.5 % of the general population.

Another remarkable resemblance between XMRV and FeLV is the fact that in humans the XMRV prevalence, according to two different studies, is considered to be 3,7% or 4% of the general population, and prevalence of FeLV in cats is 4.3%

CFS/ME specialist Professor De Meirleir described how there are three main sub-groups in CFS/ME : 3 subgroups were identified according to severity.

And now look at what we find in cats : the existence of three FeLV subgroups ! Isn't that just remarkable.

And when you google "Feline Leukemia Virus" (FeLV), you will find "What to Watch For" in cats with FeLV. And look what we can find there. Cats with FeLV have "Lethargy", which has almost the same meaning as words like "Fatigue" and "Exhaustion".

Scientists have found FeLV in cats, already in 1964.
Scientists have found XMRV in humans in 2009, no earlier than 45 years later.

Oh yeah ! I almost forget to tell you this. AZT is useful against HIV-1 infection, and scientists have found that AZT is useful against XMRV. As far as resemblances between XMRV and FeLV is concerned : AZT is not only useful against XMRV, AZT has already been known to be useful against FeLV, most probably since quite some time. So there you have a resemblance once more. People with XMRV-induced CFS/ME have problems with eating on a regular basis. That's what you also find in cats with FeLV. And let's not forget the personality changes when you get XMRV-induced CFS/ME : that's what you also find in FeLV-induced illness in cats.

If you want to know more about this, you can find more details here :

http://www.psychologytoday.com/blog/complementary-medicine/201001/xmrv-…

Does XMRV exist in three subtypes ?

FeLV (Feline Leukemia Virus), MuLV (Murine Leukemia Virus), and XMRV (Xenotropic MuLV-Related Virus) are closely related gammaretroviruses.

FeLV was discovered in 1964, XMRV in 2006.

FeLV was first thought to exist in three subtypes. But now it is known that FeLV exists in four subtypes, A, B, C, and T.

Before the discovery of XMRV, and its link to CFS/ME, Kenny De Meirleir looked at the impairments of the RNase L pathway in CFS, and he found three subgroups in CFS/ME.

FeLV has a prevalence of 0,5% in cats, and CFS/ME has a prevalence of 0,5% in humans.

FeLV exists in four subtypes. CFS/ME exists in three subgroups.

Therefore XMRV may very well exist in three subtypes as well, similarly to what was found in FeLV.

LITERATURE :

http://www.psychologytoday.com/blog/complementary-medicine/201001/xmrv-…

HIV-1 is to AIDS, what XMRV is to GRIDS (also known as CFS/ME)

HIV-1 is to AIDS, what XMRV is to GRIDS (also known as CFS/ME)

HIV-1 is to AIDS, what XMRV is to GRIDS (also known as CFS/ME)

HIV-1 is to AIDS, what XMRV is to GRIDS (also known as CFS/ME)

============================================================================================
AIDS is a LIDS syndrome : AIDS (acquired immune deficiency syndrome, or, acquired immunodeficiency syndrome) is a Lentiretrovirus-induced Immune Deficiency Syndrome, caused by the Lentiretrovirus HIV-1.
============================================================================================

CFS/ME is a GRIDS syndrome : Chronic Fatigue Syndrome - Myalgic Encephalomyelitis is a Gammaretrovirus-induced Immune Deficiency Syndrome, caused by the Gammaretrovirus XMRV.

============================================================================================

After infection with HIV-1, infected individuals may develop AIDS.

After infection with XMRV, infected individuals may develop GRIDS (also known as CFS/ME).

============================================================================================

http://www.psychologytoday.com/blog/complementary-medicine/201001/xmrv-…

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XMRV-seropositivity and hyperserotonemia in nearly 40% of autism and nearly 100% of CFS/ME
XMRV-seropositivity and hyperserotonemia in nearly 40% of autism and nearly 100% of CFS/ME
XMRV-seropositivity and hyperserotonemia in nearly 40% of autism and nearly 100% of CFS/ME

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Abnormally high levels of serotonin in those infected with XMRV

Having a strong inclination for hyperserotonemia may be the hallmark of infection with XMRV.

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General Conclusion

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High levels of serotonin have been found in about 40 percent of children with autism, and XMRV has also been found in about 40 percent of children with autism.

High levels of serotonin have also been found in CFS/ME. XMRV has been found in nearly 100 percent of those who had CFS/ME. Logical conclusion should be that XMRV has the potential to not only cause autism in children, but also CFS/ME in both children and adults.

Abnormally high levels of serotonin may be the hallmark of an infection with XMRV.

These abnormally high levels of serotonin may not always be observed, but the potential to easily reach these extremely high levels of serotonin under the influence of an external factor such as a superimposed viral infection or certain types of pharmaceutical agents should be expected to be present in each individual infected with XMRV.

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approximately 40% of children with autistic features have hyperserotonemia

approximately 40% of children with autistic features have XMRV-seropositivity

CFS/ME => hyperserotonemia

nearly 100 percent of CFS/ME patients have XMRV-seropositivity

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Having a strong inclination for hyperserotonemia may be the hallmark of infection with XMRV.

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Literature

http://www.psychologytoday.com/blog/complementary-medicine/201001/xmrv-…

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Serotonin Dysregulation in CFS/ME by XMRV-infected Astrocytes

The expression of serotonin transporter mRNA has been detected in normal human astrocytes. Serotonin regulation is a task being carried out by astrocytes in the brainstem and spinal cord, which is the place in the CNS, where inflammation and neurodegeneration is taking place in CFS/ME, on a chronically recurrent basis.

In CFS/ME abnormally high levels of serotonin have been found in the blood, which is a phenomenon also called hyperserotonemia.

So high levels of XMRV-infected astrocytes will cause chronically returning brainstem and spinal cord inflammation leading to high levels of astrocytes undergoing apoptosis, which eventually will cause a situation where normal serotonin regulation will have become outright serotonin dys-regulation.

Unfortunately, this hyperserotonemia may under circumstances lead to serotonin syndrome, which is a medical complicaton with extremely high serotonin levels, characterized as being life-threatening and potentially having a fatal outcome.

However, hyperserotonemia - because of conversion of serotonin to melatonin - also causes hypermelatonemia, showing abnormally high levels of melatonin in the blood, causing extreme numbness or fatigue, which is a waxing and waning pattern found in Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis. However, the really debilitating lethargy (fatigue) and malaise (pain) in CFS/ME may more often than not, come as a result of PRCA-related anemia caused by XMRV-induced bone marrow cell suppression, resulting in hemolytic anemia, which is a serious underdiagnosed complication in CFS/ME.

http://www.psychologytoday.com/blog/complementary-medicine/201001/xmrv-…

I suspect that Someone with Asperger's & CFS/ME also suffers from some sort of OCD.

C'mon. Is it 3 or is it 4? Youd think someone with aspergers would notice little details like that.
Also, there's still no link established between CFS and XMRV. Youd think someone with aspergers...

How to Distinguish Between Autism and OCD.

Autism and OCD (obsessive compulsive disorder) are two very separate and different diagnoses.

http://www.ehow.com/how_2330447_distinguish-between-autism-ocd.html

Paying attention to little details is important in order to establish the causal link between XMRV and CFS/ME. There is a large body of evidence out there establishing the causal link between XMRV and CFS/ME. It is no use to wait for the moon to come down to us. What is needed is that we go to the moon ourselves. Some will say, that they have already tried to go there. But it does not make sense to go there by bike, and subsequently explain to people that you could not find it, and that, if it had been there, you would have found it. Because after July 21st, 1969 mankind knows better. The moon is there, and we have always known it was there. How many times do you have to go to the moon just in order to be sure that you are not dreaming ?

October 8th, 2009 has already gone down in medical history as the day constituting one small step for Lombardi et al., but a giant leap for those suffering from the debilitating consequences of XMRV infection.

http://www.sciencemag.org/cgi/content/abstract/1179052

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BOTTOM-UP THINKING

People with autism form concepts in a different manner than others. For the autistic individual, details are assigned to categories, which then are used to form a larger concept. âI take lots of little details, and I put them together to form a whole,â said Dr. Grandin. âItâs bottom-up thinking. Itâs like putting together the pieces of a puzzle. For most people, it is top-down thinking.â

http://www.neuropsychiatryreviews.com/07apr/pictures.html

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Temple Grandin on autism

According to Temple Grandin, humankind would still be living in caves were it not for people with Asperger syndrome.

http://www.news.cornell.edu/stories/March07/Temple.Grandin.html

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The Top Ten Historical Figures generally thought to have had Asperger Syndrome :

* Thomas Jefferson â the third President of the United States, the principal author of the Declaration of Independence

* Wolfgang Amadeus Mozart

* Charles Darwin

* James Joyce â author of Ulysses

* Albert Einstein

* Isaac Newton

* Samuel Johnson â lexicographer of the first English dictionary

* Michelangelo Buonarroti

* Andy Warhol

* Michael Jackson

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Bicker, bicker, bicker then no posts for months? Seems like everyone ran out of new angles to throw stones. As merely a sufferer and not an expert, it seems to me that if the Whittemore-Peterson Institute would send a group of experts to whatever country wants to run a clinical test, it would resolve whatever issues that currently exist. With on site monitoring of other laboratories and insisting on using the same procedures and mediums, I don't see where there would be anything left to argue about.... just more definitive results. Don't argue, just please keep working.