The Virus that Time Won’t Erase

“Up to today there is actually no single scientifically really convincing evidence for the existence of HIV. Not even once such a retrovirus has been isolated and purified by the methods of classical virology.”

Dr. Heinz Ludwig Sanger, Emeritus Professor of Molecular Biology and Virology, Max-Planck-Institutes for Biochemistry, Munchen.

 

I do not know how many people developed AIDS during the 1970s, or indeed before that, I was just a child when Freddie Mercury died and too young to understand the grim significance of my constant infections. One thing I do know is that once again the fight against evil, against those trying to deny a disease, is on and this time I do understand the significance and why my Government won’t let me get better but I will fight tooth and nail to get there.

“The dominant feature of this first period was silence, for the human immunodeficiency virus (HIV) was unknown and transmission was not accompanied by signs or symptoms salient enough to be noticed. While rare, sporadic case reports of AIDS and sero-archaeological studies have documented human infections with HIV prior to 1970, available data suggest that the current pandemic started in the mid- to late 1970s. By 1980, HIV had spread to at least five continents (North America, South America, Europe, Africa and Australia). During this period of silence, spread was unchecked by awareness or any preventive action and approximately 100,000-300,000 persons may have been infected.”Jonathan Mann 1

In July 1981 Dr Curran of the CDC was reported as follows:”Dr. Curran said there was no apparent danger to non homosexuals from contagion. ‘The best evidence against contagion’, he said, ‘is that no cases have been reported to date outside the homosexual community or in women”The New York Times 11

One would assume that history had learned its lesson by the disastrous handling of the AIDS crisis in the 1980’s. The Regan Administration’s silence over the issue for almost a decade coupled with a fierce battle over patents between US Scientists Robert Gallo and the Pasteur Institute in France meant that arrogance proceeded over patient care and the sick were put at the bottom of the rubbish pile.

This time the argument isn’t over patents, it’s over fear of the existence of a retrovirus three times bigger than HIV. The respective British and American defence administrations simply can’t face up to the fact that there is another infectious pathogen in existence, causing disease and death.

In 1984-85, a considerable number of people living in a small town called Incline Village in Nevada were crippled by a devastating disease of unknown origin. Of course we now know it was M.E but at the time, one by one the citizens of Incline Village fell sick with mysterious flu-like symptoms that never eased. After the local authorities repeatedly notifying the Centres for Disease Control (CDC), they, and the National Institutes of Health (NIH) paid no heed to the disease. Five years later, scientists discovered a breakthrough in what was then coined ‘Chronic Fatigue Syndrome”. By 1988, the renowned Dr Paul Cheney joined Dr. David Bell, a pediatrician in New York, and Elaine de Freitas, a virologist at Philadelphia’s Wistar Institute, and in 1991, De Freitas uncovered an HIV-like retrovirus in the blood of patients with ME/CFS.

The CDC quickly stamped out these findings, stating they could not replicate therefore it doesn’t exist (which was exactly what the CDC did with their first XMRV study by William Switzer) and De Freitas was alienated and mysteriously vanished from the virology world.

As soon as the 2009 Science paper was published, with the retrovirus XMRV found in the blood of ME/CFS patients – people began to rejoice. “Hallelujah!” a cure is found”. Instead of welcoming the findings, the Governments in both the UK and America were quick to try and stamp them out.

British psychiatrist Professor Simon Wessely was the first on the scene in February 2010, hiring Imperial College virologist Myra McClure to do his bidding and run through a quick mash-up of the Science paper, excluding most of its main techniques for finding the virus. McClure may as well have been reading Mr Men or a manual for putting up shelving. The findings were negative – the blood taken from Kings College/The Institute of Psychiatry which in itself was highly suspicious – a virus in the blood of depressed patients seems pretty unlikely. Wessely went on the record to state “even if we did find the virus we wouldn’t do anything about it, we’re in the business of rehabilitation”.

Numerous negative papers looked like swallowing Judy Mikovits but she stood strong in her findings and in May 2010, two Dutch journalists leaked information from a lecture given by Dr Harvey Alter at a conference in Zagreb (discoverer of the virus that causes hepatitis C and winner of the Distinguished Service Medaland the 2000 Albert Lasker Award for Clinical Medical Research ) announced that he had found evidence of a retrovirus in his latest study.

Again, a battle commenced to try to stop this paper from going to publication. Someone in power wanted to stop this confirmation of a new virus in the population.

Eventually in August 2010, three months later, the paper was published in PNAS but the British press were seemingly placing an embargo on the story – not one major newspaper would print the findings. Professor Wessely appeared to have put out a Schedule D notice through his position of power at the Science and Media Centre. One Health Editor confirmed she was not writing any more on XMRV ever. It seemed that the British were bent on destroying this story.

The Science and Media Centre were quick to print a press release full of disinfo about the PNAS study and hired Professor Robin Weiss, a supposed AIDS expert to do their bidding.

A few more negative studies proceeded throughout the latter part of 2010 but then something very strange happened. One of the key British Scientists, Jonathan Kerr, who was involved in one of the earlier negative studies mysteriously, vanished off the research scene. Rumours circulated that his samples that had been had been tampered with and some that went to Dr Enlander went missing.

According to bloggers on the Phoenix Rising forums, patients did contact Dr Kerr and one rang him on his last day at St George’s but he didn’t want a fuss made. He did say to one patient who called that this would probably be the end of him working with CFS and he was not happy about this. http://forums.phoenixrising.me/showthread.php?12213-What-s-Happened-to-Dr-Jonathan-Kerr

Who got to him?

The fight was getting dirty.

The enemy then delivered a surprise Christmas Present, a dirty smear campaign against the WPI in the form of five negative papers

The key members of the anti-XMRV lobby were all there, one of Professor Peter White’s PACE TRIAL Colleagues Professor Tim Peto, Myra McClure of Imperial College who was famously involved in Wessely’s Negative XMRV study, critiqued elsewhere on this site and has been famously outspoken against the WPI and of course, Bridgette Huber of Tufts University, who accused the WPI of contamination at the Invest in M.E Conference in 2010 and again at the International XMRV Conference in September because she found mouse DNA in her positive samples (which isn’t due to contamination – it is down to amplification/PCR techniques).

What is worrying is that while I am certain of a link between M.E and XMRV and back further research on the topic, Myra McClure remains chief advisor to the National Panel for New and Emerging Infections. Presenting them with this paper will only fuel their already adamant stance, that “no public health action is required at this time”, echoing the then recent FDA Blood Working Group statement.

Professor Kenny De Meirleir announced that the purposely negative papers were “crimes against humanity” and went on to state “The contamination by mouse material was excluded in our study, that of Lo and that of Lombardi et al. We are not using PCR as a basis of the test but human prostate cancer cells that do not express RNase L so the virus from patient’s blood can grow in it. We also sequence the virus and I can assure you it is not mouse material.”

An author of one of the negative papers, Professor Greg Towers of the Wellcome Trust, famously announced, just before Christmas, that “XMRV is not the cause of Chronic Fatigue Syndrome”. His paper stated it was a contaminant. Campaigners pushed Towers to retract his statement but he refused, stating that he was “committed to understanding and identifying virus causes of human disease.”

Christmas was a sour time for the ME community and were still digesting the negative studies when the next blow was to be delivered at the NIH State of Knowledge Workshop in April 2011.

The enemy were using their next pawn.

So where next for XMRV?

The journal Science, which published the Lombardi et al  2009 paper detecting  the retrovirus in the blood of patients with chronic fatigue syndrome (CFS), has now published two follow-up papers , breaking down the walls that surrounded the cure for the disease. The final blow delivered by Science came in the form of an “editorial expression of concern” asking Lombardi et al to retract their paper, stating that there was no conclusive evidence for XMRV and that is was likely a laboratory contaminant.

Now Science could have retracted the paper themselves but that would have been too easy – instead by the editors expressing concern over the validity of the paper means that the WPI is guaranteed next to no funding – putting more pressure on patient groups to come up with more novel ways of raising funds – the Count me In Campaign being one example of patient dedication to the Whittemore Peterson Institute.

Yet the questions still linger, why does Bruce Alberts, Editor in Chief of Science decide suddenly to express concern after the recent publication of two wretched Science papers?

Over the past year and a half there have been almost a dozen other studies that failed to replicate and discover the original Lombardi et al findings, why not speak up then Dr Alters? Also, the previously mentioned four papers in Retrovirology had already stated that XMRV sequences are consistent with laboratory contamination. Is this what you truly believe? Does the fact that only one author of the original paper failed to rebutted its retraction tell you to read between the lines, this more than Science playing out before our very eyes.

Surely it is in the best interests of the patient to stop playing cat and mouse (pardon the pun) over this virus and just WAIT for the official NIH sponsored study by Lipkin et al.

This latest twist in events comes only a few months after the National Institute for Health Workshop, where former XMRV supporter and co-author of the first Science paper, John Coffin, announced that XMRV should be “leaving the virus we know as XMRV behind”. This appeared to be the final nail in XMRV’s coffin.

“The request was almost inevitable at some point,” says Jonathan Stoye, who has been on the British camp, who strongly opposed XMRV from the very beginning.  I’d be surprised if he isn’t breaking out the champagne.

Then, just as patients were simply exhausted from all the negative press, a positive study is published but it barely glimmers through the dirt. Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort by Maureen R Hanson, Li L Lee, Lin Lin, David E Bell, David Ruppert and David S Bellfinally found evidence of MLV’s in the blood of patients with ME/CFS. This was announced at the 15th International Conference on Human Retroviruses: HTLV and Related Viruses, Leuven and Gembloux, Belgium. 5-8 June 2011. Also announced at the Conference but as yet unavailable online was  Kenny De Meirleir’s presentation entitled “Serological evidence of XMRV in CFS and blood donors in Belgium”. I have heard rumours that this abstract was pulled from publication but remain hopeful. Various other studies emerging from Belgium also reveal that XMRV is more than just laboratory contamination but by this point I felt beaten, cheated, stamped upon – the very nature of our illness trodden deep into the soil to erode and die with the worms.

While the situation in America isn’t ideal, at least they have the Lipkin NIH study results as well as the findings of various other NIH sponsored studies highlighted below. In the UK, we have no research into XMRV or related MLV’s whatsoever.

Britain’s very own Dr Claw, Myra McClure, hot off the press from another negative study, is giving a presentation on XMRV on 1st July at the International Congress of the Royal College of Psychiatrists. What virology has to do with psychiatry is besides the point – it is another example of how the British Government are hell-bent on dragging XMRV down into the gutter and destroying it. At present I am trying to gain access to the Conference to shoot her down in the Q & A session. The British Government have long since denounced XMRV – instead publicising PACE and other psychiatric/NLP based protocols such as the Lightening Process.

But there is one thing that the powers that be haven’t counted on. That is the power of Judy Mikovits and the team of patient advocates across the globe who support the WPI and simply won’t let XMRV become the AIDS of its time.

With MASSIVE THANKS to the wonderful folks at XMRV Global Action for the abstract summaries from the Conference, proving once again WHY XMRV is out there and that ending work on it now is grossly premature….

XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?

http://www.retrovirology.com/content/8/S1/A219

Francois Villinger1,2*, Jaydip Das Gupta3, Nattawat Onlamoon4, Ross Molinaro1,2, Suganthi Suppiah1,2, Prachi Sharma5, Kenneth Rogers5, Christina Gaughan3, Eric Klein3, Xiaoxing Qiu6, Gerald Schochetman6,

John Hackett Jr6, Robert H Silverman3

“In fact, a single atraumatic mucosal exposure with a high dose of XMRV virus into the urethra resulted in infection of 1 out of 4 macaques providing proof of concept that such transmission is possible. However, additional work is needed to fully investigate potential modes of XMRV infection.”

Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome

http://www.retrovirology.com/content/8/S1/A230

Francis Ruscetti1*, Vincent C Lombardi2, Michael Snyderman3, Dan Bertolette4, Kathryn S Jones1, Judy A Mikovits1

“Therefore XMRV infection may accelerate the development of B cell malignancies by either indirect chronic stimulation of the immune system and/or by direct infection of the B-cell lineage . Since viral load in peripheral blood is low, these data suggest that B cells in tissues such as spleen and lymph nodes could be an in vivo reservoir for XMRV.”

 

Prevalence of XMRV in blood donors, HTLV and HIV cohorts

http://www.retrovirology.com/content/8/S1/A222

Xiaoxing Qiu1*, Priscilla Swanson1, Ning Tang2, Gregor W Leckie2, Sushil Devare1, Gerald Schochetman1, John Hackett Jr1

“XMRV seroprevalence ranged from 0 – 0.6% in US blood donors, HIV-1 infected and HTLV uninfected subjects. Notably, 4.1% of Japanese HTLV-I infected individuals were p15E reactive. Inspection of sequence homology between HTLV and XMRV revealed a high level of conservation within the immunodominant region of HTLV gp21 suggesting increased seroreactivity is due to cross-reactive antibodies.”

 

Multi-laboratory evaluations of XMRV nucleic acid detection assays

http://www.retrovirology.com/content/8/S1/A231

Graham Simmons1,2*, John M Coffin3,4, Indira K Hewlett5, Shyh-Ching Lo6, Judy A Mikovits7,8, William M Switzer9, Jeffrey M Linnen10, Francis Ruscetti11, Simone A Glynn12, Michael P Busch1,2

“The Blood XMRV Scientific Research Working Group was formed to facilitate collaborative studies into the impact of XMRV in blood donors. Studies will evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility; assess performance on specimens represented in existing blood donor repositories, and determine the prevalence of XMRV in donors.” Phase III results expected soon. Phase IV will test a blinded panel of 300 blood donor samples.

Immune correlates of XMRV infection

http://www.retrovirology.com/content/8/S1/A221

Vincent Lombardi1, Deborah Goetz2, Max Pfost1, Cassandra Puccinelli1, Judy Mikovits1*

“XMRV infection results in dysregulation of the immune response, either directly by infection of specific leukocyte subsets or indirectly through cytokine modulation.”

The effects of XMRV gene expression on the mouse prostate

http://www.retrovirology.com/content/8/S1/A223

Daniel Rauch, Sirosh Bokhari, John Harding, Lee Ratner*

“Breeding PRO-XMRV mice with PRO-XPR1 mice will allow us to test whether XMRV integration or gene expression can cause more advanced prostate pathology in vivo. With these XMRV mouse models we seek to address the question that remains unanswered to date as to whether XMRV is capable of causing prostate dysplasia or cancer in vivo.”

 

XMRV: usage of receptors and potential co-receptors

http://www.retrovirology.com/content/8/S1/A224

Mohan K H G Setty*, Krishnakumar Devadas, Ragupathy Viswanath, Veeraswamy Ravichandran, Shixing Tang,

Owen Wood, Durga S Gaddam, Sherwin Lee, Indira K Hewlett

“XMRV replication was observed in GHOST cells that express CD4, and each of the chemokine receptors ranging from CCR1- CCR8 and Bob suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors. Infection of Lung epithelial cell A549 lacking XPR1 expression clearly indicates usage of other receptors by XMRV for entry into susceptible cells.”

 

Cell line tropism and replication of XMRV

http://www.retrovirology.com/content/8/S1/A225

Krishnakumar Devadas, Mohan K H G Setty, Ragupathy Viswanath, Durga S Gaddam, Owen Wood, Shixing Tang,

Jiangqin Zhao, Xue Wang, Veeraswamy Ravichandran, Sherwin Lee, Indira K Hewlett*

“Replication of XMRV could be observed in cervical and lung epithelial cells, T-cell lines Jurkat and H9, B-cell line HL60, U937 cells and in primary PBMC and monocyte-derived macrophages. The levels of XMRV transcripts were lower in primary monocytes compared to T-cell lines suggesting less efficient replication in these cells.”

Structure of the xenotropic murine leukaemia virus-related virus matrix protein

http://www.retrovirology.com/content/8/S1/A227

Michal Doležal1,2, Iva Pichová1, Tomáš Ruml2, Richard Hrabal3, Michaela Rumlová1*

“Although the protein sequence of the XMRV-MA is very similar to that of the murine leukaemia virus matrix protein (MLV-MA), it varies in several amino acid residues. We compared the structures of the XMRV-MA and MLV-MA and found that those changes are localized in a few domains, mostly on the surface of the protein.”

 

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no ass

http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a232.pdf

William M Switzer1*, Hongwei Jia1, HaoQiang Zheng1, Shaohua Tang1, Rebecca A Garcia2, Brent C Satterfield2

“Our findings are consistent with previous negative reports and do not support an association of XMRV or MuLV in the majority of CFS cases across the US.”

Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort

http://www.retrovirology.com/content/8/S1/A234

Maureen R Hanson1 , Li L Lee1, Lin Lin1, David E Bell2, David Ruppert3 and David S Bell4

“gag sequences could be amplified from genomic DNA from LNCaP cells of some subjects after 4 or 6 subcultures following incubation with certain subjects’ plasma, indicating the presence of infectious virus in blood. All gag sequences detected in this cohort were more similar to the MLV-like sequences reported by Lo et al. (2010) than to the XMRV sequences reported by Lombardi et al. (2009). Detection of gag sequences in whole blood genomic DNAs that were negative for mouse IAP and mitochondrial DNA provides strong evidence for infection of humans with MLV-like viruses.”

 

Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns

 

http://www.retrovirology.com/content/8/S1/A235

Mattia CF Prosperi , William M Switzer, Walid Heneine and Marco Salemi

“Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution. Despite using a small dataset, a strong phylogenetic signal in the alignments and highly resolved phylogenies inferred both by full-length and sliding-window approaches, different recombination programs reported conflicting results. These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time.”

 

In vitro assembly of xenotropic murine leukemia virus-related virus CA-NC protein

http://www.retrovirology.com/content/8/S1/A236

Romana Hadravová, Jitka ¿tokrová, Michal Dole¿al, Iva Pichová, Tomá¿ Ruml and Michaela Rumlová

“We found that purified XMRV full-length CANC, starting with the conserved proline residue at the N-terminus of CA, was not able to assemble into particles. However, a modification of the N-terminus of CANC (modCANC) enabled formation of spherical particles. Moreover, the negative staining of the in vitro assembled particles of XMRV modCANC revealed different organization of protein layers in comparison to CA-NC of M-PMV.”

Human infection or lab artifact: will the real XMRV please stand up?

http://www.retrovirology.com/content/8/S1/A241

Robert H Silverman

“Xenotropic murine leukemia virus-related virus (XMRV) was first identified in 2005 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe and Asia have either observed or failed to detect XMRV in patients [prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), immunosuppressed with respiratory tract infections] or normal, healthy control individuals. Among the confounding factors are the potential for lab contamination with similar or identical viruses or viral sequences originating in mice. In some studies, relatively contamination-resistant methods (e.g. IHC, FISH, and antibody detection) suggest that either XMRV or a similar type of virus is present in some patients. Evidence for and against genuine infections of humans with this intriguing virus (and/or related viruses) will be discussed.”

 

XMRV infection in human diseases

http://www.retrovirology.com/content/8/S1/A238

Otto Erlwein email, Mark J Robinson, Steve Kaye, Myra O McClure, Marjorie M Walker, Anup Patel, Wun-Jae Kim, Mongkol Uiprasertkul, Ganesh Gopalakrishnan, Takahiro Kimura and Kikkeri Naresh

“The novel gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV) was identified in human prostate cancer tissue in 2006, confirmed in 2009 and later linked to a second human condition chronic fatigue syndrome, CFS. These investigations, all carried out in the US, have not been reproduced in Europe or in China.

We found no evidence for XMRV infection in CFS. Moreover, we failed to find evidence of XMRV infection in UK prostate cancer patients and in prostate cancer tissue taken from patients in India, Korea, Thailand and Japan, or in cancers other than that of the prostate.

Our UK CFS patients were consistently XMRV-free. We did, however, generate false-positive results from prostate cancer patient tissue, despite the fact that the no-template controls in our PCR were consistently negative and the PCR for murine mitochondrial DNA was often also negative.

Sources of this contamination will be discussed in our presentation.”

A prototype RT-PCR assay for detection of XMRV in multiple human sample

http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a220.pdf

Ning Tang1*, Andrea Frank1, Robert Kowal1, Gregor Leckie1, John Hackett Jr2, Graham Simmons3, Michael Busch3 ,Klara Abravaya

 

“We developed an automated high throughput real-time Use of this assay should assist in elucidation of the role of XMRV in human disease.”

 

——————————————————————————————

June 8, 2011 2 more have been published

 

Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue

Marta Curriu, Jorge Carrillo, Marta Massanella, Elisabet Garcia, Bonaventura Clotet, Julian Blanco, Cecilia Cabrera

http://www.retrovirology.com/content/8/S1/A208

 

XMRV could specifically infect human lymphoid tissue cells although this process does not culminate in an explicit productive infection. This infection did not result in changes of T or B cells nor in immune activation, suggesting that lymphoid tissue could latently support XMRV infection.”

 

Heme oxygenase-1 activation inhibits XMRV pathogenesis and carcinogenesis in prostate cancer cells

Subhash Dhawan

http://www.retrovirology.com/content/8/S1/A218

 

“These findings indicate a pivotal role of HO-1 as a host cell defense mechanism in prostate carcinogenesis in vitro, and may offer HO-1 induction as a potentially novel therapeutic strategy to control the pathogenesis of XMRV infection.”

 

Dr. De Meirleir’s presentation was listed in the Poster Section of the agenda and was called “Serological evidence of XMRV in CFS and blood donors in Belgium”. I don’t believe it’s available online.

 

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9 Comments (+add yours?)

  1. Angie Croix
    Jun 10, 2011 @ 23:51:14

    Thank YOU for this wonderful new blog that is an addition to the
    List of TRUTH Bloggers about this terrible disease and PANDEMIC.
    Keep up the GREAT work and I have also added you to my blogroll
    so that will give you a back-link with Google..
    KEEP posting the Truth..
    Real Scientists will NOT refute the Reality..
    just those politically influenced….

    Reply

  2. Liz Willow
    Jun 11, 2011 @ 02:18:47

    Wow! You have left nothing uncovered. I hope this post receives the attention it deserves! Thank you!

    Reply

  3. flyingmummy
    Jun 11, 2011 @ 08:19:17

    Phew, that was some read. The links with the AIDS history are getting clearer by the day. What has to happen before anyone will learn?!

    Reply

  4. Monique Martens
    Jun 11, 2011 @ 10:39:20

    Whah I love this blog. Thanks to come out for the truth and be a voice for us who are too sick

    Reply

  5. Hilde Devos
    Jun 11, 2011 @ 12:01:06

    Thanks for this blog!

    Reply

  6. dreamygirl
    Jun 11, 2011 @ 12:29:54

    viruses are popping up everywhere in disease and turn out to be responsable for so much. why do they keep denying it in this instance? same as with why no vaccine for aids: because that would mainly help africans and they don’t have money, whereas white people have the cash to pay for medicine for the rest of their lives?
    KEEP UP THE FIGHT

    Reply

  7. leelaplayeela Play
    Jun 11, 2011 @ 16:30:40

    Great blog. Will share!

    Reply

  8. Bloomy
    Jun 12, 2011 @ 03:14:10

    Very well done. Thank you. MEsince1999.

    Reply

  9. Barba
    Jun 13, 2011 @ 01:11:18

    I applaud your dedication in following the trails and making sense of the politics, as well as the science. I lost three people close to me from AIDS – one of them a family member. I remember being so angry at the betrayal of so-called scientists at that time.

    In order to pressure the UK medical research establishment into investing in proper, biomedical research into ME, please make sure you sign this: http://bit.ly/Research4ME – please also repost it far and wide.

    Reply

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