Quiet Dynamite: XMRV as an Infectious Agent

[SOC]

Dubois [du boyz] was an old-time judeo-american dude from Jersey, who started this book, many editions back. He was one of the first to draw attention to the 'neuropsychiatric' symptoms. (They do use that word.) Such symptoms tend to be neglected in favor of those that are externally quantifiable. Fatigue and cognitive problems are still relatively ignored today in diseases like Crohns and sarcoidosis, but patients consider them some of the worst symptoms.

I don't think all people in the lupus field consider the 'neurotic' symptoms to be *quite* so psychogenic, necessarily, as the author I quoted (the book is written by ~25 authors). I have no clue what Dubois himself thought. There is also a very common psychosis in lupus (5-10%), and rather few people today adhere to a psycho-genesis for frank psychoses. However, I don't think any physio-genesis has ever been nailed down for *any* of the mental phenomena of lupus, 'neurotic' or psychotic. There's not really one for schizophrenia either, according to most authors. But nonetheless, most workers stopped believing schizophrenia is likely to be caused by the psyche, for various other reasons, some of them perhaps rather intuitive.

Thanks, Eric! Unfortunately, I think my brain just exploded. Maybe a good night's sleep will give my brain enough rest that your post will sound like it's written in some language in which I am conversant [rueful grin]

How I hate having ME/CFS.

 

[Eric Johnson from I&I]

Can Stress Induce Lupus?

In 1955, McLeary et al (ref) related the onset of disease to significant crises of interpersonal relationships in 13 of 14 patients with SLE. In 1967, Otto and Mackay (ref) compared 20 patients with SLE to 20 controls. The SLE-hospitalized group experienced significantly more stress than other hospitalized, seriously ill controls before the onset of disease. All patients thought that stress provoked their illness. In another study, 18 of 36 patients with SLE (50%) who were interviewed believed that psychologic factors triggered disease onset, and an additional 25 thought that it was possible.

Luv it!

Remember, this is not understood to be discredited crap with faulty study design or premises. These studies are old, but they are still considered hard core lupus-ology as of 2007 - not necessarily true, but worth knowing about.

 

[Cort]

This paper must be why the quacks at the CDC released today the paper that we CFIDS/ME people are nuts: "The prevalence of paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders were significantly higher in CFS and ISF compared to the well controls. The CFS cases had significantly higher scores on neuroticism, and significantly lower scores on extraversion than those with ISF or the well controls. Personality features were correlated with selected composite characteristics of fatigue. Conclusions: Our results suggest that CFS is associated with an increased prevalence of maladaptive personality features and personality disorders. This might be associated with being noncompliant with treatment suggestions, displaying unhealthy behavioral strategies and lacking a stable social environment."
See V99's post on " Personality Features and Personality Disorders in Chronic Fatigue Syndrome: A Populat" http://content.karger.com/ProdukteDB...ktNr=223864#AC

I am just so sick of those guys!

Lacking a stable social environment

Sorry but they can just kiss my l...whatever.......I used to think, well they're digging down into cortisol - its no big deal - it's never going to fix CFS but at least they're finding something - but they've just bottomed out here. Ugh....

 

[Cort]

First "formal" salvo?



Abstract from 12th International Conference On Malignancies In AIDS
And Other Acquired Immunodeficiencies (ICMAOI)
April 26-27, 2010
Lister Hill Auditorium
NIH Main Campus

http://oham.cancer.gov/objects/pdf/2010ICMAOI_Program_Book.pdf (p. 33)
http://www.capconcorp.com/meeting/12thICMAOI/agenda.asp

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

P7. Repeated Detection of Infectious Xenotropic Murine Virus-Related
Virus (XMRV) in Human Neoplasia and Neuroimmune Diseases (listed as
'Pathogenic Consequences of Xenotropic Murine Virus-related Virus
(XMRV) Expression in the Development of Chronic Diseases' on website)


Francis Ruscetti1, Vincent Lombardi2, Max Pfost2, Kathryn Hagen2, Judy
Mikovits2
1Laboratory of Experimental Immunology, NCI-Frederick, Frederick, MD, USA
2Whittemore-Peterson Institute, University of Nevada, Reno, NV, USA


Background
In 2006, sequences of a novel human retrovirus, XMRV, were identified
and reported to be associated with a subset of hereditary prostate
cancer. Although the public health implications of this finding were
not immediately clear, two recent papers show XMRV is clearly a health
concern. One clearly shows that XMRV expression in the proliferating
prostate stroma and epithelium of prostate cancer patients [1]. The
second describes the detection of XMRV in about two-thirds of patients
diagnosed with chronic fatigue syndrome [2]. We will present data that
in these and other neuroimmune diseases and cancers, the host mounts a
humoral response to XMRV and infected patients are viremic.

Methods
A combination of classical retroviral methods, including RT-PCR,
full-length genomic sequencing, immunoblotting of viral expression in
activated PBMC, passage of infectious virus in plasma and PBMC to
indicator cell lines, and presence of antibodies to XMRV in plasma,
allowed XMRV detection in more than 75% of the CFS patients studied.
Since then, several publications in Europe using DNA-PCR of blood
products failed to detect XMRV sequences in patients with either
disease and have created considerable controversy. Reliable methods
for the biological and molecular amplification to detect XMRV in
unstimulated blood cells and plasma have been developed. Some DNA-PCR
negative patient blood samples represent false negatives and molecular
analysis using DNA from unstimulated blood cells is not yet sufficient
for XMRV identification.

Results
In mice, viruses related to XMRV cause B-cell lymphoma usually by
insertional mutagenesis activating a cellular oncogene as well as
causing chronic neurological diseases. We will present a case of
development of such B cell lymphoma in CFS patients. XMRV-infected
individuals with both neuroimmune disease and cancer develop an immune
response to XMRV. The isolation of infectious XMRV from prostate
cancer patients will be shown for the first time. Pathogenic
consequences of this infection will be discussed

Conclusion
XMRV, a retrovirus of unknown pathogenic potential is infectious in humans.

References
1. Schlaberg et al.: XMRV is present in malignant prostate epthelium
and is associated with prostate cancer. Proc Natl Acad Sci U S A
106:16351, 2009.
2. Lombardi et al.: Detection of an infectious retrovirus, XMRV, in
blood cells of patients with chronic fatigue syndrome. Science
326:585, 2009.
-

This is going to be good...... THANK YOU!

(Its got to be published fairly soon? No?)

 

[glenp]

I am just so sick of those guys! Sorry but they can just kiss my l...whatever.......I used to think, well they're digging down into cortisol - its no big deal - it's never going to fix CFS but at least they're finding something - but they've just bottomed out here. Ugh....

I really do try and be open, but geez there is a limit..

I do believe that stress causes conditions in the body - many different conditions.

I am 60 years old, suffered symptoms from childhood, progressively worsened until about 6 years ago when I was in pretty bad shape and not able to do my job. Over the years I was told that I suffered depression, anxiety, and panic attacks. It wasnt until just a few years ago that I saw a very good psychiatrist who suggested that I had CFS. All of those years I had continuously PUSHED myself, igmored my symptoms, believed the doctors, geez this is enough to give you some kind of mental illness. It wasnt until I saw Dr Bruce Carruthers, that I discovered those panic attacks were indeed NOT panic attacks but were part of dysautonomia. THIS HAS GOT TO STOP.

Most of us are constantly under stress, trying to figure out ourselves, how to treat this illness.

God help us all.

glen

 

[Jimk]

The implications of the lymphoma, cancer and neuroimmune illness are huge for all of us. Let's hope this galvanizes some of the cancer research money, since it's a big lobby here.
I'm a practicing psychologist with a research PhD, my research was in personality measurement, so I know the pitfalls of all the measurement techniques that are used in most of these type of studies. I'm with you, Cort, I'm so sick of this crap, and it's based on faulty measurement instruments measuring poorly selected samples. If anyone has a copy of this latest CDC sliming effort I'd love to see it to pick apart that methodology.

But if the studies keep weighing in against them on the viral side, we can just watch their careers go down the tubes without spending our precious energy on combatting the idiots. Anyway, even us crazy people can get real illness!

 

[Cort]

In retrospect I don't think this is a new study finding XMRV in 75% of study participants - I think that refers to the Science study and the 75% includes people who were diagnosed using other than PCR. THere's nothing in the results section about 75% - too bad! that would have been nice.

 

[George]

In retrospect I don't think this is a new study finding XMRV in 75% of study participants - I think that refers to the Science study and the 75% includes people who were diagnosed using other than PCR. There's nothing in the results section about 75% - too bad! that would have been nice.

Hey Cort
I think this is a separate study. I'm pretty sure the 75% is a clean number. Look at the designers of the study and the dates on this information. I think this is one of the studies that Dr. Mikovits said was in the pipeline and just hasn't been "published" yet. She said in her interview with you that they had 3 that were awaiting publishing. Plus the information in this doesn't look anything like the Science study. If I'm not totally out there I think this comes from the study that they did with the lymphoma patients that Dr. Peterson had in storage. 77 or the original 292 patients that Dr. Peterson treated from the Incline Village outbreak went on to develop Lymphoma. (confirmation Eric????)

In one of Dr. Mikovits talks I think it was the one for Dr. Cheney she stated that they tested the lymphoma patient blood and came away with a much higher number than the original study but that the additional work on the first study yielded even higher numbers. (that 95% that we keep hearing about but has never been published)

I know in one of the first talks Dr. M gave she intimated that it was Dr. Silvermans extreme concern about infectivity that had him calling on Dr. Frank Ruscetti and Frank hooked him up with Judy and the rest as they say is history.

But my point is I've been looking at it and the Science study and some of the stuff in the library this is not one of them or a report off of one of them. So my guess is the DHHS is either not watching the back door (grins) or at this point they are in a position to deal with leaks, and publications ( they finally have their test) of the nearly dozen papers that have been in the pipeline since January. The positive ones! (Big grins)

 

[Sam Carter]

Hey Cort
I think this is a separate study. I'm pretty sure the 75% is a clean number. ...

I wonder if this is where the 75% figure comes from?

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome
Judy A. Mikovits, Vincent C. Lombardi, Max A. Pfost, Kathryn S. Hagen and Francis W. Ruscetti
Virulence
Volume 1, Issue 5
September/October 2010


"""""""""""""""""""""""""""""""""""""""""""""""""""
In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS). Since our report, controversy arose after the publication of several studies that failed to detect XMRV infection in their CFS patient populations. In this addenda, we further detail the multiple detection methods we used in order to observe XMRV infection in our CFS cohort. Our results indicate that PCR from DNA of unstimulated peripheral blood mononuclear cells is the least sensitive method for detection of XMRV in subjects' blood. We advocate the use of more than one type of assay in order to determine the frequency of XMRV infection in patient cohorts in future studies of the relevance of XMRV to human disease.
"""""""""""""""""""""""""""""""""""""""""""""""""""
http://www.landesbioscience.com/journals/virulence/article/12486/

 

[Sam Carter]

The full paper can be found at: http://www.landesbioscience.com/journals/virulence/article/MikovitisVIRU1-5.pdf

It's an addendum to the original Science paper meaning the 75% figure relates to the original cohort, but I can see that the paper I've linked to is not the one referenced in post #24. (If that makes sense! Damn this brain-fog!)

 

[anciendaze]

... If I'm not totally out there I think this comes from the study that they did with the lymphoma patients that Dr. Peterson had in storage....

Now, that sentence interests me. How do I get Dr. Peterson to put me in storage until they get diagnosis and treatment options sorted out?

 

[Megan]

The full paper can be found at: http://www.landesbioscience.com/journals/virulence/article/MikovitisVIRU1-5.pdf

It's an addendum to the original Science paper meaning the 75% figure relates to the original cohort, but I can see that the paper I've linked to is not the one referenced in post #24. (If that makes sense! Damn this brain-fog!)

Sam you're right, this is a very interesting addendum to the original Science paper. Someone started a thread about this a while back when only the extract was available. It deserves it's own thread - I will stick an update on that one.

 

[dannybex]

uh...maybe this is a stupid question...

...but how did the 67% turn into 75%?

"In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS)."

 

[Dr. Yes]

...but how did the 67% turn into 75%?

"In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS)."

From the abstract Akrasia linked to (bold mine):

A combination of classical retroviral methods, including RT-PCR, full-length genomic sequencing, immunoblotting of viral expression in activated PBMC, passage of infectious virus in plasma and PBMC to indicator cell lines, and presence of antibodies to XMRV in plasma, allowed XMRV detection in more than 75% of the CFS patients studied.

 

[dannybex]

Thanks Dr. Yes.

Still don't understand however why it wasn't reported as 75% back in 2009 (since they say..."in that study"...?

As I said, my brain is not cooperating...

 

[George]

Actually Dr. Mikovits (is sort of in trouble because of) a later Addendum that lead to 95% number. That one still hasn't been published yet. (sad eyes)

Hey Cort you were kinda right though cause this is a Addendum to the original paper so technically it's still the same paper just different Authors.

Vincent C. Lombardi,1,† Francis W. Ruscetti,2,† Jaydip Das Gupta,3 Max A. Pfost,1 Kathryn S. Hagen,1 Daniel L. Peterson,1Sandra K. Ruscetti,4 Rachel K. Bagni,5 Cari Petrow-Sadowski,6 Bert Gold,2 Michael Dean,2 Robert H. Silverman,3
Judy A. Mikovits1,*

and

Judy A. Mikovits Whittemore Peterson Institute; Reno, Nevada USA
Vincent C. Lombardi Whittemore Peterson Institute; Reno, Nevada USA
Max A. Pfost Whittemore Peterson Institute; Reno, Nevada USA
Kathryn S. Hagen Whittemore Peterson Institute; Reno, Nevada USA
Francis W. Ruscetti Laboratory of Experimental Immunology, Cancer and Inflammation Program; National Cancer Institute-Frederick; Frederick, MD USA

And I was out there. This is NOT the one they did on the Lymphoma patients. (dang it and I got all excited and peed on the carpet for nothing.)

 

[Alesh]

Eric, I think "DuBois" means "From a wood" in French. Indeed he probably just came from the wilderness.

 

[Sam Carter]

Missing patients?

from: http://www.landesbioscience.com/journals/virulence/article/MikovitisVIRU1-5.pdf

"Table 4. XMRV detection results of 101 patients"

I count 93 not 101. :worried:

 

[Hope123]

from: http://www.landesbioscience.com/journals/virulence/article/MikovitisVIRU1-5.pdf

"Table 4. XMRV detection results of 101 patients"

I count 93 not 101. :worried:

Yeah, can someone check Sam and my count? I also got 93.

The subjects in Tables 1 and 2 seem to be the same as those in Table 3 by my spot-checking. I did not check every patient ID number though -- is the remaining 8 from this?

Also, the 75% figure I do not find in the text other than the abstract. If a number is in the abstract, it should also be in the text. Using Table 3, I counted the numbers of people with a positive cDNA PCR test (73) and added to the people with a negative cDNA PCR test but a positive other test (7) ----- with this, I got 80 with a positive test. 80/93 = 86%, not 75%.

Finally, people are right to be confused about the percentages. Back at the CFSAC meeting, they gave out some of this data and from my notes,
there were 33 people negative for PCR but many were positive by some other test. Adding this to the 67 positive PCRs, the number given out was that 99/101= 98% patients tested positive by at least one test. So this is different from the 75% given now as well.

[In addition, the 95% figure was thrown out in relation to antibody testing a few months ago.]

AAARRRRGGHHHHHH....................................someone check the numbers and my logic -- either it's my brain or this paper doesn't make things as clear as they could be.

 

[Hope123]

Also, I'm not sure why they picked this journal to be published in. This journal just got started this year and has an impact factor of about 7, compared to Science's 30. This should have ended up in Science as a reply to early criticisms rather than coming out now. Of course, this is all hindsight.