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Interviewing Dr. Coffin

Rrrr

Senior Member
Messages
1,591
i know! i had never heard that before either. which makes me think that i must have misheard him...? but i don't think so. there were a few sentences there, not just one, making it less likely that i misheard him. but why did i not know this info earlier???? is there anyone we can ask to confirm this info?
 

citybug

Senior Member
Messages
538
Location
NY
quote--- Scientists at nine Massachusetts research centers were awarded a total of $55.5 million in federal stimulus grants today to pay for new buildings, labs, and renovations.

It sounds like it is for construction projects.
 

jewel

Senior Member
Messages
195
Thank you, so much, Rrr. I'm with Gracenote; you deserve the flowers. This is an amazing interview, and a thoughtful set of questions. Now on the "Clinical trials" thread... good evening, J.
 

Roy S

former DC ME/CFS lobbyist
Messages
1,376
Location
Illinois, USA
Thank you very much Rrrr.

It was kind of Dr. Coffin to do this. I wonder if it would be best in the future to submit questions to him in writing so that he can answer them at his convenience and have you post them for the rest of us.
 
Messages
7
Location
germany
thank you so much, Rrrr. you're brilliant. :victory:
 

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Adam

Senior Member
Messages
495
Location
Sheffield UK
Another thank you from me. :D

When I stop to think about this I am amazed. You have made a connection with arguably the main man. Some achievement. :cool:

I trust you are glowing with pride? :victory:
 

Rrrr

Senior Member
Messages
1,591
thank you to all for thanking me. this forum is full of super appreciative people. i'm so grateful to you all for your support of me and to each other. even if we were not all sick, i could see us all being friends, couldn't you? that is lovely.

adam: i think ANY of us can make a connection with Coffin. He is open to emails. i think someone should now approach

1) the rusetti's (sp?) at the National Cancer Institute [update from a few days later: do not contact them. i will post about why in a separate post.]
2) the folks at the protein expression lab at NCI coffin mentioned
3) Brigette Huber at Tufts, who is studying XMRV,
4) Abott labs, the lab coffin said is making the XMRV test for the national blood supply.

and ask them all if they are open to a Q&A.

I like roy's suggestion of sending coffin our next set of questions (if he is open to recieving more) via email. certainly easlier on me.

i'll call him in a week and see if he is open to this. meanwhile, he seems to be open to individual emails. i just wonder if it would be better to send him our questions as a group, i.e. in one email or in one interview session, instead of individual emails? but that is up to each one of us, i guess. i mean, his email address is available for public viewing on the tufts website. in fact, ALL the xmrv researchers' emails are available to us on all their websites.

warmly,
rrrr
 

JT1024

Senior Member
Messages
582
Location
Massachusetts
Rrrrr.....

Thanks for all your hard work! Great ideas moving forward as well.

Like you, I'm (sort of) in the Boston area. Despite the number of medical facilities and doctors, the lack of competent CFS/ME/FM doctors continues to amaze me.

I had given up on doctors but due to deteriorating health, I recently started seeing another one. He absolutely believes in CFS but not sure how much he can do for me. Time will tell.

Does anyone remember who the contact person was at Abbott Labs? I remember he presented at a conference out west (? San Francisco) a while back.

I have clinical laboratory and blood bank education/experience which might help when it comes to diagnostic testing stuff.

Thanks again! ~ JT
 

JT1024

Senior Member
Messages
582
Location
Massachusetts
Just found the name of the Abbott guy... John Hackett, Jr.

Below is the abstract from the presentation from the CROI 2010 on February 19, 2010. Looks like they have an assay already set up....perhaps they're fine tuning it at this point.

I suspect much more information will be coming out fairly soon. Just my take..... Researchers on blogs online are all over XMRV. The bing search engine turns up some interesting things.... I've used google for years but was hitting a wall. One point made regarding commercial diagnostic product companies (like Abbott), they are less likely to care about the politics... If there is a buck to be made, they will make the test kits if there is any truth to a new infectious disease.


Session 41-Oral Abstracts
VirusHost Interaction: HIV and XMRV
Friday, 9:30 am-12 noon; Room 2011
Paper # 151

XMRV: Examination of Viral Kinetics, Tissue Tropism, and Serological Markers of Infection

X Qiu1, P Swanson1, K-C Luk1, J Das Gupta2, N Onlamoon3, R Silverman2, F Villinger3, S Devare1, G Schochetman1, and John Hackett, Jr*1
1Abbott Diagnostics, Abbott Park, IL, US; 2Cleveland Clin, OH, US; and 3Yerkes Natl Primate Res Ctr, Emory Univ, Atlanta, GA, US


Background: Xenotropic Murine Leukemia Virus-related Retrovirus (XMRV) is a human retrovirus recently discovered in familial prostate cancer tissue using DNA array based Virochip technology. Understanding viral replication kinetics, tissue tropism, and the host immune response is fundamental to establish the etiology of XMRV infection in human disease. Development of serologic assays to detect XMRV-specific antibodies would facilitate epidemiologic studies.

Methods: Five rhesus macaques were inoculated intravenously with XMRV. Blood was collected throughout the course of infection, and tissue from multiple organs was harvested at necropsy. Two macaques were necropsied at day 6 or 7 and one at day 144 post infection. The remaining 2 animals were re-inoculated with XMRV on day 158 and necropsied on day 291. XMRV-specific immunoreactivity was monitored by Western blot using viral lysate. Recombinant env gp70, p15E and gag p30 were utilized to develop serologic assays on the high-throughput automated ARCHITECT instrument system (Abbott Diagnostics).

Results: XMRV inoculation resulted in low transient plasma viremia, although proviral DNA persisted in circulating peripheral blood mononuclear cells for several weeks. Of interest, the earliest leukocyte targets were CD4+ T cells and NK cells followed by CD8+ enriched T and CD20+ enriched B cells (50% positive); CD14+ monocytes were negative. Animals sacrificed at the acute stage showed evidence of viral replication in spleen, lung, lymph nodes and liver. In contrast, sacrifice of 2 animals at 19 weeks post XMRV re-inoculation showed greater dissemination of XMRV DNA and RNA in various organs including the GI and urinary tract as well as in vaginal tissue of the one female. By Western blot analysis, all 3 chronically infected macaques developed antibody responses to env and gag proteins. The serologic assays demonstrated 100% sensitivity by detecting all Western blot positive serial bleeds from the XMRV-infected macaques. Preliminary results showed evidence of detectable reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors.

Conclusions: These data suggest that lymphocytes are a primary target for replication persistence (low grade replication) of XMRV in the absence of detectable plasma viremia. This study identified specific serological markers useful for detection of antibodies induced by XMRV infection. The prototype antibody assays will facilitate large-scale epidemiological studies.
 

anciendaze

Senior Member
Messages
1,841
This is marvelous! Thank you for handling this, and thank Dr. Coffin for all of us.

This is so different from my own experience I'm beginning to think this really is a new dawn in the field. Perhaps I'm dreaming.

Aside on ancient history of CFS/ME:

The term ME has a much longer history in the UK than the US. The name chronic fatigue syndrome is bad enough, but simply having chronic fatigue is considerably worse. My personal experience was that having an illness which does not exist will not prevent you from being drafted and sent to face hostile fire. My own doctor was on the local draft board. Getting to the "Incline Village" outbreak at Lake Tahoe, and widespread awareness that something was going on, takes you only to the middle of my patient history.
 

omerbasket

Senior Member
Messages
510
Regarding what Dr. Coffin said about clinical trial, I wanted to say that I think that probably Glaxo Smith Kline's XMRV study is because if their results would find association between ME/CFS and XMRV they would want to make a clinical trial with one or more of their antiretroviral drugs (unless they are doing this study with an interest of not finding XMRV, for some reason).
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
Outstanding!
Thank you, Rrrr, for interviewing Dr. Coffin and sharing it with all of us.
Appreciate your plan to follow-up with him.

Is there a way to get this interview to Dr. Deckoff-Jones?

Gemini
 

Rrrr

Senior Member
Messages
1,591
Just found the name of the Abbott guy... John Hackett, Jr.

Below is the abstract from the presentation from the CROI 2010 on February 19, 2010. Looks like they have an assay already set up....perhaps they're fine tuning it at this point.

I suspect much more information will be coming out fairly soon. Just my take..... Researchers on blogs online are all over XMRV. The bing search engine turns up some interesting things.... I've used google for years but was hitting a wall. One point made regarding commercial diagnostic product companies (like Abbott), they are less likely to care about the politics... If there is a buck to be made, they will make the test kits if there is any truth to a new infectious disease.


Session 41-Oral Abstracts
Virus–Host Interaction: HIV and XMRV
Friday, 9:30 am-12 noon; Room 2011
Paper # 151

XMRV: Examination of Viral Kinetics, Tissue Tropism, and Serological Markers of Infection

X Qiu1, P Swanson1, K-C Luk1, J Das Gupta2, N Onlamoon3, R Silverman2, F Villinger3, S Devare1, G Schochetman1, and John Hackett, Jr*1
1Abbott Diagnostics, Abbott Park, IL, US; 2Cleveland Clin, OH, US; and 3Yerkes Natl Primate Res Ctr, Emory Univ, Atlanta, GA, US


Background: Xenotropic Murine Leukemia Virus-related Retrovirus (XMRV) is a human retrovirus recently discovered in familial prostate cancer tissue using DNA array based Virochip technology. Understanding viral replication kinetics, tissue tropism, and the host immune response is fundamental to establish the etiology of XMRV infection in human disease. Development of serologic assays to detect XMRV-specific antibodies would facilitate epidemiologic studies.

Methods: Five rhesus macaques were inoculated intravenously with XMRV. Blood was collected throughout the course of infection, and tissue from multiple organs was harvested at necropsy. Two macaques were necropsied at day 6 or 7 and one at day 144 post infection. The remaining 2 animals were re-inoculated with XMRV on day 158 and necropsied on day 291. XMRV-specific immunoreactivity was monitored by Western blot using viral lysate. Recombinant env gp70, p15E and gag p30 were utilized to develop serologic assays on the high-throughput automated ARCHITECT instrument system (Abbott Diagnostics).

Results: XMRV inoculation resulted in low transient plasma viremia, although proviral DNA persisted in circulating peripheral blood mononuclear cells for several weeks. Of interest, the earliest leukocyte targets were CD4+ T cells and NK cells followed by CD8+ enriched T and CD20+ enriched B cells (50% positive); CD14+ monocytes were negative. Animals sacrificed at the acute stage showed evidence of viral replication in spleen, lung, lymph nodes and liver. In contrast, sacrifice of 2 animals at 19 weeks post XMRV re-inoculation showed greater dissemination of XMRV DNA and RNA in various organs including the GI and urinary tract as well as in vaginal tissue of the one female. By Western blot analysis, all 3 chronically infected macaques developed antibody responses to env and gag proteins. The serologic assays demonstrated 100% sensitivity by detecting all Western blot positive serial bleeds from the XMRV-infected macaques. Preliminary results showed evidence of detectable reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors.

Conclusions: These data suggest that lymphocytes are a primary target for replication persistence (low grade replication) of XMRV in the absence of detectable plasma viremia. This study identified specific serological markers useful for detection of antibodies induced by XMRV infection. The prototype antibody assays will facilitate large-scale epidemiological studies.

what does this mean? can someone translate it?

"Preliminary results showed evidence of detectable reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors."

"Conclusions: These data suggest that lymphocytes are a primary target for replication persistence (low grade replication) of XMRV in the absence of detectable plasma viremia. This study identified specific serological markers useful for detection of antibodies induced by XMRV infection. The prototype antibody assays will facilitate large-scale epidemiological studies."
 

anciendaze

Senior Member
Messages
1,841
help with terminology

I am not competent to evaluate the whole thing, but I can explain some terminology.

Lymphocytes are white blood cells connected with cellular immune response.
Viremia is the condition of having virus particles, virions, in the blood.
(Septicemia is a corresponding condition w.r.t. bacteria in the blood. This term is more common in medicine than viremia.)
Plasma viremia means the particles are found outside of blood cells.
Replication persistance means the virus is there because it is replicating in cells. Calling this low-grade means it is not replicating very rapidly.

The virus has three genes named: gag, pol, env. Inserted as DNA in cells these produce three corresponding molecules which are the antigens matched by antibodies. All three components of the virus produced immune responses which could be detected.

I'll leave the business of explaining Western Blot serial bleeds to an expert.

The specific tissues and cell types infected appear to confirm suspicions of involvement with the T-cell component of the immune system.

My take on that conclusion is that a blood test which is reasonably cheap, and does not depend on PCR, is only a matter of time, and not all that much time.
 
G

Gerwyn

Guest
what does this mean? can someone translate it?

"Preliminary results showed evidence of detectable reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors."

"Conclusions: These data suggest that lymphocytes are a primary target for replication persistence (low grade replication) of XMRV in the absence of detectable plasma viremia. This study identified specific serological markers useful for detection of antibodies induced by XMRV infection. The prototype antibody assays will facilitate large-scale epidemiological studies."


Even after a iv dose of virus which is many orders of magnitude higher than a natural infection the amount of XMRV in the blood was minimal and proviral DNA only persisted in the PMBC,s for a few weeks.The virus follows the pattern of all MULV viruses and replicates in the lymphoid tissue. There only appears to be any possibility of finding XMRV by pcr if you target lymphocytes.These are not PMBC,s they are NK cells and B and T cells.These are the cells that the WPI targeted in the science study.They also used an antibody reaction on westen blot (a kind of electrphoresis) XMRV protein GAG POL and ENV proteins.The european studies did none of those things.That fully explains why Lombardi et al could detect the virus while the Europeans could not!
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
Rrrr, you're a star! Thank you for doing this. Sorry you weren't well enough to go out. I hope you didn't wear yourself out too much and you'll be better soon. Enjoy those flowers, you deserve them.
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
Advocate,

Wonderful, you sent the interview to Dr. Deckoff-Jones with XMRV+ survey information!

The XMRV+ survey is excellent --be valuable information if XMRV+ patients on antiretrovirals like Deckoff-Jones completed it.

Gemini