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Certain HIV positive, but negative tests (Page 88)

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July 27th, 2013
Experienced User
i can assure that it will be negative as well.
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replied July 27th, 2013
Extremely eHealthy
Amen Ustas.
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replied July 27th, 2013
Experienced User
Most advanced

What was your exposure and when?
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replied July 29th, 2013
Experienced User
Hey all,

Has anyone notice their eyes being red? I think mine are more red and have red lines through them.
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replied July 29th, 2013
Extremely eHealthy
Yes, from day one - recall the girl that gave me oral had red eyes the very next day.

Best wishes.
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replied July 30th, 2013
Experienced User
I think what we need to start doing is keep notes of all our symptoms and going to specialist in the depts we are feeling the symptoms.. we can't go in acting like professionals or requesting random tests.. doctors hate when people try and play the doctor role.. I'm making an appointment today.. this skin stuff and throat thing is reallyaffecting me. Plus I'm ggaining weight even with excercise and deit. Not normal. Plus I notice when I drink sweets or sugars (redbull, monsters, coke ) my throat gets super dry and skin gets itchyeir..


Have you guys heard of Brock Lesnar ufc fighter? He was diagnozed with a rare disease aswell. So there's rare stuff out there. But only doctors can give us an a valid diagnosis. And proper treatment.


Life is so hard. These dayz.. but we gotta keep pushing..
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replied July 30th, 2013
Extremely eHealthy
Can you tell us what rare disease he has?
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replied July 30th, 2013
Experienced User
Diverticulites
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replied July 30th, 2013
Extremely eHealthy
D-man,

I understand your need to figure out what is wrong and to get a handle on it - we are all in the same boat. I went through the same crazy bloating and pain and suffering, and still do experience some pain.

However, I disagree with the claim that only doctors can diagnose us - none of us would be on this forum if doctors were able to diagnose our illness. Furthermore, doctors only rely on the tests that they run. If the test says your cholesterol is good, they say don't worry, and then you walk out of their office and immediately drop dead from a heart attack (it's actually happened).

Furthermore, doctors are in denial that HTLV even exists (i.e. it is NOT part of the standard STD screening), yet millions of people are suffering with it. You cannot trust your health and literally your life to someone who is in denial about HTLV. In countries like Brazil & Japan where HTLV is taken seriously, people are not chased out of doctors' offices for asking for HTLV testing. Recall that DFrank was committed to a mental institution because of the denial of the medical industry to accept HTLV - imagine the pure hell he must have gone through. He will probably test positive on the HTLV PCR test after a few years, just like Alberto from Italy did. Let's say for a moment that we all eventually test positive for HTLV on the PCR test in a few years like Alberto did, then what do you think will happen? Even with that diagnosis, the doctors will STILL tell us to get lost - they aren't interested in diagnosing NOR treating HTLV.

I am drawing all of this out for you to prove that doctors aren't going to give a crap before or after diagnosing, nor before or after all of us are dropping dead. So why put your fate in the hands of any doctor who is patently against diagnosing or treating HTLV? SCREW that! This is your life I'm talking about - we need to find a doctor who will actually have a serious and real dialogue with us about HTLV, and who will consider treating us before it is too late (i.e. death). I've spent 10 thousand dollars on doctors visits (and others on this forum has spent much more) to be told that I need to see a psychiatrist - you can keep barking up that tree, but I'd rather find a REAL doctor who says yes, HTLV is real, and yes, we can receive some treatment for it. When I read the incredible array of (fatal) disorders HTLV can cause, I wanted to vomit - patients with Mycosis Fungiodes (like Alberto from Italy) look like something out of a horror movie. All those little kids in wheelchairs, what a heart breaking image.

I've asked all of you to do your best in finding us a sympathetic doctor. So far only DW says that he thinks he knows someone like that. Like Scared once said, it's getting to the point where I feel like I am going to go insane and do something crazy. So please, if you know a doctor who is not a condescending a-hole, let me know. DW I am still anxiously waiting for the information on the doctor that you mentioned.

Best wishes.
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replied July 31st, 2013
Experienced User
Tony
Keep in mind that i have not talked to the(se) doctor(s) i have only talked to the person under the care of the(se) doctor(s). He told me that his doctor(s) told him that because he has done so much research about htlv and because he has such a great relationship with them they are willing to prescribe him anything he wants to try for the treatment of htlv.
I think he is afraid that we could mess his relationship with his doctor(s) therefore i was unable to get any names of his doctors.
He did however say that he is willing to give the doctors names to anyone who test positive for htlv. He told me to give his phone number to anyone who tests positive, he will absolutely give his doctors names to anyone diagnosed with htlv, so please try to find some comfort in that.

And as for mycosis fungoides you are right about how bad it could be, but that is only after decades of having mycosis fungoides without treatment.
If you want to hear a few people's story's about their diagnosis and treatment.
Please google search:
Dans mycosis fungoides
and click on the first option.

If you have any questions about what i have posted here today, feel free to call me at my phone, i believe you have my phone number, i could explain to you in more detail.
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replied August 3rd, 2013
Dear Dr,
i had sex with a female both(with condom and without condom )one time on July 17, 2013 and the status of her HIV is unknown. After that,i was afraid of HIV. After 10 days i went to hospital and they give me some tests and the results are : (
HBS AG 0.23 NEGATIVE
ANTI-HBS 0 NEGATIVE
ANTI-HCV 0.07 NEGATIVE
ANTI-HIV ENV 0.41 NEGATIVE )

so whats my situation and what should i do ?! also if i affected is there a solution ?!if im negative what is 0.41 means ?!
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replied August 3rd, 2013
Experienced User
once again,

who are interested in participating testing from colulbia university?

we will push to make it happen during this month
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replied August 5th, 2013
Extremely eHealthy
Hope,

Yes, I would like to participate!

Thanks!
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replied August 4th, 2013
Experienced User
Would be good but I won't be able to get there...
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replied August 4th, 2013
Experienced User
Same Problem with wife and kid
I also have the same problem with all you guys here. I prentending that im ok for this last 5 years. But than i cannot hide my anxiety towards HIV anymore its really gonna kill me this time. Im married last 2 years than i have a baby after 1 year and now my baby is 1 year old appear with lession and lympnodes that make me really sacry n im really2 sorry for him. Just last Saturday i ask my wife to go for HIV rapid test with both came with negative result.

Before i also do a lot of HIV antibodi elisa viraload u name it and all came back negative. Im from MALAYSIA here they dont know what HTLV is.

Is anyone in this forum help me my wife n my baby plz.
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replied August 4th, 2013
Experienced User
I have all thoes sytomp and i sahre it with my wife n my kid my Dr. said im ok but for me im not ok at all since those sytomp still with me from the begining of my exppsore in 2008.

1. Dry mouth oral health
2. Eye floters
3. Blowted stomach
4. Loose stool
5. Back pain

It pogress very well until now. All the Dr. said i was crazy depress an anxiety disoder so they ask me to seek pysctri Dr. Now iam taking Diazepam Lexpro n Stillnox. I really meed help form all of you out here.
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replied August 4th, 2013
Experienced User
Wow, since 2008?
That is a long time. The good thing is that you are way out of the window period.
What state or country are you located in?
And what was your risk exposure?
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replied August 4th, 2013
Experienced User
Im from MALAYSIA Kuala Lumpur and had an exposure in Bangkok April2008 and my wife had exposure from me in June 2011. Just last Saturday 27 July we do rapid test both came out negative what could it be if is not hiv. My baby already start have a lession around his left eye and arm. My wife have a mouth herpes that come n go. Hope there is a hope fot my family. Anyone can help me here?
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replied August 4th, 2013
Experienced User
Other than herpes what other symptoms does your wife experience?
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replied August 4th, 2013
Experienced User
I have protected vaginal penetration but unprotected oral sex whic i lick the prostitut baginal fluid. She said she clean but i dont belive her its happen in bangkok.
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replied August 4th, 2013
Experienced User
Some people here have the same risk exposure that you had.
In my opinion i don't think it's high risk.
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replied August 4th, 2013
Experienced User
So you had protected sex and oral sex by licking her.. When did u start feeling sick? How long after?
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replied August 6th, 2013
Extremely eHealthy
Hassan,

Your experience is a solid example that this can be transmitted orally - I've also transmitted it orally to others, and people here got it orally too. So the whole "oral isn't high risk" statement has been disproved.

Best wishes.
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replied August 4th, 2013
Experienced User
Get tested for htlv 1/2...
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replied August 5th, 2013
Extremely eHealthy
I agree - all of the symptoms you described sound like HTLV - all of us are experiencing similar symptoms.
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replied August 5th, 2013
Experienced User
My symtomp is

1. Dry mouth
2. Gases stomach n bloted
3. Loose stool
4. flooters eye in early morning

3 of us experince the same symtomp.

I really need help its really making me crazy hard for me to do anything. I always think this is late or silent HIV. But all the doctors wont belive me because i have all the negative test. So what should i do and where should i go?? Here in MALAYSIA there dont have HTLV test doctor said its really rare and the case ia zero here in MALAYSIA.
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replied August 5th, 2013
Experienced User
My symtomp is

1. Dry mouth
2. Gases stomach n bloted
3. Loose stool
4. flooters eye in early morning

3 of us experince the same symtomp.

I really need help its really making me crazy hard for me to do anything. I always think this is late or silent HIV. But all the doctors wont belive me because i have all the negative test. So what should i do and where should i go?? Here in MALAYSIA there dont have HTLV test doctor said its really rare and the case ia zero here in MALAYSIA.
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replied August 5th, 2013
Experienced User
What symptoms does your wife have?
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replied August 5th, 2013
Extremely eHealthy
No offense but multiple members of this forum have been infected via Asians (DF, AM, WS) so I wouldn't buy the "HTLV test doctor said its really rare" argument. Japan and Australia are huge source of HTLV and I'm sure it has spread to most of Asia and India by now.
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replied August 5th, 2013
Experienced User
Hi everyone,

I wish I had good news but I don't. I feel fatigued all the time, soft broken loose stools, diahreah, light stools, abdominal pains and discomfort, back pain, dry mouth, indigestion, abdominal mass or lump just above belly button, SEVERE DEPRESSION, thoughts of suicide everyday, nausea comes and goes, malnutrition, foul smelling stools and gas, muscle waisting, and the list goes on...

I just can't keep going on like this anymore.

I really hope and pray you all find answers soon, I don't think I'm gonna keep living like this much longer I'm tired of suffering.

God bless all of you..
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replied August 5th, 2013
Experienced User
I'm really sorry u feel this way.. Please hang in there.. How long has it been for u now?
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replied August 6th, 2013
Extremely eHealthy
Scared,

I know the hell that you are going through, because I am going through it too, as are the rest of the people here. Consider the guy who just posted who has been sick for years, and now his wife & baby are sick too, that reminds me much of Alberto from Italy, who I haven't heard from since his HTLV progressed to Mycosis Fungoides after 7 years of HTLV infection.

There's only one way of out of this, and I don't mean suicide. I mean that we have to find a doctor who will treat us. Alone each of us will be told to see a psychiatrist, but together it will be harder for the (right) doctor to ignore us. Clearly finding the right doctor is the key to being cured.

You & I have had more phone conversations than anyone else on this forum, you know that I know exactly what this is and exactly what will cure it. We have good people here who are dedicated to solving this, people like JB & WS. All we need to find is one doctor who is willing to think outside the box and give us the treatment we need. That sounds like much, but it's really not, there has to be one doctor who's willing to help us and treat us. Please do not give up - you have my number and can call me anytime.

Best wishes.
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replied August 6th, 2013
Extremely eHealthy
I just had a phone conversation with Bresh - he called me from Canada to tell me about his problems with doctors, the same problems we've all had (i.e. you're crazy, etc). Although he contracted the illness in Canada, he lived in Jamaica for 29 years and NEVER heard about HTLV, even though it's supposedly a big problem there - this points out the extent that the medical industry has gone to in order to cover up HTLV. He also got the same speech that I got twice that the HTLV serology is "very good", although it hasn't changed in decades.

Best wishes.
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replied August 7th, 2013
Extremely eHealthy
Rev Inst Med Trop Sao Paulo. 2007 Nov-Dec;49(6):361-4.
Performances of HTLV serological tests in diagnosing HTLV infection in high-risk population of So Paulo, Brazil.
Jacob F, Santos-Fortuna Ede L, Azevedo RS, Caterino-de-Araujo A.
Source
Seo de Imunologia, Instituto Adolfo Lutz, So Paulo, SP, Brasil.

Abstract
Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from So Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.
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replied August 8th, 2013
Extremely eHealthy
Here's an article that I found after researching AZT's effectiveness against MLV / XMRV, where it's proven that AZT is effective against HTLV (but not other antiretroviral drugs).

Best wishes.

J Gen Virol. 1997 May;78 ( Pt 5):1007-16.
AZT inhibits the transmission of human T cell leukaemia/lymphoma virus type I to adult peripheral blood mononuclear cells in vitro.
Macchi B, Faraoni I, Zhang J, Grelli S, Favalli C, Mastino A, Bonmassar E.
Source
Department of Experimental Medicine and Biochemical Sciences, University of Rome, Tor Vergata, Italy.
Abstract
The effect of 3'-azido-3'-deoxythymidine (AZT) on in vitro infection of peripheral blood mononuclear cells (PBMCs) isolated from normal adult individuals with human T cell leukaemia/lymphoma virus type I (HTLV-I) was evaluated. Different PBMC samples were exposed to HTLV-I by cocultivation with MT-2 (a chronically infected cell line) in the presence of 20 U/ml of human recombinant interleukin 2 (IL-2) and graded concentrations of AZT. Control and drug-treated cultures, of both infected and uninfected PBMCs, were then grown for several weeks and monitored for virological and immunological parameters. The results showed a concentration-dependent anti-proliferative effect of AZT in both infected and non-infected cultures. Production of both proviral DNA and viral RNA was inhibited not only at the higher concentrations of AZT (8 microM and 32 microM) but also at concentrations as low as 0.1-2 microM. These results were confirmed by PCR and by flow cytometry analysis for the viral core protein p19. Moreover, treatment with AZT resulted in a decreased expression of CD25 in cultures exposed to HTLV-I as well as in non-infected PBMCs. On the other hand, HLA-DR was down-regulated to a greater extent in drug-treated, virus-exposed cultures in comparison with those not infected. No evidence of the antiviral activity of AZT was observed in PBMC cultures already infected by HTLV-I or in MT-2 cells. These findings demonstrate that treatment with AZT, when given at the time of infection with HTLV-I, has a marked protective effect on PBMCs.
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replied August 9th, 2013
Experienced User
XMRV has not been proven to infect humans.
It was proved that the test they were using was contaminated with mouse DNA and that was the reason for the false positive readings.
However we are all trying to figure out every possible infectious retrovirus, or dangerous virus for that matter.
Keep us updated.
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replied August 10th, 2013
Extremely eHealthy
Blood smear test for 'flower cells'
DW,

The entire class of viruses that I've been discussing are Leukemia Viruses (LVs), whether mouse, cow, human, etc. It's not an issue of whether they can infect people, it's an issue of how many people are infected. When you have someone like Derrick from California who is infected with HTLV by installing floors, and a woman from the Carribean who is infected by cleaning floors, we know that these Leukemia viruses are common in our environment. Note that these people didn't get infected sexually like the rest of us. Prostate cancer patients have had mouse leukemia virus detected in their bodies. Rabbits can be infected with HTLV, and die from it, so should I tell my mother-in-law to stop preparing raw rabbit meat because she might have a cut on her hand? The guy in Greece with HTLV who was cured by Azacytidine - no one knows how he got it - was it via a mosquito? Did he dig up some dirt? No one even knows where ebola virus come from, yet many people have died from it.

Everyone else,

Go get tested with the blood smear test mentioned below - if you have the classic "flower cells" in your smear, then that's the first sign that you have HTLV. Certainly by now enough of our cells are infected as evidenced by our HTLV symptoms (back and leg pain) to show up on a smear test.

Here's an article (from 19 years ago) that describes the discovery of HTLV-like particles, with negative PCR for HTLV. Articles like these prove that a variant of HTLV exists that cannot be tested for, either through antibody or PCR testing. The articles I posted regarding AZT show that AZT is the only anti-HIV drug that works on HTLV, which implies that if we cannot get treated with Azacytidine, we should start taking AZT.

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

Leukemia. 1994 Jan;8(1):201-7.
HTLV-1-like particles and HTLV-1-related DNA sequences in an unambiguous case of Szary syndrome.
Bazarbachi A, Saal F, Laroche L, Lasneret J, Gessain A, Daniel MT, Pris J.
Source
UPR A0043 CNRS Rtrovirus et Rtrotransposons des Vertbrs, Hpital Saint-Louis, Paris, France.
Abstract
An unambiguous case of Szary syndrome associated with the presence of unusual retroviral infection markers is described. The blood smear showed 15% typical Szary cells but also rare atypical lymphocytes with convoluted nuclei, evocative of characteristic adult T-cell leukemia (ATL) flower cells. However, the patient did not present any clinical or biological manifestations of ATL, and human T-cell leukemia virus type 1 (HTLV-1) serology was consistently negative. After being cultured for 4 months, peripheral blood mononuclear cells (PBMC) produced typical type C retrovirus-like particles with budding forms strongly resembling HTLV-1 virions. The producer cells did not express HTLV-1-specific antigens detectable by indirect immunofluorescence (IIF). Southern blotting of uncultured PBMC DNA, submitted to digestion with the restriction enzymes PstI and SacI, and hybridized with a full genomic HTLV-1 probe, showed the presence of specific homologous sequences, absent in all of the healthy donor control PBMC DNAs. These HTLV-1-like sequences presented a restriction enzyme pattern distinct from that of the HTLV-1 prototype genome and of other HTLV-1 proviruses studied up to now. Polymerase chain reaction (PCR) with highly conserved HTLV-1 derived pol and env primers was consistently negative with the patient's DNA. All these results taken together suggest that our patient carries a retroviral agent partially homologous to, but probably different from HTLV-1. The possibility is discussed that this type of retroviral agent might be associated with a subtype of cutaneous T-cell lymphoma (CTCL) represented by a typical Szary syndrome with a very low percentage of ATL-like flower cells in the blood smear.
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replied August 11th, 2013
Experienced User
Tony
Not everyone with htlv will have flower cells, and its possible that flower cells could be found in non-infected people. Therefore, although a piece to the puzzle, its not a reliable way to diagnose or exclude htlv infection.
Here is a study.

British Journal of Haematology, 1999, 105, 758-763
Low prevalence of flower cells in U.S.A. blood donors infected with human T-lymphotrophic virus types I and II
RONALD A. SACHER,1 NAOMI L. C. LUBAN,2 DANNIE I. AMETI,3 SHIRLEY FRIEND,3 GEORGE B. SCHREIBER3
AND EDWARD L. MURPHY4 for the Retrovirus Epidemiology Donor Study Group (REDS) REDS Investigators from: 1Georgetown University Medical Center, Washington, D.C., 2Children’s National Medical Center, Washington, D.C., 3Westat, Rockville, Maryland, and 4University of California at San Francisco, California, U.S.A.
Received 2 October 1998; accepted for publication 22 February 1999

DISCUSSION
Using a systematic methodology for the identification of flower cells in a large U.S.A. HTLV cohort, significantly more HTLV-I-positive subjects had identifiable flower cells com- pared to seronegatives. However, a lower prevalence of flower cells were found in HTLV-I seropositives without ATL than reported in endemic areas of Japan. This study was unique in that it also provided an opportunity to establish whether or not flower cells occur, and if so in what frequency, in HTLV-II- positive donors. However, we found no significant differences in the proportion of flower cells between HTLV-II seroposi- tives and seronegative donors.
These results demonstrated that asymptomatic HTLV-I carriers had significantly more flower cells than seronega- tives. The clinical implications that 7% of asymptomatic HTLV-I seropositives in the REDS cohort have flower cells are unclear. In ATL patients with leukaemia, flower cells are usually monoclonally infected with HTLV-I (Kinoshita et al, 1985; Chen et al, 1995). The prevalence of abnormal lymphocytes with flower cell features (at a frequency of 1% or less of white blood cells) in asymptomatic, healthy, HTLV- I-positive Japanese subjects has been reported as high as 43 - 47% (Kinoshita et al, 1985; Yamaguchi et al, 1988;
Tachibana et al, 1992). Tachibana et al (1992) reported a correlation between the presence of flower cells and high proviral load among asymptomatic subjects. However, neither the presence of low levels of flower cells nor high HTLV-I proviral load have been proved to be risk factors for the future development of ATL. Further prospective clinical follow-up and molecular studies of the REDS cohort may help to better define the pathogenesis of, and risk factors for, ATL.
Could the lower flower cell prevalence in our study compared to Japanese studies be due entirely to differences in technique? Flower cell morphology can be subjective despite the appearance of obviously abnormal cells in smouldering and chronic ATL, because some lymphocytes may have ambiguous features. However, in this study, cells were characterized according to standardized classification cri- teria that were developed in consultation with Japanese colleagues from HTLV-endemic areas, so it is unlikely that the differences seen are a result of identifying different morphological features. Reviewers were blinded to HTLV status, therefore the morphology was evaluated in an objective uniform manner. Although there was a significant difference in the proportion of unreviewable slides between controls and HTLV-I subjects, it was a small proportion of each group and was unlikely to contribute a meaningful degree of bias to the study. Replication of the blinded method- ology from this study in Japan may help understand the reasons for differences in measured flower cell prevalence.
Unlike in endemic areas of the world, the HTLV-infected subjects enrolled in this U.S.A. study are more likely to have been recently infected. The subjects were also pre-selected as healthy blood donors, and may not represent the general U.S.A. population of HTLV-infected individuals. These reasons may also contribute to the lower prevalence of flower cells than reported in Japan. There is little variation in HTLV-I proviral DNA sequence between the U.S.A. and Japan (Gessain et al, 1996), so it is unlikely that differences in viral strain are responsible. However, the degree of clonal integration, HLA phenotypes and immune responsiveness may be significant factors in the expression of flower cells and the progression to disease states in HTLV-infected individuals.
HTLV-II-infected individuals may exhibit similar neuro- logical manifestations indicative of HAM as HTLV-I positives, and it may be associated with a subclinical immunodeficient state, as indicated by the higher incidence of bacterial and fungal infections reported in HTLV-II-infected individuals (Murphy et al, 1997b). However, HTLV-II has not been conclusively linked with haematological malignancy. Case reports of hairy cell leukaemia, large granular cell leukaemia and mycosis fungoides in HTLV-II seropositives have not been confirmed by subsequent epidemiologic studies (Murphy, 1996). Our finding of no increase in flower cells among HTLV-II subjects is consistent with this lack of haemopathology.
No correlation was apparent between the presence of flower cells in REDS subjects and clinical findings from their study examination. The lack of flower cells in a blood smear taken before diagnosis in the single ATL case in our cohort was consistent with the fact that 25% of ATL cases occur in lymphoma form with no flower cell demonstration (Matutes & Catovsky, 1994). The REDS subject with the most abundant flower cells was an HTLV-I-positive individual with HAM, which was consistent with case reports of flower cells in patients with HAM (Morgan et al, 1987).
In conclusion, the findings of this study suggest that the prevalence of flower cells is low in HTLV-I-positive indi- viduals in the United States. Additional studies will be needed to explain why flower cell prevalence was found to be lower than in Japanese HTLV-I seropositives. Finally, the levels of flower cells in HTLV-II positives were inconspicuous and found in the same frequency as seronegatives, consistent with the lack of proven haematological malignancy due to this human retrovirus.
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replied August 8th, 2013
Extremely eHealthy
Antimicrob Agents Chemother. 2008 Jan;52(1):54-64. Epub 2007 Oct 29.
Effect of phosphonated carbocyclic 2'-oxa-3'-aza-nucleoside on human T-cell leukemia virus type 1 infection in vitro.
Balestrieri E, Matteucci C, Ascolani A, Piperno A, Romeo R, Romeo G, Chiacchio U, Mastino A, Macchi B.
Source
Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00135 Rome, Italy.
Abstract
There is currently little research and development of new compounds with specific anti-human T-cell leukemia virus type 1 (HTLV-1) activity. The few antiretrovirals that have been tested against HTLV-1 in vitro have already been developed into anti-human immunodeficiency virus (HIV) drugs. Here, we show the effects of a newly synthesized family of phosphonated nucleoside compounds, phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides (PCOANs), on HTLV-1 infection in vitro. To ascertain the anti-HTLV-1 activity of PCOANs, peripheral blood mononuclear cells from healthy donors were infected in vitro by coculture with an HTLV-1 donor cell line in the presence of three prototype PCOAN compounds. PCOANs were able to completely inhibit HTLV-1 infection in vitro at a concentration of 1 microM, similar to what has been observed for tenofovir and azidothymidine. Treatment with PCOANs was associated with inhibited growth of HTLV-1-infected cells, and their effects were 100 to 200 times more potent than that of tenofovir. The mechanisms involved in the anti-HTLV-1 effects of PCOANs can mainly be ascribed to their capacity to inhibit HTLV-1 reverse transcriptase activity, as ascertained by means of a cell-free assay. PCOANs caused little reduction in proliferation or induction of apoptotic cell death of uninfected cells, showing toxicity levels similar to tenofovir and lower than azidothymidine. Overall, these results indicate that the family of PCOANs includes potential candidate compounds for long-lasting control of HTLV-1 infection.
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