posted
Rheumatoid factors induce signaling from B cells, leading to Epstein-Barr virus and B-cell activation.
Yang L, Hakoda M, Iwabuchi K, Takeda T, Koike T, Kamatani N, Takada K.
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-0815, Japan.
B-cell antigen receptor signaling is initiated upon binding of the antigen to membrane-bound immunoblobulin (Ig), and the anti-Ig antibody (Ab) mimics this signaling. In B cells latently infected with Epstein-Barr virus (EBV), the same signals induce virus activation. We examine here whether rheumatoid factors (RFs), autoantibodies directed against the Fc portion of IgG, induce EBV and B-cell activation. As a source of RFs, RF-producing lymphoblastoid cell line (LCL) clones were isolated from peripheral blood mononuclear cells (PBMC) and synovial cells from patients with rheumatoid arthritis (RA) by EBV transformation. Burkitt's lymphoma-derived Akata cells, which are highly responsive to EBV activation by anti-Ig Abs, were used for the assay of EBV activation. Akata cells expressed IgG3 as membrane-bound Ig. RFs from a synovium-derived LCL were directed to IgG3 and induced EBV activation in 16 to 18% of Akata cells, whereas RFs from another synovium-derived LCL were directed to IgG1 and did not induce EBV activation. Pretreatment of RFs with the purified Fc fragment of human IgG completely abolished EBV activation. Furthermore, B-cell activation was assessed by incorporation of [3H]thymidine. RFs from synovium-derived LCLs efficiently induced B-cell activation, and the addition of CD40 ligand had a synergistic effect. On the other hand, RFs from PBMC-derived LCLs were polyreactive, had a lower affinity to IgG, and did not induce EBV and B-cell activation. The present findings imply a possible role for RFs as EBV and B-cell activators. Copyright 2004 American Society for Microbiology
Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
Yes yes. There is.
I have a number of abstracts and have seen a number of patients.. and animals... dealing with this situation.
Thanks for sharing your info here.
Is there anything I can do to help answer a specific question?
Please note- I am scattered thin right now.. so if I don't respond.. knock on my head a few times and ring bells... and I will try to come back and assist you.
SForsgren
Frequent Contributor (1K+ posts)
Member # 7686
posted
I've also heard of a number of folks that have had lymphoma related to Bartonella. When discussing with one of my doctors about this topic, the recommendation would have been to treat the Lyme and treat the Bartonella.
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
| IP: Logged |
TO LIFE
Unregistered
posted
Hi Tincup,
You are soo funny. Thanks for always giving me a good laugh all the time. Between the lyme and co infections, it's not like wining the daily double is it? Much Love, Roz
IP: Logged |
TO LIFE
Unregistered
posted
Hi Scott,
Thanks soo much for sharing. I am one to hope for the best, but have to plan for the worst.
I did well on Gent. about 3 1/2 weeks, Vanco 4 weeks, IV Rocephin 5 months. I think I have a very resistant strain.
I am wondering if a few rounds of Chemo. could knock it out? Before it's to little to late.
Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
HA! If you laugh, I laugh.
Here are some articles/abstracts that might be interesting to you.
Scientists find way to 'turn off' cancer -
Antibiotic halts aggressive tumours in mice
Tim Radford, Science Editor, Monday October 11, 2004, The Guardian
Scientists in California have found a way to "turn off" a gene that makes cancerous cells lethal.
They eliminated aggressive, incurable liver tumours in laboratory mice in four weeks, they report in an advance paper in Nature today.
The study, based on a gene called Myc, could lead to new ways of treating cancer.
Cancer Research UK scientists in Glasgow, working with colleagues in Seattle, last year worked out the details of how Myc cranks up the rate of growth of dividing cancer cells by sending one of the cell's factories into overdrive.
In cancer, cells divide uncontrollably.
The California team based their studies on mice with genetically modified liver cells.
The type of cell that becomes cancerous is called an epithelial cell, and these form cancers in breast, colon and prostate. So the same approach might work in all of them.
Liver cancer is common and difficult to treat.
"This is a terrible cancer. Anything that is encouraging in liver cancer may be important," said Dean Felsher of Stanford University, who led the research. "The exciting thing is that you can turn cancer cells into something that appears to be normal."
The mice under study had a mutated Myc gene that was constantly on.
It produced a Myc protein that served as a kind of conductor, sending a signal to cells to divide.
Cancer cells produce too much Myc protein all the time, and are constantly dividing.
Dr Felsher and his colleagues fed the mice an antibiotic called doxycycline, which turned the gene off, and stopped the protein flow.
As long as the mice had the antibiotic diet, they remained healthy.
Once the antibiotic was withheld, they developed aggressive liver cancer in 12 weeks.
When they were put back on the diet, all of them showed rapid regression: the liver cancer was eliminated, and liver cells seemed to behave normally.
In effect, the scientists turned the Myc gene on and off like a tap, and turned cancer on and off at the same time.
They also found that some of the apparently normal cells retained the ability to become cancerous, which could explain why cancers often recur after chemotherapy.
Cancer hits one person in three, and kills one in five. In recent years, researchers have concentrated on a number of new approaches.
They have tried to cut off the blood supply to tumours, to halt their growth.
They have tested search-and-destroy toxins, designed to make for and eliminate only cancerous cells.
They have experimented with scalpels made of ultrasound, and they have tried to "burn" cancerous cells with infrared radiation.
But cancer is, above all, a disease of the DNA, and British researchers have launched a cancer genome project to collect all the genetic mutations involved in the making of a cancer.
There are more than 100. But the Myc protein seems to play a role in many cases of the disease.
The Glasgow study immediately suggested that it would be a good target. If researchers could find a drug that blocked the action of Myc, they could study its effect on cancer cases.
The Stanford study shows that they were right.
But what works in mice may not work so well in humans. The next step is to hunt for a drug that would be safe for human patients, and yet have the same impact.
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Int J Cancer. 2004 Jun 20;110(3):336-42.
Reversible lymphomagenesis in conditionally c-MYC expressing mice.
Marinkovic D, Marinkovic T, Mahr B, Hess J, Wirth T. Department of Physiological Chemistry, Ulm University, Ulm, Germany.
It is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood.
We have established a transgenic mouse model in which c-MYC is conditionally expressed in lymphoid cells using the tetracycline-regulated system of gene regulation.
Mice with continuously expressed transgenic c-MYC died of invasive T- or B-cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c-MYC dependent since doxycycline treatment led to tumor regression.
Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation.
This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination.
Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c-MYC.
We observed that overexpression of c-MYC is sufficient to induce recurrent patterns of genomic instability.
The main observation was a gain of genomic material that corresponded to chromosome 15 in several T-cell tumors, which could be identified as trisomy.
Copyright 2004 Wiley-Liss, Inc. PMID: 15095297 [PubMed - indexed for MEDLINE]
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Conditional cell transformation by doxycycline-controlled expression of the ASV17 v-jun allele. Bader, AG., et al
Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Str. 1a, Innsbruck, A-6020, Austria.
To investigate the molecular basis of oncogenesis induced by the v-jun oncogene of avian sarcoma virus 17 (ASV17), we developed a conditional cell transformation system in which transcription of the ASV17 v-jun allele is controlled by a doxycycline-sensitive transactivator (tTA) or a reverse (doxycycline-dependent) transactivator (rtTA), respectively.
Permanent cell lines of quail embryo fibroblasts conditionally transformed by a doxycycline-controlled v-jun allele revert to the normal phenotype within 3 days and lose their ability to grow in soft agar, strictly dependent on the addition or removal of the drug, respectively.
The reverted cells are rapidly retransformed on conditional activation of v-jun.
While full-level synthesis of v-jun mRNA and v-Jun protein in these cells is established within 2 and 14 h, respectively, after switching to the permissive conditions, the first morphological alterations are observed after 24 h, and as early as 2 days later the morphology has changed entirely from flat cells resembling normal fibroblasts to spindle-shaped fusiform cells showing a typical jun-transformed phenotype.
Kinetic expression analysis revealed that transcriptional activation of the direct jun target gene BKJ precisely coincides with the establishment of full-level v-Jun protein synthesis.
Furthermore, we have analyzed the expression of a novel candidate v-jun target gene, termed JAC, which shows no sequence homology to known genes.
Similar to BKJ, JAC is specifically activated in jun-transformed fibroblasts, and induction of JAC is tightly linked to the conditional expression of oncogenic v-Jun.
These results demonstrate the high stringency of the doxycycline-controlled v-jun expression system, and they also indicate that expression of v-jun in these cells is indispensable for enhanced proliferation, cell transformation, and the induction of specific expression patterns of downstream target genes.
Copyright 2000 Academic Press.
PMID: 10772983 [PubMed - indexed for MEDLINE]
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
J Am Acad Dermatol. 1997 Feb;36(2 Pt 2):311-4.
Borrelia burgdorferi-associated primary cutaneous B cell lymphoma: complete clearing of skin lesions after antibiotic pulse therapy or intralesional injection of interferon alfa-2a. Kutting, et al
Department of Dermatology, University of Munster, Germany.
We report two patients with low-grade malignant primary cutaneous B cell lymphoma in association with Borrelia burgdorferi infection.
Extracutaneous manifestations were ruled out by standard staging procedures. Infection with Borrelia burgdorferi was confirmed by cultivation from lesional skin in both patients. In the first patient skin lesions cleared completely after pulse therapy with cefotaxime, whereas in the second patient antibiotic treatment failed. I
n this patient, however, skin lesions completely cleared after intralesional injection of interferon alfa-2a.
Antibiotic treatment or intralesional injection of interferon alfa-2a should be considered as a first-line treatment of Borrelia burgdorferi-associated primary cutaneous B cell lymphoma before more aggressive conventional therapeutic modalities (e.g., radiation therapy) are applied.
Publication Types: Case Reports PMID: 9039207 [PubMed - indexed for MEDLINE]
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13601-6. Epub 2001 Nov 6.
JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis. Hartl M, et al
Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Strasse 1a, A-6020 Innsbruck, Austria. [email protected]
Using subtractive hybridization techniques, we have isolated a gene termed JAC that is strongly and specifically activated in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (ASV17), but not in cells transformed by other oncogenic agents. Furthermore, JAC is highly expressed in cell lines derived from jun-induced avian fibrosarcomas.
Kinetic analysis using a doxycycline-controlled conditional cell transformation system showed that expression of the 0.8-kb JAC mRNA is induced rapidly upon activation of the oncogenic v-jun allele.
Nucleotide sequence analysis and transcriptional mapping revealed that the JAC gene contains two exons, with the longest ORF confined to exon 2.
The deduced 68-amino acid chicken JAC protein is rich in cysteine residues and displays 37% sequence identity to mammalian high-sulfur keratin-associated proteins. The promoter region of JAC contains a consensus (5'-TGACTCA-3') and a nonconsensus (5'-TGAGTAA-3') AP-1 binding site in tandem, which are both specifically bound by the Gag-Jun hybrid protein encoded by ASV17.
Mutational analysis revealed that the two AP-1 sites confer strong transcriptional activation by Gag-Jun in a synergistic manner.
Ectopic expression of JAC in avian fibroblasts leads to anchorage-independent growth, strongly suggesting that deregulation of JAC is an essential event in jun-induced cell transformation and tumorigenesis.
The Lyme Disease Network is a non-profit organization funded by individual donations. If you would like to support the Network and the LymeNet system of Web services, please send your donations to:
The
Lyme Disease Network of New Jersey 907 Pebble Creek Court,
Pennington,
NJ08534USA http://www.lymenet.org/
UBBFriend: Email this page to someone!
![[Big Grin]](biggrin.gif)
![[lol]](graemlins/lol.gif)
![[hi]](graemlins/hi.gif)
Tincup,![[Wink]](wink.gif)
Printer-friendly view of this topic