Heroes of Lyme Cryme Part I

 

The Heroes in this segment:  Medvedev, Benach, Martin (NIH), Marques NIH) and Dorward (NIH), Harding (CWR), Justin Radolf

 

WE ARE NOT WITH ILADS OR ANY OF THE NON-PROFITS, except May12.org or MEAdvocacy.org

I will be adding to this, “Heroes of Lyme” (and there will be another on Non-Heroes of Lyme, such as the press, ILADS, LDA, etc) because, obviously, ….
… Consider all the scientists we quote in the Occam’s Razor and other charge sheets who say OspA never could have been a vaccine and that the way Lyme and LYMErix cause disease is via immunosuppression, damage to lymph nodes, and cause a pseudolymphoma.
ILADS was an anomaly and never should have arisen, formally, as an entity, since we knew by the summer of 1999 that LYMErix was causing the same chronic disease as Lyme itself and that the Dearborn case definition had been falsified (or at least was not a consensus) and only called “bad knee” a case of Lyme.
AFTER we knew LYMErix caused the same disease as chronic Lyme, and that Dearborn had been falsified, was ILADS formed.  We all have to distance ourselves from them, because we are holding the criminals to a standard of Scientific Validity:  What is OspA and one is supposed to be developing a test that detects 100% (or at least close) of the known positive samples (“Accuracy“), and should be “Specific” (does not detect something else at the same time, under the same signal), and detects the lowest concentration of the analyte in question (“Sensitivity“), not the opposite, which is what Dearborn did.

Here are the criteria for a VALID METHOD; see for yourself what are the criteria:
https://www.fda.gov/ohrms/dockets/98fr/001424gl.pdf|

Thirdly, ILADS never fought for the patients.  How could they, when they are doing everything all wrong and have never written about the mechanisms of disease so easily available to the TruthCures.org/SASH scientists?

170628_BEAUX_ILADS_2

————————-
Remember, now, when the Lyme criminals are prosecuted, there are known and unknown unknowns, such as who will and who wont get credit. And one thing we will be certain to do, is give credit to the ones who explained how LYMErix (OspA, a triacyl lipoprotein, abnd TLR2/1 agonist) never could have been a vaccine…. which means someone lied about it from the start (which was Dearborn).

 

Use your Google Machine to look up the words and word roots above for the simple reason that most people with “MD” after their names would not even know where to start and that is why “The patients know more about the cryme/disease than the ….. (everyone else).”

 

Andrei Medvedev – shows the cross tolerance or the immunosuppression caused by the TLR2/1 agonist Pam3Cys or OspA expands to tolerance against TLR4 agonists (the LPS of the more typical “bacteria.”):

 

“Development of endotoxin tolerance following the initial “cytokine storm” phase of sepsis is thought to protect the host from an overexuberant immune response and tissue damage but at the same time, may render the host immunocompromised and more susceptible to secondary infection [18,–20]. …..   Notably, IRAK4 kinase activity was found to be a prerequisite for conferring inhibition of LPS-inducible JNK and p38 MAPK activation following prior exposure to Pam3Cys. These results represent the first systematic analyses of the role of IRAK4 kinase activity in TLR homo- and heterotolerance and pave the way for improved understanding of how IRAK4 kinase dysregulation may underlie immunocompromised states in late sepsis.”
https://www.ncbi.nlm.nih.gov/pubmed/23695305 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714565/

 

 

Clifford Harding – showed OspA causes tolerance to TLR7/9 agonists like (herpes) viruses, yet another form of cross tolerance:

”… we propose that TLR2 signaling induces rapid depletion of IRAK1, which impairs IFN-I induction by TLR7/9. This novel mechanism, whereby TLR2 inhibits IFN-I induction by TLR7/9, may shape immune responses to microbes that express ligands for both TLR2 and TLR7/TLR9, or responses to bacteria/virus coinfection.”
https://www.ncbi.nlm.nih.gov/pubmed/22227568

 

Roland Martin and Adrianna Marques – NIH employees who showed OspA caused global humoral immunosuppression but with chronic brain inflammation (opposites); Also showed OspA induces tolerance to TLR5 agonists or flagellins tuning off the antibody response to those too; Later came right out and said this is probably about the reactivated herpesviruses:

” “The spirochete Borrelia burgdorferi is the agent of Lyme disease, which causes central nervous system manifestations in up to 20% of patients. We investigated the response of human brain microglial cells, glial progenitors, neurons, astrocytes, as well as peripheral blood monocytes to stimulation with B. burgdorferi. We used oligoarrays to detect changes in the expression of genes important for shaping adaptive and innate immune responses. We found that stimulation with B. burgdorferi lysate increased the expression of Toll-like receptors (TLRs) 1 and 2 in all cell types except neurons. However, despite similarities in global gene profiles of monocytes and microglia, only microglial cells responded to the stimulation with a robust increase in HLA-DR, HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In contrast, a large number of HLA-related molecules were repressed at both the RNA and the protein levels in stimulated monocytes, whereas secretion of IL-10 and TNF-alpha was strongly induced. These results show that signaling through TLR1/2 in response to B. burgdorferi can elicit opposite immunoregulatory effects in blood and in brain immune cells, which could play a role in the different susceptibility of these compartments to infection.”

https://www.ncbi.nlm.nih.gov/pubmed/16783164

Aaaand they said this about the band 41 or antiflagellar antibody as a result of exposure to OspA (“hyporesponsive” or “is not working”):

“Toll-like receptors (TLRs) trigger innate immune responses via the recognition of conserved pathogen-associated molecular patterns. Lipoproteins from Borrelia burgdorferi, the agent of Lyme disease, activate inflammatory cells through TLR2 and TLR1. We show that stimulation of human monocytes with B. burgdorferi lysate, lipidated outer surface protein A, and triacylated lipopeptide Pam3CysSerLys4 results in the up-regulation of both TLR2 and TLR1 but the down-regulation of TLR5, the receptor for bacterial flagellin, and that this effect is mediated via TLR2. TLR4 stimulation had no effect on TLR2, TLR1, and TLR5 expression. Human monocytes stimulated with TLR5 ligands (including p37 or flaA, the minor protein from B. burgdorferi flagella) up-regulated TLR5. In addition, TLR2 stimulation rendered cells hyporesponsive to a TLR5 agonist. These results indicate that diverse stimuli can cause differential TLR expression, and we hypothesize that these changes may be useful for either the pathogen and/or the host.

https://www.ncbi.nlm.nih.gov/pubmed/16479520

 

 

“When Lyme Disease Lasts and Lasts” – Jane Brody, NYTimes.com

“Complicating the picture is the fact that some people with PTLDS symptoms apparently never had Lyme disease in the first place, Dr. Marques said in an interview. There are other infectious organisms — Epstein-Barr virus, for example — that can produce similar symptoms and may be the real culprits.”
http://well.blogs.nytimes.com/2013/07/08/when-lyme-disease-lasts-and-lasts/

 

!!!  Ya think? What causes everything? MS, Lupus, Cancer, etc…, being known outcomes of The Great-, and the New Great-Imitator ??

 

 

 

Justin Radolf, explaining how Spirochetes are not like regular “bacteria,” (which have LPS in the membranes) but shedders of fungal antigens (1999), and for showing chemically that OspA was triacylated:

 

“Lyme disease and syphilis are acute and chronic inflammatory disorders caused by the spirochetal pathogens Borrelia burgdorferi andTreponema pallidum subsp. pallidum, respectively (1516). Both spirochetes lack LPS (1718); however, they do possess abundant membrane lipoproteins (19).  … More recent observations suggest that the mechanisms underlying monocytic cell activation by motile B. burgdorferi and T. pallidum are identical to those employed by their purified membrane constituents (30). These results support the notion that lipoproteins are the principle component of intact spirochetes driving the host immune response during Lyme disease and syphilis. Similarly, lipoproteins and lipopeptides derived from the human pathogen Mycoplasma fermentans are also potent activators of monocytes/macrophages and may play an important role in the inflammatory response during infection (31-33).
… We have recently found that CHO-K1 cells do not express an mRNA transcript for full-length and functional TLR2 (37). This observation raised the possibility that the lack of functional TLR2 might account for the failure of CHO/CD14 cells to respond to bacterial structures other than LPS. To test this hypothesis, we engineered stable CHO/CD14 fibroblast cell lines that express TLR2. The transfected cells were highly susceptible to activation by lipoproteins and lipopeptides fromB. burgdorferiT. pallidum, and M. fermentans, as well as to activation by live motile B. burgdorferi. In contrast, cells expressing TLR1 or TLR4 did not acquire responsiveness to bacterial lipoproteins/lipopeptides. Moreover, we observed a TLR2-mediated cell activation byMycobacterium avium, an important pathogen in AIDS. Similar studies have documented inducible responses to other bacteria as well, including staphylococci, listeria, tuberculosis, and the pneumococcus, suggestive of wide-spread recognition of bacteria by TLR2 (101138,39).2 3We propose that TLR2 mediates cellular responses to structures from numerous microbial cell wall constituents and may thus be central in host recognition of diverse bacterial pathogens. Therapies directed at the TLRs may be useful anti-inflammatory agents for a large variety of chronic and acute bacterial infections.
http://www.jbc.org/content/274/47/33419.long
Radolf, 1990:
”The pathogenic spirochete Borrelia burgdorferi contains a set of integral membrane proteins which were selectively extracted into the detergent phase upon solubilization of intact B. burgdorferi with the nonionic detergent Triton X-114. Virtually all of these hydrophobic proteins were recognized by antibodies in pooled sera from patients with chronic Lyme arthritis, demonstrating that proteins partitioning into the detergent phase of Triton X-114 encompass the major B. burgdorferi immunogens. Furthermore, most of these immunogenic proteins, including the previously characterized OspA and OspB membrane antigens, could be biosynthetically labeled when B. burgdorferi was incubated in vitro with [3H]palmitate. The OspA and OspB antigens were radioimmunoprecipitated from [3H]palmitate-labeled detergent-phase proteins with monoclonal antibodies, and [3H]palmitate was recovered unaltered from these proteins after sequential alkaline and acid hydrolyses. The combined results provide formal confirmation that the major B. burgdorferi immunogens extracted by Triton X-114 are lipoproteins. The demonstration that B. burgdorferi integral membrane antigens are lipoproteins may explain the basis of their immunogenicity and may help to improve our understanding of the surface topology of B. burgdorferi.
We previously employed Triton X-114 phase partitioning (15) to demonstrate the existence in T. pallidum of a group of highly immunogenic integral membrane proteins (46, 47); more recently, these immunogens were biochemically characterized as lipoproteins (18). In the present study, the same methods were used to demonstrate that the major immunogens of B. burgdorferi, including the well-characterized OspA and OspB (2, 4, 6-8, 10, 32), are also amphiphilic proteins that can be radiolabeled during in vitro incubation of organisms with [3H]palmitate. Furthermore, for both OspA and OspB, sequential alkaline and acid hydrolyses confirmed that fatty acids are covalently linked to these two polypeptides in a 2:1 ester-to-amide linkage that is typical of most bacterial lipoproteins (31, 58). Fatty acids in ester linkage are sensitive to mild alkaline hydrolysis, whereas amide-linked fatty acids require acid hydrolysis for their removal (17). These biochemical results are consistent with the nucleotide sequences of the OspA and OspB genes (11). Both genes contain signal sequences with consensus sites (Leu-X-Y-Cys) (58) for processing by signal peptidase II, the bacterial enzyme that processes bacterial lipoproteins (58), and for the covalent addition of fatty acids to the resulting N-terminal cysteine. Similar biochemical analyses of the other 3H-lipid-labeled B. burgdorferi proteins were not performed. However, it is reasonable to assume that these molecules also contain covalently attached fatty acids, particularly since they remained radiolabeled after boiling in SDS and electrophoresis in SDS-polyacrylamide gels. Further biochemical analyses of these other borrelial lipoproteins are necessary to determine whether fatty acids are linked to some of them in ratios other than those described for conventional bacterial lipoproteins. In addition to lipoproteins with typical 2:1 esterto-amide linkages, T. pallidum appears to contain at least one, the 47-kDa immunogen, with unconventional lipid linkages (18, 19). Putative unconventional lipoproteins in Mycoplasma caprkicolum have also been described (25). It is noteworthy that no evidence for beta oxidation, desaturation, or chain elongation of radioactive fatty acids was found, since [3H]palmitate was recovered unaltered from both Osp proteins after alkaline and acid hydrolyses. Similar results were found in previous analyses of three lipoproteins of T. pallidum (18; unpublished data), an organism in which the metabolic pathways described above have not been demonstrated (44, 49). It is interesting to speculate that B. burgdorjiri may have similar metabolic limitations (4). Furthermore, in contrast to the large number of polypeptides labeled with ‘4C-amino acids, only a discrete subset was labeled with [3Hlpalmitate. This implies that radioactive fatty acid was not degraded before incorporation into these proteins.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC258571/pdf/iai00052-0147.pdf

 

Jorge Benache talking about how the shed blebs travel around and inflame the brain.

Am J Pathol. 2010 Jun;176(6):2848-57. doi: 10.2353/ajpath.2010.091235. Epub 2010 Apr 29.

Bacterial lipoproteins can disseminate from the periphery to inflame the brain.

Londoño D1, Cadavid D.  Author information

Abstract

“The current view is that bacteria need to enter the brain to cause inflammation. However, in mice infected with the spirochete Borreliaturicatae, we observed widespread cerebral inflammation despite a paucity of spirochetes in the brain parenchyma at times of high bacteremia. Here we studied the possibility that bacterial lipoproteins may be capable of disseminating from the periphery across the blood-brain barrier to inflame the brain. For this we injected normal and infected mice intraperitoneally with lanthanide-labeled variable outer membrane lipoproteins of B. turicatae and measured their localization in blood, various peripheral organs, and whole and capillary-depleted brain protein extracts at various times. Lanthanide-labeled nonlipidated lipoproteins of B. turicatae and mouse albumin were used as controls. Brain inflammation was measured by TaqMan RT-PCR amplification of genes known to be up-regulated in response to borrelial infection. The results showed that the two lipoproteins we studied, LVsp1 and LVsp2, were capable of inflaming the brain after intraperitoneal injection to different degrees: LVsp1 was better than LVsp2 and Bt1 spirochetes at moving from blood to brain. The dissemination of LVsp1 from the periphery to the brain occurred under normal conditions and significantly increased with infection. In contrast, LVsp2 disseminated better to peripheral organs. We conclude that some bacterial lipoproteins can disseminate from the periphery to inflame the brain.
https://www.ncbi.nlm.nih.gov/pubmed/20431027

 

Dave Dorward – NIH employee who showed that that the shed blebs travel around the body, patented the original LUAT.

 

 

An NIH patent, explaining how Lyme causes LYMErix-disease:

“The invention relates to novel antigens associated with Borrelia burgdorferi which are exported (or shed) in vivo and whose detection is a means of diagnosing Lyme disease. The antigens are extracellular membrane vesicles and other bioproducts including the major extracellular protein antigen. Another object of the invention is to provide antibodies, monoclonal and/or polyclonal, labeled and/or unlabeled, that are raised against the antigens. A further object of the invention is to provide a method of diagnosing Lyme disease by detecting the antigens in a biological sample taken from a host using the antibodies in conventional immunoassay formats. Another object of the invention is to provide kits, for the diagnosis of Lyme disease, comprising the antibodies and ancillary reagents. The advantage of the antibodies used in the invention is that they react with the antigens from geographically diverse strains of Borrelia burgdorferi, but do not react with antigens from related Borrelia spirochetes.”
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=5,217,872.PN.&OS=PN/5,217,872&RS=PN/5,217,872

2011, THE BLEBS ARE COVERED IN SLYMERIX>>> “Although we uncovered the existence of at least 10 distinct OM complexes harboring several unique subunits, the complexome is dominated by the frequent occurrence of a limited diversity of membrane proteins, most notably P13, outer surface protein (Osp) A, -B, -C, and -D and Lp6.6.”

Characterization of multiprotein complexes of the Borrelia burgdorferi outer membrane vesicles.
http://www.ncbi.nlm.nih.gov/pubmed/21875077

 

 

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