Borrelia neurotoxin circulation

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Fin24
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Joined: Sat 8 Mar 2008 20:14

Re: Borrelia neurotoxin circulation

Post by Fin24 » Sat 16 May 2009 2:02

http://www3.interscience.wiley.com/jour ... 1&SRETRY=0

Journal of Neuroscience Research
Volume 85 Issue 2, Pages 231 - 237
Published Online: 5 Dec 2006
Mini-Review
Novel environmental toxins: Steryl glycosides as a potential etiological factor for age-related neurodegenerative diseases
P.T.T. Ly 1 2, S. Singh 1, C.A. Shaw

abstract excerpt:
Lipid analysis showed that some bacteria that are associated with some forms of neurodegenerative disorders have the capacity to synthesize steryl glycosides. Furthermore, certain steryl glycosides have been found to be a cell stress mediator and may have some immunomodulary effects. We hypothesize that steryl glycosides are putative neurotoxins involved in the etiopathogenesis of several age-related neurodegenerative disorders.
steryl glocisides are neurotoxic
steryl glycosides are found in many things , including cycads-used this study
some bacteria associated with neurodegenerative diseases can in fact synthesize steryl
glycosides
other steryl glycosides also are cell stress mediators and may even have immunomodulatory
effects

IF we can find out which bacteria in fact can synthesize these chemicals then maybe we will have a decent theory of linkage between toxins and tick bornes with neurodegenerative sx.

re: leptospirosis--also a pathogenic spirochete, not tick borne-transmission via contaminated water
An endotoxin-like substance is present in the cell walls of leptospires, which could induce cytokine synthesis and contribute to their pathogenicity, as well as to hemodynamic disturbance (15, 17)
.http://www.scielo.br/scielo.php?pid=S16 ... xt&tlng=en
Journal of Venomous Animals and Toxins including Tropical Diseases
versionOn-line ISSN 1678-9199
J. Venom. Anim. Toxins incl. Trop. Dis vol.14 no.3 Botucatu 2008

I wonder if anyone looked for similar in borrelia spirochetes, since cytokine mediated inflammation is associated with Lyme--they stop at the cytokines without bothering to see what induced the cytokines
http://iai.asm.org/cgi/reprint/71/10/6051.pdf--1 of many

Claudia
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Re: Borrelia neurotoxin circulation

Post by Claudia » Mon 8 Jun 2009 4:56

"llmd" Schaller weighs in on this topic with a major misrepresentation of information in The Public Health Alert, and he's settled things once and for all:

The 18 Reasons Lyme Treatments Fail: Tick-Borne Infection Medicine for the New Millennium

http://www.publichealthalert.org/Articl ... s_fail.htm

by Dr. James Schaller, M.D.

Reason Eight

Lyme appears to make many biotoxins. One is patented (Bb Tox1) and the full gene code is fully known. In past years, some LL MD's doubted the presence of Lyme biotoxins. Since this is a patented Lyme biotoxin, this issue is now obviously settled.
Obviously! :lol:

Martian
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Re: Borrelia neurotoxin circulation

Post by Martian » Mon 8 Jun 2009 17:03

Schaller wrote:Lyme appears to make many biotoxins.
Lyme appears to make many biotoxins?! Where is the evidence?
Schaller wrote:One is patented (Bb Tox1) and the full gene code is fully known. In past years, some LL MD's doubted the presence of Lyme biotoxins. Since this is a patented Lyme biotoxin, this issue is now obviously settled.
So according to Schaller, some so-called "llmds" doubted the presence of Lyme biotoxins, but not any more? Does that include all the ILADS "llmds"?

Bb Tox1 was not patented recently, but several years ago. Anyway, the presence of Lyme biotoxins is NOT obviously settled.

About the Author:
Martian is a worldwide acknowledged leading authority on Lyme disease.

Claudia
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Location: Connecticut, USA

Re: Borrelia neurotoxin circulation

Post by Claudia » Mon 8 Jun 2009 19:12

Martian wrote:
About the Author:
Martian is a worldwide acknowledged leading authority on Lyme disease.
Martian, you are much, much too modest. You are the intergalactic acknowledged leading authority on Lyme disease.

You know how else one puts lipstick on a pig in LymeLand? You call your self-published booklets "textbooks."

Fin24
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Re: Borrelia neurotoxin circulation

Post by Fin24 » Mon 8 Jun 2009 20:35

I was under the impression that as of yet you cannot patent a naturally occurring substance; that you CAN patent a lab construction and you CAN patent the PROCESS or procedure to extract, procure, identify and work with the substance

anyone know the basis for this patent?

and how does a patent prove anything?? other than its existence?? it doesnt by itslef prove where and how and hwy it occurs; let alone how to combat it.

if my vertigo lets up and my phone stops ringing ( this time of year in NJ the Lyme cases explodes and so does my advocacy work) Ill try to dig up the patent--Martian if you have a spare minute or 2, care to assist??

I already dug into the ESC cures Lyme/Amy fiasco in India/patent that was gazillions of pages of mumbo jumbo but found so many inaccuracies from the number of embryos the Dr claims to have used to the myriad of things she can "cure" for the mere price of $30,000 and a plane trip to India...that left me dizzy all weekend so any help in digging that junk up would help

thanks so kindly

Claudia
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Re: Borrelia neurotoxin circulation

Post by Claudia » Mon 8 Jun 2009 21:26

First, see the conference abstract from 1999 :
Yvonne wrote:http://www.lyme.org/conferences/99_abstract.html

A Novel Toxin (Bb Tox 1) of Borrelia burgdorferi

Mark J. Cartwright, Ph.D.*, Suzanne E. Martin, Ph.D. and Sam T. Donta, M.D.

The mechanisms responsible for many of the symptoms of Lyme disease remain to be delineated. Because many of the symptoms involve the nervous system, we postulated that the Lyme spirochetes produce a toxin that interferes with normal neurophysiological function. We have identified and cloned a gene of B. burgdorferi which encodes a protein that is a neurotoxin.

Initially, degenerate primers were designed to highly conserved regions within various toxin groups. These primers were used for amplification of DNA extracted from B. burgdorferi strain 2591 to identify genes that express proteins analogous to existing toxins. Degenerate primers designed to the highly conserved catalytic domains of diphtheria and pertussis toxins yielded an amplification product. The product was cloned, sequenced, and subsequently identified in The Institute of Genomic Research (TIGR) database as BB0755, a 37 kD protein of unknown function. The full length gene for BB0755 was cloned, expressed and purified using epitope tags in the pET30a expression system, and the resultant recombinant protein renamed Bbtox1. Using the synthetic target agmantine, Bbtox1 exhibited ADP-ribosyltransferase activity. No ADP-ribosyltransferase activity was detected using elongation factor 2 as the target. In tissue culture, Bbtox1 affected the morphology (rounding) of Y1 mouse adrenal cells and C6 rat glial cells. Bbtox1 induced cell death in both Y1 and C6 cells. C6 glial cells responded to Bbtox1 in a dose and time dependent manner. Brefeldin A, an inhibitor of the trans-golgi network, accelerated the onset of action of Bbtox1 an Y1 adrenal cells.

The effects of Bbtox1 are consistent with a mechanism of action similar to that of botulinum C2 and other cytoskeletal toxins. Studies are underway to identify the cellular target of Bbtox1 and its role in Lyme Disease. In addition, a homologous gene in Treponema pallidum of undefined function is being analyzed to determine if it codes for a toxin similar to Bbtox1.
Second, here is a link to their follow up patent (filed in 2000) that Schaller misrepresents and references:

http://patft.uspto.gov/netacgi/nph-Pars ... /6,667,038

This was an attempt to possibly capitalize financially from early research, similar to what Steere and Yale did with OspA, holding patents for its use in vaccine and diagnostic tests if it proved to be accurate and viable. Close, but no cigar.

Fin24
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Re: Borrelia neurotoxin circulation

Post by Fin24 » Tue 9 Jun 2009 1:55

forgive my "flow of consciousness style" but here is my analysis
1- primers- strands of DNA that serve as a starter/template for cloning and PCR reactions
2- degenerate primers--mixtures of similar, but not identical, primers; usually 2 uses for these
a-when trying to amplify genes from a different organism ( genes are similar but not identical)
b-when primer design is based upon protein sequence ( different codons-triad of nucleotides- can code for
the same amino acid and so you cant tell which exact codon is used so you need a mix of them)
Use of these degenerate primers greatly reduce specificity

B.b. strain 2591 is a Ct isolate which as far back as 1988 was compared to various other strains for immunological studies.But nothing about proteins and toxins--are the strains different?? and does the strain 2591 stand as a model for all the other B.b.?

they found a protein of unknown function (BB0755), cloned the gene that they thought should be the progenitor ( recall that using degenerate primers may yield different codons);and they then made another recombinant protein they renamed Bbtox1 ( with so far no proof it was toxin)

In lab tests Bbtox did exhibit toxic behavior BUT what wasnt shown is that this protein is in fact produced by any Borrelia.

we have a slew of codons in our own DNA ; some may even be identical to codons that code for feathers,and that doesnt mean we can or will ever sprout feathers.

their original capture of genes were from those of pertussis and diptheria organisms yet do those produce this type of toxin?

finding a gene sequence and then cloning it and making it produce a protein product doesnt mean the organism can or will produce that product

then I looked at the patent ( thank you Claudia!!)
and i was even more confused--its basically them patenting the method and the end product of a peptide (protein) that it seems they want to inject to induce an antibody response--ie VACCINE

the patent talks a lot about strain B31 ( not 2591) and a lot about the possible ineffectiveness and harm from steere's vaccine of 2 years previous.

the invention bldly proclaims it to be a novel way to diagnose,treat and even prevent lyme diseaase;
here is a key piece:
The invention provides isolated nucleic acid molecules, unique fragments of those molecules, expression vectors containing the foregoing, and host cells transfected with those molecules. The invention also provides isolated binding polypeptides and binding agents which bind such polypeptides, including antibodies. The foregoing can be used, inter alia, in the diagnosis or treatment of conditions characterized by the expression of a Borrelia burgdorferi toxin, Bbtox1, and by the expression of a Treponema pallidum toxin, Tptox1, nucleic acid or polypeptide.
the whole thing seems to be based upon the presumption of the existence of a toxin they havent yet shown to actually be produced in vivo ( or even in vitro by spirochetes) and the fact it cross reacts to Syphilis???dont they think thats a problem?

so from my perspective--they have this protein which acts like a toxin and they have the genetic sequence that codes for it; but no one can show IF that protein toxin actually is produced anywhere--lab or in animals--by the spirochetes.and the guess about the sequence was taken from pertussis and diptheria organisms that arent similar in behavior, or in the diseases they cause.

the patent also presumes a use for a vaccine based upon this unproven assumption that the protein/toxin is even being produced as well as antibody tests to see if anyone has this. ( have they even tested Lyme pts with CDC positives and neuro sx suggestive of "toxin" and seen if these new tests theyre patenting work?? did they find the "toxin" in pts blood??

it looks to me like they latched onto a protein and patented every possible thing about it--how to find and make it, how to use it etc without having shown that its present and manufactured in spirochetes or in the illnesses they cause.

I am impressed with the level of them yelling "mine, mine, mine" though...every variation of codon and every variation of the protein "toxin" is patented ( did that patent go thru or still pending??)
another tidbit
The polypeptide may be purified from cells/organisms (e.g., Borrelia burgdorferi, Treponema pallidum) which naturally produce the polypeptide by chromatographic means or immunological
recognition.
no references to show this to be true

NOTE==-many patents declare things that arent proven--the patent office doesnt have to nor does it insure statements are factual--all they really do is make sure its "novel" and a few other things and bam..you own the idea/process/etc

the fact that not much if any of this is in peer reviewed journals leads me to think its not "proven"

another tidbit
A. Detection and Identification of Toxin-producing B. burgdorferi

The present invention also provides methods for detecting Bbtox1 expression, including methods for quantitative analysis of toxin concentration in samples.
in patenting there doesnt have to be proof that a toxin actually exists--they can simply start with the presumption it doeas exist for which : here is the way to find and identify it

cleverly still they "contemplate" treatment with an antitoxin PLUS antibacterials. so who could say which effected successful tx??
they also discuss producing the antitoxin like they do with tetanus--in horses and other large mammals.

methods of introduction of such an antitoxin are "contemplated" not defined--how can they get ownership on "contemplation"??? the old well, maybe we will do this in tablets, maybe by IV and bam they own all ideas??

look at their definitions:
As used herein, the term "toxin" refers to a single protein or peptide that has deleterious effects in cells or subjects. "Bbtox1 toxin activity," "Tptox1 toxin activity," or "toxin activity" as used herein refer to the ability of a single protein or peptide (e.g., Bbtox1, Tptox1) to induce/cause cell death. In important embodiments it is neuronal cell death. In vitro, such activity can be manifested, for example, as ADP- ribosylation and/or elongation factor-2-ribosylation activity (see Examples section). In vivo, such activity is manifested according to any of the symptoms known in the art for Lyme disease and Syphilis.
they claim that any sx known for Lyme or syphilis can be blamed on the toxin that again hasnt been proven to exist from the spirochetes' own production

and after searhcing for references to this toxin I found these:
http://www.ncbi.nlm.nih.gov/pubmed/12194230
Polish article that simply states "Neurotoxin, produced by B. burgdorferi Bbtox1 was identified. Encephalopathy signs in Lyme borreliosis could be result of releasing toxico-metabolic products, ability of spirochetes to pass the blood-brain barrier as well as, effect of lymphocytes migration."

but I cant get into their references

and subject index of the 1998 IDSA conference
"Bbtox1 in Lyme disease, abstract 15"
but I cant find it anywhere--was an article ever accepted for publication???

often abstracts at conferences are by authors that are trying to get published but if theyre not accepted into a journal you never see the papers

I DID find this against the idea of toxins in the Borrelia genome
Sequence analysis of the B. burgdorferi genome did not reveal any obvious virulence factors such as toxins. Instead, components exposed on the surface of the organism that are capable of interacting with targets in the host may play key roles in the disease process.
http://www.jbc.org/cgi/content/full/M401691200
J. Biol. Chem., Vol. 279, Issue 40, 41706-41714, October 1, 2004

if anyone can get hold of this paper it may help
Infection and Immunity, March 2000, p. 1633-1648, Vol. 68, No. 3
0019-9567/00/$04.00+0

Comparative Genome Analysis of the Pathogenic Spirochetes Borrelia burgdorferi and Treponema pallidum

G. Subramanian,1 Eugene V. Koonin,2,* and L. Aravind2
A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi and Treponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochete
cmpleted genomes would show if in fact the codes for the protein toxin are there--but it wouldnbt show if theyre able to be turned on and the proeteins made

I was also looking for anything showing Treponema/syph making toxins and my vertigo is hitting again so..thats all for now

Claudia
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Re: Borrelia neurotoxin circulation

Post by Claudia » Wed 10 Jun 2009 14:41

In response to Dr. James Schaller's statement of absoluteness concerning Bb toxins (despite all current evidence to the contrary), with his self-promotion as a Lyme disease expert of epic proportions and standing, and as the the author of numerous "textbooks" and articles on this subject, the question brought up by hv808ct, as harsh as it is, has to be asked of Schaller:
hv808ct wrote:Fascinating…….but for the fact that B. burgdorferi does not produce any toxins.

No neurotoxins. No cytotoxins. No hemolysins. No enterotoxins. No endotoxins. No exotoxins. No exfoliative toxins.

No classical bacterial toxin. Period.

The closest anyone has come to seeing any toxin activity with B. burgdorferi was some test tube hemolysis back in 1992. And that turned out to be wrong as two guys at Wesleyan showed in 2000 (J Bacteriol. 2000 Dec;182(23):6791-7).

But why believe an online stranger. Ask Burrsanaco or Shoemaker. Ask them a couple of very fundamental questions such as….

What’s the molecular weight of this toxin?
Is it plasmid-encoded?
If it’s plasmid-encoded do all strains carry this plasmid and produce a toxin?
Is it a protein or a glycoprotein?
What’s its receptor?
Is it released or membrane-bound?
Has anyone produced commercial antibody to it?
Has it been sequenced (like the burgdorferi genome) and can I look it up in GenBank?
If it plays a role in pathogenesis, why hasn’t it been attenuated for use as a vaccine candidate?

And finally, “Are you an idiot or just a liar?”

Please let us know how either one of them responses to this last important question.
If 'llmd' Schaller's resume is accurate, "idiot" doesn't explain it.

So then, what is his reason and motivation to continue to promote such misleading, inaccurate information, and the misrepresentation of facts to the Lyme community and patients?

Maybe Drs. Schaller and/or Troy Marks will answer this important question.

FunkOdyssey
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Re: Borrelia neurotoxin circulation

Post by FunkOdyssey » Thu 11 Jun 2009 0:01

I love this forum. This is probably the only place on the internet where any sane discussion of Lyme takes place. This and LymeMD's blog.

Fin24
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Re: Borrelia neurotoxin circulation

Post by Fin24 » Thu 11 Jun 2009 1:02

LymeMD's blog??? now THAT is funny

a Dr asking and accepting advice from lay readers aka fans of his blog

wasnt impressed when he made his debut at MDJ and since that place went all viral marketing and was founded by 2 very greedy people who think it fun to be raking in the dollars off unsuspecting sick folks--Ive since left there BUT, well Im still not impressed with the LymeMD blog

I think Claudia this may be a case of trying to presume too much
the genetic coding FOR a toxin may be sitting there but it may also be alongside codons for repressing it, so its useless--just seeing similar genes that do things in other organisms is enough to guess that maybe the thing in front of you can do that too

in English: seeing that diptheria and tetanus toxins have codons that are present and amplifyable in Borrelia can lead to a logical query of " gee I wonder if Borrelia can then make toxins as well" BUT to assume it does just based upon codon presence is a big leap of faith in absence of evidence

thats the gap here---that leap over a mighty wide chasm-- BUT why does schaller et al need evidence to sell a treatment when all their other treatments are based on the same flimsy conjecture and presumption??

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