Formal Challenge

John H. johnh at faraway.hgmp.mrc.ac.uk
Sun Feb 8 06:19:25 EST 2004


Ken,


This is a completely unjustifiable response to NMF. He was been more than
patient, his posts are informative and eloquent, and he clearly makes a
concerted effort to avoid confrontation and stick to the science. NMF has
only been trying to tell you what I have been trying to tell you for too
bloody long. Remember Aristotle: When writing, think like a wise person but
write like a common person.

Ah well, b.neuro is once again lost.

John H.

Everyone thinks of changing the world, but no one thinks of changing
himself.
  --Leo Nikolaevich Tolstoy

NMF, if you're there:

You may be interested in the below. For some time now I've been trying to
unravel a potential particular susceptibility of myelin and ogcs to
immunological assault . OGCS have some rather interesting properties that
may make them vulnerable (and I find it interesting that a similiar
condition to Devics can be found in some people post infection). Thus I am
very interested in your comments about post seizure immunosuppression as it
seems to stand in contrast to the below which states excess glutamate may
play a role in sensitisation though I suspect this may have something to do
with Reactive oxygen species generated via the same and I'm really too tired
to think about it anymore ... .


 PS only found the below while looking up a quote from Bohr! Bloody
databases ... . And thanks for the BCM theory you mentioned in another post,
one of my collaborators will be very interested in this because we are
working towards a machine intelligence which will hopefully will make most
current search engines anachronistic and BCM theory appears to be useful to
at least study in that regard. Did some searches on BCM and found some
interesting empirical support for it but can't find a good review article
explaining it in full. Bloody databases ...  .

6/11/02 3:13

Mild Injury May Render Brain Cells Vulnerable to Immune Attack
Drugs to protect the brains of Alzheimer's patients could result from new
finding.

Wednesday, October 23, 2002 | Duke University Medical Center researchers
have discovered that a seemingly mild "insult" to the brain could sensitize
neurons to attack by immune system proteins that are otherwise protective.
The finding could explain why sufferers of Alzheimer's and other
neurodegenerative diseases significantly worsen following such insults.
According to the scientists, such minimal "excitotoxic insults" could
include brief seizures, mild head trauma or stroke, or even transient anoxia
from fainting while standing too quickly.
The scientists believe that drugs to selectively inhibit the immune proteins
could reduce the rate of neural damage in a wide range of neurodegenerative
diseases. Such drugs could also protect other organs against damage from
autoimmune diseases such as lupus and rheumatoid arthritis, in which the
immune system attacks body tissues, said the scientists.
In an article in the October 24, 2002, Neuron, Zhi-Qi Xiong and James
McNamara report studies of brain cell cultures that reveal how the set of
immune proteins, called "complement," can kill neurons. The research was
supported by the National Institutes of Health.
Complement proteins circulate in the blood in an inactive form, but when
triggered by infection or other invaders, they form complexes that can
attack the invaders.
"For a decade or more, there have been studies in which complement proteins
were detected in the vicinity of senile plaques of patients with Alzheimer's
disease and also in the brain of other neurodegenerative diseases," said
McNamara, who is professor and chair of the medical center's department of
neurobiology (http://www.neuro.duke.edu/) . According to McNamara, while
this association suggested that complement could harm neurons, evidence also
existed that complement could promote removal of a damaging protein that
causes the plaques in Alzheimer's disease.
The reality, Xiong and McNamara discovered, seems more complicated. The
complement immune system pathway consists of an "early activation" pathway
that can be protective in Alzheimer's disease, and a "terminal" pathway, in
which the proteins combine to create a "membrane attack complex." It is the
terminal pathway and this complex that damages neurons sensitized to
complement attack by mild brain insult, said McNamara.
"Basically, we have discovered how an insult like transient ischemic
attacks, minimal drop in blood pressure or a minimal blow to the head could
facilitate the transition from the early activation pathway to the terminal
membrane attack pathway, and transform a protective effect into a damaging
effect on the brain," said McNamara.
Initial clues that complement could attack brain cells came from the Duke
scientists' earlier studies of a rare childhood brain disease called
Rasmussen's encephalitis.
"We observed that in this autoimmune disease, even though the immune system
is constantly attacking the brain, the progressive loss of neurological
function in these children occurred in a stepwise fashion, following
flurries of seizures," said McNamara. The scientists found that the brains
of children suffering from the disease showed evidence of activation of
complement, and the complement proteins were concentrated in the neurons.
Also, said McNamara, the scientists' studies of an animal model of the
disease showed similar attack by complement.
What's more, he said, studies by other researchers had demonstrated in
animal models and cell cultures that fleeting insults can damage neurons by
causing an "excitotoxic" overload of the neurotransmitter glutamate.
Earlier brain tissue culture studies had shown that complement could damage
brain cells called astrocytes preferentially over neurons, said McNamara.
"This didn't make sense," said McNamara. "In our tissue culture studies, the
astrocytes were preferentially damaged, but in brains, the complement was
deposited on neurons. And so we reasoned that perhaps there was an
interaction between the excessive excitation mediated by glutamate and a
neuron's sensitivity to attack by complement."
In their experiments reported in Neuron, Xiong and McNamara exposed cultures
of neurons and astrocytes, first to modest levels of glutamate, as might be
generated by a mild insult to the brain. When they next exposed these same
cultures to activated complement proteins, the neurons were preferentially
killed.
Their studies also showed that the damage was specifically caused by the
membrane attack pathway of complement and not by the early activation
pathway. And, they found that the glutamate treatment sensitized neurons,
but not astrocytes, to attack by complement.
Finally, the scientists found that the excitotoxic sensitization of neurons
required both calcium and chemicals called "reactive oxygen species." While
the scientists do not understand these requirements, said McNamara, they
believe that the finding might offer further clues to the metabolic pathway
by which the neuron's defenses against complement are compromised.
Importantly, said McNamara, their finding raises the possibility of
protecting the brains of patients with neurodegenerative disease.
"The identification of a small-molecule inhibitor of the terminal pathway of
complement may prove to be tremendously beneficial to patients with
late-stage neurodegenerative disease, reducing the rate of brain injury," he
said.
What's more, said McNamara, such drugs "could be helpful in diseases of many
other organs, not just the brain, in which inappropriate activation of
complement damages the tissues, like rheumatoid arthritis, lupus and
others." McNamara emphasized the importance of basic studies of rare
diseases to such discoveries.
"I think this is one of countless examples in human biology in which study
of a rare disease, in this case Rasmussen's encephalitis, sheds light on
mechanisms of common diseases," he said. "We would have been unlikely to
have gained this invaluable insight into the immune system and the brain,
had we not been studying Rasmussen's encephalitis."

For additional information, contact:
Dennis Meredith | phone: (919) 681-8054 | email: dennis.meredith at duke.edu



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30/10/02 10:53

*Anonymous

Support your local bloodhound. Get lost. NOTE: from a T-shirt
*Anonymous

No individual raindrop ever considers itself responsible for the flood.
*Anonymous

If you're weak on the facts, pound the law; if you're weak on the law, pound
the facts; if you're weak on both, pound the table.
*Anonymous

If at first you don't succeed, welcome to the club.

*Anonymous

There is no crisis to which academics will not respond with a seminar.
*George Scialabba

Perhaps imagination is only intelligence having fun.

*Herbert Agar

Snobs talk as if they had begotten their own ancestors.
*Henry Miller

Sex is one of the 9 reasons for reincarnation ... The other eight are
unimportant.




"k p Collins" <kpaulc@[----------]earthlink.net> wrote in message
news:6KfVb.16845$GO6.9485 at newsread3.news.atl.earthlink.net...
> "NMF" <nm_fournier at ns.sympatico.ca> wrote in message
> news:aiXUb.12729$ZN1.680808 at news20.bellglobal.com...
> > HAHAHA I agree.  Good luck on pursuing
> > your theories.  (honestly).  And keep
> > on trying to get your manuscript published.
> > Do NOT give up on that.
>
> I expect that I'll not give-up.
>
> I expect I'll just Die, without anything
> changing between 'now' and then.
>
> The 'stock market': folks've been
> ripping-off this or that in the work
> I've done, in efforts to seek 'profits'.
>
> Because of all that's involved, such
> Theft [the Rights of a Citizen's with
> respect to his labors are Guaranteed
> by The Constitution of The United
> States of America - so the Offense
> is Federal], also constitutes Murder
> on a massive scale.
>
> It's why I can't 'pass gas' without
> 'upsetting' the 'stock market'.
>
> In the 'present' instance, the 'profit'-
> seekers breathed a 'sigh of relief'
> because they were 'afraid' that folks
> were about to 'open-the-door' to
> NDT's stuff [perhaps the Templeton
> Award which will be announced
> next month], but because I reacted
> 'strongly' when I saw you coming,
> on False 'premises', the 'stock mar-
> ket' 'decided' that I'd blown my
> chances.
>
> With respect to the False 'premises' -
> your request for 'data' - everyone
> who's been following my discussions
> knows that it's 'impossible' for me to
> respond to such a query in any way
> that any casual observer can follow
> [when my response is other than in-
> person, as is the case in a NG dis-
> cussion]. The reason for this 'impos-
> sibility' is Simple. I read, and synth-
> esized =all= the data that I could get
> my hands on, which means that =each=
> thing in NDT is in-there because of
> =thousands= of datasets.
>
> If I were to begin to discuss any one
> thing in NDT, exhaustively discussing
> 'the data', no one would remain inter-
> ested beyond the first week or so.
>
> It took nine 'years' of work more
> intense than I've ever heard of anyone
> else doing. [This isn't a 'boast'. When
> I realized what was at stake, I drove
> myself as if the Survival of Humanity
> depended upon the work I was doing -
> be-cause it does.]
>
> It's why, when someone asks for 'the
> data', I only 'groan', and then do as
> I've done with respect to your 'request' -
> give folks all the Neuroscience Libraries
> in the world, from which they can select
> anything.
>
> The 'point' being that, in the case of NDT,
> 'the data' is everything there is.
>
> I've has the same Formal Challenge be-
> fore the COmmunity of Scientists for
> more than twenty years.
>
> It's 'curious' to me that no one ever
> accepts.
>
> Yet there's been this False 'premise'
> about 'the data' hanging over my head
> like the sword of Damicles.
>
> It's 'funny'.
>
> Naive folks always lend credence to
> the False 'premise'.
>
> Which is 'why' the 'stock market'
> breathed a sigh of relief yesterday.
>
> And why, when I saw you coming-on
> I expressed my Disgust with respect
> to what you were doing.
>
> It doesn't matter how I respond.
>
> 'powerful' folks are 'determined' to
> keep 'me' Imprisoned, no matter what
> 'I' do.
>
> [Oh, I 'could' 'move away from' Truth -
> Lie like a Jackass to 'save my life' -
> [which is the way the 'powerful' folks
> go about their 'living'] but everyone
> knows that I 'move toward' Truth.
> Period.]
>
> So, to me, it's all Sorrowfully-'hilarious'.
>
> Truth Is.
>
> Truth does what it does, despite what
> anyone does.
>
> And the 'powerful' folks will see that
> it's so.
>
> K. P. Collins
>
>
>





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