Science in the News
kenneth Collins
Excellent Stuff, and i encourage folks to check them out.
perhaps i'll comment on their contents at a later date, but, just-now,
i've got my hands-full with the task of holding together my 'heart'.
i'll comment, here, on one article that embraces what's True, "Ishi's
Long Road Home; A California Indian's preserved brain accentuates his
tragic, mysterious life", by B. Bower, _Science News_, 8Jan2000, p24.
http://www.sciencenews.org/20000108/bob1.asp
_Science News_ is such a Woderful source because it's read by so many
Young Folks, and i Encourage my Colleagues in Science to be in contact
with folks at _SN_ with respect to the work that they do, so that Young
Folks can receive the Benefit of insights into their work that, through
its ongoing contacts with Researchers, _SN_ works to provide.
K. P. Collins
kenneth Collins
=Please= Correct me =immediately= if i transgress your Religious Belief
in what i post here.
i am not aware of the extent to which it's find structure is, in fact,
preserved, but depending on that, if, before you inter it, the brain of
the Native American who was referred to as "Ishy" by White People is
carefully sectioned, within it's fine structure, there will be a 'map'
that will disclose some of the History that this Man Lived, and it's
Nature.
this information is exceedingly-Valuable with respect to the Travail of
the Native Americans, and, if it is allowable within your Sacred
Traditions, gaining the information contained within the remains of the
brain of this Native American Man would serve Truth well.
it would be as if this Man's Spirit can, even now, reach out to
Humanity, and Testify to Truth.
this said, i must leave you to decide on your own, within the
Obligations that fall to you with respect to your Sacred Traditions.
in Truth, i must say that i'm not certain i would allow this procedure
with respect to my own brain. but i am trivial. the Sorrow of the Native
Americans is Great, and that is why i reach out to you to inform you
that this opportunity to preserve the 'record' contained within this
Native American's brain is available to you.
in sectioning, the material of the brain is thinly sliced, and chemical
procedures are used to highlight various features of the brain's
structure.
although the procedures would render it not-whole, it has already been
separated from the Man's body, and i expect that you can expect that the
researchers who would do this 'mapping' would be willing to carefully
preserve all of the material of the brain so that it could be intered at
last.
Please Forgive me if, in suggesting that this 'mapping' be done, i have
Transgressed your Sacred Traditions.
it is in my Heart to help assure that the Travail of Native American
People is Honored Truthfully.
K. P. Collins
kenneth Collins
for doing this 'Historical mapping'.
within the brains of battered and ab-used people, there will be evidence
of their neural dynamics having 'traveled' into the 'zone of randomness'
(AoK, Ap4).
such 'mapping' is well within the range of existing technique.
it will occur in a way that's analogous to nutrient-determined 'growth
rings' in trees, but will have a complex topological distribution (and
the findings that've been reported with respect to the 'accelerated
aging' of "Dolly", the cloned sheep, leads me to 'speculate' that the
Historical 'mapping' will, eventually, be extended right down into the
'DNA'.)
if the fine structure of "Ishy's" brain is, in fact, preserved, it will,
in fact, be as i've discussed.
it's possible be-cause nervous system fx does, in fact, reduce to
activation-dependent TD E/I-minimization.
that the Historical 'mapping' technique is not =already= a standard
practice is =not= my doing.
K. P. Collins
kenneth Collins wrote:
>
> to my Native American Brothers and Sisters:
>[...]
kenneth Collins
beyone the physical structure of nervous systems.
everything that nervous systems do (all behaviro that's manifested,
etc.) shows the =same= stuff be-cause all of the external stuff derives
in activation-dependent TD E/I-minimization within the internal stuff
within nervous systems.
all of History can be 'mapped', in a highly-disclosing, 'same'-way.
consider, for instance, the dynamics of 'city' creation, development,
transformation, etc.
'urban renewal'? maps with respect to it will show the 'same'
activation-dependent TD E/I-minimization 'traveling' as occurs within
the neural topology of our brains (nervous systems).
how do folks think it is that i =Analyze= 'stock-market' dynamics?
"duh"...
no 'hard feelings', but try to see yourselves through my eyes, a bit.
folks 'think' they're so 'sophistocated', yet, when the behavior of
early 'americans' toward the Native Americans is compared with the
behavior of 'modern americans' toward minorities, it's readily seen that
the 'modern' level of 'sophistocation' remains that of the early
'americans'.
try to see it through my eyes.
it's important to get all of this straight because population
demographics are shifting. (ask folks in South Africa.)
this, too, is all right-in the activation-dependent TD E/I-minimization
'maps', both internal-neurotopological, and external,
of-any-and-all-physically-material kind, all over the place.
i've been =Reading=, =Using=, and documenting, such 'maps' for decades.
Wake-Up!
kenneth Collins
that January 14th is a 'special' day for me. each year, on this day, i
'Celebrate', a bit.
Today is a Special such 'special' day, the last such day of the 2nd
Millenium.
on this day, Truth Came to Exist within the Stuff of Humanity,
henceforth, irremovable.
how it's so has been in all been in AoK all along, but today is the
fulcrum-'point'-day with respect to such.
from today, onward, Humanity's course will be on one of only two
possible paths.
on one, the Benefit of 'moving toward' Truth will be reaped.
on the other, what will be reaped will be the merciless-Consequences of
having 'moved away from' Truth.
my Hopes and Prayers are that Humanity will Choose-Well with respect to
such.
[to the one who asked me, via private email, to Demonstrate the fact
that Jesus Understood how nervous systems process-information, if you
read the activation-dependent TD E/I-minimization 'maps', in all their
various, but all-the-same-stuff, forms, you'll see that i just did so.]
"And the Word became flesh, full of Grace and Truth." (John 1:14)
K. P. Collins [Deo Gratias]
kenneth Collins
thing to do.
doing such takes advantage of knowledge with respect to
activation-dependent TD E/I-minimization, with the result that there's a
'quieting' within neural-activation dynamics.
so, i'm off to see _Anna and the King_...
...er, _Beauty and the Beast_.
cheers, y'all.
ken collins
kenneth Collins
wasn't showing 'til later, so i've got some 'time'.
anyway, =iff= Native Americans Condone such, i'll be happy to show
(in-person) Researchers, who might be interested in doing the 'mapping',
how it can be achieved.
at this stage of such 'mapping', the work will be Arduous, so it would
probably be best if a small group of Neuroscience Grad Students,
well-versed in histological 'highlighting', were to do it.
there are a couple of significant benefits that would come to these
young Researchers.
1. they'd Establish the Field of neuro-Archeology (post-mortem
neuro-Anthropology & neuro-Forensics) as a practical Science.
2. they'd learn NDT real-good.
perhaps, =pending= decisions by Native Americans, folks at UCSF would be
interested?
kenneth Collins
>
> folks who've been following my discussions of NDT & TH for years know
> that January 14th is a 'special' day for me. each year, on this day, i
> 'Celebrate', a bit.
>
> Today is a Special such 'special' day, the last such day of the 2nd
> Millenium.
>
> on this day, Truth Came to Exist within the Stuff of Humanity,
> henceforth, irremovable.
>
> how it's so has been in all been in AoK all along, but today is the
> fulcrum-'point'-day with respect to such.
>
> from today, onward, Humanity's course will be on one of only two
> possible paths.
>
> on one, the Benefit of 'moving toward' Truth will be reaped.
>
> on the other, what will be reaped will be the merciless-Consequences of
> having 'moved away from' Truth.
on, BTW, be-cause, for me, of Jesus, my own Choice is to assist folks
who Choose the first 'path', and to "jump up and down, spit wooden
nickels, singing a tune", with respect to folks who Choose the 2nd
'path'.
i can do more, and will do so, willingly, in-person.
why "in-person"?
absent the resources to write a textbook (which is my circumstance
because i've given all my earnings, after staying-alive stuff, to NDT &
TH), the level of Integration inherent in NDT demands it.
i've made it explicit in the past, but will reiterate here, it's not
Just, but if i'm just allowed to show folks, in-person, and then just
'go away', i'll be able to do such. i'll docuent such as i've documented
other stuff, in accord with Truth, but who's been 'hurt' by the
documentation i've done?
no one.
yeah, a lot of folks are 'indignant' because of what i've done in order
to Honor Truth, but 'moving toward' Truth is what i do, it's not my
doing that this or that, somehow determines other folks relationships
with Truth, is it?
nope.
folks Choose such for themselves.
and, within my Obligation to Truth, i've Guarded Free Will, all the
while "jumping up and down, spitting wooden nickels, singing a tune",
with respect to folks who Chose the 2nd 'path'.
what else could i have done?
'move away from' Truth to 'cover-up other folks' 'moving away from'
Truth?
Impossible.
what i do is work to give folks reason to Choose with respect to 'moving
toward' Truth.
the rest, i Forgive, as best i can, "seventy times seven" (endlessly),
be-cause that's what holds open the 'door' to the Future.
why all of this seemingly-'unseemly' stuff?
it's all because =just= communicating what's been in NDT all along
Exposes the rest.
as a Scientist, i'm Obligated to do the Science.
as one who Loves Jesus, i'm Obligated to "hold open the 'door'".
i'm doing the best i can to bring things in for a safe-landing.
but i encourage folks with respect to 'moving toward' Truth, because as
the Science comes forward, all that's inherent in folks 'moving away
from' Truth will become increasingly obvious to all.
ken (K. P. Collins)
kenneth Collins
kenneth Collins wrote:
it's 'difficult' for me to do so because the stuff of folks 'Fear' is
superfluous to me, but i RETRACT as below.
> i've made it explicit in the past, but will reiterate here, it's not
> Just, but if i'm just allowed to show folks, in-person, and then just
> 'go away', i'll be able to do such. i'll docuent such as i've documented
> other stuff, in accord with Truth, but who's been 'hurt' by the
> documentation i've done?
>
> no one.
well, there's been me. i can deal with whatever Consequences come to me
'because' of the work i've done.
but i realized, as i was driving to see _Anna and the King_, that i just
cannot Accept being dealt with Injustly.
to 'condone' and/or 'accept' Injustice =Invites= the recurrence of
Injustice.
so i've realized that i've Erred in the writing of what's quoted above.
i'll stand firm on behalf of Justice.
it's just 'difficult' for me to do so because what i can see, clearly,
that has 'induced' folks to behave unjustly with respect to me, is
Superfluous to me.
i regard the Freedom to =Work= as the only stuff that 'being rich'
entails.
the way folks enter into Deception so as to garner 'wealth' or 'power',
or to 'cover their butts' is so Unworthy of the Awesome-Wonder Stuff
that exists within each Human Being, that it only gives me Sorrow when i
experience folks giving themselves over to such.
i detest such because i Understand what all of such has done to
Humanity.
but, despite the fact that all i want for myself is to be =Free= to
Work, so that i can do as much as i can do, it's =Clear= to me that i
Must Stand-Firm on behalf of Justice, lest my 'failure' to do so be
"interpreted' as "my having 'condoned' injustice".
i'll endure the Costs, inherent, as the 'price' demanded of me in order
to Actually-Live the Life that Exists within me, speaking out against
Injustice whenever and wherever i encounter such, doing what i can,
regardless.
as the American Naval Hero said, "Damn the torpedoes! Full speed ahead."
me too.
K. P. Collins
kenneth Collins
> the 1Jan & 8Jan, 2000 issues of _Science News_ are =loaded= with
> Excellent Stuff, and i encourage folks to check them out.
>
> perhaps i'll comment on their contents at a later date, but, just-now,
> i've got my hands-full with the task of holding together my 'heart'.
>
> i'll comment, here, on one article that embraces what's True, "Ishi's
> Long Road Home; A California Indian's preserved brain accentuates his
> tragic, mysterious life", by B. Bower, _Science News_, 8Jan2000, p24.
>
> http://www.sciencenews.org/20000108/bob1.asp
>
> _Science News_ is such a Woderful source because it's read by so many
> Young Folks, and i Encourage my Colleagues in Science to be in contact
> with folks at _SN_ with respect to the work that they do, so that Young
> Folks can receive the Benefit of insights into their work that, through
> its ongoing contacts with Researchers, _SN_ works to provide.
to those who might be 'wondering', i'll reiterate that, since _Science
News_ only publishes reports on what's been published elsewhere, and since
none of my work has been published, it's =impossible= for me to gain
anything from 'celebrating' the work that _Science News_ does (except that,
since i read _Science News_, if more folks get their work into its pages,
i'll have ready access to their work, which'd be something that i'd 'gain',
but so would everyone else who reads _Science News_).
my general approach is to 'celebrate' good Work whenever and wherever i
encounter it, just because good Work is worth 'celebrating'.
guess i'm "ab-'normal'" in this way, but i see such as being coupled to
Obligation with respect to 'criticism'.
K. P. Collins
Austin P. So (Hae-Jin)
You're biggest difficulty in promoting your views not only lies with your
inability to be concise, but more importantly lies in your inability to prove
the validity of AoK by using it to *predict* behaviour. Anyone can use
evidence/data *after* the fact to show that their theory is correct, and this
is something that you *always* do. I have not once seen you go out on a limb to
predict an outcome. You have only used what is published in the local rags, and
say that "oh...well, AoK shows this and that". The ability to predict is the
primary point of generating these kinds of models.
In fact I can just use basic Taoist principles to do exactly the same thing
that you are doing in AoK. To me it just looks like you are just applying
Taoism applied to a dynamic system, except perhaps you are trying to convert it
into mathematics. This in itself may actually be interesting, because at some
level it appears that you are trying to develop ideas/equations based on forms
rather than traditional reductionist principles that pervade science. But you
seem to be, rather than contributing anything new, just replacing the jargon of
taoism with the jargon of mathematics, and in many respects your very unique
form of jargon.
Maybe that is in itself okay...and in some ways I can see the need for
that...but again, until you actually use your AoK to predict behaviour in a
more quantitative way or predict a phenomenon that cannot be predicted using
the models that exist today, then you are just contributing to the great big
pile in the sky...
But what do I know, right?
Cheers
austin
--
---
Austin P. So (Hae Jin)
I.I.S.G.P.
Biotechnology Laboratory
University of British Columbia
E-mail: hae...@netinfo.ubc.ca
http://www.interchange.ubc.ca/haejin/index.html (under construction)
kenneth Collins
followed the long-term discussion (as is documented in the archives i keep), you'd
understand that things've been contrary to what you've posted, quoted below.
i can't repeat everything in every post.
K. P. Collins
Austin P. So (Hae-Jin)
unlike you I actually know the biochemistry and the gene
regulation processes fairly well...Sometimes I forget the
electrophysiology, but I'll admit
it...eventually...
In fact Ken, I was probably among the first people to get a copy of your
AoK. It's too bad
too, because although you may have taken an interesting take on things,
you write like crap,
and it is an effort to sift through the piles of shite to figure out
what you are
trying to say. In fact, the one thing that annoyed me the most and if I
remember correctly, is that I think you devoted one paragraph (10
lines?) to
write down your "equation of state", and used the rest of your AoK to
demonstrate its
validity describing any and every system you could think of. Of course,
you seem to ignore that very general statements can be supported by
anything, whether that statement is verbal or mathematic. So you throw
in terms like "neurodynamics" or "activation topologies" to give
credence to your work. These could be in fact true, but until you
describe an equation for a specific situtation that maps out the
topology for that situation, rather than just verbally saying so, you
will just be considered a hack.
But like I said...you don't make predictions...you find a result that
can fit your
model, and then proceed to ramble on ad infinitum about how the
scientific world is
out to "crucify" you. Use your model to predict something
quantitatively, or something
that would not be expected from based on scientific knowledge to date.
Your
neuron-glia stuff was predicted in the epilepsy field almost 40 years
ago...look under
the term "ephaptic". It was clearly demonstrated experimentally to be
the case within
the past 4 years. Your "prediction" that people with Alzheimer's should
keep mentally
active...not new at all...your delving into behavioural
psychology...your
"conclusions" based on AoK are *obvious*. As I said also, it shares a
lot of elements
akin to taoism, and is therefore ancient. All you've done is write down
yin-yang in a
very general equation. So what? Is that supposed to be a "breakthrough"?
In fact, when it comes to aging, you are just grabbing at straws...that
is quite obvious...
My challenge: use AoK to explain the onset and progression of
Huntington's disease.
What does AoK predict as the causative factor(s)? Where do you think
intervention can
be introduced? Or do it for Lou Gehrigs disease (ALS). I don't really
care...so long
as AoK can actually provide solid predictions on what elements are
critical and what
elements are spurious (if there is such a thing).
If you can tell me this based on AoK and provide a model, then you will
be listened. No one has been able to provide a good model yet for either
yet, so the field is
open for you to clear a swath of enlightenment.
kenneth Collins wrote:
> forgive me, please, but if you knew the Neuroscience, and if you'd actually
> followed the long-term discussion (as is documented in the archives i keep), you'd
> understand that things've been contrary to what you've posted, quoted below.
>
> i can't repeat everything in every post.
You seem to do that quite naturally, Ken...in fact this newsgroup is
filled with your
unique at repeating yourself at every turn....
kenneth Collins
Prediction: sooner or later, you'll 'go away' without having any success.
K. P. collins
Austin P. So (Hae-Jin) wrote:
Austin P. So (Hae-Jin)
If you are so confident about the validity of your AoK, then even a small application will
suffice. Why don't you even try to graphically represent the topology of neuron-glia
interactions with respect to synaptic signalling. Since you have already "solved" the
problem "exactly" through AoK, and since you apparently have an equation that shows the
dynamics of this system, and since the data is out there already, this would be just a
simple exercise in math, no?
If you have an equation of state, you should be able to draw out a phase diagram
representing the "topology" you so readily claim to have worked out.
Humour me.
kenneth Collins wrote:
> Prediction: you are just another Jackass who thinks he can 'manipulate' me to his ends.
>
> Prediction: sooner or later, you'll 'go away' without having any success.
--
kenneth Collins
if you've been monitoring the discussions, and if you've the understanding you claim, you must
know that i've also done everything you cite (quoted below), except post the diagrams, right
here in B.N, along with repeatedly offering to present everything in-person.
but, after posting my prior reply to you, i realized that, although, in accord with
'traditional stadards, it was 'appropriate' for me to do so, i gave your 'challenge' short
shrift.
it's 'late in the game'. as i've previously stated, my contract with my ISP is drawing to a
close. i've, therefore, only a little 'time' left. besides this, because it's been so cold
here in New England, i've had to use more heating fuel than i'd expected, that's impacted my
expenses, so i'd decided that i had to 'quit' smoking, which always transforms me into a
'grizzly bear' for at least the first week.
then you come and post a msg that's totally 'ignorant' of the pre-NDT and 'post'-NDT 'states'
of Neuroscience, and then 'challenge' me to state that which entire research programs in ALS
and Huntington's have not yet accomplished.
all of this is flat-out absurd, and it 'hurts-likehell' that you've 'imposed' such upon me.
but while out to purchase the day's news, i called myself to task. i know that if i have a
look at refs discussing ALS and Huntington's, i will be able to contribute stuff that will
advance the understanding with respect to both diseases, so i decided that i must do so,
bought a pack of cigarettes, and will spend the evening looking through the refs i've got on
hand for clues that i can work with.
for the record, the problem i've worked on is all aspects of the functioning of ='normal'=,
organicically-intact nervous systems. of course, i've studied lesion experiments. but i've
never studied disease processes because, since there are long-standing research efforts
devoted to the study of such disease processes, studying them didn't fit into my strategy of
'looking-elsewhere'.
for the record, the 45 minutes i spent looking into Alzheimers, the other night, is the only
'time' i've spent doing so. other than that, i've caught some TV reports, and, as i discussed,
have gained some insights into good approaches to generalized aging through my efforts to
nurture my Father's well-being. (my Father is as lucid and as active as a 50 year old man, and
i work to 'goose' him as much as i can so that he'll have reason to maintain his interest in
Life.)
for the record, all i know about ALS is that i wept when viewing Lou Gherig's 'good-bye' at
Yankee Stadium, and that Stephen Hawking also suffers the disease. while i was reading re
Alzheimers the other night, i learned that ALS impacts peripheral nerve myelination. that's
all i presently know re. ALS.
for the record, i know nothing re. Huntington's except that it involves choreoform movement
'abnormalities'. in the long-former past, i saw a possible 'correlation' to the sub-thalamic
basal ganglia deficits that underpin hemi-ballism. whether or not this possible 'correlation'
is actually anything is something i've never pursued. that is all i know about Huntington's.
Austin P. So (Hae-Jin) wrote:
> Manipulate you to my own ends? Please...you do flatter yourself unnecessarily don't you?
if you're at a 'biotech' lab, if i give you 'critical' factors re. ALS & Huntington's, you and
your lab stand to gain.
i presume that you are here 'being a Jackass' with the express purpose of 'weasling' with
respect to such 'profit'-seeking stuff.
after all, you've shown up in an extremely-'time'-correlated way with respect to my having
just done the exactly-correlated thing with respect to Alzheimer's.
and, in light of the fact that everything i've done has been done in a self-funded way, and in
light of the fact that you've 'come-on' in a way calculated to superficially-'trash' the
fruits of my having given of myself for 29+ years, your intent is Obvious.
but, in the end, i realized that if i can advance knowledge re. ALS & Huntington's, then i've
Obligation, with respect to such, that transcends your 'profit'-seeking.
i expect i can, so I've the Obligation to do so, and will, at least, explore a bit in the refs
i've at hand.
> If you are so confident about the validity of your AoK, then even a small application will
> suffice.
_AoK_ is just a brief introduction to Neuroscientific Duality Theory. it only casually
addresses Tapered Harmony. NDT & TH are huge.
K. P. Collins
dag.st...@helsinki.nospam.fi
> Prediction: sooner or later, you'll 'go away' without having any success.
Prediction: KPC will never understand that people "go away" just because
they have better things to do than read his egocentric and self-repeating
stuff. This is because his TD in/out is approaching nil.
Dag Stenberg
(who fortunately for himself is university-employed, thus has obligations)
kenneth Collins
with the congregation.
it hurts so much to witness the Fact that it is myself who Knows the Least of all re. Jesus, His
Sacrifice, and all He Stood for.
i cannot go further, this day, without, first, Apologizing to you, Austin, and asking your
Forgiveness.
i've promising 'tracks' with respect to both ALS & Huntington's. with the former, there's hope
that it will make a difference. with the latter, it's too early to say. clearly, i've got to go
into the Genetics, but i've little hope of achieving success in providing anything, beyond
description, that can be usefully applied. perhaps the description of the 'big-picture'
integration, re. Huntington's will stim some thoughts of experts in Genetics?
anyway, the refs i've on-hand are good, but a bit too-general, so i'll go to the Library. i need
to get up-to-speed with respect to histology and case histories, and check my approaches against
up-to-date refs.
i'll post, next, over the weekend.
again, i am Wrong in my 'treatment' of you, and i Apologize. i'm not saying that you are
Justified. i'm saying that i am Wrong in my 'treatment' of you. i allowed the "Beast", Abstract
Ignorance, to Dictate my Being in our interaction, and i ab-used the understanding that i'm trying
to present as a Gift to the Children.
i could not have Failed in any larger way.
it's 'difficult'. all i've left to 'care' about is being able to work, and i'm up-against being
unable to even feed and shelter myself, let-alone, do the work.
and i loosed my 'outrage' upon you.
i am Wrong.
K. P. Collins
kenneth Collins
way, it will mean that ALS is preventable, and, although not curable in advanced stages, at least
surgically-treatable.
it seems that the remaining 20% will be 'difficult' going. histology re ALS is =severely= lacking,
as are case-histories.
i'll discuss the hypothesis later, after i've had something to eat and get caught-up on my sleep.
what i want to talk about now is that i've verified that my mail's got a problem of its own.
the Library i've been using is at Smith College. what a =Great= Library! man, i've got nothing but
good to say about Smith. if you've a daughter, do all you can to get her into that place. a lot of
this is it's bright, well-lighted, guiet order, with an excellent selection of journals.
Smith is where i observed the beetles 'disregarding their wings one early-summer day years ago
when i was up-there to give one of the presentations in the series i presented.
more recently, it was where i saw the 'stringy-thing' vine 'tangles' that stimmed my recent
Alzheimer's discussion.
can't walk on the Smith College campus without Discovering Treasure-Stuff.
i took another peek while at the Smith College Science Library today. there was one example of a
'stringy thing' in the 'caternary' that was so beautiful that i wanted to clip it, but i didn't
because it was still hanging-in-there, doing it's thing on behalf of the vine.
what was beautiful about it was that, where it grew out of the vine, the vine was at close to the
maximal distance from the building that 'stringy things' can handle, and this particular 'stringy
thing' was all stretched-out like a camera tripod... or, like a cartoon character that's hanging
by its toes from one cliff and its fingers from the other cliff, with an abyss in-between.
i could, literally, see the 'stringy thing' 'struggle' to gain purchase on the building, and, when
it did, everything within it 'snapping-to', so that it's other 'feet' found their ways to this
'tripod'-like configuration... all at extremum. =Beautiful=!
i was standing there wishing i could share it all with someone, and a young science student did
come by, and i did say, "This is the best Science Library on the face of the planet! You're so
lucky." but i didn't think of showing her the 'stringy things', and their deeply-meaningful stuff.
(typical... "Hi, i'm the mad scientist" :-)
i can say all of this now because, while i was applying for a computer analyst's job at Smith,
i've given-up hope with respect to it.
anyway, i left with my 80%-verified ALS hypothesis, went to another lib that had some other books
i'd indexed, came home, to you, my much-asked-of Colleagues.
i'll discuss the ALS hypothesis later. it's the most-fun hypothesis i've ever put together.
i had some 'success' with Huntington's, too, but that effort will take longer... longer than i've
'time' left on my ISP contract. if i can pull it together sufficiently, i'll post what i've got,
which is only a clear direction, without yet enabling me to point to useful action. but maybe
someone else will be able to see something that i can't with respect to this start re.
Huntington's. (for better or worse, the ALS literature that i had access to was in much-greater
quantity than was the Huntington's literature. i compounded that because, i got into other things
(brought my nickel & dime collection, and =had= to invest a-bit), and, got a bit worn-out at the
copier because i was hungry, and forgot that i'd found a text on Huntington's in the Smith Lib,
and walked out without looking it up.
oh well...
be back with the ALS hypothesis later.
because ALS is a 'Disease' process, i'll expect anyone who can to contribute, pro or con,
Forthrightly (no need for 'tip-toing' on my account), with none of our typical 'waste'. the
sufferring will, then, be in our imediate presence, and we must be 'good soldiers' on behalf of
those who suffer.
ken (k. P. Collins)
kenneth Collins
> kenneth Collins <kpa...@earthlink.net> wrote:
> > Prediction: sooner or later, you'll 'go away' without having any success.
>
> Prediction: KPC will never understand that people "go away" just because
> they have better things to do than read his egocentric and self-repeating
> stuff. This is because his TD in/out is approaching nil.
Hey! you're getting-it!
> Dag Stenberg
> (who fortunately for himself is university-employed, thus has obligations)
yeah, but my way's more Fun... the 'pay' is pretty-bad, though :-)
seriously, Academia needs to 'loosen-up'. not with respect to the rigor of it's
agreed-upon 'production', but with respect to the ability to think a
non-traditional thought without 'imploding' in feigned 'shame'.
ken
kenneth Collins
> except for posting the diagrams, i did everything you cite (quoted below) in 1975-6.
>
> if you've been monitoring the discussions, and if you've the understanding you claim, you must
> know that i've also done everything you cite (quoted below), except post the diagrams, right
> here in B.N, along with repeatedly offering to present everything in-person.
'course, i invented the Maths i use, as necessary, and i don't 'bother' with symbolic notation
because i understand what i'm doing.
but i've discussed everything in kenning-ed 'plain English', and have, in long former msgs in
another online Science 'place' asked for help with respect to 'translating' the Maths into a
traditional, symbolic, format (to no avail).
so, i offer to go in-person to present everything diagrammatically, which is actually the best way
to communicate anything, as far as i'm concerned.
in my posts, i try to 'paint pictures' using verbal symbolization... because it's most-universal.
so the stuff has been presented in AoK, and in prior posts, over and over again.
the main difference between 'traditional' stuff and NDT & TH is that NDT & TH work, and are
exceedingly-easy to move-forward in, because once the 'special topological homeomorphism' is
grasped, the rest to the symbolism involved is flat-out 'natural'.
k. p. collins
Eric
Mathematics, Physics, and Neuroscience wrote:
> but i've discussed everything in kenning-ed 'plain English', and have, in long former msgs in
> another online Science 'place' asked for help with respect to 'translating' the Maths into a
> traditional, symbolic, format (to no avail).
What? Do you mean that Ken Collins, the worlds foremost
expert in Mathematics, Physics, and Neuroscience can't
do math?
> so, i offer to go in-person to present everything diagrammatically, which is actually the best way
> to communicate anything, as far as i'm concerned.
The only thing that the math can do is to prove you
wrong.
Eric Johnson
---
kenneth Collins
>[...]
> be back with the ALS hypothesis later.
>
> because ALS is a 'Disease' process, i'll expect anyone who can to contribute, pro or con,
> Forthrightly (no need for 'tip-toing' on my account), with none of our typical 'waste'. the
> sufferring will, then, be in our imediate presence, and we must be 'good soldiers' on behalf of
> those who suffer.
first, here's a URL that gives a view into the 'genetic' approach to ALS (you might have to copy the
URL to a text file and join it back together if your browser breaks it up because of its length):
a minor 'criticism':
the article uses a genetically-altered mouse variety that does yield motor neuron atrophy, but the
article isn't clear re. whether "mitochondrial vacuoles" occur in ALS (in Humans). the article cites
refs. that refer to other papers that discuss "mitochondrial vacuoles", but the article isn't clear
whether the other refs refer to the mutated mice or Humans. (i presume it's the mice, which doesn't
get me very far along with the "mitochondrial vacuoles" hypothesis.)
a 'Looking-Elsewhere' hypothesis re. Amytrophic Lateral Sclerosis:
turns out that i worked with only the refs i had on-hand, which were:
1. _Human Neuroanatomy_ 8th Ed., by M. B. Carpenter and J. Sutin, © 1983, Williams & Wilkins, ISBN
0-683-01461-7.
2. _Principles of Neuroscience_ 3rd Ed., by E. R. Kandel, J. H. Schwartz and T. M. Jessell, © 1991,
Elsevier, ISBN 0-444-01562-0.
3. _The Human Central Nervous System; A Synopsis and Atlas_ 3rd Ed., by R. Nieuwenhuys, J. Voogd, C.
van Huijzen, © 1988, Springer-Verlag, ISBN 0-387-13441-7.
4. _Human Motor Control_, by D. A. Rosenbaum, © 1991,Academic Press, ISBN 0-12-597300-4.
5. clinical information re. chemically-induced (i.e. intravenus applications of Streptomycin,
Gentamicin) vestibular hair cell degeneration, and brain stem stroke occurrences, communicated to me
by James Michael Collins, Physical Therapist.
6. NDT (AoK+), by k. p. collins, unpublished.
i reread several hundred pages, mostly in Nieuwenhuys, et. al. (to check the neuroanatomical
plausibility of the hypothesis), i would have liked to have reread as thoroughly in Carpenter & Sutin,
but didn't have 'time', and used it for spot-checks (because it's my 'favorite' Neuroanatomy text, i'm
pretty-familiar with Carpenter & Sutin, anyway), and, since the sections i read will be obvious to
anyone who wants to follow-up, i'll let it go at that.
i relied on the discussion of ALS in Kandel, et. al. for my start. the factors that i found
significant are as follows.
the occurrence of fasciculations (visible) and fibrilations (non-visible; need myograph) muscle
('twitch') activation anomolies.
the fact that ocular motor function in ALS is entirely 'normal'.
the fact that sensation in ALS is entirely 'normal'.
the Hypothesis:
the demyelination results from a specific brain stem lesion, of a type analogous to the
chemically-induced vestibular lesion, or a stroke-induced lesion.
this hypothetical ALS-generating brain stem lesion 'releases' 'normal' function in a way that
'interjects' activation associated with the superior colliculi where activation correlated with spinal
motor activation 'normally' exists. presently, the most-likely site seems to be one that affects
inferior olivary function, most likely with reticular nucleus involvement.
as is discussed in AoK, Ap6, the inferior olive is a 'crumpled-bag' nucleus, in which inputs including
efferent activity from the joint receptors drives topological-map 'translation' as the body's 3-D
conformation varies. the inferior olive accomplishes this 'translation', with respect to which
'crumpled-bag' nuclei are topologically-optimized (allowing TD E/I-minimized 'translation'
functionality), via climbing fibers in the cerebellum, which have potent Purkinje cell excitatory
effects.
what happens is that, since the hypothesized brain stem lesion alters the 'normal' balance between
ocular motor inputs and spinal inputs to the inferior olive, activation pertaining to saccacadic
movement, or ocular motor-via-reticular nuc(s) activation, gets crossed-up with the spinal inputs,
resulting in outputs from the cerebellum getting 'out-of-sync', which, when projected back to the
ascending and descending motor fibers, is what is reflected in the fasciculations and fibrilations.
(Kandel, et. al. discusses the fact that the ALS-correlated fasciculations and fibrilations correlate
with out-of-sync motor activation.)
next the hypothesis invokes NDT's view on activation-dependent glial (myelin) trophy.
this part of the hypothesis holds that the schwan cells comprising the myelin alter their
configurations in a way that attempts to compensate with respect to the out-of-sync activation that's
occuring in the motor fibers. it's part of NDT's activation-dependent neuralglia position that, during
'normal' motor neuron function, such activation-dependent schwan cell configuration alterations
'adjust' the inter-node Ranvier spacing so that impulses travel down axons in the optimal type II
synchronized (AoK, Ap6; like gears in a clock, not like soldiers marching) way. the 'adjustment' that
converges upon 'optimal' type II synchronization occurs because, when things are out-of-sync, ionic
conductances, local to an axon, will be volumetrically-increased (which is just another another 'form'
of "TD E/I(up)"). the schwan cells are living [:-)] things that, like all glia, get their 'marching
orders' from these ionic conductances. (as i've discussed here in B.N in the past (with respect to
long-term 'memory' addressing, and global 'plasticity'), the fact that these activation-dependent
glial configuration dynamics =must= occur is why the brain is a semi-fluid 'pudding'. if anyone wants
to receive this long-term 'memory-addressing' and global-plasticity stuff again please msg.)
but, since the hypothesized brain stem lesion interjects saccadic activation, which is, innately,
relatively 'random', no matter how the schwan cells 'adjust', the motor activation remains
out-of-sync.
this 'struggle' by the schwan cells can only fail, and their continuous 'adjustment' constitutes
hyper-excitation which precipitates their cell-deaths. 'hence', no upper/lower motor neuron myelin.
but that's not the end of it.
the overall relative randomness that results from the leison-interjected saccadic activation is acted
upon by the cerebellum in the 'normal' way. the cerebellum reacts to it as if the lesion-interjected
activation is spurious TD E/I(up), which means that, as the lesion-induced 'randomness' continues, the
cerebellum will output more and more inhibitory activation both up and down the neuraxis, which,
significantly, leads to the observed shrinking of motor cortex in ALS, which feeds back into the
overall weakening of motor dynamics, augmenting the progressiveness of the atrophy.
there are other attractive rationales for this sort of hypothesis. the problem of the 35+ years
typical onset of ALS has to be explained. if there's a genetic flaw, then how is it that it shows
itself only after 35+ years? what's the 'switch' that changes fully-functional motor neurons to
dysfunctional 'motor' neurons?
and the dynamics described can account for other phenomenon such as the 'laughing' behavior,
dissociated from affect, in ALS, that's discussed in Rosenbaum, and other affective deficits and/or
fluctuations.
plus, 'sporadic ALS' can remit. if the hypothesized lesion is self-reparable, like a strong compresion
injury, or a brain stem stroke that can nevertheless be recovered from via new capilary growth, then
the remission of the ALS symptoms has an obvious means.
it's more-difficult to accept that a genetic condition can 'remit' (although immune system function is
extraordinarily-capable, which might be invoked to account for such).
the one criterion that =must= be met in order to explore this hypothesis further is, since the ocular
motor system is not affected in ALS, to culture examples of ocular motor neurons along with examples
of upper and lower motor neurons, and look for differences that would allow the ocular motor neurons
to survive while the upper/lower motor neurons would not survive.
if there's no detectable difference, then ALS is probably due to a brain stem lesion, either
chemically-induced, stroke-induced or 'contusion'-induced, not a function of single-neuron-correlated
genetics.
or, perhaps this sort of monotonic TD E/I(up)-inducing lesion paradigm could be tested in animals.
anything that would defeat type II synchronization in the motor system would do it.
caveats: the Neuroanatomy of the brainstem is Hugely-Complex. the discussion above is only one
hypothetical example. i went with the inferior olivary 'connection' because it's straight-forward to
arrive at the necessary unstoppable randomness within the inferior olive 'translation' dynamics.
there are other lesion sites that attract one's mind, such as the interstitial nucleus of Cajal, and
various reticular nuclei. (as i've said, this looking at disease conditions is a new-thing for me. i'm
not yet up-to-speed with respect to such. i've no 'examples' database. if i were 'getting paid' to do
this work, i'd not stop until i'd checked out every possible lesion locus, and worked all the brain
stem Neuroanatomy through. it could very-well be that there's a round-about route involved. the only
necessities is that there actually be a lesion, and that its result interacts with the cerebellum as
was discussed above. brainstem lesions are not that uncommon. and it's =fun=. it's like doing a Living
3-D jigsaw puzzle. what makes it 'fun' is the hope, on behalf of those who suffer, of finding
something that can be =Fixed=.)
the other thing: while i was reading, i also saw ways that a similar lesion-induced activation
abnormalities could act, in fashion analogous to what's here, upon the basal ganglia and the
substantia nigra, which makes it plausible to 'wonder' with respect to Parkinson's.
and, of course cognitive dysfunction, such as 'schizophrenia', is 'just' more of the same defeating of
type II synchronization [forcing interminable TD E/I(up)], only more globally.
which leads right back to the central concept discussed in AoK.
i've not yet continued on to Huntington's. have to go back to the Library to check out the text that i
forgot to check-out the other day.
K. P. Collins
kenneth Collins
kindly, Eric, stop taking your own words and Falsely attributing them to me.
k. p. collins
kenneth Collins
ganglia constitute a high-'level' supersystem configuration mechanism that functions in accord with the TD E/I-minimization principle over the relatively-long term.
1. this means that degeneration within the basal ganglia =must= be correlated with wide-spread correlated observables, but in nothing i've read, as yet, are such
extra-striatal considerations addressed.
2. the hypothesis that the striatal degeneration is a result of a break-down in globally-ramifying TD E/I-minimization mechanisms has greatly solidified.
3. the 'break-down' addressed in 2, above, takes the form of the approach through which i previously addressed the pathology of Alzheimer's Disease, recently, here in
bionet.neuroscience.
4. i now extend the realm of this hypothesis to include =all= 'degenerative' diseases, including Huntington's, Parkinson's, and the various Dystrophies.
5. all such diseases are variations on the single theme that was discussed in the Alzheimer's hypothesis, with the variation being correlated with differing
'points-of-failure' at levels below the diencephalon.
6. these 'points-of-failure' are variations on what's discussed below, with different 'lesions' precipitating the symptomology of the 'various' disease conditions.
7. the 'lesions' =can= have a genetic correlation, because various environmental factors can act differentially with respect to individual genetic variation. (some food
substances, for instance, are toxic to some folks, but not others. in the present hypothesis, it is probably naturally-occurring trace-element stuff, that escapes gustatory
'affect ('aversiveness'), that is responsible for the delayed onset of symptoms.
8. in this hypothesis, the degeneration that is presently being focused upon is a =result= of more-fundamental stuff, and a correlate of symptomology, rather than it's
cause. the basal ganglial 'degeneration' stuff is 'just' what happens, over the long term, when relative randomness occurs, interminably, within nervous systems. the =cause=
is located at the lower-'level' site(s) of the nervous-tissue 'break-down' at which the 'unstoppable' TD E/I(up) is interjected into, and distributed throughout, the rest of
the nervous system.
9. auto-imune activity is probably involved, as when a slowly-building reaction to a substance acquires the quality of 'toxicity' over an extended period.
10. various non-motor symptoms probably unfold in the analogous way, the difference being 'determined' by the particular low-'level' 'lesion' site involved. 'lesions' can be
anything that alters the functioning of a particular 'low-'level' site toward increased long-term TD E/I.
11. "Gulf War Syndrome" encapsulates =a lot= of what's in this hypothesis, with there being multiple low-'level' 'lesions' which 'tip-the-scales' toward TD E/I(up) at
multiple loci.
12. so-called 'recreational' drug used typically results in, at least, short-term versions of the stuff that's being discussed in this hypothesis. reversibility of such
drug-induced effects depends on whether the drug has an 'anesthetic'-like effect, or a permanently-altering effect (for instance, some 'recreational' drugs permanently alter
the body's thermal homeostasis in a way that can be observed in long-term readings of any medical thermometer. although such long-term effects allow a person to function,
they still elevate TD E/I globally, enduringly, and must, therefore, be included in this hypothesis.)
13. one long-term approach that would probably yield useful information would be rigorously-restricted dietary information (a lot of which is probably already available, but
not being integrated.)
14. at any rate, the present standard with respect to the Disease classes which this hypothesis addresses, is inadequate. first, the stuff that's being focussed-upon as
being 'pathological' ('plaques', 'tangles', 'vacuoles', etc.) is probably 'just' the result of 'normal' neural function when subjected to interminable TD E/I(up). the
present focus must be bolstered with whole-nervous-system histology and analysis, and detailed case histories which include as complete-as-possible dietary
(nutritional-intake, drug use, environmental chemo factors, etc. information) because it can be said with certainty that the striatal neural degeneration that is being
focussed upon relatively exclusively has both trophic and activation correlates in wide-spread regions of the nervous system. it cannot be that this necessarily-correlated
stuff is 'swept under the rug'. no effective treatment can possibly result from such. all that can result from 'treatments' founded upon such is a 'shifting' of symptomology
because 'compensating' for only one portion of what is actually a wide-spread dynamic, only 'shifts' the aberant TD E/I(up), rather than ameliorating it. the ideal treatment
would trace the source of the aberant TD E/I(up) down to its low-'level' 'interjection' site, and act upon that locus, with a goal of returning that locus to it's 'normal'
physiological 'state'.
comment: i understand that what's in this hypothesis is 'groaner'-stuff, but it cannot be that a 'chisel' is taken to this or that portion of exquisitly-integrated global
dynamics, with the expectation that the innate functionality will, in fact, be restored. all the mis-applied 'chisel' will accomplish is a further diminution of the overall
integration.
folks =really= need to come to terms with the integrated functioning of the nervous system, without 'taking any short cuts', =before= undertaking to 'help' the nervous
system in its information-processing dynamics.
K. P. Collins
dag.st...@helsinki.nospam.fi
> i've read enough to state, in a preliminary way, that the current focus
upon neural atrophy in the basal ganglia is 'ill-considered. as is
discussed in AoK, Ap5, the basal
> ganglia constitute a high-'level' supersystem configuration mechanism
that functions in accord with the TD E/I-minimization principle over
the relatively-long term.
Where do you find a "current focus upon... basal ganglia" in ALS
research??? Certainly not in the J.Neurosci article you cited.
> 1. this means that degeneration within the basal ganglia =must= be
correlated with wide-spread correlated observables, but in nothing
i've read, as yet, are such
> extra-striatal considerations addressed.
Don't understand. Focus in ALS is on lower motor neuron degenration in
the spinal cord, and on upper motor neuron degeneration but rather
elsewhere than in the basal ganglia, although there are indeed also reports
on basal ganglia involvement in a few cases.
> 2. the hypothesis that the striatal degeneration is a result of a
break-down in globally-ramifying TD E/I-minimization mechanisms has
greatly solidified.
You just wrote that the focus on basal ganglia is illconsidered. So why
worry about striatal degeneration.
> 4. i now extend the realm of this hypothesis to include =all=
'degenerative' diseases, including Huntington's, Parkinson's,
and the various Dystrophies.
Not surprised. But at the same time your theory becomes unusable for any
practical medical purposes.
> 5. all such diseases are variations on the single theme that was
discussed in the Alzheimer's hypothesis, with the variation being
correlated with differing
> 'points-of-failure' at levels below the diencephalon.
Well, in Alzheimer's the greatest problem is in the basal forebrain and
its neocortical projection, whereas in ALS the greatest problem is in
the spinal cord. Which "variation" are we now talking about here?
The rest was more or less a mess, so I leave it alone.
Please shorten your lines, they are about three times as long as my screen.
Dag Stenberg
John H.
close look at it yet. Isn't there a familial tendency here also?
Would someone more knowledgeable than the current authors in this thread
care to enlighten? I know something about apoptosis etc but ALS .... .
John.
kenneth Collins <kpa...@earthlink.net> wrote in message
news:389453C7...@earthlink.net...
> kenneth Collins wrote:
>
> >[...]
>
> > be back with the ALS hypothesis later.
> >
> > because ALS is a 'Disease' process, i'll expect anyone who can to
contribute, pro or con,
> > Forthrightly (no need for 'tip-toing' on my account), with none of our
typical 'waste'. the
> > sufferring will, then, be in our imediate presence, and we must be 'good
soldiers' on behalf of
> > those who suffer.
>
> first, here's a URL that gives a view into the 'genetic' approach to ALS
(you might have to copy the
> URL to a text file and join it back together if your browser breaks it up
because of its length):
>
>
http://www.jneurosci.org/cgi/content/full/18/9/3241?maxtoshow=&HITS=10&hits=
10&RESULTFORMAT=&titleabstract=Amytrophic+lateral+sclerosis&searchid=QID_NOT
_SET&FIRSTINDEX=0
>
> K. P. Collins
>
>
>
>
>
dag.st...@helsinki.nospam.fi
> I thought it may have been a SOD problem, but haven't managed to have a
> close look at it yet. Isn't there a familial tendency here also?
> Would someone more knowledgeable than the current authors in this thread
> care to enlighten? I know something about apoptosis etc but ALS .... .
Fast attempt at partial answer:
- ALS = amyotrophic lateral sclerosis in a degenreative disease
afflicting both upper (brain, especially cortex) and lower (spinal cord
plus lower brain stem) motor neurons selectively.
- It leads to progressive paralysis and muscle atrophy because of the
degeneration of lower motoneurons, and to spasticity due to the
degeneration of upper motor neurons.
- a synonym is Lou Gehrig's disease. A famous living patient is Steven
Hawkings, a most famous scientist and public figure.
- paralysis and atrophy usually start in limbs, not always symmetrically
- the last to be afflicted is brain stem: swallowing, respiration etc.
- sometimes concomitant symptoms, not clearly motor, show as emotional
instability, proneness to laughter, crying etc.
- the disease may start between 30 and 60 years of age
- it progresses in some cases until death (from respiratory paralysis)
but often stops from unknown reason, perhaps only paralyzing the legs,
making the patient wheel-chair-bound.
- no treatment yet, only symptomatic help
This about the clinical picture.
- in about 5-10% of patients there seems to be a familial predisposition
- in these there has been shown mutations in the SOD1 gene
- the article KPC wrote about is about a mouse model of lower motor
neuron degeneration
- in this article mitochondrial involvement is shown
-- I hope this is all right, have to run....
-- John, I have stored your question about the Lanfumey paper on 5HT1A.
I will get back to it, but a certain urgent project is in its final
stage.
Dag Stenberg
dag.st...@helsinki.nospam.fi
> - ALS = amyotrophic lateral sclerosis in a degenreative disease
> afflicting both upper (brain, especially cortex) and lower (spinal cord
> plus lower brain stem) motor neurons selectively.
meaning: that ALS afflicts motor neurons selectively (not sensory and
probably not interneurons), but does afflict both the upper and lower
neurons
> -- I hope this is all right, have to run....
meaning: I hope this is what you wanted
Dag Stenberg
Austin P. So (Hae-Jin)
all ALS cases, so in fact the field is still very wide open.
So...mitochondrial dysfunction is a good candidate, as is an autoimmune response
(Llinas touted this for a while before the FALS/SOD link was found...antibodies
against the P-type channel). People have speculated on a glutamate excitotoxic
source....but again nothing concrete.
"John H." wrote:
> I thought it may have been a SOD problem, but haven't managed to have a
> close look at it yet. Isn't there a familial tendency here also?
>
> Would someone more knowledgeable than the current authors in this thread
> care to enlighten? I know something about apoptosis etc but ALS .... .
--
kenneth Collins
'rewrites' what i actually posted in prior msgs.
right or wrong, i Presume that you are 'just' trying to 'instigate' further
disclosure on my part. (which, if you consider a bit, you'll discover is the
Kind 'presumption'.)
i've attached the results of two Medline searches. these, the article URL that
i posted in a previous msg, an article, "Huntington's disease progression PET
and clinical observaations", by T. A. Andrews, et. al., _Brain_(1999)
122,2353-2363, and the refs i had on hand (referenced in a prior msg), are all
i've worked with.
as i explained, i'm 'new' to explication re. 'disease' processes. a man must
begin where he must begin. i always endeavor to do so with Forthrightness,
despite the routine fact that this or that that i've to offer 'thumbs its nose'
at the 'status quo'.
one can 'submit' to the 'tyranny' of the 'status quo', or actually Do Science.
these two things are mutually-exclusive, and i routinely Choose the latter,
because 'submitting' to the former is 'Death', itself.
i will update, clarify, and correct, my prior comments in reply to my last
prior msg.
K. P. Collins
dag.st...@helsinki.nospam.fi wrote:
> kenneth Collins <kpa...@earthlink.net> wrote:
> > i've read enough to state, in a preliminary way, that the current focus
> upon neural atrophy in the basal ganglia is 'ill-considered. as is
> discussed in AoK, Ap5, the basal
> > ganglia constitute a high-'level' supersystem configuration mechanism
> that functions in accord with the TD E/I-minimization principle over
> the relatively-long term.
>
> Where do you find a "current focus upon... basal ganglia" in ALS
> research??? Certainly not in the J.Neurosci article you cited.
>
> > 1. this means that degeneration within the basal ganglia =must= be
> correlated with wide-spread correlated observables, but in nothing
> i've read, as yet, are such
> > extra-striatal considerations addressed.
>
> Don't understand. Focus in ALS is on lower motor neuron degenration in
> the spinal cord, and on upper motor neuron degeneration but rather
> elsewhere than in the basal ganglia, although there are indeed also reports
> on basal ganglia involvement in a few cases.
>
> > 2. the hypothesis that the striatal degeneration is a result of a
> break-down in globally-ramifying TD E/I-minimization mechanisms has
> greatly solidified.
>
> You just wrote that the focus on basal ganglia is illconsidered. So why
> worry about striatal degeneration.
>
> > 4. i now extend the realm of this hypothesis to include =all=
> 'degenerative' diseases, including Huntington's, Parkinson's,
> and the various Dystrophies.
>
> Not surprised. But at the same time your theory becomes unusable for any
> practical medical purposes.
>
> > 5. all such diseases are variations on the single theme that was
> discussed in the Alzheimer's hypothesis, with the variation being
> correlated with differing
> > 'points-of-failure' at levels below the diencephalon.
>
kenneth Collins
back in 1993 by the Huntington's Disease Collaborative Research Group (i learned
this from reading "Huntington's disease progression PET and clinical
observations, by T. C. Andrews, et. al., _Brain_(1999), 122, 2353-2363).
i'll comment further in reply to my last-prior post.
k. p. collins
John H. wrote:
> I thought it may have been a SOD problem, but haven't managed to have a
> close look at it yet. Isn't there a familial tendency here also?
>
> Would someone more knowledgeable than the current authors in this thread
> care to enlighten? I know something about apoptosis etc but ALS .... .
>
> John.
>
> kenneth Collins <kpa...@earthlink.net> wrote in message
> news:389453C7...@earthlink.net...
> > kenneth Collins wrote:
> >
> > >[...]
> >
> > > be back with the ALS hypothesis later.
> > >
> > > because ALS is a 'Disease' process, i'll expect anyone who can to
> contribute, pro or con,
> > > Forthrightly (no need for 'tip-toing' on my account), with none of our
> typical 'waste'. the
> > > sufferring will, then, be in our imediate presence, and we must be 'good
> soldiers' on behalf of
> > > those who suffer.
> >
> > first, here's a URL that gives a view into the 'genetic' approach to ALS
> (you might have to copy the
> > URL to a text file and join it back together if your browser breaks it up
> because of its length):
> >
> >
kenneth Collins
k. p. collins
dag.st...@helsinki.nospam.fi wrote:
> John H. <joh...@netsprintXXXX.net.au> wrote:
> > I thought it may have been a SOD problem, but haven't managed to have a
> > close look at it yet. Isn't there a familial tendency here also?
>
> > Would someone more knowledgeable than the current authors in this thread
> > care to enlighten? I know something about apoptosis etc but ALS .... .
>
> Fast attempt at partial answer:
> - ALS = amyotrophic lateral sclerosis in a degenreative disease
> afflicting both upper (brain, especially cortex) and lower (spinal cord
> plus lower brain stem) motor neurons selectively.
> - It leads to progressive paralysis and muscle atrophy because of the
> degeneration of lower motoneurons, and to spasticity due to the
> degeneration of upper motor neurons.
> - a synonym is Lou Gehrig's disease. A famous living patient is Steven
> Hawkings, a most famous scientist and public figure.
> - paralysis and atrophy usually start in limbs, not always symmetrically
> - the last to be afflicted is brain stem: swallowing, respiration etc.
> - sometimes concomitant symptoms, not clearly motor, show as emotional
> instability, proneness to laughter, crying etc.
> - the disease may start between 30 and 60 years of age
> - it progresses in some cases until death (from respiratory paralysis)
> but often stops from unknown reason, perhaps only paralyzing the legs,
> making the patient wheel-chair-bound.
> - no treatment yet, only symptomatic help
> This about the clinical picture.
>
> - in about 5-10% of patients there seems to be a familial predisposition
> - in these there has been shown mutations in the SOD1 gene
> - the article KPC wrote about is about a mouse model of lower motor
> neuron degeneration
> - in this article mitochondrial involvement is shown
>
> -- I hope this is all right, have to run....
kenneth Collins
as is most-often the case, in my prior posts in this thread, i've been 'looking-elsewhere', Trusting that folks who work in the traditional ways are able to do better, in those
ways, than anything i can, presently, add to those traditional ways.
it seems that there aren't many folks who agree with me, but my view is that the stuff that's converged-upon while 'looking-elsewhere' is always Valuable stuff because it tends
to be 'invisible' to folks who work in traditional ways, and it, so, it tends to present the opportunity to 'check-things-out' in ways that were 'impossible' before the
'looking-elsewhere'.
['editorial' comment: although i'm long-accustomed to it, the way that my 'looking-elsewhere' approach elicits unthinking 'criticism', nevertheless, gives me Sorrow.]
at any rate, in rereading my prior posts in this thread, it became apparent that i can 'brifge', a bit, between the new hypothesis that i've developed and the stuff of the
traditional, molecularly-focussed approach to Alzheimer's, ALS and Huntington's. i'll do so, a bit, below.
my 'time' online is drawing to a close. this may be the last thing i post until i can get back online at some unforseeable 'time' in the future (if ever).
kenneth Collins wrote:
>i've read enough to state, in a preliminary way, that the
>current focus upon neural atrophy in the basal ganglia is
>'ill-considered. as is discussed in AoK, Ap5, the basal
>ganglia constitute a high-'level' supersystem configuration
>mechanism that functions in accord with the TD
>E/I-minimization principle over the relatively-long term.
in response to comments, elsewhere, by Dag, i stand on what i've posted. perhaps my view is skewed because my reading in this subject area has been only very-limited, but i
stand on what i've posted. there is a focus on striatal stuff, but an absence of discussion of stuff that's necessarily-correlated with striatal stuff.
and, 'of course' (from the approach of the traditional perspective on these diseases), the 'lesion can be located in the DNA. disease-causing 'mutations' are 'lesions' in the
DNA, in a way that's completely-analogous to the way that lesions in the neural architecture are substrates for neurological dysfunction.
although it's been implicit in the hypothesis i'm discussing, i'll make it explicit by re-stating that activation-dependence is =continuous= from the 'level' of the DNA to the
'level' of the complete organism.
that is, as i discussed in the recent past with respect to nervous system development, the particular 'state' of a nervous-tissue cell's development 'addresses' the correlated
activation-dependencies in its correlated DNA, which invokes the next sequential developmental contribution of the DNA. this interaction is =continuous= at all 'levels', up to
the 'level' of the whole body. thus, in the cortical-'stripe' formation stuff, for instance, in my view, the stuff that can be considered to be 'molecular markers' is =in= the
DNA itself, and is 'triggered', in an activation-dependent way, by the current 'state' of the cells to which the DNA in question is correlated. it's be-cause of this that, in
the transplant experiment examples that i've discussed recently in another thread, the rewiring of frogs' optic nerves shows a 'group discipline'. the 'group-discipline' results
from the fact that all the neurons involved are experiencing relatively-similar activation-dependent trophic dynamics. 'exceptions' include all 'boundary conditions', in which
the asymmetric nature of the activation-dependent dynamics are what maintains the 'boundary' (i.e. of a neural tract), thus, giving the tract it's 'confined place' within the
rest of the nervous system.
'of course', if the DNA is activated in different activation-dependent ways, there will be different correlated metabolic by-products of such differentiated activation of the
DNA. such metabolic by-products can diffuse from the cellular structure of a cell, and these diffused by-products might function as 'signals' to other cells, but these diffused
by-products cannot be termed as 'molecular markers' because doing so artificially-separates a sub-part of the whole, and calls it 'the whole', which is =just=
activation-dependence "all the way down" (no 'turtles' :-).
i understand that this sub-discussion must seem 'persnickety', but the fact that all there is is activation-dependence must be gotten across.
>8. in this hypothesis
which focusses upon striatal stuff
>, the degeneration that is presently
>being focused upon is a =result= of more-fundamental stuff,
>and a [=]correlate[=] of symptomology, rather than it's
>cause. the basal ganglial 'degeneration' stuff is 'just' what
>happens, over the long term, when relative randomness occurs,
>interminably, within nervous systems. the =cause= is located
>at the lower-'level' site(s) of the nervous-tissue
>'break-down' at which the 'unstoppable' TD E/I(up) is
>interjected into, and distributed throughout, the rest of the
>nervous system.
>9. auto-imune activity is probably involved, as when a
>slowly-building reaction to a substance acquires the quality
>of 'toxicity' over an extended period.
i. e. an acquired 'alergic' reactivity
>10. various non-motor symptoms probably unfold in the
>analogous way, the difference being 'determined' by the
>particular low-'level' 'lesion' site involved. 'lesions' can
>be anything that alters the functioning of a particular
>'low-'level' site toward increased long-term TD E/I.
including mutated DNA that enters into activation-dependent dynamics that result in the development of 'lesion'-equivalents in the neural architecture.
in other words, the stuff that i addresed as chemically- or injury-induced lesions in the previous discussion clearly can derive in the DNA.
and so can specific mutations with respect to specific metabolic steps.
i was not 'arguing against' such in my prior discussion. i was =only= discussing the probability that the diseases in question result from dynamics that have globally-integrated
involvements, and not 'just' some single aberrant DNA-driven metabolic step.
the hypothesis i'm discussing is in these globally-integrated dynamics, an example of such i've outlined, including the way that demyelination in ALS is a =result= of
dysfunction at higher 'levels' of the neuraxis, and not the 'cause' of the disease.
this is a significant, and meaningful, difference from the traditional hypothesis.
>11. "Gulf War Syndrome" encapsulates =a lot= of what's in this
>hypothesis, with there being multiple low-'level' 'lesions'
>which 'tip-the-scales' toward TD E/I(up) at multiple loci.
>12. so-called 'recreational' drug use[...] typically results
>in, at least, short-term versions of the stuff that's being
>discussed in this hypothesis. reversibility of such
>drug-induced effects depends on whether the drug has an
>'anesthetic'-like effect, or a permanently-altering effect
>(for instance, some 'recreational' drugs permanently alter
>the body's thermal homeostasis in a way that can be observed
>in long-term readings of any medical thermometer. although
>such long-term effects allow a person to function,
>they still elevate TD E/I globally, enduringly, and must,
>therefore, be included in this hypothesis.)
>13. one long-term approach that would probably yield useful
>information would be rigorously-restricted dietary information
>(a lot of which is probably already available, but not being
>integrated.)
the main thing that stimmed this 'dietary' stuff was with respect to the problem represented by the 'late onset' of the disease conditions, which needs explication. if, in
accord with the traditional view, it actually is the case that a single DNA mutation results it the entirety of the disease condition(s), then why is it that the stuff of that
mutation is activated in such a delayed way?
of course, there's a lot of stuff that's analogous, such as 'baldness', which 'normally' occurs in a delayed fashion. with respect to the hypothesis i'm discussing, the
correlation that i'm focussing upon is like the one i've observed with respect to my use of this or that shampoo and the rate at which i experience hair loss. (which is why,
BTW, i'm a devoted 'fan' of Johnson's Baby Shampoo... minimizes hair-loss.) and by careful study with respect to this & that shampoo's effect on hair-loss, one can uncover the
way that external stuff 'pushes' the DNA's activation-dependence one way or the other with respect to hair-loss. which is exactly-analogous to the way that this or that external
stuff 'pushes' the DNA's activation-dependence one way or the other with respect to disease processes.
i'd ask if anyone knows if the study of such 'time'-hierarchical genetic activation is an established field of study, but no one ever answers when i ask such questions, so i
won't bother. (please forgive my 'sarcasm', if you can. i'm weary from the one-way flow of information, and the 'opinion' of me that's reflected in-it.)
anyway, it might be that, through restriction of normally-ingested stuff, the late-onset triggering of the disease processes can be controlled. (if so, it'd probably be
trace-element stuff. otherwise, there'd likely be an 'aversive' reaction that'd accompany ingestion of disease-triggering stuff.)
>14. at any rate, the present standard with respect to the
>Disease classes which this [striatal stuff] addresses, is
>[...]
[myelinated]
this 'delayed-onset' might be triggered by the unfolding of 'normal' biological dynamics, such as the onset of puberty, or other genetically-'staged' dynamics. in this
sub-hypothesis, the newly-activated (within an individual body's biological functioning) dynamics modify what had been functional genetic unfolding, so that the the
(formerly-functional stuff + the newly-triggered stuff) yields a non-functional 'state' that precipitates motor neuron degeneration.
if this sort of thing occurs, then the disease is treatable through methods that eliminate the functionality of the newly-triggered stuff, with, of course, side-effects with
respect to the elimination of the dysfunctional version of stuff that would, otherwise, be part of 'normal' Life.
at any rate, an explanation for the observed delayed onsets of Alzheimer's, ALS and Huntington's is necessary, and it will probably be the case that, when such delayed onset is
explained, treatment strategies will become apparent within such explanation. so explication of the delayed onset is an important problem.
>> and the dynamics described can account for other phenomenon
>> such as the 'laughing' behavior, dissociated from affect, in
>> ALS, that's discussed in Rosenbaum, and other affective
>> deficits and/or fluctuations.
>>
>> plus, 'sporadic ALS' can remit. if the hypothesized lesion
>> is self-reparable, like a strong compresion injury, or a
>> brain stem stroke that can nevertheless be recovered from
>> via new capilary growth, then the remission of the ALS
>> symptoms has an obvious means.
>>
>> it's more-difficult to accept that a genetic condition can
>> 'remit' (although immune system function is
>> extraordinarily-capable, which might be invoked to account
>> for such).
>>
>> the one criterion that =must= be met in order to explore
>> this hypothesis further is, since the ocular motor system is
>> not affected in ALS, to culture examples of ocular motor
>> neurons along with examples of upper and lower motor
>> neurons, and look for differences that would allow the
>> ocular motor neurons to survive while the upper/lower motor
>> neurons would not survive.
>>
>> if there's no detectable difference, then ALS is probably
>> due to a brain stem lesion, either chemically-induced,
>> stroke-induced or 'contusion'-induced, not a function of
>> single-neuron-correlated genetics.
i repeat, i'm taking this position in this hypothesis because all of the so-called 'indicators' that i've read of can result from excitotoxic activation, which means that it's
possible that the 'indicators' are nothing of the kind, but 'only' by-products of a more-globally-correlated set of dynamics, such as those that i've been discussing in this
hypothesis.
an analogy from familiar experience is the way that some automobile electrical-system problems seem like one thing ("get a new battery"), when they are actually something quite
different (i. e. a shorted alternator armature).
the lack of 'charge' in the battery is not due to the battery being inoperable, but the electrical supply for the whole electrical system, of which the battery is just one small
part, having worn-out (having been 'lesioned').
no matter how many fully-charged batteries are put in-there, the problem will recure until the worn-out alternator is fixed or replaced.
the batteries just run-down because they experience the automobile version of 'excito toxicity" (more 'out-go' than 'in-come'... which, just-now, gains my sympathy :-))
anyway, that's my contribution(?) to the efforts to extinguish these diseases. i could do more, but despite the fact that i've done this stuff at my own expense, i've only been
'ridiculed' for having tried (even though there are two "Jewels" of NDT discussed, publicly, in this hypothesis for the first time... which is the 'ridiculous' thing, no?
K. P. Collins
kenneth Collins
as is most-often the case, in my prior posts in this thread, i've been
'looking-elsewhere', Trusting that folks who work in the traditional
ways are able to do better, in those ways, than anything i can,
presently, add to those traditional ways.
it seems that there aren't many folks who agree with me, but my view is
that the stuff that's converged-upon while 'looking-elsewhere' is always
Valuable stuff because it tends to be 'invisible' to folks who work in
traditional ways, and it, so, it tends to present the opportunity to
'check-things-out' in ways that were 'impossible' before the
'looking-elsewhere'.
['editorial' comment: although i'm long-accustomed to it, the way that
my 'looking-elsewhere' approach elicits unthinking 'criticism',
nevertheless, gives me Sorrow.]
at any rate, in rereading my prior posts in this thread, it became
apparent that i can 'brifge', a bit, between the new hypothesis that
i've developed and the stuff of the traditional, molecularly-focussed
approach to Alzheimer's, ALS and Huntington's. i'll do so, a bit, below.
my 'time' online is drawing to a close. this may be the last thing i
post until i can get back online at some unforseeable 'time' in the
future (if ever).
kenneth Collins wrote:
>i've read enough to state, in a preliminary way, that the
>current focus upon neural atrophy in the basal ganglia is
>'ill-considered. as is discussed in AoK, Ap5, the basal
>ganglia constitute a high-'level' supersystem configuration
>mechanism that functions in accord with the TD
>E/I-minimization principle over the relatively-long term.
in response to comments, elsewhere, by Dag, i stand on what i've posted.
perhaps my view is skewed because my reading in this subject area has
been only very-limited, but i stand on what i've posted. there is a
focus on striatal stuff, but an absence of discussion of stuff that's
necessarily-correlated with striatal stuff.
>1. this means that degeneration within the basal ganglia
and, 'of course' (from the approach of the traditional perspective on
a neural tract), thus, giving the tract it's 'confined place' within the
rest of the nervous system.
'of course', if the DNA is activated in different activation-dependent
ways, there will be different correlated metabolic by-products of such
differentiated activation of the DNA. such metabolic by-products can
diffuse from the cellular structure of a cell, and these diffused
by-products might function as 'signals' to other cells, but these
diffused by-products cannot be termed as 'molecular markers' because
doing so artificially-separates a sub-part of the whole, and calls it
'the whole', which is =just= activation-dependence "all the way down"
(no 'turtles' :-).
i understand that this sub-discussion must seem 'persnickety', but the
fact that all there is is activation-dependence must be gotten across.
>8. in this hypothesis
which focusses upon striatal stuff
>, the degeneration that is presently
>being focused upon is a =result= of more-fundamental stuff,
>and a [=]correlate[=] of symptomology, rather than it's
>cause. the basal ganglial 'degeneration' stuff is 'just' what
>happens, over the long term, when relative randomness occurs,
>interminably, within nervous systems. the =cause= is located
>at the lower-'level' site(s) of the nervous-tissue
>'break-down' at which the 'unstoppable' TD E/I(up) is
>interjected into, and distributed throughout, the rest of the
>nervous system.
>9. auto-imune activity is probably involved, as when a
>slowly-building reaction to a substance acquires the quality
>of 'toxicity' over an extended period.
i. e. an acquired 'alergic' reactivity
>10. various non-motor symptoms probably unfold in the
>analogous way, the difference being 'determined' by the
>particular low-'level' 'lesion' site involved. 'lesions' can
>be anything that alters the functioning of a particular
>'low-'level' site toward increased long-term TD E/I.
including mutated DNA that enters into activation-dependent dynamics
that result in the development of 'lesion'-equivalents in the neural
architecture.
in other words, the stuff that i addresed as chemically- or
injury-induced lesions in the previous discussion clearly can derive in
the DNA.
and so can specific mutations with respect to specific metabolic steps.
i was not 'arguing against' such in my prior discussion. i was =only=
discussing the probability that the diseases in question result from
dynamics that have globally-integrated involvements, and not 'just' some
single aberrant DNA-driven metabolic step.
the hypothesis i'm discussing is in these globally-integrated dynamics,
an example of such i've outlined, including the way that demyelination
in ALS is a =result= of dysfunction at higher 'levels' of the neuraxis,
and not the 'cause' of the disease.
this is a significant, and meaningful, difference from the traditional
hypothesis.
>11. "Gulf War Syndrome" encapsulates =a lot= of what's in this
>hypothesis, with there being multiple low-'level' 'lesions'
>which 'tip-the-scales' toward TD E/I(up) at multiple loci.
>12. so-called 'recreational' drug use[...] typically results
>in, at least, short-term versions of the stuff that's being
>discussed in this hypothesis. reversibility of such
>drug-induced effects depends on whether the drug has an
>'anesthetic'-like effect, or a permanently-altering effect
>(for instance, some 'recreational' drugs permanently alter
>the body's thermal homeostasis in a way that can be observed
>in long-term readings of any medical thermometer. although
>such long-term effects allow a person to function,
>they still elevate TD E/I globally, enduringly, and must,
>therefore, be included in this hypothesis.)
>13. one long-term approach that would probably yield useful
>information would be rigorously-restricted dietary information
>(a lot of which is probably already available, but not being
>integrated.)
the main thing that stimmed this 'dietary' stuff was with respect to the
>14. at any rate, the present standard with respect to the
>Disease classes which this [striatal stuff] addresses, is
>K. P. Collins
>kenneth Collins wrote:
[myelinated]
this 'delayed-onset' might be triggered by the unfolding of 'normal'
biological dynamics, such as the onset of puberty, or other
genetically-'staged' dynamics. in this sub-hypothesis, the
newly-activated (within an individual body's biological functioning)
dynamics modify what had been functional genetic unfolding, so that the
the (formerly-functional stuff + the newly-triggered stuff) yields a
non-functional 'state' that precipitates motor neuron degeneration.
if this sort of thing occurs, then the disease is treatable through
methods that eliminate the functionality of the newly-triggered stuff,
with, of course, side-effects with respect to the elimination of the
dysfunctional version of stuff that would, otherwise, be part of
'normal' Life.
at any rate, an explanation for the observed delayed onsets of
Alzheimer's, ALS and Huntington's is necessary, and it will probably be
the case that, when such delayed onset is explained, treatment
strategies will become apparent within such explanation. so explication
of the delayed onset is an important problem.
>> and the dynamics described can account for other phenomenon
>> such as the 'laughing' behavior, dissociated from affect, in
>> ALS, that's discussed in Rosenbaum, and other affective
>> deficits and/or fluctuations.
>>
>> plus, 'sporadic ALS' can remit. if the hypothesized lesion
>> is self-reparable, like a strong compresion injury, or a
>> brain stem stroke that can nevertheless be recovered from
>> via new capilary growth, then the remission of the ALS
>> symptoms has an obvious means.
>>
>> it's more-difficult to accept that a genetic condition can
>> 'remit' (although immune system function is
>> extraordinarily-capable, which might be invoked to account
>> for such).
>>
>> the one criterion that =must= be met in order to explore
>> this hypothesis further is, since the ocular motor system is
>> not affected in ALS, to culture examples of ocular motor
>> neurons along with examples of upper and lower motor
>> neurons, and look for differences that would allow the
>> ocular motor neurons to survive while the upper/lower motor
>> neurons would not survive.
>>
>> if there's no detectable difference, then ALS is probably
>> due to a brain stem lesion, either chemically-induced,
>> stroke-induced or 'contusion'-induced, not a function of
>> single-neuron-correlated genetics.
i repeat, i'm taking this position in this hypothesis because all of the
so-called 'indicators' that i've read of can result from excitotoxic
activation, which means that it's possible that the 'indicators' are
nothing of the kind, but 'only' by-products of a
more-globally-correlated set of dynamics, such as those that i've been
discussing in this hypothesis.
an analogy from familiar experience is the way that some automobile
electrical-system problems seem like one thing ("get a new battery"),
when they are actually something quite different (i. e. a shorted
alternator armature).
the lack of 'charge' in the battery is not due to the battery being
inoperable, but the electrical supply for the whole electrical system,
of which the battery is just one small part, having worn-out (having
been 'lesioned').
no matter how many fully-charged batteries are put in-there, the problem
will recure until the worn-out alternator is fixed or replaced.
the batteries just run-down because they experience the automobile
version of 'excito toxicity" (more 'out-go' than 'in-come'... which,
just-now, gains my sympathy :-))
>>
anyway, that's my contribution(?) to the efforts to extinguish these
dag.st...@helsinki.nospam.fi
> i've reformatted my prior post to make online reading easier.
Nope. Extremely long lines. Too hard to read.
Dag Stenberg
dag.st...@helsinki.nospam.fi
> i've reformatted my prior post to make online reading easier.
Ah, now it is all right.
Most points in your previous message are now clearly explained.
I think that (descrambled) hypothesis is quite worth to read. It may be
way off road, but at least the details and reasoning deserve thinking
about.
> the main thing that stimmed this 'dietary' stuff was with respect to the
> problem represented by the 'late onset' of the disease conditions, which
> needs explication. if, in accord with the traditional view, it actually
> is the case that a single DNA mutation results it the entirety of the
> disease condition(s), then why is it that the stuff of that mutation is
> activated in such a delayed way?
For comparison: in prion diseases, it takes times for anomalous PrP to
develop and for deposits to accumulate.
> >> i relied on the discussion of ALS in Kandel, et. al. for my
> >> start. the factors that i found significant are as follows.
> >> the Hypothesis:
I had not earlier been able to find this among the over-long lines.
> >> the demyelination results from a specific brain stem lesion,
> >> of a type analogous to the chemically-induced vestibular
> >> lesion, or a stroke-induced lesion.
> >> ...
I do not see any explanation for the fact that brain stem symptoms are
usually later in appearance than limb involvement. It also seems to
neglect observable peripheral pathology.
> >> there are other attractive rationales for this sort of
> >> hypothesis. the problem of the 35+ years typical onset of
> >> ALS has to be explained. if there's a genetic flaw, then how
> >> is it that it shows itself only after 35+ years? what's the
> >> 'switch' that changes fully-functional motor neurons to
> >> dysfunctional 'motor' neurons?
Interesting question, no doubt.
> if this sort of thing occurs, then the disease is treatable through
> methods that eliminate the functionality of the newly-triggered stuff,
...
How would you diagnose the disease 35+ years before outbreak?
> at any rate, an explanation for the observed delayed onsets of
> Alzheimer's, ALS and Huntington's is necessary, and it will probably be
> the case that, when such delayed onset is explained, treatment
> strategies will become apparent within such explanation. so explication
> of the delayed onset is an important problem.
> >> the one criterion that =must= be met in order to explore
> >> this hypothesis further is, since the ocular motor system is
> >> not affected in ALS, to culture examples of ocular motor
> >> neurons along with examples of upper and lower motor
> >> neurons, and look for differences that would allow the
> >> ocular motor neurons to survive while the upper/lower motor
> >> neurons would not survive.
This seems to me a profitable approach. Objections, anyone?
> i repeat, i'm taking this position in this hypothesis because all of the
> so-called 'indicators' that i've read of can result from excitotoxic
> activation, which means that it's possible that the 'indicators' are
> nothing of the kind, but 'only' by-products of a
> more-globally-correlated set of dynamics, such as those that i've been
> discussing in this hypothesis.
Logical. Not necessarily true, but logical.
> anyway, that's my contribution(?) to the efforts to extinguish these
> diseases. i could do more, but despite the fact that i've done this
> stuff at my own expense, i've only been 'ridiculed' for having tried
I think this (descrambled) hypothesis is quite worth to read. It may be
way off road, but at least the details and reasoning deserve thinking
about.
Dag Stenberg
kenneth Collins
>>i can 'brifge', a bit<<
i can 'bridge', a bit, too.
>[...]
ken
John H.
I remembered the article so will cite it here (good read for me):
"Sealing one's fate: control of cell death in neurons"
Louise Bergeron and Junying Yuan
Current Opinion in Neurobiology 1998, 8:55-63
p 60
In humans, ALS is characterized by the progressive loss of motor neurons int
he brain stem and spinal cord [ain't that great news Ken], leading to muscle
weakness and atrophy followed by paralysis and death. While most cases are
sporadic, 5-10% are familial (FALS). A breakthrough came ... SOD1. ...
Kostic et al crossed transgenic mice overexpressing BCL-2 neurons with mice
carrying the FALS SOD1 mutation. BCL-2 was effective at delaying the onset
of the disease, thus increasing lifespan of themice by about 19%; however,
once symptoms appeared, progression to paralysis and death remained
unchanged. BCL-2 delayed both the loss of motor neurons and theincrease in
expression oftyhe early markers of cell injury, c-Jun and ubiquitin. ... "
BCL-2 can useful in delaying apoptosis in other pathologies also. A paper I
read recently suggested that the p53 gene may regulate apoptosis via the
BCL-2\BAX etc ratios. So I'm not sure how significant this BCL-2 delay is,
except for the possibility that mitachondrial membrane permeability or
dysfunction is probably involved. Once cytochrome c and AIF are away in the
cytoplasm and the caspase cascade is away I think cell death is inevitable.
(?)
Perhaps BCL-2, at least in motor neurons, is particularly sensitive to some
type of oxidative stress.
I need to brush up, find out if oxidative stress alone can activate
procapase 9. Haven't even looked at motor neurons though.
Little by little,
John H.
Austin P. So (Hae-Jin) <hae...@netinfo.ubc.caX> wrote in message
news:3895CA2F...@netinfo.ubc.caX...
> Familial ALS has been linked to SOD mutations....but that accounts for <
5% of
> all ALS cases, so in fact the field is still very wide open.
>
> So...mitochondrial dysfunction is a good candidate, as is an autoimmune
response
> (Llinas touted this for a while before the FALS/SOD link was
found...antibodies
> against the P-type channel). People have speculated on a glutamate
excitotoxic
> source....but again nothing concrete.
>
>
> "John H." wrote:
>
> > I thought it may have been a SOD problem, but haven't managed to have a
> > close look at it yet. Isn't there a familial tendency here also?
> >
> > Would someone more knowledgeable than the current authors in this thread
> > care to enlighten? I know something about apoptosis etc but ALS .... .
>
dag.st...@helsinki.nospam.fi
> to my understanding, SOD1 was identified as being correlated with Huntington's
I suppose SOD is implicated every time someone cries "free radicals"
Dag Stenberg
kenneth Collins
a little 'story'. yesterday, i, apparently, missed the usual courtesy
call that my landlord give his tennants when our building's parking lot
is being plowed after a snowfall.
as a result, my car got plowed-in.
when i went out to survey the situation, i thought, "no problem", got
out my trusty square-blade Sears [& Roebuck] garden shovel, and removed
the compacted snow from around my car, one shovel-full at a time. took a
couple of hours, but when i was done, my parking spot, and the area of
the sidewalk upon which snow had been plowed because the snow-removal
vehicle had to work around my truck, were 'works of art'.
why this 'story'?
while i was shoveling my car out of the piled-up snow, i was also
thinking about the ALS hypothesis that i'd posted, and realized that all
that it entailed had much in common with the 'predicament' in which my
car existed.
with respect to the hypothes, too, "no problem"... 'one-shovel-full' at
a time will transform it into a 'work of art'.
it's the same, 'grinding', leave no stones unturned' 'style' with which
i do any and all work. it =always= leads to the same success,
=eventually=. all that matters is keeping-at the 'shoveling'.
dag.st...@helsinki.nospam.fi wrote:
>
> kenneth Collins <kpa...@earthlink.net> wrote:
> > i've reformatted my prior post to make online reading easier.
>
> Ah, now it is all right.
i Apologize for the inconvenience. i'd detected that my comm computer
had been compromised, and so i rebuilt it. but i failed to set my news
reader correctly, leaving my posts in HTML. i noted, and fixed the
problem, when, after taking the 'time' to reformat the long prior msg,
the lines were still very-long after i posted the reformatted msg. (in
the future, if a msg appears with HTML formatting, if it is saved as a
'.HTM' file, it can, then, be read in a web browser, and 'saved' as a
text file, which will (at least in some browsers and word processors)
eliminate the HTML format characters.)
>
> Most points in your previous message are now clearly explained.
> I think that (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
yes, i agree, it surely needs more 'shoveling'-work. because i'm a
'newbie' to explication of disease processes, it was never my intention
to do anything more than to do something that would allow folks to view
the problem of ALS, Huntington's, etc., through a new 'lens'.
i've seen enough, however, to be able to say, with certainty, that the
hypothesis does, at least in some of it's parts, already advance the
Science.
>
> > the main thing that stimmed this 'dietary' stuff was with respect to the
> > problem represented by the 'late onset' of the disease conditions, which
> > needs explication. if, in accord with the traditional view, it actually
> > is the case that a single DNA mutation results it the entirety of the
> > disease condition(s), then why is it that the stuff of that mutation is
> > activated in such a delayed way?
>
> For comparison: in prion diseases, it takes times for anomalous PrP to
> develop and for deposits to accumulate.
yes, there's also stuff like the gradual absorption of toxins which
would build to a threshold at which the body cannot prevent the onset of
a disease process that's correlated to the toxin.
there was a short unsigned article in today's _New York Times_ "Science
Times" section, "Exploring Alzheimer's Early Roots" that discusses a
study by V. M. Moceri of the U. of Washington. Moceri studied long-term
correlations between Alzheimer's pathology and environmental factors,
and found strong positive correlations with respect to 'poverty'.
which is in line with the ALS, etc. hypothesis that i've been
discussing.
i skimmed a strikingly-similar similar study in one of the two texts
(which were with respect to ALS) that i spent some with at the Hampshire
College Library the other day. unfortunately, in my notes, all i have
are the texts' library call numbers. and one of the refs in one of the
Medline searches i posted includes roughly-similar findings (with
respect to disease dynamics in India).
so the included-emphasis of the hypothesis i posted on the need for
detailed case histories is substantiated, as is the main emphasis on the
need for a more-generalized approach.
>
> > >> i relied on the discussion of ALS in Kandel, et. al. for my
> > >> start. the factors that i found significant are as follows.
>
> > >> the Hypothesis:
>
> I had not earlier been able to find this among the over-long lines.
my fault, as explained at the top of this post. i apologize for the
unnecessary difficulty my failure imposed upon you.
>
> > >> the demyelination results from a specific brain stem lesion,
> > >> of a type analogous to the chemically-induced vestibular
> > >> lesion, or a stroke-induced lesion.
> > >> ...
>
> I do not see any explanation for the fact that brain stem symptoms are
> usually later in appearance than limb involvement. It also seems to
> neglect observable peripheral pathology.
it's in the hypothesis that the percipitation 'lesion' acts through the
modification of 'normal' integrated dynamics. in the example offered
with the hypothesis, a lesion alters the information-processing of the
cerebellum (which, in NDT, is a powerful 'passive', globally-acting, TD
E/I-minimization mechanism; see AoK, Ap5).
one must put-things-together. the lesion alters cerebellar function,
which results in abnormal motor-system dynamics, because, the
interminable TD E/I(up) condition that the lesion interjects prevents
normal achievment of 'type II synchronization" (as evidences in ALS
fasciculations and fibrilations.
the late onset of respiratory functionality would, therefor, be
correlated with the 'time' at which the motor-neuron's 'struggle' with
long-enduring TD E/I(up) was coming to a close, because, up until that
'time', the lesion-cerebellum couple still has feedback from the
out-of-sync motor-neuron activity with which to deal.
in this view, the onset of the respiratory dysfunction results from a
further =release= phenomenon that occurs when the motor feedback becomes
so weak that its functionality within the global TD E/I-minimization
dynamics falls below a threshold (determined by brain-stem neural
architecture) at which the brain stem areas correlated with respiration
gain precedence within the ongoing activation 'state' (i took notes on
all of the underlying nuclear groups while reading the other night. msg
back if you want specific details. but be quick. i'm being 'forced', by
my financial circumstances, to go offline.)
in other words, the demise of the motor neurons results in an =actual=
're-engineering of the neural topology of the brain stem, and, as a
result, the relationship between the respiratory nucs of the brain stem
with respect to TD E/I-minimization becomes rewired, and what remains of
the supersystem 'blindly' 'seeks-out', and 'attacks' the 'normal'
respiratory functionality as a TD E/I(up)-condition, which results in
the aberrant 'shutting-down of respiratory functionality.
it's important to be aware that, in the above dynamics, the supersystem
is 'just' 'striving', in 'normal' ways, to achieve TD E/I(min). it's
be-cause the lesioned tissue interjects 'perpetually-random',
non-minimizable activation into the TD E/I-minimization dynamics that
the 'normal' TD E/I-minimization dynamics generate the hyper-stressing
'struggle' to achieve type II synchronization back upon the motor
neurons, which constitutes an 'excito-toxic' condition with respect to
the motor neurons' metabolic functioning, which kills them, resulting in
the =obvious= disease observables that have been focussed upon, while
the more-subtle, more-globally-occurring, and much-more-significant
disease-generating stuff had gone unrecognized.
[it's off-topic, but =all= psychological & cognitive dysfunction bears
these sames 'signs', albeit, to a very-much-more subtle degree. what
happens in these psychological dysfunctions is that interminable TD
E/I(up) that's interjected from the experiential environment drives the
'normal' TD E/I-minimization dynamics in aberrant ways, with much the
same results (that is, with physically-real neural atrophic
consequences) as are described in this hypothesis. it's a =CERTAINTY=
that such more-subtle stuff enters into the onsets of what have been
considered to be 'totally-organic' diseases such as Alzheimer's, ALS,
Huntington's, etc. the discussion of these more-subtle, but nevertheless
highly-significant, considerations (which i''ve been addressing, all
along, via a trying-to-be-Gentle 'baby-talk' 'style', so as not to
'panic' folks, goes on-and-on within NDT. it's one of the things i'm
talking about when i say that "there's not sufficient 'time' left in my
Life to discuss everything that was long-ago reified, even if such
discussion is all i do with the rest of my Life. hence, my Sorrow, with
respect to the fact that no one will meet with me, in-person, to discuss
the core of such stuff.]
>
> > >> there are other attractive rationales for this sort of
> > >> hypothesis. the problem of the 35+ years typical onset of
> > >> ALS has to be explained. if there's a genetic flaw, then how
> > >> is it that it shows itself only after 35+ years? what's the
> > >> 'switch' that changes fully-functional motor neurons to
> > >> dysfunctional 'motor' neurons?
>
> Interesting question, no doubt.
>
> > if this sort of thing occurs, then the disease is treatable through
> > methods that eliminate the functionality of the newly-triggered stuff,
> ...
> How would you diagnose the disease 35+ years before outbreak?
=iff= there's anything to the hypothesis that i've been discussing,
contemporary 'scanning' methods would disclose the aberrant TD
E/I-minimization 'struggle', through which, what has been considered to
be the disease condition, is generated (precipitated). and sensitive
versions of those scanning methods should be able disclose the TD
E/I(up)-generating 'lesion' location. of course, all such work can only
occur with respect to deviations from a background database that tracks
'normal' (average) activation 'states'. building this
background-comparison database would, itself, be a major undertaking,
but would definitely, itself, become o font of useful insight.
>
> > at any rate, an explanation for the observed delayed onsets of
> > Alzheimer's, ALS and Huntington's is necessary, and it will probably be
> > the case that, when such delayed onset is explained, treatment
> > strategies will become apparent within such explanation. so explication
> > of the delayed onset is an important problem.
>
> > >> the one criterion that =must= be met in order to explore
> > >> this hypothesis further is, since the ocular motor system is
> > >> not affected in ALS, to culture examples of ocular motor
> > >> neurons along with examples of upper and lower motor
> > >> neurons, and look for differences that would allow the
> > >> ocular motor neurons to survive while the upper/lower motor
> > >> neurons would not survive.
>
> This seems to me a profitable approach. Objections, anyone?
>
> > i repeat, i'm taking this position in this hypothesis because all of the
> > so-called 'indicators' that i've read of can result from excitotoxic
> > activation, which means that it's possible that the 'indicators' are
> > nothing of the kind, but 'only' by-products of a
> > more-globally-correlated set of dynamics, such as those that i've been
> > discussing in this hypothesis.
>
> Logical. Not necessarily true, but logical.
it's an hypothesis, done to 'goose' folks' 'wondering', and, hopefully,
their experimental explorations. by now, i've gone over the stuff of the
hypothesis sufficiently to be able to say, with certainty, that at least
some portions of it will withstand all tests.
so, in it, i've kept my word about advancing the Science.
>
> > anyway, that's my contribution(?) to the efforts to extinguish these
> > diseases. i could do more, but despite the fact that i've done this
> > stuff at my own expense, i've only been 'ridiculed' for having tried
>
> I think this (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
Thank you, Sir. i, again, Apologize. i'd not realized that it was my
=inadvertant= posting in HTML that had interjected 'TD E/I(up)' into our
interaction.
k. p. collins
kenneth Collins
John H. wrote:
>
> Thanks Dag and Austin,
>
> I remembered the article so will cite it here (good read for me):
>
> "Sealing one's fate: control of cell death in neurons"
> Louise Bergeron and Junying Yuan
>
> Current Opinion in Neurobiology 1998, 8:55-63
>
> p 60
> In humans, ALS is characterized by the progressive loss of motor neurons int
> he brain stem and spinal cord [ain't that great news Ken],
yes, thanks for posting this stuff.
>leading to muscle
> weakness and atrophy followed by paralysis and death. While most cases are
> sporadic, 5-10% are familial (FALS). A breakthrough came ... SOD1. ...
> Kostic et al crossed transgenic mice overexpressing BCL-2 neurons with mice
> carrying the FALS SOD1 mutation. BCL-2 was effective at delaying the onset
> of the disease, thus increasing lifespan of themice by about 19%; however,
> once symptoms appeared, progression to paralysis and death remained
> unchanged. BCL-2 delayed both the loss of motor neurons and theincrease in
> expression oftyhe early markers of cell injury, c-Jun and ubiquitin. ... "
from the perspect of the hypothesis i've been discussing, i expect that
what the adminstered agents are doing is augmenting the neurons'
abilities to cope with 'excito-toxic' conditions that're generated by
the decrease of type II synchronization.
what's actually needed is a tracking-doen of the 'lesion' through which
the interminable TD E/I(up) condition is being interjected into the
supersystem, and fixing things at the 'lesion' site.
of course, if, contrry to the hypothesis i've been discussing, the
'lesion' is, in fact, a genetic 'lesion' that's distributed theougout
the supersystem, then it seems that the only way to possibly attack the
'lesion' would be through globally-distributed chemo approach, with
respect to which, i'm out of my depth.
it's just that it doesn't seem to be globally-distributed because
sensory fx is unaffected. and, on the motor side, things are obviously
'chained', with both feedback and feed-forward dynamics, so the
possibility of finding a low-'level', relatively-'discrete' TD E/I(up)
interjecting site, at which dysfunction can be 'fixed', is real.
k. p. collins
kenneth Collins
as this.
(of course, the same 'naivete' is a 'double-edged-sword' that exposes me
to having to 'learn the hard way'. but i've got my 'shovel', and am
willing to 'shovel' whatever it is that needs 'shoveling :-)
ken
dag.st...@helsinki.nospam.fi wrote:
>
> kenneth Collins <kpa...@earthlink.net> wrote:
kenneth Collins
>[...]
> it's in the hypothesis that the p[re]cipitation 'lesion' acts through the
> modification of 'normal[ly]' integrated dynamics. in the example offered
> with the hypothesis, a lesion alters the information-processing of the
> cerebellum (which, in NDT, is a powerful 'passive', globally-acting, TD
> E/I-minimization mechanism; see AoK, Ap5).
>
> one must put-things-together. the lesion alters cerebellar function,
> which results in abnormal motor-system dynamics, because, the
> interminable TD E/I(up) condition that the lesion interjects prevents
> normal achievment of 'type II synchronization" (as evidence[d] in ALS
> fasciculations and fibrilations.
>[...]
> it's important to be aware that, in the above dynamics, the supersystem
> is 'just' 'striving', in 'normal' ways, to achieve TD E/I(min). it's
> be-cause the lesioned tissue interjects 'perpetually-random',
> non-minimizable activation into the TD E/I-minimization dynamics that
> the 'normal' TD E/I-minimization dynamics generate the hyper-stressing
> 'struggle' to achieve type II synchronization back upon the motor
> neurons, which constitutes an 'excito-toxic' condition with respect to
> the motor neurons' metabolic functioning, which kills them, resulting in
what, in the traditional approach have been considered to 'constitute'
> the =obvious= [']disease['] observables that have been focussed upon,
> while the more-subtle, more-globally-occurring, and much-more-significant
=actual=
> disease-generating stuff had gone unrecognized.
i repeat, i'm taking this position in this hypothesis because all of the
so-called 'indicators' that i've read of can result from excitotoxic
activation, which means that it's possible that the 'indicators' are
nothing of the kind, but 'only' by-products of a
more-globally-correlated set of dynamics, such as those that i've been
discussing in this hypothesis.
'fixing' what is not broken only augments dysfunction.
it appears, to me, that such is the case with respect to the traditional
aproach to these motor-neuron degeneration diseases.
forgive me. if it, in fact, is so, it's =solely= be-cause NDT's
understanding has been Censored, even while 'profit'-seekers have been
rampantly 'borrowing' bits and pieces of NTD (which it's, now, become
apparent to me, that True significance of which is not comprehended, and
so what's been 'borrowed' can have only been ab-used).
these Treacherously-Predatory dynamics, which 'exist' where only Truth
has a Right to Exist, must be at an end.
it's not in my purpose to be 'overly-critical', but the circumstances of
NDT's Censorship are unthinkably-offensive to all of Humanity, and the
'Difficult' thing =must= be said.
the Censorship of NDT's understanding =must= be at an end.
K. P. Collins
dag.st...@helsinki.nospam.fi
kenneth Collins <kpa...@earthlink.net> wrote:
(about long lines)
> the lines were still very-long after i posted the reformatted msg. (in
> the future, if a msg appears with HTML formatting, if it is saved as a
> '.HTM' file, it can, then, be read in a web browser, and 'saved' as a
> text file, which will (at least in some browsers and word processors)
> eliminate the HTML format characters.)
Well, I would have to press s(save) in my unix newsreader to save the
message, then switch to ftp and get the file to my PC, then open the web
browser... lot of trouble (don't normally use browser for news, tin is
more practical and does not open possible virus-infected files
automagically).
Dag Stenberg
dag.st...@helsinki.nospam.fi
> > > >> the Hypothesis:
> > I had not earlier been able to find this among the over-long lines.
> my fault, as explained at the top of this post. i apologize for the
> unnecessary difficulty my failure imposed upon you.
No worries about the difficulty, but the fact was that I never saw that
there was a hypothesis, because the entire message consisted of three
or four superlines...
> one must put-things-together. the lesion alters cerebellar function,
> which results in abnormal motor-system dynamics,
Please, do not even try to explain the pathology in ALS through the
cerebellum. It does not work, lower motor symptoms could NOT occur that
way.
> because, the
> interminable TD E/I(up) condition that the lesion interjects prevents
> normal achievment of 'type II synchronization" (as evidences in ALS
> fasciculations and fibrilations.
Can't see that. The fasciculations and fibrillations are not due to
disturbed coordination, but to denervation, which dissolves the motor
units plus induces muscle membrane hypersensitivity. The spasticity is
another thing altogether.
> the late onset of respiratory functionality ...
The pathology seems to ascend in a rostral direction. Your explanation
is too complicated, and all of it, illustrated by the citation below,
seems totally hopelessly untrue.
> in other words, the demise of the motor neurons results in an =actual=
> 're-engineering of the neural topology of the brain stem, and, as a
> result, the relationship between the respiratory nucs of the brain stem
> with respect to TD E/I-minimization becomes rewired, and what remains of
> the supersystem 'blindly' 'seeks-out', and 'attacks' the 'normal'
> respiratory functionality as a TD E/I(up)-condition, which results in
> the aberrant 'shutting-down of respiratory functionality.
> > How would you diagnose the disease 35+ years before outbreak?
> =iff= there's anything to the hypothesis that i've been discussing,
> contemporary 'scanning' methods would disclose the aberrant TD
> E/I-minimization 'struggle', through which, what has been considered to
> be the disease condition, is generated (precipitated). and sensitive
> versions of those scanning methods should be able disclose the TD
> E/I(up)-generating 'lesion' location. of course, all such work can only
> occur with respect to deviations from a background database that tracks
> 'normal' (average) activation 'states'. building this
> background-comparison database would, itself, be a major undertaking,
> but would definitely, itself, become o font of useful insight.
Yeah, you earlier asked for a scanning method do discriminate excitatory
from inhibitory activity. We are not there yet. Actually imaging
techniques do not seem to be moving in that direction at all. I have
been impressed lately by proton imaging of lactic acid accumulation, but
even that does not take us anywhere in a TD I/E direction.
> so, in it, i've kept my word about advancing the Science.
Er - I think that is still a very premature conclusion, sorry.
As I mentioned some time last year, I had a boss who had a all-encompassing
'neurodarwinist' theory (not Edelman, who also proposed another neurodarwinist
theory). Unfortunately, all my former boss's theorizing has never advanced
science at all, whereas actual measuring has during the same decades
advanced neuroscience hugely.
Dag Stenberg
dag.st...@helsinki.nospam.fi
> .... even while 'profit'-seekers have been
> rampantly 'borrowing' bits and pieces of NTD (which it's, now, become
> apparent to me, that True significance of which is not comprehended, and
> so what's been 'borrowed' can have only been ab-used).
I do not really believe a word of that profit-seeker stuff and the
borrowing stuff. I call for an ablution of that delusion.
Dag Stenberg
dag.st...@helsinki.nospam.fi
> of course, if, contrary to the hypothesis i've been discussing, the
> 'lesion' is, in fact, a genetic 'lesion' that's distributed theougout
> the supersystem, then it seems that the only way to possibly attack the
> 'lesion' would be through globally-distributed chemo approach, with
> respect to which, i'm out of my depth.
> it's just that it doesn't seem to be globally-distributed because
> sensory fx is unaffected.
A genetic lesion can be in all cells and still be expressed only in a
subsystem (target tissue, cell type or whatever). There has to be some
coincidence (like something specific to motor neurons that makes the
global lesion activate in them only).
Dag Stenberg
John H.
<dag.st...@helsinki.nospam.fi> wrote in message
news:8766kn$bad$1...@oravannahka.helsinki.fi...
> kenneth Collins <kpa...@earthlink.net> wrote:
> > i've reformatted my prior post to make online reading easier.
>
>
> I think that (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
>
> > problem represented by the 'late onset' of the disease conditions, which
> > needs explication. if, in accord with the traditional view, it actually
> > is the case that a single DNA mutation results it the entirety of the
> > disease condition(s), then why is it that the stuff of that mutation is
> > activated in such a delayed way?
Cancer.
> For comparison: in prion diseases, it takes times for anomalous PrP to
> develop and for deposits to accumulate.
>
> > >> i relied on the discussion of ALS in Kandel, et. al. for my
> > >> start. the factors that i found significant are as follows.
>
> > >> the Hypothesis:
>
> I had not earlier been able to find this among the over-long lines.
>
> > >> the demyelination results from a specific brain stem lesion,
> > >> of a type analogous to the chemically-induced vestibular
> > >> lesion, or a stroke-induced lesion.
> > >> ...
>
> I do not see any explanation for the fact that brain stem symptoms are
> usually later in appearance than limb involvement. It also seems to
> neglect observable peripheral pathology.
>
> > >> there are other attractive rationales for this sort of
> > >> hypothesis. the problem of the 35+ years typical onset of
> > >> ALS has to be explained. if there's a genetic flaw, then how
> > >> is it that it shows itself only after 35+ years? what's the
> > >> 'switch' that changes fully-functional motor neurons to
> > >> dysfunctional 'motor' neurons?
>
> Interesting question, no doubt.
Remember Huntingtons, 45 copies or repeats and away it goes, but that takes
until middle age, although non symptomatic pathology is present for quite a
while. I don't see these things as turn on\turn off objects. There is a
battle going on here but time gives pathology the inevitable edge. The
question of late onset does not concern me too much. I suppose my view is
that the brain begins with a head start (literally) but time eventually
takes its toll. Live long enough and we'll all be fascinated by Teletubbies.
>
> > if this sort of thing occurs, then the disease is treatable through
> > methods that eliminate the functionality of the newly-triggered stuff,
> How would you diagnose the disease 35+ years before outbreak?
> > at any rate, an explanation for the observed delayed onsets of
> > Alzheimer's, ALS and Huntington's is necessary, and it will probably be
> > the case that, when such delayed onset is explained, treatment
> > strategies will become apparent within such explanation. so explication
> > of the delayed onset is an important problem.
>
> > >> the one criterion that =must= be met in order to explore
> > >> this hypothesis further is, since the ocular motor system is
> > >> not affected in ALS, to culture examples of ocular motor
> > >> neurons along with examples of upper and lower motor
> > >> neurons, and look for differences that would allow the
> > >> ocular motor neurons to survive while the upper/lower motor
> > >> neurons would not survive.
>
> This seems to me a profitable approach. Objections, anyone?
Thanks Ken, I wasn't aware of this. Another item for the database. Can you
ref?
The differences you may need to find could take forever. Interesting idea
though. Practically I have no idea if the two cell types can be in suitably
similiar cultures and even if possible the setup may mitigate the benefits.
The problem may lie outside the cells. Transporters? It may not be anything
specific deficit, a subtle allele that tips the balance, this or that
doesn't work so well over time and it's just going downhill faster. The
brain is a chaos fighter, but some brains just can't win against some chaos.
I can't see any switches, I'm running with James Clerk Maxwell on this one,
"The laws of probability is the true logic of nature."
Need to know exactly where the ocular muscles receive innervation. Eg. v.
close to eyeball, on or very close to its surface. Perhaps the ocular
nerves, being that close to the CNS, receive a relatively rich supply of NGF
or acetycholine, thus prolonging their life. Perhaps very late in ALS there
is motor ocular pathology. (help with neuroanatomy!)
Vaguely, remember reading something about eyes being "immune privileged".
Not sure what that means and know it refers to inside the eyeball, but I do
wonder if it may be relevant.
> > i repeat, i'm taking this position in this hypothesis because all of the
> > so-called 'indicators' that i've read of can result from excitotoxic
> > activation, which means that it's possible that the 'indicators' are
> > nothing of the kind, but 'only' by-products of a
> > more-globally-correlated set of dynamics, such as those that i've been
> > discussing in this hypothesis.
I'm not sure that AD is a result of excitotoxic activation. I am much more
inclined to think of each pathology specifically, from what I've seen lately
the exact opposite can also initiate cell death: excito nothing. Nerves
cells need innervation. The middle way?
John.
> Logical. Not necessarily true, but logical.
>
> > anyway, that's my contribution(?) to the efforts to extinguish these
> > diseases. i could do more, but despite the fact that i've done this
> > stuff at my own expense, i've only been 'ridiculed' for having tried
>
> I think this (descrambled) hypothesis is quite worth to read. It may be
> way off road, but at least the details and reasoning deserve thinking
> about.
>
> Dag Stenberg
kenneth Collins
> > rampantly 'borrowing' bits and pieces of NTD (which it's, now, become
> > apparent to me, that True significance of which is not comprehended, and
> > so what's been 'borrowed' can have only been ab-used).
>
> I do not really believe a word of that profit-seeker stuff and the
> borrowing stuff. I call for an ablution of that delusion.
there's much more to the 'profit'-seeking stuff than i've allowed myself
to discuss online. it, in fact, involves primarily fields of 'endeavor'
that are not the province of this NG.
there's no 'delusion'. i can =Demonstrate= the actuality inherent in the
stuff i address, but, because of the Ethics to which i adhere, am bound
to 'hold open the door', and the only way that i can foresee in which a
complete account of all that's entailed will be delivered is if i'm
forced to take an Oath in Court of Law.
however, it's becoming clear to me that one result of my trying to 'hold
the door open' is that folks who've been Victimized by the efforts to
Censor NDT's stuff have considered my 'cryptic' comments to be directed
'at them'. this is not the case.
folks in Neuroscience do not have access to NDT's understanding because
the understanding has been deliberately withheld from them through the
actions of folks who've sought to 'profit' from the understanding, and
to protect their abilities to 'profit' from the understanding by
actively withholding the understanding from others, including
Neuroscience Professionals.
K. P. COllins
kenneth Collins
>[...]
> the MD-80 plane crash yesterday. the stabilizer problem is analogous to
> the nervous system 'lesion'. the pilots tried desperately to correct for
> the malfunction induced by the stabilizer failure, but because the
> failure of the stabilizer =separated= the stabilizer's functionality
> from the rest of the plane's controlable dynamics, the efforts of the
> pilots 'only' led to the deterioration of the functionality of the
> remaining control systems.
>
> [an asside TO THE AVIATION AUTHORITIES: i've been analyzing plane crash
> dynamics for years, and have converged upon a 'core' set of things that
> might be of some use with respect to in-flight failure. this analysis
> focusses upon the alterations of flight configurations that 'surround'
> the instances of failure (such as this stabilizer failure). the
> underpinning rationale derives in the fact that it's relatively-obvious
> that in-flight reconfiguration, probably most-significantly power-down,
> as was apparently the case with this MD-80 yesterday, is a
> failure-precipitation factor. so, it =might= be possible, in some
> instances of in-flight failure, to 'reverse' the failure by reversing
> the in-flight reconfiguration. if the failure was precipitated by
> power-down, then power-up. of course, if there's a mechanical failure
> that 'locks-up' control mechanisms, it can be the case that reversing
> the failure-precipitating flight reconfiguration will be to no avail.
> but since these events are so catostrophic, why not explore the
> possibility, which is sort of like 'kicking a fender', while one's
> riding one's bike, to get the fender to stop rubbing on the tire. of
> course, reversing a power-down leaves the plane powered-up, which
> creates landing problems. these could be addressed via a carrier-type
> arresting apparatus that replaces the cable and hook with a net that's
> activated during landing emergencies. this setup would allow planes to
> touch-down at full-power, maximizing the functionality of control
> systems that remain effective. (before such safety apparatus could be
> installed, if reversing the failure-precipitating dynamics works, it
> would, at least, allow pilots to fly and 'ditch' closer to rescue.) i
> =understand= that this discussion, itself, has a lot of possible
> points-of-failure, but trying anything is better than 'abandoning' folks
> in the air, no? so why not, at least, explore the possibility of doing
> the 'reverse' thing? if it works, train pilots to attempt it when all
> else fails. sorry about having do do this, here. it's a long-shot, but
> it is a possibility, so i had to put it 'out-there' so that Engineers,
> and other folks responsible for flight safety, can consider it, explore,
> implement/reject it.]
of course, by 'full-power landing', i meant =until= the point of contact
with the ground. then, do everything possible to decrease the plane's
inertia. the whole idea of this, in and of itself, highly-undesireable
condition is to maintain some semblance of 'stable' in-flight trim after
flight-control 'failure'. (i understand that commercial aircraft are not
designed to handle the stress of such landings. but there's runway foam,
and the possibility of the proposed arresting apparatus, =iff= the
'disabled' aircraft can maintain sufficient flight trim to make it to a
landing site.
the control-surface failures are more like a consequence of an
overly-forceful, or overly-rapid in-flight system reconfiguration, which
is more like instances in which a bicycle's too-loose chain falls off
it's sprockets when one rides through a pot hole.
it's a bit 'alarming' to see it, but if in-flight reconfiguration is
done in less-'violent' ways, that would decrease the possibility of a
weakened control element's failure.
one routinely experiences the correlates of such in-flight
reconfigurations with respect to take-off's, take-off/level-flight
transitions, level-flight/landing transitions, and landings. there must
be some routinely-invoked rationale for such rapid flight-control
reconfigurations (perhaps less-rapid transitions are susceptible to
'instability'?), and that rationale would have to be weighed against the
opposing rationale of routinely minimizing stress on aircraft components
through more-gradual in-flight control reconfigurations.
what i'm talking about is the in-flight equivalent of riding one's
bicycle through a pot hole =gently= so that it's too-loose chain will
not be jarred into a disconnected-from-the-sprocket configuration.
in the in-flight circumstance, for the 'reversal' of the precipitating
conditions view that i wrote of earlier (quoted above) to be effective,
the pilots would have to have a keen sense for their aircrafts'
control-surface feedback, and 'reverse' the reconfiguration dynamics
=quickly= if it's to be successful.
i don't know whether such feed-back 'time' is, in fact, available. in
the case of a stabilizer, for instance, it's a long way from it to the
cockpit. feedback devices could be engineered into new aircraft designs
(at a cost of the added weight and flight-system complexity).
that's why, upon arising this morning, the strategy of =gentle=
control-surface reconfigurations, routinely applied, seems to be a
better overall strategy.
gentle transitions would also significantly increase the comfort
inherent in passengers' flight experiences, even as it minimized
in-flight wear-and-tear on the aircraft.
so, if, over the life times of commercial aircraft, all such transitions
were done more-gradually (less-forcefully), that would also tend to
lengthen the life-'times' of the control elements that are routinely
reconfigured.
which, all things considered, seems extremely-desirable, because control
components' receiving less mechanical stress last longer.
which reminds me of the rationale with which Jackie Stewart raced. he
won a =lot= of races, with his mind set on preserving the structural
integrity of his vehicle through the minimization of routine
acceleration and braking, etc., operations, and by driving a 'smooth'
line.
anyway, i wanted to address this stuff because there are obviously some
easy adjustments that, if applied, can make flying safer for all.
seeing such, there's Obligation, which i've fulfilled in these msgs.
ken (k. p. collins)
>[...]
kenneth Collins
kenneth Collins wrote:
>[...]
> which reminds me of the rationale with which Jackie Stewart raced. he
> won a =lot= of races, with his mind set on preserving the structural
> integrity of his vehicle through the minimization of
the 'violence' inherent in
> routine acceleration[, shifting] and braking, etc., operations, and by
> driving a 'smooth' line.
a race car driver doesn't win many races by 'minimizing acceleration'
:-)
if it seems that i do a lot of this sort of 'skipping' words, take that
as a measure of the Brutality of the 'solitary confinement' into which i
was long-ago cast.
within my solitude, i've no use for verbal symbols, and only invoke
'words' when i 'translate' out of the mode in which i think, when
describing this or that for others.
anyway, i've considered further, and this 'being gentle' in flight
transitions, while a =good= practice, would, because of the increased
aircraft longevity that would follow from it, probably 'just' result in
even more laxity with respect to aircraft maintenance.
so, in the end, thorough maintenance, by folks who realize that their
work is what carries folks in the air, is the necessary thing.
it's the same in Neuroscience (and everything else). if folks don't care
about doing their work all-the-way, then folks who could've, otherwise
benefitted, 'crash-and-burn', instead.
it's always seemed extraordinarily-non-sensical when i witness such, no
matter what's involved.
it's a 'big-gamble', in which folks 'climb on each others' backs',
trying to not be the one whose 'butt-hits-the-floor' when 'the music
stops', when all that's necessary is for folks to care about their
contributions to "the music's" enduring without fail.
"Whoops!"
ken
kenneth Collins
the 'ALS' hypothesis that i've discussed has been in AoK, and the refs
cited in AoK, all along.
some of it, such as the schwan cell 'adjustments' of node of Ranvier
stuff, is 'implicit', though (in this case, in NDT's glial position,
which is in AoK).
AoK was written as an integrating 'overlay' with respect to the
traditional literature.
it's why it's been so 'heart'-breaking that AoK has been Censored. it's
integration of everything makes a =lot= of stuff relatively
straight-forward. (there's no way around coming to terms with the
details of the Neuroanatomy, however.)
i had to 'smile' as this 'ALS' hypothesis developed, because one of the
routine strategies that i used while developing NDT was to do
"thought-lesions" to the neural architecture, and 'watch' (literally)
the altered neural activation that happened as a result.
it's why the hypothesis came together so quickly (it was as it's been
presented when i posted the msg citing its "80%-verified" status, which
was early-on).
seems i had an "examples database" after all. developed it while
developing NDT, but never applied it to 'disease' conditions because i
"didn't think i could contribute" anything with respect to 'disease'
conditions.
anyway, NDT (at the 'level' of AoK) allows the same thing to be done
with respect to lesions anywhere in the CNS.
it's why the theory is useful.
other matter: i'm not certain yet, but because i've still not found
employment, i might extend my ISP agreement so that i can have an online
presence with respect to finding employment.
ken (k. p. collins)
kenneth Collins
the possibility of doing the reverse of the in-flight reconfiguration
that precipitated the failure should still be explored.
'kick that fender'.
ken
Arthur T. Murray
>> the MD-80 plane crash yesterday. the stabilizer problem is analogous to
>> the nervous system 'lesion'. the pilots tried desperately to correct for
>> the malfunction induced by the stabilizer failure, but because the
>> failure of the stabilizer =separated= the stabilizer's functionality
>> from the rest of the plane's controlable dynamics, the efforts of the
>> pilots 'only' led to the deterioration of the functionality of the
>> remaining control systems.
The following may be a dumb and naive question, and may have already
been asked, but:
Could the Alaska Airline pilots have saved the aircraft by asking
all the passengers to walk to the back of the cabin, thus, by their
body weight, forcing down the tail area which had been elevated by
a jammed stabilizer wing? Would the weight of 88 passengers and crew
have been enough to level out the flight of the airplane?
A hideous thought because it is in hindsight, but, might it have worked?
--
http://www.geocities.com/Athens/Agora/7256/mind4th.html PD AI
kenneth Collins
vertical axis, but only in an extremely-loosely-'coupled' way.
unless stuff is attached to the airframe, it's pretty-much like liquid
in a bottle, and tends to destabilize because it has its own inertia
that doesn't cooperate with the airframe, and actually damps flight
control inputs.
it's why the 'fasten your seatbelts' light comes on during demanding
flight operations.
one-'language' ken
kenneth Collins
>
> there's the possibility of contributing to dynamics with respect to the
> vertical axis, but only in an extremely-loosely-'coupled' way.
>
> unless stuff is attached to the airframe, it's pretty-much like liquid
> in a bottle, and tends to destabilize because it has its own inertia
> that doesn't cooperate with the airframe, and actually damps flight
> control inputs.
>
> it's why the 'fasten your seatbelts' light comes on during demanding
> flight operations.
that is, the primary (and almost only) purpose of 'seat belting' folks
is to 'attach' them to the airframe, and prevent their
would-otherwise-be-uncoupled inertia from mucking-up an aircraft's trim.
seat belts are a safety factor, but almost wholly with respect to the
aircraft's trim, which means that seatbelts are actually for the plane's
dynamics (upon which everyone's survival depends), not passengers.
kenneth Collins
kenneth Collins wrote:
>[...]
> that is, the primary (and almost only) purpose of 'seat belting' folks
> is to 'attach' them to the airframe, and prevent their
> would-otherwise-be-uncoupled inertia from mucking-up an aircraft's trim.
>
> seat belts are a safety factor, but almost wholly with respect to the
> aircraft's trim, which means that seatbelts are actually for the plane's
> dynamics (upon which everyone's survival depends), not passengers.
forgot about in-flight turbulence, with respect to which, seatbelts come
in right-handy with respect to keeping one's noggin away from the hard
stuff. same with hard landings, and aborted take-offs.
ken
Hugh Dickson
Arthur T. Murray wrote:
> Somebody wrote in bionet.neuroscience (of all places!):
>
> >> the MD-80 plane crash yesterday. the stabilizer problem is analogous to
> >> the nervous system 'lesion'. the pilots tried desperately to correct for
> >> the malfunction induced by the stabilizer failure, but because the
> >> failure of the stabilizer =separated= the stabilizer's functionality
> >> from the rest of the plane's controlable dynamics, the efforts of the
> >> pilots 'only' led to the deterioration of the functionality of the
> >> remaining control systems.
>
> The following may be a dumb and naive question, and may have already
> been asked, but:
>
> Could the Alaska Airline pilots have saved the aircraft by asking
> all the passengers to walk to the back of the cabin, thus, by their
> body weight, forcing down the tail area which had been elevated by
> a jammed stabilizer wing? Would the weight of 88 passengers and crew
> have been enough to level out the flight of the airplane?
>
> A hideous thought because it is in hindsight, but, might it have worked?
>
>
Aloha, Only time I know of that pax were used to change
CG during an emergency was Pan Am, B-747, SFO, very early 70s.
Hugh
Andrew K Fletcher
found in neurological conditions. In laypersons terms preferably.
Regards
Andrew
kenneth Collins <kpa...@earthlink.net> wrote in message
news:389453C7...@earthlink.net...
> kenneth Collins wrote:
Bill Skaggs
> Has anyone any knowledge of the make up of the scar tissue in the plaques
> found in neurological conditions. In laypersons terms preferably.
The plaques seen in Alzheimer's Disease are made of a substance called
amyloid, which is a fragment of a protein called, straightforwardly
enough, amyloid precursor protein or APP. (I'm sorry, there is no
layperson's term for "amyloid".)
-- Bill
Andrew K Fletcher
What I am looking for is to see if the "amyloid precursor protein or APP" is
part of solidified myelin and cerebrospinal fluid. If the make up is the
same it might lead to understanding how these plaques develop. For example,
a scab results from blood, so presumably it must have the same compound base
as blood.
I don't know who to approach with this, perhaps you might be able to suggest
an avenue.
Kind regards
Andrew
Bill Skaggs <ska...@bns.pitt.edu> wrote in message
news:m7zotdz...@skaggs.bns.pitt.edu...
Bill Skaggs
> Hi Bill, thank you for your reply.
>
> What I am looking for is to see if the "amyloid precursor protein or APP" is
> part of solidified myelin and cerebrospinal fluid. If the make up is the
> same it might lead to understanding how these plaques develop. For example,
> a scab results from blood, so presumably it must have the same compound base
> as blood.
>
Sorry, amyloid does not have anything to do with myelin or
cerebrospinal fluid -- it forms inside nerve cells, but myelin is
formed by a different type of cell in the brain.
For a lot of useful information about Alzheimers, mainly for patients
and laymen, you could take a look at some of the links at:
http://www.alzforum.org/public/general_dir/news_info.html
-- Bill
John H.
9/02/00 0:06
Somewhere amongst all this Ken raised the idea of searching for something
specific about the death of motoneurons. While not specifically addressing
his question, the paper below touches on this matter in another way
The Journal of Neuroscience, January 1, 1998, 18(1):104-111
Motoneuron Apoptosis Is Blocked by CEP-1347 (KT 7515), a Novel
Inhibitor of the JNK Signaling Pathway
Anna C. Maroney,1 Marcie A. Glicksman,1 Alie N. Basma,1 Kevin M. Walton,1
Ernest Knight Jr,1
Carol A. Murphy,1 Becky A. Bartlett,1 James P. Finn,1 Thelma Angeles,1
Yuzuru Matsuda,2 Nicola T. Neff,1 and
Craig A. Dionne 1
Abstract:
"Neurons undergoing apoptosis can be rescued by trophic fac-tors that
simultaneously increase the activity of extracellular signal-regulated
kinase (ERK) and decrease c-Jun N-terminal kinase (JNK) and p38. We
identified a molecule, CEP-1347 (KT7515), that rescues motoneurons
undergoing apoptosis and investigated its effect on ERK1 and JNK1 activity.
Cultured rat embryonic motoneurons, in the absence of trophic factor, be-gan
to die 24-48 hr after plating. During the first 24 hr ERK1 activity was
unchanged, whereas JNK1 activity increased four-fold. CEP-1347 completely
rescued motoneurons for at least 72 hr with an EC50 of 20 6 2 nM. CEP-1347
did not alter ERK1 activity but rapidly inhibited JNK1 activation. The IC50
of CEP-1347 for JNK1 activation was the same as the EC50 for mo-toneuron
survival. Inhibition of JNK1 activation by CEP-1347 was not selective to
motoneurons. CEP-1347 also inhibited JNK1 activity in Cos7 cells under
conditions of ultraviolet irra-diation, osmotic shock, and inhibition of
glycosylation. Inhibi-tion by CEP-1347 of the JNK1 signaling pathway
appeared to be selective, because CEP-1347 did not inhibit p38-regulated
mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP2)
activity in Cos7 cells subjected to osmotic shock. The direct molecular
target of CEP-1347 was not JNK1, be-cause CEP-1347 did not inhibit JNK1
activity in Cos7 cells cotransfected with MEKK1 and JNK1 cDNA constructs.
This is the first demonstration of a small organic molecule that pro-motes
motoneuron survival and that simultaneously inhibits the JNK1 signaling
cascade. Key words: motoneurons; indolocarbazole; CEP-1347; sur-vival;
apoptosis; c-Jun N-terminal kinase; mitogen-activated protein kinase; p38"
Quick extracts
"In an effort to identify small molecules that promote neuronal survival, we
selected CEP-1347, also known as KT7515, for its ability to induce choline
acetyl transferase (ChAT) activity in cultures prepared from embryonic
spinal cord and basal forebrain tissue (Kaneko et al., 1997)."
------
"The morphology of motoneuron cultures was assessed in the presence of
CEP-1347. In contrast to control cultures that rapidly underwent neurite
retraction and cellular fragmentation, those cells treated with CEP-1347
displayed a flattened cell body mor-phology with extensive neuritic
processes for at least 5 d (Fig. 3a,b). To determine whether cells in
control cultures were dying by apoptosis, we examined chromatin condensation
by staining the DNA with fluorescent Hoechst dye. By 48 hr a significant
proportion of untreated motoneurons exhibited clear hallmarks of chromatin
condensation, consistent with a previous report that cultures of enriched
motoneurons in the absence of neurotrophic factors die in an apoptotic
manner (Fig. 3c) (Comella et al., 1994; Milligan et al., 1994). In contrast,
CEP-1347-treated cultures exhibited diff use nuclear staining, consistent
with the survival activity detected by the calcein assay (Fig. 3d)."
Acetylcholine promoting survival??? This protective effect is selective, but
neurons other than motoneurons are involved. Good guess John.
Now Ken, do you know if the ocular motoneurons are always saved or just take
longer to die?
Thanks,
John.
kenneth Collins <kpa...@earthlink.net> wrote in message
news:3897A68B...@earthlink.net...
> of course, if, contrry to the hypothesis i've been discussing, the
> 'lesion' is, in fact, a genetic 'lesion' that's distributed theougout
> the supersystem, then it seems that the only way to possibly attack the
> 'lesion' would be through globally-distributed chemo approach, with
> respect to which, i'm out of my depth.
>
> it's just that it doesn't seem to be globally-distributed because