Goa iMAMarry randall man man TAR baby - CP-690550 = Tasocitinib - Jak STAT & (ER)= (endoplasmic reticulum) pathWHEYs -- NAC-->Glutathione redux
randall
Susan,
I'm not hate filled, i'm a MAD MAN fan...
So i'm getting prepared last night at 10:00pm for my MAD MAN fix and
it's not here or there?
LAST week they said this week was the finale?
Or so i thought....
What will madmenmaniacs do NOW?
Wait for the next season?
Right.
Or become a madison av man and walk around like don draPPer?
Nah.. sounds to creeePy.
http://www.nytimes.com/2010/10/25/business/media/25adco.html?src=busln
What the heck is zeta buzz from zetainteractive?
Do i have to twitter to get it?
What about the sex factors?
I only hope and pray they do a glee type shot with don draPer's X
splashed on
some steamy COVER.
But will i even LOOK?
Let's make BOOK?
With Susan?
OK.... i sorta droPPed her last attemPPPPt to .....
I can argue the nature of hatred and how democrats use it so
successfully?
But if i was an iman and she was a girl in a burPa in the back of the
womb and she
said i was a hate filled cannelloni would she last HOW LONG before the
boys stoned her to within a fraction of HER hate filled life? LOL
Whoops i meant room. As those rooms don't allow wombs in them when
the men are in charge and that imam rules the roost. But would i be a
shia or sunni imamanista?
Gosh maybe islame is better then what the west was tricked in to by
those greeks?
Oh wait... their doomed to our fate:
(Sadia Imam) Ary Drama " Chubhan " - Title Song
http://www.youtube.com/watch?v=_tTMjuaDFLw
If Sadia's DAD doesn't ban the boys and put her in a burka 24/7 the
poopulation explosion in the eAST will Go nuclear. LOL
Doesn't middle eastern DAD know that Girls just wanna have FUN?
As to women in the media in the WEST which isn't BEST anymore?
Moralistical quizzicalist katie couric going hyperbolated over glee
nudie cutie shots, what can we expect for mad men? LOL
Brings up even more odd i ties no doubt?
How did tar baby randall get his sweet monkier?
Easy... LONG long ago in a weird land they gave this TAR toPical drug
to little psor heads.
And when their friends smelled the TAR they said, yuck. YOU smell BAD.
Which made little psor folks SAD.
In other lands they gave them GOA stuff..
TAR is TAR from now or FAR far away times...
But nothing changes under the sun?
http://en.wikipedia.org/wiki/Dithranol
[...] Dithranol accumulates in mitochondria where it interferes with
the supply of energy to the cell, probably by the oxidation of
dithranol releasing free radicals.
http://en.wikipedia.org/wiki/Anthracene
Tree resin or GOA powder
http://en.wikipedia.org/wiki/Araroba_powder
[...] The general practice amongst modern dermatologists is to use
only chrysophanic acid, which may be applied externally and given by
the mouth in doses of about one grain in cases of psoriasis and
chronic eczema
<snip>
It's a pretty tree (Andira Araroba ):
http://en.wikipedia.org/wiki/File:Andira_humilis.jpg
On pubmed, anthralin alone gets 1009 hits - pubmed: (667 have the
kicker psoriasis term)
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=anthralin
21 hits for anthralin mitochondria - pubmed
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=anthralin+mitochondria
As if it matters. No pharma gives a rats arse about this stuff. Duh,
21 hits, that's pathetic.
No it isn't randall mammary tar head.....
Pharma is made up of MAD MEN and their ADs need the BIG bucks to
pay for the research to turn GOa in to a mitochondrial lock and key
whiz
drug.....
So eat dung randall tar beetle baby...
OK if i was a worm i'd eat it all day long. LOL
I'd do it in the oval ovoid with my worm buds.... :)
Soros are you out there?
Come home george i'll do what you want to make a trillion bucks.
That's easy, just like in germany after the war...
Oh, oh i saw Flame and Citron and GOOD.
Good was GREAT:
Professor John Halder (Viggo Mortensen) has a lot on his plate -- a
neurotic wife, two small children and a mother suffering from dementia
-- in this drama set in World War II Germany. But his life changes
after he writes a book promoting compassionate euthanasia. When the
Nazi party embraces his ideas, Halder faces a series of subtle ethical
choices that gradually compromise his morality and his relationships.
More then a warning for ALL HUMANs.... no doubt. xlnt film...about
hate and
love and the grey area between them.
OK back to GOA and TAR land...
But it does work:
http://www.ncbi.nlm.nih.gov/pubmed/15802490
Really... how primitive.
Just for big pharma to make a BUCK..
Really?
Their still using this tar preparation and it's not preparation H is
it?
No, no prep- H is a steroid drug and a susan hpa-axis thingy. LOL
http://www.ncbi.nlm.nih.gov/pubmed/20967195
J Clin Aesthet Dermatol. 2010 Oct;3(10):42-5.
Coal tar 2% foam in combination with a superpotent corticosteroid foam
for plaque psoriasis: case report and clinical implications.
Frankel AJ, Zeichner JA, Del Rosso JQ.
Abstract
Psoriasis is a chronic, inflammatory, immune-mediated, multi-system
disease that is treated with a variety of medicines, including topical
corticosteroids and, historically, coal tar. In this case, the authors
evaluated whether combination therapy with coal tar foam 2% and a
topical corticosteroid would induce a remission and maintain clearance
of plaque-type psoriasis over an eight-week period. A 59-year-old
Caucasian woman with plaque psoriasis of her elbows presented to the
authors' dermatology clinic and was treated with clobetasol propionate
0.05% emollient foam in combination with coal tar 2% foam twice daily
to her elbows for two weeks. After two weeks, the patient was switched
to a maintenance regimen of twice-daily coal tar 2% foam during the
week and twice-daily application of the corticosteroid on the
weekends. The patient exhibited very favorable clearance of her plaque
psoriasis on this regimen at her eight-week follow-up visit. In this
case, the combination of coal tar 2% foam and clobetasol propionate
0.05% emollient foam twice daily was used effectively to induce
remission of localized plaque psoriasis followed by an efficacious
maintenance regimen, which incorporated intermittent therapy with both
topical agents.
PMID: 20967195
COAL TAR gets 2,550 hits in the P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=coal+tar
According to the first one it's better then sex?
Oh come ON.... for most of your gals having clear skin over sex would
be like a 1,000 times better. LOL... hey i'm only telling the truth?
And once past mentalpause quite possibly a million billion zillion
times better? <w>
Oh come on now randall...
Your being a little tar baby again perhaPs?
OK, so think what you mink... i'm always right one way or the udder
whey.
Why?
Cause GOD loves me. LOL
But NOT YOUR Gawds.... sheesshh....
I've got the skin of a baby and the gut of a pig and healthier then an
ox.
But i suppose something could GO OUT some day?
Hey i'm only HUman and just barely like YOU> LOL
OK so are you in need of a new lung or kidney?
Then you want the BEST drug?
Yes, yes please doctor, what is it?
I've always distrusted my kidney's due to what
chinese tradional medicine says about psoriasis and
hate in the kidney's.
Yu mean fire, stupidly man child randall tar and feather boy...
Oh reight. Thanks for keePing me clear btw.
Without you living in my head it would all go-a by to fast.
http://www.ncbi.nlm.nih.gov/pubmed/20420793
Clin Nephrol. 2010 May;73(5):333-43.
Novel immunosuppressive agents in kidney transplantation.
[...] CP-690550, a JAK3 inhibitor, are small molecules in Phase II
studies. Everolimus is derived from the mTOR inhibitor sirolimus and
is in Phase III study. Belatacept is a humanized antibody that
inhibits T-cell costimulation and has shown encouraging results in
multiple Phase II and III trials. Alefacept and Efaluzimab are
humanized antibodies that inhibit T-cell adhesion and are in Phase I
and II clinical trials. This article reviews the mechanisms of action
as well as published and preliminary results of the Phase I-III
clinical trials involving these novel immunosuppressive agents.
PMID: 20420793
<sniP>
How about a liver transplant?
Then your gonna need the up to date immune drugs.
OK, which one?
The one that will take down your psoriasis in the process?
Yes, yes, and isn't that how mtx and cyclo were found in the first
place?
Yes... you NOW got a NEW OrGAN and less skin disease.
COOL...:)
What could be BETTER?
Dreams of jaK-ing off your psoriasis? lol
Yes, yes, uh... well.... maybe that doesn't work, jerk?
OK, think or COME again friend:
http://www.medicalnewstoday.com/articles/201306.php
[...] "The Jak-3 inhibitor tasocitinib will capture the largest
patient share of non-TNF-alpha inhibitor therapies by the end of 2013,
achieving a similar patient share to that of Bristol-Myers Squibb's
Orencia and surpassing by a slight margin the patient shares of
Rituxan and Actemra," said Decision Resources Analyst Benjamin
Guikema, Ph.D. "Tasocitinib's oral composition and efficacy could
position this agent in early lines of RA therapy, potentially even
before the TNF-alpha inhibitors."
<sniP>
http://en.wikipedia.org/wiki/Tasocitinib
Whoops NO page yet...
Paging mister no link...
Ok... make your point.
Huh?
Do i have one?
I suppose.
Do you wish to stoP blocking those pesky TNF suckers?
Yes-----> it's so bio ill logical.
Unless you NAIL the exact amount of dosage and that might entail
knowing how much
Th17 is inducted by SFB in your ileum?
OK
Right, as that is what randall has said a million zillion times.
Or maybe 46 or so....or i don't know exactly.
But let's think about blocking jak stat instead.
Jak3 does gork with CD247 and we've only got one hit in the P NG for
that:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=cd247&start=0&scoring=d&hl=en&
So what is cd247 doing on our cell membranes?
http://en.wikipedia.org/wiki/CD247
T-cell surface glycoprotein CD3 zeta chain also known as T-cell
receptor T3 zeta chain or CD247 (Cluster of Differentiation 247) is a
protein that in humans is encoded by the CD247 gene.[1]
Interactions
CD247 has been shown to interact with Janus kinase 3[3] and Protein
unc-119 homolog.
Function
T-cell receptor zeta, together with T-cell receptor alpha/beta and
gamma/delta heterodimers and CD3-gamma, -delta, and -epsilon, forms
the T-cell receptor-CD3 complex. The zeta chain plays an important
role in coupling antigen recognition to several intracellular signal-
transduction pathways. Low expression of the antigen results in
impaired immune response. Two alternatively spliced transcript
variants encoding distinct isoforms have been found for this gene.[2]
<sniP>
Since it seems like i've been going BLIND recently maybe this is
important? LOL
http://en.wikipedia.org/wiki/Protein_unc-119_homolog
OK back to this mib or what ever it is..
You know this pathway as your cells do it a zillion times a day:
http://upload.wikimedia.org/wikipedia/commons/2/29/Signal_transduction_v1.png
OK... so why block the jak stat?
Is tyrosine (say cheese) evil or do we simply NOT have enought
glutathione via NAC?
http://en.wikipedia.org/wiki/Tyrosine
Well... the idea is to slow cellular proliferation.
It makes money for pharma?
But does it make sense?
http://en.wikipedia.org/wiki/JAK-STAT_pathway
The JAK-STAT signaling pathway transmits information from chemical
signals outside the cell, through the cell membrane, and into gene
promoters on the DNA in the cell nucleus, which causes DNA
transcription and activity in the cell. The JAK-STAT system is a major
signaling alternative to the second messenger system. The JAK-STAT
system consists of three main components: a receptor, JAK and STAT.[1]
[...] The JAK-STAT pathway is evolutionarily conserved, from slime
molds and worms to mammals (but not fungi or plants). Disrupted or
dysregulated JAK-STAT functionality (which is usually by inherited or
acquired genetic defects) can result in immune deficiency syndromes
and cancers.[1]
<sniP>
-------------
TRIALs running on JAK-3 (Janus Kinase) inhibitor for PsA and
psoriasis?
http://en.wikipedia.org/wiki/Janus_kinase_3
Jak (just another kinase) STAT and jump back FAT.
What huh?
Eat that fat high in omega-3.... and then WE live
Right the FISH religion...sushi please?
http://en.wikipedia.org/wiki/Janus_kinase
Janus kinase --is a family of intracellular non-receptor tyrosine
kinases that transduce cytokine-mediated signals via the JAK-STAT
pathway. They were initially named "just another kinase" 1 & 2 (since
they were just two of a large number of discoveries in a PCR-based
screen of kinases[1]), but were ultimately published as "Janus
kinase". The name is taken from the two-faced Roman god of doorways,
Janus, because the JAKs possess two near-identical phosphate-
transferring domains. One domain exhibits the kinase activity while
the other negatively regulates the kinase activity of the first.
http://en.wikipedia.org/wiki/Tyrosine_kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group
from ATP to a protein in a cell.
JAKs come off the glial cells?
How glee full filled they must be? Or susan as the hpa-axis comes in
to PLAY. <w>
http://en.wikipedia.org/wiki/Cytokine
Cytokines (Greek cyto-, cell; and -kinos, movement) are small cell-
signaling protein molecules that are secreted by the glial cells of
the nervous system and by numerous cells of the immune system and are
a category of signaling molecules used extensively in intercellular
communication. Cytokines can be classified as proteins, peptides, or
glycoproteins; the term "cytokine" encompasses a large and diverse
family of regulators produced throughout the body by cells of diverse
embryological origin.[1]
<sniP>
OTOH it does say immune cells and pDC's aren't hpa-axis critters are
they? LOL
Or RA...
http://www.oraltrials.com/about-the-study-drug/about-cp-690550/
About tasocitinib (CP-690,550)
Rheumatoid Arthritis (RA) is a chronic disease characterized by
inflammation, or swelling, in the lining of the joints that can lead
to joint pain and stiffness, muscle pain, weakness and flu-like
symptoms. While the exact cause of RA is unknown, it is known to be
connected to the body’s immune system and is considered an autoimmune
disease because people with RA have an abnormal immune system
response. While the immune system normally fights infection, the
immune system of someone with RA may be overactive, mistaking healthy
tissue for a threat and attacking it as if it were a virus or
bacteria.
The investigational drug in the ORAL trials is called tasocitinib
(CP-690,550) and is being developed as a non-biologic potential DMARD
(Disease Modifying Anti-Rheumatic Drug). Tasocitinib (CP-690,550) is a
pill taken by mouth, unlike many current RA treatments which are
injected under the skin or infused.
Over 1,000 RA patients have been treated with tasocitinib (CP-690,550)
to date and it has been generally well-tolerated. The most frequently
reported adverse events include headaches, infections and
gastrointestinal symptoms such as nausea, vomiting and diarrhea: most
were mild to moderate in severity and were manageable with routine
medical care. These and additional potential risks are explained in
detail in the informed consent document that you will receive from
your physician.
Tasocitinib (CP-690,550) is not yet approved by the US Food and Drug
Administration (FDA) or by any other responsible regulatory agency
around the world. Regulatory agencies, including the FDA, require that
before an investigational study drug can be made available to the
public, it must undergo rigorous studies in a specific number of
patients approved by them to determine safety, tolerability and
effectiveness. The responsible regulatory agency, including the FDA in
the US, has approved the procedures and processes to be followed in
this study, as has the Institutional Review Board and/or Ethics
Committee of the study site.
<sniP>
All groups -ONLY 52 hits -tasocitinib -
http://groups.google.com/groups/search?hl=en&q=tasocitinib&btnG=Search&sitesearch=
As i'm not getting much online i'll go to pubmed instead?
OK..
45 hits for tasocitinib (which also resolves as CP-690550)
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=tasocitinib
So i best also try CP-690550 and i get 42 hits:
CP-690550
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=CP-690550
===================
OK move on dot dork randall tar head.
This next author: JJ O'Shea, i think i like?
HE's ALL jak -- STAT able?
He is?
He wrote:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692054/
The Current ____STATus____ of lymphocyte signaling: new roles for old
players (STATs in lymphocyte signaling)
Adewole S. Adamson,a*b Kalonji Collins,a Arian Laurence,a and John J.
O’Sheaa
<sniP>
____STATus___ is COOL... STAT's inside of us being what they are of
course.
http://en.wikipedia.org/wiki/STAT_protein
The STAT protein (Signal Transducer and Activator of Transcription, or
Signal Transduction And transcription) regulates many aspects of
growth, survival and differentiation in cells.
<snip>
GO to the ER STAT.... young cytokine or Miz interleukin? LOL
In this CASE er is ER and mister STAT best be on the way:
http://en.wikipedia.org/wiki/Endoplasmic_reticulum
73 results for Endoplasmic reticulum - in the P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=Endoplasmic+reticulum&start=0&scoring=d&hl=en&
by relevance and not chrono order as above:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Endoplasmic+reticulum&qt_g=Search+this+group
STAT----> stop the stress in the ER?
How often have i brought up the very thing that does that?
Glutathione? Many many times?
This ONE is one of them. LOL
And there are another nine more with ER in the same thread:
9 results for Endoplasmic reticulum glutathione - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Endoplasmic+reticulum+glutathione
But there are 411 hits for Glutathione in the entire P NG- thank-you
very much
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=glutathione&qt_g=Search+this+group
And since glutathione is destroyed by stomach acid take NAC as a
precusor or eat the right foods.
Like asparagus, brocolli, brocolli sprouts, cauliflower, cabbage,
garlic etc.
Some hits for this bit of knowledge:
8 results for glutathione destroyed acid stomach - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=glutathione+destroyed+acid+stomach
Why glutathione from NAC is so damn imPortant:
http://www.nanotechnologystore.com/Glutathione.html
http://en.wikipedia.org/wiki/Acetylcysteine
Acetylcysteine (rINN; pronounced /əˌsɛtəlˈsɪstiːn/), also known as N-
acetylcysteine or N-acetyl-L-cysteine (abbreviated NAC), is a
pharmaceutical drug and nutritional supplement used primarily as a
mucolytic agent and in the management of paracetamol (acetaminophen)
overdose. Other uses include sulfate repletion in conditions, such as
autism, where cysteine and related sulfur amino acids may be depleted.
[1]
<snip>
One of the key's to longevity is NAC.
I had to NOT take it to get results in my psoriasis supplementation
trials. LOL
IOWs another one of those turbo chargers that works to WELL. LOL
http://www.ncbi.nlm.nih.gov/pubmed/18845913
{...] A carbazole derivative protects cells against endoplasmic
reticulum
(ER) stress and glutathione depletion.
[...] PMID: 18845913
OK and back to the STAT of the SFB in the ileum and the odyssesy it
creates with Th17?
Maybe JJ O'Shea doesn 't know about Dan Littman's discovery yet???
I'll ask him soon. :)
Hey one of these will stick a cookie in you?
The cookie monster?
No the pharma dorks...
http://www.pharmalive.com/News/Index.cfm?articleid=737763
OR:
http://www.bioresearchonline.com/article.mvc/NIH-Scientists-Discover-Secrets-Of-Helper-0001?VNETCOOKIE=NO
NIH Scientists Discover Secrets Of Helper T Cells Involved In
Autoimmunity
October 21, 2010
WHAT
Scientists at the National Institutes of Health have redefined the
roles of several cytokines involved in the generation of immune cells
implicated in severe autoimmune diseases. The study in mice showed
that development of Th17 immune cells can occur without the presence
of transforming growth factor (TGF)-beta, a mediator thought to be
required for Th17 cell development. The study demonstrates that the
interaction of three inflammatory cytokines (proteins that influence
the behavior of cells) - interleukin-6 (IL-6), IL-1-beta and IL-23 -
is responsible for the creation of Th17 cells that are more active in
promoting autoimmunity than Th17 cells generated with IL-6, IL-1-beta
and TGF-beta. These findings reemphasize the separate roles of IL-23
and TGF-beta in immunity and autoimmunity, and open up possibilities
for the development of new therapies. The study appears in the current
issue of the journal Nature.
The immune systems of mice and humans mainly consist of B cells and T
cells. While B cells fight infections and can induce autoimmunity by
producing antibodies that directly target foreign antigens or a
person's own tissue, T cells are involved in overall cell-mediated
immunity. Importantly, how a T helper (Th) cell differentiates
(develops from an immature, unspecialized cell into a mature,
specialized cell) determines how it mediates immune responses. Th17
cells produce IL-17, a powerful inflammatory cytokine, and have been
implicated in multiple autoimmune diseases, including rheumatoid
arthritis, psoriasis and multiple sclerosis. The established belief
has been that Th17 cells initially differentiate in response to
activation by IL-6 and TGF-beta. However, previous research has shown
that TGF-beta is primarily associated with suppressing immune
functions and promoting regulatory T cells (Treg), which can produce
inhibitory cytokines that dampen inflammatory immune responses.
In the present study, the NIH scientists first looked at the
conditions to differentiate Th17 cells from naïve T cells outside of
the mouse (in vitro) and tried several different cocktails of
cytokines to see which combinations would promote Th17 development.
They found two combinations that efficiently induced Th17
differentiation. As previously described, IL-6, IL-1-beta, and TGF-
beta-1 together created Th17 cells. Surprisingly, IL-6, IL-1-beta, and
IL-23 without TGF-beta also created Th17 cells. Most interestingly,
the action of Th17 cells generated with IL-23, designated Th17(23),
was different from the action of Th17 cells generated with TGF-beta
(Th17(beta)). The researchers compared transcription factors,
receptors and mediators of the two Th17 subtypes and looked at the
pathogenic activity of both Th17 subtypes in mice during experimental
autoimmune encephalomyelitis (EAE), a common model of autoimmunity
that mimics some aspects of multiple sclerosis. They found that
Th17(23) cells provoked significantly more severe disease than did
Th17(beta) cells.
These findings suggest a new model for Th17 generation and the
existence of functionally different subtypes of Th17 cells. This study
also provides a better understanding of the array of immune components
involved in autoimmunity and suggests possibilities for new targeted
therapies.
NIH scientists contributing to this study are affiliated with the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS), the National Institute of Dental and Craniofacial Research
(NIDCR), and the National Institute of Allergy and Infectious Diseases
(NIAID). Additional support was provided by Merck Research
Laboratories (Schering-Plough Biopharma), Palo Alto, Calif.
REFERENCE
Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel J,
Ramos HL, Wei L, Davidson T, Bouladoux N, Grainger J, Chen Q, Kanno Y,
Watford WT, Sun HW, Eberl G, Shevach E, Belkaid Y, Cua DJ, Chen W,
O'Shea JJ. Enhanced Pathogenicity of Th17 cells Generated in the
Absence of Transforming Growth Factor-ß Signaling. Nature. 2010
October 21;467(7318): 967-971.
OK so i'm awaiting their abstract pmid #. LOL
In the meantime:
====================
Knowing the GUT helps...
http://www.ncbi.nlm.nih.gov/pubmed/20962772
Mucosal Immunol. 2010 Oct 20.
Intestinal macrophages and response to microbial encroachment.
Smith PD, Smythies LE, Shen R, Greenwell-Wild T, Gliozzi M, Wahl SM.
Department of Medicine (Gastroenterology) University of Alabama at
Birmingham, Birmingham, Alabama, USA.
Abstract
Macrophages in the gastrointestinal mucosa represent the largest pool
of tissue macrophages in the body. In order to maintain mucosal
homeostasis, resident intestinal macrophages uniquely do not express
the lipopolysaccharide (LPS) co-receptor CD14 or the IgA (CD89) and
IgG (CD16, 32, and 64) receptors, yet prominently display Toll-like
receptors (TLRs) 3-9. Remarkably, intestinal macrophages also do not
produce proinflammatory cytokines in response to TLR ligands, likely
because of extracellular matrix (stromal) transforming growth factor-β
(TGF-β) dysregulation of nuclear factor (NF)-κB signal proteins and,
via Smad signaling, expression of IκBα, thereby inhibiting NF-κB-
mediated activities. Thus, in noninflamed mucosa, resident macrophages
are inflammation anergic but retain avid scavenger and host defense
function, an ideal profile for macrophages in close proximity to gut
microbiota. In the event of impaired epithelial integrity during
intestinal infection or inflammation, however, blood monocytes also
accumulate in the lamina propria and actively pursue invading
microorganisms through uptake and degradation of the organism and
release of inflammatory mediators. Consequently, resident intestinal
macrophages are inflammation adverse, but when the need arises, they
receive assistance from newly recruited circulating monocytes.Mucosal
Immunology advance online publication 20 October 2010. doi:10.1038/mi.
2010.66.
PMID: 20962772
And knowing about
748 hits - endoplasmic reticulum glutathione
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=endoplasmic+reticulum+glutathione
http://www.ncbi.nlm.nih.gov/pubmed/18507007
Anticancer Res. 2008 Mar-Apr;28(2A):681-6.
Implications of the involvement of the endoplasmic reticulum stress
pathway in drug-induced apoptosis.
Cory AH, Chen J, Cory JG.
Department of Biochemistry and Molecular Biology, Brody School of
Medicine, East Carolina University, Greenville, NC 27834, USA.
Abstract
Apoptosis occurs by distinct pathways that involve the cell surface,
mitochondria or the endoplasmic reticulum. Previous studies had shown
that deoxyadenosine-resistant L1210 cells (Y8) proceeded to apoptosis
under conditions in which the parental L1210 cell line (WT) did not
undergo an apoptotic response. Combinations of drugs, acting at
different molecular targets, markedly potentiated the apoptotic
response in the Y8 cells without inducing apoptosis in the WT cells.
In the present study, induction of apoptosis by parthenolide and BAY
11-7085, drugs that targeted nuclear factor kappa B activation, was
blocked by the presence of N-acetylcysteine (NAC). On the other hand,
the levels of apoptosis induced by parthenolide or BAY 11-7085 were
increased by pre-treatment of the cells with glutathione lowering L-
buthionine-(S,R)-sulfoximine (BSO). Western blot analyses showed that
the levels of the stress proteins, Grp 78 and Gadd 153 were reduced in
the parthenolide-treated Y8 cells, but not in those co-treated with
NAC. Protection of the cells from apoptosis induced by parthenolide or
BAY 11-7085 by NAC was relatively specific as the induction of
apoptosis in the Y8 cells by MG-132, flavopiridol, Gemcitabine or
PRIMA-1 was not decreased by NAC. These data suggest that multiple
pathways, one of which is ER-stress induced, may ultimately be
involved and interactive in the induction of apoptosis in specific
cell lines.
PMID: 18507007
So guy from New Jersey a democrat d'caprio? Said obama can shove it?
Wow...
He said it live... LOL
The oval office honey moon is over the toP.
randalll... randall ... randalloidtarbabymanmad...