Inner-- OUTER CRAP
randall
I wanted a new thread.
But this is PART II to this one:
On Nov 20, 11:45 am, randall <ranhu...@aol.com> wrote:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/921cc5d1132f6307
Subject: Re: Crohn's - BIG MAC -- IL-27- GOOD vs EVIL Gut FLORA --
Leaky Guts redux - LPS
So i'll create a new subject for it?
Sure:
randall said:
> PMID: 12730867
>
> WOW this is a biggie. PPAR and LPS and crohn's all in a psor post....
> thread..
>
> randall... mostly ALL a huge RE-thread from one of FIVE Thousand LPS
> posts. LOL
OK, so i've gone over board on LPS.
But really?
PPAR is still in current articles the same as LPS and even
a LTA mention in the other post today. :)
http://en.wikipedia.org/wiki/Lipoteichoic_acid
Good flora or bad flora or when good becomes BAD.
Does make one MAD. :(
So much for commensalism or socialism perhaPs?
How do they go out of balance?
It's a power trip.
But inside crap it's genetics and mother nurture?
Let's get specific..
This next one is for crohn's, PPAR's and BIG MAC.
Wait.... this is for lupus and PPAR-delta and macrophages and crap
building up systemic WIDE.
So?
Well----> with either crohn's or lupus or psoriais we have excess
CRAP.
If you don't believe me find the CD98hc thread and look.
And while I nearly nailed it in the previous post, i thought i would
toss a few more stones at it.
Why?
Why not?
The body needs to detox or you fill uP with it.
With proper
http://en.wikipedia.org/wiki/Metabolism
and a
http://en.wikipedia.org/wiki/Basal_metabolic_rate
You can keeP a clean shop:
VIA
http://en.wikipedia.org/wiki/Detoxification#Metabolic_detoxification
http://en.wikipedia.org/wiki/Xenobiotic_metabolism
http://en.wikipedia.org/wiki/Glutathione_S-transferase
http://en.wikipedia.org/wiki/Cytochrome_P450
OK, that was fun
Let's move down the line
Where is TGF-beta for psoriatics & crohn's folks?
http://en.wikipedia.org/wiki/TGF_beta
Susan would remind us:
Serotonin:
http://en.wikipedia.org/wiki/Serotonin
Serotonin is a monoamine neurotransmitter. It is found extensively in
the gastrointestinal tract of animals, and about 80 to 90 percent of
the human body's total serotonin is located in the enterochromaffin
cells in the gut, where it is used to regulate intestinal movements.
[...]
Serotonin affects insulin-like signaling and the TGF beta signaling
pathway,
<sniP>
And look at the actions between L-trytophan and serotonin in the hpa-
axis
http://en.wikipedia.org/wiki/Hypothalamic-pituitary-adrenal_axis#Research
Susan is a Genius in this area. :)
OK, so much for patting ourselves on the BACK.
That could go on all day... But i still have a small patch of you know
what back there. LOL
Back to WORK.
I'll work with psor first, as it's either north or south of foxp3
genetics.
721 returns: foxp3 + TGF-beta [pubmed]
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=tgf-beta+foxp3&log$=activity
The most recent:
www.ncbi.nlm.nih.gov/pubmed/19918314
Induction of antigen-specific immune tolerance by TGF-beta-induced
CD4+Foxp3+ regulatory T cells.
Fan H, Wang J, Zhou X, Liu Z, Zheng SG.
Like natural CD4(+)CD25(+) Treg cells, TGF-beta-induced Treg cells
also prevent allograft rejection in MHC-mismatched organ
transplantation models. In analyzing this effect with greater detail,
we determined that injection of TGF-beta-induced, alloactivated CD4(+)
CD25(+) cells induces antigen-specific immune tolerance in vivo.
Increased CD4(+)CD25(+) cells in recipients contribute to this immune
tolerance. In addition, adoptive transfer of TGF-beta-induced CD4(+)
CD25(+) cells did not result in significant toxic and side effects in
recipients. These results indicate that TGF-beta-induced,
alloactivated CD4(+)CD25(+) cells may provide a safe and effective
approach to protect MHC-mismatched organ grafts from rejection in a
clinical setting.
PMID: 19918314
With foxp3 and rorc2
www.ncbi.nlm.nih.gov/pubmed/18469800
(fourth post of this pmid #)
Which brings up the inverse relationship of rorc2 to foxp3.
www.ncbi.nlm.nih.gov/pubmed/19648312
Th17 transcription factor RORC2 is inversely correlated with FOXP3
expression in the joints of children with juvenile idiopathic
arthritis.
Olivito B, Simonini G, Ciullini S, Moriondo M, Betti L, Gambineri E,
Cantarini L, De Martino M, Azzari C, Cimaz R.
Department of Paediatrics, Rheumatology and Immunology Unit,
University of Florence, Anna Meyer Children's Hospital, Florence,
Italy. b.ol...@meyer.it
OBJECTIVE: To investigate the relationship between interleukin 17
(IL-17) producing T cells (Th17) and CD4+CD25+FOXP3+ regulatory T
cells (Tregs) in blood and synovial fluid (SF) of patients with
juvenile idiopathic arthritis (JIA). METHODS: Sixty-five children with
JIA (18 males and 47 females, median age 6.2 yrs; 45 with
oligoarticular and 20 with polyarticular course) and 75 age- and sex-
matched healthy controls were studied. Flow cytometry was used to
analyze the forkhead box P3 (FOXP3)-positive Treg cells in peripheral
blood (PB) and synovial fluid mononuclear cells (SFMC). FOXP3 and
retinoic-acid related orphan receptor C isoform 2 (RORC2) messenger
RNA (mRNA) were assessed by real-time polymerase chain reaction
analysis. Cytokines (IL-17 and Th1/Th2 related cytokines) were
measured in culture supernatants of 11 paired PBMC and SFMC activated
with PMA and ionomycin. RESULTS: FOXP3+ T cells and FOXP3 mRNA amounts
were significantly lower in PB of children with JIA as compared with
controls (p = 0.0002 and p = 0.001, respectively) and a higher
percentage of Treg cells with concomitant higher level of FOXP3
transcript levels were observed in SF when compared with their PB
counterparts (both p < 0.0001). SF CD4+FOXP3+ T cells were
characterized by higher amounts of FOXP3 protein per cell when
compared with peripheral CD4+FOXP3+ T cells, as revealed by the
difference in FOXP3 median fluorescence intensity (median +/- SD,
arbitrary units, 54 +/- 22.6 vs 19.5 +/- 4.2; p < 0.001). RORC2
transcript levels were higher in JIA joints when compared with matched
PB samples (median fold increase 3.9, p < 0.0001) but negatively
correlated with FOXP3 mRNA levels (r = -0.623, p = 0.04). Stimulated
SFMC displayed an impaired ability to produce IL-17 when compared with
PBMC and, interestingly, an inverse relationship between IL-17 levels
and the percentage of CD4+CD25+FOXP3+ SF T cells (r = -0.510, p =
0.047) was seen. CONCLUSION: We demonstrated for the first time an
increased synovial expression of the transcription factor of Th17,
RORC2, in JIA, and its inverse relationship with FOXP3 mRNA. These
results extend research on "Th17" and Tregs in JIA.
PMID: 19648312
But don't forget Unutmaz.
www.ncbi.nlm.nih.gov/pubmed/19499530
[...]
The orphan nuclear receptor ROR gamma t/RORC2 (mice/humans) is the
master transcription factor that can drive Th17 cell differentiation
in both mice and humans; however, it is not completely clear how much
of the human Th17 lineage function and phenotype can be recapitulated
by only RORC2 expression. In this issue of the European Journal of
Immunology, a study reports that ectopic expression of RORC2 in
primary human T cells induces, in addition to IL-17 production, a
cytokine and chemokine receptor profile consistent with bona fide
human Th17 cells. In addition, programming of human Th17 cells by
RORC2 results in partial resistance of these T cells to suppression by
Tregs. These findings support the notion that RORC2 is a master switch
that initiates a wide range of phenotypic and functional programming
during Th17 cell differentiation.
PMID: 19499530
<sniP>
Nine returns for keyword: rorc2 - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=rorc2&log$=activity
http://en.wikipedia.org/wiki/RAR-related_orphan_receptor_gamma
----
www.ncbi.nlm.nih.gov/pubmed/19912251
Translational Mini-Review Series on Th17 Cells: Induction of
interleukin-17 production by regulatory T cells.
Afzali B, Mitchell P, Lechler RI, John S, Lombardi G.
MRC Centre for Transplantation and NIHR Biomedical Research Centre,
King's College, Guy's Hospital, London, UK.
Summary Uncommitted (naive) CD4(+) T helper cells (Thp) can be induced
to differentiate to specific lineages according to the local cytokine
milieu, towards T helper type 1 (Th1), Th2, Th17 and regulatory T cell
(T(reg)) phenotypes in a mutually exclusive manner. Each phenotype is
characterized by unique signalling pathways and expression of specific
transcription factors, notably T-bet for Th1, GATA-3 for Th2, forkhead
box P3 (FoxP3) for T(regs) and receptor-related orphan receptor (ROR)
alpha and RORgammat for Th17 cells. T(regs) and Th17 cells have been
demonstrated to arise from common precursors in a reciprocal manner
based on exposure to transforming growth factor (TGF)-beta or TGF-beta
plus interleukin (IL)-6 and carry out diametrically opposing
functions, namely suppression or propagation of inflammation,
respectively. However, while epigenetic modifications in Th1 and Th2
differentiated cells prevents their conversion to other phenotypes,
Th17 cells generated in vitro using TGF-beta and IL-6 are unstable and
can convert to other phenotypes, especially Th1, both in vitro and in
vivo. T(regs) are generated from naive precursors both in the thymus
(natural, nT(regs)) and in the periphery (induced, iT(regs)). The
highly suppressive function of T(regs) enables them to control many
inflammatory diseases in animals and makes them particularly
attractive candidates for immunotherapy in humans. The stability of
the T(reg) phenotype is therefore of paramount importance in this
context. Recent descriptions of T(reg) biology have suggested that
components of pathogens or inflammatory mediators may subvert the
suppressive function of T(regs) in order to allow propagation of
adequate immune responses. Unexpectedly, however, a number of groups
have now described conversion of T(regs) to the Th17 phenotype induced
by appropriate inflammatory stimuli. These observations are
particularly relevant in the context of cell therapy but may also
explain some of the dysregulation seen in autoimmune diseases. In this
paper, we review T(reg) to Th17 conversion and propose some potential
mechanisms for this phenomenon.
PMID: 19912251
---
Littman with akdis?
www.ncbi.nlm.nih.gov/pubmed/19917773
Transcription factors RUNX1 and RUNX3 in the induction and suppressive
function of Foxp3+ inducible regulatory T cells.
Klunker S, Chong MM, Mantel PY, Palomares O, Bassin C, Ziegler M,
Rückert B, Meiler F, Akdis M, Littman DR, Akdis CA.
Swiss Institute of Allergy and Asthma Research Davos, University of
Zurich, CH-7270 Davos-Platz, Switzerland.
Forkhead box P3 (FOXP3)(+)CD4(+)CD25(+) inducible regulatory T (iT
reg) cells play an important role in immune tolerance and homeostasis.
In this study, we show that the transforming growth factor-beta (TGF-
beta) induces the expression of the Runt-related transcription factors
RUNX1 and RUNX3 in CD4(+) T cells. This induction seems to be a
prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX
binding sites in the FOXP3 promoter. Inactivation of the gene encoding
RUNX cofactor core-binding factor-beta (CBFbeta) in mice and small
interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in
human T cells resulted in reduced expression of Foxp3. The in vivo
conversion of naive CD4(+) T cells into Foxp3(+) iT reg cells was
significantly decreased in adoptively transferred Cbfb(F/F) CD4-cre
naive T cells into Rag2(-/-) mice. Both RUNX1 and RUNX3 siRNA silenced
human T reg cells and Cbfb(F/F) CD4-cre mouse T reg cells showed
diminished suppressive function in vitro. Circulating human CD4(+) CD25
(high) CD127(-) T reg cells significantly expressed higher levels of
RUNX3, FOXP3, and TGF-beta mRNA compared with CD4(+)CD25(-) cells.
Furthermore, FOXP3 and RUNX3 were colocalized in human tonsil T reg
cells. These data demonstrate Runx transcription factors as a
molecular link in TGF-beta-induced Foxp3 expression in iT reg cell
differentiation and function.
PMID: 19917773
Littman with Rudensky [posted yesterday--Nov 17, 2009 psor group]
www.ncbi.nlm.nih.gov/pubmed/19767756
--------
Is it simply a 02 thing?
Reoxygenation of hypoxia-differentiated dentritic cells induces Th1
and Th17 cell differentiation.
Wang Q, Liu C, Zhu F, Liu F, Zhang P, Guo C, Wang X, Li H, Ma C, Sun
W, Zhang Y, Chen W, Zhang L.
Department of Immunology, Shandong University School of Medicine, 44#
Wenhua Xi Road, Jinan 250012, China.
Dendritic cells (DCs) are often exposed to various oxygen tensions
under physiological and pathological conditions. However, the effects
of various oxygen tensions on DC functions remain unclear. In this
study, we showed that hypoxia-differentiated DCs expressed lower
levels of MHC-II molecule, co-stimulatory molecules (CD80, CD86) and
proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), but higher
levels of immunoregulatory cytokine transforming growth factor-beta
(TGF-beta) than normoxia-differentiated DCs. Unexpectedly, re-exposure
of hypoxia-differentiated DCs to saturated oxygen (reoxygenation)
completely restored their mature phenotype and function. Specifically,
the reoxygenated DCs induced naïve CD4(+) T cells to differentiate
into Th1 and Th17 effector cells, but deceased the generation of CD4(+)
CD25(+)Foxp3(+) regulatory T cells (Tregs). The data indicate that
hypoxic microenvironment suppresses the maturation and function of
murine DCs. Reoxygenation of hypoxia-differentiated DCs however
results in complete recovery of their mature phenotype and function,
and has strong ability to drive immune response toward a
proinflammatory direction, suggesting reoxygenated DCs may contribute
to inflammation of ischemia-reperfusion injury.
PMID: 19910049
Ok, already..
One more with GARP..
Ok, then already.
www.ncbi.nlm.nih.gov/pubmed/19904770
The Tregs' world according to GARP.
Battaglia M, Roncarolo MG.
San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) Milano,
Italy.
Naturally occurring CD4(+)CD25(high) regulatory T cells (nTregs) are
essential for maintaining tolerance. FOXP3 has been established as a
molecular marker of nTregs; however, FOXP3 cannot be used as a
reliable marker for bona fide human nTregs since effector T cells also
up-regulate FOXP3 expression upon activation. Despite the important
function of nTreg, the underlying molecular mechanisms of nTreg-
mediated suppression are far from defined. Previous studies have
demonstrated that the TGF-beta latency-associated peptide (LAP) is
expressed on the surface of nTregs, and that immunosuppression can be
mediated by membrane TGF-; however, it remains unknown how LAP is
bound to nTregs and what is the functional significance of its
selective expression on activated nTregs. The nTregs' world may now
change according to GARP, an orphan toll-like receptor composed of
leucine-rich repeats. In this issue of the European Journal of
Immunology, a study provides further demonstration that GARP is
selectively expressed only in activated human nTregs and nTreg cell
clones but not in activated effector T cells, confirming GARP as a
bona fide nTreg marker. In addition, GARP binds directly to LAP; yet
GARP over-expression is insufficient to induce modification of latent
TGF- into active TGF- further clarifying its role in nTreg-mediated
suppression.
PMID: 19904770
-------------------
The perfect helminth for psoriatics?
Or another DEATH traP via some sneaky BUG?
You've made your WHEY from helminth to prezident and much in you is
still worm?
SWEET!!! LOL
Who said DAT?
And wots a helminth?
Real fodder to ruminate perhaps.
We all end up worm food.
But OH to BE clear in the mean time?
http://en.wikipedia.org/wiki/Parasitic_worm
&
From Thus Spoke Zarathustra:
http://en.wikiquote.org/wiki/Friedrich_Nietzsche#Thus_Spoke_Zarathustra_.281885.29
[...]
Ihr habt den Weg vom Wurme zum Menschen gemacht, und Vieles ist in
euch noch Wurm. Einst wart ihr Affen, und auch jetzt ist der Mensch
mehr Affe, als irgend ein Affe.
You have evolved from worm to man, but much within you is still worm.
Once you were apes, yet even now man is more of an ape than any of the
apes.
<sniP>
Did Nietzsche really say that woman was god's second mistake?
And :
Ah, women. They make the highs higher and the lows more frequent.
Yep according to that brainyquote site.
but was it a mistake and whose on FIRST?
http://www.quotesdaddy.com/quote/1289976/friedrich-nietzsche/woman-was-gods-second-mistake
-----
I know, i know... it's a complete FLUKE?
What?
That some pinworm can give you a Th2 skew and wipe out your psor rash?
http://en.wikipedia.org/wiki/Parasitic_worm#Immune_response
Or a demo jack ass can become an oval office denizen?
Even LBJ was one.
One what?
http://www.sodahead.com/living/another-failed-presidency---geoffrey-p-hunt/question-687155/?page=4
or almost the same thing:
Another Failed Presidency
http://www.americanthinker.com/2009/08/another_failed_presidency.htm
Now that's a segue. LOL
But will our FEAR mongering prez own the NEXT depression?
Yeah with glib fibs from a teleprompter and Prez..FDR must be jealous.
LOL
The czar of three terms for a wORM. LOL
Yet Bush gave free drugs to old folks to the tune of billions/
trillions/zillions.
http://www.forbes.com/2009/11/19/republican-budget-hypocrisy-health-care-opinions-columnists-bruce-bartlett.html
Repub deficit hypocrisy
SO obama said he spent to much.
THEN obama proved he's a bigger jackASS by spending 10 times more?
Takes us back to Nietzsche.
Is there a perfect worm, fluke or helminth for psor HEADs and or
Prezident?
REALLY?
Don't actually know till i eat some. <W>
Helminth du JOUR:
www.ncbi.nlm.nih.gov/pubmed/19917714
Major secretory antigens of the helminth Fasciola hepatica activate a
suppressive dendritic cell phenotype that attenuates Th17 cells but
fails to activate Th2 immune responses.
Dowling DJ, Hamilton CM, Donnelly S, La Course J, Brophy PM, Dalton J,
O'Neill SM.
Parasite Immune Modulation Group, School of Nursing, Faculty of
Science and Health, Dublin City University, Glasnevin, Dublin,
Ireland; Department of Biology, National University of Ireland
Maynooth, Kildare, Ireland; University of Liverpool, Liverpool, L69
7ZJ, UK; Aberystwyth University, Aberystwyth, Ceredigion, Wales, UK;
Institute of Parasitology, McGill University, 21,111 Lakeshore Road,
Sainte Anne de Bellevue, QC H9X 3V9, Canada.
Fasciola hepatica is a helminth pathogen that drives Th2/Treg immune
responses in its mammalian host. The parasite releases a large number
of molecules that are critical to inducing this type of immune
response. Here we have selected recombinant forms of two major F.
hepatica secreted molecules, the protease cathepsin L (rFhCL1) and
anti-oxidant, sigma class glutathione transferase (rFhGST-si), to
examine their interactions with dendritic cells (DCs). Despite
enzymatic and functional differences between these molecules, both
induced IL-6, IL-12p40 and MIP-2 secretion from DCs and enhanced CD40
expression. While this induction was mediated by toll-like receptor 4
(TLR4), their subsequent intracellular signalling pathways differed;
rFhCL1 signalled through p38 and rFhGST-si mediated its effect via
JNK, p38, p-NF-kappaBp65 and IRF5. Neither rFhCL1 nor rFhGST-si
enhanced DC phagocytosis or induced Th2 immune responses in vivo.
However, DCs matured in the presence of either enzyme attenuated IL-17
production from OVA-specific T-cells in vivo. In addition, DCs exposed
to either antigen secreted reduced levels of IL-23. Therefore, both F.
hepatica FhCL1 and FhGST-si modulate host immunity by suppressing
responses associated with chronic inflammation - an immune modulatory
mechanism that may benefit the parasites survival within the host.
PMID: 19917714
Lowers Th17 and leaves the rest (Th2) alone?
Is it a halofuginone protein or look alike?
From a FLUKE?
-----
The more unintelligent a man is, the less mysterious existence seems
to him.
Arthur Schopenhauer
All truth passes through three stages. First, it is ridiculed. Second,
it is violently opposed. Third, it is accepted as being self-evident.
Arthur Schopenhauer
When you find out that the GARDEN of EDEN may be inside you, will you
ridicule it or harvest health?
Glowing cLEAR skin?
I believe... i want to?
Faith dies another death on top of a psor RASH. LOL
Back to the grind....
The path is long and the journey twists.
Twisted sister?
No, no.... not now. LOL
oK, IBD has a IL-27 genetic variant.
How does IL-27 uPregulate Th17 to cause gut mayham?
http://news.biocompare.com/News/NewsStory/299282/NewsStory.html
Largest Gene Study of Childhood IBD Identifies 5 New Genes
In the largest, most comprehensive genetic analysis of childhood-onset
inflammatory bowel disease (IBD), an international research team has
identified five new gene regions, including one involved in a
biological pathway that helps drive the painful inflammation of the
digestive tract that characterizes the disease.
A research team led by Hakon Hakonarson, M.D., Ph.D., director of the
Center for Applied Genomics at The Children's Hospital of
Philadelphia, says that the findings advance the scientific
understanding of how IBD develops. "This is an evolving story of
discovering what genes tell us about the disease," said Robert N.
Baldassano, M.D., a co-first author of the study and director of the
Center for Pediatric Inflammatory Bowel Disease at Children's
Hospital. "Pinpointing how specific genes act on biological pathways
provides a basis for ultimately personalizing medicine to an
individual's genetic profile."
The study appears online today in Nature Genetics.
IBD is a painful, chronic inflammation of the gastrointestinal tract,
affecting about two million children and adults in the United States.
Of that number, about half suffer from Crohn's disease, which can
affect any part of the GI tract, and half have ulcerative colitis,
which is limited to the large intestine.
Most gene analyses of IBD have focused on adult-onset disease, but the
Center for Applied Genomics—one of the world's largest pediatric
genotyping programs—at Children's Hospital has concentrated on
childhood-onset IBD, which tends to be more severe than adult-onset
disease. The researchers performed a genome-wide association study on
DNA from over 3,400 children and adolescents with IBD, plus nearly
12,000 genetically matched control subjects, all recruited through
international collaborations in North America and Europe.
In a genome-wide association study, automated genotyping tools scan
the entire human genome seeking gene variants that contribute to
disease risk.
The study team identified five new gene regions that raise the risk of
early-onset IBD, on chromosomes 16, 22, 10, 2 and 19. The most
significant finding was at chromosome locus 16p11, which contains the
IL27 gene that carries the code for a cytokine, or signaling protein,
also called IL27. "This cytokine acts on a biological pathway, the T-
helper 17 pathway, which plays a key role in causing intestinal
inflammation," said Hakonarson. T helper 17 cells are recently
discovered cells that lead to severe inflammation and tissue injury in
autoimmune diseases. IBD is an autoimmune disease, in which a person's
immune system runs out of control and attacks the body.
"There are many cytokines in our immune system, but our research
strongly suggests that IL27 has a primary causative role in IBD,"
added Hakonarson. "This gene discovery makes sense in terms of our
functional understanding of the disease."
Some current IBD drugs are monoclonal antibodies that act on another
cytokine, called tumor necrosis factor, which contributes to
inflammation. Although much research remains to be done, the current
study may provide a basis for developing drugs that target the
cytokine IL27's action, for patients with the disease-causing IL27
gene variant.
One strength of the current study, in addition to its large sample
size, is the collaboration of many leading pediatric IBD research
programs. In addition to The Children's Hospital of Philadelphia,
other centers with principal investigators who played key roles were
the Hospital for Sick Children of the University of Toronto; the
University of Edinburgh, UK; Cedars Sinai Medical Center, Los Angeles;
Emory University, Atlanta; and the IRCCS-CSS Hospital, S. Giovanni
Rotondo, Italy.
------------------
Is IL-27 the one gene that psoriatics are OK with?
Or do we get the Th17, not from SFB's, but due to genetics?
And look at this next one. They say their turning on the GUT
inflammation light.
How come i'm not seeing it. LOL
www.ncbi.nlm.nih.gov/pubmed/19915978
Synergy of IL-23 and Th17 Cytokines: New Light on Inflammatory Bowel
Disease.
Shen W, Durum SK.
Laboratory of Molecular Immunoregulation, Cancer Inflammation Program,
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Frederick, MD, 21702, USA.
Inflammatory bowel diseases (IBDs), including Crohn's disease and
ulcerative colitis, involve an interplay between host genetics and
environmental factors including intestinal microbiota. Animal models
of IBD have indicated that chronic inflammation can result from over-
production of inflammatory responses or deficiencies in key negative
regulatory pathways. Recent research advances in both T-helper 1 (Th1)
and T-helper 17 (Th17) effect responses have offered new insights on
the induction and regulation of mucosal immunity which is linked to
the development of IBD. Th17 cytokines, such as IL-17 and IL-22, in
combination with IL-23, play crucial roles in intestinal protection
and homeostasis. IL-23 is expressed in gut mucosa and tends to
orchestrate T-cell-independent pathways of intestinal inflammation as
well as T cell dependent pathways mediated by cytokines produced by
Th1 and Th17 cells. Th17 cells, generally found to be proinflammatory,
have specific functions in host defense against infection by
recruiting neutrophils and macrophages to infected tissues. Here we
will review emerging data on those cytokines and their related
regulatory networks that appear to govern the complex development of
chronic intestinal inflammation; we will focus on how IL-23 and Th17
cytokines act coordinately to influence the balance between tolerance
and immunity in the intestine.
PMID: 19915978
OK, now this next one has some MEAT in the taco...
www.ncbi.nlm.nih.gov/pubmed/19915062
SLAT/Def6 Plays a Critical Role in the Development of Th17 Cell-
Mediated Experimental Autoimmune Encephalomyelitis.
Canonigo-Balancio AJ, Fos C, Prod'homme T, Bécart S, Altman A.
*Division of Cell Biology, La Jolla Institute for Allergy and
Immunology, La Jolla, CA 92037.
SWAP-70-like adapter of T cells (SLAT; also known as Def6) is a novel
guanine nucleotide exchange factor for Rho GTPases that has been
previously shown to play a role in CD4(+) T cell activation and Th1/
Th2 differentiation. However, the role of SLAT/Def6 in autoimmunity
and its associated Th1- and Th17-specific responses has not yet been
clearly elucidated. We used a prototypical and pathologically relevant
Th1/Th17-mediated autoimmune model, that is, experimental autoimmune
encephalomyelitis, to assess the role of SLAT/Def6 in autoantigen-
specific T cell response. We found that T cell-expressed SLAT/Def6 was
critical for experimental autoimmune encephalomyelitis development and
pathogenesis, as evidenced by the resistance of Def6-deficient (Def6
(-/-)) mice to clinical signs of the disease associated with a lack of
CNS inflammation and demyelination in myelin oligodendrocyte
glycoprotein-immunized Def6(-/-) mice. Moreover, Def6 deficiency
resulted in a severely diminished myelin oligodendrocyte glycoprotein-
specific CD4(+) T cell proliferation as well as a defect in IFN-gamma
and IL-17 production in secondary lymphoid organs and the CNS. Lastly,
Def6(-/-) CD4(+) T cells were grossly deficient in their ability to
differentiate into Th17 cells both in vitro and in vivo in a T cell-
intrinsic manner. Therefore, our study establishes T cell-expressed
SLAT/Def6 as a pivotal positive regulator of Th17 inflammatory
responses and, thus, essential in controlling autoimmune and
inflammatory diseases.
PMID: 19915062
This one is rocking the LPS and TLr's:
www.ncbi.nlm.nih.gov/pubmed/19915052
TLR2 Promotes Th2/Th17 Responses via TLR4 and TLR7/8 by Abrogating the
Type I IFN Amplification Loop.
Wenink MH, Santegoets KC, Broen JC, van Bon L, Abdollahi-Roodsaz S,
Popa C, Huijbens R, Remijn T, Lubberts E, van Riel PL, van den Berg
WB, Radstake TR.
*Department of Rheumatology, Radboud University Nijmegen Medical
Center, Nijmegen, The Netherlands.
TLR2 plays an important role in the removal of Gram-positive bacteria;
contrastingly, it also appears to have important protective effects
against unrestrained inflammation and subsequent organ injury during
infection and autoimmunity. We hypothesized that TLR2 tunes the
phenotype of dendritic cells (DCs) activated through other TLRs,
thereby fulfilling a crucial role in the modulation of the immune
response. TLR2 potently inhibited TLR4- and TLR7/8-induced cytokine
production by human DCs. The inhibitory effect of TLR2 on the release
of TNF-alpha but not of IL-12p70 was mediated by PI3K. TLR2 inhibits
the production of IL-12p70 by dampening the type 1 IFN amplification
loop. When DCs were triggered with the potent synergistic combination
of LPS (TLR4) and R848 (TLR7/8) in conjunction with a TLR2 ligand, a
clear shift to more Th2- and Th17-prone responses in the naive and
memory T cell subpopulations was observed. This shift in T cell
responses was inherent to the inability of TLR2-stimulated DCs to
produce IL-12p70 and was dependent on the production of IL-1 and IL-6.
PMID: 19915052
======================
In my last post i said to use Forskolin, NAC (raises glutathione for
detox etc) and
sweet whey and and and..
EAT a TON of LARD. LOL
That will keep you on your feet unless you took that advice. <G>
Let's target a key player for autoimmunity.
http://news.biocompare.com/News/NewsStory/298366/NewsStory.html
Targeting PKC-Theta Protein: A Way To Inhibit Harmful Immune
Responses?
[...]
A team of researchers, led by Amer Beg and Xue-Zhong Yu, at the H. Lee
Moffitt Cancer Center and Research Institute, Tampa, has now
identified the protein PKC-theta as a potential drug target in this
context by determining that it is required in mice for GVHD induction
but not for GVL or protective responses to infectious agents.
<sniP>
----------
www.ncbi.nlm.nih.gov/pubmed/19907075
PKCtheta is required for alloreactivity and GVHD but not for immune
responses toward leukemia and infection in mice.
Valenzuela JO, Iclozan C, Hossain MS, Prlic M, Hopewell E, Bronk CC,
Wang J, Celis E, Engelman RW, Blazar BR, Bevan MJ, Waller EK, Yu XZ,
Beg AA.
When used as therapy for hematopoietic malignancies, allogeneic BM
transplantation (BMT) relies on the graft-versus-leukemia (GVL) effect
to eradicate residual tumor cells through immunologic mechanisms.
However, graft-versus-host disease (GVHD), which is initiated by
alloreactive donor T cells that recognize mismatched major and/or
minor histocompatibility antigens and cause severe damage to
hematopoietic and epithelial tissues, is a potentially lethal
complication of allogeneic BMT. To enhance the therapeutic potential
of BMT, we sought to find therapeutic targets that could inhibit GVHD
while preserving GVL and immune responses to infectious agents. We
show here that T cell responses triggered in mice by either Listeria
monocytogenes or administration of antigen and adjuvant were
relatively well preserved in the absence of PKC isoform theta
(PKCtheta), a key regulator of TCR signaling. In contrast, PKCtheta
was required for alloreactivity and GVHD induction. Furthermore,
absence of PKCtheta raised the threshold for T cell activation, which
selectively affected alloresponses. Most importantly, PKCtheta-
deficient T cells retained the ability to respond to virus infection
and to induce GVL effect after BMT. These findings suggest PKCtheta is
a potentially unique therapeutic target required for GVHD induction
but not for GVL or protective responses to infectious agents.
PMID: 19907075
The whole study for this:
http://www.jci.org/articles/view/39692?key=zd7vNZFNtFlFYjT9Mfn6
==========
30 hits on pubmed for :: PKC + psoria*
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=psoria*+AND+PKC&log$=activity
The most recent:
www.ncbi.nlm.nih.gov/pubmed/19876790
Sotrastaurin, a protein kinase C inhibitor for the prevention of
transplant rejection and treatment of psoriasis.
Manicassamy S.
Emory University, Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA
30329, USA. sma...@emory.edu
Blocking T-cell activation has a central role in the control of
inflammatory diseases and in the prevention of graft rejection.
Historically, immunosuppressive drugs have been used to prevent
allograft rejection and to promote transplant tolerance. Several
immunosuppressive drugs are effective in suppressing T-cell
activation, but are often associated with severe adverse effects. The
development of effective immunosuppressants that promote long-term
graft survival with minimal adverse effects is therefore of great
interest. As PKC has a critical role in the regulation of immune cell
function, drugs that are highly specific for PKC are considered
potentially useful for treating allograft rejection, as well as
autoimmune and other inflammatory diseases. Novartis AG is developing
the pan-PKC-specific inhibitor sotrastaurin (AEB-071) for the
prevention of transplant rejection and for the treatment of
inflammatory diseases. In vivo data from rodents and non-human
primates confirmed the potential of sotrastaurin for preventing
allograft rejection and reducing the inflammatory response. Data from
an initial clinical trial in patients with psoriasis demonstrated that
treatment with sotrastaurin resulted in improvements in clinical and
histological assessments; however, data from early trials in kidney
transplant recipients were less encouraging. Sotrastaurin is
undergoing phase I trials for liver transplantation, and phase II
trials for renal transplantation and psoriasis treatment. Although
sotrastaurin appears to be well tolerated based on published clinical
trial data, long-term data need to be reported to confirm the safety
and efficacy profile of this novel compound.
PMID: 19876790
The next one in the search of PKC + P:
Sotrastaurin is (AEBO71) -- Just so you KNOW.
-----
The PKC inhibitor AEB071 may be a therapeutic option for psoriasis.
Skvara H, Dawid M, Kleyn E, Wolff B, Meingassner JG, Knight H,
Dumortier T, Kopp T, Fallahi N, Stary G, Burkhart C, Grenet O, Wagner
J, Hijazi Y, Morris RE, McGeown C, Rordorf C, Griffiths CE, Stingl G,
Jung T.
Department of Dermatology, Division of Immunology, Allergy and
Infectious Diseases, Medical University of Vienna, Vienna, Austria.
PKC isoforms tau, alpha, and beta play fundamental roles in the
activation of T cells and other immune cell functions. Here we show
that the PKC inhibitor AEB071 both abolishes the production of several
cytokines by activated human T cells, keratinocytes, and macrophages
in vitro and inhibits an acute allergic contact dermatitis response in
rats. To translate these findings into humans, single and multiple
ascending oral doses of AEB071 were administered to healthy volunteers
and patients with psoriasis, respectively. AEB071 was well tolerated
with no clinically relevant laboratory abnormalities. Ex vivo
stimulation of lymphocytes from subjects exposed to single doses of
AEB071 resulted in a dose-dependent inhibition of both lymphocyte
proliferation and IL2 mRNA expression. Clinical severity of psoriasis
was reduced up to 69% compared with baseline after 2 weeks of
treatment, as measured by the Psoriasis Area Severity Index (PASI)
score. The improvement in psoriasis patients was accompanied by
histological improvement of skin lesions and may be partially
explained by a substantial reduction of p40+ dermal cells, which are
known to mediate psoriasis. These data suggest that AEB071 could be an
effective novel treatment regimen for psoriasis and other autoimmune
diseases, and that AEB071 warrants long-term studies to establish
safety and efficacy.
PMID: 18688284 [PubMed - indexed for MEDLINE]
There isn't a wiki page for AEB071 yet:
http://en.wikipedia.org/wiki/Sotrastaurin_acetate
If your a pharma technocrat with computer ability i'm sure
you could lower the list of pharma terms needing a page:
http://en.wikipedia.org/wiki/Wikipedia:Requested_articles/list_of_missing_pharmacology
===============
Eat Mastic to kill h. pylori....
Like eating kimchi to kill SFB?
Sure, I hope that's what happening.
http://www.life-enhancement.com/article_template.asp?ID=659
Mastic Creates Gastrointestinal Harmony
By Will Block
Herbal product provides counterpoint to triple drug therapy
he renowned nineteenth-century violinist Niccolò Paganini's
gastrointestinal problems may have been caused by the bacterium
Helicobacter pylori (H. pylori), which has only in the last two
decades been revealed as a cause of dyspepsia, ulcers, and stomach
cancer. Ironically, Paganini might have soothed that beastly bacterium
if he had added mastic - an ingredient in the varnish used by the
legendary violinmakers of Cremona, Italy - to his diet.
<sniP>
======
First mastic to kill h. pylori and now nano bubble gum for Gut drug
delivery
http://www.medicalnewstoday.com/articles/170424.php
Of the many characteristic traits a drug can have, one of the most
desirable is the ability for a drug to be swallowed and absorbed into
the bloodstream through the gut. Some drugs, like over-the-counter
aspirin, lend themselves to this mode of delivery and are trivial to
take. They can be pressed into a pill and swallowed. Other drugs
cannot be swallowed and must be administered instead through more
complicated routes. Insulin, for instance, must be injected.
The reason why insulin and many other drugs cannot be swallowed is
that they cannot survive the trip through the digestive tract --
wherein they are first plunged into the acid bath of the stomach and
then passed into the intestines, which are filled with enzymes
designed to break down molecules like insulin. Aspirin does fine in
the gut because its active ingredient is a small chemical that doesn't
get broken down. But insulin is quickly degraded.
Tejal A. Desai (University of California, San Francisco) is looking at
ways to enhance the "oral availability" of drugs by designing new
delivery devices that will help their absorption in the gut, which she
will present on November 12 at a meeting of the scientific society AVS
in San Jose. Working with a Bay-area biotechnology company, she is
making devices that are sort of like spiny beads filled with drugs.
The spines on these beads are silicon nanowires designed to form an
adhesive interface with the tiny, hair-like cilia that cover the cells
lining the gut. They are designed to stick like burrs to the cells
lining the gut and slowly release their drugs there. Localized in one
spot, the drugs have a better chance of diffusing into the
bloodstream.
Desai is currently fine-tuning the geometry of the nanowires in order
to optimize their adhesion. Her laboratory has done a number of
toxicity studies with the beads, and their plan next is to look at how
effectively they can deliver proteins, peptides, and other
macromolecules that are not usually taken orally.
One of the advantages of this approach, Desai says, is that it may be
applicable for delivering drugs to other part of the body as well,
such as mucosal tissues like the insides of the nose, lungs, or
vagina, where the surface cells are also coated with such cilia.
<sniP>
================
What the Inventor of the Flu Shot NOW Thinks of the Vaccine...
Posted by: Dr. Mercola
http://articles.mercola.com/sites/articles/archive/2009/11/17/Obama-Administration-Launches-Deceptive-Swine-Flu-Propaganda-Blitz.aspx
President Obama and his top health officials are engaging in a major
public relations effort to divert attention away from whether its
swine flu vaccine is effective and safe by focusing attention on
whether there is enough of it to go around. And the media is
cooperating fully.
Increasing numbers of scientists and doctors are issuing harsh
criticisms of the government’s plan to vaccinate virtually the entire
U.S. population with a poorly tested vaccine that is not only
ineffective against swine flu, but could cripple and even kill many
more people than it helps.
The CDC’s public relations campaign has been running “scare” ads that
portray swine flu as a full-blown “pandemic” responsible for snuffing
out countless lives. But scientists and health officials throughout
the world have called the governments claims unjustified and
deliberately misleading.
Sources:
The article above, written by Richard Gale, a former Senior Research
Analyst in the biotechnology and genomic industries, and Dr. Gary
Null, author of Vaccine Nation, highlights one of the latest
propaganda techniques used to frighten you into action, namely
“scarcity of H1N1 vaccines.”
We’ve seen this tactic used before, with great effect, as people rush
to the nearest vaccination facility to make sure they don’t miss the
opportunity to be the one to get this rare life sustaining elixir.
It amazes me that despite all the evidence to the contrary, health
officials and mass media are still saying the swine flu could kill
some 90,000 Americans – if we don’t all get vaccinated.
There is simply NO evidence to support this outlandish projection. The
evidence actually points to the exact opposite, that this season will
have LESS deaths from flu than last year.
The data is very clear that it’s a milder than normal virus, only a
few percent of all cases with the designation “swine flu” are actually
the H1N1 virus, and in the Southern Hemisphere, people got over the
wave of the flu just fine, before the vaccine was even available.
Government's Claims Unjustified and Deliberately Misleading
<sniP>
LOOK at this picture and you tell me:
http://articles.mercola.com/imageserver/public/2009/November/H1N1over-estimatedCBS.gif
============
GAS group A sTREPtococci
http://www.medicalnewstoday.com/articles/170441.php
The whole taco for above GAS story:
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000651
Abstract Top
Group A streptococcus (GAS) causes a wide variety of human diseases,
and at the same time, GAS can also circulate without producing
symptoms, similar to its close commensal relative, group G
streptococcus (GGS). We previously identified, by transposon-tagged
mutagenesis, the streptococcal invasion locus (sil). sil is a quorum-
sensing regulated locus which is activated by the autoinducer peptide
SilCR through the two-component system SilA-SilB. Here we characterize
the DNA promoter region necessary for SilA-mediated activation. This
site is composed of two direct repeats of 10 bp, separated by a spacer
of 11 bp. Fusion of this site to gfp allowed us to systematically
introduce single-base substitutions in the repeats region and to
assess the relative contribution of various positions to promoter
strength. We then developed an algorithm giving different weights to
these positions, and performed a chromosome-wide bioinformatics search
which was validated by transcriptome analysis. We identified 13 genes,
mostly bacteriocin related, that are directly under the control of
SilA. Having developed the ability to quantify SilCR signaling via GFP
accumulation prompted us to search for GAS and GGS strains that sense
and produce SilCR. While the majority of GAS strains lost sil, all GGS
strains examined still possess the locus and ~63% are able to respond
to exogenously added SilCR. By triggering the autoinduction circle
using a minute concentration of synthetic SilCR, we identified GAS and
GGS strains that are capable of sensing and naturally producing SilCR,
and showed that SilCR can be sensed across these streptococci species.
These findings suggest that sil may be involved in colonization and
establishment of commensal host-bacterial relationships.
<sniP>
=====================
http://www.medicalnewstoday.com/articles/170978.php
Need A Helping Hand? Just Infect A Stranger With A Cooperative Gene
Cooperation is seen in every corner of life from microbes to humans,
many times with no obvious advantages to those that provide it at high
costs. Given the existence of "freeloading cheaters" ready to exploit
the resources of those cooperating, why is it that cooperation
persist? In an article now published in the journal Current Biology
Nogueira and colleagues suggest that in bacteria this can result from
highly mobile genes that "jump" from one cell to the next carrying the
cooperative traits, effectively turning everyone into a cooperator.
They also show that, at least in Escherichia coli (E. coli), this new
population remains stable through "punisher" genes that impose a mafia-
like strategy of "cooperation or death", ensuring that the new
cooperators do not revert to freeloading. The work by shedding some
light on the complex interactions of microbes that ultimately
determine which bacteria thrive or disappear can have important
implications for both human health and economy.
Scientists now agree that cooperation thrives if it benefits the
cooperator or/and its relatives. The logic behind this last behaviour
resides in the fact that to benefit relatives - which are genetically
very similar to the cooperator is to increase the probability that
shared genes, including the cooperative traits, will pass to the next
generation. Natural selection that preserves cooperative behaviours
benefiting relatives sometimes even at a cost to the cooperator's
survival and/or reproduction is called kin selection. Classic examples
of kin selection in action are "watchers" individuals that, at the
expense of their own security, guard and raise the alarm in the
community or the sterile workers found in ants and honey bees
colonies. So cooperation is affected not only by its costs and
benefits, but also by the genetic similarity between cooperator and
those benefiting from the behaviour, with higher relatedness
increasing the probability of cooperation occur.
Following this idea Teresa Nogueira (Centre for Environmental Biology,
Univ. Lisbon, and Superior School of Health Technology of Oporto,
Portugal), Eduardo P.C. Rocha and colleagues, at the Institute Pasteur
and the UPMC Univ. Paris 06 (Paris, France) while trying to understand
cooperation among bacteria wondered if horizontal gene transfer a non-
sexual process, very common in bacteria, where genes "jump" from one
individual to another by increasing the genetic similarity between
"infected" individuals, could lead to cooperation via kin selection.
Using mathematical tools and adding the effect of horizontal gene
transfer to costs, benefits and genetic similarity the researchers
confirmed that theoretically at least highly mobile genes carrying
cooperative traits should promote cooperation, which is then be
maintained by kin selection.
To confirm this hypothesis Nogueira and colleagues looked at E.coli,
which is an abundant microorganism in the human gut flora, where the
bacteria typically live in a mutually beneficial relationship with
humans. However, changes in its social interactions with other
microbes and/or the human host can turn E. coli into an extremely
virulent organism, making it a particular interesting subject for this
study. Not only that, but many of E. coli vital functions depend on
secreted proteins (the so called secretome) that are easily exploited
by other microbes, turning E. coli into a potential "collaborator",
even if an unintentional one.
The work now published analyses 21 E. coli genomes and their secretome
genes and starts by finding that only a very small percentage of them
are part of the "core genome" those genes shared by all the strains of
the species so, supposedly, those linked to functions crucial for
survival what agrees with the idea that the secretome contains
cooperative traits, since, by definition, cooperative genes can be
easily lost by natural selection.
Next Nogueira and colleagues try to identify the proteins of the
secretome by comparing them to a large known sample from the human
gut. And in fact, several of them were potential cooperative traits
but, and even more interesting, they also found many E. coli secretome
genes in other bacteria. This agrees with Nogueira's prediction that
cooperative traits accumulate in highly mobile genes that, by "moving
around", increase the genetic similarity of previously unrelated
bacteria (in this case, even across species). This conclusion was
further supported by the fact that large part of the secretome was
found to be coded by a piece of extra-chromosomal DNA called plasmid,
which is, simply, the most mobile part of the whole bacterial genome
Finally, secreted proteins are costly as they are not recycled and if
Nogueira's hypothesis was correct - as cooperative traits liable to be
exploited by cheaters, they should be under intense selection
pressure. And indeed the secretome was found to comprise the proteins
least expensive to produce in the entire organism, consistent with
cooperation costs.
A last question remained - if highly mobile cooperative genes, by
jumping between individuals, turn everyone into a cooperator, in the
same way their mobility should lead them to be easily lost, creating,
yet again, a new freeloading population. So how is this avoided? One
way would be by imposing punishments and this possibility led Nogueira
and colleagues to search for proteins known to stabilize gene
integration by "punishing" the organism if the gene is lost.
And indeed they found two such mechanisms - the "Restriction
Modification" and the "Bacterial Toxin Antitoxin" system. Both systems
work as a complex of two genes where one provokes the death of the
host if the other goes missing. In E. coli these systems were found
next to the secretome genes suggesting that the stability of the new
cooperator population is maintained by making the cost of losing the
cooperative trait higher then the benefit of becoming a freeloader.
In conclusion, Nogueira and colleagues' work showed that the secreted
proteins of E. coli behave as cooperative traits - they are part of
the "disposable" part of the genome, show signs of intense selective
pressure and some were even identified as potential cooperative
traits. In agreement with the researchers' model most of the genes
coding for the secretome are located in the highest mobile part of the
bacterial genome and found to be shared by other bacteria. This last
increased genetic similarity allows the cooperative traits to stay in
the population through kin selection, while "punisher" genes further
assure the stability of the new population via a "cooperate or die"
policy.
These results strongly suggests that like Nogueira proposed
cooperation among bacteria can be enforced by extremely mobile genes
containing the cooperative traits that jumping between individuals
turn them into cooperators. This new population is then maintained by
kin selection and punishment.
Microbes are used in a variety of jobs important for humans, from
cleaning petroleum oil of the oceans or wastage treatment to food
growth, and, of course, they are crucial agents of disease and health.
They are also extremely social organisms normally living in a mix of
many different species - the flora of the human gut is a good example
with different populations growing more or less in result of the
social interaction between them and/or the host. Nogueira, Rocha and
colleagues' work is an important step in the understanding of these
complex relationships and might contribute one day for better ways of
manipulating bacterial growth, whether with the intention of stopping
pathogenic populations or to stimulate beneficial ones. In the
specific case of E. coli this knowledge is particularly important as
many of its cooperative traits are virulence factors capable of
turning a normally innocuous bacteria into a life-threatening
dangerous pathogen.
================
Talent hits a target no one else can hit; Genius hits a target no one
else can see.
Arthur Schopenhauer
First and last, what is demanded of genius is love of truth.
Johann Wolfgang von Goethe
Some in this country are in LOVE with their LIEs....
Barney Frank did the tANGO with Bush. LOL
And the fifth rail of PAL- o- tics...
Kissing the behind of the weak and stupidly minded to garner democrap
or puboCRAP control
of the gov...
What a bummer.
http://en.allexperts.com/e/g/ge/george_w._bush.htm
[...]
Bush made it the centerpiece of his agenda despite contrary beliefs in
the media and in the U.S. Congress, which saw the program as the
"fifth rail of politics," with the American public being suspicious of
any attempt to change it.
<snip>
And now we eat crap served by the filth rail of socialist PALotics,
aka the mainstream media for OBAMAnation.
When are the three BIG PIG sisters of the media gonna stop lying?
Never...
Their all the wicked byatch of the WEST now.
The third rail or fifth rail to serfdom:
http://seniorliving.about.com/od/socialsecurity101/a/socialsecurity.htm
It was former U.S. House Speaker Thomas “Tip” O’Neill who first called
Social Security the “third rail of American politics,” and O’Neill did
as much as anyone to make Social Security a deadly political issue.
How Did Social Security Become the Third Rail of American Politics?
Social Security had become a difficult political issue long before the
early 1980s when Tip O’Neill designated it the third rail of American
politics. When Barry Goldwater lost the presidency to Lyndon Johnson
in 1964, for example, many observers believed the loss was due in part
to voter perception that Goldwater wanted to dismantle Social
Security.
[...]
Politicians often call Social Security the “third rail of American
politics.” But what does that mean?
What is a Third Rail?
Many trains that are powered by electricity, such as subways and other
rapid transit railway systems, are attached to a third rail that runs
alonside the tracks. The third rail provides electricity, which powers
the train.
This is a good thing for trains. But for a person, touching the third
rail means instant electrocution, or death by electrical shock.
What are Third Rail Issues in U.S. Politics?
In politics, a “third rail” issue is one that is so politically
charged and controversial that any politician who dares to touch it
risks destroying his or her career.
<sniP>
Give me LIberty or give me...
Liberty not gov mandated big pig gov socialism....
----
The state of a free person; exemption from subjection to the will of
another claiming ownership of the person or services; freedom; --
opposed to slavery, serfdom, bondage, or subjection.
<sniP>
How about freedumb from tyranny?
From a dip wad prez?
NO WAY he's so kewl... and we LOVE him..
You do?
https://www.hillsdale.edu/news/imprimis/archive/issue.asp?year=2009&month=10
http://www.hillsdale.edu/news/imprimis/archive/issue.asp?year=2009&month=07
==============
http://www.wellnessresources.com/health/articles/nac_reduces_biofilm_formation/
NAC Reduces Biofilm Formation
Wednesday, November 18, 2009 - Byron Richards, CCN
Germ gangs, otherwise known as biofilms, indicate that a “call to war”
is linking bacteria together in a hostile mode that attacks the human
host. A new study shows that NAC (N-acetyl-cysteine) can reduce
biofilm formation by 62% - a rather astounding finding for a nutrient.
The researchers tested NAC against a wide variety of problematic
bacteria, including Staphylococcus aureus, Staphylococcus epidermidis,
Escherichia coli, Klebseilla pneumoniae, Pseudomonas aeruginosa and
Proteus vulgaris. Once these organisms form biofilms they are often
resistance to antibiotics and very difficult to get rid of. Too bad
NAC wasn’t tested against Candida albicans biofilms, as I bet it works
on them too.
The precise mechanism of how NAC works its anti-biofilm magic is
unknown. NAC is an important antioxidant that fuels the production of
cellular glutathione. NAC is known to dissolve mucous and is an
excellent respiratory support nutrient. Low levels of NAC reduce the
functionality of immune troops that patrol mucosal surfaces. However,
to dissolve a biofilm there must be a direct communication into the
germ gang that fools its defense shield. Right now we don’t know how
it works – we just know it works.
<snip>
========
Th22 subset:
www.ncbi.nlm.nih.gov/pubmed/19920355
Th22 cells represent a distinct human T cell subset involved in
epidermal immunity and remodeling.
Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S,
Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR,
Schmidt-Weber CB, Cavani A.
Th subsets are defined according to their production of lineage-
indicating cytokines and functions. In this study, we have identified
a subset of human Th cells that infiltrates the epidermis in
individuals with inflammatory skin disorders and is characterized by
the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or
IL-17. In analogy to the Th17 subset, cells with this cytokine profile
have been named the Th22 subset. Th22 clones derived from patients
with psoriasis were stable in culture and exhibited a transcriptome
profile clearly separate from those of Th1, Th2, and Th17 cells; it
included genes encoding proteins involved in tissue remodeling, such
as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary
human keratinocytes exposed to Th22 supernatants expressed a
transcriptome response profile that included genes involved in innate
immune pathways and the induction and modulation of adaptive immunity.
These proinflammatory Th22 responses were synergistically dependent on
IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound
healing in an in vitro injury model, which was exclusively dependent
on IL-22. In conclusion, the human Th22 subset may represent a
separate T cell subset with a distinct identity with respect to gene
expression and function, present within the epidermal layer in
inflammatory skin diseases. Future strategies directed against the
Th22 subset may be of value in chronic inflammatory skin disorders.
PMID: 19920355
=================
Lipopolysaccharide exposure is linked to activation of the acute phase
response and growth failure in pediatric Crohn's disease and murine
colitis.
Pasternak BA, D'Mello S, Jurickova II, Han X, Willson T, Flick L,
Petiniot L, Uozumi N, Divanovic S, Traurnicht A, Bonkowski E,
Kugathasan S, Karp CL, Denson LA.
Department of Pediatric Gastroenterology, Phoenix Children's Hospital,
Phoenix, Arizona.
BACKGROUND:: Systemic exposure to lipopolysaccharide (LPS) has been
linked to clinical disease activity in adults with inflammatory bowel
disease (IBD). We hypothesized that markers of LPS exposure and the
acute phase response (APR) would be increased in pediatric IBD
patients with growth failure, and that LPS signaling would be required
for induction of the APR in murine colitis. METHODS:: Serum markers of
LPS exposure, endotoxin core IgA antibody (EndoCAb), and the APR, LPS
binding protein (LBP) were quantified in pediatric IBD patients and
controls. LBP and cytokine production were determined after
administration of trinitrobenzene sulfonic acid (TNBS) enemas to mice
with genetic deletion of Toll-Like receptor 4 (TLR4), and wildtype
(WT) controls. RESULTS:: Serum EndoCAb and LBP were significantly
elevated in patients with Crohn's disease (CD), compared to disease
controls with ulcerative colitis (UC) and healthy controls (P <
0.001). This was independent of disease activity or location. CD
patients with elevated serum EndoCAb and LBP exhibited linear growth
failure which persisted during therapy. Serum LBP increased in WT mice
following TNBS administration, in conjunction with increased serum TNF-
alpha, IL-6, and IL-10, and expansion of regulatory T-cell numbers.
Both the APR and expansion of foxp3+ T cells were abrogated in TLR4-
deficient mice, in conjunction with a reduction in acute weight loss.
CONCLUSIONS:: LPS exposure and a persistent APR are associated with
growth failure in pediatric CD. LPS signaling is required for the APR
in murine colitis. Therapies targeting this pathway may benefit the
subset of patients with refractory growth failure. (Inflamm Bowel Dis
2010).
PMID: 19924809
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Charts and things:
B cells ---> T Cells --> Th1 or Th2 --- Th17 or IL-10
That is the question.
http://www.mayoclinic.com/images/image_popup/r7_immunesystem.jpg
http://www.lymphomation.org/images/leukocytes-normal.gif
http://www.mhhe.com/biosci/esp/2001_gbio/folder_structure/an/m10/s3/anm10s3_1.htm
http://www.jci.org/articles/view/28508/figure/1
http://img.medscape.com/article/588/101/588101-fig1.jpg
D0 you use biolegend?
http://www.biolegend.com/media_assets/pfeatured/Chemokine_Family-Circlev4.jpg
http://images.google.com/imgres?imgurl=http://www.biolegend.com/media_assets/pfeatured/Chemokine_Family-Circlev4.jpg&imgrefurl=http://www.biolegend.com/index.php%3Fpage%3Dpfeatured%26id%3D10&usg=__bDQj9hBGpDTelbLIOicCb-G6rBs=&h=558&w=682&sz=266&hl=en&start=8&sig2=VFcYH05r6wwxHld1t1Z7qA&tbnid=_rRJI-7U5Am8SM:&tbnh=114&tbnw=139&prev=/images%3Fq%3DT%2Bcells%2BTh1%2BTh2%2BTh22%26hl%3Den%26sa%3DG&ei=EsQKS62FOKiqnAfgzqDSCw
http://www.biolegend.com/index.php?page=pfeatured&id=7
=================
randall ... crap is almost funny after a while