Current ABSTRACTs - Psors4 - - Autophagy --MIF --M1 M2 with Th1 Th2 -- IL-19 much much turbo on speed more +++++
randall
for me:
http://www.ncbi.nlm.nih.gov/pubmed/21148126
Sci Transl Med. 2010 Dec 8;2(61):61ra90.
Gene from a psoriasis susceptibility locus primes the skin for
inflammation.
Wolf R, Mascia F, Dharamsi A, Howard OM, Cataisson C, Bliskovski V,
Winston J, Feigenbaum L, Lichti U, Ruzicka T, Chavakis T, Yuspa SH.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research,
National Cancer Institute, Bethesda, MD 20892, USA.
Abstract
Psoriasis is a common complex genetic disease characterized by
hyperplasia and inflammation in the skin; however, the relative
contributions of epidermal cells and the immune system to disease
pathogenesis remain unclear. Linkage studies have defined a psoriasis
susceptibility locus (PSORS4) on 1q21, the epidermal differentiation
complex, which includes genes for small S100 calcium-binding proteins.
These proteins are involved in extracellular and intracellular
signaling during epithelial host defense, linking innate and adaptive
immunity. Inflammation-prone psoriatic skin constitutively expresses
elevated concentrations of S100A7 (psoriasin) and S100A15
(koebnerisin) in the epidermis. Here, we report that genetically
modified mice expressing elevated amounts of doxycycline-regulated
mS100a7a15 in skin keratinocytes demonstrated an exaggerated
inflammatory response when challenged by exogenous stimuli such as
abrasion (Koebner phenomenon). This immune response was characterized
by immune cell infiltration and elevated concentrations of T helper 1
(T(H)1) and T(H)17 proinflammatory cytokines, which have been linked
to the pathogenesis of psoriasis and were further amplified upon
challenge. Both inflammation priming and amplification required
mS100a7a15 binding to the receptor of advanced glycation end products
(RAGE). mS100a7a15 potentiated inflammation by acting directly as a
chemoattractant for leukocytes, further increasing the number of
inflammatory cells infiltrating the skin. This study provides a
pathogenetic psoriasis model using a psoriasis candidate gene to link
the epidermis and innate immune system in inflammation priming,
highlighting the S100A7A15-RAGE axis as a potential therapeutic
target.
PMID: 21148126
I worry about calcium and stroking OUT via these gene sets.
Yikes... it's IN our GENEs...
OK be in the here and NOW boy..
Right...
Did psors4 with ERAP1 iirc recently:
Yep - 3 weeks ago & only 13 hits for OUR ENTIRE GROUp?
OK make it 14 hits and do it RIGHT?
Right.
psors4
http://www.ncbi.nlm.nih.gov/gene/10547
a note for psors4:
http://www.ncbi.nlm.nih.gov/pubmed/15598222
[...] Characterization of the loricrin (LOR) gene as a positional
candidate for the PSORS4 psoriasis susceptibility locus.
[...] This rules out the LOR gene as a candidate for the PSORS4 locus
pmid: 15598222
WELL if erap was with it or not i'm blurbing ERap1:
Erap1:
http://www.ncbi.nlm.nih.gov/gene/51752
Official Full Name endoplasmic reticulum aminopeptidase 1
[...] Also known as ALAP; A-LAP; ARTS1; ERAAP; APPILS; ARTS-1; ERAAP1;
PILSAP; PILS-AP; KIAA0525; ERAP1
Summary The protein encoded by this gene is an aminopeptidase involved
in trimming HLA class I-binding precursors so that they can be
presented on MHC class I molecules. The encoded protein acts as a
monomer or as a heterodimer with ERAP2. This protein may also be
involved in blood pressure regulation by inactivation of angiotensin
II. Three transcript variants encoding two different isoforms have
been found for this gene.
<snip>
--------
Autophagy has been BIG recently as WELL:
http://www.ncbi.nlm.nih.gov/pubmed/21160040
J Immunol. 2010 Dec 15.
Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via
Scaffolding Protein p62/SQSTM1.
Lee HM, Shin DM, Yuk JM, Shi G, Choi DK, Lee SH, Huang SM, Kim JM, Kim
CD, Lee JH, Jo EK.
Department of Microbiology, Chungnam National University, Daejeon
301-747, South Korea;
Abstract
The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be
an autophagy receptor that acts as a link between the ubiquitination
and autophagy machineries. However, the roles of autophagy and p62 in
human keratinocytes are not well understood. In this study, we show
that keratinocyte autophagy negatively regulates p62 expression, which
is essential for the prevention of excessive inflammation and the
induction of cathelicidin in human keratinocytes. Stimulation of
TLR2/6 or TLR4 in primary human keratinocytes robustly activated
autophagy pathways and up-regulated p62 expression through induction
of NADPH oxidases 2 and 4 and the generation of reactive oxygen
species. MyD88 and TNFR-associated factor 6, key signaling molecules
that mediate TLR activation, played an essential role in the induction
of autophagy and p62 expression. Additionally, blockade of autophagy
significantly increased the generation of inflammatory cytokines and
expression of p62 in primary human keratinocytes. Notably, silencing
hp62 through RNA interference resulted in a significant decrease in NF-
κB activation, inflammatory cytokine production, cathelicidin
expression, and cell proliferation (as well as cyclin D1 expression)
in keratinocytes. Epidermal expression of p62 was further found to be
significantly higher in psoriatic skin than in skin affected by atopic
dermatitis or from healthy controls. Collectively, our data provide
new insights into the roles of autophagy and p62 in controlling
cutaneous inflammation.
PMID: 21160040
I'd BET $'s to donuts that we dont' have one of these in the P NG? LOL
You'd be a doughNUT if you did. <w>
188 hits- p62+SQSTM1 - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=p62+SQSTM1
83 of these have kicker tERm : autophagy
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=p62+SQSTM1+autophagy
http://en.wikipedia.org/wiki/Autophagy
How does autophagy work with skin cells that blast
off 10-1000 times faster then normal 30 day skin cells?
Turbo autophagy?
Autophagy on sPeed?
Or does aPoPtosis over ride the turbo?
Wow i found the go to GUY for popPing off.
http://www.ncbi.nlm.nih.gov/pubmed/18336289
To die or not to die: that is the autophagic question.
Galluzzi L, Vicencio JM, Kepp O, Tasdemir E, Maiuri MC, ___Kroemer
G___
[...] Thus, autophagy occupies a crucial position within the cell's
metabolism, and its modulation may represent an alternative
therapeutic strategy in several pathological settings including cancer
and neurodegeneration. Here, we present a general outline of autophagy
followed by a detailed analysis of organelle-specific autophagic
pathways and of their intimate connections with cell death.
PMID: 18336289
Kroemer is HOT and shakes it up. :)
563 hits for him --pumbed
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kroemer%20G%22%5BAuthor%5D
His most recent is cancer in the ER.. yikes.. it must be a SIGN?
http://www.ncbi.nlm.nih.gov/pubmed/21151176
Oncogene. 2010 Dec 13. [Epub ahead of print]
Restoration of the immunogenicity of cisplatin-induced cancer cell
death by endoplasmic reticulum stress.
<snip>
-----
Back to that protein please?
OK.. your right... i'm wrong for going LONG.
http://www.ncbi.nlm.nih.gov/gene/8878
Official Symbol SQSTM1provided by HGNC
Official Full Name sequestosome 1
[...] Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata;
Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates;
Haplorrhini; Catarrhini; Hominidae; Homo
Also known as p60; p62; A170; OSIL; PDB3; ZIP3; p62B; SQSTM1
Summary This gene encodes a multifunctional protein that binds
ubiquitin and regulates activation of the nuclear factor kappa-B (NF-
kB) signaling pathway. The protein functions as a scaffolding/adaptor
protein in concert with TNF receptor-associated factor 6 to mediate
activation of NF-kB in response to upstream signals. Alternatively
spliced transcript variants encoding either the same or different
isoforms have been identified for this gene. Mutations in this gene
result in sporadic and familial Paget disease of bone.
<sniP>
OK your miffing me OFF.
Move on dot dork..
Right.
------------
http://www.ncbi.nlm.nih.gov/pubmed/21158933
Exp Dermatol. 2011 Jan;20(1):1-6. doi: 10.1111/j.
1600-0625.2010.01194.x.
MIF: a key player in cutaneous biology and wound healing.
Gilliver SC, Emmerson E, Bernhagen J, Hardman MJ.
Faculty of Life Sciences, University of Manchester, Manchester, UK
Department of Biochemistry & Molecular Cell Biology, RWTH Aachen
University, Aachen, Germany.
Abstract
Owing to its implication in a range of pathological conditions,
including asthma, rheumatoid arthritis, atherosclerosis, inflammatory
bowel disease and cancer, the pleiotropic cytokine macrophage
migration inhibitory factor (MIF) has been the subject of intensive
recent investigation. In the field of dermatology, MIF is believed to
be a detrimental factor in diseases such as systemic sclerosis, atopic
dermatitis, psoriasis, eczema and UV radiation damage. However, its
contribution to other aspects of cutaneous biology is currently
unclear. Although its expression in intact skin is well characterized,
little is known about MIF's role in cutaneous homoeostasis. However,
recent data do identify MIF as a key player in the immune privilege of
hair follicles. Similarly, although MIF is rapidly released and its
local expression significantly induced upon wounding, its primary role
in the ensuing repair process remains a source of contention. MIF has
been identified as being a key effector of the beneficial effects of
estrogen on wound repair, yet studies employing Mif null mice,
recombinant MIF, and neutralizing anti-MIF antibodies have failed to
provide a consensus as to whether it benefits or inhibits healing. In
fact MIF appears to be able to exert both positive and negative
effects, with the cell-specific relevancy of MIF in wound healing
still unclear. Thus, if MIF and/or its downstream targets are to be
therapeutically useful in the context of cutaneous repair, more needs
to be done to establish the nature and mechanism of action of MIF and
its receptors in healing wounds.
© 2010 John Wiley & Sons A/S.
PMID: 21158933
1754 hits:: mif+migration+factor - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=mif+migration+factor
---
http://www.ncbi.nlm.nih.gov/gene/4282
MIF macrophage migration inhibitory factor (glycosylation-inhibiting
factor) [ Homo sapiens ]
[...] Also known as GIF; GLIF; MMIF; MIF
Summary This gene encodes a lymphokine involved in cell-mediated
immunity, immunoregulation, and inflammation. It plays a role in the
regulation of macrophage function in host defense through the
suppression of anti-inflammatory effects of glucocorticoids. This
lymphokine and the JAB1 protein form a complex in the cytosol near the
peripheral plasma membrane, which may indicate an additional role in
integrin signaling pathways.
<snip>
------
for kofi:
http://www.ncbi.nlm.nih.gov/pubmed/21155006
pmid: 21155006
Boring...
OK give me less boring.
ALL RIGHT:
For Kofi and crohniac's-->m1/m2-> redux:
http://www.medicalnewstoday.com/articles/211108.php
Link Between Immune System Changes And Inflammatory Bowel Disease
<M1 & M2 vs Th1 & Th2 ?> Is it a IL-19 thing?>
Only three hits for: IL-19/IBD and two hits for IL-19 crohn's -
pubmed:
Not having FUN now. LOL
I did the other day.
Go back in time.. time child:
The DAY before Yesterdays post:
Had this link:
http://en.wikipedia.org/wiki/Leo_Tolstoy#Religious_and_political_beliefs
After reading Schopenhauer's The World as Will and Representation,
Tolstoy gradually became converted to the ascetic morality upheld in
that work as the proper spiritual path for the upper classes: "Do you
know what this summer has meant for me? Constant raptures over
Schopenhauer and a whole series of spiritual delights which I've never
experienced before. ... no student has ever studied so much on his
course, and learned so much, as I have this summer"[21]
In Chapter VI of A Confession, Tolstoy quoted the final paragraph of
Schopenhauer's work. It explained how the nothingness that results
from complete denial of self is only a relative nothingness, and is
not to be feared. The novelist was struck by the description of
Christian, Buddhist, and Hindu ascetic renunciation as being the path
to holiness. After reading passages such as the following, which
abound in Schopenhauer's ethical chapters, the Russian nobleman chose
poverty and formal denial of the will:
But this very necessity of involuntary suffering (by poor people) for
eternal salvation is also expressed by that utterance of the Savior
(Matthew 19:24): "It is easier for a camel to go through the eye of a
needle, than for a rich man to enter into the kingdom of God."
Therefore those who were greatly in earnest about their eternal
salvation, chose voluntary poverty when fate had denied this to them
and they had been born in wealth. Thus Buddha Sakyamuni was born a
prince, but voluntarily took to the mendicant's staff; and Francis of
Assisi, the founder of the mendicant orders who, as a youngster at a
ball, where the daughters of all the notabilities were sitting
together, was asked: "Now Francis, will you not soon make your choice
from these beauties?" and who replied: "I have made a far more
beautiful choice!" "Whom?" "La poverta (poverty)": whereupon he
abandoned every thing shortly afterwards and wandered through the land
as a mendicant.[22]
Tolstoy's Christian beliefs centered on the Sermon on the Mount,
particularly the injunction to turn the other cheek, which he saw as a
justification for pacifism, nonviolence and nonresistance. Various
versions of "Tolstoy's Bible" have been published, indicating the
passages Tolstoy most relied on, specifically, the reported words of
Jesus himself.[23] Tolstoy believed being a Christian required him to
be a pacifist; the consequences of being a pacifist, and the
apparently inevitable waging of war by government, made him a
philosophical anarchist.
Tolstoy believed that a true Christian could find lasting happiness by
striving for inner self-perfection through following the Great
Commandment of loving one's neighbor and God rather than looking
outward to the Church or state for guidance.
<snip>
notes:
http://bible.cc/matthew/19-24.htm
Tolstoy and Pax et bonum?
Francis Bernadone and Tolstoy?
And Christ in the WEST via Rome stinks, according to Leo Tolstoy? LOL
Is that what his problem with Shakespeare is?
Pax et bonum!
http://wiki.answers.com/wiki/Francis_of_Assisi used to greet those he
met on the road with the greeting Pax et bonum, which means Peace and
all good. Here is the translation of Pax et bonum in a number of
languages (sorted alphabetically according to language):
http://wiki.answers.com/Q/Definition_of_pax_et_bonum
Vrede en alles wat goed is! (Afrikaans)
السلام و كل خير (Arabic)
Xanti aru sob Bhaal (Axomiya)
Peoc'h ha madelezh! (Breton)
Мир и всичко добро! (Bulgarian)
Pau i Be! (Catalonian)
平安幸福! (Chinese tr.)
Mir i dobro! (Croatian)
Pokoj a dobro! (Czech)
Fred og alt godt! (Danish)
Vrede en alle goeds! (Dutch)
Vrede en al het goede (Dutch, alternative)
Peace and all good! (English)
Pacon kaj ĉiu bonon (Esperanto)
Bakea eta ongia! (Euskera-Basque)
Rauhaa ja kaikkea hyvää! (Finnish)
Paix et bonheur! (French)
Paz e ben! (Galician)
Friede und alles Gute! (German)
Freden un all Good! (German, Plattdeutsch)
Eirini kai Kalo! (Greek)
Eirene kai agatha! (old Greek)
Ka maluhia a me ka maika'i wale nō! (Hawaiian)
Shalom v'kol tuv! http://wiki.answers.com/wiki/File:PaxEtBonumHewbrew.gif
(Hebrew)
Shanti aur shubh kaamnaa (Hindi)
Frere un hääl (Hinner-pälzisch)
Aldas, Bekesseg! (Hungarian)
Damai Dan Segala Yang Baik (Indonesia / Bahasa Indonesian)
Siochan agus maitheas! (Irish)
Pace e bene! (Italian)
Shanti matthu Summanisina Hosathana (Kannada, India)
Samaadan aani Boremponn (Konkanni, India)
ئاشتى و هه موو باشية ك (Kurdish)
Pax et bonum! (Latin)
Paċi u risq! (Maltese)
Fred og alt godt! (Norwegian)
Pokój i dobro! (Polish)
Paz e Bem ! (Portuguese - Portugal/Brazil)
Pacea si Binele! (Romanian)
Мир и всево хорошево! (Russian)
Мир і добрo! (Serbian)
Runyararo ne Kunaka! (Shona)
Pokoj a dobro! (Slovak)
Mir in dobro! (Slovenian)
¡Paz y bien! (Spanish)
Fred och allt gott ! (Swedish)
Kapayapaan at kabutihan! (Tagalog, Philippines)
Samathanamum nallathum (Tamil, Sri Lanka)
அமைதியும் அனைத்து நன்மையும் (Tamil, Tamilnadu)
Shanti mariyu shubhamu (Telugu, India)
Dame Dohot Sude Na Denggan (Toba-batak, Sumatra, Indonesia)
Huzur ve iyilik üstüne olsun! (Turkish)
Мир і всього добра! (Ukrainian)
Kaane Wöön und ollas Guade! (Viennese)
Bình An và Thiện Hảo (Vietnamese)
Jamm ak lu bax rek (Wolof)
OK did i miss the Chinese pax et bonum? LOL
Get bablefish?
No.. go long.
======
IL-19 a Psor GUT triP or WHAT?
http://www.ncbi.nlm.nih.gov/pubmed/21157117
J Pharmacol Sci. 2010 Dec 9.
Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical
for Colonic Protection.
Azuma YT, Matsuo Y, Nakajima H, Yancopoulos GD, Valenzuela DM, Murphy
AJ, Karow M, Takeuchi T.
Laboratory of Veterinary Pharmacology, Division of Veterinary Science,
Osaka Prefecture University Graduate School of Life and Environmental
Science, Japan.
Abstract
The cytokine, interleukin (IL)-19, is a member of the IL-10 family
that includes IL-20, IL-22, IL-24, and IL-26. Recent studies have
shown that IL-19 is produced by keratinocytes, epithelial cells,
macrophages, and B-cells. Little is known about the exact biological
role of IL-19 in immunological regulation, although there is an
increasing body of data demonstrating that IL-19 is associated with
the development of Th2 responses and the pathogenesis of psoriasis. In
this review, I shall attempt to discuss current knowledge about the
role of IL-19 on macrophages and the potential role in inflammatory
bowel disease.
PMID: 21157117
Done in with an iL-10 sub family member?
Oh, how cruel...
http://en.wikipedia.org/wiki/Interleukin_19
Alt. symbols , MDA1, ZMDA1, IL-10C
Interleukin-19 is a cytokine that belongs to the IL-10 family of
cytokines along with several other interleukins including IL-10,
IL-20, IL-22, IL-24, IL-26, and several virus-encoded cytokines. It
signals through the same cell surface receptor (IL-20R) that is used
by IL-20 and IL-24. The IL-19 gene is expressed in resting monocytes
and B cells. It is up-regulated in monocytes following stimulation
with granulocyte-macrophage colony-stimulating factor (GM-CSF) or
lipopolysaccharide.[1]
<snip>
http://en.wikipedia.org/wiki/Interleukin_10
Symbols IL10; CSIF; IL-10; IL10A; MGC126450; MGC126451; TGIF
http://en.wikipedia.org/wiki/Interleukin_10#Function
It is capable of inhibiting synthesis of pro-inflammatory cytokines
like IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as
macrophages and regulatory T-cells
IL-10 also displays potent abilities to suppress the antigen
presentation capacity of antigen presenting cells.
However, it is also stimulatory towards certain T cells, mast cells
and stimulates B cell maturation and antibody production.
Expression
It is mainly expressed in monocytes and Type 2 T helper cells (TH2),
mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain
subset of activated T cells and B cells. Said et al. showed that IL-10
can also be produced by monocytes upon PD-1 triggering in this cells.
[5]
It is released by cytotoxic T-cells to inhibit the actions of NK cells
during the immune response to viral infection.
========================
Macrophage polar(bear)realizations of M1 and M2?
Is it more plasticity and coming of AGE?
Yes.. how'd you know?
http://www.cell.com/immunity/retrieve/pii/S1074761305003134
+++++++
M-1/M-2 Macrophages and the Th1/Th2 Paradigm from 2000:
OK do it:
J Immunol. 2000 Jun 15;164(12):6166-73.
M-1/M-2 macrophages and the Th1/Th2 paradigm.
Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM.
Department of Surgery, University of Minnesota, Minneapolis 55455,
USA. mill...@tc.umn.edu
Abstract
Evidence is provided that macrophages can make M-1 or M-2 responses.
The concept of M-1/M-2 fomented from observations that macrophages
from prototypical Th1 strains (C57BL/6, B10D2) are more easily
activated to produce NO with either IFN-gamma or LPS than macrophages
from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates
Th2, but not Th1, macrophages to increase arginine metabolism to
ornithine. Thus, M-1/M-2 does not simply describe activated or
unactivated macrophages, but cells expressing distinct metabolic
programs. Because NO inhibits cell division, while ornithine can
stimulate cell division (via polyamines), these results also indicate
that M-1 and M-2 responses can influence inflammatory reactions in
opposite ways. Macrophage TGF-beta1, which inhibits inducible NO
synthase and stimulates arginase, appears to play an important role in
regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are
independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or
SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities
are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages
cause CB6F1 lymphocytes to increase IFN-gamma production, while BALB/c
SCID macrophages increase TGF-beta production. Together, the results
indicate that M-1- or M-2-dominant macrophage responses can influence
whether Th1/Th2 or other types of inflammatory responses occur.
PMID: 10843666
Free Article
http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10843666
check out the articles citing this one:
http://www.jimmunol.org/content/164/12/6166.abstract
(like 100 of them? Wow... sir... i'm IMPRESSED)
I should read this one:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783278/
Alternatively activated macrophages in infection and autoimmunity
DeLisa Fairweather and Daniela Cihakovab
<snip>
OK give me their pmid and abstract.
sure
PMID: 19819674
http://www.ncbi.nlm.nih.gov/pubmed/19819674
J Autoimmun. 2009 Nov-Dec;33(3-4):222-30. Epub 2009 Oct 12.
Alternatively activated macrophages in infection and autoimmunity.
Fairweather D, Cihakova D.
Department of Environmental Health Sciences, Johns Hopkins University,
Bloomberg School of Public Health, Baltimore, MD 21205, USA.
dfai...@jhsph.edu
Abstract
Macrophages are innate immune cells that play an important role in
activation of the immune response and wound healing. Pathogens that
require T helper-type 2 (Th2) responses for effective clearance, such
as parasitic worms, are strong inducers of alternatively activated or
M2 macrophages. However, infections such as bacteria and viruses that
require Th1-type responses may induce M2 as a strategy to evade the
immune system. M2 are particularly efficient at scavenging self
tissues following injury through receptors like the mannose receptor
and scavenger receptor-A. Thus, M2 may increase autoimmune disease by
presenting self tissue to T cells. M2 may also exacerbate immune
complex (IC)-mediated pathology and fibrosis, a hallmark of autoimmune
disease in women, due to the release of profibrotic factors such as
interleukin-1beta, transforming growth factor-beta, fibronectin and
matrix metalloproteinases. We have found that M2 comprise anywhere
from 30% to 70% of the infiltrate during acute viral or experimental
autoimmune myocarditis, and shifts in M2 populations correlate with
increased IC deposition, fibrosis and chronic autoimmune pathology.
Thus, women may be at an increased risk of M2-mediated autoimmunity
due to estrogen's ability to increase Th2 responses.
PMID: 19819674
+++++++
LOOK at groups for awhile?
OK..
213 hits - m1 m2 macrophage - all groups:
http://groups.google.com/groups/search?hl=en&qt_s=1&q=m1+m2+macrophage
http://www.citeulike.org/blog/Zephyrus/5117
-----
http://archives.focus.hms.harvard.edu/2008/062008/research_briefs.shtml
Insight into Immune Switch Powers Hope for Intervention in Metabolic
Disease
Though chronic inflammation is associated with metabolic dysfunction,
the specific mechanisms underlying this connection have remained
obscure. Now, a team of researchers from Chih-Hao Lee’s lab at HSPH
has uncovered a molecular switch linking metabolic regulation to
inflammation control. Their research appears in the June Cell
Metabolism.
<snip>
-----
http://www.google.com/search?hl=en&q=gut+m1+m2+macrophage+ppar&aq=f&aqi=&aql=&oq=&gs_rfai=
i see one that looks familiar:
http://journals.lww.com/co-clinicalnutrition/Abstract/2010/09000/Dietary_conjugated_linoleic_acid_and_n_3.11.aspx
Dietary conjugated linoleic acid and n-3 polyunsaturated fatty acids
in inflammatory bowel disease
Bassaganya-Riera, Josep; Hontecillas, Raquel
Purpose of review: Inflammatory bowel disease (IBD) is a debilitating
and widespread immune-mediated illness of unknown etiology. Current
treatments are modestly successful and with significant side-effects.
The purpose of this review is to summarize the current understanding
of mechanisms of action underlying the anti-inflammatory actions of
conjugated linoleic acid (CLA) and n-3 polyunsaturated fatty acids
(PUFAs) in IBD.
Recent findings: Nutrition-based interventions that target peroxisome
proliferator-activated receptors (PPARs) such as dietary CLA and n-3
PUFA have demonstrated anti-inflammatory efficacy in animal models of
IBD. Clinical data on n-3 PUFA in IBD remains generally unimpressive,
although results of a recent human study demonstrate that IBD
remission can be maintained by maintaining the n-3: n-6 ratio more
than 0.65 via n-3 PUFA intervention. In mice, CLA prevented
inflammation-driven colorectal cancer by activating PPAR γ and
modulating regulatory T cells and macrophages. CLA is the subject of
an ongoing clinical study in Crohn's disease patients.
Summary: Compelling evidence demonstrates that n-3 PUFA and CLA
prevent or ameliorate IBD in animal models. However, this basic
knowledge has not been translated into novel nutrition-based clinical
interventions. For both compounds there is an urgent need for placebo-
controlled, large-scale, multicenter clinical trials.
<snip>
But i don't see M1 and M2?
Next abstract?
OK it was this one:
Dietary conjugated linoleic acid and n-3 polyunsaturated fatty acids
in inflammatory bowel disease
Bassaganya-Riera, Josep; Hontecillas, Raquel
Current Opinion in Clinical Nutrition & Metabolic Care. 13(5):569-573,
September 2010.
doi: 10.1097/MCO.0b013e32833b648e
<snip>
They just didn't mention them in the abstract, perhaPs.
Whatever moron boy. LOL
Let's find free jpgs?
OK
WOW--> great M1 M2 BIG MAC attack in the gut jpg:
http://www.nature.com/ni/journal/v11/n10/images_article/ni.1937-F1.jpg
http://www.nature.com/ni/journal/v11/n10/images_article/ni.1937-F3.jpg
Oh, oh this is a good m1/m2 jpg
http://www.nature.com/ni/journal/v11/n10/images_article/ni.1937-F2.jpg
<randumb note: this is like Th1 and Th2 with LPS, cePt it's M1 M2-->
LPS, LOL>
Warning:
This one get's wormy... crohniac's beware... waring over...
OK you've been warned:
http://www.ncbi.nlm.nih.gov/pubmed/20729857
Nat Immunol. 2010 Oct;11(10):936-44. Epub 2010 Aug 22.
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host
responses against helminth infection.
Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y,
Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui
K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S.
Laboratory of Host Defense, World Premiere Initiative Immunology
Frontier Research Center, Osaka University, Osaka, Japan.
Comment in:
Nat Immunol. 2010 Oct;11(10):879-81.
Abstract
Polarization of macrophages to M1 or M2 cells is important for
mounting responses against bacterial and helminth infections,
respectively. Jumonji domain containing-3 (Jmjd3), a histone 3 Lys27
(H3K27) demethylase, has been implicated in the activation of
macrophages. Here we show that Jmjd3 is essential for M2 macrophage
polarization in response to helminth infection and chitin, though
Jmjd3 is dispensable for M1 responses. Furthermore, Jmjd3 (also known
as Kdm6b) is essential for proper bone marrow macrophage
differentiation, and this function depends on demethylase activity of
Jmjd3. Jmjd3 deficiency affected trimethylation of H3K27 in only a
limited number of genes. Among them, we identified Irf4 as encoding a
key transcription factor that controls M2 macrophage polarization.
Collectively, these results show that Jmjd3-mediated H3K27
demethylation is crucial for regulating M2 macrophage development
leading to anti-helminth host responses.
PMID: 20729857
Since the fliP side of autoimmune is cancer let's do one M1/M2 cancer
abstract?
Why?
Cause i wanna> :P
Duh, huh?
OK, have your sweet whey like a democraP dork with his DRD4 snp in a
tizzy, lizzy!
http://groups.google.com/groups/search?hl=en&qt_s=1&q=drd4+snp
Thank you very mush, brain drain.
I will do the cancer M1 M2 Big MAC, PPAR, CANCER abstract:
http://www.ncbi.nlm.nih.gov/pubmed/18615187
PPAR Res. 2008;2008:169414.
Macrophages, PPARs, and Cancer.
Van Ginderachter JA, Movahedi K, Van den Bossche J, De Baetselier P.
Laboratory of Cellular and Molecular Immunology, Department of
Molecular and Cellular Interactions, VIB, 1050 Brussels, Belgium.
Abstract
Mononuclear phagocytes often function as control switches of the
immune system, securing the balance between pro- and anti-inflammatory
reactions. For this purpose and depending on the activating stimuli,
these cells can develop into different subsets: proinflammatory
classically activated (M1) or anti-inflammatory alternatively
activated (M2) macrophages. The expression of the nuclear peroxisome
proliferator-activated receptors (PPARs) is regulated by M1- or M2-
inducing stimuli, and these receptors are generally considered to
counteract inflammatory M1 macrophages, while actively promoting M2
activation. This is of importance in a tumor context, where M1 are
important initiators of inflammation-driven cancers. As a consequence,
PPAR agonists are potentially usefull for inhibiting the early phases
of tumorigenesis through their antagonistic effect on M1. In more
established tumors, the macrophage phenotype is more diverse, making
it more difficult to predict the outcome of PPAR agonism. Overall, in
our view current knowledge provides a sound basis for the clinical
evaluation of PPAR ligands as chemopreventive agents in chronic
inflammation-associated cancer development, while cautioning against
the unthoughtful application of these agents as cancer therapeutics.
PMID: 18615187
-------------------
OK abstract time.
No, i don't wanna do it now.
OK i'll compromise like obama.
I'll do one and then you and then i'll tax you 15 trillion $'s.
Fair enough oh TAX crack snorting ONE.
But Bush started it with medicare and the war so there.
And his bush dad did free stuff and we democraPs are the
only party of DRD4 snp people who get votes based on FREE stuff.
So move it you RIGHT wing ding a ling.
--------------
I'll be BASIC.
one plus one plus one = psoriasis...
http://www.ncbi.nlm.nih.gov/pubmed/21152006
PLoS Comput Biol. 2010 Dec 2;6(12):e1001024.
A systems model for immune cell interactions unravels the mechanism of
inflammation in human skin.
Valeyev NV, Hundhausen C, Umezawa Y, Kotov NV, Williams G, Clop A,
Ainali C, Ouzounis C, Tsoka S, Nestle FO.
St. John's Institute of Dermatology, King's College London, London,
United Kingdom.
Abstract
Inflammation is characterized by altered cytokine levels produced by
cell populations in a highly interdependent manner. To elucidate the
mechanism of an inflammatory reaction, we have developed a
mathematical model for immune cell interactions via the specific, dose-
dependent cytokine production rates of cell populations. The model
describes the criteria required for normal and pathological immune
system responses and suggests that alterations in the cytokine
production rates can lead to various stable levels which manifest
themselves in different disease phenotypes. The model predicts that
pairs of interacting immune cell populations can maintain homeostatic
and elevated extracellular cytokine concentration levels, enabling
them to operate as an immune system switch. The concept described here
is developed in the context of psoriasis, an immune-mediated disease,
but it can also offer mechanistic insights into other inflammatory
pathologies as it explains how interactions between immune cell
populations can lead to disease phenotypes.
PMID: 21152006
Free Article
http://dx.plos.org/10.1371/journal.pcbi.1001024
------------
Now it's my turn:
HA HA HA------> blocking for skin rePair:
http://www.medicalnewstoday.com/articles/211245.php
Ubiquitous Sugar Molecule Could Be Key To Repairing Deep Wound Without
Scarring
Blocking fragments of the sugar molecule hyaluronan that triggers
inflammation could be the key to robust healing and less scarring in
deep wounds, Canadian researchers reported at the American Society for
Cell Biology's 50th Annual Meeting in Philadelphia.
In laboratory rats, the small peptide, named 15-1, which blocks
fragments of the ubiquitous sugar molecule, hyaluronan, promoted wound
healing, minimized scarring and forged stronger new tissue.
These effects did not occur in the untreated animals in the study,
according to Cornelia Tölg, Ph.D., of the London (Ontario) Regional
Cancer Program.
With collaborators in Canada and the U.S., Tölg identified peptide
15-1 for its ability to cap molecular receptors in epithelial and
dermal cells that react to fragments of the hyaluronan molecule by
setting off a cellular pathway linked to inflammation.
A single dose of peptide 15-1 reduced wound contraction, collagen
deposits, inflammation and growth of unwanted new blood vessels in lab
animals. The researchers said that these findings may have clinical
implications for human wound healing.
A major component in skin, hyaluronan has been known to play a
complicated although unclear role in closing deep wounds and
minimizing fibrotic scarring in repaired tissue.
Until the late 1970s, hyaluronan was considered to be little more than
the inert "goo" that filled the extracellular matrix, but has since
emerged as a biological star in a wide range of biological processes,
from embryonic heart development to tumor metastasis to wound repair.
The relationship between hyaluronan levels and tissue regeneration is
paradoxical according to Tölg. Hyaluronan levels are extremely high in
developing embryos and newborns, which can recover readily from
surgery without scarring.
But throughout adult life, levels of intact hyaluronan drop while the
proportion of broken hyaluronan molecules increases.
Thus, while the intact hyaluronan molecule promotes strong healing,
hyaluronan fragments engage the receptor for hyaluronan-mediated
motility (RHAMM), setting off inflammation that can result in fibrotic
scarring and weak granulated tissue.
Tölg and colleagues used microscopic beads coated with hyaluronan to
pinpoint two small peptides that bound to the shape of the molecule.
One of them, peptide 15-1, showed an affinity for fastening itself to
hyaluronan fragments, effectively keeping them from the RHAMM.
Notes:
Tölg presented: "Use of Hyaluronan Binding Peptides for Control of
Wound Repair Associated Fibrosis" Sunday, Dec. 12, 2010, 1-2:30 pm,
Epithelia, Exhibit Halls A/B/C; Program 619, Board B1002,
---------
Hyaluronan in the P NG:
34 results for Hyaluronan - P NG
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Hyaluronan&qt_g=Search+this+group
But 127 results for Hyaluronic P NG:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=Hyaluronic
zzzzzzzzzzzzzzzzzzzzz
But i want more:
No...
YES mORE i tell YOU.
Well OK...
http://www.medicalnewstoday.com/articles/210647.php
Bioactive Peptides Found To Promote Wound Healing
Newly-created bioactive peptides promote wound healing through the
growth of new blood vessels and epithelial tissue, such as skin. These
wound-healing peptides, synthesized by researchers at the Tufts Center
for Innovations in Wound Healing Research, increased angiogenesis in
vitro by 200 percent. The discovery, reported online in advance of
print this week in Wound Repair and Regeneration, provides a better
understanding of the mechanisms regulating wound healing and may lead
to new therapies for acute and chronic wound healing.
"We identified specific bioactive peptides that are produced from
collagenase treatment of extracellular matrix, which stimulate the
healing process within a wound. By creating combinations of several
key peptide fragments, we were able to synthesize an entirely novel
class of wound-healing peptides that promote the fundamental response
to injury: blood vessel formation and epithelialization," said senior
author Ira Herman, PhD, a professor of molecular physiology and
pharmacology at TUSM; member of the cell, molecular & developmental
biology, and cellular & molecular physiology program faculties at the
Sackler School of Graduate Biomedical Sciences; and director, Tufts
Center for Innovations in Wound Healing Research.
"This is the first time these peptides have been identified and
synthesized and we hope that these discoveries and new technologies
will have broad implications for acute, chronic, burn, and scarless
wound healing," Herman continued.
The team from Tufts used a three-dimensional wound model to examine
the effect of the bioactive peptides on wound healing. After three
days, wounds treated with the peptides showed signs of robust repair,
while controls did not.
"We found that collagenase enzyme derived from Clostridium
histolyticum bacteria releases biologically active fragments peptides
from extracellular mammalian proteins. These peptides stimulate
proliferation of capillary endothelial cells, enhance microvascular
remodeling in the 2-D model, and induce endothelial sprouting in a 3-D
model of injury repair, and therefore are likely to have potential to
stimulate blood vessel formation and promote healing in response to
injury in animals and humans," said first author Tatiana Demidova-
Rice, BS, a PhD candidate in the cell, molecular and developmental
biology program at the Sackler School of Graduate Biomedical Sciences
at Tufts.
Angiogenesis, the formation of new blood vessels from existing
vessels, is a key step in all types of wound healing from knee scrapes
to venous stasis ulcers, pressure sores and diabetic foot ulcers. In
order for tissues to be repaired, there must be an adequate blood
supply bringing nutrients, oxygen, and signaling molecules to the site
of the injury. Collageneses are enzymes that remodel extracellular
matrix by cleaving one of its key components, collagen.
"The most potent wound-healing peptide is a 'combinatorial' peptide
synthesized from bioactive fragments derived from the collagenase
treatment of biosynthesized matrix. Outcomes of these studies suggest
that it could be possible to create personalized regenerative medicine-
based wound healing therapies and platforms that would be tailored to
individuals. We are currently testing the efficacy of these fragments
in an effort to develop better treatments for wound healing.
Formulation of the bioactive peptides into heat-stable and portable
materials could be of extreme value to soldiers injured in combat,"
said Herman.
As director of the Tufts Center for Innovations in Wound Healing
Research (TIWR), Herman brings together investigators from a broad
range of disciplines to advance wound healing research and
therapeutics. Researchers combine recent insights and advances in
wound-healing biology, materials sciences, and bioengineering to
create fully-vascularized organ constructs for personalized
regenerative medicine, while offering new and innovative opportunities
for drug screening, discovery and development. TIWR investigators are
currently developing cutting-edge technologies in biomaterials
sciences and nano-fabrication processing to create personalized wound
healing therapeutics, including "next generation" wound care products
for civilian and soldier use.
An additional author on the study is Anita Geevarghese, a student in
the School of Arts and Sciences at Tufts University. She participated
in the Tufts Summer Scholars Program, funded through the Office of the
Provost, which offers research apprenticeships to undergraduate
students.
This work was supported by the National Eye Institute, part of the
National Institutes of Health, and Healthpoint, Inc. A patent
application related to the study has been filed by Tufts University.
===========
That was GREAT, got MORE?
For cyber huMANs YES:
http://www.medicalnewstoday.com/articles/210649.php
Self-Healing Autonomous Material Comes To Life
[...] The novel autonomous material developed by Henry Sodano and
colleagues uses "shape-memory" polymers with an embedded fiber-optic
network that functions as both the damage detection sensor and thermal
stimulus delivery system to produce a response that mimics the
advanced sensory and healing traits shown in biological systems. An
infrared laser transmits light through the fiber-optic system to
locally heat the material, stimulating the toughening and healing
mechanisms
<snip>
=============
Psor stuff & abstracts:
----
http://www.ncbi.nlm.nih.gov/pubmed/21157640
Curr Opin Investig Drugs. 2010 Nov;11(11):1211-20.
Targeting the IL-1 family members in skin inflammation.
Jensen LE.
Temple University School of Medicine, Department of Microbiology and
Immunology, 1158 MERB, 3500 North Broad Street, Philadelphia, PA
19140-4106, USA.
Abstract
The IL-1 family of cytokines comprises 11 proteins with pro- and anti-
inflammatory functions that are mediated through an equally large
group of receptors and coreceptors. Dysregulation of the IL-1 system
may lead to diseases such as psoriasis, atopic dermatitis, contact
dermatitis and cutaneous lupus erythematosus. These inflammatory skin
conditions greatly affect quality of life and life expectancy, and
their frequencies are increasing. However, treatment options for these
diseases are unsatisfactory. This review briefly summarizes new
findings, reported in the past 2 years, implicating IL-1 family
members in skin inflammation. Furthermore, how the biological
activities of the IL-1 family members may be inhibited is discussed.
PMID: 21157640
http://en.wikipedia.org/wiki/Interleukin_1
Interleukin-1 alpha (IL-1α) is a protein that in humans is encoded by
the IL1A gene.[1][2]
The protein encoded by this gene is a cytokine of the interleukin-1
family. Interleukin-1 alpha possesses a wide spectrum of metabolic,
physiological, haematopoietic activities, and plays one of the central
roles in the regulation of the immune responses. It binds to the
interleukin-1 receptor
[...] Members of the transforming growth factor beta superfamily
belong to this group, including TGF-β1, TGF-β2 and TGF-β3.
<snip>
http://en.wikipedia.org/wiki/TGF_beta_1
http://en.wikipedia.org/wiki/TGF_beta_1#TGF-.CE.B21_and_T_cells
http://en.wikipedia.org/wiki/IL1ra
=============
Not enough apoptosis in those psor CELLs?
http://www.ncbi.nlm.nih.gov/pubmed/21151024
Cell Death Differ. 2010 Dec 10.
p75 neurotrophin receptor mediates apoptosis in transit-amplifying
cells and its overexpression restores cell death in psoriatic
keratinocytes.
Truzzi F, Marconi A, Atzei P, Panza MC, Lotti R, Dallaglio K, Tiberio
R, Palazzo E, Vaschieri C, Pincelli C.
Institute of Dermatology, School of Biosciences and Biotechnologies,
University of Modena and Reggio Emilia, Modena, Italy.
Abstract
p75 neurotrophin receptor (p75NTR) belongs to the TNF-receptor
superfamily and signals apoptosis in many cell settings. In human
epidermis, p75NTR is mostly confined to the transit-amplifying (TA)
sub-population of basal keratinocytes. Brain-derived neurotrophic
factor (BDNF) or neurotrophin-4 (NT-4), which signals through p75NTR,
induces keratinocyte apoptosis, whereas β-amyloid, a ligand for
p75NTR, triggers caspase-3 activation to a greater extent in p75NTR
transfected cells. Moreover, p75NTR co-immunoprecipitates with NRAGE,
induces the phosphorylation of c-Jun N-terminal kinase (JNK) and
reduces nuclear factor kappa B (NF-κB) DNA-binding activity. p75NTR
also mediates pro-NGF-induced keratinocyte apoptosis through its co-
receptor sortilin. Furthermore, BDNF or β-amyloid cause cell death in
TA, but not in keratinocyte stem cells (KSCs) or in p75NTR silenced TA
cells. p75NTR is absent in lesional psoriatic skin and p75NTR levels
are significantly lower in psoriatic than in normal TA keratinocytes.
The rate of apoptosis in psoriatic TA cells is significantly lower
than in normal TA cells. BDNF or β-amyloid fail to induce apoptosis in
psoriatic TA cells, and p75NTR retroviral infection restores BDNF- or
β-amyloid-induced apoptosis in psoriatic keratinocytes. These results
demonstrate that p75NTR has a pro-apoptotic role in keratinocytes and
is involved in the maintenance of epidermal homeostasis.Cell Death and
Differentiation advance online publication, 10 December 2010; doi:
10.1038/cdd.2010.162.
PMID: 21151024
http://www.ncbi.nlm.nih.gov/pubmed/21154861
Hepatology. 2010 Oct 21.
combination of retinoic acid and ursodeoxycholic acid attenuates liver
injury in bile duct-ligated rats and human hepatic cells.
He H, Mennone A, Boyer JL, Cai SY.
From the Yale Liver Center, Department of Internal Medicine, Yale
University School of Medicine, New Haven, CT.
Abstract
Cholestasis leads to liver cell death, fibrosis, cirrhosis, and
eventually liver failure. Despite limited benefits, ursodeoxycholic
acid (UDCA) is the only Food and Drug Administration-approved
treatment for cholestatic disorders. Retinoic acid (RA) is a ligand
for nuclear receptors that modulate bile salt homeostasis. RA also
possesses immunomodulatory effects and is used to treat acute
promyelocytic leukemia and inflammatory disorders such as psoriasis,
acne, and rheumatoid arthritis. To test whether the supplementation of
RA with UDCA is superior to UDCA alone for treating cholestasis, male
Sprague-Dawley rats underwent common bile duct ligation (BDL) for 14
days and were treated with phosphate-buffered saline (PBS), UDCA, all-
trans retinoic acid (atRA), or UDCA and atRA by gavage. Treatment with
UDCA and atRA substantially improved animal growth rates,
significantly reduced liver fibrosis and bile duct proliferation, and
nearly eliminated liver necrosis after BDL. Reductions in the bile
salt pool size and liver hydroxyproline content were also seen with
treatment with atRA or atRA and UDCA versus PBS and UDCA. Furthermore,
atRA and UDCA significantly reduced liver messenger RNA and/or protein
expression of transforming growth factor β1 (Tgf-β1), collagen 1a1
(Col1A1), matrix metalloproteinase 2 (Mmp2), cytokeratin 19, α-smooth
muscle actin (α-SMA), cytochrome P450 7A1 (Cyp7a1), tumor necrosis
factor α, and interleukin-β1. The molecular mechanisms of this
treatment were also assessed in human hepatocytes, hepatic stellate
cells, and LX-2 cells. atRA alone or in combination with UDCA greatly
repressed CYP7A1 expression in human hepatocytes and significantly
inhibited COL1A1, MMP2, and α-SMA expression and/or activity in
primary human hepatic stellate cells and LX-2 cells. Furthermore, atRA
reduced TGF-β1-induced Smad2 phosphorylation in LX-2 cells.
Conclusion: Our findings indicate that the addition of RA to UDCA
reduces the bile salt pool size and liver fibrosis and might be an
effective supplemental therapy with UDCA for cholestatic diseases.
(HEPATOLOGY 2010;.).
PMID: 21154861
======================
http://www.ncbi.nlm.nih.gov/pubmed/21152809
An Bras Dermatol. 2010 Oct;85(5):747-749.
[Immunopathogenesis of psoriasis.]
[Article in Portuguese]
Sanchez AP.
Serviço de Dermatologia, Complexo Hospitalar Padre Bento de Guarulhos,
São Paulo, SP, Brasil.
Abstract
Psoriasis is a common inflammatory disease affecting 1% of the
Brazilian population. Th17 and Th1 cells are involved with the
immunopathogenisis of psoriasis. In this article it is discussed the
interaction between the innate immunity (especially dendritic cells
and keratinocytes) and adaptive immunity (T lymphocytes) in the
pathogenesis of psoriasis.
PMID: 21152809
Free Article
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962010000500028&lng=en&nrm=iso&tlng=en
======================
http://www.ncbi.nlm.nih.gov/pubmed/21152805
An Bras Dermatol. 2010 Oct;85(5):729-731.
[Case for diagnosis.]
[Article in Portuguese]
Gon AD, Minelli L, Franzon PG.
Universidade Estadual de Londrina, Londrina, PR, Brasil.
Abstract
Inflammatory linear verrucous epidermal nevus (Ilven) is a rare
variant of epidermal verrucous nevus that commonly affects females.
Clinically is characterized by the appearance, since birth, of
recurrent inflammatory phenomena with chronic eczematous or
psoriasiform aspects, usually unilateral, with severe pruritus, and
refractory to therapy.
PMID: 21152805 free article available
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962010000500024&lng=en&nrm=iso&tlng=en
---------------------
http://www.ncbi.nlm.nih.gov/pubmed/21152786
An Bras Dermatol. 2010 Oct;85(5):625-629.
[Inter-rater concordance study of the PASI (Psoriasis Area and
Severity Index).]
[Article in Portuguese]
Faria JR, Aarão AR, Jimenez LM, Silva OH, Avelleira JC.
Instituto de Dermatologia Prof. Rubem David Azulay, Santa Casa de
Misericórdia do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Abstract
BACKGROUND: Developed in 1978, the PASI (Psoriasis Area and Severity
Index) is a method to rate psoriasis severity. Since then, it has been
criticized for being extremely long, complex and for yielding
significantly divergent interpretations.
OBJECTIVE: To determine the PASI inter-rater reliability among three
independent evaluators examining the same patients.
METHODS: Cross-sectional study conducted in 2007 at a psoriasis
treatment center, where 20 patients were selected. The patients were
evaluated by three postgraduate students of Dermatology who
independently determined the PASI of each patient. The inter-rater
reliability coefficient was determined by employing intraclass
correlation coefficients (ICC) and Bland & Altman plots.
RESULTS: An ICC of 0.729 (IC 95%: 0.440 - 0.882) showed a significant
degree of concordance among evaluators. By graphic means, the Bland &
Altman plot method presents concordance gap ranges. As shown in this
study, narrow gap ranges indicate a good concordance degree. It was
also observed that for high PASI values, wider concordance gap ranges
predominate.
CONCLUSION: Based on this analysis, we may conclude that the PASI is a
reliable indicator of psoriasis severity because it shows significant
concordance when independent evaluations are performed.
PMID: 21152786
Free Article
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962010000500005&lng=en&nrm=iso&tlng=en
====================
Rituximab psoria* - 37 hits - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=Rituximab+psoria*
drop Psoria* and get 7184 hits- for your info:~)
----------
http://www.ncbi.nlm.nih.gov/pubmed/20641609
Cy5.5-Rituximab.
Leung K.
[...] Rituximab (RIT), a humanized monoclonal antibody (mAb) directed
toward CD20
[...] pmid: 20641609
What is Cy5.5?
Why?
I wanna know.
OK
http://www.ncbi.nlm.nih.gov/pubmed/20641862
2-(1E,3E,5E)-5-3-(R)-1-(1-(R)-2-(R)-2-[2-(4-(Benzo[d]thiazol-2-
ylamino)phenyl)\acetamido]-6-(E)-3-(pyridin-3-
yl)acrylamido)hexanamido)-5-carboxypentanamido)cyclohexyl)-27-
carbamoyl-1,9,13,21,25,33-hexaoxo-5,17-dioxa-2,8,14,20,26,32-hexa-
azaheptatriacontan-37-yl)-1,1-dimethyl-6,8-disulfonato-1H-
benzo[e]indol-2(3H)-ylid-ene)penta-1,3-dienyl)-3-ethyl-1,1-dimethyl-1H-
ben-zo[e]indolium-6,8-disulfonate.
Leung K.
[...] PMID: 20641862
16 hits for: Cy5.5 lymphocyte - pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=Cy5.5+lymphocyte
Look at #3 in this search:
http://www.ncbi.nlm.nih.gov/pubmed/20641549
Cy5.5-CGRRRQRRKKRG-Labeled T lymphocytes .
Zhang H.
In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet].
Bethesda (MD): National Center for Biotechnology Information (US);
2004-2010.
2008 Jul 10 [updated 2008 Aug 27].
Excerpt
T cells are responsible for regulating immune responses and
maintaining immune tolerance via recognition of peptide antigens that
are bound to human leukocytes (1). Some T cells possess autoimmunity
or self-tolerance through recognition of self-antigens. Loss of this
required self-tolerance can result in an autoimmune disorder. For
instance, experimental allergic encephalomyelitis (EAE) is one of
immune-mediated diseases in which immune cells become reactive against
myelins, which leads to the destruction of myelin sheets (2). EAE can
be induced in rodents by adoptive transfer of CD4+ T cells specific to
myelin basic protein (MBP), an autoantigen of myelin (3). As an animal
model for the inflammatory disease, EAE can reproduce many clinical
neuropathological and immunological aspects of multiple sclerosis (MS)
and thus has been widely used in therapeutic development for MS (4).
The evolution of inflammatory lesions in EAE involves several steps
(1, 3). After intravenous administration, the injected MBP-specific T
cells cross the blood–brain barrier to recognize the T cell antigen
located on perivascular microglia. This antigen-specific interaction
produces a plethora of inflammatory cytokines and mediators, leading
to amplification of the inflammatory reaction. The blood–brain barrier
then opens to allow antigen-independent recruitment of various
mononuclear inflammatory cells into the central nervous system,
including additional T cells, macrophages, and granulocytes.
Consequently, the inflammatory lesions evolve into severe neurological
dysfunctions such as ascending paraparesis and paralysis. Because the
activated T cells are involved in the entire process, the trafficking
of the activated MBP-specific T cells in EAE can reflect their immune
activity in every evolutionary phase (2). Labeling T cells with
imaging probes will allow non-invasive tracking of the migration of T
cells in vivo. The imaging probes can be internalized into cells with
the use of cell-penetrating peptides (CPP) as vector/nuclear delivery
vehicles of conjugated cargo (5). In general, CPP comprise a protein-
transduction domain formed by small peptides (<20 amino acids) for
cell membrane translocation. A commonly used CPP is a peptide
truncated from the 86-mer transactivating transcriptional activator
(Tat) protein in human immunodeficiency virus type 1 (HIV) (6). In
particular, Tat(47-57) is widely used in cellular delivery of
peptides, proteins, genetic material, antibodies, nanoparticles, and
liposomes (5). Tat(47-57) contains an α-helical structure with a
charged face formed by six arginine and two lysine residues (6). Tat-
mediated internalization consists of multiple steps: the binding of
Tat to the cell surface, stimulation of macropinocytotic uptake of Tat
and transfer into macropinosomes, and finally endosomal escape into
the cytoplasm (7). A T lymphocyte is labeled with Cy5.5-Cys-Gly-Arg-
Arg-Arg-Gln-Arg-Arg-Lys-Lys-Arg-Gly (CGRRRQRRKKRG) (Cy5.5-Tat-T cell)
for optical imaging (2). This agent contains a near-infrared
fluorescence (NIRF) dye shuttled across the cell membrane of T cells
via Tat(48-57). The fluorescence probe Cy5.5 is a cyanine dye
consisting of two quaternized heteroaromatic bases (A and A’) joined
by a polymethine chain with five carbons (8), and it is bound to
cysteine-terminated Tat(48-57) via a maleimide group as a spacer (2).
Cy5.5 has a delocalized positive charge in its chromophore and
possesses high quantum yield (0.22 at 678 nm), good chemical
stability, easy conjugation, and high sensitivity (mole extinction
coefficient ~250,000 mol/cm) (9, 10). The excitation/emission
wavelength is 674/692 nm for Cy5.5, where hemoglobin and water have
their lowest absorption coefficient. The labeled cargo Cy5.5-Tat is
translocated through the plasma membrane of cells by an energy-
dependent process involving endocytosis (2). The produced Cy5.5-Tat-T
cells can be adoptively transferred to EAE rats for visualization and
quantification of T cells activity in the early inflammation stages of
EAE.
PMID: 20641549
free article:
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=micad&part=Cy55Tat
===============================================
http://www.physorg.com/news/2010-12-immune-cell-unexpected-role-autoimmune.html
Immune cell plays unexpected role in autoimmune disease
December 16, 2010 A new study provides fascinating insight into the
underlying pathology associated with the autoimmune disease, systemic
lupus erythematosus (SLE). The research, published by Cell Press in
the December issue of the journal Immunity, reveals an unexpected role
for a key type of immune cell and provides a potential new therapeutic
strategy for SLE and, potentially, other autoimmune diseases
SLE is a chronic systemic disease that can affect many regions of the
body and, as a result, presents with diverse clinical symptoms. As is
characteristic of other autoimmune disease, in SLE the immune system
attacks and damages the body's own cells and tissues. Previous
research had shown that SLE is associated with activation of the two
main parts of the adaptive immune system, B cells and T cells.
"We were interested in examining the contribution of another type of
immune cell, the dendritic cell (DC), to SLE pathology," explains
senior study author Dr. Mark J. Shlomchik from Yale University School
of Medicine in New Haven, Connecticut. "DCs initiate and control the
adaptive immune response to infection and have the potential to
influence SLE in many different ways."
Dr. Shlomchik and colleagues deleted DCs in a mouse model of SLE and
observed that although DCs contributed to the expansion and
differentiation of T cells, they were surprisingly not required for
the initial activation of T cells. These findings were unexpected
because it is well established that DC cells initiate the T and B cell
immune response to pathogens. Alternatively, DCs were very important
for the invasion of target organs by inflammatory cells, including T
cells. SLE-prone mice lacking DCs had markedly reduced kidney and skin
disease. DCs also markedly affected the quantity and quality of the
classic autoantibody response associated with lupus.
Taken together, the observations indicate that the way DC cells
function in autoimmune disease is quite different from their role in
the immune response to pathogens. "Our findings reveal that DCs
operate not to initiate but rather to amplify disease in a mouse model
of lupus which is in contrast to how they are thought to work in
response to infection," concludes Dr. Shlomchik. "Although there is
much more work to do in defining the roles of DCs in autoimmunity our
current data validate DCs as a potential new therapeutic target in
autoimmunity as well as point to future studies to determine how DCs
promote local tissue inflammation and to test if depleting DCs will be
therapeutic during disease."
=======================
http://www.physorg.com/news/2010-12-source-immune-cells-pregnancy.html
Researchers find new source of immune cells during pregnancy
December 16, 2010 UCSF researchers have shown for the first time that
the human fetal immune system arises from an entirely different source
than the adult immune system, and is more likely to tolerate than
fight foreign substances in its environment.
The finding could lead to a better understanding of how newborns
respond to both infections and vaccines, and may explain such
conundrums as why many infants of HIV-positive mothers are not
infected with the disease before birth, the researchers said.
It also could help scientists better understand how childhood
allergies develop, as well as how to manage adult organ transplants,
the researchers said. The findings are described in the Dec. 17 issue
of Science.
Until now, the fetal and infant immune system had been thought to be
simply an immature form of the adult system, one that responds
differently because of a lack of exposure to immune threats from the
environment. The new research has unveiled an entirely different
immune system in the fetus at mid-term that is derived from a
completely different set of stem cells than the adult system.
"In the fetus, we found that there is an immune system whose job it is
to teach the fetus to be tolerant of everything it sees, including its
mother and its own organs," said Joseph M. McCune, MD, PhD, a
professor in the UCSF Division of Experimental Medicine who is a co-
senior author on the paper. "After birth, a new immune system arises
from a different stem cell that instead has the job of fighting
everything foreign."
The team previously had discovered that fetal immune systems are
highly tolerant of cells foreign to their own bodies and hypothesized
that this prevented fetuses from rejecting their mothers' cells during
pregnancy and from rejecting their own organs as they develop.
The adult immune system, by contrast, is programmed to attack anything
it considers "other," which allows the body to fight off infection,
but also causes it to reject transplanted organs.
"The adult immune system's typical role is to see something foreign
and to respond by attacking and getting rid of it. The fetal system
was thought in the past to fail to 'see' those threats, because it
didn't respond to them," said Jeff E. Mold, first author on the paper
and a postdoctoral fellow in the McCune laboratory. "What we found is
that these fetal immune cells are highly prone to 'seeing' something
foreign, but instead of attacking it, they allow the fetus to tolerate
it."
The previous studies attributed this tolerance at least in part to the
extremely high percentage of "regulatory T cells"– those cells that
provoke a tolerant response – in the fetal immune system. At mid-term,
fetuses have roughly three times the frequency of regulatory T cells
as newborns or adults, the research found.
The team set out to assess whether fetal immune cells were more likely
to become regulatory T cells. They purified so-called naïve T cells –
new cells never exposed to environmental assault – from mid-term
fetuses and adults, and then exposed them to foreign cells. In a
normal adult immune system, that would provoke an immune attack
response.
They found that 70 percent of the fetal cells were activated by that
exposure, compared to only 10 percent of the adult cells, refuting the
notion that fetal cells don't recognize outsiders. But of those cells
that responded, twice as many of the fetal cells turned into
regulatory T cells, showing that these cells are both more sensitive
to stimulation and more likely to respond with tolerance, Mold said.
Researchers then sorted the cells by gene expression, expecting to see
similar expression of genes in the two cell groups. In fact, they were
vastly different, with thousands of genes diverging from the two cell
lines. When they used blood-producing stem cells to generate new cell
lines from the two groups, the same divergence occurred.
"We realized they there are in fact two blood-producing stem cells,
one in the fetus that gives rise to T cells that are tolerant and
another in the adult that produces T cells that attack," Mold said.
Why that occurs, and why the immune system appears to switch over to
the adult version sometime in the third trimester, remains unknown,
McCune said. Further studies will attempt to determine precisely when
that occurs and why, as well as whether infants are born with a range
of proportions of fetal and adult immune systems – information that
could change the way we vaccinate newborns or treat them for such
diseases as HIV.
More information: Paper: www.sciencemag.org/content/330/6011/1695.full.html
Accompanying scientific commentary:
=====================
http://www.vrp.com/heart-health/slow-your-bodys-clock-with-a-single-natural-compound?utm_content=article3103&utm_source=hn20101216
Slow Your Body’s “Clock” With a Single Natural Compound
by VRP Staff
Imagine a strong, healthy heart…flexible, free-flowing arteries…
boundless energy and comfortable, mobile joints…all well into your
60s, 70s, 80s and beyond. True, this might sound like make-believe—but
emerging science shows that it’s anything but.
Trans-resveratrol—a compound found in red grapes, wine and Japanese
Giant Knotweed—has captivated the scientific community for over ten
years with its unique ability to put the brakes on biological aging.
After discovering that this phytonutrient can increase the lifespan of
yeast cells by as much as 70 percent, researchers at Harvard and MIT
began exploring its potential effects on mammals in a series of
groundbreaking studies that have delivered near-miraculous results.
For starters, data showed that resveratrol supplementation can block
the negative impact of weight gain on critical factors such as liver
function and blood sugar control, plus heart and muscle health, in
mice fed high-calorie diets. As a result, overfed mice receiving
resveratrol were just as healthy as their calorie-restricted
counterparts—with the effects of a high-calorie diet being inhibited
in an astounding 94 percent of biochemical pathways in this group,
despite the mice being significantly overweight.1
Further research has revealed that these initial results were no
fluke: Another subsequent study showed that healthy young mice
receiving large amounts of resveratrol experienced dramatic
improvements in aerobic capacity, physical endurance, oxygen
consumption efficiency and grip strength. What’s more, an increase in
the size and number of mitochondria—which function as the energy
generators for all living cells—meant that the mice taking resveratrol
were able to burn most of their calories instead of storing them as
fat, thereby curbing weight gain.2
It’s still uncertain how resveratrol is able to achieve these amazing
results—but scientists believe that this natural compound activates a
longevity gene called SIRT1, which is triggered in times of famine. As
a consequence, resveratrol mimics the biological effects of calorie
restriction—on everything from cardiovascular function to motor
functions and bone and eye health—without prolonged dieting or hunger.
3 But that’s not all it does.
Studies have also found that resveratrol acts on a signaling pathway
called AMPK, which boosts neuronal energy and exerts a protective
effect on aging brain cells, while combating fat accumulation in the
liver.4-5 And its effects on heart health are even more incredible,
with research indicating that it can slow biological aging of the
heart (as measured by gene-expression profiles) by as much as 92
percent—resulting in enhanced cardiac function, clear and flexible
arteries, a strong heart muscle, balanced blood pressure and increased
antioxidant activity.6-13
As if all that’s not enough, emerging research now shows that
resveratrol may promote cartilage strength and restore healthy
inflammatory responses in subjects struggling with joint concerns—
offering just one more reason to add this supernutrient to your
supplement regimen today.14 Resveratrol is available now from Vitamin
Research Products, as part of the daily formula Extension Resveratrol—
which combines the most clinically effective form of this natural
compound with red wine polyphenols plus the antioxidant powerhouse,
quercetin, for maximum bioavailability.
References:
<snip>
I like longevinex.com for my suPPlementation of resveratrol.
And i'm not longer such a TROL..off the resERvation. LOL <w>
===========
Drink up that japanese knotweed under the bough with a jug and thou?
If only...and in the blue stream of consciousNESS? Like island time?
Cheap flight round triP to them places now...and how. :)
I wanna molokai it. LOL
http://www.lef.org/newsletter/2010/1214_Pomegranate-May-Help-Prevent-Prostate-Cancer-Metastasis.htm
Pomegranate may help prevent prostate cancer metastasis
[...] The current research conducted by Dr Martins-Green's lab
identified phenylpropanoids, hydrobenzoic acids, flavones and
conjugated fatty acids as compounds responsible for the effects in the
cancer cells that were not destroyed. In addition to inhibiting the
growth of the tumor cell lines, the compounds inhibited their
migration and attraction to a signal that promotes metastasis to the
bone.
<snip>
===============
Mercola drinking WATER
http://waterfilters.mercola.com/drinking-water-filter.aspx
Dr. Mercola Discusses Water Filters - 15 minutes youtube:
http://www.youtube.com/watch?v=fynTwZ6pPAk&feature=player_embedded
==============
mercola RAW MILK
http://articles.mercola.com/sites/articles/archive/2010/12/15/the-war-over-raw-milk.aspx
Time Magazine: What's Fueling the Battle Over Raw Milk?
By Josh Ozersky Sunday, Sep. 26, 2010
Read more: http://www.time.com/time/magazine/article/0,9171,2017205,00.html
or
http://www.time.com/time/magazine/article/0,9171,2017205,00.htm
===============
Mercola, drugs,
<see link for video>
[...] Many people are still completely unaware of the many ways in
which they are being manipulated into taking dangerous and unnecessary
drugs.
There's the $5 billion direct-to-consumer marketing, of course, which
is rather obvious. But physicians also play a major role, and the
manipulation that takes place on this level is more obscure.
Drug reps often give 'gifts' to convince doctors to prescribe the
medications that they represent. These drug reps usually have no
medical or science education. Instead, they're armed with some of the
most potent brainwashing techniques used throughout the world, which
I'll discuss in a moment.
Perhaps the manipulation technique most difficult to detect is the
'education' given by doctors, to doctors.
Here, it's very easy to forget that the doctor presenting the material
is working entirely on the drug company's behalf, and not as an
independent, well-educated, appropriate source of objective
information.
And then there's the insidious Drug Industry sponsored "education"
that takes place in medical schools across the US.
For example, out of Harvard's 8,900 professors and lecturers, 1,600
admit that they or a family member have ties to drug companies that
could bias their teaching or research. In 2008 alone the
pharmaceutical industry contributed more than $11.5 million to Harvard
for "research and continuing education classes."
All of these tactics (and others) are employed on a massive scale in
the name of "education," but nothing could be further from the truth.
Is Your Doctor Paid to Promote a Drug?
<snip>
Hey, why treat a condition with no etiology?
I've only asked my self that for HOW many decades now?
If psoriasis is merely compensatory, then blocking it might
create worse dis EASE then a plaque ugly patch of scales on you?
======================
Top 10 Food Additives to Avoid - Mercola:
http://articles.mercola.com/sites/articles/archive/2010/12/17/top-10-food-additives-to-avoid.aspx
[...] Artificial Sweeteners
Aspartame, also known as Nutrasweet and Equal, is believed to be
carcinogenic and accounts for more reports of adverse reactions than
all other foods and food additives combined.
The artificial sweetener Acesulfame-K has been linked to kidney
tumors. All artificial sweeteners are bad news.
High Fructose Corn Syrup
High fructose corn syrup (HFCS) increases your LDL ("bad") cholesterol
levels and contributes to the development of diabetes.
Monosodium Glutamate (MSG)
MSG is used as a flavor enhancer. It is an excitotoxin, a substance
that overexcites cells to the point of damage or death.
Trans Fat
Numerous studies show that trans fat increases LDL cholesterol levels
and increases your risk of heart attacks, heart disease and strokes.
Common Food Dyes
Artificial colorings may contribute to behavioral problems in children
and lead to a significant reduction in IQ.
Sodium Sulphite
This is a preservative used in processed foods. People who are sulfite
sensitive can experience headaches, breathing problems, and rashes. In
severe cases, sulfites can actually cause death.
Sodium Nitrate/Sodium Nitrite
This common preservative has been linked to various types of cancer.
BHA and BHT
Butylated hydroxyanisole (BHA) and butylated hydrozyttoluene (BHT) are
preservatives that affect the neurological system of your brain, alter
behavior and have the potential to cause cancer.
Sulphur Dioxide
Sulphur additives are toxic and in the U.S., they have been prohibited
in raw fruit and vegetables. Adverse reactions include bronchial
problems, low blood pressure, and anaphylactic shock.
Potassium Bromate
This additive is used to increase volume in some breads. It is known
to cause cancer in animals, and even small amounts can create problems
for humans.
<snip>
<randall note: durk and sandy might not go along with BHA/BHT?>
yeppers- they sell it. LOL
http://www.life-enhancement.com/product.asp?id=4
maybe you can add it to your raw milk and extra VIRGIN olive oil?
And they'll stay fresher?
=======================
UVB makes vitamin D3 in the skin and can make your skin immortal.
To BAD YOU don't follow suit? LOL
I want to be an SCC or BCC that lives forever...!
My life as bloob of goo over the eons:
http://www.medicalnewstoday.com/articles/210697.php
Skin Cancer Cells Appear To Thrive On Ultraviolet Light
Non-melanoma skin cancer cells appear to thrive on ultraviolet light
because it boosts an essential DNA repair enzyme that helps them stay
alive and multiply, according to a new study from the US that revealed
yet another way that cancer cells exploit natural cell functions.
The study was the work of researchers from the Medical College of
Georgia and the Charlie Norwood VA Medical Center, both in Augusta,
Georgia, and appeared on 6 December as an advance online publication
in the journal Oncogene.
Corresponding author Dr Wendy Bollag, a cell physiologist at both
research centers, and colleagues investigated the enzyme protein
kinase D (PKD), which plays an important role in skin biology by
regulating the growth of new cells and repairing DNA in damaged cells.
Non-melanoma skin cancers form in keratinocytes, which comprise about
90 per cent of skin cells. Melanomas form in the less common
melanocytes, the cells responsible for skin color.
In previous studies, Bollag and colleagues had already established
that PKD was upregulated in BCC or basal cell carcinoma, a common non-
melanoma skin cancer. And since the biggest risk factor for BCC is
exposure to the sun, they wondered if there was a link between PKD and
sunlight.
In this study they found that the sun's ultraviolet B or UVB rays
appear to increase PKD activity in a dose-dependent manner, that is
more exposure equals more activity. But while this process is
essential for skin repair and renewal as we constantly shed cells to
the environment, when it goes awry, it can give cancer a chance to
grow.
As Bollag explained to the press:
"The skin has to continually divide to replace cells that get lost to
the environment."
Even wearing clothes causes the skin to lose cells and creates demand
for new ones, said Bollag.
"So, protein kinase D is good under normal conditions, when it's
regulated appropriately. But what can happen is it starts
misbehaving," she added.
By "misbehaving" Bollag means they found that under certain
conditions, PKD even repaired skin cells with a lot of DNA damage,
preventing them from self-destructing and being cleared away by the
immune system, and thus increasing the chance they will become
cancerous.
Using cell cultures, they verified that PKD activity was induced by
UVB light, and they also found that pretreatment with antioxidants
appeared to reduce the activity, suggesting that free radicals or
reactive oxygen species, by-products of excess cell activity or oxygen
use, also play a part.
"We are living longer and getting a lot of UV radiation in the
process," said Bollag, explaining that she and her colleagues also
found that the effects were cumulative and dose-dependent, that is
more UV exposure was linked to more PKD activity.
She said this was another "wake up call" urging us to be careful with
sun exposure as we age, and that drugs that inhibit the activity of
PKD, already under development for other cancers, may also work for
skin cancer.
Bollag and colleagues also established that the path through which UVB
increased PKD activity was that which involves "Src family tyrosine
kinases" rather than "protein kinase C (PKC)".
They concluded that:
"... our data indicate that UVB irradiation of keratinocytes induces
Src-mediated activation of PKD, which protects cells from UVB-
stimulated apoptosis, providing a possible explanation for the
observed upregulation of PKD in BCC."
Bollag and colleagues now want to research the effect of UV on PKD in
the more deadly melanoma cancers, and to find out if PKD activity
slows with age, as other hormones do. They have a hunch that it does,
because cell turnover slows with age.
But what they are interested in is finding out whether as we age, the
mechanisms that repair skin cells focus more on survival and and less
on sun damage.
Bollag stressed that it was important to get some exposure to UV
light. It's a good source of vitamin D, which we can't get from our
food and is essential for bone, breast and blood vessel health, among
others.
In fact, Bollag pointed out, in some parts of the US, some types of
cancer such as prostate cancer, have been linked to lower sun
exposure.
"Ultraviolet B irradiation and activation of protein kinase D in
primary mouse epidermal keratinocytes."
S N Arun, I Kaddour-Djebbar, B A Shapiro, W B Bollag.
Oncogene, advance online publication 6 December 2010.
DOI:10.1038/onc.2010.540
--------------
Maybe adding some BHA BHT to your UVB's will lower cancinogenic
affects? LOL
============================
This one is for me:
http://www.signaling-gateway.org/update/featured/index.html
Apoptosis: two faces of insulin and IGF-1 receptors
Unliganded insulin and IGF-1 receptors promote apoptosis independently
of tyrosine kinase activity, whereas insulin and IGF-1 binding
stimulates cell survival through kinase activity.
Insulin and insulin-like growth factor 1 (IGF-1) are known as anti-
apoptotic hormones that bind their receptors—IR and IGF1R, respectively
—and activate downstream PI(3)K-Akt and Ras-Raf-MEK signaling
pathways, thereby promoting cell survival and growth. A new study by
Jeremie Boucher, Ronald Kahn and colleagues in Science Signaling now
reports that, surprisingly, cells lacking both IR and IGF1R become
resistant to apoptosis, whereas re-expressing either or both receptors
in these cells restores apoptosis in the absence of a ligand and
independently of tyrosine kinase activity. This demonstrates that, in
addition to the role of insulin and IGF-1 in regulation of apoptosis,
unoccupied IR and IGF1R act as dependence receptors, promoting cell
survival when ligand-bound and inducing apoptosis in the absence of a
ligand.
Using immortalized brown pre-adipocyte cells, the authors showed that
double knockout (DKO) of both IR and IGF1R were resistant to
apoptosis, as assessed by measurements of DNA fragmentation, caspase 3
cleavage, chromatin condensation and annexin binding. The DKO cells
were also resistant to treatments with inducers of intrinsic
(mitochondrially-mediated) and extrinsic (mediated by ligands such as
tumor necrosis factor-alpha and Fas ligand) apoptotic pathways,
suggesting that absence of IR and IGF1R inhibits apoptosis mediated by
both pathways. Further investigation revealed that protein levels of
Bax, a pro-apoptotic Bcl-2 family protein, was reduced by half in DKO
cells, whereas the levels of the anti-apoptotic proteins Bcl-2, Bcl-
xL, Flip and XIAP were increased when compared to the wild-type cells.
As no change was detected in mRNA levels of most of these proteins,
these data indicate that lack of IR and IGF1R inhibits apoptosis
mainly through a posttranscriptional mechanism.
Next, they demonstrate that stable expression of IR, IGF1R, or both in
serum-deprived DKO cells restored the ability of the cells to induce
caspase 3 cleavage and undergo apoptosis. Interestingly, expression of
a catalytically inactive IR in serum-deprived DKO cells also induced
caspase 3 cleavage and restored the abundance of key apoptotic
proteins to levels similar to wild-type cells. This suggests a kinase-
independent pro-apoptotic role for unliganded IR and IGF1R.
Consistently, in wild type cells, PI(3)K or MAPK inhibitors did not
induce apoptosis, and insulin stimulation failed to affect the
abundance of apoptotic proteins.
Altogether, this study demonstrates that IR and IGF1R have
bidirectional roles in the control of apoptosis: when bound to a
ligand they inhibit apoptosis through their tyrosine kinase activity,
whereas in the absence of a ligand they promote apoptosis through a
kinase-independent pathway. Further research will help elucidate the
pro-apoptotic mechanism activated by unliganded IR and IGF1R.
Iley Ozerlat
Signaling Gateway
Reference:
Boucher et al.
A kinase-independent role for unoccupied insulin and IGF-1 receptors
in the control of apoptosis.
Sci. Signal. 3, ra87 (2010)
full text
http://stke.sciencemag.org/cgi/content/full/sigtrans;3/151/ra87
You need a subscriPtion for it. :(
OK now think insulin and your brain cells:
I posted this recently:
http://www.foodconsumer.org/newsite/Nutrition/Food/coconuts_1212100709.html
[...] "Brain Starvation" is a Hallmark of Alzheimer's Disease
Ketone bodies - coconut mct's for clear mental sailings.
Room at the MARK... <w>
-----
Vasp: surfing on actin
Vasp acts as a processive actin polymerase that binds to actin
monomers and targets them to the barbed end of filaments.
The actin cytoskeleton modulator Vasp is known to promote correct
lamellipodia assembly and filopodia formation at the leading edge of
migrating cells. However, the molecular mechanisms underlying the role
of Vasp in F-actin assembly have remained controversial. In Journal of
Cell Biology, Hansen and Mullins now reconcile some of these
controversies by visualizing the interactions of Vasp with monomeric
and filamentous actin in vitro using total internal fluorescence
microscopy.
In the absence of G-actin, tetrameric Vasp uses its FAB (F-actin
binding) and GAB (G-actin binding) domains to bind along the side of F-
actin. These lateral interactions are antagonized by monomeric actin
which binds the GAB domain and targets Vasp to the barbed end of
filaments.
Under actin polymerization conditions, Vasp displays persistent barbed-
end binding before eventually dissociating, much like Vasp surfing
along the growing filament end. Mechanistically, Vasp associates with
F-actin processively by delivering actin monomers to the barbed end.
The rate of filament elongation is affected by buffer ionic strength
and is greatly enhanced in the presence of the G-actin binding protein
profilin, but antagonized by capping protein.
Thus, Vasp acts as a processive actin polymerase that delivers
profilin-bound actin monomers to the barbed end to promote elongation
and to antagonize filament capping.
Alexia-Ileana Zaromytidou
Nature Cell Biology
Reference:
Hansen and Mullins
VASP is a processive actin polymerase that requires monomeric actin
for barbed end association.
J. Cell Biol., 191 571-584 (2010)
<snip>
I'm looking at the FMR1 gene and dehydroepiandrosterone (DHEA)
supplementation with
DRD4 snp, season of bith and iodine supplementation effects via
epistasis and epigenetics.
Yeah right you moron.
Hey glass is half emPty like your brain boy, i try.
What do you DO?
Go along for the ride in the here and NOW on acid or peyote?
But i'm in contact via ibogaine from african tree bark you nit wit
scientist wanna BE.
I just BE...
You BE part of ME you goon geek here / now pow wow.
So shut the oBLAME HOLe uP...
hey, i'm going here and now desPite your science time child weirding
out.
RiP... me.
But mayBE our mom needed
http://nutritiondietnews.com/dhea-supplementation-has-new-advantage-in-treatment-of-infertility/85724/
while we were in the womb room?
Yeah right... don't make me think now while i'm here/now.
And don't call me the moron:
http://en.wikipedia.org/wiki/FMR1
you are..
no you..
yin/yang of life never ends with left/right thinking?
randall... born again and still living perhaPs?