Peptide T//Revelations from Ben B//abstracts-Ann Bowcock-P-DNA-etc.
randall
Spring has sPrung and march madness fades from view. Will psor
heads clear or flare this sPringy time of year? Is global warming
a boom or bust for psor heads?
And what of P cures with aPril fools so close?
We have a final four in March Madness and will have
a #1 in the next week. And we will have a P cure.
But when? READ on to the abstracts or skiP to
them.... some amazing stuff this past few days.
First:
Found this somewhere the other day. A man made
peptide used a few times for Th1 (psoriasis) and Th2
(Aids) conditions with some efficacy. Well?
Maybe?
And IF the trigger is upstream of th1/th2 will it work?
Peptide T, aka-DAPTA, and D-Ala-peptide T amide.
A wiki link for what real ones look like,
http://en.wikipedia.org/wiki/Peptide
Dapta tested well for psoriasis in the mid 90's
http://www.nature.com/jid/journal/v110/n4/abs/5600024a.html
Effects of [D-Ala1[ Peptide T-NH2 and HIV Envelope Glycoprotein Gp120
on Cyclic AMP Dependent Protein Kinases in Normal and Psoriatic Human
Fibroblasts
<sniP>
--------------------
And used for Aids/hiv:
http://www.ingentaconnect.com/content/ben/chr/2003/00000001/00000001/art00005
Update on D-Ala-Peptide T-Amide (DAPTA): A Viral Entry Inhibitor that
Blocks CCR5 Chemokine Receptors
-----------------
Ok then. Let's look at the most recent one.
http://www.ncbi.nlm.nih.gov/pubmed/18046961?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and
inhibition of CCR5-mediated apoptosis in neuronal cells.
Pollicita M, Ruff MR, Pert CB, Polianova MT, Schols D, Ranazzi A,
Perno CF, Aquaro S.
Department of Experimental Medicine and Biochemical Science,
University of Rome Tor Vergata, Rome, Italy.
Monocytes/macrophages (M/M) are strategic reservoirs of HIV-1,
spreading the virus to other cells and inducing apoptosis in T-
lymphocytes, astrocytes and neurons. M/M are commonly infected by R5
HIV-1 strains, which use the chemokine receptor CCR5. D-Ala-peptide T-
amide (DAPTA), or Peptide T, named for its high threonine content
(ASTTTNYT), is a synthetic peptide comprised of eight amino acids
(185-192) of the gp120 V2 region and functions as a viral entry
inhibitor by targeting selectively CCR5. The anti-HIV-1 activity of
DAPTA was evaluated in M/M infected with R5 HIV-1 strains. DAPTA at
10(-9) M inhibited HIV-1 replication in M/M by > 90%. PCR analysis of
viral cDNA in M/M showed that DAPTA blocks HIV entry and in this way
prevents HIV-1 infection. Moreover, DAPTA acts as a strong inhibitor
and was more active than the non-peptidic CCR5 antagonist TAK-779 in
inhibiting apoptosis (mediated by RS HIV-1 strains produced and
released by infected M/M) on a neuroblastoma cell line. Our results
suggest that antiviral compounds which interfere with receptor
mechanisms such as CCR5 could be important, either alone or in
combination with other antiretroviral treatments, in preventing HIV
infection in the central nervous system and the consequential neuronal
damage that leads to neuronal AIDS.
PMID: 18046961
Chalk one up for the antiviral camp with dapta it looks like. If
psoriasis
is 100% antiviral it should work just peachy.
But look at this next one and what the last link says it works on.
http://en.wikipedia.org/wiki/CCR5
To bad CCR5 doesn't play a significant role in psoriasis:
http://www.ncbi.nlm.nih.gov/pubmed/17647003?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
[...]
We conclude that although CCR5 expression is increased in psoriatic
lesions, this receptor does not play a crucial role in the
pathogenesis of psoriasis.
PMID: 17647003
-------
Is it doing something elsewhere that isn't clear yet?
Finding the patents:
http://www.google.com/search?hl=en&q=dapta+patent&btnG=Google+Search
========================
If we use dapta to spur Th2 will it then kick butt on Th1?
Knock back the P th1 and lower PASi?
This abstract may lead us to think so.
http://www.ncbi.nlm.nih.gov/pubmed/12461524?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Interleukin-4 therapy of psoriasis induces Th2 responses and improves
human autoimmune disease.
Ghoreschi K, Thomas P, Breit S, Dugas M, Mailhammer R, van Eden W, van
der Zee R, Biedermann T, Prinz J, Mack M, Mrowietz U, Christophers E,
Schlöndorff D, Plewig G, Sander CA, Röcken M.
Department of Dermatology and Allergology, Ludwig-Maximilians
University Munich, Munich, Germany.
Selective skewing of autoreactive interferon-gamma (IFN-gamma)-
producing T helper cells (Th1) toward an interleukin-4 (IL-4)-
producing (Th2) phenotype can in experimental animals alleviate
autoimmune disease without inducing general immunosuppression. In a
prospective dose escalation study, we assessed treatment with human
IL-4 (rhuIL-4) in 20 patients with severe psoriasis. The therapy was
well tolerated, and within six weeks all patients showed decreased
clinical scores and 15 improved more than 68%. Stable reduction of
clinical scores was significantly better at 0.2-0.5 microg rhuIL-4
than at < or =0.1 microg rhuIL-4 (P = 0.009). In psoriatic lesions,
treatment with 0.2-0.5 microg/kg rhuIL-4 reduced the concentrations of
IL-8 and IL-19, two cytokines directly involved in psoriasis; the
number of chemokine receptor CCR5+ Th1 cells; and the IFN-gamma/IL-4
ratio. In the circulation, 0.2-0.5 microg/kg rhuIL-4 increased the
number of IL-4+CD4+ T cells two- to three-fold. Thus, IL-4 therapy can
induce Th2 differentiation in human CD4+ T cells and has promise as a
potential treatment for psoriasis, a prototypic Th1-associated
autoimmune disease.
PMID: 12461524
=======================================================
=======================================================
While talking with Ben B. last night. We came to endotoxins (LPS) and
a possible connection
with ssRNA for a possible insult to DNA in the P battles. The
endotoxins
would be from all foreign critter's that live on and in us and thrive
due to our diets. We both agree that starvation is one way to draw
down their influence.
Ben's take at this time is to stop/slow/reverse aging, live well and
LONG and the P will
clear uP in the process.
Hey? What can I say? I'm on this triP for as long as it lasts.
What's not to like with LIVE a LONG LIFE? And if the P clear's in the
process
so much the better.
--------------------------------------
OK... now on to recent abstracts.
http://www.ncbi.nlm.nih.gov/pubmed/18371115?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Interferon-alpha and viral triggers promote functional maturation of
human monocyte-derived dendritic cells.
Farkas A, Tonel G, Nestle FO.
Department of Dermatology, University Hospital of Zurich,
Gloriastrasse 31, 8091 Zurich, Switzerland.
Background Type I interferons (IFNs) play an important role in the
pathogenesis of many autoimmune disorders including psoriasis. In the
presence of IFN-alpha and granulocyte/macrophage colony-stimulating
factor (GM-CSF), monocytes differentiate into dendritic cells (DCs)
referred to as IFN-DCs. IFN-DCs potentially mimic DC populations
involved in psoriasis and express a wide range of Toll-like receptor
(TLR) subtypes. Objectives Recently, it was shown that single-stranded
RNA (ssRNA) triggers TLR7 and TLR8; therefore we studied ssRNA, as a
surrogate for ssRNA viruses and their impact on IFN-DCs. Methods We
established culture conditions for IFN-DCs, generated from plastic
adherent monocytes using GM-CSF plus IFN-alpha. For DC stimulation
ssRNA40, a 20-mer ssRNA oligonucleotide was used. The phenotypic
analysis of DC preparations was performed using flow cytometry. The
production of various cytokines was analysed by enzyme-linked
immunosorbent assay, and real-time quantitative polymerase chain
reaction was used to quantify TLR and cytokine gene expression. The
ability of IFN-DCs to stimulate allogeneic T-cell proliferation was
evaluated in a mixed leucocyte reaction. Results We found that IFN-DCs
express mRNA for TLR7 and TLR8 and that ssRNA stimulation
significantly improves their costimulatory molecule expression,
stabilizes their phenotype and enhances their capacity to stimulate
naive T-cell proliferation. Unstimulated IFN-DCs did not produce
bioactive interleukin (IL)-12 and produced low levels of other
proinflammatory cytokines. In contrast, ssRNA stimulation led to a
significant production of IL-12p70, IL-1beta, IL-6 and tumour necrosis
factor alpha. IFN-DCs contained mRNA for IL-12p35, IL-12p40, IL-23p19,
IL-27p28 and IL-27EBI, which was further increased by incubation with
ssRNA. Conclusions Our study sheds light on a potential role for IFN-
alpha and viral infections in triggering DC populations in psoriasis.
These results provide additional data for the better understanding of
human autoimmune and antiviral responses and may also have
implications for strategies developing cancer immunotherapy.
PMID: 18371115
================================================
WOW, wow, bow wow..wait no bow wow... just WOW.
A monster DNA study from a BUNCH of Scientific Heavy hitters.
And Dr. Anne Bowcock is the LEAD.
http://www.ncbi.nlm.nih.gov/pubmed/18369459?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
A genome-wide association study of psoriasis and psoriatic arthritis
identifies new disease Loci.
Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A,
Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I,
Kwok PY, Menter A, Krueger J, Barton A, Saccone NL,
______________Bowcock AM.________________
Division of Human Genetics, Department of Genetics, Washington
University School of Medicine, St. Louis, Missouri, United States of
America.
A genome-wide association study was performed to identify genetic
factors involved in susceptibility to psoriasis (PS) and psoriatic
arthritis (PSA), inflammatory diseases of the skin and joints in
humans. 223 PS cases (including 91 with PSA) were genotyped with
311,398 single nucleotide polymorphisms (SNPs), and results were
compared with those from 519 Northern European controls. Replications
were performed with an independent cohort of 577 PS cases and 737
controls from the U.S., and 576 PSA patients and 480 controls from the
U.K.. Strongest associations were with the class I region of the major
histocompatibility complex (MHC). The most highly associated SNP was
rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8x10(-11),
GWA scan; P = 1.8x10(-30), replication; P = 1.8x10(-39), combined;
U.K. PSA: P = 6.9x10(-11)). However, rs2395029 encoding the G2V
polymorphism within the class I gene HCP5 (combined P = 2.13x10(-26)
in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and
3.2 respectively). This variant is associated with low viral set point
following HIV infection and its effect is independent of rs10484554.
We replicated the previously reported association with interleukin 23
receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA
cohorts (IL23R: rs11209026, U.S. PS, P = 1.4x10(-4); U.K. PSA: P =
8.0x10(-4); IL12B:rs6887695, U.S. PS, P = 5x10(-5) and U.K. PSA, P =
1.3x10(-3)) and detected an independent association in the IL23R
region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel
associations replicated in the U.S. PS cohort included the region
harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric
golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P
= 2x10(-6) for rs7993214; OR = 0.71), the late cornified envelope gene
cluster (LCE) from the Epidermal Differentiation Complex (PSORS4)
(combined P = 6.2x10(-5) for rs6701216; OR 1.45) and a region of LD at
15q21 (combined P = 2.9x10(-5) for rs3803369; OR = 1.43). This region
is of interest because it harbors ubiquitin-specific protease-8 whose
processed pseudogene lies upstream from HLA-C. This region of 15q21
also harbors the gene for SPPL2A (signal peptide peptidase like 2a)
which activates tumor necrosis factor alpha by cleavage, triggering
the expression of IL12 in human dendritic cells. We also identified a
novel PSA (and potentially PS) locus on chromosome 4q27. This region
harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and
was recently shown to be associated with four autoimmune diseases
(Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid
Arthritis).
PMID: 18369459
How do I get UNassociated from rs10484554?
That doesn't look easy.
http://www.ncbi.nlm.nih.gov/sites/gquery?term=rs10484554
I'm looking at you Dr. Bowcock....
Cure us. Cure us...
Anne's lab:
http://hg.wustl.edu/bowcock/
&
http://dbbs.wustl.edu/dbbs/website.nsf/FA/B3996309339695C986256D4E005B2CCB
================================
And even More HUGE P GENETICs from London:
http://www.ncbi.nlm.nih.gov/pubmed/18364390?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Identification of ZNF313/RNF114 as a novel psoriasis susceptibility
gene.
Capon F, Bijlmakers MJ, Wolf N, Quaranta M, Huffmeier U, Allen M,
Timms K, Abkevich V, Gutin A, Smith R, Warren RB, Young HS,
Worthington J, Burden AD, Griffiths CE, Hayday A, Nestle FO, Reis A,
Lanchbury J, Barker JN, Trembath RC.
King's College London, Division of Genetics and Molecular Medicine,
London, UK.
Psoriasis is an immune-mediated skin disorder that is inherited as a
multifactorial trait. Linkage studies have clearly identified a
primary disease susceptibility locus lying within the Major
Histocompatibility Complex (MHC), but have generated conflicting
results for other genomic regions. To overcome this difficulty, we
have carried out a genome-wide association scan, where we analyzed
more than 408,000 SNPs in an initial sample of 318 cases and 288
controls. Outside of the MHC, we observed a single cluster of disease-
associated markers, spanning 47 kb on chromosome 20q13. The analysis
of two replication datasets confirmed this association, with SNP
rs495337 yielding a combined P value of 1.4 x 10 (-8), in an overall
sample of 2,679 cases and 2,215 controls. Rs495337 maps to the SPATA2
transcript and is in absolute linkage disequilibrium with 5 SNPs lying
in the adjacent ZNF313 gene (also known as RNF114). Real-time PCR
experiments showed that, unlike SPATA2, ZNF313 is abundantly expressed
in skin, T-lymphocytes and dendritic cells. Furthermore, an analysis
of the expression data available from the Genevar database indicated
that rs495337 is associated with increased ZNF313 transcripts levels
(P = 0.003), suggesting that the disease susceptibility allele may be
a ZNF313 regulatory variant tagged by rs495337. Homology searches
indicated that ZNF313 is a paralogue of TRAC-1, an ubiquitin ligase
regulating T-cell activation. We performed cell-free assays and
confirmed that like TRAC-1, ZNF313 binds ubiquitin via an ubiquitin-
interaction motif. These findings collectively identify a novel
psoriasis susceptibility gene, with a putative role in the regulation
of immune responses.
PMID: 18364390
MORE WOW, wow....
OK i know. This isn't like watching hockey, unless you don't get it.
LOL
In which case it is.
===============================
More GOOD news in the Psoriasis GENETIC area. Closing in on
pathogenesis.
http://www.ncbi.nlm.nih.gov/pubmed/18364739?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Association analysis of the skin barrier gene cystatin A at the PSORS5
locus in psoriatic patients: evidence for interaction between PSORS1
and PSORS5.
Vasilopoulos Y, Walters K, Cork MJ, Duff GW, Sagoo GS, Tazi-Ahnini R.
1School of Medicine and Biomedical Sciences, University of Sheffield,
Sheffield, UK.
Family-based analysis has revealed several loci for psoriasis and the
locus, PSORS5, on chromosome 3q21 has been found in two independent
studies. In this region, cystatin A (CSTA) encodes a skin barrier
cystein protease inhibitor found in human sweat and it is over-
expressed in psoriatic skin. Three CSTA markers at positions -190
(g.-190T>C), +162 (c.162T>C) and +344 (c.344C>T) were analysed in 107
unrelated patients and 216 matched controls. There was a significant
trend for association with CSTA c.162T>C and psoriasis (odds ratio
(OR)=3.45, P<0.001). Analysis of constructed haplotypes showed a
highly significant association between disease and CSTA -190T/+162C/
+344C (CSTA TCC) (P=10(-6)). In independent study, a TDT analysis in
126 nuclear families confirmed the over-transmission of CSTA TCC
(P=0.0001). The presence of statistical interaction between CSTA TCC
haplotype and HLA-Cw6 at PSORS1 locus was detected by performing TDT
analysis on CSTA haplotypes stratified by the presence or absence of
the risk allele at HLA-Cw6 locus. To estimate the disease risk we
employed conditional logistic regression on the family data. The CSTA
TCC haplotype is only associated with psoriasis in those individuals
carrying the risk allele at the HLA-Cw6 locus (OR=2.22, P=0.0004, 95%
CI= 1.42, 3.49). These results represent a major step towards the
dissection of genetic factors involved in the pathogenesis of
psoriasis.European Journal of Human Genetics advance online
publication, 26 March 2008; doi:10.1038/ejhg.2008.40.
PMID: 18364739
=====================
Biologicals have side effects... some may KILL you. How clear is that?
http://www.ncbi.nlm.nih.gov/pubmed/18366773?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
A transient benign lymph node-based proliferation of T-cells
simulating non-Hodgkin lymphoma in a patient with psoriasis treated
with tumor necrosis factor alpha and CD11a antagonists.
Hurley MY, George MN, Leonardi CL, Frater JL.
ABSTRACT: BACKGROUND: Therapeutic biologic agents are uncommonly
associated with lymphoma. CASE PRESENTATION: We report a patient with
psoriasis treated with the biologic agents efalizumab (Raptiva) and
etanercept (Enbrel), who developed painless lymphadenopathy with
peripheral lymphocytosis during treatment, simulating a non-Hodgkin
lymphoma clinically and pathologically. Lymphocytosis and
lymphadenopathy spontaneously remitted following cessation of
etanercept therapy and have not recurred. CONCLUSION: Distinction
between clinically benign lymphoid proliferations related to
antipsoriasis therapy and malignant lymphoma avoids the unnecessary
use of anti-lymphoma chemotherapy.
PMID: 18366773
======================
IRON on the line again?
http://www.ncbi.nlm.nih.gov/pubmed/18363910?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Haptoglobin from psoriatic patients exhibits decreased activity in
binding haemoglobin and inhibiting lecithin-cholesterol
acyltransferase activity.
Cigliano L, Maresca B, Salvatore A, Nino M, Monfrecola G, Ayala F,
Carlucci A, Pugliese RC, Pedone C, Abrescia P.
Dipartimento delle Scienze Biologiche, Università di Napoli Federico
II, Naples, Italy.
OBJECTIVE: The aim of this work was to assess whether psoriasis is
associated with phenotype prevalence and altered activity of
haptoglobin (Hpt). BACKGROUND: Hpt is a plasma acute-phase
glycoprotein, displaying in humans three phenotypes. Phenotype
prevalence or structure modification of Hpt was associated with
several diseases. The Hpt main function is to bind and carry to the
liver free haemoglobin for degradation and iron recycling. Hpt was
recently found able to bind the apolipoprotein A-I (ApoA-I), thus
impairing its stimulation on the activity of the enzyme lecithin-
cholesterol acyl-transferase (LCAT). STUDY DESIGN: Hpt was isolated
from patients with psoriasis vulgaris, and its activity in haemoglobin
or ApoA-I binding and LCAT inhibition was compared with that of normal
protein. METHODS: Two affinity chromatography steps, the first using
resin-coupled haemoglobin and the second anti-Hpt antibodies, were
used to purify Hpt. The protein phenotype was assessed by
electrophoresis. Binding experiments were performed by Enzyme-linked
immunosorbent assay with stationary haemoglobin or ApoA-I, Hpt in
solution and anti-Hpt antibodies for detection of bound Hpt. Standard
LCAT assays were carried out in the presence of Hpt purified from
patients or healthy subjects. RESULTS: Phenotype prevalence of Hpt in
psoriasis was not found. After affinity chromatography by haemoglobin,
albumin and ApoA-I were routinely found heavily contaminating only Hpt
from normal subjects. Isolated Hpt from patients had lower activity
than normal protein in both haemoglobin binding and LCAT inhibition.
CONCLUSIONS: In psoriasis, Hpt displays some structure
modification(s), which might be associated with the protein function
in the disease.
PMID: 18363910
Heavy Metal and PSOR heads don't mix in my book. And for that reason
I use IP6 now and then... Especially if eating loads of red meat.
=========================
I ADAM 10 report to the station... Unit call HQs...
http://www.ncbi.nlm.nih.gov/pubmed/18363768?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Overexpression of ADAM 10 and ADAM 12 in lesional psoriatic skin.
Oh ST, Schramme A, Stark A, Tilgen W, Gutwein P, Reichrath J.
Department of Dermatology, Saarland University Hospital, 66421 Homburg/
Saar, Germany.
PMID: 18363768
Keywords for a pubmed search: A Disintegrin And Metalloprotease (ADAM)
Most recent post to pubmed:
http://www.ncbi.nlm.nih.gov/pubmed/18342566?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
=========================
TREGs and Foxp3
http://www.ncbi.nlm.nih.gov/pubmed/18363755?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Profiles of Foxp3+ regulatory T cells in eczematous dermatitis,
psoriasis vulgaris and mycosis fungoides.
Fujimura T, Okuyama R, Ito Y, Aiba S.
Department of Dermatology, Tohoku University Graduate School of
Medicine, Seiryo-machi 1-1, Aoba-ku, Sendai 980-8574, Japan.
Background It is well known that regulatory T cells (Tregs),
identified by their expression of CD4, CD25 and Foxp3, play a crucial
role in maintaining peripheral tolerance. Recently, it has been
demonstrated that a Treg population resides in normal human skin.
However, only a few studies have demonstrated the presence of Foxp3+
Tregs in inflammatory skin disorders. Objectives In this study, we
immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs
in the lesional skin of psoriasis vulgaris, mycosis fungoides and
eczematous dermatitis. Methods We used immunohistochemistry to examine
the presence of Foxp3+ Tregs in fixed sections of the lesional skin
from 16 patients with psoriasis vulgaris, 17 patients with mycosis
fungides and 18 patients with eczematous dermatitis in addition to 10
normal skin samples. Results In normal skin, epidermal and dermal
Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and
eczematous dermatitis samples contained substantial numbers of
epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis
contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells
than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+
cells was significantly lower in eczematous dermatitis than in
psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+
cells was significantly lower in psoriasis vulgaris than in eczematous
dermatitis or mycosis fungoides. Conclusions The lower percentage of
epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis
vulgaris, respectively, might contribute to their pathogenesis.
PMID: 18363755
===========================
Will Peptide T block P selectins?
http://www.ncbi.nlm.nih.gov/pubmed/18360560?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Inhibitors of selectin functions in the treatment of inflammatory skin
disorders.
Schön MP.
Rudolf Virchow Center, DFG Research Center for Experimental
Biomedicine and Department of Dermatology, Julius-Maximilians-
University Würzburg, Germany.
Selectins mediate tethering and rolling of leukocytes to the vascular
endothelium, the first adhesive step in the recruitment of immune
cells to inflamed tissues. Thus, selectins play a key role in the
pathogenesis of common inflammatory skin disorders such as atopic
dermatitis or psoriasis. As a consequence of their key functions,
selectins have received much attention as potential target structures
for new therapies. Indeed, a number of agents including small-molecule
as well as peptide compounds interfering with selectin functions have
been developed to treat inflammatory disorders. However, many of the
selectin-directed compounds have not held up to the high expectations,
in some cases due to overlapping and mutually compensating functions
of selectins or suboptimal pharmacokinetic properties of the
compounds, while other agents appear to be more promising candidates
and have already entered clinical trials. Selectively targeting the
functions of one or several selectins involved in the cascade of
leukocyte recruitment promises exciting new therapeutic options, but,
at the same time, bears considerable imponderables, which will be
discussed in this review article.
PMID: 18360560
===========================
For the 99th time. The Chinese Hans and their P susceptibility
http://www.ncbi.nlm.nih.gov/pubmed/18369457?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Fine Mapping of the Psoriasis Susceptibility Locus PSORS1 Supports HLA-
C as the Susceptibility Gene in the Han Chinese Population.
Fan X, Yang S, Huang W, Wang ZM, Sun LD, Liang YH, Gao M, Ren YQ,
Zhang KY, Du WH, Shen YJ, Liu JJ, Zhang XJ.
Institute of Dermatology and Department of Dermatology at No. 1
Hospital, Anhui Medical University, Hefei, Anhui, China.
PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility
locus for psoriasis. Several fine-mapping studies have highlighted a
300-kb candidate region of PSORS1 where multiple biologically
plausible candidate genes were suggested. The most recent study has
indicated HLA-Cw6 as the primary PSORS1 risk allele within the
candidate region in a Caucasian population. In this study, a family-
based association analysis of the PSORS1 locus was performed by
analyzing 10 polymorphic microsatellite markers from the PSORS1 region
as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of
psoriasis. Five marker loci show strong evidence (P<10(-3)), and one
marker locus shows weak evidence (P = 0.04) for association. The
haplotype cluster analysis showed that all the risk haplotypes are Cw6
positive and share a 369-kb region of homologous marker alleles which
carries all the risk alleles, including HLA-Cw6 and CDSN*TTC,
identified in this study. The recombinant haplotype analysis of the
HLA-Cw6 and CDSN*TTC alleles in 228 Chinese families showed that the
HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotype is clearly not associated
with risk for psoriasis (TratioNT = 29:57, p = 0.0025) in a Chinese
population, suggesting that the CDSN*TTC allele itself does not confer
risk without the presence of the HLA-Cw6 allele. The further exclusion
analysis of the non-risk HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotypes
with common recombination breakpoints has allowed us to refine the
location of PSORS1 to a small candidate region. Finally, we performed
a conditional linkage analysis and showed that the HLA-Cw6 is a major
risk allele but does not explain the full linkage evidence of the
PSORS1 locus in a Chinese population. By performing a series of family-
based association analyses of haplotypes as well as an exclusion
analysis of recombinant haplotypes, we were able to refine the PSORS1
gene to a small critical region where HLA-C is a strong candidate to
be the PSORS1 susceptibility gene.
PMID: 18369457
Whats the demographics on early and late onsets here?
I know I've looked more then a few times. One more won't hurt.
But in the light of the above, the winds have waned on the han sail.
================================
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==============================
randall...
JXStern
wrote:
>Biologicals have side effects... some may KILL you. How clear is that?
>
>http://www.ncbi.nlm.nih.gov/pubmed/18366773?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
>A transient benign lymph node-based proliferation of T-cells
>simulating non-Hodgkin lymphoma in a patient with psoriasis treated
>with tumor necrosis factor alpha and CD11a antagonists.
>Hurley MY, George MN, Leonardi CL, Frater JL.
>
>ABSTRACT: BACKGROUND: Therapeutic biologic agents are uncommonly
>associated with lymphoma. CASE PRESENTATION: We report a patient with
>psoriasis treated with the biologic agents efalizumab (Raptiva) and
>etanercept (Enbrel), who developed painless lymphadenopathy with
>peripheral lymphocytosis during treatment, simulating a non-Hodgkin
>lymphoma clinically and pathologically. Lymphocytosis and
>lymphadenopathy spontaneously remitted following cessation of
>etanercept therapy and have not recurred. CONCLUSION: Distinction
>between clinically benign lymphoid proliferations related to
>antipsoriasis therapy and malignant lymphoma avoids the unnecessary
>use of anti-lymphoma chemotherapy.
>
>PMID: 18366773
Treated with the two drugs sequentially or together?
J.
Benjamin
>
> =======================================================
> =======================================================
>
> While talking with Ben B. last night. We came to endotoxins (LPS) and
> a possible connection
> with ssRNA for a possible insult to DNA in the P battles. The
> endotoxins
> would be from all foreign critter's that live on and in us and thrive
> due to our diets. We both agree that starvation is one way to draw
> down their influence.
>
> Ben's take at this time is to stop/slow/reverse aging, live well and
> LONG and the P will
> clear uP in the process.
>
> Hey? What can I say? I'm on this triP for as long as it lasts.
>
> What's not to like with LIVE a LONG LIFE? And if the P clear's in the
> process
> so much the better.
>
After our talk I re-realized that all the sites of my psoriasis are on
old scratching and squeezing sites on my body. Maybe your the same
way? I was a very active child and had many accidents, these sites
became my Psoriaisis sites.
What seems to be happening is Tinea allows small changes to occur in
how your DNA is expressed. Allowing all kinds of things to cross your
now compromised immune system. This is what aging really is. THE
DISEASE that psoriasis is part of. Stop this DNA corruption and our
Psoriasis goes away!
Where I had mosquito bites and scratched were the worst Psoriasis
spots, where I had squeezed blackheads on my back as a child, I have
two small persistent spots of Psoriaisis. Where a young woman had
scratched my back while learning about sex, I had spots that matched
her fingernails. On my shins, where on one, I had an axe accident, and
the other where having hit the same spot many dozens of times on my
boat, I had a carbunkle and psoriasis.
If you look at Grey's Anatomy, you will read that TInea is a very
contagious fungal infection, and the pictures remarkably similar to
Psoriasis, yet in all my years I have yet to have my dozens of doctors
note mine! Tinea can be as subtle as the "bleach" spots in your tan!
Yet its my estimate that since we don't treat it; after 50 years it is
a serious problem.
THE only way I have cleared my Psoriasis, is the two fasts early in my
life, as we get older the accumulations get worse. Making it harder to
get better.
My method of taking Antigungals and Antibiotics, is a way to mimic
this fasting process without being hungry or knowing the right foods
to eat. My appetite wanes, on this regime, my cholesterol drops to
160, I lose weight quickly and my sin shrinks along with the weight. I
now weigh 160 down from 240 and a cholesterol of 330.
Please don't take this course unless your sure you can maintain it. I
ran out twice of my prescription drugs and twice gained 30 pounds and
had my cholesterol shoot up back to 330, in one month. This caused me
several seizures; all due to this stoppage. All tests that were done
at the hospitals came up negative for any cause other than my
explanation.
This is where I lose most people, I didn't guess this to create it, it
is my literal interpetation of the oral history written down in
Genesis. This is only part I think attributable to being written down
by Moses. Also, I say we can see from history that Jesus and Mohamed
were very well admired in their own time for looking and being VERY
different. I say not god, but pure homo sapien! We are so compromised
with other orgamisms, that our measure of beauty is how little
infection you have. They both fasted for a month or more. It was this
action by them, that cleared out all the organisms, no pharmaceuticals
required. I say it was the probable cause of Adam and those that
followed abilities to live long and have children all their lives. DNA
like CD can replicate perfectly, if it isn't there is your disease!
Everything will be found to be a symptom of this cause.
BTW- As an aside - The reason that civilization exists, is of all the
microbes we harbor. This caused man to lose his innate abilites in
nature, making him go to work repalcing what came naturally with all
you see around us today. To my eye here is no free will, only ongoing
chemical reaction.
Benjamin Blavat
randall
Hey Benjamin,
To your aside, if we evolved with the bugs we live with them.
The one area I've figured was critical was the Gi tract and
have already mentioned this and will again.
We seemingly experience the world through our skin and I'm going
banana's at the moment.
That would be using the B peel skins on my plaque areas.
That's right, something I read in the group a while back.
This is my second day. I looked a little crunchy the last few
weeks, keeping in form with the time of year and while
coleus root (forskohlii or forslean) is helping it's not the
end all and be all. I still can't eat with impunity. Never
could come to think of it.
As the B peel thing is only the second day I'm reticent to
speculate, but at the risk of sliPPing on one I'll try nevertheless.
I'm wondering if the peel isn't putting a slight mucous like occlusion
patch
on the plaque? Plus, whatever keeps the banana fresh in
the skin is acting as some type of antioxidant?
Which raises a host of questions with using unripe
fruit as opposed to ripened etc.
Oh well, to early to tell, since I just smush some on
as a topical and it will take a few hours for the
effects. <w>
I'll save this post and comment later in the day.
As to your post Benjamin, it takes me back to when
I didn't have psoriasis as well. I had every other Th2 skin condition
prior to becoming psoriatic at an early age. In retrospect
i've wondered if breast feeding would have helped?
Or at the very least have postponed it till my late
forties, as is the case with other family members.
How many times have i wondered that breast milk thing?
Almost 50 hits come up for the keywords. LOL
But!
I'm a born again breast feeder with the wit kit from
David Webster & AHS
http://www.thewholewhey.com/prodesc.php?pro_id=23&PHPSESSID=f08281a933cee529df38c8cb84959e91
Going on nine years with it. I'm gonna do some fasting and strict
dieting to
get even clearer this year and supplement with sweet whey which I do
everyday already.
Will I become a
http://en.wikipedia.org/wiki/Methuselah ???
I sorta doubt it. OTOH all bets are off once someone
can control the,
http://en.wikipedia.org/wiki/Telomeres
We are front loaded at most for 120 spins of the dirt
ball around the hot ball of gas. lol
http://en.wikipedia.org/wiki/Hayflick_limit
Which defeated Carrel's immortal cell theory
http://en.wikipedia.org/wiki/Alexis_Carrel#Cellular_Senescence
If aging wasn't such a b i itch i'd like to think the
melatonin i've taken for the last half dozen years was
adding some time to the bottom line.
Or that GOD was so kind to give us
all a crack at the 120 goal without
senescence. DNA is a roll of the dice
as far as rolling double 6's or 120 years of life.
We all can't be as lucky as Jeanne Calment
http://en.wikipedia.org/wiki/Jeanne_Calment
http://en.wikipedia.org/wiki/Longevity
http://en.wikipedia.org/wiki/Maximum_life_span
---------------------
Linus Pauling lived till 93 and took 6-18 grams a day of
Vitamin C and other supplements.
http://en.wikipedia.org/wiki/Linus_Pauling
http://en.wikipedia.org/wiki/Vitamin_C
===========================
OK... I started this post over five hours ago.
The skin looks good. Once I wash it off and give it
time to dry off will it look better then without the peel?
Time now: 2:00 pm pst
------------------------------------------------
OK.. it's all washed off now. Time: 3:00 pm pst
Looking slightly better then without the b peel.
------------------------------------------
I'm waiting to see how it looks some time from now.
Ok it's 4:30 pm pst now.
I'm clearly going to have to eat or use the b peels
after bathing from now on. LOL
Since I freeze these guys for shakes I could keep
up my trial for another week or so. Then buy more
and go longer.
OK... what were we talking about?
Oh.. LPS and bugs that leave their leftover's in us
and that affects DNA. If that is in fact what happens?
Now I have homework.
http://www.ncbi.nlm.nih.gov/pubmed/18261321?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
[Protective role of Pim-3 gene in intestinal mucosa damaged by burn or
lipopolysaccharide]
[Article in Chinese]
Chen JY, Shen XW, Zhang JX.
Department of Gastroenterology, Second Affiliated Hospital of Nanchang
University, Jiangxi Provincial Key Laboratory of Molecular Medicine,
Nanchang, China.
OBJECTIVE: To explore the protective role of Pim-3 gene in intestinal
mucosa damaged by burn or lipopolysaccharide (LPS). METHODS: (1)
Ninety Wister mice were randomly divided into 3 equal groups: Group A,
undergoing 30% grade III burning on the back; Group B, undergoing
intraperitoneal injection of LPS; and Group C, undergoing
intraperitoneal injection of normal saline. 3, 6, 12, 24, and 48 hours
after the treatment 5 rats from each group were killed with their
small intestine tissues taken out. RT-PCR was used to detect the mRNA
expression of Pim-3, a serine/threonine kinase, occludin,
intercellular adhesion molecule (ICAM)-1, and Western blotting was
used to detect the protein expression of Pim-3 and occludin. (2)
Intestinal endothelial cells (IECs) of newborn Wistar rats were
collected, cultured, and divided into 6 groups: Group (1), treated
with LPS (endotoxin), Group (2), transfected with blank plasmid pEGFP-
N(2) and treated with LPS, Group (3), transfected with recombinant
pEGFP-N(2)/Pim-3and treated with LPS, Group (4), as normal control
group, Group (5), transfected with blank plasmid pEGFP-N(2), and Group
(6), transfected with recombinant plasmid pEGFP-N(2)/Pim-3. Six hours
later RT-PCR was used to detect the mRNA expression of Pim-3, ICAM-1,
and occludin. The apoptosis of the cells was examined by flow
cytometry. RESULTS: (1) In Groups A and B the mRNA expression of Pim-3
began to increase 3 h later, peaked 6 h later, and then gradually
decreased. The Pim-3 mRNA expression of Group C, however, remained
always at a low level. The ICAM-1 mRNA expression levels of Groups A
and B were constantly up-regulated 6 h later, all significantly higher
than those of Group C (all P < 0.01). The occludin mRNA expression
levels of Groups A and B began to increase 3 hours later, and peaked
12 hours later, all significantly higher than those of Group C (all P
< 0.05). (2) The mRNA expression levels of Pim-3 and occludin of Group
(6) was significantly higher than those of Groups (4) and (5) (both P
< 0.05). However, there was no significant difference in ICAM-1 mRNA
expression among Groups (4), (5), and (6). The mRNA expression levels
of Pim-3, occluding, and ICAM-1 of Groups (3) were all significantly
higher than those of Groups (1) and (2) (all P < 0.05). The mRNA
expression levels of ICAM-1 of Groups (1), (2), and (3) were all
significantly lower than those of Groups (4), (5), and (6) (all P <
0.05). The apoptotic rates of groups (4), (5), and (6) were all very
low. The apoptotic rates of Groups (1) and (2) were 41.3% and 44.80%
respectively, both significantly higher than that of Group (3)
(36.03%, both P < 0.05). CONCLUSION: Both burning and LPS stimulate
endogenous Pim-3 gene expression in small intestine which lasts a
short time. Pim-3 gene not only suppresses the apoptosis of IECs, but
also strengthens the occludin expression and inhibits the intestinal
tract inflammatory reaction induced by LPS. LPS induces ICAM-1
expression, which can be inhibited by Pim-3.
PMID: 18261321
So ICAM-1 is induced by tnf
http://en.wikipedia.org/wiki/ICAM-1
I see a pim1 but no pim-3
http://en.wikipedia.org/wiki/PIM1
--------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/18078689?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Intestinal alkaline phosphatase detoxifies lipopolysaccharide and
prevents inflammation in zebrafish in response to the gut microbiota.
Bates JM, Akerlund J, Mittge E, Guillemin K.
Institute of Neuroscience, University of Oregon, Eugene, OR 97403,
USA.
Vertebrates harbor abundant lipopolysaccharide (LPS) in their gut
microbiota. Alkaline phosphatases can dephosphorylate and detoxify the
endotoxin component of LPS. Here, we show that expression of the
zebrafish intestinal alkaline phosphatase (Iap), localized to the
intestinal lumen brush border, is induced during establishment of the
gut microbiota. Iap-deficient zebrafish are hypersensitive to LPS
toxicity and exhibit the excessive intestinal neutrophil influx
characteristic of wild-type zebrafish exposed to LPS. Both of these
Iap mutant phenotypes are dependent on Myd88 and Tumor Necrosis Factor
Receptor (Tnfr), proteins also involved in LPS sensitivity in mammals.
When reared germ-free, the intestines of Iap-deficient zebrafish are
devoid of neutrophils. Together, these findings demonstrate that the
endogenous microbiota establish the normal homeostatic level of
neutrophils in the zebrafish intestine through a process involving
Iap, Myd88, and Tnfr. Thus, by preventing inflammatory responses, Iap
plays a crucial role in promoting mucosal tolerance to resident gut
bacteria.
PMID: 18078689
I wonder if this is the same for humans?
Well, I'm not finding what I want. I'll give it some time and think of
better
keywords.
As to the rest, I require one now. LOL
randall...
randall
>
> Hey Benjamin,
>
> We seemingly experience the world through our skin and I'm going
> banana's at the moment.
>
> That would be using the B peel skins on my plaque areas.
> That's right, something I read in the group a while back.
>
> This is my second day. I looked a little crunchy the last few
> weeks, keeping in form with the time of year and while
> coleus root (forskohlii or forslean) is helping it's not the
> end all and be all. I still can't eat with impunity. Never
> could come to think of it.
>
> As the B peel thing is only the second day I'm reticent to
> speculate, but at the risk of sliPPing on one I'll try nevertheless.
>
> I'm wondering if the peel isn't putting a slight mucous like occlusion
> patch
> on the plaque? Plus, whatever keeps the banana fresh in
> the skin is acting as some type of antioxidant?
> Which raises a host of questions with using unripe
> fruit as opposed to ripened etc.
>
> Oh well, to early to tell, since I just smush some on
> as a topical and it will take a few hours for the
> effects. <w>
>
> I'll save this post and comment later in the day.
>
> <sniP>
>
> OK... I started this post over five hours ago.
>
> The skin looks good. Once I wash it off and give it
> time to dry off will it look better then without the peel?
>
> Time now: 2:00 pm pst
>
> ------------------------------------------------
>
> OK.. it's all washed off now. Time: 3:00 pm pst
>
> Looking slightly better then without the b peel.
>
Day 3 with the B peels.
You know how the peel turns brown after it's peeled?
Well the stuff that is rubbed on the skin looks like that
after a while and it dries on.
I'm not sure if I want to scrape it off as it doesn't rub
off easily. But if it's not in a visible area I suppose just
put on clothes and don't worry about it.
Feeling sorta encouraged about this one.
We could cocktail in coconuts and some of the
other things from over the years. <w>
A low dose topical Tropical fruit treatment if you will. <g>
And with a Tommy Bahama theme for attire we'll be COOL.
I'm still doing other supplements with many worthy supplements
taken out of the current regime so as to identify the stalwarts
in the bunch.
The mainstay of the day if I'm reading the current trial
correctly is Forslean (forskohlii root from coleus).
Which is really cheap like banana peels as well.
I bought 50 grams and started using it July 1st,
2007. The suggested dosage is 150 mg.s giving
333 servings per container. Cost is $18.50 and
i've still got a month or so left. For only
$18 bucks I've gotten nine months so far.
Now that is cheap. lol
Mind you i'm on the sweet whey supplement and
other supplements, like Rhodiola Rosea, Fo-Ti
etc.
OH oh, almost forgot started taking 100 mg
Trans Resveratrol from Longevinex about
45 days now. Haven't a clue as to what it's
doing.
Suppose to be like X amount of glasses of
red wine. To find out more:
www.longevinex.com
randall... happy to live till 90-122 without a glitch or two...?
JXStern
wrote:
>Day 3 with the B peels.
We'll call you mellow yellow, quite rightly.
FWIW, I seem to have hit upon a combo recently which seems to give me
a bit more relief, unfortunately it's two things (on top of twenty
others), but the two things are (a) more fish for omega-3 and dietary
D, and (b) add a little cinnamon (about 50mg I estimate by gosh and
golly) to my turmeric (twice a day).
And, oh yes, (c), decided to drop my primrose oil for a while. So,
three things. But I'd tried that before.
And (d), I'm experimenting with taking occassional mid-sized doses of
vitamin D, especially after a couple of days I do not manage to get
any sun, but so far, haven't been able to associate any visibile
results from that. Maybe it at least equates to getting the sun, but
there's an element of heat prostration (sweating, relaxation ...
sleep!) I also get from sitting in the sun which I think is somehow
beneficial and the D alone does not provide.
I had actually been mostly avoiding fish the last couple of years, too
much fish for whatever reason seemed to increase my tendency to bleed.
And we've both tried cinnamon in the past, for whatever reasons I
forget, and found that too much cinnamon seems to aggravate.
Well, I'm adding these back now on top of turmeric, horseradish, and
the DHA I get in those gold circle eggs. And it seems to best
preserve me at the best shape I've seen for years, with perhaps a
little bit of slow clearing.
So, my hope is that I can start cutting back some other various stuff
in the direction of a balanced amount of (a) turmeric, (b)
horseradish, (c) fish, (d) cinnamon.* At least (c) and (d) can be in
amounts too large, so one has to watch it (and there are two types of
cinnamon, one type has much more coumadin in it, and there's no way
short of a lab to tell which you have got).
Anyway, that's my current bulletin, state, and experiment.
J.
*also a bunch of other nutrition, topical, dietary etc, less likely to
have direct effects, perhaps the most likely to be significant is
onion.
randall
> On Tue, 1 Apr 2008 11:38:08 -0700 (PDT), randall <ranhu...@aol.com>
> wrote:
>
> >Day 3 with the B peels.
>
> We'll call you mellow yellow, quite rightly.
>
Thanks, but i'm sorta brownish yellow after
squishing b peels topically.
It was a good one for some:
http://www.youtube.com/watch?v=EQz_s8Yw1Us
But,
Will the B peels turn out to be a big BUST like
folic acid?
I could have gotten colon cancer!
http://www.health.harvard.edu/press_releases/folic-acid-and-cancer-risk.htm
Glad I stoPPed that trial prematurely
========================================
I did buy some herring from costco after the vitamin D thread
started by skeats last week...
And then flared for a few days.
Don't know why I stoPPed taking the high DHA eggs. They
certainly seemed to help.
How much bang for your buck have you gotten percentage wise?
For this time of year i'm feeling like (guessing) i'm down
about 43.2%. Give or take 9-43%. LOL
Know what I mean jelly bean?
randall... still working for truth, honor & the psoriatic whey
zzznot
"randall" <ranh...@aol.com> wrote in message
news:c3c41d09-c46d-4c9e...@u10g2000prn.googlegroups.com...
> On Apr 1, 12:01 pm, JXStern <JXSternChange...@gte.net> wrote:
> I did buy some herring from costco after the vitamin D thread
> started by skeats last week...
>
> And then flared for a few days.
Sorry.
> Don't know why I stoPPed taking the high DHA eggs. They
> certainly seemed to help.
>
> How much bang for your buck have you gotten percentage wise?
>
> For this time of year i'm feeling like (guessing) i'm down
> about 43.2%. Give or take 9-43%. LOL
>
>
> Know what I mean jelly bean?
>
> randall... still working for truth, honor & the psoriatic whey
I don't vary that much, I have a couple of percent that's been coming and
going, and it's mostly going. And the other areas are - calmer.
JxStern
Benjamin
> x-no-archive: yes
>
> Benjamin wrote:
> > My method of taking Antigungals and Antibiotics, is a way to mimic
> > this fasting process without being hungry or knowing the right foods
> > to eat. My appetite wanes, on this regime, my cholesterol drops to
> > 160, I lose weight quickly and my sin shrinks along with the weight. I
> > now weigh 160 down from 240 and a cholesterol of 330.
>
> from the antifungal's effect of suppressing your HPA axis. In fact,
> ketoconazole is used in Cushing's disease for this very function.
>
> It would explain the loss of appetite (cortisol = hunger) and the lipids
> improvement.
>
> Susan
Sorry Susan,
YOU ARE WRONG, there is no basis for what you are saying. Its
defintiely an accummulation problem An accumulation of floras that
eats constantly, and having nearly the same DNA (all DNA is within
4%), they have the same capability to create hunger or have it as you
say, cortisol. On reading the Wiki, I would say that the whole concept
of Cushing disease is wrong. Its not your own body cells running amok
but an outside agent. That is why taking the antifungals and
antibiotics is able to lower the concentrations. Now without their
hormones to cause you to be hungry, you aren't! Our bodies are just
fine its the outside agents that cause the troubles. So much more than
Psoriasis gets better from treating it this way.
Why does fasting work in your model Susan? I was COMPLETELY clear on
two separate occassions due to fasting (btw I also had bad diarhea,
more proof to me that purging the gut can help). Its my theory
developed from these events, is that we feed something, and it is its
poop that is expressed in our skins damaged areas, now an infected
scab site. I have have had old infections come back, time, and time
again. The most recent being the case of 'sunpoisoning' I got in
Florida when I was six, 53 years ago. Treating it this time with my
regimen its gone in two days.
I had a lucky occurence here in Mexico, I couldn't get the sizes of
Keflex, Doxycyline and Ketocanozole, that I normally get. These larger
versions, have made big steps overnight to my finishing, clearing my
Psoriasis. ( I hope!)
The concept that it is something wrong with our biology and DNA is
sheer Science Belief. And the definition of belief is 'hopeful
guessing'.
Using my theory I can stop impact injuries from causing ANY black and
blue, let alone yellow and green. Here is something you can do to
PROVE to yourself that my model is closer than any used today. Next
time you hit your thumb with a hammer, take a bad fall on your knee,
try this, take two Itracanosole 100 mg capsules immediately, those
injuries will not persist. There will be no swelling or pain, it is my
theory that black and blue is caused by crushed cells being eaten by
cruising microbes, their growth causes the expansion that is the
swelling and pain of the injury. DMSO also works for the same reason.
cruiser
>
> And IF the trigger is upstream of th1/th2 will it work?
>
Randall,
You mention the trigger. I presume you are aware that calcium channel
blockers will intiated a psoriasis outbreak in those genetically
predisposed to psoriasis, even if they have no history of psoriasis.
There's your trigger, calcium channel impairment.
Are you aware the VDRs are overexpressed in psoriasis and that calcium
is deficient in psoriatic cells?
Have you reasoned that anything in the body that is overexpressed, is
overexpressed due to a failure of the homeostatic off switch to switch
off, which should indicate that the normal expected result of such
expression is not being accomplished?
What should turn off the overexpression of VDRs?
Waht should turn off the overexpression of NOS?
You have to be aware that vitamin D mitigates psoriasis when applied
topically, and that UV radiation used to treat psoriasis, and known to
be effective, promotes the synthesis of vitamin D.
Have you explored this at all?
cruiser
Benjamin
>
> Ketoconazole shuts down cortisol excess. Fasting raises cortisol levels.
> Cushing's pituitary tumors excrete hormones and cause deficiencies in
> some others, variable with the individual, making results highly erratic
> and individual.
>
> Susan- Hide quoted text -
>
> - Show quoted text -
Hi Susan,
I am having very good luck with it, all the remaining Psoriasis is
waning or all ready gone. Please remember, I in 1994, I was 93%
covered in bleeding plaques sores. All my cysts of 50 years plus are
drained or waning too. The arthritis that stopped me from sailing in
the 80's is gone, no pains what so ever! My glaucoma and cataracts are
gone and presbyopia is nearly gone I have an appointment at Nova
Southeastern U, for tests come May.
Remember that everything I have written has been tested out on myself.
As you write, these events of Cushing DIsease are very errattic,
making it likely for the information to be incorrect. Unfortunately,
too many Scientists do the same quality of work as President Bush, and
they get paid either way! LOL! there is a lot of bad information in
Science now. Too many scientists are believers in religion. You can't
make correct dedutions when you have fixed assumptions.
All scars from all over my body are clearing up. The nicks in my shins
bones are filling! In otherwords my DNA is making a comeback. The new
clarity of thought I have, has been very satisfying, I am all
assertive, and not passive aggressive in the least anymore. So many
things we associate with free will and personality is proving to be
caused by our little visitors.
What we have in common is our homo sapienism, what differentiates us
is the different faunas and floras we acquire over time, they find a
home in us becuase we are so overfed. We are unaware of their presence
till it's too late to do anything about.
There are only two diseases in mankind today, everything else is a
symptom caused by them; one is the original one, that is how we lost
9/10 of our abiltiy to access our minds (an undiagnosed symptom) which
make us scramble to live outside of nature as we do now. And the other
that our DNA gets impressed by other organisms, morphing us to change
as we get older. I will keep the group informed of my progress or lack
of.
Its my theory that these are/were caused by plaque, and the only cause
of plaque I have found in all of medicine is Tinea.
With good thoughts,
Benjamn Blavat
randall
> Hi,
> <huge snip>
> ================================================
>
> WOW, wow, bow wow..wait no bow wow... just WOW.
>
> A monster DNA study from a BUNCH of Scientific Heavy hitters.
>
>
> ================================
> <snip>
It's only four days since the above abstract was posted here.
If the banana peel was an april fool's day hoax and the jury seems
to be sliPPing on that one, the bowcock genetics study certainly was
for real.
And the media is getting the notice now that something happened? LoL
The entire study to go with the above abstract.
http://www.plosgenetics.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pgen.1000041
Alert... alert-- something haPPened. LOL
http://www.eurekalert.org/pub_releases/2008-04/plos-run032808.php
Researchers uncover new genetic links to psoriasis
In a comprehensive study of the genetic basis of psoriasis,
researchers at Washington University School of Medicine in St. Louis
have discovered seven new sites of common DNA variation that increase
the risk of this troublesome skin condition. They also found that
variations in one genetic region link psoriasis and psoriatic
arthritis to other autoimmune disorders. These results appear April 4
in the open-access journal PLoS Genetics.
An estimated 7 million Americans have psoriasis, an autoimmune disease
that occurs when the body's immune cells mistakenly attack the skin.
The condition is characterized by red, scaly patches that can be
itchy, painful or both. Some 10 to 30 percent of patients with
psoriasis develop psoriatic arthritis, a condition that is often
excruciatingly painful and debilitating.
"Common diseases like psoriasis are incredibly complex at the genetic
level," says lead investigator Anne Bowcock, Ph.D., professor of
genetics at the School of Medicine. "Our research shows that small but
common DNA differences are important in the development of psoriasis.
Although each variation makes only a small contribution to the
disease, patients usually have a number of different genetic
variations that increases their risk of psoriasis and psoriatic
arthritis."
In their study, the researchers focused on points of common variation
in the genome called single nucleotide polymorphisms, or SNPs. While
most of the 3 billion nucleotides that comprise DNA are thought to be
identical from one person to the next, some 10 million SNPs build
variation into the genome and make each individual unique. Some of
these SNPs play a crucial role in a person's predisposition to disease
or good health.
Using an approach known as whole genome association, the investigators
scanned more than 300,000 SNPs in the genomes of 223 psoriasis
patients, including 91 who had psoriatic arthritis. They compared the
DNA variations in people with psoriasis to those found in 519 healthy
control patients, looking for specific differences that may be linked
to the disease. They then replicated their findings in a larger set of
patients - 577 with psoriasis and 576 with psoriatic arthritis - and
more than 1,200 healthy controls.
Bowcock and her team found seven novel DNA variations linked to
psoriasis. Notably, DNA variations on chromosome 4 were strongly
linked to psoriatic arthritis. These same variations were also
associated with psoriasis and had been previously linked to type 1
diabetes, rheumatoid arthritis, Grave's disease (caused by an
overproductive thyroid gland), and celiac disease (caused by the
inability to digest gluten).
The variations identified by this research team point to different
biological pathways that underlie psoriasis and may eventually lead to
new targeted drugs and treatments that hit specific pathways, Bowcock
says.
Bowcock is now involved in a larger genome-wide association study of
psoriasis patients and says she expects it will uncover additional
genetic variations that are associated with psoriasis. Eventually, she
predicts, such studies will lead to more effective, better-targeted
therapies.
###
-----------------------
Really.. I mean really. MN today got it four days late as well.
http://www.medicalnewstoday.com/articles/102245.php
[...]
There are many factors that may come into play in this condition,
which make it difficult to study. This is true concerning its genetics
as well. "Common diseases like psoriasis are incredibly complex at the
genetic level," says lead investigator Anne Bowcock, Ph.D.. "Our
research shows that small but common DNA differences are important in
the development of psoriasis. Although each variation makes only a
small contribution to the disease, patients usually have a number of
different genetic variations that increases their risk of psoriasis
and psoriatic arthritis."
The study, performed at the Washington University School of Medicine
in St. Louis, was a comprehensive examination of the genetic basis of
psoriasis. The researchers directed their attentions to points of
common variation in the genome, known as single nucleotide
polymorphisms (SNPs.) A large portion of the 3 billion nucleotides
that make up the genome are identical from one person to the next, but
some 10 million SNPs make someone unique. Of these, certain SNPs can
influence disease and health in a person.
In a whole genome association study, the investigators scanned over
300,000 SNPs in the genomes of 223 psoriasis patients. This included
91 with psoriatic arthritis. The DNA of these patients was compared to
that of 519 healthy patients in a control group, seeking specific
differences between the groups. Then, a second study was performed
with 577 psoriasis patients, 576 with psoriatic arthritis, and over
1,200 healthy controls.
The team discovered seven new variations that were linked to
psoriasis. Additionally, the DNA variations that were located on
chromosome 4 were strongly linked to psoriatic arthritis. These
variations were also associated with type 1 diabetes, rheumatoid
arthritis, Grave's disease (the result of an overproductive thyroid
gland), and celiac disease (an inability to digest gluten).
These variations point scientists in the direction of different
biological pathways that could underlie psoriasis on a basic level.
This could eventually lead to new targeted drugs and treatments that
attack specific pathways, according to Bowcock. She is now conducting
a larger, genome-wide association study of psoriasis patients, and she
expects to find additional genetic variations that are associated with
the disease.
<sniP>
--------------------------------------------------
http://www.webmd.com/skin-problems-and-treatments/psoriasis/news/20080403/psoriasis-7-new-genetic-clues
Psoriasis: 7 New Genetic Clues
Newly Discovered Genetic Variations May Make Psoriasis More Likely,
Study Shows
By Miranda Hitti
WebMD Medical News
Reviewed by Louise Chang, MD
April 3, 2008 -- Scientists have discovered seven genetic variations
linked to psoriasis.
If confirmed in other studies, those gene variants may make good
targets for new psoriasis drugs, note the researchers, who included
Anne Bowcock, PhD, genetics professor at Washington University School
of Medicine in St. Louis.
"Common diseases like psoriasis are incredibly complex at the genetic
level," Bowcock says in a news release. "Our research shows that small
but common DNA differences are important in the development of
psoriasis. Although each variation makes only a small contribution to
the disease, patients usually have a number of different genetic
variations that increases their risk of psoriasis and psoriatic
arthritis."
Bowcock's team compared DNA from 223 psoriasis patients (including 91
with psoriatic arthritis) and 519 people without psoriasis, and also
from two other large groups of people with and without psoriasis.
Through those comparisons, the researchers identified seven genetic
variations linked to psoriasis and psoriatic arthritis and confirmed
other variations already linked to psoriasis.
One of the newly discovered variants is in a genetic region tied to
four other autoimmune diseases: celiac disease, type 1 diabetes,
Grave's disease, and rheumatoid arthritis.
Further studies are needed to confirm the findings, Bowcock and
colleagues note in the April 4 online edition of Public Library of
Science Genetics.
--------------------------------------------------------------
http://www.washingtonpost.com/wp-dyn/content/article/2008/04/03/AR2008040301961.html
(How'd they put this one in with the preceding doesn't make sense. Oh
well)
==================================
randall... thanks anne for your dedication to solving the P equation..
randall
GEN News picks up the Bowcock et al story today. (2 hours ago)
Is the west the best for the race for the P Grail?
Maybe not. See todays abstracts after these first two hits.
http://www.genengnews.com/news/bnitem.aspx?name=33197668
Investigators Discover Eight SNPs Related to Psoriasis
GEN News Highlights
Researchers discovered eight sites of common DNA variation that
increase the risk of psoriasis (PS). They also found that variations
in one genetic region link psoriasis and psoriatic arthritis (PSA) to
other autoimmune disorders.
The study "revealed that the MHC (multiple histocompatibility locus
antigen cluster) is truly the most important risk factor for PS and
that it plays a very major role in PSA, confirmed recently identified
associations with interleukin 23 receptor and interleukin 12B in both
PS and PSA, and identified new associations," wrote the researchers.
The new associations "include a region on chromosome 4q27 that
contains genes for interleukin 2 and interleukin 21 that has been
recently implicated in other autoimmune diseases and seven additional
regions that include chromosome 13q13 and 15q21."
Using whole-genome association, the investigators scanned more than
300,000 SNPs in the genomes of 223 psoriasis patients including 91 who
had psoriatic arthritis. They compared the DNA variations in people
with psoriasis to those found in 519 healthy control patients. They
then replicated their findings in a larger set of patients--577 with
psoriasis and 576 with psoriatic arthritis--and more than 1,200 healthy
controls.
<sniP>
=============================
Thai Indian news 12 hours ago jumPs on board:
http://www.thaindian.com/newsportal/world-news/researchers-uncover-seven-new-genetic-clues-linked-to-psoriasis_10034275.html
Researchers uncover seven new genetic clues linked to psoriasis
Washington , Apr 4 (ANI): Researchers at Washington University School
of Medicine in St. Louis conducted a study of the genetic basis of
psoriasis and found seven new sites of common DNA variation leading to
elevated risk of this debilitating inflammatory disease.
The study, led by Anne Bowcock, Ph.D., professor of genetics at the
School of Medicine , also cited that variations in one genetic region
link psoriasis and a related joint disorder, psoriatic arthritis, to
four autoimmune diseases: type 1 diabetes, Grave's disease, celiac
disease and rheumatoid arthritis.
"Common diseases like psoriasis are incredibly complex at the genetic
level. Our research shows that small but common DNA differences are
important in the development of psoriasis. Although each variation
makes only a small contribution to the disease, patients usually have
a number of different genetic variations that increases their risk of
psoriasis and psoriatic arthritis," said Bowcock.
She said that these DNA variations indicate different biological
pathways leading to psoriasis and may even help in developing new-
targeted drugs and treatments aiming at specific pathways.
Psoriasis is an autoimmune disease that occurs when the body's immune
cells mistakenly attack the skin and is characterized by red, scaly
patches that can be itchy, painful or both. Many psoriatic patients
develop psoriatic arthritis, a condition that is often unbearably
painful and debilitating.
In the study, the researchers mainly focused on points of common
variation in the genome called single nucleotide polymorphisms, or
SNPs, a number of them exclusive to an individual and have a crucial
role in a person's predisposition to disease or good health. They used
an approach called whole genome association for scanning over 300,000
SNPs in the genomes of 223 psoriasis patients, including 91 having
psoriatic arthritis.
They found seven novel DNA variations linked to psoriasis and
confirmed four other previously identified variations to be associated
with the disease.
According to the scientists, the strongest genetic risk for psoriasis
lies in a region of the genome that contains the major
histocompatibility complex (MHC), a collection of genes involved in
distinguishing the body's own cells from foreign invaders.
"Although this region has been known to play a major role in
psoriasis, DNA variations in the MHC alone have been known to not be
enough to trigger disease. Only 10 percent of patients with variations
in the major histocompatibility complex developed psoriasis. This
tells us that other genetic or environmental factors also contribute
to the disease," said Bowcock.
The researchers pointed out that one MHC variation linked to psoriasis
and psoriatic arthritis occurs in the gene HCP5, and this variation
has recently been reported to delay the onset of AIDS in people with
HIV.
Particularly, DNA variations on chromosome 4 were strongly linked to
psoriatic arthritis. These same variations were also associated with
psoriasis and were earlier linked to type 1 diabetes, rheumatoid
arthritis, Grave's disease (caused by an overproductive thyroid gland)
and celiac disease (caused by the inability to digest gluten).
The same region of chromosome 4 contains genes that code for the
signalling molecules IL2 and IL21, paving the way for finding out if
existing drugs that block either molecule may be effective in some
psoriasis patients, especially those with psoriatic arthritis.
The researchers also found significant DNA variations on chromosome 13
in a genetic region involved in modifying proteins, and on chromosome
15, in a region responsible for producing a protein that activates TNF
alpha (tumor necrosis factor-alpha) in a specialized immune cell known
as a dendritic cell. While TNF alpha normally helps fight infections,
it is thought to be a major player in psoriasis and psoriatic
arthritis. A number of FDA-approved psoriasis medications act by
binding to TNF-alpha, and thats how they prevent it from communicating
with cells.
"The goal of this study and other genome-association studies is to get
to personalized medicine, where you can diagnose a disease and ask
what genetic risk factors this person has that points to altered
pathways. Then, we can target those pathways for specific therapeutic
interventions," said Bowcock.
The results of the study appear in the latest issue of the open-access
journal PLoS Genetics. (ANI)
==========================================
Abstracts:
From Croatia & back to Lectins for P:
http://www.ncbi.nlm.nih.gov/pubmed/18386024?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
The expression of syndecan-1 in psoriatic epidermis.
Tomas D, Vučić M, Situm M, Krušlin B.
Ljudevit Jurak Department of Pathology, Sestre Milosrdnice University
Hospital, Vinogradska 29, 10000, Zagreb, Croatia, dto...@kbsm.hr.
Psoriasis is a chronic inflammatory skin disease characterized by
exaggerated keratinocyte proliferation. Current opinion indicates that
psoriasis is driven by T cell-mediated immune responses targeting
keratinocytes. However, psoriasis cannot be explained solely on the
basis of T-cell activation, and it is likely that an intrinsic
alteration in epidermal keratinocytes plays a very important role in
disease expression. Syndecans comprise a major family of cell surface
heparan sulfate proteoglycans. Several studies indicate their role in
adhesion, cell-extracellular matrix interactions, migration,
keratinocyte proliferation and differentiation, inflammation, and
wound healing. To determine the expression of syndecan-1 in psoriasis,
skin samples from 29 patients with fully developed psoriasis and skin
samples from 14 healthy volunteer persons with no personal or family
history of psoriasis were immunohistochemically examined using
monoclonal antibody against syndecan-1. The expression of syndecan-1
was analyzed in whole mount section of psoriatic and non-psoriatic
skin biopsies under high magnification (400x). In addition, the
intensity and topography of reaction in the cell, as well as
localization of positive cells in the epidermis were evaluated. Strong
syndecan-1 reactivity in epidermal cells in all non-psoriatic and
psoriatic samples was observed. Statistical analysis showed no
significant differences between two analyzed groups (P > 0.05). In
normal skin syndecan-1 was expressed in full thickness of the
epidermis. The strongest reaction was observed in membranes and
intercellular junctions of spinous and granular layer while basal
cells showed weaker expression that was confined to cytoplasm. In
psoriatic skin syndecan-1 was expressed in the membrane and
intercellular junction of cells located in thickened and elongated
rete ridges of the epidermis. The strongest reaction was in basal and
suprabasal layers and expression diminished through spinous layer.
Cells in spinous layer lose syndecan-1 expression, which is opposite
pattern to normal skin. Our results suggest that aberrant skin
expression of syndecan-1 may be involved in the development of
psoriasis.
PMID: 18386024
--------
http://en.wikipedia.org/wiki/Syndecan_1
Syndecan 1 is a proteoglycan.
The protein encoded by this gene is a transmembrane (type I) heparan
sulfate proteoglycan and is a member of the syndecan proteoglycan
family. The syndecans mediate cell binding, cell signaling, and
cytoskeletal organization and syndecan receptors are required for
internalization of the HIV-1 tat protein. The syndecan-1 protein
functions as an integral membrane protein and participates in cell
proliferation, cell migration and cell-matrix interactions via its
receptor for extracellular matrix proteins. Altered syndecan-1
expression has been detected in several different tumor types. While
several transcript variants may exist for this gene, the full-length
natures of only two have been described to date. These two represent
the major variants of this gene and encode the same protein.[1]
<snip>
I love this lectin angle.
74 hits worth:
http://groups.google.com/groups/search?qt_s=1&q=lectin+randall+psoriasis
We pick up a dozen more with lectin(s)
http://groups.google.com/groups/search?q=lectins+randall+psoriasis&qt_s=Search
And adding keyword: LPS (45 hits)
http://groups.google.com/groups/search?q=lectins+randall+psoriasis+lps&qt_s=Search
-----------------------------------------
From Turkey today
http://www.ncbi.nlm.nih.gov/pubmed/18386026?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Surfactant proteins in inflammatory skin diseases: controlled study.
Akman A, Kankavi O, Ciftcioglu MA, Alpsoy E.
Department of Dermatology and Venerology, Akdeniz University School of
Medicine, 07070, Antalya, Turkey, aak...@akdeniz.edu.tr.
ABSTACT: Surfactant proteins (SP) have recently been reported to be
expressed in human skin tissue. SP is thought to play an essential
role in the firstline defense of skin. In this study, we aimed to
investigate if the SP may play a role in inflammatory skin diseases.
Seven volunteers with psoriasis (n = 3), atopic dermatitis (n = 2),
lichen planus (n = 1) and Behcet's disease (n = 1) participated in the
study. Biopsies from each lesion and adjacent (approximately 2 cm
distant) normal-appearing skin in patients were performed. Expression
and localization of the SP-A, -B, -C, and -D in fresh tissues were
studied by an immunohistochemical technique. In all patients, there
was a weak cytoplasmic staining with SP-A and SP-D and nuclear
staining with SP-B and SP-C in the epidermis of normal-appearing skin
samples. However, epidermal staining with SP was observed to be
stronger in all lesional samples. In addition, there was a prominent
staining in inflammatory cells infiltrating dermis. This expression
represents a previously unknown immunologic response in the
inflammatory skin diseases and may represent an important step in the
pathogenesis of these disorders.
PMID: 18386026
http://en.wikipedia.org/wiki/Surfactant_protein_A
Is a:
http://en.wikipedia.org/wiki/Collectin
Collectins are soluble pattern recognition receptors (PRRs) belonging
to the superfamily of collagen containing C-type lectins.
Eight collectins have been identified including mannan-binding lectin
(MBL), surfactant protein A (SP-A), surfactant protein D (SP-D),
collectin liver 1 (CL-L1), collectin placenta 1 (CL-P1), conglutinin,
collectin of 43 kDa (CL-43) and collectin of 46 kDa (CL-46).
These molecules have been implicated as major modulators of the innate
immune system where they have a key role in the first line of defense
against invading microorganisms.
Functionally, collectins are usually trimers with the number of
trimeric units differing among the collectin family.
The collectin monomers comprise four structural domains;
* a cysteine-rich domain at the N-terminus.
* a collagen domain.
* a coiled-coil neck domain .
* a C-type lectin domain that is also called a carbohydrate
recognition domain (CRD). Collectins selectively bind to specific
complex carbohydrates of microbes using their CRDs.[1]
[edit] Responses
The binding of collectins to microbes causes several immune related
responses.
* They cause the formation of aggregates of the microorganisms,
opsonize the microorganisms to increase their phagocytosis and some
upregulate of the activity of other PRRs such as the mannose receptor.
* Collectins can also induce the production of pro-inflammatory
molecules like cytokines, and reactive oxygen species in phagocytes by
interacting with other cell surface receptors or by scavenging of
bacterial molecules like lipopolysaccharide (LPS).
* Some collectins (e.g. MBL) activate of the lectin pathway of the
complement system to increase membrane permeability of microorganisms
and cause the destruction of that microbe.[1]
<sniP>
-----
Cute. The turks and croatians are on the same toPical page with
lectins.
Will we find a third hit to round out the crowd?
------------------------------------------------
From England and back to the IgG theory of P
Humoral Autoimmune Responses to the Squamous Cell Carcinoma Antigen
Protein Family in Psoriasis.
El-Rachkidy RG, Young HS, Griffiths CE, Camp RD.
1Department of Infection, Immunity and Inflammation, University of
Leicester, Leicester, UK.
Substantial evidence indicates that psoriasis is a T-lymphocyte-
mediated autoimmune disease. However, longstanding data also indicate
IgG and complement deposition in upper epidermis of psoriasis plaques.
This led us to propose that autoantigen-autoantibody interactions in
the skin may also be of pathogenic importance. Here, we have confirmed
the presence of IgG in upper lesional epidermis and used high-
resolution two-dimensional immunoblotting of extracts from this
tissue, and laser desorption mass spectrometry of tryptic peptides, to
define a series of epidermal proteins that bind IgG from psoriatic
serum. The most prominent of these autoantigens are homologues of the
serpin, squamous cell carcinoma antigen (SCCA), the other autoantigens
identified including arginase 1, enolase 1, and keratin 10. Blood
levels of IgG autoantibodies that bind to SCCA proteins were
significantly higher in psoriasis than healthy controls (P=0.005), but
were not detectable in sera from patients with active atopic
dermatitis. To our knowledge, SCCA proteins have not previously been
described as autoantigenic in animals or humans and form complexes
with IgG that are associated with complement deposition. These
findings expose potentially pathogenic humoral immunologic events and
thus possible therapeutic targets in psoriasis.Journal of
Investigative Dermatology advance online publication, 3 April 2008;
doi:10.1038/jid.2008.71.
PMID: 18385761
-------------------------------
And for cruiser to add to his endothelin EHDF post today. This looks
like I may have to exert brain cells. Calmodulin has that effect on
Ca2+
and now i'm bound to exploration. LOL
http://www.ncbi.nlm.nih.gov/pubmed/18385762?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
K6PC-5, a Direct Activator of Sphingosine Kinase 1, Promotes Epidermal
Differentiation Through Intracellular Ca(2+) Signaling.
Hong JH, Youm JK, Kwon MJ, Park BD, Lee YM, Lee SI, Shin DM, Lee SH.
1Department of Oral Biology, Brain Korea 21 Project, Oral Science
Research Center, Center for Natural Defense System, Yonsei University
College of Dentistry, Seoul, Korea.
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite,
regulates multiple cellular responses such as Ca(2+) signaling,
growth, survival, and differentiation. Because sphingosine kinase
(SphK) is the enzyme directly responsible for production of S1P, many
factors have been identified that regulate its activity and subsequent
S1P levels. Here we synthesized a previously unidentified SphK
activator, K6PC-5, and have studied its effects on intracellular
Ca(2+) signaling in HaCaT cells and epidermal differentiation in
murine skin. K6PC-5, a hydrophobic compound chemically named N-(1,3-
dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide, activated SphK (obtained
from C57BL/6 murine blood and F9-12 cell lysates) in a dose-dependent
manner. K6PC-5 induced both intracellular Ca(2+) concentration
([Ca(2+)](i)) oscillations in HaCaT cells and Ca(2+) mobilization in
hairless mouse epidermis. Both dimethylsphingosine (DMS) and
dihydroxysphingosine (DHS), SphK inhibitors, and transfection of SphK1-
siRNA blocked K6PC-5-induced increases in [Ca(2+)](i). The K6PC-5-
induced [Ca(2+)](i) oscillations were dependent on thapsigargin-
sensitive Ca(2+) stores and Ca(2+) entry, but independent of the
classical phospholipase C-mediated pathway. In addition, K6PC-5
enhanced the expression of involucrin and filaggrin, specific
differentiation-associated marker proteins in HaCaT cells, whereas
transfection of SphK1-siRNA blocked the increase of involucrin.
Topical K6PC-5 also enhanced the expression of involucrin, loricrin,
filaggrin, and keratin 5 in intact murine epidermis. Finally, topical
K6PC-5 inhibited epidermal hyperplasia by exerting antiproliferative
effects on keratinocytes in murine epidermis. These results suggest
that K6PC-5 acts to regulate both differentiation and proliferation of
keratinocytes via [Ca(2+)](i) responses through S1P production. Thus,
regulation of S1P levels may represent a novel approach for treatment
of skin disorders characterized by abnormal differentiation and
proliferation, such as atopic dermatitis and psoriasis.Journal of
Investigative Dermatology advance online publication, 3 April 2008;
doi:10.1038/jid.2008.66.
PMID: 18385762
Doesn't this one look huge? K6PC-5 will it be PC for P? How fast do
we need to turn it down? Will banana peels regulate it? LOL
Will we flake less, sooner or later? Will calmodulin bind the excess
Ca2+?
Do we want it to do that?
Or will revelations of this abstract take us back to arachidonic acids
and bad lipids?
S1P
http://en.wikipedia.org/wiki/S1p
Or or is S1P the good witch? I mean the good lipid?
Are they hooked up with sterols?
Or is the magic right here, *an enzyme ubiquitously found in the
cytosol and endoplasmatic reticulum (ER) of various types of cells*,
LL-37 in the ER and S1P???
Didn't Michel Gilliet say that LL-37 was in the ER and that wasn't
Kosher?
Can we get BJ to think this one over for us? LOL
(I'm not being sarcastic BJ, I want your brain cells. LOL)
And it...
Makes me wonder.
Some lead zePPlin perhaps?
Sure. It really makes me wonder.
http://www.youtube.com/watch?v=lKg4g9zMeHI
Will there be a stairway to heaven here?
Or will Anne Bowcock's genetic revelations get us somewhere
faster?
To much gold is being spent on a false heaven now...
can we say biologicals? Killing me softly?
http://www.youtube.com/watch?v=4mpqXu0z3wU
===============================
randall... no banana peels today... seems clearer- wondering- really
cruiser
I have to retract part of this. I got some bad information.
Upon further investigation, I have to say the VDRs are not
overexpressed in psoriasis.
VDR polymorphisms are being attributed to reduced efficacy of VDR
function in psoriasis.
Studies have shown the VDRs expression in psoriatic skin compares to
non-psoriatic skin and to controls who do not have psoriasis.
Sorry for passing on bad info.
However, there is a definite link between psoriasis and calcium
channels.
I am still investigating, hoping to find something I can use.
cruiser