Martin Pall's thesis connects MCS (and CFS) with EHS
news....@googlemail.com
I redirect your message to all.
Regards
Philippe Hug
----- Message transféré de andy.davidson-----
Date : Thu, 19 Feb 2009 22:03:52 -0000
De : Andy Davidson
Objet : Re: MCS
À : a...@alerte.ch
I should say so, Philippe. You might like to circulate this:
It goes back to Martin Pall's thesis too, that connects MCS (and CFS)
with EHS.
Once again, nitric oxide is a central factor in much of what we know
about either symptoms of EMF exposure, or mechanisms for cellular damage
from EMF exposure. What is most interesting here is that in a world
where the same outcomes arise from biological insults of various
sources, diagnosis of unique factor causality is almost impossible.
Below the line, some of the p53-related articles implicating NO as a
factor in carcinogenesis.
best regards
Andy
________________________________________
http://www.pnas.org/cgi/content/abstract/95/15/8823
Up-regulation of inducible nitric oxide synthase expression in
cancer-prone p53 knockout mice (1998)
Proc Nat Acad Sciences, Vol. 95, Issue 15, 8823-8828, July 21, 1998
Stefan Ambs*,, Mofolusara O. Ogunfusika*, William G. Merriam*, William
P. Bennett*, Timothy R. Billiar, and Curtis C. Harris*,§
* Laboratory of Human Carcinogenesis, National Cancer Institute,
National Institutes of Health, Bethesda, MD 20892; and Department of
Surgery, University of Pittsburgh, Pittsburgh, PA 15261
Communicated by Theodore T. Puck, Eleanor Roosevelt Institute for Cancer
Research, Bethesda, MD, May 11, 1998 (received for review March 24, 1998)
High concentrations of nitric oxide (NO) cause DNA damage and apoptosis
in many cell types. Thus, regulation of NO synthase (NOS) activity is
essential for minimizing effects of cytotoxic and genotoxic nitrogen
oxide species. We have shown previously that NO-induced p53 protein
accumulation down-regulates basal and cytokine-modulated inducible NOS
(NOS2) expression in human cells in vitro. To further characterize the
feedback loop between NOS2 and p53, we have investigated NO production,
i.e., urinary nitrate plus nitrite excretion, and NOS2 expression in
homozygous p53 knockout (KO) mice. We report here that untreated p53 KO
mice excreted 70% more nitrite plus nitrate than mice with wild-type
(wt) p53. NOS2 protein expression was constitutively detected in the
spleen of untreated p53 KO mice, whereas it was undetectable in the
spleen of wt p53 controls. Upon treatment with heat-inactivated
Corynebacterium parvum, urinary nitrite plus nitrate excretion of p53 KO
mice exceeded that of wt controls by approximately 200%. C. parvum
treatment also induced p53 accumulation in the liver. Splenectomy
reduced the NO output of C. parvum-treated p53 KO mice but not of wt p53
controls. Although NO production and NOS2 protein expression were
increased similarly in KO and wt p53 mice 10 days after injection of C.
parvum, NOS2 expression returned to baseline levels only in wt p53
controls while remaining up-regulated in p53 KO mice. These genetic and
functional data indicate that p53 is an important transrepressor of NOS2
expression in vivo and attenuates excessive NO production in a
regulatory negative feedback loop.
also:
http://www.biomedcentral.com/1471-2407/2/8
Expression of p53, inducible nitric oxide synthase and vascular
endothelial growth factor in gastric precancerous and cancerous lesions:
correlation with clinical features (2002)
Chang Wei Feng, Li Dong Wang, Lian Hua Jiao, Bin Liu, Shu Zheng and Xin
Ji Xie
BMC Cancer 2002, 2:8
Background
The growth and metastasis of tumors depend on the development of an
adequate blood supply via angiogenesis. Recent studies indicate that the
inducible nitric oxide synthase (iNOS), vascular endothelial growth
factor (VEGF) and the tumor suppressor p53 are fundamental play-markers
of the angiogenic process. Overexpression of iNOS and VEGF has been
shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by
down-regulating VEGF and iNOS. The correlation of expression of p53,
VEGF and iNOS and clinical features in gastric carcinogenesis, however,
has not been well characterized.
Methods
The expression of p53, iNOS and VEGF in gastric precancerous and
cancerous lesions and its relation with the clinical features was
determined with immunohistochemistry (avidin-biotin-peroxidase complex
method) on 55 randomly selected GC patients and 60 symptom-free subjects
from the mass survey in the high-incidence area for GC in Henan,
northern China.
Results
The positive immunostainig rates for p53, iNOS and VEGF in gastric
carcinomas were 51%, 44% and 51%, respectively, and correlated well with
TNM stages, but did not show significant difference among the groups
with different degrees of gastric wall invasion depth by GC. A positive
immunostaining reaction for the iNOS protein was significantly
correlated with lymph node metastasis (p = 0.019; Spearman correlation
coefficient). P53 protein accumulation was higher in the
poorly-differentiated gastric carcinoma than in well-differentiated one.
In gastric biopsies, no positive immunosatining was observed for p53,
iNOS and VEGF in the histologically normal tissue and chronic
superficial gastritis (CSG). However, p53, iNOS and VEGF positive
immunostaining was observed in the tissues with different severities of
lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM)
and dysplasia (DYS), and the positive rates increased with the lesion
progression from CAG to IM to DYS. A high coincidental positive and
negative immunostaining rate for p53, iNOS and VEGF was observed both in
biopsy samples with CAG, IM and DYS from the symptom-free subjects and
in gastric cancer tissue from the GC patients.
Conclusions
The present results indicated that p53 protein accumulation and
increased expression of iNOS and VEGF might be responsible for gastric
carcinogenesis and tumor aggressiveness of gastric cancer.
also:
http://content.karger.com/ProdukteDB/produkte.asp?Doi=66519
Association between Inducible Nitric Oxide Synthase Expression and p53
Status in Human Esophageal Squamous Cell Carcinoma (2003)
Manabu Matsumoto, Mutsuo Furihata, Atsushi Kurabayashi, Keijiro Araki,
Shiro Sasaguri, Yuji Ohtsuki
Oncology 2003;64:90-96
Nitric oxide (NO) produced by the NO synthase (NOS), a family of enzymes
such as inducible NOS (iNOS), has been suggested to play an important
role in tumor bioloty. We immunohistochemically examined iNOS and p53
protein expression in 105 patients with esophageal squamous cell
carcinoma (ESCC). Direct sequence analysis for the p53 gene was
performed in 51 of 105 tumors. In total, 56 of 105 (53.3%) tumors
exhibited intracytoplasmic staining for anti-iNOS antibody, including 17
(16.2%) cases of homogeneous and intense immunostaining (++) and 39
(37.1%) of heterogeneous staining (+). Of 62 p53 protein-positive
tumors, 40 (63.5%) were positive for iNOS, and of 43 p53
protein-negative tumors, 27 (62.8%) were negative for iNOS. Of 34
iNOS-positive tumors, 23 (67.6%) carried a p53 gene mutation, and of 17
iNOS-negative tumors, 12 (70.6%) had wild-type p53 gene. There was a
significant relationship between iNOS immunoreactivity and p53 protein
overexpression (p = 0.0058) as well as p53 mutation frequency (p =
0.0163). No association was found between iNOS immunoreactivity and p53
mutation type, any clinicopathological factor and patient prognosis. Our
in vivo findings suggest that iNOS activity might be associated with p53
alteration and contribute to tumorigenesis in ESCC.
email: The Tobacco Coverup AND Could RFs also "leave a clear fingerprint
on p53" ?
From: Imelda O'Connor
SUNDAY TIMES MAGAZINE's (6 Aug) article ("The Miracle Worker") on the
vital link between gene p53 and cancer a few paragraphs highly relevant
to our own campaign. The entire article is pasted in below the excerpt.
Lung cancer is the most common cause of death in the UK, with one person
newly diagnosed every 15 minutes, according to Action on Smoking and
Health. For decades the tobacco industry sought to undermine the case
against smoking by claiming that evidence of a link between tobacco and
lung cancer, first mooted in the 1950s, was purely circumstantial -
there was no physical proof that smoking caused the disease. But p53 has
finally nailed the case against tobacco. Since the early 1990s, the
International Agency for Research on Cancer (IARC) in Lyons, France, has
kept a database of the mutations found in p53 in different tumour types.
In the lung cancer of smokers, p53 is overwhelmingly mutated at a
particular "hot spot" on the gene. In other words, the gene carries the
fingerprint of the cancer-causing agent. Scientists found
benzo(a)pyrene, a component of tobacco smoke, is the culprit. The first
paper pinning it down was published in 1996, followed closely by another
presenting the evidence from the database. But Big Tobacco had been
waiting in the wings. When the papers appeared, it launched an attack
questioning the science and challenging the scientists via learned
journals. "We're used to trust within the scientific community, and you
expect people to be fair," says Pierre Hainaut of the IARC. "So the
first reaction when you see a paper attacking your work is: 'Oh my God,
I've missed something important; I've made a big mistake!'" But when
he set out to answer his critics, Hainaut discovered a network of
scientists and journal editors not only being paid by the tobacco
industry to do their own research on p53, but colluding with the
industry to hide the source of their funding and frustrate the
scientific debate. They used their contacts to alert tobacco companies
to forthcoming publications and helped to prepare papers challenging the
data and get them into print as quickly and prominently as possible.
Hainaut followed the trail to secretive institutes set up by the tobacco
industry, into the boardrooms of key journals and even the labs of some
eminent scientists, and he was shocked. "It may seem very naive, but I
had no idea something like this could happen," he says. "It was like
falling into a detective story." However, the battle, which turned
nasty and personal at times and is well documented in a Lancet article
of 2005, did have some positive spin-offs. The rules about declaring
conflicts of interest when publishing scientific papers have been
tightened. And Hainaut and his colleagues acknowledged the weakness of
some data they used to make their original case, and started again from
scratch to generate watertight data on the effect of tobacco on p53.
Their paper was published in 2005. Tobacco isn't the only
cancer-causing agent to leave a fingerprint on p53. Many cases of skin
cancer have p53 mutations characteristic of ultraviolet radiation from
sunlight. And most liver cancers in tropical countries are caused by
aflatoxin, a poison secreted by a fungus that infects grains and
peanuts, and leave a clear fingerprint on p53. . . . END OF EXCERPT
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