| randall 2006-08-29, 9:26 pm |
| Hi,
Since i've figured the gut is ground zero, wrongly or rightly it is
the one area i've made the most advances in clearing my own
psoriasis.
This area may one day be key to a cure for P.
For now using all that we can glean from current research isn't a bad
idea.
http://www.medicalnewstoday.com/med...d=50433&nfid=nl
Researchers at UT Southwestern Medical Center have identified a protein
that is made in the intestinal lining and targets microbial invaders,
offering novel insights into how the intestine fends off pathogens and
maintains friendly relations with symbiotic microbes.
The study, published today in the journal Science, might lead to new
medications aimed at helping patients with inflammatory bowel disease.
The findings might also aid in understanding the effectiveness of
probiotics - mixtures of beneficial bacteria that are added to food
products - in boosting the immune system, said Dr. Lora Hooper,
assistant professor of immunology and the paper's senior author.
Scientists have known for decades that microbial cells in the human gut
outnumber the body's own cells by about 10 to 1. Humans offer a safe
haven to these microbes because they help us to break down food that we
can't digest by ourselves. But it hasn't been clear how we keep these
microscopic gut dwellers from invading our tissues and causing
infections.
To help answer this question, Dr. Hooper's research team used mice
raised inside sterile plastic bubbles. Because they are never in
contact with the outer, microbe-filled world, these mice do not have
the bacteria that normally colonize the gut. By exposing these
"germ-free" mice to different types of gut bacteria, the researchers
were able to observe how the epithelial cells lining the intestine
react to microbial invaders.
"We found that when the gut lining comes into contact with bacteria, it
produces a protein that binds to sugars that are part of the bacterial
outer surfaces," Dr. Hooper said. "Once bound, these proteins quickly
destroy their bacterial targets. They're killer proteins with a sweet
tooth."
The protein, called RegIIIgamma in mice and HIP/PAP in humans, belongs
to a protein class called lectins, which bind to sugar molecules. These
particular lectins' seek-and-destroy mission may help to create an
"electric fence" that shields the intestinal surface from invading
bacteria, Dr. Hooper said.
The findings of this study may offer researchers new clues about the
causes of inflammatory bowel disease. Most healthy people have a
friendly relationship with their gut microbes, but in patients with
inflammatory bowel disease this tolerant relationship turns sour and
the immune system mounts an attack on the gut's microbial inhabitants
that can lead to painful ulcers and bloody diarrhea. What triggers this
attack is not clear, but the fact that these patients have elevated
HIP/PAP production suggests that they are coping with increased numbers
of invading intestinal bacteria.
The study may also help scientists devise more effective treatments for
intestinal infections. "We are now working to understand the mechanism
by which the intestinal lining senses bacterial threats. What turns
this protein antibiotic on?" Dr. Hooper asked. "We want to explore
whether this is something we can stimulate artificially to stave off
pathogenic infections."
###
Other contributors to the study, all from UT Southwestern's Center for
Immunology, are co-lead authors Heather Cash, a former graduate
student; and Cecilia Whitham, research assistant, and Cassie Behrendt,
research associate.
The research was supported by grants from the National Institutes of
Health, the Crohn's and Colitis Foundation of America, and a Burroughs
Wellcome Career Award in the Biomedical Sciences.
This news release is available on our World Wide Web home page at
http://www.utsouthwestern.edu/home/news/index.html
Dr. Lora Hooper -
http://www.utsouthwestern.edu/findf...6,60931,00.html
Contact: Toni Heinzl
UT Southwestern Medical Center
---------
And the abstract to go along with it.
http://www.ncbi.nlm.nih.gov/entrez/...l=pubmed_docsum
Symbiotic bacteria direct expression of an intestinal bactericidal
lectin.
* Cash HL,
* Whitham CV,
* Behrendt CL,
* Hooper LV.
Center for Immunology, university of Texas Southwestern Medical Center
at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Lora.Hooper@UTSouthwestern.edu
The mammalian intestine harbors complex societies of beneficial
bacteria that are maintained in the lumen with minimal penetration of
mucosal surfaces. Microbial colonization of germ-free mice triggers
epithelial expression of RegIIIgamma, a secreted C-type lectin.
RegIIIgamma binds intestinal bacteria but lacks the complement
recruitment domains present in other microbe-binding mammalian C-type
lectins. We show that RegIIIgamma and its human counterpart, HIP/PAP,
are directly antimicrobial proteins that bind their bacterial targets
via interactions with peptidoglycan carbohydrate. We propose that these
proteins represent an evolutionarily primitive form of lectin-mediated
innate immunity, and that they reveal intestinal strategies for
maintaining symbiotic host-microbial relationships.
PMID: 16931762
Now i've got hip/pap to follow.
HiP hiP hooray for
Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein !
I know. It sounds like pap.
----------------------
Is Mucus in the Gi tract a good or bad thing?
http://www.medicalnewstoday.com/med...d=50288&nfid=nl
How Roughage Keeps You "Regular" Scientists Learn More
If you ever wondered just how a high-fiber diet helps keep you, well,
"regular," scientists may have the answer.
Their results suggest that as these bulky foods make their way down the
gastrointestinal tract, they run into cells, tearing them and freeing
lubricating mucus within.
More mucus is good, says Dr. Paul L. McNeil, cell biologist at the
Medical college of Georgia and corresponding author on the study
published online Aug. 21 and scheduled for the September print issue of
PloS Biology. "When you eat high-fiber foods, they bang up against the
cells lining the gastrointestinal tract, rupturing their outer
covering. What we are saying is this banging and tearing increases the
level of lubricating mucus. It's a good thing."
The fact that consuming roughage increases mucus production was known,
and years ago, Dr. McNeil discovered frequent cell injury and repair
occur when we eat.
The new research ties the two together.
"It's a bit of a paradox, but what we are saying is an injury at the
cell level can promote health of the GI tract as a whole," says Dr.
McNeil. Even though epithelial cells usually live less than a week,
they are regularly bombarded, in most of us at least three times a day
as food passes by. "These cells are a biological boundary that
separates the inside world, if you will, from this nasty outside world.
On the cellular scale, roughage, such as grains and fibers that can't
be completely digested, are a mechanical challenge for these cells,"
says Dr. McNeil.
But in what he and colleague Dr. Katsuya Miyake view as an adaptive
response, most of these cells rapidly repair damage and, in the
process, excrete even more mucus, which provides a bit of cell
protection as it eases food down the GI tract.
In research published in 2003 in Proceedings of the National Academy of
Sciences, Dr. McNeil showed proof of his then decade-old hypothesis
that cells with internal membranes use those membranes to repair
potentially lethal outer-membrane injuries. A recent paper published in
Nature in collaboration with Dr. Kevin Campbell's laboratory at the
University of Iowa showed how human disease, including certain forms of
muscular dystrophy, can result from a failure of this mechanism.
An outer membrane tear is like an open door through which calcium just
outside the cell rushes in. Too much calcium is lethal but that first
taste signals the vulnerable cell it better do something quick. With
epithelial cells, several of the internal mucus-filled compartments
fuse together within about three seconds, forming a patch to fix the
tear. In the process the compartments expel their contents so, almost
like a bonus, extra mucus becomes available to lubricate the GI tract.
"We have found a very natural way we can enhance mucus production,"
says Dr. Miyake, cell biologist and the study's first author. He and
Dr. McNeil suspected for years that mucus escaped cells as a result of
injury. "You might have predicted it, but science is about testing
predictions," says Dr. McNeil.
To test their theory, Dr. Miyake, co-director of MCG Cell Imaging Core
Laboratory, began working on a method to reproduce cell injuries. "Dr.
Miyake developed a very potent cutting edge technology involving the
two photon laser that allowed us to blast small holes in cells,
mimicking what happens in the living animal. It also allowed us to
assess in those living cells whether they could reseal, repair the
damage and how they might respond biologically, namely in this case,
whether they responded by secreting mucus as part of the healing
process," Dr. McNeil says.
They found time and again that most cells did just that, including
intact cells in a section of the GI tract. "Epithelial cells are
high-turnover cells but they have a built-in survivability," Dr. McNeil
says.
The scientists aren't certain how many times cells can take a hit, but
they suspect turnover is so high because of the constant injury.
Potentially caustic substances, such as alcohol and aspirin, can
produce so much damage that natural recovery mechanisms can't keep up.
But they doubt a roughage overdose is possible.
----------------------------
randall... these lectin things are making a come back!
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