|
Medical news
Headlines provided by Moreover
Link to Oxford University
Scientists at Wake Forest University Baptist Medical Center are about to embark on a human trial to test whether a new
cancer treatment will be as effective at eradicating cancer in humans as it has proven to be in mice. The treatment
will involve transfusing specific white blood cells, called granulocytes, from select donors, into patients with advanced
forms of cancer. A similar treatment using white blood cells from cancer-resistant mice has previously been highly successful,
curing 100 percent of lab mice afflicted with advanced malignancies. Zheng Cui, Ph.D., lead researcher and associate
professor of pathology, announced the study June 28 at the Understanding Aging conference in Los Angeles. The study,
given the go-ahead by the U.S. Food and Drug Administration, will involve treating human cancer patients with white blood
cells from healthy young people whose immune systems produce cells with high levels of cancer-fighting activity. The
basis of the study is the scientists' discovery, published five years ago, of a cancer-resistant mouse and their subsequent
finding that white blood cells from that mouse and its offspring cured advanced cancers in ordinary laboratory mice. They
have since identified similar cancer-killing activity in the white blood cells of some healthy humans. "In mice, we've
been able to eradicate even highly aggressive forms of malignancy with extremely large tumors," Cui said. "Hopefully, we will
see the same results in humans. Our laboratory studies indicate that this cancer-fighting ability is even stronger in healthy
humans." The team has tested human cancer-fighting cells from healthy donors against human cervical, prostate and
breast cancer cells in the laboratory - with surprisingly good results. The scientists say the anti-tumor response primarily
involves granulocytes of the innate immune system, a system known for fighting off infections. Granulocytes are the
most abundant type of white blood cells and can account for as much as 60 percent of total circulating white blood cells in
healthy humans. Donors can give granulocytes specifically without losing other components of blood through a process called
apheresis that separates granulocytes and returns other blood components back to donors. In a small study of human
volunteers, the scientists found that cancer-killing activity in the granulocytes was highest in people under age 50. They
also found that this activity can be lowered by factors such as winter or emotional stress. They said the key to the success
for the new therapy is to transfuse sufficient granulocytes from healthy donors while their cancer-killing activities are
at their peak level. For the upcoming study, the researchers are currently recruiting 500 local potential donors who
are 50 years old or younger and in good health to have their blood tested. Of those, 100 volunteers with high cancer-killing
activity will be asked to donate white blood cells for the study. Cell recipients will include 22 cancer patients who have
solid tumors that either didn't respond originally, or no longer respond, to conventional therapies. The study will cost $100,000
per patient receiving therapy, and for many patients (those living in 22 states, including North Carolina) the costs may be
covered by their insurance company. There is no cost to donate blood. Click here for general information about insurance coverage of clinical trials. For more information about qualifications for
donors and participants, go to http://www.wfubmc.edu/LIFT (Web site will be available the evening of 6/27.) Cancer-killing ability in these cells is highest during the summer, so
researchers are hoping to find volunteers who can afford the therapy quickly. "If the study is effective, it would
be another arrow in the quiver of treatments aimed at cancer," said Mark Willingham, M.D., a co-researcher and professor of
pathology. "It is based on 10 years of work since the cancer-resistant mouse was first discovered." Volunteers who
are selected as donors - based on the observed potential cancer-fighting activity of their white cells - will complete the
apheresis, a two- to three-hour process similar to platelet donation, to collect their granulocytes. The cancer patients will
then receive the granulocytes through a transfusion - a safe process that has been used for more than 30 years. Normally,
the treatment is used for patients who have antibiotic-resistant infectious diseases. The treatment will be given for three
to four consecutive days on an outpatient basis. Up to three donors may be necessary to collect enough blood product for one
study participant. "The difference between our study and the traditional white cell therapy is that we're selecting
the healthy donors based on the cancer-killing ability of their white blood cells," said Cui. The scientists are calling the
therapy Leukocyte InFusion Therapy (LIFT). The goal of the phase II study is to determine whether patients can tolerate
a sufficient amount of transfused granulocytes for the treatment. Participants will be monitored on a regular basis, and after
three months scientists will evaluate whether the treatment results in clear clinical benefits for the patients. If this phase
of the study is successful, scientists will expand the study to determine if the treatment is best suited to certain types
of cancer. ---------------------------- Article adapted by Medical News Today from original press release.----------------------------
Yikong Keung, M.D., a medical oncologist, is the chief clinical investigator of the study. Gregory Pomper, M.D., assistant
professor of pathology and the director of the Wake Forest Baptist blood bank, will oversee the blood banking portion of the
study. Wake Forest University Baptist Medical Center ( http://www.wfubmc.edu/) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University
Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad
Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of
"America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by
America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third
in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Jonnie Rohrer Wake Forest University Baptist Medical Center
Spinal cord injury eased by stem cells
Study finds adult source works in rats
Results hopeful
for paralysis research
Mar. 29, 2006. 03:04 PM
SHERYL UBELACKER
CANADIAN PRESS
Canadian researchers
have used stem cells to repair spinal cord damage in laboratory rats, restoring significant mobility in the animals and bringing
the search for a human therapy another step closer.
A team led by Toronto neuroscientist Dr. Michael Fehlings extracted
stem cells from adult mice, which were transplanted into rats whose spines had been crushed. The stem cells developed into
one type of cell destroyed by the injury — the kind that produces myelin, the insulating layer that cocoons the bundle
of nerve fibres that make up the cord.
Injuries that crush or compress the spinal cord destroy its
ability to regenerate myelin-forming cells, leading to paralysis. Without the myelin sheath, "nerve fibres don't conduct the
signals, they kind of short out and you don't get signals crossing," said Fehlings, medical director of the Krembil Neuroscience
Centre at Toronto Western Hospital.
Dr. Oswald Steward, director of the Reeve-Irvine Research Centre
for spinal cord injury at the University of California, said the concept of using stem cells for spinal cord cell regeneration
has been applied by other scientists. But Fehlings' work "breaks new ground in a couple of ways": by showing that adult stem
cells work as well as the more ethically controversial fetal or embryonic stem cells and that the drug minocycline improved
their survival, Steward said.
Fehlings said, however, that his transplanted cells, called
neural precursor cells, are not as versatile as embryonic stem cells because they can give rise only to cells of the nervous
system.
In Fehlings' experiments, rats whose crushed spinal cords were
injected with adult stem cells and given a cocktail of drugs — growth hormone, cyclosporine to prevent rejection and
the anti-inflammatory minocycline — were found to walk with better co-ordination and weight-bearing ability.
As well, researchers were able to get those results even when
the stem cells were injected two weeks after the injury. Current therapies that attempt to save spinal cord tissue from trauma-induced
destruction must be given within hours of injury.
"Our strategy wasn't to get perfect regeneration or to try
to regrow the whole spinal cord," said Fehlings. "Our approach was really to try to replace one missing cell type.
The success appears to be due to minocycline, which reduced
inflammation of the spinal cord and limited cell damage, said Fehlings, adding it also seemed to boost survival of stem cells.
Someday, stem cells might be taken from the brains of patients
with spinal cord injuries for their own treatment, Fehlings said. His study appears in today's edition of The Journal of
Neuroscience.
|
|
|
Scientists
probe anti-ageing gene |
|
By Roland Pease
BBC Science Correspondent
08-26-05 |
|
|
|
| 
Klotho seems to delay the effects
of old age in mice
|
Scientists in the United States have discovered a gene that can keep mice alive for 30% longer than normal. They say the gene has a key role to play
in many of the processes related to ageing.
Because humans have a very similar
version of the gene, the hope is that it will show a way to improve our declining years.
The gene studied in the new research
is called Klotho, named after a minor Greek goddess who spins life's thread.
The gene certainly seems to do that.
Mice - and people - with defective forms of the gene appear to age prematurely.
Now researchers have shown that by
boosting the activity of the gene, they can extend the natural lives of male mice from two to three years.
The effect is not quite so strong in
female mice.
Downsides
"It could be one of the significant
steps for developing anti-ageing therapy," Dr Makoto Kuro-o, assistant professor of pathology at the University of Texas'
Southwestern Medical Center and senior author of the study, told Science magazine.
Klotho seems to delay many of the effects
of old age, like the weakening of bones, clogging of the arteries and loss of muscle fitness.
This is important for those researching
the causes of ageing, whose intention is not so much to prolong life as to improve the quality of our final years.
But there may be downsides with Klotho.
The long-lived mice in the new experiments tend to be less fertile.
And the gene may also predispose people
to diabetes.
The trick for researchers will be to
find ways of getting the life-enhancing results of Klotho while avoiding the drawbacks.
|
08-03-05
www.bath.ac.uk/news/articles/releases/tripletcode020805.html
Scientists
crack 40-year-old DNA puzzle and point to ‘hot soup’ at
the origin of life
A new theory that explains
why the language of our genes is more complex than it needs to be also suggests that the primordial soup where life began
on earth was hot and not cold, as many scientists believe.
In a paper published in the Journal of Molecular Evolution
this week, researchers from the University of Bath describe a new theory which they believe could solve a puzzle that has
baffled scientists since they first deciphered the language of DNA almost 40 years ago.
In
1968, Marshall Nirenberg, Har Gobind Khorana and Robert Holley received a Nobel Prize for working out how proteins are produced
from the genetic code. They discovered that three letter ‘words’ - known as codons - are read from the DNA code and then translated into one of 20 amino acids. These amino
acids are then strung together in the order dictated by the DNA code and folded into complex shapes to form a specific protein.
As the DNA ‘alphabet’ contains four letters - called bases - there
are as many as 64 three-letter words available in the DNA dictionary. This is because it is mathematically possible to produce 64 three-letter words from
any combination of four letters.
But why there should be 64 words in the DNA dictionary which translate into just 20 amino acids, and why a process that
is more complex than it needs to be should have evolved in the first place, has puzzled scientists for the last 40 years.
Dozens
of scientists have suggested theories to solve the puzzle, but these have been quickly discounted or failed to explain some
of the other quirks in protein synthesis.
“Why there are so many more codons than amino acids has puzzled scientists
ever since it was discovered how the genetic code works,” said Dr Jean van den Elsen from the Department of Biology
and Biochemistry.
“It meant the genetic code did not have the mathematical brilliance you would expect from something
so fundamental to life on earth.”
One of quirks of the genetic code is that there are groups of codons which
all translate to the same amino acid. For example, the amino acid leucine can be translated from six different codons whilst
some amino acids, which have equally important functions and are translated in the same amount, have just one.
The
new theory builds on an original idea suggested by Francis Crick - one of the discoverers of the structure of DNA - that the three-letter code evolved from a simpler two-letter
code, although Crick thought the difference in number was simply an accident “frozen in time”.
The University of Bath researchers suggest that the primordial ‘doublet’ code was
read in threes - but with only either the first two ‘prefix’ or last two ‘suffix’ pairs of bases being
actively read.
By combining arrangements of these doublet codes together, the scientists can replicate the table of
amino acids - explaining why some amino acids can be translated from groups of 2, 4 or 6 codons. They can also show how the
groups of water loving (hydrophilic) and water-hating (hydrophobic) amino acids emerge naturally in the table, evolving from
overlapping ‘prefix’ and ‘suffix’ codons.
“When you evolve our theory for a doublet system
into a triplet system, you get an exact match up with the number and range of amino acids we see today,” said Dr van
den Elsen, who has worked with Dr Stefan Babgy and Huan-Lin Wu on the theory.
“This simple theory explains many
unresolved features of the current genetic code. No one has ever been able to do this before, so we are very excited.”
The
theory also explains how the structure of the genetic code maximises error tolerance. For instance, ‘slippage’
in the translation process tends to produce another amino acid with the same characteristics, and explains why the DNA code is so good at maintaining its integrity.
“This
is important because these kinds of mistakes can be fatal for an organism,” said Dr van den Elsen. “None of the
older theories can explain how this error tolerant structure might have arisen.”
The new theory also highlights
two amino acids that can be excluded from the doublet system and are likely to be relatively recent ‘acquisitions’
by the genetic code. As these amino acids - glutamine and asparagine - are unable to hold their shape in high temperatures,
this suggests that heat prevented them from being acquired by the code at some point in the past.
One possible reason
for this is that the Last Universal Common Ancestor (LUCA), which evolved into all life on earth, lived in a hot sulphurous
pool or thermal vent. As it moved into cooler conditions, it was able to take up these two additional amino acids and evolve
into more complex organisms. This provides further evidence for the debate on whether life emerged from a hot or cold primordial
soup.
“There are still relics of a very old simple code hidden away in our DNA and in the structures of our cells,” said Dr van den Elsen, who points
to several aminoacyl-tRNA synthetases - molecules involved in protein synthesis - which only look at pairs of bases in triplet
codons, as well as other physical evidence in support of the theory.
“As the code evolved it has been possible
for it to adapt and take on new amino acids. Whether we could eventually reach a full complement of 64 amino acids I don’t
know, a compromise between amino acid vocabulary and its error minimising efficiency may have fixed the genetic code in its
current format.”
July 02, 2005
Drug
find offers a glimmer of hope to Parkinson's sufferers
By Sam Lister, Health Correspondent
The
Times (London)
The
Times (London)
SCIENTISTS
are hailing a potential breakthrough in the treatment of Parkinson’s disease and other neurological conditions following
research into an experimental drug that prompts the regrowth of lost nerve fibres.
Analysis
of the brain of a Parkinson’s sufferer has shown that the treatment, a tissue- protecting protein known as GDNF, triggered
repair of damaged nerve fibres and improved body movement in patients. Scientists believe that the drug could now be applied
to other nerve growth factors used in Alzheimer’s disease and Motor Neuron disease. More than 120,000 people in the
UK suffer from Alzheimer’s, which effects movement, and although treatments are available, no cure has yet been
found.
The
analysed patient, a man aged 62, was one of five people in a pilot study carried out by Steven Gill, at Frenchay Hospital, Bristol. In the study, GDNF — glial cell line-derived
neurotrophic factor — was pumped through a catheter into a damaged part of the brain.
Within
months, patients were noticing dramatic improvements in their ability to move, which continued over almost four years of treatment.
Even after ceasing medication, the patients’ progress has been maintained.
Following
the death of the man from an unrelated heart attack in December, scientists at Bristol University studied the side of his
brain injected with GDNF and compared it with the untreated area. In Parkinson’s disease nerves containing the chemical
messenger dopamine are lost from a region of the brain known as the putamen, leading to tremors and other motor abnormalities
characteristic of the disease.
On examining
the GDNF brain, Seth Love, a professor at Frenchay Hospital’s Institute of Clinical Neurosciences, found that dopamine-containing
nerve fibres had sprouted back in the putamen. Mr Gill, a neurosurgeon, said that the evidence, which is published this month
in the journal Nature Medicine, was compelling.
He said:
“This is the first time that there has been evidence of resuscitation of dying neurons and rewiring of the brain to
restore function.”
GDNF
is not available to patients with Parkinson’s after its manufacturer, Amgen, ceased production over concerns about its
toxicity and a mediocre improvement rate in users.
However,
the Bristol team developed a much more refined and direct means of injecting the drug into the brain tissue, which has been credited
with the dramatically improved outcomes. To date, the most commonly used Parkinson’s drug has been L-Dopa, which only
controls the symptoms for most patients.
| |
Korea Advances One Step Closer
to Stem Cell Therapy | |
By Kim Tae-gyu
Staff Reporter
Korean scientists have taken another gigantic step in their plan for gene
therapy by advancing technologies of growing stem cells into specific cells.
The team, headed by Seoul National University professor Moon Shin-yong,
said yesterday that it developed human embryonic stem cells into insulin-secreting cells, one step before making beta cells
of the pancreas.
``Scientists have typically depended on gene manipulation to harvest specific
cells from stem cell batches. But we adopted a new way of using protein to make progress,’’ the 57-year-old Moon
said.
Moon’s team injected protein into embryonic stem cells and saw them
differentiate into insulin-secreting cells, which can develop into the pancreas’ beta cells.
``If we can make beta cells of the pancreas, they can be used to deal with
diabetes. We found that proteins might open the door to the differentiation of stem cells,’’ Moon’s top
lieutenant Kwon Young-do said.
The differentiation technology is currently the most sought-after segment
by international embryologists, including world-famous cloning scientist Hwang Woo-suk.
Hwang, who cloned a human embryo for the first time in history in 2003,
said the next goal for the world would be to solve the differentiation riddles.
In fact, Moon is a close friend of Hwang and he is also a coauthor of the
embryonic stem cell research papers, printed on the Science last year and this year, led by Hwang.
Geneticists hope versatile stem cells might someday produce tissue to repair
spinal-cord injuries, diabetes or yield therapies for degenerative diseases such as Parkinson’s and Alzheimer’s.
The medical breakthrough of Moon’s team will be featured in the next
edition of international journal Molecular Therapy.
A Step
Forward In Stem Cell Research
Memorial
Sloan-Kettering Cancer Cente
From: http://www.sciencedaily.com/releases/2005/06/050627005555.htm
June 27 2005
NEW YORK, June 27, 2005 -- According to research published today, investigators from Memorial Sloan-Kettering Cancer Center (MSKCC) have used new techniques in the laboratory that
allowed them for the first time to derive unlimited numbers of purified mesenchymal precursor cells from human embryonic stem
cells (HESCs). Mesenchymal precursor cells are capable of giving rise to fat, cartilage, bone, and skeletal muscle cells,
and may potentially be used for regenerative stem cell therapy in bone, cartilage, or muscle replacement.
The new
study, demonstrating the specialized techniques for isolating mesenchymal precursors and generating, purifying, and differentiating
those cells in culture, is published online and freely available in the journal PLoS Medicine (Public Library of Science).
Researchers
took two lines of completely undifferentiated HESCs and by culturing them in the presence of mouse cells, stimulated them
to turn into mesenchymal cells. They then treated these cells with compounds to make them change into specialized bone, cartilage,
fat, and muscle cells. According to the study, researchers were able to confirm that these cells were all human cells and
that there was no evidence that the cells became cancerous.
Mesenchymal
precursors derived from HESCs are different from adult mesenchymal cells because they can efficiently differentiate into skeletal
muscle (adult mesenchymal cells do not) in addition to fat, cartilage, and bone. Limited numbers of mesenchymal stem cells
have been isolated from adult bone marrow and connective tissues, but harvesting these cells from any of these sources requires
invasive procedures and the availability of a suitable donor. The capacity of these cells for long-term proliferation is also
poor. In contrast, HESCs could provide an unlimited number of specialized cells.
According
to Lorenz Studer, MD, PhD, Head of the Stem Cell and Tumor Biology Laboratory at MSKCC and senior author of the PLoS Medicine
study, the high purity, unlimited availability, and multi-potentiality of mesenchymal precursors derived from HESCs will provide
the basis for preclinical mouse studies to assess the safety of these cells. The investigators have already taken the next
step in this research and are testing the therapeutic potential of embryonic stem cell-derived muscle cells in animal models
of muscle disorders.
|
|
|
|
|
|
|
|
University of California, Davis - Medical Center |
24.06.2005 |
|
|
|
|
|
|
UC Davis researchers discover receptor pathway for C-reactive protein and its effects |
|
|
|
|
|
|
|
For
the first time, scientists have discovered how C-reactive protein, or CRP, is able to access endothelial cells. The UC Davis
researchers’ findings will be published in the July issue of Arteriosclerosis, Thrombosis, and Vascular Biology, one
of the American Heart Association’s leading journals.
CRP is a known risk marker for heart disease and, in
a study published earlier this year, UC Davis researchers Ishwarlal Jialal and Sridevi Devaraj found that endothelial cells
also produce CRP, which is increased 100-fold when cytokines are secreted by human macrophages, a key finding that helps to
explain how plaque formation is initiated.
Devaraj and Jialal have now discovered how CRP affects endothelial cells,
cells that line the cerebral and coronary arteries, and promotes plaque rupture, leading to heart attacks and strokes. CRP
appears to bind to a family of immunoglobulin-processing receptors known as Fc-gamma receptors.
"In this study we convincingly
show that CRP binds to two members of the Fc-gamma receptor family, CD64 and CD32, and that by blocking these receptors with
specific antibodies, we can reverse the detrimental effects of CRP on endothelial cells," said Jialal, the Robert E. Stowell
Chair of Experimental Pathology and director of the Laboratory of Atherosclerosis and Metabolic Research at UC Davis Medical
Center.
"This is the first time that anyone has shown how CRP is able to get into the human aortic endothelial cells.
Fc-gamma receptors CD32 and CD64 are the culprits," said Sridevi Devaraj, associate professor of pathology at UC Davis School
of Medicine and Medical Center.
Work
at UC Davis and other institutions has shown that CRP induces endothelial cell dysfunction, thus promoting plaque rupture.
CRP causes endothelial cells to produce less nitric oxide and to increase the number of cell adhesion molecules. This, in
turn, allows damaging leukocytes to enter the vessels. Devaraj and Jialal also showed, in a previous study, that CRP induces
endothelial cells to produce plasminogen activator inhibitor, or PAI-1, which promotes clot formation. In addition, recent
studies suggest that plaque tissue also produces CRP.
"In future studies, we will examine the precise pathways by which
these receptors are able to mediate CRP effects so that more specific therapies can be developed to target inflammation,"
said Jialal.
Coronary heart disease is the nation’s single leading cause of death. According to the American
Heart Association, approximately 1.2 million Americans will have a coronary attack this year. Almost a half million of these
people will die. About 7.1 million Americans have survived a heart attack. And another 6.4 million Americans have experienced
chest pain or discomfort due to reduced blood supply to the heart.
Reducing the concentration of CRP with drugs, such
as statins, has been shown to reduce cardiovascular events. Treating other risk factors such as smoking, obesity, high blood
pressure with angiotensin receptor blockers and diabetes with thiazolidinediones and metformin are also shown to reduce the
levels of CRP.
|
|
|
|
Stem Cell Therapy Helps Heart Failure Patients
Quito, Jun 7 2005 (Prensa Latina)
Patients with advanced heart failure significantly improved after receiving stem cell therapy,
according to results of a clinical trial presented at the annual meeting of the International Society for Minimally Invasive
Cardiothoracic Surgery (ISMICS) in New York.
The study showed, 30 days after receiving the injection of stem cells into their hearts,
patients improved an average of 41 percent in their heartsī pumping efficiency. The distance they could walk nonstop increased
by 72 percent in a standard test widely used to assess heart patients.
After 90 days, the heart-pumping improvement was sustained and patients further increased
the distance they could walk in the standard test.
The study is the first to use human fetal-derived stem cell therapy in patients with heart failure.
Drs. Federico Benetti, Luis Geffner, Yuliy Baltaytis and Teodoro Maldonado at Luis Vernaza Hospital
in Guayaquil, Ecuador, performed the surgical procedure.
Advanced heart failure is an incurable and usually fatal condition. Other than heart transplanting,
current medical treatments cannot reverse the course of the disease, and only slow its progression or help control its symptoms.
mh/ima/mf
http://antwrp.gsfc.nasa.gov/apod/ap041013.html
New study explains process
leading to many proteins from one gene
15 Apr 2005
New findings from researchers
at UT Southwestern Medical Center help explain how the 20,000 to 25,000 genes in the human genome can make the hundreds of
thousands of different proteins in our bodies.
Genes are segments of DNA that carry
instructions for making proteins, which in turn carry out all of life's functions. Through a natural process called "alternative
splicing," information contained in genes is modified so that one gene is capable of making several different
proteins.
"Alternative splicing is a key mechanism for achieving a diverse range of proteins, which contributes to the complexity of
higher organisms," said Dr. Harold "Skip" Garner, professor of biochemistry and internal medicine at UT Southwestern and senior
author of a new study aimed at understanding how and why alternative splicing occurs in humans.
The study is available
online and will be published in the April 15 issue of the journal Bioinformatics.
Errors in alternative splicing can
result in truncated or unstable proteins, some of which are responsible for human diseases such as prostate cancer and schizophrenia, Dr. Garner said. But errors also can result in proteins with new functions
that help drive evolutionary changes.
"Alternative splicing appears to occur in 30 percent to 60 percent of human
genes, so understanding the regulatory mechanisms guiding the process is fundamentally important to almost all biological
issues," said Dr. Garner.
Alternative splicing can be likened to alternative versions of a favorite cookie recipe.
If the original recipe (the gene) calls for raisins, walnuts and chocolate chips, and you copy the recipe but leave out the
raisins, you'll still get a cookie (protein) from your version, just a different cookie. Omit a necessary ingredient, such
as flour, and you'll have a mess (nonfunctioning or malfunctioning protein).
Similarly, the information in genes is
not directly converted into proteins, but first is copied by special enzymes into RNA, or more specifically, pre-messenger
RNA.
While the entire gene is copied into pre-mRNA, not all of that information will be used to make a protein. RNA
segments called exons carry the protein-making information, while the segments between exons, called introns, are snipped
out of pre-mRNA by special proteins. Exons also may be snipped out. Once snipping is complete, the remaining exons are spliced
back together to form a fully functional, mature mRNA molecule, which goes on to create a protein.
Using computers,
the UT Southwestern researchers scanned the human genome and found that the presence of certain DNA
sequences called "tandem repeats" that lie between exons are highly correlated with the process of alternative splicing. They
found a large number of tandem repeats on either side of exons destined to be spliced out of the pre-mRNA. The tandem repeat
sequences also were complementary and could bind to each other.
"The complementary tandem repeat sequences on either
side of an exon allow the DNA to loop back on itself, bind together, pinch off the loop
containing a particular exon and then splice it out," Dr. Garner explained.
The chemical units that make up an organism's
DNA are abbreviated with the letters A, C, T and G. Strings of these letters form genes
and spell out genetic instructions. Tandem repeats have DNA sequences with the same series
of letters repeated many times, such as CACACACACACA.
Tandem repeats are "hot spots" where errors can easily be made
during the copying process; for example, an extra CA could be added or deleted from the correct sequence. These errors could
then result in a gene improperly splicing out an exon, thus making the wrong protein, Dr. Garner said. His research group
has previously shown that these sequences are highly variable in cancer, and he said the new findings could go a long way
toward understanding the genetic nature of how cancers start and progress.
"With this new understanding, we can now
predict all genes that can re-arrange in this way and even predict which might splice improperly, resulting in disease," he
said.
Former UT Southwestern research associate Dr. Yun Lian was a co-author of the study.
The research was
funded by the National Cancer Institute, the National Heart, Lung and Blood Institute and the M.R. and Evelyn Hudson Foundation.
Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
University of Texas Southwestern
Medical Center at Dallas
http://www.swmed.edu
http://www.medicalnewstoday.com/medicalnews.php?newsid=22857&nfid=mnf
|
