News 21 aug 2009
Less than 50 percent of women with
abnormal paps receive follow-up care
Less than half of Ontario women with abnormal Pap tests receive recommended and
potentially life-saving follow-up care, according to a new women's health study by
researchers at St. Michael's Hospital and the Institute for Clinical Evaluative Sciences
(ICES). What's more, low-income women are less likely to be screened for cancer compared
to their high-income counterparts. "Cervical cancer is one of the most preventable
forms of cancer, yet in Ontario more than one million women have not been screened, and a
disproportionate number of these are women living in lower-income communities," says
Dr. Arlene Bierman, a physician at St. Michael's Hospital and principal investigator of
the Project for an Ontario Women's Health Evidence-Based Report (POWER). "We need to
make special efforts to reach women who are screened, but do not receive the necessary
follow-up and may eventually fall through the cracks. To improve surveillance and
treatment, we need a system that ensures all abnormal Pap tests are followed-up so that
Ontario women can receive the best care possible," added Dr. Bierman, a researcher at
ICES. The joint study titled POWER (the Project for an Ontario Women's Health
Evidence-Based Report), from St. Michael's Hospital and the Institute for Clinical
Evaluative Sciences (ICES), is the first in the province to provide a comprehensive
overview of women's health in relation to gender, income, education, ethnicity and
geography. The findings are detailed in the report titled Cancer — the second to be
released this year as part of the study. Findings can be used by policymakers and
health-care providers to improve access, quality and outcomes of care for Ontario women.
Dr. Monika Krzyzanowska, a medical oncologist at Princess Margaret Hospital/University
Health Network is the lead author on the cancer chapter. The POWER Study is funded by
Echo: Improving Women's Health in Ontario, an agency of the Ontario Ministry of Health and
Long-Term Care.
Diabetes drug linked to increased
risk of heart failure
Rosiglitazone, a drug used to treat type 2 diabetes, is associated with an increased risk
of heart failure and death among older patients compared to a similar drug (pioglitazone),
concludes a study published on bmj.com today. As such, the researchers say it is difficult
to advocate continued use of rosiglitazone for most patients. Rosiglitazone and
pioglitazone belong to a class of drugs called thiazolidinediones and are widely used for
the treatment of type 2 diabetes. They help to control blood sugar levels, but both drugs
can also cause side effects including weight gain, fluid retention and heart failure. It
is unclear whether there are clinically important differences in the cardiac safety of
these two drugs, so researchers in Canada compared the risk of heart attack, heart failure
and death in patients treated with rosiglitazone and pioglitazone. Using prescription
records, they identified nearly 40,000 patients aged 66 years and older who started
treatment with either rosiglitazone or pioglitazone between April 2002 and March 2008.
Data on hospital admission for either a heart attack or heart failure during the six-year
study period were recorded and deaths were identified from a national database.
Little known type of cholesterol
may pose the greatest heart disease risk
Health-conscious people know that high levels of total cholesterol and LDL cholesterol
(the so-called "bad" cholesterol) can increase the risk of heart attacks. Now
scientists are reporting that another form of cholesterol called oxycholesterol —
virtually unknown to the public — may be the most serious cardiovascular health
threat of all. Scientists from China presented one of the first studies on the
cholesterol-boosting effects of oxycholesterol here today at the 238th National Meeting of
the American Chemical Society. The researchers hope their findings raise public awareness
about oxycholesterol, including foods with the highest levels of the substance and other
foods that can combat oxycholesterol's effects. "Total cholesterol, low-density
lipoprotein cholesterol (LDL), and the heart-healthy high-density lipoprotein cholesterol
(HDL) are still important health issues," says study leader Zhen-Yu Chen, Ph.D., of
Chinese University of Hong Kong. "But the public should recognize that oxycholesterol
is also important and cannot be ignored. Our work demonstrated that oxycholesterol boosts
total cholesterol levels and promotes atherosclerosis ["hardening of the
arteries"] more than non-oxidized cholesterol." Fried and processed food,
particularly fast-food, contains high amounts of oxycholesterol. Avoiding these foods and
eating a diet that is rich in antioxidants, such as fresh fruits and vegetables, may help
reduce its levels in the body, the researchers note. Scientists have known for years that
a reaction between fats and oxygen, a process termed oxidation, produces oxycholesterol in
the body. Oxidation occurs, for instance, when fat-containing foods are heated, as in
frying chicken or grilling burgers or steaks. Food manufacturers produce oxycholesterol
intentionally in the form of oxidized oils such as trans-fatty acids and
partially-hydrogenated vegetable oils. When added to processed foods, those substances
improve texture, taste and stability. Until now, however, much of the research focused on
oxycholesterol's effects in damaging cells, DNA, and its biochemical effects in
contributing to atherosclerosis. Chen believes this is one of the first studies on
oxycholesterol's effects in raising blood cholesterol levels compared to non-oxidized
cholesterol. In the new study, Chen's group measured the effects of a diet high in
oxycholesterol on hamsters, often used as surrogates for humans in such research. Blood
cholesterol in hamsters fed oxycholesterol rose up to 22 percent more than hamsters eating
non-oxidized cholesterol. The oxycholesterol group showed greater deposition of
cholesterol in the lining of their arteries and a tendency to develop larger deposits of
cholesterol. These fatty deposits, called atherosclerotic plaques, increase the risk for
heart attack and stroke.
Plastics in oceans decompose,
release hazardous chemicals, surprising new study says
In the first study to look at what happens over the years to the billions of pounds of
plastic waste floating in the world’s oceans, scientists are reporting that plastics
— reputed to be virtually indestructible — decompose with surprising speed and
release potentially toxic substances into the water. Reporting here today at the 238th
National Meeting of the American Chemical Society (ACS), the researchers termed the
discovery “surprising.” Scientists always believed that plastics in the oceans
were unsightly, but a hazard mainly to marine animals that eat or become ensnared in
plastic objects. “Plastics in daily use are generally assumed to be quite
stable,” said study lead researcher Katsuhiko Saido, Ph.D. “We found that
plastic in the ocean actually decomposes as it is exposed to the rain and sun and other
environmental conditions, giving rise to yet another source of global contamination that
will continue into the future.”
'Housekeeping' genes play important
role in developmental pathways of cells
A study from the Center for Molecular Genetics at the University of California, San Diego
School of Medicine shows that a gene called HPRT plays an important role in setting the
program by which primitive or precursor cells decide to become normal nerve cells in the
human brain. This unconventional view of metabolic genes known as "housekeeping"
genes is now online at the journal Molecular Therapy. "Housekeeping" genes are
expressed in most cells under most conditions, and scientists usually regard them as
having simple metabolic functions that regulate normal metabolism, or that can cause
serious disease when the genes don't function properly. But they were not previous thought
to be involved with setting developmental pathways that determine how stem cells and other
primitive cells decide to become neurons, muscle cells, bone or blood cells ."We
showed that HPRT carries out an important new role by causing mistakes in the ways in
which a number of super-regulatory genes called transcription factors genes are expressed
– some up, some down, but many incorrectly," said Theodore Friedmann, MD,
professor of pediatrics and director of the Gene Therapy Program at the UC San Diego
School of Medicine. The researchers propose that many other housekeeping genes in addition
to HPRT may also be found to regulate important developmental pathways. The study also
provides the first direct experimental support for a possible role that HPRT plays in the
development of the devastating neurological disorder in Lesch Nyhan disease, a rare,
X-linked inherited disorder caused by a deficiency of an enzyme produced by mutations in
the HPRT gene. Complications of the disease usually appear in boys during their first year
of life, and may result in severe gout and kidney problems, poor muscle control, and
neurological problems that cause the boys to injure themselves uncontrollably. The study
by the Friedmann group now supports the idea that the HPRT gene defects cause neurological
problems by directly interfering with the birth and function of brain neurons, especially
the ones that rely on dopamine for nerve transmission.
How Meningitis Bacteria Attack the
Brain
A specific protein on the surface of a common bacterial pathogen allows the bacteria to
leave the bloodstream and enter the brain, initiating the deadly infection known as
meningitis. The new finding, which may guide development of improved vaccines to protect
those most vulnerable, including young infants and the elderly, is now available online in
the Journal of Experimental Medicine."Streptococcus pneumoniae, commonly known as
pneumococcus, is responsible for half the cases of bacterial meningitis in humans,"
said the study's senior author, Victor Nizet, MD, professor of pediatrics and pharmacy at
the University of California, San Diego’s School of Medicine and Skaggs School of
Pharmacy and Pharmaceutical Sciences. “As many as 30 percent of patients can die from
this rapidly progressing infection, while half of survivors may be left with permanent
neurological problems including deafness, seizures, intellectual deficits or motor
disabilities.”
Anti-Aging Gene Linked to High
Blood Pressure
Researchers at the University of Oklahoma Health Sciences Center have shown the first link
between a newly discovered anti-aging gene and high blood pressure. The results, which
appear this month in the journal Hypertension, offer new clues on how we age and how we
might live longer. Persistent hypertension, or high blood pressure, is a risk factor for
stroke, heart attack, heart failure, arterial aneurysm and is the leading cause of chronic
kidney failure. Even a modest elevation of arterial blood pressure leads to shortened life
expectancy. Researchers, led by principal investigator Zhongjie Sun, tested the effect of
an anti-aging gene called klotho on reducing hypertension. They found that by increasing
the expression of the gene in laboratory models, they not only stopped blood pressure from
continuing to rise, but succeeded in lowering it. Perhaps most impressive was the complete
reversal of kidney damage, which is associated with prolonged high blood pressure and
often leads to kidney failure. “One single injection of the klotho gene can reduce
hypertension for at least 12 weeks and possibly longer. Klotho is also available as a
protein and, conceivably, we could ingest it as a powder much like we do with protein
drinks,” said Sun, M.D., Ph.D., a cardiovascular expert at the OU College of
Medicine. Scientists have been working with the klotho gene and its link to aging since
1997 when it was discovered by Japanese scientists. This is the first study showing that a
decline in klotho protein level may be involved in the progression of hypertension and
kidney damage, Sun said. With age, the klotho level decreases while the prevalence of
hypertension increases.
Watching Stem Cells Repair the
Human Brain
There is no known cure for neurodegenerative diseases such as Huntington's, Alzheimer's
and Parkinson's. But new hope, in the form of stem cells created from the patient's own
bone marrow, can be found — and literally seen — in laboratories at Tel Aviv
University. Dr. Yoram Cohen of TAU's School of Chemistry has recently proven the viability
of these innovative stem cells, called mesenchymal stem cells, using in-vivo MRI. Dr.
Cohen has been able to track their progress within the brain, and initial studies indicate
they can identify unhealthy or damaged tissues, migrate to them, and potentially repair or
halt cell degeneration. His findings have been reported in the journal Stem Cells.
LSUHSC research discovers new
targets for treatment of invasive breast cancer
Research led by Suresh Alahari, PhD, Associate Professor of Biochemistry and Molecular
Biology at LSU Health Sciences Center New Orleans, has shown for the first time that a
tiny piece of RNA appears to play a major role in the development of invasive breast
cancer and identified a gene that appears to inhibit invasive breast cancer. The research
is published in the August 21, 2009 issue of the Journal of Biological Chemistry. The
LSUHSC researchers are the first to demonstrate that miR-27b, a novel microRNA, not only
inactivates the ST14 gene which they found suppresses the growth of breast tumor cells,
but also that miR-27b stimulates the breast cancer to invade other cells. MicroRNAs are a
new class of small, single-stranded RNA molecules which play an important regulatory role
in cell biology. They bind to target genes and decrease their function. MicroRNAs may act
as oncogenes (a gene that contributes to cancer development) or tumor suppressors. In this
study working with a line of human breast cancer cells, Dr. Alahari's team found that
aggressively invasive breast tumor cells contain a large quantity of miR-27b molecules,
while normal cells do not. Further analysis revealed that miR-27b increases during cancer
progression, in direct proportion to the decrease in function of the ST14 gene. They found
that miR-27b promotes cell growth and cell invasion, suggesting that miR-27b acts as a
breast cancer oncogene. They also found that ST14 inhibits both cell growth and cell
invasion, suggesting that ST14 is a breast cancer tumor suppressor gene and that it may
also serve as a marker for the early detection of breast cancer.
Progesterone leads to inflammation,
a breast cancer risk factor
Scientists at Michigan State University have found exposure to the hormone progesterone
activates genes that trigger inflammation in the mammary gland. This progesterone-induced
inflammation may be a key factor in increasing the risk of breast cancer. Progesterone is
a naturally occurring steroid hormone and promotes development of the normal mammary
gland. Progesterone previously has been identified as a risk factor for breast cancer, and
in a study published in the Journal of Steroid Biochemistry and Molecular Biology, MSU
scientists examined the genes activated by progesterone and the effects of their
activation in a mouse model system. Exposure to progesterone in normal amounts and in
normal circumstances causes inflammation, which promotes breast development. However,
exposure to progesterone in menopausal hormone therapy is known to increase breast cancer
risk. “Progesterone turns on a wide array of genes involved in several biological
processes, including cell adhesion, cell survival and inflammation,” said physiology
professor Sandra Haslam, co-author of the paper and director of the Breast Cancer and the
Environment Research Center at MSU. “All of these processes may be relevant to the
development of breast cancer.” The study shows progesterone significantly regulates
162 genes in pubertal cells, 104 genes in adult cells and 68 genes at both developmental
stages. A number of these genes make small proteins, called chemokines, which control the
process of inflammation.
Study reveals new metabolic
safeguards against tumor cells
Cells don't like to be alone. In the early stages of tumor formation, a cell might be
pushed out of its normal home environment due to excessive growth. But a cell normally
responds to this homeless state by dismantling its nucleus, packing up its DNA, and
offering itself to be eaten by immune system cells. Simply put, the homeless cell kills
itself. This process, known as apoptosis, typically stops potential cancer cells before
they have a chance to proliferate.Now, researchers from the lab of Harvard Medical School
professor of cell biology Joan Brugge have uncovered another mechanism that kills these
precancerous, homeless cells. By studying two different types of human breast epithelial
cells, the researchers found that when separated from their natural environment, these
cells lose their ability to harvest energy from their surroundings. Eventually, they
starve."We originally thought that in order for cells to survive outside their normal
environment, they would simply need to suppress apoptosis," says Brugge, senior
author on the paper, which will appear August 19 online in Nature. "But our studies
indicate that this activity is not sufficient to prevent the demise of homeless cells.
Even if they escape apoptosis, these cells can't transport enough glucose to sustain an
energy supply." Surprisingly, metabolic function is restored if antioxidant activity
is increased inside the cells, allowing the cells to use energy pathways that don't rely
on glucose. "It raises the interesting idea that antioxidants, which are typically
thought to be protective because they prevent genomic damage, might be allowing these
potentially dangerous cells to survive," says first author Zachary Schafer, assistant
professor at the University of Notre Dame and a former postdoc in Professor Brugge's lab.
New approach to wound healing may
be easy on skin, but hard on bacteria
In a presentation today (Aug. 19) to the American Chemical Society meeting, Ankit Agarwal,
a postdoctoral researcher at the University of Wisconsin-Madison, described an
experimental approach to wound healing that could take advantage of silver's
anti-bacterial properties, while sidestepping the damage silver can cause to cells needed
for healing. Silver is widely used to prevent bacterial contamination in wound dressings,
says Agarwal, "but these dressings deliver a very large load of silver, and that can
kill a lot of cells in the wound." Wound healing is a particular problem in diabetes,
where poor blood supply that inhibits healing can require amputations, and also in burn
wards. Agarwal says some burn surgeons avoid silver dressings despite their constant
concern with infection. Using a new approach, Agarwal has crafted an ultra-thin material
carrying a precise dose of silver. One square inch contains just 0.4 percent of the silver
that is found in the silver-treated antibacterial bandages now used in medicine. In tests
in lab dishes, the low concentration of silver killed 99.9999 percent of the bacteria but
did not damage cells called fibroblasts that are needed to repair a wound. Agarwal builds
the experimental material from polyelectrolyte multilayers — a sandwich of ultra-thin
polymers that adhere through electrical attraction. To make the sandwich, Agarwal
alternately dips a glass plate in two solutions of oppositely charged polymers, and
finally adds a precise dose of silver. "This architecture is very easily tuned to
different applications," Agarwal says, because it allows exact control of such
factors as thickness, porosity and silver content. The final sandwich may range from a few
nanometers to several hundred nanometers in thickness. (One nanometer is one-billionth of
a meter; a human hair is about 60,000 nanometers in diameter.) Nicholas Abbott, a
professor of chemical and biological engineering who advises Agarwal, says during the past
decade, "about a bazillion papers have been published on polyelectrolyte multilayers.
It's been a tremendous investment by material scientists, and that investment is now ripe
to be exploited."
Future angst? Brain scans show
uncertainty fuels anxiety
Anyone who has spent a sleepless night anguishing over a possible job loss has experienced
the central finding of a new brain scan study: Uncertainty makes a bad event feel even
worse. A new study by UW-Madison brain researcher Jack Nitschke shows that the emotional
centers in the brain respond much more strongly to disturbing photos if the person didn't
know what was coming.
Romantic, candle-lit dinners - An
unrecognized source of indoor air pollution
Burning candles made from paraffin wax –– the most common kind used to infuse
rooms with romantic ambiance, warmth, light, and fragrance –– is an unrecognized
source of exposure to indoor air pollution, including the known human carcinogens,
scientists reported here today. Levels can build up in closed rooms, and be reduced by
ventilation, they indicated in a study presented at the 238th National Meeting of the
American Chemical Society (ACS). In the study, R. Massoudi Ph.D., and Amid Hamidi , Ph.D.,
said that that candles made from bee's wax or soy, although more expensive, apparently are
healthier. They do not release potentially harmful amounts of indoor air pollutants while
retaining all of the warmth, ambience and fragrance of paraffin candles (which are made
from petroleum). "An occasional paraffin candle and its emissions will not likely
affect you," Hamidi said. "But lighting many paraffin candles every day for
years or lighting them frequently in an un-ventilated bathroom around a tub, for example,
may cause problems." Besides the more serious risks, he also suggested that some
people who believe they have an indoor allergy or respiratory irritation may in fact
actually be reacting to air pollutants from burning candles.
Scientists help explain effects of
ancient Chinese herbal formulas on heart health
New research at The University of Texas Health Science Center at Houston suggests that
ancient Chinese herbal formulas used primarily for cardiovascular indications including
heart disease may produce large amounts of artery-widening nitric oxide. Findings of the
preclinical study by scientists in the university's Brown Foundation Institute of
Molecular Medicine for the Prevention of Human Diseases (IMM) appear in the Sept. 15 print
issue of the journal Free Radical Biology & Medicine. Nitric oxide is crucial to the
cardiovascular system because it signals the inner walls of blood vessels to relax, which
facilitates the flow of blood through the heart and circulatory system. The messenger
molecule also eliminates dangerous clots, lowers high blood pressure and reduces
artery-clogging plaque formation. The results from this study reveal that ancient Chinese
herbal formulas "have profound nitric oxide bioactivity primarily through the
enhancement of nitric oxide in the inner walls of blood vessels, but also through their
ability to convert nitrite and nitrate into nitric oxide," said Nathan S. Bryan,
Ph.D., the study's senior author and an IMM assistant professor. Herbal formulas are a
major component of traditional Chinese medicines (TCMs), which also include acupuncture
and massage. "TCMs have provided leads to safe medications in cancer, cardiovascular
disease and diabetes," said C. Thomas Caskey, M.D., IMM director and CEO. "The
opportunity for Dr. Bryan's work is outstanding given that cardiac disease is the No. 1
cause of death in the United States." In the study, researchers performed laboratory
tests on DanShen, GuaLou and other herbs purchased at a Houston store to assess their
ability to produce nitric oxide. Ancient Chinese herbal formulas used primarily for
cardiovascular indications are made up of three to 25 herbs. The formulas can be
administered as tablets, elixirs, soups and teas.
How meningitis bacteria attack the
brain
A specific protein on the surface of a common bacterial pathogen allows the bacteria to
leave the bloodstream and enter the brain, initiating the deadly infection known as
meningitis. The new finding, which may guide development of improved vaccines to protect
those most vulnerable, including young infants and the elderly, is now available online in
the Journal of Experimental Medicine. "Streptococcus pneumoniae, commonly known as
pneumococcus, is responsible for half the cases of bacterial meningitis in humans,"
said the study's senior author, Victor Nizet, MD, professor of pediatrics and pharmacy at
the University of California, San Diego's School of Medicine and Skaggs School of Pharmacy
and Pharmaceutical Sciences. "As many as 30 percent of patients can die from this
rapidly progressing infection, while half of survivors may be left with permanent
neurological problems including deafness, seizures, intellectual deficits or motor
disabilities." Meningitis develops when bacteria penetrate the "blood-brain
barrier." Comprised of a single layer of highly specialized microvascular endothelial
cells, the blood-brain barrier prevents most large molecules from entering into the
cerebrospinal fluid, preserving an optimal biochemical environment for brain function. The
UC San Diego team investigated the functions of a protein known as NanA in order to
discover how an entire bacterium can breech the blood-brain barrier and gain access to the
central nervous system. NanA is produced by all strains of pneumococcus and displayed
prominently on the bacteria's outer surface. Through genetic manipulations, the
researchers were able to remove the entire NanA protein, or just specific sections of the
molecule, from the pathogen. They found that while normal pneumococci were able to bind,
enter and penetrate through human brain microvascular endothelial cells, mutant bacteria
lacking the NanA protein –or those expressing only a truncated version of the protein
– largely lost these abilities. Conversely, when the full-length pneumococcal NanA
protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the
transformed bacteria gained the ability to bind and enter the same endothelial cells.
Mutation in renin gene linked to
inherited kidney disease
A mutation in a gene that helps regulate high blood pressure is a cause of inherited
kidney disease, according to a new study by researchers at Wake Forest University School
of Medicine, Charles University in Prague and colleagues. The discovery provides insight
into a protein, renin, that is important in blood pressure regulation, and reveals the
cause of one type of inherited kidney disease occurring in adults and children, said
co-investigator Anthony Bleyer, M.D., professor of internal medicine-nephrology at the
School of Medicine. The study is now available online and in the Aug. 14 issue of American
Journal of Human Genetics. While more than 25,000 articles have been written about renin,
this is the first article to identify a mutation in the renin gene as a cause of kidney
disease. Renin is a key component of blood pressure regulation. When blood pressure drops,
kidney cells detect the change and release renin into the blood stream, where it converts
inactive forms of the hormone angiotensin into angiotensin I. With the help of a molecule
in the lungs called angiotensin-converting enzyme (ACE), angiotensin I is then converted
to a much more powerful hormone, called angiotensin II, which acts directly on blood
vessels to cause blood pressure increases. Because of the significant role renin plays, an
entire class of medications used to treat high blood pressure, called ACE inhibitors, are
dedicated to preventing blood pressure from rising by blocking the renin from activating
angiotensin. A genetic mutation in the gene that encodes renin was first identified as the
cause of an hereditary kidney disease by a research group led by Stanislav Kmoch, Ph.D.,
at Charles University in Prague. Working with Kmoch and Suzanne Hart, Ph.D., at the
National Institutes of Health, Bleyer identified the condition among American families in
his study group of families with rare, inherited kidney disease. Bleyer works with about
100 families throughout the world to identify the causes of inherited kidney disease that
run in their families. Families identified with the specific genetic mutation investigated
in this study suffer from anemia in childhood and progressive kidney disease resulting in
the need for dialysis, a mechanical way to cleanse the blood. Children typically have
relatively low blood pressure. Adults suffer from gout and worsening kidney disease.
Scripps Research, UCSD, and
University of Oslo team ties genetic variations to brain size
Using advanced brain imaging and genomics technologies, an international team of
researchers co-led by Scripps Research Institute scientists has shown for the first time
that natural variations in a specific gene influence brain structure. By establishing this
link, the researchers have opened the door to a range of potential research efforts that
could reveal gene variations responsible for a number of neurological conditions such as
autism. The work was reported in an advance, online Early Edition of the Proceedings of
the National Academy of Sciences (PNAS) the week of August 17, 2009. The research grew out
of a larger project called the Thematic Organized Psychosis (TOP) study, led by Ole
Andreassen at Ullelvål University Hospital and Institute of Psychiatry at the University
of Oslo in Norway. TOP called for using extensive magnetic resonance imaging (MRI)
scanning of hundreds of patients, including many with severe mental disorders, in
collaboration with Anders Dale of the University of California, San Diego (UCSD), School
of Medicine. Recognizing the potential of genetic studies conducted in conjunction with
the braining imaging, the team reached out to include Nicholas Schork, a genetics expert
at Scripps Research. In deciding a first target, the group decided to focus on a gene
known as MECP2 because it plays major roles in controlling brain development. Past studies
with mice have shown that MECP2 regulates the activity of a wide range of other genes
important in brain development. Substantial mutations in the gene also cause the rare
disease Retts syndrome, in which brain growth slows, leading to a range of debilitating
neurological problems and mental retardation. MECP2 has also been linked to autism.
Elevated arginase levels contribute
to vascular eye disease such as diabetic retinopathy
Elevated levels of the enzyme arginase contribute to vascular eye damage and Medical
College of Georgia researchers say therapies to normalize its levels could halt
progression of potentially blinding diseases such as diabetic retinopathy. Their work,
published in the August issue of The American Journal of Pathology, is the first to make
the connection between eye disease and arginase, an enzyme known to be a player in
cardiovascular disease, according to researchers at MCG and Charlie Norwood Veterans
Affairs Medical Center. "The goal is to find a new strategy for preventing
progression of diabetic retinopathy," says Dr. Ruth Caldwell, a cell biologist at the
MCG School of Medicine and VA Medical Center, and the study's corresponding author.
Because they could measure arginase levels in the blood, it also could become a biomarker
for a disease process that can work silently in the eye for months or even years, she
says. More broadly, understanding just how arginase regulates inflammation should lead to
new therapies for many acute and chronic inflammatory diseases in the eyes and other
organs, says Dr. Wenbo Zhang, postdoctoral fellow in Dr. Caldwell' lab and the paper's
first author. The researchers suspect an elevated arginase level is a red flag of early
vascular damage in the eyes as well as the heart, kidneys and other organs. "We don't
think this is going to be specific to the retina," Dr. Caldwell says, noting that
inflammation often precedes full blown vascular disease. "We know that people with
diabetes have a greater incidence of heart attack and we know that vision is a sense that
suffers greatly in diabetes," says Dr. R. William Caldwell, study co-author who
chairs the Department of Pharmacology and Toxicology in the MCG School of Medicine.
"We are finding arginase is a common player."
Study shows how to boost value of
Alzheimer's-fighting compounds
The polyphenols found in red wine are thought to help prevent Alzheimer's disease, and new
research from Purdue University and Mount Sinai School of Medicine has shown that some of
those compounds in fact reach the brain. Mario Ferruzzi, a Purdue associate professor of
food science; Connie Weaver, Purdue's head of foods and nutrition; and Elsa Janle, a
Purdue associate professor of foods and nutrition, found that the amount of polyphenols
from grapeseed extract that can reach a rat's brain is as much as 200 percent higher on
the 10th consecutive day of feeding as compared to the first. Many previous experiments,
in which absorption was measured after single or sporadic doses, often found very little,
if any, of the bioactive polyphenols reaching brain tissues. However, more chronic
exposure appears to improve absorption. "This shows that reasonable and chronic
consumption of these products may be the way to go, rather than single, high doses,
similar to drugs," said Ferruzzi, who collaborated on the research with Mount Sinai's
Dr. Giulio Pasinetti. "It's like eating an apple a day, not a case of apples over two
days every month."
MS Patients Who Smoke Show More
Brain Atrophy, More Lesions, than MS Nonsmokers
Persons with multiple sclerosis who smoked for a little as six months during their
lifetime had more destruction of brain tissue and more brain atrophy than MS patients who
never smoked, a study by neuroimaging specialists at the University at Buffalo has shown.
Research published in the Aug. 18, 2009, issue of Neurology®, the medical journal of the
American Academy of Neurology, showed that "ever-smokers" had more brain lesions
and greater loss of brain volume, as well as higher scores on the Expanded Disability
Status Scale (EDSS), than MS patients who had no history of smoking.
Research points to new target for
stopping colon cancer
Drugs that target the epidermal growth factor receptor, or EGFR, have been used for a
number of cancers. But these drugs called EGFR inhibitors, such as cetuximab, have not
been very effective against colon cancer. The new study, however, shows that drugs that
target the closely related receptor ERBB3 would probably be much more effective than EGFR
inhibitors at treating most colorectal cancers, said David Threadgill, Ph.D., adjunct
professor in the department of genetics at UNC and lead author of the study. He also is a
member of the UNC Lineberger Comprehensive Cancer Center and a professor in the genetics
department at North Carolina State University. The researchers genetically blocked ERBB3
in a mouse model of colon cancer and in human colon cancer cell lines. “If you
genetically remove ERBB3, as you would if you were pharmacologically targeting it, then
the mice rarely develop colon cancer,” Threadgill said.
NIH researchers identify key factor
that stimulates brain cancer cells to spread
Researchers funded by the National Institutes of Health have found that the activity of a
protein in brain cells helps stimulate the spread of an aggressive brain cancer called
glioblastoma multiforme (GBM). In a move toward therapy, the researchers showed that a
small designer protein can block this activity and reduce the spreading of GBM cells grown
in the laboratory. GBM is the most lethal form of brain cancer, with about half of
patients expected to die within a year of diagnosis. GBM is named for the fact that the
cancerous cells have properties of support cells in the brain called glial cells. Rather
than simply growing in a single tumor mass, GBM cells tend to migrate throughout the
brain, making it difficult to remove them surgically. As the cells spread and multiply,
they also tend to become resistant to radiation and chemotherapy. "Interventions to
control the spreading of glioblastoma multiforme have the potential to slow the clinical
course of the disease and improve overall survival rates," says Jane Fountain, Ph.D.,
a program director at NIH's National Institute of Neurological Disorders and Stroke
(NINDS). NINDS funded the new study through an initiative that encourages research on why
brain tumor cells are so highly invasive and how to therapeutically target these cells.
The study's senior author is Susann Brady-Kalnay, Ph.D., a neuroscientist at Case Western
Reserve University in Cleveland and an expert on the development of the retina. For years,
she has studied how cells migrate to their proper places in the developing retina. In
particular, she studied how this process is regulated by cell adhesion molecules –
proteins at a cell's surface that can keep the cell stuck to its surroundings, or help the
cell move. She has shown that a cell adhesion molecule called PTPmu is required for
retinal cell migration. Investigating the role of PTPmu in GBM dispersal was a logical
extension, she says. "We know that cell adhesion is important for development, and
that there are many parallels between what happens during development and what happens in
cancer," says Dr. Brady-Kalnay. For instance, she notes there is some evidence that
cancer cells have turned back the developmental clock and reverted to an embryonic stem
cell-like state.
How mercury becomes toxic in the
environment
Naturally occurring organic matter in water and sediment appears to play a key role in
helping microbes convert tiny particles of mercury in the environment into a form that is
dangerous to most living creatures. This finding is important, say Duke University
environmental engineers, because it could change the way mercury in the environment is
measured and therefore regulated. This particularly harmful form of the element, known as
methylmercury, is a potent toxin for nerve cells. When ingested by organisms, it is not
excreted and builds up in tissues or organs. In a series of laboratory experiments, Amrika
Deonarine, a graduate student in civil and environmental engineering at Duke's Pratt
School of Engineering, found that organic matter and chemical compounds containing sulfur
– known as sulfides -- can readily bind to form mercury sulfide nanoparticles. Since
they are more soluble than larger particles, these nanoparticles may be the precursors to
a process known as methylation.
Fatigue related to radiotherapy may
be caused by inflammation
Patients who experience fatigue during radiotherapy for breast or prostate cancer may be
reacting to activation of the proinflammatory cytokine network, a known inflammatory
pathway, according to a report in Clinical Cancer Research, a journal of the American
Association for Cancer Research. Julie Bower, Ph.D., an associate professor in the
Department of Psychology and Psychiatry at the University of California, Los Angeles, and
colleagues, conducted an observational study among 28 patients with breast cancer and 20
patients with prostate cancer, all early stage. Patients completed questionnaires and
provided blood samples so researchers could determine the level of proinflammatory
markers. As expected, there was a strong link between radiotherapy treatment and fatigue.
In a new finding, the researchers noted that increases in serum markers of cytokine
activity, specifically IL-1 receptor antagonist and C-reactive protein, were also linked
with fatigue. "This study suggests that exposure to radiation is releasing these
inflammatory cytokines and that may be contributing to fatigue," said Bower.
Tobacco plants yield the first
vaccine for the dreaded 'cruise ship virus'
Scientists have used a new vaccine production technology to develop a vaccine for
norovirus, a dreaded cause of diarrhea and vomiting that may be the second most common
viral infection in the United States after the flu. Sometimes called the "cruise ship
virus," this microbe can spread like wildfire through passenger liners, schools,
offices and military bases. The new vaccine is unique in its origin — it was
"manufactured" in a tobacco plant using an engineered plant virus. Researchers
are enlisting plants in the battle against norovirus, swine flu, bird flu, and other
leading infectious diseases. This plant biotechnology opens the door to more efficient,
inexpensive ways to bring vaccines quickly to the public, especially critical in times
when viruses mutate into unpredictable new strains, said Charles Arntzen, Ph.D., who
reported on the topic today at the 238th National Meeting of the American Chemical Society
(ACS). "The recent outbreak of H1N1 influenza virus has once again reminded us of the
ability of disease-causing agents to mutate into new and dangerous forms," Arntzen
points out. "It will be at least six months until a vaccine for this new strain will
be available, and it will take even longer to create large stock piles of vaccine. For a
case like the H1N1 influenza virus, you want to be able to move very rapidly and introduce
a commercial vaccine in the shortest possible time. We think we have a major advantage in
using engineered plant viruses to scale-up vaccine manufacture within weeks instead of
months."Noroviruses are always mutating, making it a moving target for vaccine
developers. Arntzen says this has presented an obstacle for big pharmaceutical companies
who might have considered developing a vaccine. Production costs can skyrocket when a
single disease may frequently require new vaccines that must be developed and tested for
safety and effectiveness. As a result, vaccines do not exist for many diseases that sicken
enormous numbers of people each year. Arntzen notes that plant biotechnology could create
a cheaper, quicker vaccine manufacturing technique uniquely suited to combat mutating
viruses like norovirus and the flu. Norovirus temporarily disables its victims, giving
them severe diarrhea or nausea for up to three days. While not as life-threatening as the
flu, Arntzen says it is equally important.
Researchers find genetic link
between physical pain and social rejection
UCLA psychologists have determined for the first time that a gene linked with physical
pain sensitivity is associated with social pain sensitivity as well. Their study indicates
that variation in the mu-opioid receptor gene (OPRM1), often associated with physical
pain, is related to how much social pain a person feels in response to social rejection.
People with a rare form of the gene are more sensitive to rejection and experience more
brain evidence of distress in response to rejection than those with the more common form.
The research was published Aug. 14 in the early online edition of Proceedings of the
National Academy of Sciences and will appear in the print version in the coming weeks. The
findings give weight to the common notion that rejection "hurts" by showing that
a gene regulating the body's most potent painkillers — mu-opioids — is involved
in socially painful experiences too, said study co-author Naomi Eisenberger, UCLA
assistant professor of psychology and director of UCLA's Social and Affective Neuroscience
Laboratory. In the study, researchers collected saliva samples from 122 participants to
assess which form of the OPRM1 gene they had and then measured sensitivity to rejection in
two ways. First, participants completed a survey that measured their self-reported
sensitivity to rejection. They were asked, for example, how much they agreed or disagreed
with statements like "I am very sensitive to any signs that a person might not want
to talk to me."
Mother's immune system may block
fetal treatments for blood diseases
Pediatric researchers have resolved an apparent contradiction in the field of prenatal
cell transplantation— a medical approach that holds future promise in correcting
sickle cell disease and other serious congenital blood disorders. In a new study in
animals, the researchers showed that the mother's immune response interferes with the
offspring's earlier ability to tolerate transplanted donor cells. The study team concludes
that focusing on transplant techniques that avoid the maternal immune response may allow
scientists to take advantage of fetal tolerance to achieve a long-sought goal of treating
blood diseases prenatally. While cautioning that much work must be done to understand how
these animal findings apply to humans, the current findings are "surprising but
reassuring," said study leader Alan W. Flake, M.D., of the Children's Center for
Clinical Research at The Children's Hospital of Philadelphia. The study appeared online
August 3 in the Journal of Clinical Investigation. For over 50 years, explained Flake, it
has been a fundamental precept of immunology that a fetus tolerates foreign antigens in a
window-of-opportunity period before its immune system fully develops the capacity to mount
an immune response. Scientists assumed that by carefully introducing donor cells and
stimulating a fetus to develop tolerance to those cells, one could set the stage for a
later organ or cellular transplant that would not be rejected by a more mature immune
system. As prenatal diagnosis has continued to become available for a greater number of
congenital diseases, scientists have considered the possibility of correcting blood
disorders such as sickle cell disease or thalassemia. After first transplanting a small
number of healthy cells in an early-stage fetus to establish tolerance, a second dose of
transplanted cells later in gestation would proliferate, and treat the blood disorder
before birth. Researchers use hematopoietic cells—stem cells that that develop into
blood cells—in this technique, in utero hematopoietic cell transplantation (IUHCT).
Antioxidants not associated with
increased melanoma risk
Antioxidant supplements do not appear to be associated with an increased risk of melanoma,
according to a report in the August issue of Archives of Dermatology, one of the
JAMA/Archives journals. A recent randomized trial of antioxidants for cancer prevention
found that daily supplementation with nutritionally appropriate doses of vitamins C and E,
beta carotene, selenium and zinc appeared to increase the risk of melanoma in women
four-fold, according to background information in the article. Because an estimated 48
percent to 55 percent of U.S. adults use vitamin or mineral supplements regularly, the
potential harmful effects of these nutrients is alarming, the authors note. Maryam M.
Asgari, M.D., M.P.H., of Kaiser Permanente Northern California, Oakland, and colleagues
examined the association between antioxidants and melanoma among 69,671 women and men who
were participating in the Vitamins and Lifestyle (VITAL) study, designed to examine
supplement use and cancer risk. At the beginning of the study, between 2000 and 2002,
participants completed a 24-page questionnaire about lifestyle factors, health history,
diet, supplement use and other cancer risk factors. Intake of multivitamins and
supplements during the previous 10 years, including selenium and beta carotene, was not
associated with melanoma risk in either women or men. The researchers also examined the
risk of melanoma associated with long-term use of supplemental beta carotene and selenium
at doses comparable to the previous study and found no association. "Consistent with
the present results, case-control studies examining serologic [blood] levels of beta
carotene, vitamin E and selenium did not find any association with subsequent risk of
melanoma," the authors write. "Moreover, the Nurses' Health Study reported no
association between intake of vitamins A, C and E and melanoma risk in 162,000 women
during more than 1.6 million person-years of follow-up."
Does sugar feed cancer?
Researchers at Huntsman Cancer Institute at the University of Utah have uncovered new
information on the notion that sugar "feeds" tumors. The findings may also have
implications for other diseases such as diabetes. The research is published in the journal
Proceedings of the National Academy of Sciences. "It's been known since 1923 that
tumor cells use a lot more glucose than normal cells. Our research helps show how this
process takes place, and how it might be stopped to control tumor growth," says Don
Ayer, Ph.D., a Huntsman Cancer Institute investigator and professor in the Department of
Oncological Sciences at the University of Utah. During both normal and cancerous cell
growth, a cellular process takes place that involves both glucose (sugar) and glutamine
(an amino acid). Glucose and glutamine are both essential for cell growth, and it was long
assumed they operated independently, but Ayer's research shows they are inter-dependent.
He discovered that by restricting glutamine availability, glucose utilization is also
stopped. "Essentially, if you don't have glutamine, the cell is short circuited due
to a lack of glucose, which halts the growth of the tumor cell" Ayer says. The
research, spearheaded by Mohan Kaadige, Ph.D., a postdoctoral fellow in Ayer's lab,
focused on MondoA, a protein that is responsible for turning genes on and off. In the
presence of glutamine, MondoA blocks the expression of a gene called TXNIP. TXNIP is
thought to be a tumor suppressor, but when it's blocked by MondoA , it allows cells to
take up glucose, which in turn drives tumor growth. Ayer's research could lead to new
drugs that would target glutamine utilization, or target MondoA or TXNIP. Ayer says the
next step in his research is to develop animal models to test his ideas about how MondoA
and TXNIP control cell growth. "If we can understand that, we can break the cycle of
glucose utilization which could be beneficial in the treatment of cancer," Ayer says.
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