News 21 april 2009
Pesticide exposure found to
increase risk of Parkinson's disease
The fertile soil of California's Central
Valley has long made it famous as one of the nation's prime crop-growing regions. But it's
not just the soil that allows for such productivity. Crops like potatoes, dry beans and
tomatoes have long been protected from bugs and weeds by the fungicide maneb and the
herbicide paraquat. Scientists know that in animal models and cell cultures, such
pesticides trigger a neurodegenerative process that leads to Parkinson's disease. Now,
researchers at UCLA provide the first evidence for a similar process in humans. In a new
epidemiological study of Central Valley residents who have been diagnosed with Parkinson's
disease, researchers found that years of exposure to the combination of these two
pesticides increased the risk of Parkinson's by 75 percent. Further, for people 60 years
old or younger diagnosed with Parkinson's, earlier exposure had increased their risk for
the disease by as much as four- to six-fold. Reporting in the April 15 issue of the
American Journal of Epidemiology, Beate Ritz, professor of epidemiology at the UCLA School
of Public Health, and Sadie Costello, a former doctoral student at UCLA who is now at the
University of California, Berkeley, found that Central Valley residents who lived within
500 meters of fields sprayed between 1974 and 1999 had a 75-percent increased risk for
Parkinson's.In addition, people who were diagnosed with Parkinson's at age 60 or younger
were found to have been at much higher risk because they had been exposed to maneb,
paraquat or both in combination between 1974 and 1989, years when they would have been
children, teens or young adults. The researchers enrolled 368 longtime residents diagnosed
with Parkinson's and 341 others as a control group.
Controlling our brain’s
perception of emotional events
Research performed by Nicole Lauzon and Dr.
Steven Laviolette of the Schulich School of Medicine & Dentistry at The University of
Western Ontario has found key processes in the brain that control the emotional
significance of our experiences and how we form memories of them. A lack of proper brain
function in this area is what lies beneath such conditions as Schizophrenia and
Post-Traumatic Stress Disorder (PTSD). In people who suffer from these conditions
emotional experiences can become distorted, causing the person to ‘lose touch’
with reality. The findings have been published online by The Journal of Neuroscience.
Lauzon, a Doctoral graduate student in the Laviolette laboratory, discovered that specific
receptors for the neurotransmitter dopamine can control how the brain processes
emotionally significant information as well as memories for those experiences. Using a
rodent model of emotional learning and memory formation, the researchers found by
increasing the activity of a specific dopamine receptor in a region of the brain called
the pre-frontal cortex, it was able to transform a normally insignificant emotional
experience into a very strong emotional memory. In contrast, when a different subtype of
the dopamine system was activated, it was able to block the ability to recall an
emotionally charged experience. “Our findings have profound implications for
understanding how specific brain receptors can control the magnitude of emotional
experience and memory formation,” says Laviolette.
Acupuncture Eases Radiation-Induced
Dry Mouth in Cancer Patients
Twice weekly acupuncture treatments relieve
debilitating symptoms of xerostomia - severe dry mouth - among patients treated with
radiation for head and neck cancer, researchers from The University of Texas M. D.
Anderson Cancer Center report in the current online issue of Head & Neck. Xerostomia
develops after the salivary glands have been exposed to repeated doses of therapeutic
radiation. People who have cancers of the head and neck typically receive large cumulative
doses, rendering the salivary glands incapable of producing adequate saliva, said Mark S.
Chambers, M.S., D.M.D., a professor in the Department of Dental Oncology. Saliva
substitutes, lozenges and chewing gum bring only temporary relief, and the commonly
prescribed medication, pilocarpine, has short-lived benefits and bothersome side effects
of its own. "The quality of life in patients with radiation-induced xerostomia is
profoundly impaired," said Chambers, the study's senior author. "Symptoms can
include altered taste acuity, dental decay, infections of the tissues of the mouth, and
difficulty with speaking, eating and swallowing. Conventional treatments have been less
than optimal, providing short-term response at best." M. Kay Garcia, LAc, Dr.P.H., a
clinical nurse specialist and acupuncturist in M. D. Anderson's Integrative Medicine
Program and the study's first author, noted that patients with xerostomia may also develop
nutritional deficits that can become irreversible.
Study Finds Blood Cells Can Be
Reprogrammed to Act as Embryonic Stem Cells
In a recent study, U.S. researchers have
reprogrammed cells found in circulating blood into cells that are molecularly and
functionally indistinguishable from embryonic stem cells, a revolutionary achievement that
provides a readily accessible source of stem cells and an alternative to harvesting
embryonic stem cells. The findings were prepublished online in Blood, the official journal
of the American Society of Hematology.
Embryonic stem cells have long been coveted for their potential to treat a multitude of
diseases as a result of their unique properties of nearly indefinite self-renewal and
pluripotency (the ability to develop into any type of cell in the body), but their use has
been the subject of political controversy. “Our findings provide the first proof that
cells from human blood can morph into stem cells,” said senior study author George Q.
Daley, MD, PhD, an investigator for the Howard Hughes Medical Institute at Children’s
Hospital, Boston. “Making pluripotent stem cells from blood, which is one of the
easiest tissues to obtain, provides an easy strategy for generating patient-specific stem
cells that are valuable research tools and may one day be used to treat a number of
diseases.” To generate induced pluripotent stem cells (dubbed iPS cells), blood was
collected from a 26-year-old male donor. From the blood sample, the researchers isolated
CD34+ cells, a type of stem cell that produces only blood cells, and cultured them in
growth factors for six days to increase their number. During the culture, the scientists
infected the CD34+ cells with viruses carrying reprogramming factors, genes normally
expressed in embryonic stem cells that can reset the blood cells to an embryonic state.
Colonies of cells exhibiting physical characteristics similar to embryonic stem (ES) cells
appeared about two weeks after the procedure. To determine whether these cells were also
functionally similar to ES cells, the scientists analyzed the CD34+ iPS cell lines to see
if they had acquired stem cell “markers,” the unique combination of proteins
that coat the cells’ surface and distinguish them from other types of cells. Indeed,
the iPS cell lines expressed the same markers as ES cells and further shared the capacity
to differentiate into a variety of specialized cell types.
Researchers probe kidney damage,
protection in lupus
Kidney damage associated with the
autoimmune disease lupus is linked to a malfunction of immune cells that causes them to
congregate in and attack the organs, researchers at UT Southwestern Medical Center have
discovered in a mouse study. In a separate study with an international team, the
researchers also found that a certain set of genes appears to protect the kidneys from a
different sort of immune attack in both mice and humans. “These studies, taken
together, uncover two important molecules that underlie the pathology of lupus,
particularly kidney disease,” said Dr. Edward Wakeland, chairman of immunology at UT
Southwestern and co-senior author of the studies. “In addition, they highlight a
certain molecule as a potential target for treating this disease,” he said.
Witnessing violence affects
kids’ health
Study finds link between exposure to
community violence and a disruption to the stress pathways in the body. School-aged
children who witness violence in urban communities show symptoms of post-traumatic stress.
They also suffer physiological effects with a disruption to their normal cortisol
production pattern during the day, which may have long-term negative effects on their
health. According to Dr. Shakira Franco Suglia, from the Harvard School of Public Health,
and her team lead by Dr. Rosalind J. Wright from Brigham and Women’s Hospital,
Harvard Medical School in Boston, USA, because these children are not diagnosed with
post-traumatic stress disorder, these abnormal physiological symptoms are unlikely to be
picked up by their doctors. The study1 has just been published online in Springer’s
International Journal of Behavioral Medicine.
Sugar On Bacteria Surface Serves As
Base For A Web Of Resistance
The bacteria responsible for chronic
infections in cystic fibrosis patients use one of the sugars on the germs’ surface to
start building a structure that helps the microbes resist efforts to kill them, new
research shows. Scientists have determined that the bacterial cell-surface sugar, a
polysaccharide called Psl, is anchored on the surface of the bacterium as a helix,
providing a structure that encourages cell-to-cell interaction. When multiple bacterial
cells join together with the help of such a structure, they form what is called a biofilm,
a persistent community of bugs that is able to resist the effects of a human immune
response, as well as antibiotic drugs. In the case of the bacterium being studied,
Pseudomonas aeruginosa, the results of biofilm development can be lethal. Chronic
infection with these bacteria is what causes the death of most patients with cystic
fibrosis, a genetic disease characterized in part by excess mucus in the lungs – a
condition that can foster creation of the biofilm.
Too much or too little sleep
increases risk of diabetes
Researchers at Université Laval's Faculty
of Medicine have found that people who sleep too much or not enough are at greater risk of
developing type 2 diabetes or impaired glucose tolerance. The risk is 2˝ times higher for
people who sleep less than 7 hours or more than 8 hours a night. The findings were
published recently on the website of the journal Sleep Medicine. The researchers arrived
at this conclusion after analyzing the life habits of 276 subjects over a 6-year period.
They determined that over this timespan, approximately 20% of those with long and short
sleep duration developed type 2 diabetes or impaired glucose tolerance versus only 7%
among subjects who were average duration sleepers. Even after taking into account the
effect attributable to differences in body mass among the subjects, the risk of diabetes
and insulin resistance was still twice as high among those with longer and shorter sleep
duration than average sleepers. The researchers also point out that diabetes is not the
only risk associated with sleep duration. A growing number of studies have shed light on a
similar relationship between sleep and obesity, cardiovascular disease, and overall
mortality. The authors observe that among adults, between 7 and 8 hours of nighttime sleep
appears to be the optimum duration to protect against common diseases and premature death.
Moms who breastfeed less likely to
develop heart attacks or strokes
The longer women breastfeed, the lower
their risk of heart attacks, strokes and cardiovascular disease, report University of
Pittsburgh researchers in a study published in the May issue of Obstetrics &
Gynecology. "Heart disease is the leading cause of death for women, so it's vitally
important for us to know what we can do to protect ourselves," said Eleanor Bimla
Schwarz, M.D., M.S., assistant professor of medicine, epidemiology, and obstetrics,
gynecology and reproductive sciences at the University of Pittsburgh. "We have known
for years that breastfeeding is important for babies' health; we now know that it is
important for mothers' health as well." According to the study, postmenopausal women
who breastfed for at least one month had lower rates of diabetes, high blood pressure and
high cholesterol, all known to cause heart disease. Women who had breastfed their babies
for more than a year were 10 percent less likely to have had a heart attack, stroke, or
developed heart disease than women who had never breastfed. Dr. Schwarz and colleagues
found that the benefits from breastfeeding were long-term ? an average of 35 years had
passed since women enrolled in the study had last breastfed an infant. "The longer a
mother nurses her baby, the better for both of them," Dr. Schwarz pointed out.
"Our study provides another good reason for workplace policies to encourage women to
breastfeed their infants." The findings are based on 139,681 postmenopausal women
enrolled in the Women's Health Initiative study of chronic disease, initiated in 1994.
Dark hair? Don't burn? Your genes
may still put you at risk for melanoma
New genetic research suggests that the
traditional risk factors for melanoma may not be as helpful in predicting risk in all
people as previously thought, according to data presented at the American Association for
Cancer Research 100th Annual Meeting 2009. "Traditionally, a clinician might look at
a person with dark hair who did not sunburn easily and classify them as lower risk for
melanoma, but that may not be true for all people in the population," said Peter
Kanetsky, Ph.D., M.P.H., assistant professor of epidemiology at the University of
Pennsylvania. Kanetsky and his colleagues have identified that genetic variants in MC1R
could help to predict melanoma risk in people who are not usually classified as high risk.
While this link previously has been observed, Kanetsky said it is now time to begin
discussing genetic factors as part of the overall melanoma risk model. For the current
study, researchers analyzed 779 patients with melanoma from the Pigmented Lesion Clinic of
the University of Pennsylvania and compared them with 325 healthy control patients.
Overall, the presence of certain MC1R variants was associated with a more than two-fold
risk of melanoma, but this risk was largely confined to those patients who would not
usually be considered to be at elevated risk.
Researchers identify gene
associated with muscular dystrophy-related vision problems
Skeletal muscle disease and vision deficits
might seem unrelated, but a frog model of muscular dystrophy shows it is not such a leap.
Facioscapulohumeral muscular dystrophy, or FSHD, is the world's third most common type of
muscular dystrophy. It is characterized by progressive skeletal muscle weakening in the
face, shoulders, and upper arms. Over half of FSHD patients (also known as
Landouzy-Dejerine syndrome) also have abnormal blood vessels in the back of the eye, which
can cause vision problems. Over 95% of FSHD patients carry a genetic abnormality proposed
to affect expression of the FRG1 gene, and previous studies of FRG1 in frogs demonstrate
that it is important for skeletal muscle development. Therefore, University of Illinois
scientists investigated the possibility that the FRG1 gene might also be responsible for
the blood vessel abnormalities in FSHD patients' eyes. Their report published in Disease
Models & Mechanisms (DMM), describes how they examined the FRG1 gene in the frog and
found the protein that it encodes for is highly expressed in blood vessels. Additional
experiments show that normal FRG1 protein expression is important for blood vessel growth
and organization.
Natural protein may halt colorectal
cancer's spread
Medical College of Wisconsin Cancer Center
researchers in Milwaukee have learned that a protein, CXCL12, that normally controls
intestinal cell movement, has the potential to halt colorectal cancer spreading. These
studies represent a potential mechanism by which CXL12 may slow cancer spreading.
Controlling this process could lead to new biological therapies for colorectal cancers.
"Colorectal cancer ranks third in cancer-related deaths in the United States in
2008," says principal investigator Michael Dwinell, Ph.D., professor of microbiology
and molecular genetics. "Finding therapies to prevent its spread to secondary organs
would increase patient prognosis considerably." Luke Drury, a graduate student in the
interdisciplinary program for biomedical research at the Medical College, was his research
associate. Their abstract will be presented at the American Association for Cancer
Research meeting in Denver, April 21. Normal intestinal cells stick to underlying
proteins, which provide survival signals to maintain cell health. If they become unstuck,
the floating cells undergo a programmed cell death. In cancer, cells have acquired genetic
changes that allow them to survive during loss of attachment. Previously, the researchers
found that colorectal cancer cells lacked CXCL12 expression. In these studies, they
re-introduced CXCL12 expression in colorectal cancer cells which prevented their ability
to adhere to underlying proteins. Plus, the floating cells underwent programmed cell
death.
Exercise protects against damage
causing leakage in the blood-brain barrier
Regular exercise can prevent the disruption
of the blood brain barrier that normally occurs with a dose of methamphetamine comparable
to that used by heavy meth users. A University of Kentucky study is the first to look at
the protective effects of exercise on the vascular effects of methamphetamine, effects
that have been found clinically to contribute to serious, lasting, and sometimes fatal
cardiovascular and neurological problems. Results of the study, conducted in young male
mice, were reported April 22 at the Experimental Biology 2009 meeting in New Orleans. The
presentation was part of the scientific program of The American Physiological Society.
Principal investigator Dr. Michal Toborek says the level of the protective effects of
exercise on the integrity of the blood brain barrier after the human equivalent of one
gram of methamphetamine was surprising even to the research team. The results provide new
understanding of the mechanisms through which the brain reacts to methamphetamine,
particularly those related to oxidative stress. Results also suggest why exercise might
help delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's in
which leakiness of the blood brain barrier is a characteristic. The researchers placed 25
young male mice – aged three months, equivalent to the 20s in humans -- in cages
where they had access to exercise wheels. For five weeks, the animals took advantage of
the wheels to run continually. Another 25 young mice were housed in similar cages but
without access to wheels. At the end of this "endurance exercise training"
period, all mice were injected with 10 mg. of methamphetamine over a 24-hour period. All
the mice displayed some of the same effects of meth as seen in humans: they appeared
agitated and increased their physical activity, and their body temperature rose. But in
terms of what was happening in the capillaries of the brain, there was a marked difference
between the mice who had been exercising extensively for the previous five weeks and those
who had been sedentary. In the sedentary group of mice, the small capillaries in the brain
experienced increased oxidative stress, causing the blood brain barrier to become more
permeable. Toxins and inflammatory cells previously prevented from crossing the blood
brain barrier then had access to the brain. The exercise group showed no such changes.
Changes in the blood brain barrier, especially the role of oxidative reactions, have been
little studied in the past, says Dr. Toborek; the University of Kentucky study is the
first to observe that meth administration produced an upregulation of NADPH oxidase, a
major enzyme that causes oxidative stress. This is a significant finding, says Dr.
Toborek, because it delineates a mechanism for how meth causes oxidative stress. It also
was significant that the exercise mice were markedly protected from such upregulation and
consequently from the oxidative stress that weakened the capillaries in the brains of the
non-exercise mice.
New hope for treatment of
neurodegenerative disorder
Researchers from the University of Southern
California have taken an important first step toward protecting against Huntington disease
using gene therapy. Huntington Disease is an incurable neurological disorder characterized
by uncontrolled movements, emotional instability and loss of intellectual faculties. It
affects about 30,000 people in the United States, and children of parents with the disease
have a 50 percent chance of inheriting it themselves. "Our findings allow for the
possibility that controlled over-expression of RCAN1-1L might in the future be a viable
avenue for therapeutic intervention in Huntington disease patients," said Kelvin J.
A. Davies, professor of gerontology in the USC Davis School of Gerontology and professor
of biological sciences in the USC College of Letters, Arts and Sciences. In a paper in the
June 2009 issue of Journal of Biological Chemistry, now available online, Davies and his
coauthors use cell culture findings to show that a form of the gene RCAN1, known as
RCAN1-1L, is dramatically decreased in human brains affected by Huntington disease.
RCAN1-1L was first discovered in Davies' lab. The investigators also show that increasing
levels of RCAN1-1L rescues cells from the toxic effects of Huntington disease, a result
that could someday lead to new avenues of treatment, according to Davies. "Our
discovery offers real hope and may even have wide-ranging implications for a variety of
other important CAG repeat-related diseases," Davies said.
Genetic source of rare childhood
cancer found; gene is implicated in other cancers
The search for the cause of an inherited
form of a rare, aggressive childhood lung cancer has uncovered important information about
how the cancer develops and potentially sheds light on the development of other cancers.
The finding by researchers at Washington University School of Medicine in St. Louis,
Children's National Medical Center in Washington, D.C., the International Pleuropulmonary
Blastoma Registry at Children's Hospitals and Clinics of Minnesota, and other
collaborating institutions adds the final link to the chain connecting the gene DICER1 to
cancer development — something that had been suspected but until now not definitively
demonstrated. The results were presented April 19, 2009, at the 100th Annual Meeting of
the American Association of Cancer Research in Denver. The study shows that some children
with the rare cancer pleuropulmonary blastoma (PPB) are born with a deleterious mutation
in DICER1, a master controller gene that helps regulate the expression of other genes. The
children studied came from families with a history of PPB or related disorders. "PPB
is the first malignancy found to be directly associated with inherited DICER1 mutations,
making the cancer an important model for understanding how mutations and loss of DICER1
function lead to cancer," says lead author D. Ashley Hill, M.D., chief of pathology
at Children's National Medical Center. "Additionally, we now believe that PPB tumors
arise from an unusual mechanism in which cells carrying mutations induce nearby cells to
become cancerous without becoming cancerous themselves." Hill was principal
investigator of the study, which began while she was on the Washington University faculty.
