News 31 march 2009
New brain analytical tool developed
by Hebrew University scientists
An interdisciplinary team of scientists at
the Hebrew University of Jerusalem has developed a new analytical tool to answer the
question of how our brain cells record outside stimuli and react to them. Although much
progress has been made in understanding the brain in recent decades, scientists still know
relatively little about how these processes function. The two key problems in making
progress in this field are that there will never be enough real data in terms of measuring
what the brain actually does, and even if there were, there haven't been enough methods
for analyzing such data and using them to answer the question of how neural coding
actually takes place.
The analytical method developed by the Hebrew University researchers should be able to
provide an indication, for example, of how many neurons encode a given stimulus such as
reactions to a face or a movement and how they collaborate to do it. Current technology
allows researchers only a very partial view of brain activity. For example, one cannot
record the activity of more than a few hundred nerve cells from the cortex of a behaving
animal. Methods like MRI imaging can map larger brain areas, but cannot be used to measure
single neurons. A key question then remains of what one can learn from such a partial
view. The Hebrew University researchers, headed by Dr. Amir Globerson of the Rachel and
Selim Benin School of Computer Science and Engineering, have formulated the novel
principle of Minimum Mutual Information (MinMI) to tackle the issue. An article detailing
their findings has been published online in the Proceedings of the National Academy of
Sciences (PNAS) in the US.
CT scans - Too much of a good thing
can be risky
Patients who undergo numerous CT scans over
their lifetime may be at increased risk for cancer, according to a study published in the
April issue of Radiology. "We found that while most patients accrue small cumulative
cancer risks, 7 percent of the patients in our study had enough recurrent CT imaging to
raise their estimated cancer risk by 1 percent or more above baseline levels," said
Aaron Sodickson, M.D., Ph.D., assistant director of Emergency Radiology at Brigham and
Women's Hospital and researcher at the Center for Evidence-Based Imaging in Boston.
"The techniques implemented in our study can be used to identify higher risk patients
who might benefit from enhanced radiation protection efforts." CT has proven to be a
valuable clinical tool, and its use has grown rapidly. According to a 2008 IMV Medical
Information Division report, approximately 68.7 million CT exams were performed in the
U.S. in 2007, up from 62 million in 2006. CT provides detailed images of internal organs
and is a common technique used to make medical diagnoses and help guide medical treatment
decisions. However, CT uses a higher radiation dose than most other imaging exams. For the
study, the researchers developed new methodology to estimate cumulative CT radiation doses
and associated radiation-induced cancer risks at the level of the individual patient, by
extracting each patient's CT history from the electronic medical record and applying
standard risk-estimation models that incorporate patient gender and age at exposure. The
study group was comprised of 31,462 adult patients who had diagnostic CT scans at Brigham
and Women's Hospital or the Dana-Farber Cancer Center in 2007 and had undergone a total of
190,712 CT exams over the prior 22 years. Approximately 33 percent of the patients
underwent five or more lifetime CT exams, 5 percent underwent more than 22 exams, and 1
percent underwent more than 38 exams. Fifteen percent received estimated cumulative
effective radiation doses of more than 100 millisieverts (mSv), equivalent to the dose one
would receive from 1,000 chest x-rays. Four percent received over 250 mSv, and 1 percent
received over 399 mSv. The researchers used the BEIR-VII (Biological Effects of Ionizing
Radiation) risk model to estimate lifetime attributable risk (LAR) of cancer for each
patient, based on their CT exposures. Approximately 7.3 percent of the study group had an
estimated LAR of greater than 1 percent, meaning that due to cumulative CT radiation
exposure, their risk of developing cancer increased by 1 percent above the baseline US
cancer risk rate of 42 percent. Among the 315 patients in the top percentile of cumulative
LAR, risk increased by 2.7 to 12 percent.
Eye cells believed to be retinal
stem cells are misidentified
Cells isolated from the eye that many
scientists believed were retinal stem cells are, in fact, normal adult cells,
investigators at St. Jude Children's Research Hospital have found. If retinal stem cells
could be obtained, they might provide the basis for treatments to restore sight to
millions of people with blindness caused by retinal degeneration. Stem cells are immature
cells capable of producing large numbers of adult cells, such as retinal cells.
Researchers believe that stem cells offer the promise of regenerating tissue in organs
such as the eye, brain and heart, damaged by trauma or disease.
The new findings suggest that research on cell therapies to restore blindness should not
concentrate on these eye cells previously believed to be retinal stem cells. More
promising, the scientists said, is research aimed at re-engineering stem cells to develop
into the light-sensitive photoreceptor cells that are lost as a result of retinal
degeneration. Such studies could lead to implantation of such engineered photoreceptor
cells into the eye to restore sight. Led by Michael Dyer, Ph.D., the researchers published
their findings March 30, 2009, in the online early edition of the Proceedings of the
National Academy of Sciences. Dyer is a member of the St. Jude Department of Developmental
Neurobiology. In studies reported in 2000, scientists proposed that the layer of ciliary
epithelial cells lining the inside of the eye, contains retinal stem cells because when
grown in culture dishes these cells formed tiny spheres of about a thousand cells, said
Dyer, the paper's senior author. These spheres, in turn, could be cultured to give rise to
more spheres, reminiscent of the self-renewing capability of stem cells. Also, the
cultured sphere cells showed activation of genes characteristic of adult eye cells.
"The first clue that these cells were not stem cells was that they were
pigmented," Dyer said. "Neural stem cells, in general, and retinal progenitor
cells, in particular, are not pigmented. Nevertheless, the previous finding was met with a
tremendous amount of enthusiasm because of the promise of introducing these cells into the
eye to regenerate photoreceptors lost to blindness." In their studies, Dyer and his
colleagues analyzed the sphere-forming cells in detail to determine whether they were
really retinal stem cells. Painstaking microscopy studies of each cell in the spheres
revealed all were pigmented and had features of ciliary epithelial cells. The researchers
also compared the structure of the sphere-forming cells with those of confirmed stem cells
and other immature cells in the developing retina called progenitor cells. That comparison
revealed fundamental differences between the sphere-forming cells and established stem or
progenitor cells.
The researchers also found that simply culturing the sphere-forming cells in the same
growth medium as is used for stem cells caused them to activate genes characteristic of
stem cells, yet remain adult ciliary epithelial cells.
New approach discovered to lowering
triglycerides
Studies done with laboratory rats suggest
that supplementation of their diet with lipoic acid had a significant effect in lowering
triglycerides, which along with cholesterol levels and blood pressure are one of the key
risk factors in cardiovascular disease.
In the lab animals, supplements of lipoic acid lowered triglyceride levels up to 60
percent. If the effect were the same in humans – which is not yet clear – that
would be a greater impact than found with other dietary supplements, and similar to the
effects of some prescription drugs. The results were just published in the Archives of
Biochemistry and Biophysics, a professional journal. "The extent of triglyceride
reduction was really dramatic, we didn't expect it to be this profound," said Regis
Moreau, an assistant professor with the Linus Pauling Institute at Oregon State
University. "The potential is good that this could become another way to lower blood
triglycerides and help reduce the risk of atherosclerosis. It's pretty exciting."
Lipoic acid is a natural compound found at low levels in some foods, including red meat
and green leafy vegetables. A powerful antioxidant, it's been of considerable research
interest in recent years for its apparent ability to reduce mitochondrial decay in cells
and perhaps slow the process of aging. And it's been used in Europe for decades as a
treatment for the neuropathic complications of diabetes. "Lipoic acid is known to
influence glucose uptake, and bring down blood glucose by increasing its transport into
skeletal muscle," Moreau said. "Less has been done to study its potential value
in reducing triglycerides." Until about 10 years ago, Moreau said, high blood levels
of triglycerides – basically a form of fat – were not thought to be as
significant as cholesterol at predicting atherosclerosis and heart disease. That
perspective has changed, he added, and most experts now see triglycerides as a third
important risk factor for atherosclerosis, along with levels of "good" HDL and
"bad" LDL cholesterol. Widely prescribed medications are often taken to
influence all of these issues, especially when efforts to control them with diet,
exercise, and proper weight have not been effective. However, some of these medications
have unwanted side effects that remain a concern. In this research, it was found that
supplements of lipoic acid appeared to affect triglyceride levels through two pathways.
After eating, lipoic acid supplementation increased the rate of disappearance of
triglycerides in the bloodstream. And supplements also reduced the genetic expression of
enzymes in the liver that synthesize triglycerides.
A missing enzyme conveys major
heart protection in pre-clinical work
Mice born without a certain enzyme can
resist the normal effects of a heart attack and retain nearly normal function in the
heart's ventricles and still-oxygenated heart tissue, according to a study by researchers
at Duke University Medical Center. The findings raise the possibility of a therapy that
could stimulate the growth of blood vessels and limit damage from a heart attack as well
as prevent an attack from occurring at all, the scientists said. Normal mice that went
through the same experiment had full heart attacks, suffering damage to their heart pumps
and a lack of oxygen in their heart tissues, which are typical effects of a heart attack.
The scientists found that in mice lacking the enzyme GNSOR (or S-nitrosoglutathione
reductase) the blood was able to get around the blockage point that normally would cut off
blood to the heart because of remarkable capillary growth in these animals. "There
were blood vessels everywhere in these mice born without the enzyme," said Jonathan
Stamler, M.D., a Duke professor of medicine and biochemistry and author of the study
published in the Proceedings of the National Academy of Sciences online on March 27.
"The hope is that this discovery someday could result in a therapy for new blood
vessel growth that could be a sort of natural bypass in humans. Perhaps it could also
benefit patients with peripheral artery disease, who cannot walk, for example, but who
might be able to grow new blood vessels in their legs." Stamler said his research
group might look into the question of improving peripheral artery disease.
Researchers discover link between
schizophrenia and diabetes
People with schizophrenia are at increased
risk for type 2 diabetes, Medical College of Georgia researchers have found. In a study of
50 people newly-diagnosed with schizophrenia or a related psychotic disorder with no other
known risk factors, 16 percent had either diabetes or an abnormal rate of glucose
metabolism, says Dr. Brian Kirkpatrick, vice chair of the MCG Department of Psychiatry and
Health Behavior. In a similar size control group of people without schizophrenia, none had
signs of or had developed the disease. People with diabetes cannot produce or properly use
insulin, a hormone that converts glucose, starches and other food into energy. “These
findings point toward there being some shared environmental factors or genetic factors
between the development of schizophrenia and diabetes,” he says.
Stem cell breakthrough - Monitoring
the on switch that turns stem cells into muscle
In a genetic engineering breakthrough that
could help everyone from bed-ridden patients to elite athletes, a team of American
researchers—including 2007 Nobel Prize winner Mario R. Capecchi—have created a
"switch" that allows mutations or light signals to be turned on in muscle stem
cells to monitor muscle regeneration in a living mammal. For humans, this work could lead
to a genetic switch, or drug, that allows people to grow new muscle cells to replace those
that are damaged, worn out, or not working for other reasons (e.g., muscular dystrophy).
In addition, this same discovery also gives researchers a new tool for the study of
difficult-to-treat muscle cancers. The full report containing details of this advance is
available online in The FASEB Journal.
"We hope that the genetically-engineered mouse models we developed will help
scientists and clinicians better understand how to make muscle stem cells regenerate
muscle tissue," said Charles Keller, M.D., assistant professor at the University of
Texas Health Science Center and a senior researcher involved in the work. "For our
own work on childhood muscle cancers, we also hope to understand how tumors start and
progress, and to develop therapies that are less toxic than chemotherapy."
The scientists made their discovery by breeding special mice with a specific gene, called
"Cre," which, when activated, can trigger mutations in muscle stem cells. This
Cre trigger is restricted to muscle stem cells and requires a special drug for it to be
activated. In one part of the study, using fluorescent techniques, the researchers were
able to visualize stem cells and their derivatives in order to pinpoint exactly where
muscle tissue was being made. In another part of the study, the scientists were able to
activate tumor-causing mutations in muscle stem cells, providing valuable insights into
the origins of muscle tumors, which have been previously elusive.
UW-Madison study reveals new
options for people with PKU
For people with the genetic condition known
as phenylketonuria (PKU), diet is a constant struggle. They can eat virtually no protein,
and instead get their daily dose of this key macronutrient by drinking a bitter-tasting
formula of amino acids. Yet drink it they must; deviating from this strict dietary regimen
puts them at risk of developing permanent neurological damage.In the near future,
fortunately, a better option may become available. In April, a team of University of
Wisconsin-Madison researchers will publish the second of two key papers showing that a
unique protein derived from whey — known as glycomacropeptide, or GMP — is safe
for people with PKU to eat. GMP is the first known natural protein that is safe for this
group, and these findings are poised to revolutionize the PKU diet. Already, Cambrooke
Foods, a Massachusetts company that specializes in the manufacture of medical foods, is in
the process of developing GMP-fortified snack foods for commercial sale. "It's so
important to individuals on the PKU diet to have new options, to have their diet
liberalized. It's a quality-of-life issue," says Denise Ney, a professor of
nutritional sciences who led the two studies. "Adolescents have an especially
difficult time [staying on the diet], but it's so critical that they do." People with
PKU are born without the enzyme responsible for breaking down phenylalanine, one of the 20
major amino acids that form the proteins we eat in everyday foods. While small amounts of
phenylalanine are essential for PKU patients, excess amounts stay in their bodies
indefinitely and interfere with brain function. Those who go off-diet often suffer from
concentration problems and depression. Some even sustain permanent brain damage. The GMP
protein isolated from whey, on the other hand, is the only known dietary protein that
contains only trace amounts of phenylalanine; absolutely pure GMP, in fact, is completely
phenylalanine-free. The first GMP human feeding trial was published in February in the
Journal of Inherited Metabolic Disorders. In it, Ney and her team describe the experience
of an individual with PKU who volunteered to consume an all-GMP diet for 10 weeks. As the
paper explains, not only did the subject enjoy the GMP-fortified snack bar, pudding and
sports beverage that supplied most of his daily protein, but the amount of phenylalanine
in his blood actually starting going down after he ate these items for a couple of weeks.
Study examines the use of light in
medical therapy
A study published in a special issue of
Photochemistry and Photobiology examines the emerging practice of drug delivery systems
which use the application of light to activate medications in the body. The process uses
biocompatible materials that are sensitive to certain physiological variables or external
physicochemical stimuli. Changes in external or internal body conditions can be used to
achieve control of the delivery. There are drug delivery systems that can respond to small
changes in light, temperature, pH or the concentration of specific substances. Current
research on the drug delivery systems is focused on developing systems capable of
delivering the adequate dose of drug at the target site, avoiding collateral effects and
enhancing the therapeutic efficiency. In the case of cancer, light-sensitive systems are
particularly useful for direct treatment of malignant cells and minimizing damage to
healthy cells.External control of drug delivery offers a number of advantages. The process
enables an easy and precise control of the medication. Switching the light on and off also
triggers or stops the release of medication. This can often be done by the patient.
"Near-infrared (NIR) light is particularly useful as an agent capable of triggering
the drug release," says Carmen Alvarez-Lorenzo, co-author of the study. "NIR is
innocuous, does not cause significant heating in the area of its application and can be
useful in the difficult to access areas of the body."
Time of conception linked to birth
defects in United States
A study published in the April 2009 issue
of the medical journal Acta Pædiatrica is the first to report that birth defect rates in
the United States were highest for women conceiving in the spring and summer. The
researchers also found that this period of increase risk correlated with increased levels
of pesticides in surface water across the United States. Studying all 30.1 million births
which occurred in the U.S. between 1996 and 2002, the researchers found a strong
association between the increased number of birth defects in children of women whose last
menstrual period occurred in April, May, June or July and elevated levels of nitrates,
atrazine and other pesticides in surface water during the same months. While many of these
chemicals, including the herbicide atrazine which is banned in European countries but
permitted in the U.S., are suspected to be harmful to the developing embryo, this is the
first study to link their increased seasonal concentration in surface water with the peak
in birth defects in infants conceived in the same months. The correlation between the
month of last menstrual period and higher rates of birth defects was statistically
significant for half of the 22 categories of birth defects reported in a Centers for
Disease Control database from 1996 to 2002 including spina bifida, cleft lip, clubfoot and
Down's syndrome. "Elevated concentrations of pesticides and other agrochemicals in
surface water during April through July coincided with significantly higher risk of birth
defects in live births conceived by women whose last menstrual period began in the same
months. While our study didn't prove a cause and effect link, the fact that birth defects
and pesticides in surface water peak during the same four months makes us suspect that the
two are related," said Paul Winchester, M.D., Indiana University School of Medicine
professor of clinical pediatrics, the first author of the study. "Birth defects,
which affect about 3 out of 100 newborns in the U.S., are one of the leading causes of
infant death. What we are most excited about is that if our suspicions are right and
pesticides are contributing to birth defect risk, we can reverse or modify the factors
that are causing these lifelong and often very serious medical problems," said Dr.
Winchester, a Riley Hospital for Children neonatalogist. Birth defects are known to be
associated with risk factors such as alcohol, smoking, diabetes or advanced age. However,
the researchers found that even mothers who didn't report these risk factors had higher
overall birth defect rates for babies conceived from April to July. The study relies on
findings by U.S. Geological Survey, the U.S. Environmental Protection Agency and other
agencies on the seasonal variations in nitrates, atrazine and other pesticides in the
surface water.
