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NIH Scientists Find Cause of Rare Immune Disease
Thursday, January 12, 2012

Investigators at the National Institutes of Health have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function. Symptoms of this condition include immune deficiency, autoimmunity, inflammatory skin disorders and cold-induced hives, a condition known as cold urticaria.

The study was led by Joshua Milner, M.D., in the Laboratory of Allergic Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), and Daniel Kastner, M.D., Ph.D., scientific director at the National Human Genome Research Institute (NHGRI). It will appear in the online edition of the New England Journal of Medicine on Jan. 11, 2012.

The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID. "Investigating rare diseases gives researchers more clues about how the healthy immune system functions," says NIAID Director Anthony S. Fauci, M.D. "More importantly, identifying the genetic cause of these disorders opens up possibilities for better disease management and potentially a cure for people who may have spent their entire lives debilitated by severe and unexplained symptoms."

The NIH study involved 27 people from three separate families who all suffered from an inherited form of cold urticaria, an allergic disease characterized by the formation of itchy, sometimes painful hives, episodes of fainting and, in certain cases, life-threatening reactions in response to cold temperatures.

Blood sample analysis revealed that many patients produced antibodies to their own cells and tissues (autoantibodies), making them more susceptible to developing autoimmune disease. More than half had a history of recurrent infections, and laboratory tests revealed that most had low levels of infection-fighting antibodies and low numbers and reduced activity of circulating immune B cells — all symptoms of immune deficiency disease. In three cases, patients had common variable immunodeficiency, a disease that requires frequent intravenous infusions of immune globulin to prevent severe infections. Seven patients suffered from granulomas, inflamed masses of tissue, which formed on their fingers, ears, nose and other parts of their skin.

"This is one of few examples in which the allergy symptom directed us to a genetic syndrome," says Dr. Milner. "In trying to understand the link between this group of conditions — autoimmunity, chronic infections and cold urticaria—we not only identified a disease-causing mutation but uncovered a unique and fascinating genetic mechanism at the crux of allergy, immune defense and self-tolerance."

"This study illustrates the power of multidisciplinary teamwork involving clinicians, geneticists and basic immunologists to get to the heart of seemingly insoluble medical mysteries," says Dr. Kastner. "Our team and colleagues working in the field now have much better odds of improving health outcomes for people with PLAID and for understanding this gene's role in other disorders."

The NIAID investigators teamed up with gene hunting experts in Dr. Kastner's laboratory and found the PLCG2 mutation after performing gene analysis and DNA sequencing studies. The mutation caused the PLCG2 enzyme to function without shutting off. Despite the fact that the enzyme was constantly turned on, immune cells ignored its signaling and did not activate normally.

Investigators performed a series of laboratory experiments to understand how the PLCG2 mutation affects B cells and mast cells, immune cells that contain histamine and other chemicals that are released during an allergic response. Patients' B cells containing the mutated gene fail to turn on normally, leading to their inability to produce antibody, but also an inability to sense when they are producing autoantibodies. Laboratory-developed mast cells containing the mutated gene released chemicals on exposure to cool temperatures, which could explain why the patients developed cold-induced hives.

According to the investigators, their findings suggest that inhibiting PLCG2 activity could be a therapeutic strategy to treat cold-induced hives, autoimmunity and immune deficiency in people with PLAID, but more studies are needed. The study findings also suggest that people previously diagnosed with common variable immunodeficiency disease or with granulomatous diseases could have a PLCG2 gene mutation. Further study is needed to understand PLAID and how mutations in PLCG2 could contribute to other allergic and immunologic disorders.

"These findings are gratifying both for researchers and for people with this disorder," says NHGRI Director Eric Green, M.D., Ph.D. "Furthermore, this study illustrates how genome-analysis methods can empower efforts to unravel the molecular basis of rare genetic diseases."

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Source: NIH
Permalink: http://www.sflorg.com/comm_center/medical/p1016_107.html
Time Stamp: 1/12/2012 at 2:31:59 PM UTC
 

Under Embargo Till: 01:30 UTC March 11, 2010
Posted: 01:30 UTC 03/11/2010

Seaweed Extract May Hold Promise for Non-Hodgkin's Lymphoma Treatment

Thursday, March 11, 2010

Seaweed extract may eventually emerge as a lymphoma treatment, according to laboratory research presented at the second AACR Dead Sea International Conference on Advances in Cancer Research.

Lymphoma is a cancer of the immune system and is classified into Hodgkin’s and non-Hodgkin’s types, which are then further classified into B-cell and T-cell groups.

Some forms of B-cell lymphoma are especially resistant to standard treatment and thus new therapies are needed,” said Mohammad Irhimeh, Ph.D., assistant professor of hematoncology and stem cells at the Hashemite University in Jordan. “In this study, we looked at a new treatment strategy using novel active compounds derived from a natural source of seaweed.”

Seaweeds containing fucoidan, a sulfated polysaccharide similar to heparin in chemical structure, have been reported to have anti-tumor activity in mice and some cell lines.

For the current study, Irhimeh and colleagues at the University of California, Berkeley, and Royal Hobart Hospital in Australia treated lymphoma cell lines with a commercially available seaweed extract.

They found that the extract had an inhibitory effect on the growth of lymphoma cell lines, while leaving the control healthy cells intact. The researchers also noted a significant pattern of activity in the genes known to be linked with apoptosis, or cell death, in lymphoma.

Irhimeh said they would continue to study the mechanism of action for these biological effects and had a goal of conducting phase II or III clinical trials.

Source: American Association for Cancer Research
Permalink: http://www.sflorg.com/comm_center/medical/p1000_106.html
Time Stamp: Time Stamp: 3/11/2010 at 01:30:00 UTC
 

Under Embargo Till: 21:00 UTC March 10, 2010
Posted: 21:00 UTC 03/10/2010

Years of Smoking Associated with Lower Parkinson’s Risk, Not Number of Cigarettes Per Day

Wednesday, March 10, 2010

Researchers have new insight into the relationship between Parkinson's disease and smoking. Several studies have shown that smokers have a lower risk of developing Parkinson’s disease. A new study published in the March 10, 2010, online issue of Neurology ®, the medical journal of the American Academy of Neurology, shows that smoking for a greater number of years may reduce the risk of the disease, but smoking a larger number of cigarettes per day may not reduce the risk.

These results could guide the development of studies on various tobacco components with animal models to help understand the relationship between smoking and Parkinson’s disease,” said study author Honglei Chen, MD, PhD, of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “Research to reveal the underlying chemicals and mechanisms is warranted; such studies may lead to a better understanding of the causes of Parkinson’s disease. However, given the many adverse consequences of smoking, no one would suggest smoking in order to prevent Parkinson’s disease.”

The study involved 305,468 AARP members age 50 to 71 who completed a survey on diet and lifestyle at the time and again about 10 years later. During that time, 1,662 of the people had developed Parkinson’s disease, or about one-half of one percent.

Current smokers were 44 percent less likely to develop Parkinson’s disease than people who had never smoked. People who had smoked in the past and quit were 22 percent less likely to develop Parkinson’s than people who had never smoked.

People who smoked for 40 or more years were 46 percent less likely to develop Parkinson’s disease than people who never smoked. Those who smoked for 30 to 39 years were 35 percent less likely to have the disease than nonsmokers. In contrast, those who smoked for one to nine years were only eight percent less likely to get the disease.

The risk of developing Parkinson’s disease did not change based on how many cigarettes a person smoked per day.

Chen noted that studies have shown that smoking is not associated with a slower progression of the disease once Parkinson’s develops or a reduced risk of death, so he said there is no evidence to support the use of nicotine or other smoking-related chemicals in treating the disease.

The study was supported by the National Institutes of Health, the National Institute of Environmental Health Sciences and the National Cancer Institute.

The American Academy of Neurology, an association of more than 22,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Parkinson’s disease, ALS (Lou Gehrig’s disease), dementia, West Nile virus, and ataxia.

Source: American Academy of Neurology
Permalink: http://www.sflorg.com/comm_center/medical/p999_105.html
Time Stamp: 3/10/2010 at 21:00:00 UTC
 

Under Embargo Till: 21:00 UTC March 09, 2010
Posted: 21:00 UTC 03/09/2010

Vaccinating Children For Flu May Help Prevent Transmission

Tuesday, March 9, 2010

Immunizing children and adolescents with inactivated influenza vaccine resulted in reduced rates of influenza in their community compared to a similar community in which children did not receive the vaccine, suggesting that vaccinating children may help prevent transmission of the virus and offer protection for unimmunized community residents, according to a study in the March 10 issue of JAMA.

Influenza is a major cause of illness and death, resulting in an estimated 200,000 hospitalizations and 36,000 deaths annually in the United States alone. “Current vaccine policy focuses on immunizing those at high risk of complications of influenza. As a component of a broader policy to prevent the spread of influenza and reduce its complications, using immunization to interrupt community-wide transmission of influenza may be effective for protecting the entire population, including those at high risk,” the authors write. They add that children and adolescents appear to play an important role in the transmission of influenza, and that selective vaccination against influenza among this group may interrupt virus transmission and protect those not vaccinated.

Mark Loeb, M.D., M.Sc., of McMaster University, Hamilton, Ontario, Canada, and colleagues assessed whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members. Because randomizing entire communities to test the indirect benefit of vaccinating children and adolescents against influenza is not feasible in most settings, the researchers conducted their study among Hutterite (of the Anabaptist faith) colonies, which are rural communities found mostly in western Canada. “These tightly knit communities resemble extended families but are composed of single families each residing in their own house, where children and adolescents between the ages of 3 years and 15 years attend school. Approximately 60 to 120 people reside on each colony,” the authors write.

This trial included 947 Canadian children and adolescents ages 3 to 15 years who received study vaccine and 2,326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta, Saskatchewan, and Manitoba. Follow-up began in December 2008 and ended in June 2009. Children were randomly assigned according to community to receive standard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine, which was used as a control.

The average vaccine coverage among healthy children of clusters assigned to the influenza vaccine was 83 percent, which was similar to the average vaccine coverage among colonies assigned to hepatitis A vaccine (79 percent). Laboratory-confirmed influenza was detected in 119 nonrecipients: 39 (3.1 percent) in the colonies assigned to influenza immunization and 80 (7.6 percent) in colonies assigned to hepatitis A. The level of indirect vaccine protective effectiveness was 61 percent.

Among all study participants (those who were and those who were not vaccinated), 80 of 1,773 (4.5 percent) in the influenza vaccine colonies and 159 of 1,500 (10.6 percent) in the hepatitis A vaccine colonies had confirmed influenza illness for an overall protective effectiveness of 59 percent. No serious vaccine adverse events were observed.

Considering for instance the rapid spread of influenza A(H1N1) in the 2009 pandemic, understanding whether influenza transmission can be prevented or reduced by immunizing children is of high priority so that groups such as pregnant women and aboriginal populations who are at high risk of complications may potentially be indirectly protected,” the authors write.

Our findings offer experimental proof to support selective influenza immunization of school aged children with inactivated influenza vaccine to interrupt influenza transmission. Particularly, if there are constraints in quantity and delivery of vaccine, it may be advantageous to selectively immunize children in order to reduce community transmission of influenza.”

Source: American Medical Association
Permalink: http://www.sflorg.com/comm_center/medical/p997_104.html
Time Stamp: 3/9/2010 at 21:00:00 UTC
 

Under Embargo Till: 18:00 UTC March 09, 2010
Posted: 18:00 UTC 03/09/2010

Reovirus May be a Novel Approach to Prostate Cancer Treatment

Tuesday, March 9, 2010

Researchers in Canada have detected a novel oncolytic viral therapy against prostate cancer with use of a virus called the reovirus, according to study results published in Cancer Research, a journal of the American Association for Cancer Research.

The respiratory, enteric, orphan virus (commonly known as reovirus) is a non-attenuated, environmental virus that has shown oncolytic potential against many types of cancer, specifically lymphoid, ovarian, breast, pancreatic and high grade glioma cancer, according to the study. This is the first time the virus has been studied against prostate cancer.

The reovirus is a very common, ubiquitous virus that most people are exposed to. As far as we know, it doesn’t cause any significant illness in humans, even though when someone is exposed to it, it manifests, at most, as a mild respiratory infection or mild diarrhea,” said researcher Don Morris, M.D., Ph.D., medical oncologist in the Department of Oncology at the Tom Baker Cancer Center in Alberta, Canada.

For the treatment of localized prostate cancer, we found that the reovirus is safe and has evidence of specific tumor vs. normal prostate cell efficacy,” added Morris.

Using preclinical and clinical settings, Morris and colleagues examined the efficacy of the reovirus as an experimental therapeutic for prostate cancer in vitro and in vivo. Among the six patients who participated in the study, all had early-stage, organ-confined prostate cancer. Each patient underwent a single intralesional virus injection into a suitable prostate cancer nodule via transrectal ultrasound guidance. Three weeks later, Morris and colleagues removed the prostate as part of the patient’s standard treatment for correlative science analysis.

Findings showed safety and efficacy with minimal toxicity and no viral replication in the normal parts of the prostate, according to Morris. Cancer cell death was evident in the prostate. Studies to date have suggested that the virus’ side effects are relatively modest, consisting of mild, self-limiting, flu-like symptoms.

Our results are a stepping stone into future prostate cancer clinical trials with another category of cancer therapeutics,” he said.

Robert Clarke, Ph.D., D.Sc., professor of oncology at Lombardi Comprehensive Cancer Center at Georgetown University and an editorial board member of Cancer Research, agreed, stating that he believes this study is worthy of subsequent clinical trials of the reovirus as a possible way of treating some prostate cancers.

People have known of this application of the reovirus in trials, but no one to my knowledge has conducted studies in prostate cancer,” said Clarke, who was not associated with this study. “I think this is an interesting approach. There is not a lot done in oncolytics, but clearly it is an area that is getting increasing attention, and we need everything we can get our hands on to make a difference in these patients.”

Funding for this research was provided by the Alberta Cancer Foundation, Oncolytics Biotech Inc. and the Prostate Cancer Research Foundation of Canada.

Source: American Association for Cancer Research
Permalink: http://www.sflorg.com/comm_center/medical/p994_103.html
Time Stamp: 3/9/2010 at 18:00:00 UTC
 

Under Embargo Till: 18:00 UTC March 09, 2010
Posted: 18:00 UTC 03/09/2010

Obesity Linked to Poor Colon Cancer Prognosis

Tuesday, March 9, 2010

Obese patients with colon cancer are at greater risk for death or recurrent disease compared to those who are within a normal weight range, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Obesity has long been established as a risk factor for cancer, but our study in colon cancer patients shows that obesity predicts a poorer prognosis after the cancer is surgically removed,” said Frank A. Sinicrope, M.D., professor of medicine and oncology at the Mayo Clinic in Rochester.

There are approximately 150,000 new cases of colon cancer diagnosed each year in the United States, and colon cancer tends to affect men and women equally, said James Abbruzzese, M.D., chairman of the Department of Gastrointestinal Medical Oncology at The University of Texas M. D. Anderson Cancer Center and an editorial board member of Clinical Cancer Research.

More studies are now demonstrating that obesity plays a role as an independent risk factor for poorer patient prognosis that is unrelated to stroke or heart disease,” said Abbruzzese.

Remarkably though, many patients remain unaware of the risk associated between obesity and cancer. Results of a recent survey from the American Institute for Cancer Research showed that only 51 percent of the participants knew about the link between obesity and cancer, compared with 94 percent who were aware of the increased cancer risk associated with tobacco use, and 87 percent who knew of the increased cancer risk associated with sun exposure.

For the current study, Sinicrope and colleagues evaluated 4,381 patients with stage II or stage III colon cancer who had received adjuvant chemotherapy in clinical trials. Of these patients, 20 percent were obese.

Obesity was significantly linked with poorer overall survival and was independent of other variables analyzed. The prognostic impact was stronger in men than in women, and men in the highest body mass index category for obesity had a 35 percent increased risk of death compared to normal weight patients. The weaker effect in women is consistent with studies that have shown a lower risk of developing colon cancer in obese women compared to obese men.

We do not know if this is due to biology or the way we measure obesity,” said Sinicrope. “Body mass index is a limited measure and there is evidence that abdominal fat may be a better predictor of colon cancer risk and perhaps prognosis in men than in women. There is also the potential influence of menopausal status and hormone replacement therapy in women.”

Source: American Association for Cancer Research
Permalink: http://www.sflorg.com/comm_center/medical/p993_102.html
Time Stamp: Time Stamp: 3/9/2010 at 18:00:00 UTC
 

Secondary Stroke Prevention Needs Improvement

Tuesday, February 16, 2010

New research finds that one out of 12 people who have a stroke will likely soon have another stroke, and one out of four will likely die within one year. Researchers say the findings highlight the vital need for better secondary stroke prevention. The study is published in the February 16, 2010, issue of Neurology®, the medical journal of the American Academy of Neurology.

For the study, scientists searched a state hospital discharge database and identified 10,399 people in South Carolina with an average age of 69 who had a stroke in 2002. Of the participants, 23 percent were younger than 65 years old at the time of the initial stroke. Eighteen percent went on to have a recurrent stroke within four years. The study also included the number of heart attacks or deaths within this time period.

The study found 25 percent of people who had a stroke died within one year and eight percent of people had another stroke within one year. The risk for both events rose steadily after one year. The cumulative risk at the end of four years, for example, was: 18.1 percent for recurrent stroke, 6.2 percent for heart attack, 41.3 percent for death by any cause, 26.7 percent for vascular death and 52.5 percent for combined events, any recurrent stroke, heart attack or death, whichever occurred first.

“Furthermore, the risk of recurrent stroke was between three and six times higher than the risk of heart attack at different points during the study,” said author Wuwei (Wayne) Feng, MD, MS, with the Department of Neuroscience at the Medical University of South Carolina. “Our findings suggest that South Carolina and possibly other parts of the United States may have a long way to go in preventing and reducing the risk factors for recurrent strokes.”

The risk of a recurrent stroke, heart attack or death was higher for African-Americans compared to Caucasians and also increased with age and number of other disorders in addition to stroke itself.

Stroke is the third leading cause of death in the United States and South Carolina had the second highest stroke death rate in the nation in 2003.

The study was supported by the South Carolina Center for Economic Excellence in Stroke and Health Sciences South Carolina.

The American Academy of Neurology, an association of more than 22,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as multiple sclerosis, restless legs syndrome, Alzheimer’s disease, narcolepsy, and stroke.

Source: American Academy of Neurology
Permalink: http://www.sflorg.com/comm_center/medical/p989_101.html
Time Stamp: 2/16/2010 at 2:09:08 AM UTC
 

Non-Invasive Technique Blocks a Conditioned Fear in Humans

Wednesday, December 9, 2009

Scientists have for the first time selectively blocked a conditioned fear memory in humans with a behavioral manipulation. Participants remained free of the fear memory for at least a year. The research builds on emerging evidence from animal studies that reactivating an emotional memory opens a 6-hour window of opportunity in which a training procedure can alter it.

"Our results suggest a non-pharmacological, naturalistic approach to more effectively manage emotional memories," said Elizabeth Phelps, Ph.D., of New York University, a grantee of the National Institutes of Health’s National Institute of Mental Health (NIMH).

Phelps and NIMH grantee and NYU colleague Joseph LeDoux, Ph.D., led the research team that reports on their discovery online Dec. 9, 2009 in the journal Nature.

"Inspired by basic science studies in rodents, these new findings in humans hold promise for being translated into improved therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD)," said NIMH Director Thomas R. Insel, M.D.

The results add support to the hypothesis that emotional memories are reconsolidated — rendered vulnerable to being modified — each time they are retrieved. That is, reactivating a memory opens what researchers call "reconsolidation window," a time-limited period when it can be changed.

"This adaptive update mechanism appears to have evolved to allow new information available at the time of retrieval to be incorporated into the brain’s original representation of the memory," explained Phelps.

Earlier this year, LeDoux and colleagues exploited this potentially clinically important insight to erase a fear memory in rats. They first conditioned rats to fear a tone by pairing it with intermittent shocks. A day later, the rats were re-exposed to the tone, reactivating the fear memory. They then underwent a process to rewrite the fear, called extinction training, in which the tone was repeatedly presented without shocks.

However, the timing of this extinction training proved critical. Fear of the stimulus was erased only in rats trained within a 6-hour reconsolidation window after re-exposure to the feared tone. Fear responses returned in animals trained after the window closed, when the memory had apparently already solidified.

Normally, extinction training suppresses but does not erase the original fear memory. By first reactivating it — sounding the tone — just prior to extinction training, LeDoux and colleagues permanently erased the fear memory. In the new study, Phelps and colleagues similarly conditioned human participants to fear colored squares by intermittently pairing them with mild wrist shocks.

As with the rats, a day later, the memory was first reactivated by re-exposing participants to the feared squares. A measure of nervous system arousal confirmed that they experienced a fear response. Extinction training — repeated trials of exposure to the colored squares without shocks — followed.

Again as in the rats, a day later, the fear response was banished only in human participants who underwent the extinction training soon after the fear reactivation. Those trained after the 6-hour consolidation window remained afraid of the squares — as did a control group that received extinction training without first experiencing reactivation of the fear memory.

In a follow-up experiment to gauge long-term effects a year later, 19 of the original participants received a potent regimen to re-instate the fear: four shocks followed by presentations of the colored squares.

Remarkably, those who had undergone extinction training within the reconsolidation window were largely spared significant effects. By contrast, those whose training had been delayed 6 hours or who hadn’t experienced fear memory reactivation prior to extinction training experienced significant reinstatement of the fear response.

In a similar experiment, the researchers also confirmed that the fear memory was blocked only for the specific colored square for which fear memory was reactivated prior to extinction training. The effect did not generalize to a differently colored square associated with the shocks. This indicated that memory re-writing during reconsolidation is highly specific and that prior reactivation with the specific stimuli is critical.

"Timing may have a more important role in the control of fear than previously appreciated," Phelps suggested. "Our memory reflects our last retrieval of it rather than an exact account of the original event."

Evidence suggests that the behavioral manipulation may work through the same molecular mechanisms as experimental medications under study for quelling traumatic emotional memories.

"Using a more natural intervention that captures the adaptive purpose of reconsolidation allows a safe and easily implemented way to prevent the return of fear," suggest the investigators.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure.

More Information: Anxiety Disorders
More Information: Post-Traumatic Stress Disorder (PTSD)
Source: NIH
Permalink: http://www.sflorg.com/comm_center/medical/p984_100.html
Time Stamp: 12/9/2009 at 7:01:12 PM UTC
 

Under Embargo Till: 20:00 UTC December 07, 2009
Posted: 20:00 UTC 12/07/2009

With Amino Acid Diet, Mice Improve After Brain Injury

Monday, December 7, 2009

Neurology researchers have shown that feeding amino acids to brain-injured animals restores their cognitive abilities and may set the stage for the first effective treatment for cognitive impairments suffered by people with traumatic brain injuries.

We have shown in an animal model that dietary intervention can restore a proper balance of neurochemicals in the injured part of the brain, and simultaneously improves cognitive performance,” said study leader Akiva S. Cohen, Ph.D., a neuroscientist at The Children’s Hospital of Philadelphia.

If these results in mice can be translated to human medicine, there would be a broad clinical benefit. Every 23 seconds, a man, woman or child in the United States suffers a traumatic brain injury (TBI). The primary cause of death and disability in children and young adults, TBI also accounts for permanent disabilities in more than 5 million Americans. The majority of those cases are from motor vehicle injuries, along with a rising incidence of battlefield casualties.

Although physicians can relieve the dangerous swelling that occurs after a TBI, there are currently no treatments for the underlying brain damage that brings in its wake cognitive losses in memory, learning and other functions.

The animals in the current study received a cocktail of three branched chain amino acids (BCAAs), specifically leucine, isoleucine and valine, in their drinking water. Previous researchers had shown that people with severe brain injuries showed mild functional improvements after receiving BCAAs through an intravenous line.

BCAAs are crucial precursors of two neurotransmitters—glutamate and gamma-aminobutyric acid, or GABA, which function together to maintain an appropriate balance of brain activity. Glutamate excites neurons, stimulating them to fire, while GABA inhibits the firing. Too much excitement or, too little, and the brain doesn’t work properly. A TBI upsets the balance.

In particular, a TBI frequently damages the hippocampus, a structure deep in the brain involved in higher learning and memory. In the current study, the researchers found that an injury to the hippocampus reduced levels of BCAAs. Although overall levels of glutamate and GABA were unchanged, the loss of BCAAs disturbed the critical balance of neurotransmitters in the hippocampus, making some localized regions more excitable and others less excitable. Cohen’s team tested the hypothesis that providing dietary BCAAs would restore the balance in neural response.

In this study, Cohen’s study team first created standardized brain injuries in mice, and one week later compared the animals’ conditioned fear response to that of uninjured mice. A week after receiving a mild electric shock in a specific cage, normal mice tend to “freeze” when placed in the same cage, anticipating another shock. The brain-injured mice demonstrated fewer freezing responses—a sign that they had partially lost that piece of learning.

On the other hand, brain-injured mice that received a diet of BCAAs showed the same normal response as the uninjured mice. The BCAA cocktail had restored their learning ability.

In addition to the behavioral results, the team conducted electrophysiological experiments in slices of hippocampus from brain-injured and non-injured mice, and showed that BCAA restored a normal balance of neural activity. “The electrophysiological results were consistent with what we saw in the animals’ functional recovery,” said Cohen.

If the results in mice can be reproduced in people, patients with traumatic brain injuries could receive the BCAAs in a drink. Cohen suggests that BCAAs as a dietary supplement could have a more sustained, measured benefit than that seen when patients receive BCAAs intravenously, in which the large IV dose may flood brain receptors and have more limited benefits.

Although much work remains to be done to translate the finding into a therapy, Cohen expects to collaborate over the next year with other researchers in an early-phase clinical trial of dietary BCAAs in patients with mild to moderate TBI.

The National Institutes of Health provided funding for this study. Cohen’s co-authors were Jeffrey Cole, Ph.D., Christina M. Mitala, Ph.D., Suhali Kundu and Itzhak Nissim, Ph.D., all of Children’s Hospital; Jaclynn A. Elkind of the University of Pennsylvania; and Ajay Verma, M.D., Ph.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md. Cohen and Nissim are also on the faculty of the University of Pennsylvania School of Medicine.

The study appears today in the online issue of the Proceedings of the National Academy of Sciences.

Source: Children's Hospital of Philadelphia
Permalink: http://www.sflorg.com/comm_center/medical/p974_99.html
Time Stamp: 12/7/2009 at 20:00: UTC
 

First Human Embryonic Stem Cell Lines Approved for Use Under New NIH Guidelines

Friday, December 4, 2009

NIH Director Francis S. Collins, M.D., Ph.D., today announced the approval of the first 13 human embryonic stem cell (hESC) lines for use in NIH-funded research under the NIH Guidelines for Human Stem Cell Research adopted in July 2009.

"I am happy to say that we now have human embryonic stem cell lines eligible for use by our research community under our new stem cell policy," Dr. Collins said. "In accordance with the guidelines, these stem cell lines were derived from embryos that were donated under ethically sound informed consent processes. More lines are under review now, and we anticipate continuing to expand this list of responsibly derived lines eligible for NIH funding."

Children's Hospital Boston developed 11 of the approved lines and Rockefeller University in New York City developed two of the approved lines. An additional 96 lines have been submitted to NIH for either internal administrative review or consideration by the external Working Group for Human Embryonic Stem Cell Eligibility Review and the NIH Advisory Committee to the Director (ACD), including more than 20 that will be considered by the ACD on December 4, 2009. The working group provides findings to the ACD, which makes recommendations to the NIH Director, who decides whether the hESCs may be used in NIH-funded research and lists those deemed eligible on the NIH Human Embryonic Stem Cell Registry.

Research using hESCs is already yielding information about the complex events that occur during human development. Researchers hope that eventually cells differentiated from hESCs may be used to treat a myriad of diseases, conditions, and disabilities and to test the safety of new drugs in the laboratory.

On March 9, 2009, President Obama issued Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The executive order states that the Secretary of Health and Human Services, through the Director of NIH, may support and conduct responsible, scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent permitted by law.

The guidelines implement the executive order, as it pertains to extramural NIH-funded stem cell research, establish policy and procedures under which the NIH will fund such research, and help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law.

Children's Hospital Boston and Rockefeller University submitted information about the informed consent process for embryo donation to the NIH administrative review process, which confirms that the submissions met specific requirements regarding informed consent for embryo donation as detailed in the guidelines.

More than 30 NIH grants funded in the 2009 fiscal year totaling more than $20 million proposed to use hESCs; these grants have been restricted until approved lines became available on the NIH registry. With today's announcement and following NIH approval, these principal investigators may obtain registry-listed hESCs, if they are appropriate for their project, from the owners of the lines and proceed with their research. This group of grants includes research using hESCs for the therapeutic regeneration of diseased or damaged heart muscle cells, developing systems for the production of neural stem cells and different types of neurons from hESCs in culture, and developing a cell culture system for the large scale production and self-renewal of hESCs.

In addition, a number of Challenge Grant applications, which could be funded through the American Recovery and Reinvestment Act in the 2010 fiscal year, proposed to use hESCs. Researchers examining other topics that could benefit from the use of hESCs are encouraged to apply for funding using these approved lines.

More Information:
The NIH Guidelines for Human Stem Cell Research: http://stemcells.nih.gov/policy/2009guidelines.htm.
Human Embryonic Stem Cell Registry of approved hESCs: http://grants.nih.gov/stem_cells/registry/current.htm
For additional information on stem cells and NIH research: http://stemcells.nih.gov/
Source: NIH
Permalink: http://www.sflorg.com/comm_center/medical/p969_98.html
Time Stamp: 12/4/2009 at 3:30:39 AM UTC
 

Under Embargo Till: 21:00 UTC December 02, 2009
Posted: 21:00 UTC 12/02/2009

Ecstasy May Be Linked to Sleep Apnea

Wednesday, December 2, 2009

New research shows that recreational users of the drug known as ecstasy may be at a higher risk for sleep apnea.

People who use ecstasy need to know that this drug damages the brain and can cause immediate and dangerous problems such as sleep apnea,” said study author Una McCann, MD, of The John Hopkins School of Medicine in Baltimore.

Sleep apnea is a common disorder that causes one or more pauses in breathing during sleep. It has been linked to cognitive problems as well as stroke and heart attack. An estimated 15 million Americans are affected by sleep apnea. For the study, researchers tested 71 people who had used ecstasy, also known as MDMA, 25 times or more, and 62 people who had never used ecstasy. Participants were hooked up to a machine which measured their breathing and nasal pressure while they were asleep.

The study found that ecstasy users had more than eight times the risk of sleep apnea compared to people who did not use the drug. The two groups had a similar rate of people with mild apnea (21 percent of MDMA users and 27 percent of non-users), but only ecstasy users had moderate or severe apnea, with eight cases (13 percent) of moderate apnea and one case (about one percent) of severe apnea.

The study also found that the longer a person had used ecstasy, the higher the rate of sleep apnea episodes. Obesity has been shown to be a risk factor for sleep apnea. The study found that the risk of apnea was higher for ecstasy users than for those who were obese.

Our findings may be explained by how ecstasy damages neurons related to serotonin, a chemical in the brain that is involved in sleep regulation and breathing, among other important functions,” said McCann. “Sleep apnea in itself is dangerous, but it can also contribute to thinking problems in people who use ecstasy because chronic sleep disruption is known to have a negative effect on how a person functions during the daytime.”

The study was supported by the National Institute on Drug Abuse.

The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson’s disease, and multiple sclerosis.

The study is published in the December 2, 2009, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Source: American Academy of Neurology
Permalink: http://www.sflorg.com/comm_center/medical/p964_97.html
Time Stamp: 12/2/2009 at 21:00:00 UTC

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