2/02/2009

Crippled communication network in brain may be associated with autism

The two most prevalent forms of genetic mental retardation, Fragile X and Down syndromes, may share a common cause, according to researchers at Stanford University School of Medicine. The problem, a crippled communication network in the brain, may also be associated with autism.Although the genetics...

The two most prevalent forms of genetic mental retardation, Fragile X and Down syndromes, may share a common cause, according to researchers at Stanford University School of Medicine. The problem, a crippled communication network in the brain, may also be associated with autism.



Although the genetics of the disorders are very different, the end result for the brain seems to be the same, said Daniel Madison, PhD, associate professor of molecular and cellular physiology. "It's as if you had every light in your house wired to just one or two switches, rather than having many switches that can be flipped on or off in complex combinations to control the lighting in one room," he said.


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Madison is the senior author of a paper on Fragile X syndrome in mice, which will be published in the April 11 issue of the Journal of Neuroscience. He published a related study on mice with Down syndrome symptoms in the Feb. 15 issue of the Journal of Physiology.



Madison is a member of Stanford's Down Syndrome Research Center, started in 2003 by researchers at the School of Medicine and Lucile Packard Children's Hospital to accelerate the application of research to effective treatments for the condition.



In the latest study, Madison and postdoctoral scholar Jesse Hanson, PhD, studied Fragile X syndrome, which is a leading cause of mental retardation in this country. Affected people tend to have learning disabilities, distinct physical characteristics such as enlarged ears and a long face, and such behavioral problems as attention deficit disorder, speech disturbances and unusual responses to various sights or sounds. Although it's not known why, about one-third of people with Fragile X also develop autism - a much higher percentage than in the general population. This makes Fragile X, which can be studied in mice, the only genetic model for autism.



As the syndrome's name suggests, the responsible gene, called Fmr1, is located on the X chromosome. Because boys have only one X chromosome while girls have two, boys are usually more severely affected when Fmr1 is mutated. Girls are not immune to the condition, however. A phenomenon called X-inactivation, which randomly silences one member of every X chromosome pair, creates a mosaic of affected and unaffected nerve cells in the brain.



In some conditions linked to the X chromosome, such as hemophilia, the normal cells can cover for their useless peers. Not so for an elite corps of brain neurons. Here, where cooperation and communication are key, a few deadbeats in the mix can be disastrous.



The researchers' discovery of the muddled communication networks in the brain hinged on two advances. One was their creation of an Fmr1 mosaic mouse with brain characteristics similar to those of people with Fragile X. The other was the use of specialized microscopes and tiny needles to eavesdrop directly on individual conversations between two cells. Before this study, investigators relied on a strain of mice in which every cell carried a mutated Fmr1 gene, and they inferred how cells communicated by results from experiments on groups of cells.



The new approach allowed Madison's team to see that cells with a mutated Fmr1 gene have a very selective flaw: they are less likely than normal cells to reach out and form connections, or synapses, with their neighbors. Although normal cells in the mosaic brain can reroute around these potential dead ends, the resulting neural network has fewer cells and is less complex. "If, for example, 10 percent of normal nerve cells are now responsible for half your neural network, the information-carrying capacity of your brain goes down," he said.



Madison said the findings from this study point researchers in a new direction. "Until now the emphasis in the field has been on the receiving, or post-synaptic, side of the synapse," he said. "But these results unequivocally show that the pre-synaptic cells are the important ones in this defect."



The result paralleled the researchers' earlier finding in the brains of the mice with Down syndrome symptoms: more connections are made by fewer cells. "We believe that these reduced-complexity networks are the basis for the mental retardation that occurs with both syndromes," Madison said.



If so, the problem is rooted in early development. Synapse formation appears at first to be completely disordered, with connections between neurons making random paths like hairline cracks racing across a breaking sheet of ice. But as the person or animal begins to learn and remember, the more well-trodden paths, or cracks, connect in purposeful, yet unique ways.



"No two nerve cells will always be connected in the same way in different people," said Madison. "But populations of cells will develop similar connections as the developing brain practices using its own network. If we can compensate for the synaptic deficiency of the mutant cells, we may begin to start to think about ways to increase the mental capacity of patients with Down syndrome or Fragile X."



Source: Stanford University


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More research into genetic link to Alzheimer's disease

Scientists have known for more than a decade that individuals with a certain gene are at higher risk for developing Alzheimers disease. Now a new study helps explain why this is so.The research, led by scientists at the Oklahoma Medical Research Foundation (OMRF), has uncovered a molecular mechanism...

Scientists have known for more than a decade that individuals with a certain gene are at higher risk for developing Alzheimer%26#8217;s disease. Now a new study helps explain why this is so.



The research, led by scientists at the Oklahoma Medical Research Foundation (OMRF), has uncovered a molecular mechanism that links the susceptibility gene to the process of Alzheimer%26#8217;s disease onset. The findings appear in the April 11 issue of The Journal of Neuroscience and may lead to new pathways for development of Alzheimer%26#8217;s therapeutics.


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Approximately 15 percent of the population carries a gene that causes their bodies to produce a lipoprotein%26#8212;a combination of fat and protein that transports lipids (fats) in the blood%26#8212;known as apolipoprotein (Apo) E4. Studies have found that those who inherit the E4 gene from one parent are three times more likely than average to develop Alzheimer%26#8217;s, while those who get the gene from both parents have a tenfold risk of developing the disease.



In the new study, OMRF%26#8217;s Jordan J.N. Tang, Ph.D., and his colleagues discovered that ApoE4 (along with other apolipoproteins) attaches itself to a particular receptor on the surface of brain cells. That receptor, in turn, adheres to a protein known as amyloid precursor protein. The brain cells then transport the entire protein mass inside.



Once inside, cutting enzymes%26#8212;called proteases%26#8212;attack the amyloid precursor protein. These cuts create protein fragments that, when present in the brain for long periods of time, are believed to cause the cell death, memory loss and neurological dysfunction characteristic of Alzheimer%26#8217;s.



Although researchers have known for more than a decade that ApoE4 was involved%26#8212;somehow%26#8212;in development of Alzheimer%26#8217;s, Tang%26#8217;s new study is the first to connect the process of protein fragment formation to ApoE4.



While roughly 1 in 7 people carry the E4 gene, the remainder of the population carry only two variations%26#8212;known as E2 and E3%26#8212;of that gene. These individuals have a markedly lower incidence of Alzheimer%26#8217;s than those who carry the E4 gene. The new study found that ApoE4 produced more protein fragments than did E2 or E3.



%26#8220;ApoE4 apparently interacts better with the receptor than its cousins,%26#8221; said Tang. %26#8220;This may explain why people who carry the E4 gene have a higher risk of developing Alzheimer%26#8217;s.%26#8221;



%26#8220;These findings may allow us to investigate the possibility of therapeutic intervention at different points in the process,%26#8221; said Tang. For example, he said, such efforts might focus on developing a compound to interfere with the receptor%26#8217;s ability to adhere to ApoE4.



%26#8220;There currently is no effective treatment for Alzheimer%26#8217;s disease, so we must explore every possible option to find a way to stop it,%26#8221; he said.



%26#8220;Dr. Tang%26#8217;s study shows a beautiful biochemical connection between a genetic risk factor and the development of a disease,%26#8221; said OMRF President Stephen Prescott, M.D. %26#8220;This work opens the door to the development of alternate methods for treating%26#8212;and perhaps even preventing%26#8212;Alzheimer%26#8217;s.%26#8221;



ApoE4 also has been linked to coronary artery disease. %26#8220;Ultimately, this work could pave the way for similar study of the pathogenesis of other diseases,%26#8221; said Prescott.



Source: Oklahoma Medical Research Foundation


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Stress may make prostate and breast cancer cells resistant to cell death

Scientists from Wake Forest University School of Medicine are the first to report that the stress hormone epinephrine causes changes in prostate and breast cancer cells that may make them resistant to cell death."These data imply that emotional stress may contribute to the development of cancer and ...

Scientists from Wake Forest University School of Medicine are the first to report that the stress hormone epinephrine causes changes in prostate and breast cancer cells that may make them resistant to cell death.



"These data imply that emotional stress may contribute to the development of cancer and may also reduce the effectiveness of cancer treatments," said George Kulik, D.V.M., Ph.D., an assistant professor of cancer biology and senior researcher on the project.



The study results are reported on-line in the Journal of Biological Chemistry and will appear in a future print issue.


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Levels of epinephrine, which is produced by the adrenal glands, are sharply increased in response to stressful situations and can remain continuously elevated during persistent stress and depression, according to previous research. The goal of the current study was to determine whether there is a direct link between stress hormones and changes in cancer cells.



While a link between stress and cancer has been suggested, studies in large groups of people have been mixed.



"Population studies have had contradictory results," said Kulik. "We asked the question, %26#8216;If stress is linked to cancer, what is the cellular mechanism?%26#8217; There had been no evidence that stress directly changes cancer cells."



Studying prostate and breast cancer cells in the laboratory, Kulik and colleagues found that a protein called BAD %26#8211; which causes cell death %26#8211; becomes inactive when cancer cells are exposed to epinephrine.



Kulik said that connection between stress and prostate cancer has been largely unexplored. However, recent studies suggest that these laboratory findings may apply to cancer patients.



"A study from Canada showed that men who took beta blockers for hypertension for at least four years had an 18 percent lower risk of prostate cancer," said Kulik. "These drugs block the effects of epinephrine, which could explain the finding. Another study of men after radical prostatectomy reported increased mood disturbances, which are often associated with elevated stress hormones. Although these studies do not directly address the role of stress hormones, they suggest that stress hormones may play an important role in prostate cancer."



Kulik said the findings have several implications for patients and for researchers.



"It may be important for patients who have increased responses to stress to learn to manage the effects," said Kulik. "And, the results point to the possibility of developing an intervention to block the effects of epinephrine."



Kulik is now studying blood samples of prostate cancer patients to determine if there is a link between levels of stress hormones and severity of disease and has begun studying the effects of epinephrine in mice with prostate cancer.



Source: Wake Forest University Baptist Medical Center


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Milk protein is significantly better than soy at building muscle mass

Got milk? Weightlifters will want to raise a glass after a new study found that milk protein is significantly better than soy at building muscle mass.The study, conducted by a team of researchers at McMaster Universitys Department of Kinesiology, was recently published in the American Journal of Cli...

Got milk? Weightlifters will want to raise a glass after a new study found that milk protein is significantly better than soy at building muscle mass.



The study, conducted by a team of researchers at McMaster University%26#8217;s Department of Kinesiology, was recently published in the American Journal of Clinical Nutrition. It compared how much muscle protein young men gained after completing a heavy weight workout followed by consumption of equivalent amounts of protein as either fluid skim milk or a soy drink.


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"Our thinking going into the study was that milk would be better than soy. We suspected this would be the case because of work done by French researchers. However, we were really impressed by how much greater the gains in muscle protein with milk were," says Sarah Wilkinson, lead researcher and a graduate student in the department of kinesiology.



The findings would suggest that if men consume only skim milk (two cups) after each of their workouts, they would gain almost twice as much muscle in 10 weeks than if they drank the same amount of protein as a soy drink.



"This is an interesting finding, since soy and milk proteins are considered to be complete proteins that are basically equivalent from a nutritional standpoint," explains Stuart Phillips, associate professor of kinesiology, who was also involved in the study. "Our findings clearly show that milk proteins are a superior source of protein in producing muscle mass gains in response to weightlifting."



Scientists also analyzed the composition of milk and soy proteins and did not find remarkable differences. At this stage, researchers are uncertain why milk proteins were so much more effective than soy. However, the two main types of proteins in milk, whey and casein, may have intrinsic properties that are advantageous in terms of supporting muscle growth.



"The plan at this point is to follow this up with a long-term study to see if the findings from this short-term study can be replicated," says Phillips.



Source: McMaster University


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Biodegradeable nanoparticles can infiltrate cancer cells while leaving normal ones alone

Tiny, biodegradable particles filled with medicine may also contain answers to some of the biggest human health problems, including cancer and tuberculosis. The secret is the size of the package.Using an innovative technique they invented, a Princeton University-led research team has created particl...

Tiny, biodegradable particles filled with medicine may also contain answers to some of the biggest human health problems, including cancer and tuberculosis. The secret is the size of the package.



Using an innovative technique they invented, a Princeton University-led research team has created particles that can deliver medicine deep into the lungs or infiltrate cancer cells while leaving normal ones alone. Only 100 to 300 nanometers wide -- more than 100 times thinner than a human hair -- the particles can be loaded with medicines or imaging agents, like gold and magnetite, that will enhance the detection capabilities of CT scans and MRIs.


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"The intersection of materials science and chemistry is allowing advances that were never before possible," said Robert Prud'homme, a Princeton chemical engineering professor and the director of a National Science Foundation-funded team of researchers at Princeton, the University of Minnesota and Iowa State University. "No one had a good route to incorporate drugs and imaging agents in nanoparticles."



Prud'homme will discuss the work April 11 in a talk titled "How Size Matters in the Retention of Nanomaterials in Tissue," to be given at the National Academy of Sciences meeting on Nanomaterials in Biology and Medicine in Washington, D.C.



The new technique, dubbed "Flash NanoPrecipitation," allows the researchers to mix drugs and materials that encapsulate them. Similar mixing techniques previously have been used to create bulkier pharmaceutical products and have proven practical on a commercial scale. The Princeton-led team, which includes chemical engineering professors Yannis Kevrekidis and Athanassios Panagiotopoulos, is the first to apply the technology to the creation of nanoparticles, which are particles measured in billionths of meters.



The nanoparticles are too large to pass through the membrane of normal cells, but will pass through larger defects in the capillaries in rapidly growing solid tumors, Prud'homme said.



Particles in this size range also could improve the delivery of inhaled drugs because they are large enough to remain in the lungs, but too small to trigger the body's lung-clearing defense systems, he said. This trait could maximize the effectiveness of inhaled, needle-free vaccination systems. Prud'homme's research group is part of a Grand Challenges in Global Health research project led by David Edwards of Harvard University and funded by the Bill and Melinda Gates Foundation to develop nanoparticle-based aerosol vaccines for tuberculosis and diphtheria.



"Professor Prud'homme and his group have developed novel nanoparticle systems that are particularly attractive for applications in the developing world" because of their potential for use on a large scale at relatively low cost, Edwards said.



The success of NanoPrecipitation depends in large part on the fact that some molecules are hydrophobic, or water-fearing, while others are hydrophilic, or water-loving. Hydrophobic substances, such as oil, do not mix well with water. Many pharmaceutical compounds, including many current cancer treatments, are hydrophobic, making it difficult to deliver the medications through the bloodstream, given its high concentration of water.



In NanoPrecipitation, two streams of liquid are directed toward one another in a confined area. The first stream consists of an organic solvent that contains the medicines and imaging agents, as well as long-chain molecules called polymers. The polymer chain is like a necklace of pearls with half of the pearls being hydrophopic and the other half being hydrophilic. The second stream of liquid contains pure water.



When the streams collide, the hydrophobic medicines, metal imaging agents and polymers precipitate out of solution in an attempt to avoid the water molecules. The polymers immediately self-assemble onto the drug and imaging agent cluster to form a coating with the hydrophobic portion attached to the nanoparticle core and the hydrophilic portion stretching out into the water. By carefully adjusting the concentrations of the substances, as well as the mixing speed, the researchers are able to control the sizes of the nanoparticles.



The stretched hydrophilic polymer layer keeps the particles from clumping together and prevents recognition by the immune system so that the particles can circulate through the bloodstream. The hydrophobic interior of the particles ensures that they are not immediately degraded by watery environments, though water molecules will, over time, break the particles apart, dispersing the medicine.



Ideally, the particles would persist for six to 16 hours after they were administered intravenously, Prud'homme said, which would theoretically allow enough time for the potent packages to slip into the solid tumor cells they encountered throughout the body.



In the lab, this is precisely the amount of time it takes for water molecules to work their way into the centers of the nanoparticles and degrade them. The team made their particles even more resistant to early degradation by attaching hydrophobic substances, including vitamin E, to the medicines and imaging agents before incorporating them into the particles. Further studies of the controlled release technique currently are under way.



Prud'homme's technique is essentially the opposite of previous techniques for improving drug delivery, which is to attach molecules to drugs to make them more water soluble. "Our advance is to use this technique and turn it around so the drugs stay inside our particles until we want them to leave," he said.



Beyond using size alone to target cancer cells, the team is working with Princeton mechanical and aerospace engineering professor Wole Soboyejo to create nanoparticles that have specific linking molecules on their surfaces. These particles will bond to substances that are more prevalent in cancer cells than normal ones.



Source: Princeton University, Engineering School


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Scientists learn inner workings of cells involved in regenerating livers

The way the liver renews itself may be simpler than what scientists had been assuming. A new study, appearing in the April 13 issue of The Journal of Biological Chemistry, provides new information on the inner workings of cells from regenerating livers that could significantly affect the way physici...

The way the liver renews itself may be simpler than what scientists had been assuming. A new study, appearing in the April 13 issue of The Journal of Biological Chemistry, provides new information on the inner workings of cells from regenerating livers that could significantly affect the way physicians make livers regrow in patients with liver diseases such as cirrhosis, hepatitis, or cancer.


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"The human liver is one of the few organs in the body that can regenerate from as little as 25 percent of its tissue," says Seth Karp, assistant professor of surgery at Harvard Medical School, Boston, and main author of the study. "It is not known how the liver does it, but our results provide some details of what makes the liver so unique."



Although organ regeneration has been observed in many animals, the details of how it happens at the cellular level are still not completely understood. So far, scientists have shown that cells that participate in tissue regeneration behave as if they were part of a growing organ in an embryo. In other words, the cells act as if the liver is growing, as do other organs in a developing embryo.



Many of the proteins that induce organ regeneration have been identified and scientists are now trying to make organs regrow by stimulating these proteins. Regrowing livers this way would be especially useful for patients whose livers are so damaged %26#8211; say, by a tumor that has spread to most of the liver %26#8211; that a large part would be removed. Unless such patients receive the right amount of liver transplant from an organ donor, they do not always survive. Quickly stimulating the growth of the remaining portion of their liver could be their only chance of survival.



To investigate how the liver regenerates, Karp and his colleagues set out to determine which proteins are involved in the regenerating cells. The scientists were also interested in testing whether regenerating cells behave like embryonic ones, as is commonly assumed for other organs. New processes may explain why the liver is so uniquely capable of renewal and repair after injury, the scientists thought.



Karp's team considered two samples of mice. The first consisted of embryonic mice at various stages of development while the second was composed of adult mice to which two-thirds of their liver were removed. Using techniques such as DNA microarrays %26#8211; which determine which genes are active in a cells %26#8211; and software programs that analyze the collected information, the scientists listed all the proteins that help the cells grow and proliferate in both samples.



The results were unexpected. The researchers noticed that only a few proteins were common to both processes. Proteins called transcription factors, which affect DNA in the cell's nucleus, were highly involved in the development of embryos' livers but not in adult liver regeneration. Instead, proteins that help cells proliferate were active in both the developing and regenerating livers.



These findings showed that a regenerating liver does not behave as a developing embryo. Instead, regeneration could actually be only due to an increase in cells that multiply through regular cell divisions, a process called hyperplasia.



The new results may also have important medical implications. Transcription factors are known to be more difficult to manipulate than the other identified proteins. Since the transcription factors were not present in regenerating livers, it might be easier to stimulate liver regeneration by only activating the other identified proteins.



"These results are very encouraging," Karp says. "Not only did we discover that the number of proteins involved in liver regeneration is relatively low, but they don't include transcription factors, so we may be closer to being able to stimulate liver regeneration than we thought."



The next step will be for scientists to understand whether the regenerating cells are stem cells. Studies have shown that adult stem cells are involved in the repair of many organs, but in the case of the liver, the cells repairing it through regeneration may simply be regular cells, not stem cells.



"We think that the liver regrows through a relatively simple process, which could explain its prodigious ability to repair itself," Karp says.



Source: American Society for Biochemistry and Molecular Biology


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Additional genetic risk factors for Crohn's disease identified

An international research teamincluding investigators from Massachusetts General Hospital (MGH) and the Broad Institute of Harvard University and Massachusetts Institute of Technologyhas identified several novel genetic variations associated with the risk of Crohn's disease. One of the identified ge...

An international research team %26#8211; including investigators from Massachusetts General Hospital (MGH) and the Broad Institute of Harvard University and Massachusetts Institute of Technology %26#8211; has identified several novel genetic variations associated with the risk of Crohn's disease. One of the identified genes establishes a role for autophagy, a previously unsuspected biological pathway, in Crohn's disease pathology; and the report documents functional studies which establish that this gene is integral to immune responses to intestinal bacteria. The report will appear in the journal Nature Genetics and is receiving early online release.


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"Our discovery of several new genetic risk factors for Crohn's should improve understanding of the true causes of this disease and reveal new causal pathways that can be targeted therapeutically," says Mark Daly, PhD, of the MGH Center for Human Genetics Research and the Broad Institute, co-senior author of the Nature Genetics paper. "The study takes advantage of new knowledge of genetic variation patterns and new technology for assessing genetic variation that have only recently become available."



A chronic inflammatory bowel disease for which no single causative factor has been identified, Crohn's usually affects the small intestine, causing abdominal pain and chronic diarrhea. Serious symptoms can include ulceration, bleeding, the development of fistulas %26#8211; openings from affected areas into other organs %26#8211; or intestinal blockage. About half a million people in the U.S.are affected by Crohn's, and another half-million have a related condition called ulcerative colitis. Since Crohn's can run in families and is more common in some ethnic populations, it is likely to have genetic components. Previous studies have identified two genetic variations as increasing the risk for Crohn's, but those factors only account for a small percentage of inherited cases.



One of the known risk genes was identified in 2001 at the Broad Institute by Daly and John Rioux, PhD, first author of the current study. That study was instrumental to identifying the structure of human genetic variation, leading to the HapMap project to catalog common variation patterns as a tool for accelerating medical genetic research. The recent completion of HapMap, an effort on which Daly and Broad Institute colleagues played a significant role, has paved the way for the current generation of genome-wide association studies, of which this is an early success story.



In an effort to identify additional genetic risk factors, the research team scanned the entire genome of approximately 1,000 Crohn's patients and 1,000 healthy controls. They tested more than 300,000 genetic variations %26#8211; also called single nucleotide polymorphisms or SNPs %26#8211; and identified several that were strongly associated with Crohn's. Those findings were tested in two additional sets of patients and controls, and the results confirmed strong associations with variations in two genes %26#8211; one of which was identified in a preliminary study this group published in 2006 %26#8211; and one gene-free segment of the genome. They also found likely risk factors may be associated with three other genes.



One of the newly identified genes, called ATG16L1, has been thought to be required for autophagy, a process that leads to programmed cell death and is involved in the process of inflammation. When the research team used RNA interference to suppress the gene's activity in bacterially infected cells, decreased molecular action associated with autophagy confirmed that the process depends on ATG16L1 activity.



"We have shown that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria," says co-author Ramnik Xavier, MD, of the Center for the Study of Inflammatory Bowel Disease in the MGH Gastroenterology Unit and the MGH Center for Computational and Integrative Biology. "We propose that variation in the ATG16L1 gene alters how the body uses autophagy and may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease." Xavier is an assistant professor of Medicine at Harvard Medical School, as is Daly.



Among the other potential genetic risk factors identified are a gene called PHOX2B, which may relate to the activity of neuroendocrine cells in the intestinal lining, and one called NCF4, which like ATG16L1 plays a role in the immune system's response to bacteria. Additional risk factors may exist in areas of the genome not associated with specific genes but possibly regulating the activity of other genes. Further understanding of how these variations contribute to the development of Crohn's should identify new targets for drug development, the authors write.



Source: Massachusetts General Hospital


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Integrating drugs targeted to specific cancer proteins improves efficacy of chemotherapy

Integrating the use of drugs targeted to specific cancer proteins into current chemotherapy regimens to improve the efficacy of systemic treatment is an important clinical goal at Fox Chase Cancer Center. Fox Chase research presented during the 97th Annual Meeting of the American Association for Can...

Integrating the use of drugs targeted to specific cancer proteins into current chemotherapy regimens to improve the efficacy of systemic treatment is an important clinical goal at Fox Chase Cancer Center. Fox Chase research presented during the 97th Annual Meeting of the American Association for Cancer Research in Los Angeles has found that a new chemical agent, MCP110, has a synergistic effect both in vitro and in vivo when used with current chemotherapy drugs such as taxanes (Taxol and Taxotere) and vinca-alkaloid compounds such as vincristine.


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This synergistic effect%26#8212;in which the effect of two agents is greater than the sum of their individual effects%26#8212;appeared when using the combination of MCP110 and Taxol on laboratory cell cultures of human Kaposi%26#8217;s sarcoma and mouse models carrying human lung and colon cancer cells.



%26#8220;Together, these findings indicate that MCP compounds have potential to be effective in combination with other anticancer agents,%26#8221; the authors concluded.



Vladimir Khazak, Ph.D., now director of biology at NexusPharma, Inc., in Langhorne, Pa., and formerly a postdoctoral associate in the Fox Chase laboratory of molecular biologist Erica A. Golemis, Ph.D., presented the research in an AACR poster session. The work also appears in the March 1 issue of the AACR journal Molecular Cancer Therapeutics (%26#8220;In vitro and in vivo synergy of MCP compounds with mitogen-activated protein kinase pathway%26#8212;and microtubule-targeting inhibitors%26#8221;).



The work builds on prior findings published by the team in the Proceedings of the National Academy of Sciences, which first identified MCP compounds, and demonstrated that MCP compounds have the ability to inhibit the growth of cultured cancer cells that depend on interactions of the Ras and Raf oncogenes%26#8212;growth-promoting genes that can transform cells to cancerous ones if the oncogene is activated inappropriately.



The growth signals sent by these oncogenes use a well-traveled enzyme pathway called MAPK (mitogen-activated protein kinase). This pathway is responsible for cell response to various growth factors and is involved in the action of many cancer-causing genes.



A number of new cancer drugs in development such as MCP110 target this pathway to inhibit one or more steps in the growth signaling process. However, many established cancer chemotherapy drugs are cytotoxic%26#8212;cell-killing%26#8212;drugs that work in different ways, such as damaging their DNA or attacking the cells%26#8217; architecture. Several widely used drugs, including paclitaxel (Taxol), docetaxel (Taxotere) and long-time standby vincristine, take the latter approach, targeting important cell components called microtubules.



%26#8220;Very few clinical agents are as successful by themselves as they are in combination,%26#8221; Golemis pointed out. %26#8220;Combination chemotherapies may use two drugs that either have the same target or two different targets. Another approach%26#8212;the one we%26#8217;ve taken here%26#8212;is to combine a pathway-targeted drug with conventional chemotherapy.



%26#8220;We%26#8217;ve found that MCP110 synergizes both with other small molecules targeting the MAPK pathway and with multiple cytotoxic drugs. These studies predict that MCP110 is a potentially useful treatment agent for combination chemotherapy.%26#8221;



Source: Fox Chase Cancer Center


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Important target for development of new therapy for leukemia

Leukemia, or cancer of the bone marrow, strikes some 700 Belgians each year. Scientists are still searching for the cause of many forms of leukemia, including T-cell acute lymphoblastic leukemia, or T-ALL. Now, VIB researchers connected to the Katholieke Universiteit Leuven have identified a new pla...

Leukemia, or cancer of the bone marrow, strikes some 700 Belgians each year. Scientists are still searching for the cause of many forms of leukemia, including T-cell acute lymphoblastic leukemia, or T-ALL. Now, VIB researchers connected to the Katholieke Universiteit Leuven have identified a new player in the development of some 10% of the T-ALL cases: MYB. The scientists have discovered that patients in this group have a duplication of the MYB gene, which increases MYB concentrations. Further research has indicated that MYB might well be an important target for therapies for this group of T-ALL patients.


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T-cell acute lymphoblastic leukemia (T-ALL)



Our bodies%26#8217; white blood cells combat foreign intruders such as viruses and bacteria. However, in leukemia, the formation of white blood cells is disrupted. The cells in the bone marrow that should develop into white blood cells multiply out of control without fully maturing. These blood cells do not function properly and thus jeopardize the production of normal blood cells. Among other consequences, this makes patients more susceptible to infections. T-ALL is a certain form of leukemia in which immature T-cells (a specific type of blood cells) build up very rapidly. T-ALL is the most prevalent form of cancer in children under 14 years of age, striking children between the ages of 2 and 3 in particular. Today, with optimal treatment using chemotherapy, more than half of the children are cured.



Combined action of several players



The search for the mechanisms that cause T-ALL goes on ceaselessly. Discovering these mechanisms will enable the development of targeted therapies, which are preferred over chemotherapy. Scientists know that T-ALL arises only when defects occur in several genes simultaneously. So it is not only important to identify the genes that underlie T-ALL, but also to discover which combinations trigger the disease. This is an important step in the development of specific combination therapies, which are much more effective than therapies that focus on just one target.



A new player



Idoya Lahortiga and Jan Cools in Peter Marynen%26#8217;s group, working with colleagues from Ghent (Belgium) and Rotterdam (the Netherlands), have recently identified MYB as a major player in certain T-ALL cases. Studying the DNA of 107 patients, they found that the MYB gene was duplicated in 9 of them. This duplication results in increased MYB concentrations. The MYB transcription factor is important for the proliferation, survival and differentiation of the precursor cells that precede the formation of blood cells. Scientists also know that MYB is involved in several other forms of cancer.



On the way to a new therapy



The researchers are convinced that MYB can be an important target for the development of a new therapy for T-ALL. They are particularly encouraged by the results they obtained when they suppressed the expression of MYB in T-ALL cell lines. This produced a limited - but therapeutically significant - effect on the cancer cells.



They also obtained a much more significant effect by suppressing two genes at the same time: MYB and NOTCH1. NOTCH1 has recently been identified as an important factor in the development of nearly 70% of T-ALL cases. The effect of inhibiting NOTCH1 is currently being tested on T-ALL patients. This is going very well, but the NOTCH1 inhibitors turn out to have toxic side effects, whereby some patients have to stop the treatment. The results from the VIB researchers in Leuven now demonstrate that the combined inhibition of NOTCH1 and MYB in T-ALL cell lines is very effective. These results raise hopes that scientists will be able to develop a very effective combination therapy - in which the concentration of the toxic NOTCH1 inhibitors is reduced - for the group of patients in which MYB and NOTCH1 play a role. The quest for this therapy will also be a part of the further research efforts of Lahortiga, Cools and Marynen.



Source: Flanders Interuniversity Institute of Biotechnology


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Novel way to clone antigen may aid development of vaccines not only for cancer but also for infectious diseases

In recent years, researchers have worked to develop a number of vaccines to help the immune system fight tumors. Cancer vaccines are not intended to prevent cancer; rather, they are used to boost immune responses to preexisting tumors. Unlike traditional chemotherapy, vaccines have relatively low to...

In recent years, researchers have worked to develop a number of vaccines to help the immune system fight tumors. Cancer vaccines are not intended to prevent cancer; rather, they are used to boost immune responses to preexisting tumors. Unlike traditional chemotherapy, vaccines have relatively low toxicity and, potentially, a high degree of efficacy.



To date, these vaccines have rarely been designed to directly stimulate one of the body's most critical immune responders, the helper T cells. Though helper T cells contain receptors on their cell surfaces that are capable of recognizing and binding to tumor-related antigens, scientists have been stymied by the complex and time-consuming process required to isolate and clone the antigens for vaccine development.


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In working to identify a key tumor antigen in melanoma and other cancers, scientists at The Wistar Institute have now developed a novel way to clone an antigen recognized by a helper T cell. Already, Herlyn's group has used the new cloning technique to identify a new tumor antigen called ribosomal protein L8, or RPL8. Findings on the new cloning method and the newly identified tumor antigen will be published as a Priority Report in the April 15 issue of Cancer Research.



The new antigen-cloning approach may allow scientists to design vaccines capable of directly stimulating helper T cells, aiding the development of vaccines not only for cancer but also for infectious diseases, says Dorothee Herlyn, D.V.M., senior author on the study and a professor in the Molecular and Cellular Oncogenesis and Immunology programs at Wistar.



"Most of the melanoma vaccines currently in development work to activate a type of white blood cell called cytotoxic T-lymphocytes, or CTL," says Herlyn. "Though CTL have the ability to destroy cancer cells, they don't have the ability to call upon the full capabilities of the immune system, as do the helper T cells."



The new tumor antigen discovered in her lab, RPL8, is an ideal vaccine candidate because it has the potential for eliciting both helper T cells and CTL responses, Herlyn says. RPL8 is a protein involved in protein synthesis and is also expressed in normal cells. Herlyn's study shows that RPL8 is over-expressed not only in melanoma, but also in breast cancer cells and gliomas, the most common type of brain tumor, indicating that it has potential as a vaccine for patients with these tumors.



In their study, the researchers used their new cloning technique to clone copies of the RPL8 antigen from a melanoma. The scientists then showed that a peptide of RPL8 could stimulate a response in helper T cell clones and lymphocytes in four out of nine melanoma patients. The antigen created no response in cells taken from healthy donors.



The study also showed that RPL8 might contain multiple regions that are capable of eliciting an immune response, suggesting that RPL8 may be an ideal vaccine target for patients that display this antigen in tumors. According to Herlyn, these findings are important because there aren't many vaccines in development to trigger a helper T cell response for many types of cancer.



"Most of the cloned melanoma antigens that are known to target helper T cells are mutated and individual-specific, meaning that they may work in treating a single individual but will be ineffective in treating a large percentage of patients," Herlyn says.



Herlyn notes that the new antigen-cloning technique developed for this study is a major advance over the cumbersome method previously required to accomplish the task, and she anticipates that experimental vaccine developers will find it of significant value in their work.



Both the new and the old methods begin with the same steps. In order to identify and clone an antigen, researchers start with a melanoma cell or other cell of interest likely to contain relevant antigens. Based on the genes in that cell, they then make a complementary DNA (cDNA) library. Using the resulting cDNA library, the investigators can then express sequences of individual genes in recipient cells to find the cell or cells with cDNA able to stimulate T cells.



The old approach to cloning antigens adds an additional layer of complexity to the process. It requires knowing which cellular marker, or class II human leukocyte antigen (HLA), serves as a restriction element for specific T cells. Researchers must clone this restriction element and other class II HLA and transfer them into recipient cells, along with the cDNA library.



With her new technique, Herlyn expresses the cDNA library in bacteriophages that are incubated with B cells from the same patient from whom the T cells were derived. Because B cells are antigen-presenting cells, once they have picked up, or "eaten," the phages, the B cells will express the peptides that are encoded by the cDNA library. The new process eliminates the need to transfer the HLA genes into recipient cells and match the genes to each T cell type as it permits the B cells to present the peptide to the T cells in context with their own HLA class II.



Herlyn and her group now plan to use the RPL8 antigen to develop a melanoma vaccine for patients with advanced disease. "And because the RPL8 antigen is expressed by breast cancer and gliomas, we may be able to develop a vaccine that could be used to treat these types of cancer, as well."



Source: The Wistar Institute


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Drug selectively kills cancer cells

A drug under study to treat various cancers selectively kills cancer cells because of its affinity for a modified version of a critical heat shock protein they contain, researchers have found.They found in cancer a modified version of heat shock protein 90, or hsp90, which like most heat shock prote...

A drug under study to treat various cancers selectively kills cancer cells because of its affinity for a modified version of a critical heat shock protein they contain, researchers have found.



They found in cancer a modified version of heat shock protein 90, or hsp90, which like most heat shock proteins, promotes cell survival.



They then showed that in breast cancer and leukemia, this modification, called acetylation, confers a strong attraction to investigational drug 17-AAG, says Dr. Yonghua Yang, postdoctoral fellow in molecular oncology in the laboratory of Dr. Kapil Bhalla, director of the Medical College of Georgia Cancer Center.


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"17-AAG blocks the activity of hsp90, which normally binds with ATP, an energy source for cells," says Dr. Yang, who received a training award to present his research at the American Association for Cancer Research Annual Meeting April 14-18 in Los Angeles.



An unfortunate side effect is that 17-AAG also immediately induces hsp70, which can compensate for the cell-supporting activity of hsp90, says Dr. Yang, noting that like hsp90, hsp70 presents a modified form in cancer.



The net effect is that while the drug ably finds its target, to maximize effectiveness it may need to be modified or used in conjunction with another drug to also block hsp70, Dr. Yang says. MCG researchers are in discussions with Novartis and Kosan Pharmaceuticals about how to make one or the other happen.



17-AAG doesn't seem to care much for normal hsp90 or hsp70 in healthy individuals, he says. Modifications in cancer result from environmental triggers, including stress and eating a lot of oxidated foods, such as foods fried at high temperatures or stored for a long time %26#8211; more good reasons to relax and eat a well- balanced diet, Dr. Yang says.



The MCG researchers are now looking at the relationship between the modified hsp90 and breast cancer metastasis and developing antibodies that target hsp90.



Heat shock proteins are called molecular chaperones because of their caretaker role. They activate genes that ultimately make proteins, move proteins around cells and fold them into the proper shape so they'll have the proper function. Chaperones even help proteins group properly and discard old proteins.



Misfolding of proteins, for example, can cause cancer. Molecular chaperones are highly expressed in human cancer and seem resistant to radiation therapy and chemotherapy, according to Dr. Bhalla.



Source: Medical College of Georgia


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Early Alzheimer’s could be diagnosed with electroencephalogram

In a $1.1-million National Institutes of Healths National Institute on Aging study that team members conducted during the last three years, they determined early Alzheimers could be diagnosed with a high rate of accuracy evaluating electroencephalogram (EEG) signals. The study may lead to an earlier...

In a $1.1-million National Institutes of Health%26#8217;s National Institute on Aging study that team members conducted during the last three years, they determined early Alzheimer%26#8217;s could be diagnosed with a high rate of accuracy evaluating electroencephalogram (EEG) signals. The study may lead to an earlier diagnosis, and therefore earlier treatment and improved quality of life, for people at the earliest stages of the disease.


[More:]


According to the Alzheimer%26#8217;s Association, the condition affects more than 5 million Americans, approximately 1.5 percent of the population. That number is only expected to grow. (For information on Alzheimer%26#8217;s disease, visit http://www.alz.org/documents/FSADFacts.pdf.)



Rowan University electrical and computer engineering associate professor Dr. Robi Polikar conducted the research with Dr. Christopher Clark, associate professor of neurology, associate director of the NIH-sponsored Alzheimer's Disease Center at Penn and director of the Penn Memory Center, and with Dr. John Kounios, a Drexel psychology professor.



%26#8220;Individuals in the earliest stage of Alzheimer%26#8217;s disease are often not aware of their progressing memory loss, and family members often believe the changes are simply due to aging,%26#8221; Clark said. %26#8220;Even the patient%26#8217;s personal physician may be reluctant to initiate an evaluation until a considerable degree of brain failure has occurred. The advantage of using a modified EEG to detect these early changes is that it is non-invasive, simple to do, can be repeated when necessary and can be done in a physician%26#8217;s office. This makes it an ideal method to screen elderly individuals for the earliest indication of this common scourge of late life.%26#8221;



The researchers employed signal processing and automated neural network analysis of event related potentials (ERPs) of the EEG signals, monitoring how the patients%26#8217; brains reacted to a series of auditory stimuli.



Clark%26#8217;s team conducted neuropsychological tests, including memory tests, of research subjects and evaluated their scores to decide whether they were suited for the study.



Kounios and his team acquired the EEG data from the participants. They used a specific protocol, called the %26#8220;oddball paradigm with novel sounds,%26#8221; to collect the EEG signals, during which patients hear a series of low- and high-frequency tones as well as some novel sounds. Patients were asked to respond by pressing a button every time they heard the high frequency tone, also known as the %26#8220;oddball%26#8221; tone, which generates ERPs in the EEG. Generally, in the ERP of a person without Alzheimer%26#8217;s, that response registers a peak, the P300, about 300 milliseconds after the %26#8220;oddball%26#8221; tone. People with dementia, particularly Alzheimer%26#8217;s, may exhibit that peak much later than 300 milliseconds, show a much weaker peak or have no peak at all, according to Polikar. Kounios said the P300 signal is generated by areas of the brain that seem to be attacked at an early phase of Alzheimer%26#8217;s disease, but the results are not always conclusive.



Polikar and his students analyzed the data using sophisticated signal processing, pattern recognition and artificial intelligence techniques to explore the hypothesis that the entire ERP signal, not just the P300 indicator, reveals markers that previously have not been associated with Alzheimer%26#8217;s disease.



The teams conducted several experiments, ultimately evaluating the parietal and occipital regions of the brains of 71 patients, some already diagnosed with Alzheimer%26#8217;s and some without Alzheimer%26#8217;s. Their diagnostic accuracy rate was 82 to 85 percent using the EEGs (e.g., it matched evaluations conducted at Penn 82 to 85 percent of the time). Alzheimer%26#8217;s disease cannot be confirmed until a patient has died and his or her brain has been examined. Gold standard tests administered at world-class research facilities, such as Penn, have a 90-percent accuracy rate. However, most people are evaluated at community hospitals and clinics, where the diagnostic accuracy is estimated to be around 75 percent.



Though the study%26#8217;s accuracy rate is under that 90-percent figure, it still means the test potentially could have great value to physicians and patients and their families, and the results are particularly significant for patients who have limited access to teaching hospitals, where they may undergo six to 12 months of evaluation for a diagnosis.



%26#8220;Currently, the state-of-the-art evaluation for Alzheimer%26#8217;s disease is only available to those who have geographic proximity and/or financial ability to access research hospitals, where expert neuropsychologists continuously interview patients and caregivers over six to 12 months to make a diagnosis,%26#8221; said Polikar, principal investigator on the project at Rowan. %26#8220;But most people don%26#8217;t have access to such facilities and instead go to community clinics and hospitals. Our methodology involves just one %26#8216;snapshot%26#8217; that in itself is highly accurate and will be especially beneficial in these locations.%26#8221;



"Modern engineering methods are enabling us to take EEG, an 80-year-old technique for measuring brain activity, and turn it into a cutting-edge tool for diagnosing Alzheimer's disease," Kounios added.



The team members hope that eventually they or other researchers will develop a hand-held device that can be used to conduct similar evaluations as those done by the Rowan/Penn//Drexel group.



%26#8220;We don%26#8217;t envision this replacing a neurologist,%26#8221; Polikar said. %26#8220;We hope it can serve as a first test for those folks who don%26#8217;t have access to research facilities.%26#8221; If the initial test indicates a possible problem, physicians could refer the patient to a research hospital for further evaluation.



%26#8220;Our ultimate goal is to increase the number of patients who are diagnosed earlier so they can start treatment sooner and slow the progress of Alzheimer%26#8217;s and improve their quality of life,%26#8221; Polikar said.



Source: Rowan University


Read More...

Early Alzheimer’s could be diagnosed with electroencephalogram

In a $1.1-million National Institutes of Healths National Institute on Aging study that team members conducted during the last three years, they determined early Alzheimers could be diagnosed with a high rate of accuracy evaluating electroencephalogram (EEG) signals. The study may lead to an earlier...

In a $1.1-million National Institutes of Health%26#8217;s National Institute on Aging study that team members conducted during the last three years, they determined early Alzheimer%26#8217;s could be diagnosed with a high rate of accuracy evaluating electroencephalogram (EEG) signals. The study may lead to an earlier diagnosis, and therefore earlier treatment and improved quality of life, for people at the earliest stages of the disease.


[More:]


According to the Alzheimer%26#8217;s Association, the condition affects more than 5 million Americans, approximately 1.5 percent of the population. That number is only expected to grow. (For information on Alzheimer%26#8217;s disease, visit http://www.alz.org/documents/FSADFacts.pdf.)



Rowan University electrical and computer engineering associate professor Dr. Robi Polikar conducted the research with Dr. Christopher Clark, associate professor of neurology, associate director of the NIH-sponsored Alzheimer's Disease Center at Penn and director of the Penn Memory Center, and with Dr. John Kounios, a Drexel psychology professor.



%26#8220;Individuals in the earliest stage of Alzheimer%26#8217;s disease are often not aware of their progressing memory loss, and family members often believe the changes are simply due to aging,%26#8221; Clark said. %26#8220;Even the patient%26#8217;s personal physician may be reluctant to initiate an evaluation until a considerable degree of brain failure has occurred. The advantage of using a modified EEG to detect these early changes is that it is non-invasive, simple to do, can be repeated when necessary and can be done in a physician%26#8217;s office. This makes it an ideal method to screen elderly individuals for the earliest indication of this common scourge of late life.%26#8221;



The researchers employed signal processing and automated neural network analysis of event related potentials (ERPs) of the EEG signals, monitoring how the patients%26#8217; brains reacted to a series of auditory stimuli.



Clark%26#8217;s team conducted neuropsychological tests, including memory tests, of research subjects and evaluated their scores to decide whether they were suited for the study.



Kounios and his team acquired the EEG data from the participants. They used a specific protocol, called the %26#8220;oddball paradigm with novel sounds,%26#8221; to collect the EEG signals, during which patients hear a series of low- and high-frequency tones as well as some novel sounds. Patients were asked to respond by pressing a button every time they heard the high frequency tone, also known as the %26#8220;oddball%26#8221; tone, which generates ERPs in the EEG. Generally, in the ERP of a person without Alzheimer%26#8217;s, that response registers a peak, the P300, about 300 milliseconds after the %26#8220;oddball%26#8221; tone. People with dementia, particularly Alzheimer%26#8217;s, may exhibit that peak much later than 300 milliseconds, show a much weaker peak or have no peak at all, according to Polikar. Kounios said the P300 signal is generated by areas of the brain that seem to be attacked at an early phase of Alzheimer%26#8217;s disease, but the results are not always conclusive.



Polikar and his students analyzed the data using sophisticated signal processing, pattern recognition and artificial intelligence techniques to explore the hypothesis that the entire ERP signal, not just the P300 indicator, reveals markers that previously have not been associated with Alzheimer%26#8217;s disease.



The teams conducted several experiments, ultimately evaluating the parietal and occipital regions of the brains of 71 patients, some already diagnosed with Alzheimer%26#8217;s and some without Alzheimer%26#8217;s. Their diagnostic accuracy rate was 82 to 85 percent using the EEGs (e.g., it matched evaluations conducted at Penn 82 to 85 percent of the time). Alzheimer%26#8217;s disease cannot be confirmed until a patient has died and his or her brain has been examined. Gold standard tests administered at world-class research facilities, such as Penn, have a 90-percent accuracy rate. However, most people are evaluated at community hospitals and clinics, where the diagnostic accuracy is estimated to be around 75 percent.



Though the study%26#8217;s accuracy rate is under that 90-percent figure, it still means the test potentially could have great value to physicians and patients and their families, and the results are particularly significant for patients who have limited access to teaching hospitals, where they may undergo six to 12 months of evaluation for a diagnosis.



%26#8220;Currently, the state-of-the-art evaluation for Alzheimer%26#8217;s disease is only available to those who have geographic proximity and/or financial ability to access research hospitals, where expert neuropsychologists continuously interview patients and caregivers over six to 12 months to make a diagnosis,%26#8221; said Polikar, principal investigator on the project at Rowan. %26#8220;But most people don%26#8217;t have access to such facilities and instead go to community clinics and hospitals. Our methodology involves just one %26#8216;snapshot%26#8217; that in itself is highly accurate and will be especially beneficial in these locations.%26#8221;



"Modern engineering methods are enabling us to take EEG, an 80-year-old technique for measuring brain activity, and turn it into a cutting-edge tool for diagnosing Alzheimer's disease," Kounios added.



The team members hope that eventually they or other researchers will develop a hand-held device that can be used to conduct similar evaluations as those done by the Rowan/Penn//Drexel group.



%26#8220;We don%26#8217;t envision this replacing a neurologist,%26#8221; Polikar said. %26#8220;We hope it can serve as a first test for those folks who don%26#8217;t have access to research facilities.%26#8221; If the initial test indicates a possible problem, physicians could refer the patient to a research hospital for further evaluation.



%26#8220;Our ultimate goal is to increase the number of patients who are diagnosed earlier so they can start treatment sooner and slow the progress of Alzheimer%26#8217;s and improve their quality of life,%26#8221; Polikar said.



Source: Rowan University


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Human bone marrow stem cells used to create early-stage sperm cells

Human bone marrow has been used to create early-stage sperm cells for the first time, a scientific step forward that will help researchers understand more about how sperm cells are created.The research published today (Friday, April 13 2007), in the academic journal Reproduction: Gamete Biology, was...

Sperm cells from bone marrowHuman bone marrow has been used to create early-stage sperm cells for the first time, a scientific step forward that will help researchers understand more about how sperm cells are created.



The research published today (Friday, April 13 2007), in the academic journal Reproduction: Gamete Biology, was carried out in Germany by a team of scientists led by Professor Karim Nayernia, formerly of the University of G%26#246;ttingen but now of the North-east England Stem Cell Institute (NESCI), based at the Centre for Life in Newcastle upon Tyne.


[More:]


For the experiment, Prof Nayernia and his team took bone marrow from male volunteers and isolated the mesenchymal stem cells. These cells have previously been found to grow into other body tissues such as muscle.



They cultured these cells in the laboratory and coaxed them into becoming male reproductive cells, which are scientifically known as %26#8216;germ cells%26#8217;. Genetic markers showed the presence of partly-developed sperm cells called spermatagonial stem cells, which are an early phase of the male germ cell development. In most men, spermatagonial cells eventually develop into mature, functional sperm but this progression was not achieved in this experiment.



Earlier research led by Prof Nayernia using mice, published in Laboratory Investigations, also created spermatagonial cells from mouse bone marrow. The cells were transplanted into mouse testes and were observed to undergo early meiosis - cell division - the next stage to them becoming mature sperm cells, although they did not develop further.



Talking about his newly published research paper, Prof Nayernia, of Newcastle University, said : "We%26#8217;re very excited about this discovery, particularly as our earlier work in mice suggests that we could develop this work even further.



"Our next goal is to see if we can get the spermatagonial stem cells to progress to mature sperm in the laboratory and this should take around three to five years of experiments. I%26#8217;ll be collaborating with other NESCI scientists to take this work forward.



Prof Nayernia says a lengthy process of scientific investigation is required within a reasonable ethical and social framework to be able to take this work to its next stage or to say if it has potential applications in terms of fertility treatments in humans.



Prof Nayernia gained worldwide acclaim in July 2006 when he announced in the journal Developmental Cell that he and colleagues had created sperm cells from mouse embryonic stem cells and used these to fertilise mice eggs, resulting in seven live births.



Source: University of Newcastle, Tyne


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