January 13, 2010, 8:15 AM CT

How Melanoma Ivades Immune System

Melanoma, if not detected in its early stages, transforms into a highly deadly, therapy-resistant cancer. Eventhough the immune system initially responds to melanoma and mounts anti-tumor attacks, these assaults are generally ineffective, allowing more advanced melanomas to win the battle and spread beyond the primary site. Now, scientists at Children's Hospital Boston and Brigham and Women's Hospital (BWH) shed light on how melanomas stimulate, yet ultimately evade, a patient's immune system. Their work, published online January 12 by the journal Cancer Research, also suggests ways drugs might block these tactics.

In 2008, the same team, led by Markus Frank, MD, of the Transplantation Research Center of Children's and BWH, and George Murphy, MD, chief of Dermatopathology at BWH, showed in the journal Nature that a key reason for melanoma virulence is a small group of tumor stem cells that are able to grow despite chemotherapy drugs, allowing the tumor to re-grow and progress. They also showed that targeting these cells (identifiable by a molecule on their surface known as ABCB5) could successfully inhibit tumor growth in mice. (The ABCB5 technology has been licensed and is currently in clinical drug development.)

In their new paper, first author Tobias Schatton, PhD, of the Transplantation Research Center, and his colleagues show that these ABCB5-positive cells also produce molecules that inhibit the body's natural immune attack, known as PD-1 and B7.2. These molecules work, they found, by triggering white blood cells known as regulatory T cells (T-regs), to dampen the normal anti-melanoma response. The T-regs are thus tricked into protecting the deadly melanoma stem cells from the body's own defenses......... Posted by: George      Read more         Source

January 12, 2010, 8:56 AM CT

ADHD: Disconnect Between Brain Regions

Two brain areas fail to connect when children with attention deficit hyperactivity disorder attempt a task that measures attention, as per scientists at the UC Davis Center for Mind and Brain and M.I.N.D. Institute.

"This is the first time that we have direct evidence that this connectivity is missing in ADHD," said Ali Mazaheri, postdoctoral researcher at the Center for Mind and Brain. Mazaheri and colleagues made the discovery by analyzing the brain activity in children with ADHD. The paper appears in the current online issue of the journal Biological Psychiatry.

The scientists measured electrical rhythms from the brains of volunteers, particularly the alpha rhythm. When part of the brain is emitting alpha rhythms, it shows that it is disengaged from the rest of the brain and not receiving or processing information optimally, Mazaheri said.

In the experiments, children with diagnosed ADHD and normal children were given a simple attention test while their brain waves were measured. The test consisted of being shown a red or blue image, or hearing a high or low sound, and having to react by pressing a button. Immediately before the test, the children were shown either a letter "V" to alert them that the test would involve a picture (visual), or an inverted "V" representing the letter "A" to alert them that they would hear a sound (auditory)......... Posted by: JoAnn      Read more         Source

January 12, 2010, 8:49 AM CT

Mind-Body Techniques for Treating Celiac Disease

For adults and children diagnosed with celiac disease, the only therapy is a gluten-free diet, which can be very challenging. Gastroenterologists at Rush University Medical Center are conducting a newly released study to see if mind/body techniques could help patients with celiac disease adhere to the very strict diet.

Celiac disease is a lifelong, digestive disease affecting children and adults. People who have celiac disease cannot tolerate gluten, a protein found in almost all food products as well as medicines, vitamins and lip balms. Gluten can damage the small intestine and interfere with absorption of nutrients from food.

"Eating even a small amount of gluten can damage the small intestine," said Dr. Ali Keshavarzian, vice chairman of medicine and gastroenterologist at Rush. "The damage will occur in anyone with the disease, including people without noticeable symptoms".

Hidden sources of gluten are sometimes additives such as modified food starch, preservatives and stabilizers made with wheat. Also, a number of corn and rice products are produced in factories that also manufacture wheat products, and can be contaminated with wheat gluten.

"The purpose of this study is to determine whether participation in one of two mind/body courses can help patients cope with the restricted diet," said Keshavarzian. "It can be very hard and stressful for people with celiac disease to stick to a gluten-free diet."........ Posted by: Sue      Read more         Source

January 12, 2010, 8:40 AM CT

Sticking to diets is about more than willpower

A number of people think the success of dieting, seemingly a national obsession following the excesses and resolutions of the holiday season, depends mostly on how hard one tries -- on willpower and dedication. While this does matter, new research has observed that a much more subtle aspect of the diets themselves can also have a big influence on the pounds shed -- namely, the perceived complexity of a diet plan's rules and requirements.

Cognitive researchers from Indiana University and the Max Planck Institute for Human Development in Berlin compared the dieting behavior of women following two radically different diet plans and observed that the more complicated people thought their diet plan was, the sooner they were likely to drop it.

"For people on a more complex diet that involves keeping track of quantities and items eaten, their subjective impression of the difficulty of the diet can lead them to give up on it," reported Peter Todd, professor in IU's Department of Psychological and Brain Sciences.

Jutta Mata, now a professor of psychology at Stanford University, said this effect holds even after controlling for the influence of important social-cognitive factors including self-efficacy, the belief that one is capable of achieving a goal like sticking to a diet regimen to control one's weight......... Posted by: JoAnn      Read more         Source

January 12, 2010, 8:38 AM CT

'Weekend Effect' Makes People Happier

From construction laborers and secretaries to physicians and lawyers, people experience better moods, greater vitality, and fewer aches and pains from Friday evening to Sunday afternoon, concludes the first study of daily mood variation in employed adults to be reported in the January 2010 issue of the Journal of Social and Clinical Psychology. And that 'weekend effect' is largely linked to the freedom to choose one's activities and the opportunity to spend time with loved ones, the research found.

"Workers, even those with interesting, high status jobs, really are happier on the weekend," says author Richard Ryan, a professor of psychology at the University of Rochester. "Our findings highlight just how important free time is to an individual's well-being." Ryan adds. "Far from frivolous, the relatively unfettered time on weekends provides critical opportunities for bonding with others, exploring interests and relaxing - basic psychological needs that people should be careful not to crowd out with overwork," Ryan cautions.

The study tracked the moods of 74 adults, aged 18 to 62, who worked at least 30 hours per week. For three weeks, participants were paged randomly at three times during the day, once in the morning, the afternoon and the evening. At each page, participants completed a brief questionnaire describing the activity in which they were engaged and, using a seven-point scale, they rated their positive feelings like happiness, joy, and pleasure as well as negative feelings of anxiety, anger, and depression. Physical symptoms of stress, such as headaches, digestive problems, respiratory ills, or low energy, also were noted......... Posted by: JoAnn      Read more         Source

January 11, 2010, 8:16 AM CT

Calcium and taste perception

Calcium may not come to mind when you think of tasty foods, but in a study appearing in the January 8 issue of JBC, Japanese scientists have provided the first demonstration that calcium channels on the tongue are the targets of compounds that can enhance taste.

In addition to molecules that directly trigger specific taste buds (salty, sweet etc.), there are other substances which have no flavor of their own but can enhance the flavors they are paired with (known as kokumi taste in Japanese cuisine).

Exploiting this enhancement could have practical uses in food modulation; for example, creating healthy foods that contain minimal sugar or salt but still elicit strong taste. At the moment, though, the mode of action for these substances is poorly understood.

However, Yuzuru Eto and his colleagues examined whether calcium channels which sense and regulate the levels of calcium in the body might be the mechanism involved; they noted that calcium channels are closely correlation to the receptors that sense sweet and umami (savory) tastes and that glutathione (a common kokumi taste element) is known to interact with calcium channels.

To test their possibility, they created several small molecules that resembled glutathione and analyzed how well these compounds activated calcium channels in cell samples. Next, they diluted the same test substances in flavored water (salt water, sugar water, etc.) and asked volunteers (all trained in discriminating tastes) to rate how strong the flavors were......... Posted by: Scott      Read more         Source

January 11, 2010, 8:00 AM CT

Why migraine headaches get worse with light exposure?

BOSTON Ask anyone who suffers from migraine headaches what they do when they're having an attack, and you're likely to hear "go into a dark room." And eventhough it's long been known that light makes migraines worse, the reason why has been unclear.

Now researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a new visual pathway that underlies sensitivity to light during migraine in both blind individuals and in individuals with normal eyesight. The findings, which appear today in the Advance On-line issue of Nature Neuroscience, help explain the mechanism behind this widespread condition.

A one-sided, throbbing headache linked to many symptoms, including nausea, vomiting, and fatigue, migraines are notoriously debilitating and surprisingly widespread, affecting more than 30 million individuals in the U.S. alone. Migraine pain is believed to develop when the meninges, the system of membranes surrounding the brain and central nervous system, becomes irritated, which stimulates pain receptors and triggers a series of events that lead to the prolonged activation of groups of sensory neurons.

"This explains the throbbing headache and accompanying scalp and neck-muscle tenderness experienced by a number of migraine patients," explains the study's senior author Rami Burstein, PhD, Professor of Anesthesia and Critical Care Medicine at BIDMC and Harvard Medical School......... Posted by: Daniel      Read more         Source

January 11, 2010, 7:51 AM CT

Autism is a brain 'connectivity' disorder

Studying a rare disorder known as tuberous sclerosis complex (TSC), scientists at Children's Hospital Boston add to a growing body of evidence suggesting that autism spectrum disorders, which affect 25 to 50 percent of TSC patients, result from a miswiring of connections in the developing brain, leading to improper information flow. The finding may also help explain why a number of people with TSC have seizures and intellectual disabilities. Findings were published online in Nature Neuroscience on January 10.

TSC causes non-malignant tumors throughout the body, including the brain. But patients with TSC may have autism, epilepsy or intellectual disabilities even in the absence of these growths. Now, scientists led by Mustafa Sahin, MD, PhD, of Children's Department of Neurology, provide evidence that mutations in one of the TSC's causative genes, known as TSC2, prevent growing nerve fibers (axons) from finding their proper destinations in the developing brain.

Studying a well-characterized axon route between the eye's retina and the visual area of the brain Sahin and his colleagues showed that when mouse neurons were deficient in TSC2, their axons failed to land in the right places. Further investigation showed that the axons' tips, known as "growth cones," did not respond to navigation cues from a group of molecules called ephrins. "Normally ephrins cause growth cones to collapse in neurons, but in tuberous sclerosis the axons don't heed these repulsive cues, so keep growing," says Sahin, the study's senior investigator......... Posted by: JoAnn      Read more         Source

January 11, 2010, 7:49 AM CT

Repairing a defective alcohol metabolism enzyme

An experimental compound repaired a defective alcohol metabolism enzyme that affects an estimated 1 billion people worldwide, as per research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The findings, published Jan. 10, 2010 in the advance online edition of Nature Structural and Molecular Biology, suggest the possibility of a therapy to reduce the health problems linked to the enzyme defect.

"This intriguing finding could have broad public health implications," said NIAAA Acting Director Kenneth R. Warren, Ph.D. "We look forward to further research aimed at translating these laboratory discoveries into possible therapys for people".

"We recently identified a molecule called Alda-1 that activates the defective enzyme, and in the current study, we determined how this activation is achieved," said the study's senior author, Thomas D. Hurley, Ph.D., professor and associate chairman of biochemistry and molecular biology at Indiana University School of Medicine in Indianapolis. Initial investigations of Alda-1 were led by co-author Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford University School of Medicine.

After alcohol is consumed, it is first metabolized, or broken down, into acetaldehyde, a toxic chemical that causes DNA damage. Aldehyde dehydrogenase 2 (ALDH2) is the main enzyme responsible for breaking down acetaldehyde into acetate, a nontoxic metabolite in the body. It also removes other toxic aldehydes that can accumulate in the body......... Posted by: Scott      Read more         Source

January 11, 2010, 7:47 AM CT

Genetic research related to ankylosing spondylitis

Work done in part by scientists at The University of Texas Health Science Center at Houston has led to the discovery of two new genes that are implicated in ankylosing spondylitis (AS), an inflammatory and potentially disabling disease. In addition, the international research team pinpointed two areas along stretches of DNA that play an important role in regulating gene activity linked to the arthritic condition.

The findings, a critical milestone in the understanding of AS, are reported in the recent issue of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. "This helps us better understand what is driving this disease and gives us direction for new therapys and diagnostic tests," said John D. Reveille, M.D., the study's principal investigator and professor and director of the Division of Rheumatology and Clinical Immunogenetics at The University of Texas Medical School at Houston.

Reveille, the university's Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders, and Matthew A. Brown, M.D., professor of immunogenetics at Australia's University of Queensland, led the research by the Triple "A" Spondylitis Consortium Genetic Study (i.e. the TASC or Australo-Anglo-American Spondylitis Consortium). Based on work from a genome-wide association scan, the team identified genes ANTXR2 and IL1R2 as well as two gene deserts, segments of DNA between genes on chromosomes 2 and 21 that are linked to ankylosing spondylitis. Importantly, the study also confirmed the Triple "A" Australo-Anglo-American Spondylitis Consortium's previously reported associations of genes IL23R and ERAP1, formerly known as ARTS1......... Posted by: Mark      Read more         Source