Washington, Oct 22 (ANI): In a collaborative study, UCLA and Dutch researchers have identified three new candidate genes for schizophrenia that may contribute to a better understanding of how the disease evolves.

For the study, Roel A. Ophoff, an assistant professor with the Center for Neurobehavioral Genetics at the Semel Institute for Neuroscience and Human Behavior at UCLA, and his colleagues examined the genetic makeup of 54 Dutch patients diagnosed with deficit schizophrenia, a particularly severe form of the disease that is both chronic and debilitating.

Specifically, they looked at a number of large but rare deletions and duplications in the genome of the patients, known as copy number variants, or CNVs.

Scientists suspect that such missing or duplicated segments of DNA could be responsible for increased susceptibility to a number of diseases.

In this study, the researchers showed that three of these rare CNVs interrupted genes associated with brain function.

"These genes were not implicated in schizophrenia before. So next, we tested these three genes in a large follow-up study of more than 750 general-schizophrenia patients and 700 controls. And what surprised us is that roughly 1 percent of schizophrenia patients harbor these genomic deletions," said Ophoff.

Ophoff said that the changes in these three genes are rare but seem to dramatically increase the risk of developing schizophrenia.

The identification of these new candidate genes will provide a better insight into the underlying biology of schizophrenia and explain why some individuals are at risk to develop the disease.

"Another important step will be to assess the inheritance patterns of such CNVs. Since this is an inherited disease affecting approximately 1 percent of the population, this would be valuable toward establishing the clinical relevance of this important class of genomic variations," Ophoff said. The study is published in the October issue of the American Journal of Human Genetics. (ANI)

Be first to comment this article | Add as favourites (8)

Washington, Oct 22 (ANI): A new study indicates a possible link between childhood exposure to general anesthesia and an increased risk of behavioral and developmental disorders in young kids.

Recent animal studies have shown that commonly used anesthetic agents may have serious neurotoxic effects on the developing brain.

To assess whether the experimental animal data can be applied to humans, Lena S. Sun, M.D., professor of anesthesiology and paediatrics and colleagues at Columbia University College of Physicians and Surgeons, the Mailman School of Public Health and the Columbia University School of Nursing, performed an analysis of a group of children born into the New York State Medicaid Program between 1999 and 2000.

Over a 4 year period, 625 children under the age of three were exposed to general anesthesia as part of uncomplicated hernia repair.

When compared to a random sample of 5,000 children with no history of anesthesia exposure, the children exposed to anesthetic agents were twice as likely to be (subsequently) diagnosed with a developmental or behaviour disorder.

"Given that the study subjects were taken from a Medicaid population, one limitation of the data is the demographic factors of this group that may vary from the general population. The excess risk of developmental and behavioral disorders in the children exposed to anesthesia cannot be completely explained by demographic factors or confounding health factors including premature birth or low birth weight," the authors said.

Researchers stress the need for more rigorous studies to assess the long-term health effects of exposure to anesthesia in young children.

"This current analysis only examined two or three years of post-exposure data. To determine long-term effects of exposure, it is essential to continue and expand the efforts of this study with continued follow-up with the study subjects and design additional studies in which direct neurodevelopmental outcomes could be assessed," Dr. Sun said.

"It is important to emphasize that given the limitations and preliminary nature of the study, these results should be interpreted with caution; parents should not keep their children from having necessary surgical procedures," Dr. Sun added.

The study has been presented at the 2008 Annual Meeting of the American Society of Anesthesiologists. (ANI)

Be first to comment this article | Add as favourites (6)

Washington, Oct 22 (ANI): People who are physically active before suffering a stroke may have less severe problems as a result and recover better compared to those who did not exercise before having a stroke, according to a new study. For the study, researchers reviewed the medical records of 265 people with an average age of 68 who had a stroke and were able to walk on their own.

Other stroke risk factors and other diseases and conditions that might interfere with their ability to exercise were considered.

The participants were interviewed after filling out a questionnaire about their exercise habits and the number of hours they were active during a one-week period.

Researchers found that the top 25 percent of people who exercised the most were two-and-a-half-times more likely to suffer a less severe stroke compared with people who were in the bottom quarter of the group. The most active also had a better chance of long-term recovery.

"Exercise is one possible risk factor for stroke that can be controlled. Staying fit doesn't have to be a scheduled regimen. For the people in this study, exercise included light housework, taking a walk outside, lawn care, gardening or participating in a sport," said study author Lars-Henrik Krarup, MD, of the Bispebjerg University Hospital in Copenhagen, Denmark.

The study is published in the October 21, 2008, print issue of Neurology. (ANI)

Be first to comment this article | Add as favourites (6)

Washington, Oct 22 (ANI): Using multiple tactics to boost both innate and adaptive immunity in mice, scientists at Scripps Research Department of Immunology have successfully enhanced their body's ability to fight cancer.

The researchers hope that their work may pave the way for developing new human immunotherapy.

"The problem with cancer is that it becomes part of what the immune system identifies as 'self' and there are ways the body learns to tolerate 'self' to prevent immune attack. Hitting it with these new tools basically gets the immune system to pay attention to the cancer, and go after it," said the study's senior investigator, Dr. Linda Sherman.

She added: "What is needed is effective and non-toxic immunotherapy for cancer patients, and we believe this work provides a foundation for that. The concepts we have shown are directly translatable to human therapy."

Scientists used two different strategies for their study - the first one involved forcing T cells, the killer cells of immune system, to become active and grow in the presence of tumour "antigens".

Antigens are the proteins on the outside of cancer cells that can stimulate an immune response. When T cells recognize the tumour antigens, their response to them becomes chronically weak because they are 'self'.

"We have been working for years to find ways to coax these so-called low affinity T cells to work better," said Sherman.

During this study, the investigators tested a novel complex, which combines Interleukin-2 (IL-2) with an IL-2 antibody. IL-2 is a well-known stimulator of the growth of activated T cells, and is often used to boost immune system response in human therapy; T cells have IL-2 receptors on their surface.

Earlier it was found that when IL-2 was combined with a specific type of IL-2 antibody, it enabled the complex to bind better to activated T cells and resulted in the production of a more robust T cell response. "The beauty of this complex is that, as we demonstrate in this paper, it has a much greater ability to bind to low affinity T cells, which IL-2 itself cannot do very well," says Sherman.

Thus, for triggering an immune reaction, the researchers primed T cells with this complex, which after binding with T cells, grow and mature and deliver a signal to release cytotoxic granules that enter tumour cells and promote apoptosis, or cell death.

"A number of nice things begin to happen. T cell growth is promoted as well as their killing function. There is a lot of good activity," said Sherman.

But, the moment the IL-2 complex is withdrawn the T cells die quickly.

The second strategy was to also deliver an agent, called poly(l:C), that keeps T cells surviving longer. Poly (l:C) also enhances the killing power of the T cells by stimulating the innate immune system, which provides an immediate defence against invaders.

"It is this trick of really stimulating T cell proliferation and killing functions, and then keeping the T cells alive, that provides the double whammy. The T cells are hitting all their bases, and that is when we see the killing of tumors," said Sherman.

The scientists tested the system in mice that spontaneously develop tumours by delivering tumour antigen, the IL2 complex, and poly(l:C) together at the same time. They showed that the strategy was quite safe and effective.

The study is published in an early edition issue of the Proceedings of the National Academy of Sciences (PNAS). (ANI)

Be first to comment this article | Add as favourites (7)