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UCLA researchers discover novel pathway that may promote immune system balance

06-07-2007 · EurekAlert!

Researchers at UCLA's Jonsson Cancer Center have discovered a novel anti-inflammatory cell signaling pathway that may serve as a vital Yin-Yang mechanism to maintain the delicate balance of immune response.

Keywords: ucla, researchers, discover, novel, pathway, promote, immune, system, balance, researcher

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U of M researchers discover a pathway to turn off immune system cells
01-31-2008 · EurekAlert!
University of Minnesota researchers have discovered a new way to turn genes off in human T cells, a type of white blood cell that helps the immune system fight infections.Turning off genes, through a process known as mRNA decay, is important for regulating the body's immune response after fighting infection. This research could lead to development of new drugs that turn off the immune system in patients with autoimmune diseases -- such as rheumatoid arthritis and lupus.
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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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UC Davis researchers discover novel pathway to increased inflammation in diabetes patients
11-27-2007 · EurekAlert!
Researchers at UC Davis Health System have discovered a novel pathway that results in increased inflammation of blood vessels in patients with type 1 diabetes.
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Researchers discover new way to predict survival in older women with lung cancer
11-01-2007 · EurekAlert!
Researchers at UCLA's Jonsson Comprehensive Cancer Center have discovered a novel mechanism to predict survival in older women with early-stage lung cancer. The finding may have significant implications for new treatment approaches.
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Jefferson researchers boost immune 'killer cells,' increase antibody effectiveness against cancer
04-18-2007 · EurekAlert!
Researchers have devised a novel method to expand the number of immune system "natural killer (NK)" cells from blood cells outside the body. They have shown in laboratory studies that adding such cells to anti-cancer therapies involving monoclonal antibody drugs such as Herceptin, which targets the HER2/neu protein on breast cancer cells, is more effective in killing cancer cells, and perhaps someday may improve treatments.
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UCSD researchers discover inflammation, not obesity, cause of insulin resistance
11-06-2007 · EurekAlert!
Researchers at the University of California, San Diego School of Medicine have discovered that inflammation provoked by immune cells called macrophages leads to insulin resistance and type 2 diabetes. Their discovery may pave the way to novel drug development to fight the epidemic of type 2 diabetes associated with obesity, the most prevalent metabolic disease worldwide.
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Penn researchers discover pathway that eliminates genetic defects in red blood cells
08-01-2007 · EurekAlert!
Researchers have discovered a unique molecular pathway that detects and selectively eliminates defective messenger RNAs from red blood cells. Knowing how this specific surveillance system works can help researchers better understand hereditary diseases.
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Potential New Target For Leukemia Treatment
10-10-2006 · ScienceDaily
Cincinnati Children's Hospital Medical Center researchers have identified the crucial role and novel mechanism of action of the protein RhoH GTPase in the development and activation of cells critical to the immune system. The findings suggest that RhoH GTPase may provide a target for therapeutic intervention in some types of leukemia. The paper is due to appear in an upcoming edition of the journal, Nature Immunology.
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Cornell researcher seeks clues to how tuberculosis infects cells
12-21-2007 · EurekAlert!
Cornell researchers are using advanced genetic techniques to better understand the relationship between the bacteria that cause tuberculosis and the human immune system defense cells that engulf them.
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UBC researchers discover 'instruction manual' that tells cancers how to hide from immune system
11-08-2007 · EurekAlert!
A mechanism that creates an "invisibility cloak" for certain cancer cells and allows them to hide from the immune system has been uncovered by a team of researchers at the University of British Columbia.
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