Prakash laboratory conducts preliminary ...

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Asthma episodes are caused by the notorious pollution in Beijing, some athletes refused to events in the 2008 Summer Olympics, and other planned restoration therapy to protect their lungs from damage. As Chinese government officials have temporarily closed plants and limit traffic to reduce the particles that can trigger asthma episodes, Mayo Clinic researchers working on a more permanent solution to a huge burden on health systems, creating asthma. Mayo immunologist, who runs the clinic, has produced eight weeks of symptoms of asthma model mice by administration of antibodies recently identified as a potential method of cancer treatment. And the husband and wife team of research and are anesthesiologists and physiologists investigate cellular mechanisms in smooth muscle airways that trigger asthma episodes. During his stay in pediatric Japan, two of the most memorable patients Dr. Keith were young girls, which was very allergic to eggs and a teenager who does not respond well to asthma therapy. These young patients to lasix drug heart increase their motivation to study immunological responses to the environment. In 1988, Dr. Keith Mayo began doctoral fellowship in immunology. He quickly assimilated and adopted a joint research clinic on Wednesday. Returning home, he found that Japanese culture studies did not meet his temperament, and he decided to seek faculty positions back to Mayo. Many times, it helps the study were unplanned meetings, joint cooperation for the rich culture of Mayo. "All you have to do is go outside your office," says Dr. Kita. "And when you come up with other researchers and doctors, just ask what they do."

That was four years ago when he collided with, co-director. Dr. Pease excitedly told her. B7 is a family of natural molecules, which are the cells that activate T lymphocytes (immune cells). DC stands for dendritic cells, branched cells, which affixes the tumor surface. B7-DC antibody binds to B7-DC, to stimulate it. Research Dr. Pease demonstrated a method that uses B7-DC antibodies to prevent tumor growth (

Cancer Research in July 2004). "Larry observations suggested that the immune system can respond to autoimmune and allergic diseases is similar to how it reacts to cancer or cancer treatment," explains Dr. Keith. "But maybe it works differently."

In immunological diseases such as asthma, immune system reacts to the patient's environment, Dr. Keith suspect may be similar to the hyperactive response of cancer cell growth. He knew that cause cancer immunity, it is necessary to activate certain T cells. He suggested that cancer T-cell response may be appropriate, but the opposite effect on the overactive immune response. "It's almost like opposite sides of one coin," says Dr. Keith, describing how he came to his hypothesis. "We call upon the response of cancer patients in the immunotherapy of T-helper 1 (Th-1) response. But there are two types of reactions, Th-1 (good for cancer patients) and Th-2 (bad for patients with immunological or autoimmune diseases). For good health, should be a balance between Th-1 and Th-2 ".

B7-DC antibodies seems key to the control response. Then Dr. Keith wondered "what if you could manipulate the Th-1 and Th-2 balance of asthma patients using antibodies? Does that prevent overactive immune responses to the environment? "

Dr. Keith collaborated with Dr. pea on studies that showed B7-DC blocked inflammatory diseases of the respiratory tract in experimental animals (

Journal of Allergy and Clinical Immunology , 2005

with further research in European Journal of Immunology, 2008

). Since antibodies currently in clinical trials performed in patients with melanoma have a testimony about how B7-DC affects people. Knowledge gained from the human research potential will accelerate delivery of B7-DC antibodies as a new treatment for patients with asthma worldwide. "Clinical trials may begin within three years," says Dr. Kita. Buildings, doctor. Prakash and Pabelick work side by side in their spectacular flower gardens and vegetable. At Mayo, they work side by side gathering knowledge of the laboratory of cellular physiology. This dynamic team met the study 10 years ago while studying calcium regulation in the laboratory physiologist

Their collaboration with Dr. Sieck, world-renowned expert on the smooth muscles of the airways, continues to this day. Dr. Prakash and Pabelick focus on advancing our understanding of how factors such as gender, and proteins such as neurotrophins and kaveolinom affect the physiological response airway smooth muscle in asthma. Scientists also anesthesitistsa that Dr. Prakash said, led him to more interested in airway smooth muscle research. "Classically, asthma wheezing illnesses," says Dr. Prakash. "When the attack is caused by environmental irritants such as industrial contaminants (eg in Beijing), airway smooth muscle constriction of bronchial openings shrink them to protect the body from inhaling potentially harmful substances."

As well as increasing muscle tissue as an athlete trains, bronchial airway smooth muscle walls thicken with asthma caused by episodes of contraction and relaxation, reduction of bronchial wall and further limit the exchange of air, causing shortness of breath sound. Not a good situation for anyone, let alone Olympic champion. Scientists call this thickening of the muscles "reconstruction." The more this happens, the more difficult to treat asthma. So the doctor.

Prakash and Pabelick looking for new ways to prevent excessive remodeling. Calcium is one of the most evolutionarily ancient cellular "signaling" molecules. Without it, muscles can not be reduced, including bronchial smooth muscle airways. When cells have too much calcium they contract too much wrong signal and provide inadequate answers to stimulationsuch, as in the more-reactive asthmatic smooth muscle airways. Research Dr. Pabelick found that one potential factor in the normal to abnormal calcium signaling is the presence kaveol, pit-like "scaffolding" structures within the cell membranes. Kaveol include many types of molecules that correspond to triggers, such as histamine and other factors that make smooth muscle is reduced. Dr. Pabelick and her team found that airway smooth muscle inflammation (as occurs in asthma) lead to higher levels kaveol and corresponding proteins, known as kaveolinom. Preliminary data show that if the respiratory tract tissue is not so much kaveol kaveolinom or less of calcium inside cells, which reduces the inflammatory response in the airways and reduces the "effect of reconstruction." Doctor Pabelick suggests that kaveol or proteins may be altered, leading to possible therapy for patients with asthma. Dr. Prakash Laboratory conducts a preliminary investigation to find out how and why men and women differ in frequency and severity of asthma. They focus on the role of sex hormones such as estrogen and progesterone. In a small preliminary clinical study to asthma in women, this new basic research can be based on violation. "We know that women are protected from coronary heart disease before menopause," says Dr. Prakash. "But some epidemiological data on asthma suggest that during puberty asthma is increased in girls, oral contraceptives can aggravate symptoms, and after menopause in women may be less asthma. On the other hand, women with asthma can be better when they are pregnant. So much more research is needed to understand the role of sex hormones in asthma. "

Laboratory study of how estrogen and progesterone affect the behavior of smooth muscle cell inflammation. Their goal is to find out the sex hormones will make things better or worse. Their results have the potential to determine the risks and benefits of estrogen replacement therapy and other similar approaches to address asthma in women during puberty, pregnancy and menopause. The third project is husband and wife team to explore how neurotrophins, agents that were previously considered to stimulate growth and development of the nervous system include mechanisms of smooth muscle airways. Dr. Prakash learned of neurotrophins, studying his PhD in Dr. Sieck in the early nineties. "While we thought worked their magic neurotrophins only in brain and spinal cord. We know that neurotrophins present in places that we had not expected them to, "says Dr. Prakash. They found two neurotrophins is in airway smooth musclebrain neurotrophic factor (BDNF) and neurotrophins-3. The presence of BDNF may affect the immune response, increasing the contraction of the smooth muscles of the airways. On the other hand, neurotrophins-3 tends to "dumb down" the answer, says Dr. Prakash. Create or neurotrophins breaking immune cells or smooth muscle itself, and understanding their role in the lung and the mechanisms that control them, will allow the team focused on these new mechanisms. Their goal will be to develop therapeutic agents for prevention of respiratory muscles smooth airway remodeling and hyperreactivity. Asthma is a complex, common and fatal disease. Mayo Clinic researchers working on bringing new treatments and potential cures for asthma patients worldwide. Prevention of remodeling, stop the overactive immune response in our environment, turn off this diseasethat Mayo researchers hope asthma. Kelly DeBrine, September 2008.