Characterization Of Mast Cell Basophil Haematopoesis In Patients With Asthma And Drug Allergies.
Funder
National Health and Medical Research Council
Funding Amount
$412,379.00
Summary
The major emphasis of this investigation is to analyse blood for specific cells thought to be implicated in allergic disease from patients undergoing allergic reactions to medications and in patients with asthma and other allergies. Certain cells in the circulation of these patients are thought to be involved in the clinical manifestation seen in patients with asthma and other allergies. These cells have certain characteristics and for the first time our laboratory has identified a particular ce ....The major emphasis of this investigation is to analyse blood for specific cells thought to be implicated in allergic disease from patients undergoing allergic reactions to medications and in patients with asthma and other allergies. Certain cells in the circulation of these patients are thought to be involved in the clinical manifestation seen in patients with asthma and other allergies. These cells have certain characteristics and for the first time our laboratory has identified a particular cell in the circulation of patients with asthma which we believe may be important in the pathogenesis of this condition. We propose to examine these cells in patients with asthma, those experiencing allergic reactions to drugs and other allergies and determine their characteristics and their growth responses to a number of growth factors which have been demonstrated to affect the growth of cells known as mast cells in the test tube. Once we have characterised these cells in terms of what particular proteins and other products they contain we will then try to correlate the number and type of cell with the clinical allergic state of the patient. Blood will be obtained from patients undergoing acute asthma and those in remission to determine if there is any specific relationship of these cells with acute allergic reactions. We will be also looking at how these cells regulate other physiological systems in the body, in particular possible explanations why patients that suffer acute allergic reactions develop significant drops in blood pressure. We can identify these cells with a specific antibody that we have used in our preliminary studies. This antibody binds the surface of these cells, however the specific protein to which this antibody binds has not been identified. We propose to identify this protein by using molecular biology techniques. These studies will provide us with important insights on the nature of these cells and may lead to new therapies.Read moreRead less
Predictors And Consequences Of Allergies That Impact On Children Getting A Healthy Start To Life:a Prospective Study
Funder
National Health and Medical Research Council
Funding Amount
$893,559.00
Summary
Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. ....Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. For example some infants with eczema continue to have eczema or develop hay fever and asthma, while others do not. The aim of this study is to determine what factors cause allergies and what factors influence these changes. This will provide evidence to guide health policy and clinical practice. Looking at the different conditions in family members over time is a good way to answer these types of questions, because parents and siblings share similar exposures, but not all the same genes. This helps to disentangle the effects of the environment and genes. The Melbourne Atopic Cohort Study (MACS) is amongst the world�s major studies on the development of allergies. MACS commenced in 1991-94 by recruiting 620 babies prior to birth. Only infants born into families with a history of allergic disease were included. MACS is unique because all family members and the home environment were assessed at the time of birth of the child. These children have been followed regularly over the first ten years of their life. The MACS now provides a unique opportunity to conduct a family study that can examine genes, childhood environment and individual risk factors for allergies. This will also allow exploration of the impact of allergies on families and the health care system, and how we can reduce that impact. Such information will provide evidence to guide health care policy and clinical practice. Also, the current study will provide a platform for future studies to investigate the progression of allergies in this family cohort. This will be the world's only longitudinal family follow-up of allergies that spans all of childhood. It will assist in reducing the impact of these common conditions, and the findings will be original and significant not only in Australia but also internationally.Read moreRead less
Effects Of Upper Versus Lower Respiratory Infections On The Induction Of Atopic Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$386,483.00
Summary
Asthma is more common now in developed countries than it was 20-30 years ago. Many fewer children have asthma in developing countries and there does not appear to have been the same increase in asthma in recent years. Children in developed countries tend to have fewer respiratory infections and recent studies suggest that this may be partly responsible for the increase in asthma. An understanding of why asthma has increased in developed countries may lead to strategies to prevent asthma. In orde ....Asthma is more common now in developed countries than it was 20-30 years ago. Many fewer children have asthma in developing countries and there does not appear to have been the same increase in asthma in recent years. Children in developed countries tend to have fewer respiratory infections and recent studies suggest that this may be partly responsible for the increase in asthma. An understanding of why asthma has increased in developed countries may lead to strategies to prevent asthma. In order to understand the role that respiratory infections may play in the induction of asthma, it is necessary to study babies from birth, documenting each respiratory inflection and monitoring their diet. In a recent large study we have shown that parental reports of common colds and chest infections do influence how many children have asthma at age 6. Also in this study, breast feeding for at least 4 months seemed to be protective against developing asthma. However, we were not able to verify how many infections the children in that study actually had. We are currently studying a population of 236 infants, all of whom are at high risk of developing asthma and allergies. At the end on November 1998, 163 of these infants had reached one year of age. During the first year of life, these infants had a total of 669 respiratory infections, with individual babies having between 0 and 11 infections. We now plan to monitor these children until they turn 5, when we will determine how many have asthma and allergies. In this way we will be able to determine whether children who have more respiratory infections early in life are more or less likely to have asthma and allergies at 5 years of age. We will also be able to tell whether breast-feeding is able to decrease the chance of developing asthma and allergies.Read moreRead less
Cholera Toxin Co-receptor Interaction In The Prevention Of Inflammatory Autoimmune Disorders
Funder
National Health and Medical Research Council
Funding Amount
$359,577.00
Summary
Vaccination is undoubtedly one of mankind's greatest achievements. While infections continue to be the major cause of morbidity and mortality in the developing world, heart disease, cancer, chronic allergies and autoimmune disorders are taking their toll in advanced societies. Our expanding knowledge of these 'modern diseases' shows that the immune system plays a central role and hence it is important to learn if new immunologically-based therapies can be developed for such chronic human disorde ....Vaccination is undoubtedly one of mankind's greatest achievements. While infections continue to be the major cause of morbidity and mortality in the developing world, heart disease, cancer, chronic allergies and autoimmune disorders are taking their toll in advanced societies. Our expanding knowledge of these 'modern diseases' shows that the immune system plays a central role and hence it is important to learn if new immunologically-based therapies can be developed for such chronic human disorders. This project takes advantage of our recent discoveries on the immunological properties of a hitherto feared molecule - cholera toxin. We have shown that one portion of the toxin, the B-subunit, responsible for binding to cell membranes, possesses remarkable immunomodulatory properties that prevent the development of inflammatory autoimmune disorders such as rheumatoid arthritis in animal models. The B-subunit, in contrast to the whole cholera toxin, is non-toxic and has no adverse effects in humans. This has sparked considerable interest in the development of such molecules as novel anti-inflammatory agents and highlighted the necessity to better understand the B-subunit's mode of action. Current theory specifies that the B-subunit mediates its immunomodulatory effects by binding and cross-linking a ubiquitous plasma membrane glycosphingolipid, GM1 ganglioside. The essential role of GM1-interaction was recently challenged by our discovery that a mutant B-subunit (H57A) was unable to modulate the immune system even though it still bound to GM1; suggesting that the B-subunits interact with another receptor (or co-receptor), and that it is this second interaction that directs the immune system to prevent development of autoimmune disease. The primary aims are to characterize the nature of B-subunit interaction with the cell membrane and to identify the co-receptor. This work has the potential to provide a new target for drug discovery and development of immunotherapeutics.Read moreRead less