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Physiological Mechanisms Of Efficacy Of Cervical Flexor Muscle Retraining
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therap ....Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therapeutic exercise works. It has been argued that parameters such as changes in muscle strength, endurance, joint position sense or muscle coordination may be responsible for the clinical efficacy. It is difficult to disentangle the effective component of exercise strategies and thus prescribe the most effective exercise strategies. This series of experiments will evaluate the physiological factors that change with a specific exercise intervention and to compare different exercise modalities in order to identify the most effective means to induce these changes. Cervical muscle training, using a proven exercise intervention strategy for chronic neck pain and headache, has been chosen as the model to investigate these questions. This exercise strategy has been chosen not only because it has been shown to be effective, but also because it does not conform to contemporary rationales for strength or endurance training. Thus while effective in relieving pain, it is unlikely to produce changes in these parameters. Thus other mechanisms are likely to be responsible for the clinical change. This research stands to make a significant contribution to exercise therapeutics by identifying the effective components of different exercise methods and investigating the pain relieving effects of the specific exercise. This knowledge will lead to the construction of a research based exercise program for neck pain patients, rather than have the current situation of often arbitrary choice of exercise.Read moreRead less
A -induced Cell Death Signalling By The P75 Neurotrophin Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$546,382.00
Summary
The amyloid peptide A is central to the cause of Alzheimer's disease. We have recently found that A can activate the cell death receptor p75NTR which is found in the nerve cells that die in Alzheimer's disease. This project will study whether this death pathway underpins the neuronal death associated with Alzheimer's disease. It will also determine the mechanism by which A activates p75NTR death signalling, and identify biochemical ways to prevent this from occurring.
This project will characterise the biological and functional properties of a novel human pro-inflammatory S100 protein. The protein is a natural component of the innate immune system and is regulated in cells by mediators of inflammation and infection. Our preliminary experiments indicate that this protein can activate mast cells. These cells reside in almost all body tissue and are located close to blood vessels and nerves. This location makes them prime targets to trigger vascular and inflamma ....This project will characterise the biological and functional properties of a novel human pro-inflammatory S100 protein. The protein is a natural component of the innate immune system and is regulated in cells by mediators of inflammation and infection. Our preliminary experiments indicate that this protein can activate mast cells. These cells reside in almost all body tissue and are located close to blood vessels and nerves. This location makes them prime targets to trigger vascular and inflammatory events. They are known to be important in allergy and infection and have a proposed role in chronic inflammatory processes. Although the mechanisms of mast cell activation contributing to acute responses in allergic reactions are well accepted, ways in which they are activated in asthma and other chronic inflammatory disease are virtually unknown. We will use lung biopsies from patients with asthma to detect patterns of expression of the protein and determine its effects on lung mast cells. A murine model will be used to define the characteristics of inflammation induced by the S100 protein and the role of mast cells in this process. Structural studies will define the parts of the protein necessary for mast cell activation. We will attempt to identify its receptor on mast cells to enable future studies to define how the protein triggers the cells to produce mediators such as histamine and those causing blood vessel changes. This knowledge could lead to design of novel drugs that could regulate this process. Results from this project will provide new knowledge of chronic inflammatory processes and could result in designing novel strategies to regulate these. Studies are relevant to infectious diseases and many other conditions with a chronic inflammatory basis, including asthma, rheumatoid arthritis, cardiovascular disease, cystic fibrosis and infection.Read moreRead less
How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Bombesin Like Peptides As Autocrine Growth Factors In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now kn ....Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. We will study the expression and production of GRP and its receptors at the gene and protein level, the ability of GRP to stimulate growth, the chemical structures of GRP, and the potential of antagonists of GRP to modulate growth. Studies will be performed in patients with bowel cancer, in animal models of bowel cancer, and with bowel tumours removed from patients and bowel cancer cell lines. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as GRP receptor antagonists and radiolabelled GRP analogues for radiotherapy.Read moreRead less