ANALYSIS OF KNEE KINEMATICS- An MRI Study Of The Normal, Anterior Cruciate Injured, And Reconstructed Knee.
Funder
National Health and Medical Research Council
Funding Amount
$161,320.00
Summary
People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one norma ....People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one normal knee. The subjects will simulate a squat inside the MRI magnet against a weighted footplate. The images will be taken at fifteen degree intervals of knee movement. The contact points between the joint surfaces will be measured and compared to the normal knee. This imaging will be repeated after surgical repair, and then again two years later, to assess whether the normal movement pattern has been restored.Read moreRead less
Interactions Between Systems That Control Sodium Channels In Renal Epithelia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The transport of sodium ions by the kidney, gut and lungs not only regulates blood pressure, it also regulates the amount of fluid in the gut and in the lungs. One of the most important proteins that underlie the transport of sodium in these tissues is the so-called epithelial sodium channel. The activity of these epithelial sodium channels is regulated by a wide variety of systems. Some of these regulatory systems act in response to changes in the body's requirements for sodium transport. Other ....The transport of sodium ions by the kidney, gut and lungs not only regulates blood pressure, it also regulates the amount of fluid in the gut and in the lungs. One of the most important proteins that underlie the transport of sodium in these tissues is the so-called epithelial sodium channel. The activity of these epithelial sodium channels is regulated by a wide variety of systems. Some of these regulatory systems act in response to changes in the body's requirements for sodium transport. Others act in response to changes in capacity of cells in which the sodium channels are found to continue transporting sodium. In this project we will study the mechanisms that regulate the activity of the epithelial sodium channels, and in particular, how these mechanisms interact so as to maintain a level of sodium channel activity that is appropriate to both the needs of the organism and to the needs of the sodium transporting cells. The outcomes of this project will be improved understanding of the function of the kidney, gut and lungs in both health and disease. It may also lead to novel drug targets for treatment of major diseases in which the activity of sodium channels is abnormal. These disease include hypertension, cystic fibrosis, pulmonary oedema and influenza.Read moreRead less
Young People With Old Knees: Knee Ligament Reconstruction And Early Joint Changes
Funder
National Health and Medical Research Council
Funding Amount
$782,727.00
Summary
Individuals who have undergone a knee reconstruction are at increased risk of knee osteoarthritis - 'younger people with older knees'. This may be partly due to increased knee load. This study aims to investigate whether muscle strength and activation as well as walking patterns influence changes in the knee joint structure as measured on magnetic resonance imaging. This may lead to rehabilitation strategies to address these factors so as to prevent the premature onset of knee osteoarthritis.
Growth-factor Induced Signalling Pathways Involved In The Regulation Of Lens Cell Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Cataract, the loss of transparency of the eye lens, is a major cause of blindness in the world. A cure for cataract depends on a better understanding of the molecular processes in the normal and cataractous lens. Lens growth is regulated by controlled proliferation of epithelial cells and their precise localised differentiation into fibres. As disruption of this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation may provide insights ....Cataract, the loss of transparency of the eye lens, is a major cause of blindness in the world. A cure for cataract depends on a better understanding of the molecular processes in the normal and cataractous lens. Lens growth is regulated by controlled proliferation of epithelial cells and their precise localised differentiation into fibres. As disruption of this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation may provide insights into the mechanisms involved in cataract formation. Following cataract surgery, for example, a number of patients develop aftercataract which results from the response of lens cells remaining after surgery. These residual cells, unlike those tightly regulated in the normal lens, begin to divide and differentiate in an attempt to form a new lens. The main aim of this study is to understand what regulates the proliferation and differentiation of lens cells. Growth factors are key regulators of cell behaviour and our studies provide evidence that members of the FGF, PDGF and IGF growth factor families play pivotal roles in the lens by influencing cell proliferation and differentiation. Growth factors stimulate cellular processes by activating specific cell surface receptors. Once activated, these receptors switch on specific intracellular signalling pathways leading to a specific cellular response. To understand how different growth factors mediate and regulate lens cell proliferation and fibre differentiation, we plan to examine the role of FGF-, PDGF- and IGF-induced signalling in normal lens biology. To do this, we will use a well established lens explant culture system to dissect the signalling pathway(s) downstream of specific receptor activation and correlate this with a specific cellular response. By understanding the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.Read moreRead less
Roles For MAPK-ERK1-2, -catenin-TCF And Smad3 Mediated Signalling Pathways In TGF -induced Cataract
Funder
National Health and Medical Research Council
Funding Amount
$339,071.00
Summary
Posterior capsular opacification (PCO) is a common and costly complication of cataract surgery that is caused by aberrant growth of lens cells. The TGF growth factor family causes PCO. TGF activates three signalling pathways in the lens, MAPK-ERK1-2, -catenin-TCF and Smad3; however currently we do not know which one induces PCO. This project will identify the pathway(s) that prevent TGF from causing cataracts. This is critical for the development of pharmaceuticals to prevent PCO.
Studies Of Antigen Presenting Cells In The Anterior Segment Of The Eye And Their Role In Immune-mediated Ocular Disease
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated imm ....Dendritic cells (DC) are considered the 'sentinels' of the immune system because they are capable of trapping antigenic material derived from invading organisms such as bacteria and viruses in peripheral tissues-organs (skin, gut, respiratory tract etc) and then transporting these antigens to the lymphoid organs where they 'alert' the immune system to potential 'dangers' and elicit appropriate T cell responses. If the antigens are novel this mechanism forms the basis of primary cell-mediated immune responses. Previously 'educated' T cells may upon contact with antigens in the periphery (when presented by other antigen presenting cells [APCs], such as macrophages) become activated. This forms the basis for secondary immune responses. Immune and inflammatory responses in the eye are held in check to avoid permanent damage to the delicate tissues and maintain visual function. The mechanisms which regulate immunological responses in the eye are only now becoming clear. Studies in the Chief Investigators laboratory over the last 7 years have been aimed at unravelling the life cycle and function of APCs in the eye. The present study has three specific aims: 1) Determining whether DC in the eye once they have taken up antigens migrate to the spleen or local lymph nodes? 2) The second aim of this project is to use an animal model of uveitis and transfer fluorescent labelled donor T cells to study the events in the living eye which lead to autoimmune uveoretinitis. In particular we wish to identify the cells that present antigen to infiltrating lymphocytes. 3) Patients often develop posterior uveitis (an autoimmune condition) after a cold or bacterial infection. We aim to mimic conditions of acute inflammation in the eye to see whether this may secondarily predispose the eye to attack by autoreactive lymphocytes.Read moreRead less