The Role Of Capsulin, A New BasicHelix-Loop-Helix Factor, In Differentiation And Repair Of The Gastric Mucosa.
Funder
National Health and Medical Research Council
Funding Amount
$131,812.00
Summary
We aim to understand the role that a new factor plays in the processes whereby the lining of the stomach is continually renewed, and also repaired after injury due to inflammation and ulceration. Once we understand the role of this factor and how it works, we may be able to use this factor as a therapeutic to prevent the initial formation of inflammation and ulceration in the stomach that can lead to more serious diseases, such as cancer.
Mechanics Of Normal And Disordered Gastric Emptying Studied Using Simultaneous Ultrasound And High Resolution Manometry
Funder
National Health and Medical Research Council
Funding Amount
$145,626.00
Summary
Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties ....Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties food is incomplete, and there is little information as to the mechanisms by which diseases cause abnormal stomach emptying. Recent developments in recording methods mean that we can now simultaneously measure stomach contractions, the pressures these generate and flow from the stomach. This information is synchronised and displayed for analysis using computer techniques. In this project these novel methods will be used initially to examine the normal processes by which meals with a variety of compositions and consistencies empty from the stomach. This will provide information as to which aspects of the way the stomach functions are important for breaking down food into particles, and which aspects control the flow of food from the stomach into the intestine. The mechanisms by which the rate of emptying of the stomach is controlled by feedback signals caused by the presence of foodstuffs in the small intestine will be investigated by examining the effects of infusing nutrients into the intestine on the motions of the stomach wall, pressures within the stomach and the passage of stomach contents into the small intestine. The mechanism of action of drugs and diseases which slow stomach emptying will then be examined by measuring the movements, pressures and emptying of the stomach in subjects receiving the drug, or in patients with dibetes, and comparing this information with the processes observed during normal stomach emptying.Read moreRead less
POST-OPERATIVE CROHNS DISEASE RECURRENCE: EVALUATION OF AETIOLOGIC FACTORS And AN ALGORITHM And TRIAL TO MODIFY RECURRENCE.
Funder
National Health and Medical Research Council
Funding Amount
$123,472.00
Summary
Eighty percent of patients with Crohn’s disease (CD) need an operation at some stage. The disease invariably returns, and in 70% of patients further surgery is required. This project aims to determine whether particular bacteria cause the disease to recur and will look at the value of antibiotic treatment to prevent severe disease recurring. It will also assess whether adjusting treatment based on changes seen at the operative site during follow-up influences disease recurrence .
Relationships Between Diet And Gastric Motor Function In Functional Dyspepsia
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Functional dyspepsia (FD) is a condition characterised by abdominal symptoms without a cause that is identifiable by conventional diagnostic tests. Symptoms (eg fullness, bloating) are frequently induced by eating. 20 - 40 % of the adult population in Western countries are affected by FD, and the condition, therefore, represents a considerable financial burden to the health care system. FD affects quality of life adversely. In many people with FD, stomach contractions and the 'sensitivity' of th ....Functional dyspepsia (FD) is a condition characterised by abdominal symptoms without a cause that is identifiable by conventional diagnostic tests. Symptoms (eg fullness, bloating) are frequently induced by eating. 20 - 40 % of the adult population in Western countries are affected by FD, and the condition, therefore, represents a considerable financial burden to the health care system. FD affects quality of life adversely. In many people with FD, stomach contractions and the 'sensitivity' of the stomach are abnormal. Often, people with FD avoid fatty foods in the belief that these cause or exacerbate symptoms. There is, however, little information about the potential role of dietary habits in causing symptoms, the relationship between eating and disturbances in stomach function, and the impact of dietary changes on symptoms. Our previous studies suggest an important role for nutrients, particularly fat, in FD. We will address the hypothesis that dietary factors, particularly fat intake, have substantial implications for the pathophysiology and treatment of FD. Our studies will involve physiological (stomach emptying, appetite and food intake) and epidemiological (dietary habits, dyspeptic symptoms and quality of life-related aspects) measurements. The subjects-patients with FD will receive standardised test meals of varying nutrient composition, and we will study the effects on their stomach and on symptoms. We will also test some medications in an attempt to alleviate symptoms during and after food ingestion, particularly after fatty foods. Other studies will assess the dietary habits of patients with FD in relation to symptom occurrence and investigate the possibility that dietary intervention (reduction of fat content in the diet, exclusion of offending foods) will benefit these patients. The proposed studies will provide the most comprehensive studies to date of the relationship between symptoms in patients with FD with dietary habits and stomach function.Read moreRead less
Cooperative Motor Control Of The Pyloric Junction By Myogenic And Neuronal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$271,527.00
Summary
The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little infor ....The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little information is available about the interaction between nerve, muscle and pacemaker cells during this coordinated movement. In this project, we will investigate how the nerve, muscle and pacemaker cells work together to control this coordinated movement. We will study this mechanism at both cellular and organ levels and try to establish the patterns of muscle movement and their coordination between the stomach and the small intestine. The interaction between the nerve and pacemaker cells will be characterised in these studies. Our work will provide structural evidence for this activity. It includes identification of the nerve pathways connecting between the small intestine and stomach and determination of whether the pacemaker cell network is an uniform continuous or a discontinuous or a transitional structure across the junction. These studies will reveal the correlation between pacemaker cell mediated activity and the density of these cells in each junctional region. We will also determine whether the difference in propagation activity across the junction is due to differences in the number of cells for signal conduction or electrical connections between the cells. This study will advance our knowledge for understanding how the nerve, muscle and pacemaker cells work in concert in this junction, which is an important step for further clinical investigation of related disease.Read moreRead less
Factors Controlling Leucocyte Migration In Healthy Intestine And In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$195,217.00
Summary
Inflammatory bowel diseases (IBD) are relapsing and remitting disorders of the intestine that create substantial disability in a relatively young population of patients. Our treatments for these conditions have changed little in the last 30 years and they are commonly accompanied by side effects. Research into the mechanisms controlling the gut inflammation offers promise for the development of novel, targeted and less toxic therapies. The major mediators of damage in IBD are white blood cells r ....Inflammatory bowel diseases (IBD) are relapsing and remitting disorders of the intestine that create substantial disability in a relatively young population of patients. Our treatments for these conditions have changed little in the last 30 years and they are commonly accompanied by side effects. Research into the mechanisms controlling the gut inflammation offers promise for the development of novel, targeted and less toxic therapies. The major mediators of damage in IBD are white blood cells recruited from the circulation to affected intestine. This recruitment is induced by the production in damaged intestine of chemokines, proteins of the immune system that attract and activate white blood cells. Chemokines act through chemokine receptors on the surface of white blood cells, and earlier research by our group has demonstrated that these chemokine receptors can be functionally modulated by neuropeptides, proteins unrelated to chemokines that normally transmit messages within the nervous system. This project aims to explore the chemokines and chemokine receptors responsible for the recruitment of white blood cells to normal and IBD-affected intestine, in order to determine therapeutic targets for novel treatments. Moreover, the role of neuropeptides in modulating the recruitment of white blood cells to the intestine will be examined in cells from the human intestine, both normal and IBD-affected, as well as in an animal model of IBD. This project will provide an understanding of the signals responsible for the attraction of damaging white blood cells to sites of inflammation in the bowel and will indicate mechanisms used by the immune system to regulate those signals. It has the potential to direct us to new therapies that use highly targeted and physiologically appropriate approaches to controlling white blood cell trafficking in health and disease.Read moreRead less
Factors Regulating Initiation, Progression And Submucosal Invasion In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associa ....Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associated) genes are more strongly associated with cancer development after long-term infection than others. We have recently developed a genetically modified mouse which has a minor defect in a regulatory pathway which controls some aspects of gut inflammation. Surprisingly 100% of these mice rapidly develop gastric cancer which has many similarities with the human disease, including inflammation, loss of structure of the stomach lining and penetration of cancerous cells into the muscle layers below. The objectives of this project are to work out whether HP induces similar changes in normal stomach cells as occurs in our defined mouse model of gastric cancer. Specifically we will determine if HP disturbs the way a particular mediator of inflammation works, and if so the way this impacts on certain stomach genes which detect cancerous cells and prevent tumor growth.Read moreRead less
Functional Relationships Of Gastrin And Its Regulators In The Developing And Diseased Gastrointestinal Tracts
Funder
National Health and Medical Research Council
Funding Amount
$607,832.00
Summary
Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and by c ....Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and by cancers of the colon. It seems that the different types of gastrins have different effects and act through distinct receptors. The production and effects of gastrin are mediated in part by the local factor histamine and modified by the hormone somatostatin. The amount, type and activity of gastrin, and the interactions with histamine and somatostatin, will be measured in foetal and newborn animals, and people with or at risk of developing colon cancer.Read moreRead less
Gastric Cancer: Early Detection Of Disease, Relapse And Prediction Of Extent Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$421,800.00
Summary
Gastric cancer (GC) is the second commonest cause of cancer in the world. The mainstay of treatment for GC is surgical resection, but despite improvements in surgical interventions the mortality rate remains high. The 5 year survival rate of GC is about 30% over 5 years. Accurate staging is fundamental to the management of GC and current investigations are inadequate. It has become possible to measure the activity of thousands of genes to identify those genes that predict whether a patient will ....Gastric cancer (GC) is the second commonest cause of cancer in the world. The mainstay of treatment for GC is surgical resection, but despite improvements in surgical interventions the mortality rate remains high. The 5 year survival rate of GC is about 30% over 5 years. Accurate staging is fundamental to the management of GC and current investigations are inadequate. It has become possible to measure the activity of thousands of genes to identify those genes that predict whether a patient will survive or succumb to their disease. We propose to use gene expression profiling to predict the risk of recurrence of gastric cancer in patients. We will examine over 270 tumours and use an independent group of patients to evaluate the test. We aim to develop a test that will help the clinician decide the type of surgical resection to perform or whether to give adjuvant chemotherapy. The test may also guide the use of more specific anticancer drugs. Early detection of GC is very important because patients with early stage GC have better outcome. We have already analysed over 60 GC tumours with microarrays and found genes that are specifically expressed by the tumours that are potential candidates as cancer markers. We plan to examine more cases of GC, both to find more genes and validate our candidate genes as tumour markers. We also want to look for patterns of proteins in blood of patients that identifies GC and use this pattern to follow patient progress to treatment.Read moreRead less