B cells make antibodies that help combat pathogens. The B cell receptor, chemokine receptors and integrins on the cell surface are molecules that send signals to regulate B cell migration and adhesion. These processes are essential for B cells to enter the lymphatic system and to identify and adhere to foreign molecules (antigens) for the purpose of mounting a protective immune response. Proteins called Rap GTPases and Pyk2 are important in controlling B cell migration and adhesion, but the mechanisms involved are not well understood. Kathy Tse is investigating how Rap regulates Pyk2 and how Pyk2 promotes B cell migration and adhesion. Specifically, she is examining the localization and activity of Pyk2 during cell migration and adhesion. Knowledge from this study will allow better understanding of normal B cell movement and activation, and has potential for identifying drug targets for treating immune system diseases, including cancer.
Year: 2005
Respiratory muscle training and attenuation of the metaboreflex
The heart pumps oxygen-rich blood throughout the body. Because a limited volume of blood circulates, the body must decide how to distribute the available blood. Research indicates that during intense exercise, the respiratory muscles begin to demand a greater proportion of the total blood flow thus limiting the blood available to the other exercising musces of the body. In healthy people, strenuous exercise fatigues the diaphragm, the primary muscle that controls breathing. Jonathan Witt is studying whether daily training sessions to strengthen breathing capacity will improve the diaphragm’s efficiency, reduce the amount of blood required when breathing harder, and improve blood flow to the legs. The findings could help patients with chronic obstructive pulmonary disorder (COPD) and cystic fibrosis, whose breathing muscles are overworked, and those with chronic heart failure, who pump even less blood from the heart. The research could lead to new therapies to improve strength and functional capacity in these patients.
Mending and maintaining the quality of lives: Evaluating the treatment programs provided for mentally disordered offenders in British Columbia
The Forensic Psychiatric Hospital in British Columbia is currently evaluating approximately 30 rehabilitation programs offered to psychiatric patients who are found not criminally responsible for offenses because of severe mental illnesses, such as major mood disorders, schizophrenia and other psychotic disorders. While standard outcome indicators are needed to evaluate the effectiveness of these programs, these are difficult to develop because each patient experiences different symptoms and disabilities. Carol Wong is assessing a patient-centered evaluation tool (called Goal Attainment Scaling) for measuring patient improvement. Using this approach, the treatment team identifies and evaluates the most important goals and outcomes for each patient to achieve in a particular timeframe. Carol is also examining whether a patient’s readiness for treatment has an impact on outcomes, as this factor has consistently been overlooked in practice. The results of this research should help improve the effectiveness of rehabilitation programs, therefore reducing the likelihood of repeat offenses and improving mental health and quality of life for forensic psychiatric patients and their families.
Cardiovascular disease risk in patients with spinal cord injury before and after exercise rehabilitation
Eighty percent of spinal cord injuries happen to people under 30 years of age. Medical advances have increased life expectancy for these individuals, and consequently, they are susceptible to the same chronic conditions as able-bodied persons. However, people with spinal cord injuries have a much higher risk for cardiovascular disease. About 25 percent of the general population has a form of cardiovascular disease, but 60 to 70 percent of people with spinal cord injuries have a form of the disease. Physical inactivity is a major risk factor for cardiovascular disease, and people with spinal cord injury are often inactive and have poor cardiovascular fitness. Dominik Zbogar is investigating whether an arm cycling training program could improve aerobic fitness, heart function, muscle function, vascular (blood vessel) health, and psychological well-being in people with spinal cord injuries. This research could clarify the importance of exercise rehabilitation to overall health and quality of life for people with spinal cord injuries, and contribute to prevention and treatment of cardiovascular disease.
Reducing pain and complications following total knee arthroplasty by minimizing patellofemoral contact loads intra-operatively
The primary reason for someone to undergo a knee replacement is to reduce pain due to arthritis. Unfortunately, some people who have the surgery will have similar, or even more, pain after their knee replacement. It is difficult to predict which patients will have this outcome and it is difficult to treat the pain post-operatively. Much of the pain is likely related to points of high pressure (high contact loads) between the kneecap (patella) and the thigh bone (femur), or unusually stretched soft tissues between the bones. A potential way to minimize pain and other problems following surgery would be to detect these points of high pressure during the operation and make adjustments to the positions of the implants or the tensions of the soft tissues to reduce the contact loads. If the contact loads could be minimized during the surgery, the outcome would be less pain and fewer subsequent surgeries due to wear, loosening or fracture of the components. Dr. Carolyn Anglin intends to reduce pain and improve the outcome of knee replacement surgery by developing a computer-aided system to help identify pressure points during surgery. In addition to performing a cadaver study to investigate the effects of different placements of the artificial components on cadaver specimens, she will review X-rays, patient charts and patient-completed questionnaires to determine the relationship between the placement of components and the resulting quality of life after surgery. Her ultimate goal is to develop a system that can measure the forces between the kneecap and the thigh bone, then display them on a computer screen. This will allow the surgeon to choose the best positions for the components. Such a system could dramatically reduce the incidence of pain and complications following knee replacement surgery.
Intermittent hypoxia and the chemoreflex control of ventilation
Exposure to high altitude can have adverse physiological effects, including altitude illness and decreased occupational and athletic performance. People can acclimatize to high altitude by making a gradual ascent and taking certain medications, but these drugs can have negative side effects, and gradual ascent is not always possible. Dr. Michael Koehle is researching whether daily exposure to intermittent hypoxia (low oxygen gas) could potentially reduce altitude illness and improve exercise performance at higher altitudes. Intermittent hypoxia is a commercially available treatment that has been shown to increase breathing capacity at rest after six days of the treatment. However, the treatment’s risks and benefits are poorly understood, and its effects on breathing during exercise are unknown. Michael is studying how intermittent hypoxia affects breathing in healthy individuals during rest and exercise. The results could be used to determine the most effective protocol for increasing breathing capacity, and could indicate the optimal dose for preventing altitude illness. The research may also have clinical applications for treating other conditions such as sleep apnea, when repetitive pauses in breathing occur during sleep.
Effectiveness of a fall risk reduction program for a community dwelling stroke sample: An RCT with economic evaluation
Stroke is the number one cause of neurological disability in Canada. Each year, 50,000 Canadians have a stroke, and of those who survive, 76 per cent are left with a significant disability. Mobility impairment is the major problem faced by most people who have had a stroke, but there are few community exercise programs to maintain mobility and function after formal therapy ends. Poor cardiovascular fitness and a decrease in bone density put people who have experienced a stroke at greater risk for depression, cardiovascular disease, recurrent stroke, falls and fragility fractures. Dr. Maureen Ashe is investigating whether a community-based exercise and education program reduces these secondary complications, by improving balance, strength, bone density and overall level of fitness. While other research has looked at the short-term benefits of exercise in a clinical setting, this is the first Canadian study to examine if exercise improves health among people living in the community following a stroke, and to evaluate the cost-effectiveness of this approach in reducing falls.
Protein-targeting to the mitochondrion-like organelle of microsporidia
Microsporidia are a group of parasites that infect animals and immunocompromised humans. In infected individuals, they cause severe diseases, like encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach). As organisms that are dependent upon their host for survival, some of the microsporidia’s organelles (internal structures) and metabolic functions are missing or deficient in comparison to other single-celled organisms. One example is the mitochondrion, an organelle that normally contains many enzymes important for cell metabolism, including those responsible for the conversion of sugar to usable energy. A highly reduced relic of the mitochondrion was recently discovered in microsporidia. The role and metabolic function of this deficient organelle remain unclear. Dr. Lena Burri’s research project is to identify and characterize proteins that are imported into the mitochondrion, how these proteins are directed to their final destination and in which metabolic pathway they are involved. Understanding the function of the relic mitochondria in microsporidia may provide ways to combat these organisms, as mitochondrial functions are important potential drug targets.
Identification and characterization of mycobacterial secreted protein that interacts with the actin-binding protein coronin-1/TACO in human macrophages
The recent increase in cases of tuberculosis, mainly due to an association with human immunodeficiency virus, poor living conditions, and the emergence of drug-resistant strains, has been described as a “”global emergency”” by the World Health Organization. New therapeutic strategies are urgently needed and this requires a better understanding of the interaction of the causal agent, Mycobacterium tuberculosis, with the host cells, which include macrophages. Macrophages possess a powerful intracellular killing mechanism and play an essential role in immunity, but they are also the principal targets for mycobacterium. Mycobacterium inhibits the intracellular killing as well as antigen presentation at the cell surface to stimulate adaptive immunity. Dr. Ala-Eddine Deghmane is studying the molecular mechanisms by which pathogenic mycobacteria interferes with macrophage functions. His research aims to advance understanding of the host cells’ failure in resisting to mycobacterial infection and may lead to preventive and therapeutic anti-TB strategies.
Activity of identified spinal interneurons during wakefulness and sleep
Although they severely affect the lives of millions of individuals, Restless Leg Syndrome (RLS) and rapid eye movement behavior disorder (RBD) are two sleep disorders that are not commonly diagnosed. Unlike more common conditions like sleepwalking, RLS and RBD movements occur during REM sleep or natural active sleep (AS), which are usually characterized by a state of atonia, or sleep paralysis. During AS, sensory transmissions to the brain are reduced; spinal inhibitory interneurons (neurons confined wholly within the spinal cord) are thought to underlie this reduction. However, virtually nothing is known on how these spinal interneurons are regulated. Dr. Yanshen Deng is investigating how the activity of certain spinal interneurons change as a consequence of alterations in behavioural state e.g. wakefulness vs. sleep. She is researching how these spinal interneurons are triggered to inhibit specific spinal sensory channels, and whether such interneurons are facilitated during AS. Yanshen’s research aims to advance basic sleep and spinal cord science and may help advancement of knowledge in sleep-related sensorimotor disorders such as RLS and RBD and pain following spinal cord injury.