Browsing by Author "Ho, May"

Now showing 1 - 7 of 7
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    Hepatitis E in a Canadian Traveller
    (1995-01-01) Akai, Peter S; Fonseca, Kevin; Horne, Duff; Ho, May
    Hepatitis E is clinically indistinguishable from hepatitis A and is caused by an enterically transmitted rna virus that is endemic in developing countries of Asia, Africa, the Middle East and North America. This report describes a Canadian traveller to Nepal, Thailand and India with one of the first confirmed cases of hepatitis E reported in Canada. Although this disease is usually self-limited with no known sequelae, it may produce fulminant hepatitis with a high case fatality rate in pregnancy. Diagnosis can be confirmed by serological tests. Apart from strict food and beverage hygiene, there are presently no prophylactic measures against this disease, and pregnant women in the third trimester should avoid travel to endemic areas.
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    Regulation of endothelial cell function by p. falciparum
    (2012) Gillrie, Mark; Ho, May
    Plasmodiumfalciparum is a protozoan infection of human erythrocytes. Despite optimal therapy, mortality due to multi-organ failure in severe falciparum malaria remains high at 5 to 20%. Correlation of disease severity to multiple clinical markers of endothelial activation suggest a central role for endothelial cells in the pathophysiology of severe malaria. Detailed studies in models of other systemic infections, including bacterial sepsis, have highlighted the central role of endothelial cells in pathogen recognition, barrier function and proinflammatory signaling in determining organ failure and mortality. We hypothesized that in addition to providing points of attachment for sequestering infected red blood cells (IRBC), microvascular endothelial cells can directly recognize parasite products released by adherent IRBC at the time of schizogony through innate receptors. Using clinical P. falciparum isolates we showed that parasite sonicates but not intact IRBC disrupted primary human dermal and lung endothelial cell barrier function in a Src-family kinase-dependent manner. Increased endothelial permeability was characterized by redistribution of junctiona1 proteins Z0-1 and VE-cadherin away from sites of cell-cell contact. The active parasite component appeared to be a merozoite­associated protein. We further examined the ability of P. falciparum sonicates and merozoites to induce proinflammatory signaling and discovered production of broad proinflammatory responses including endothelial chemokines and adhesion molecules. We defined a critical role for Src-family kinase Lyn and downstream p38 MAPK in endothelial proinflammatory responses to P. falciparum sonicate using IL-8 protein production as a functional readout. Further characterization of the active component in P. falciparum sonicates and merozoites revealed parasite histones as an activator of both endothelial permeability and proinflamrnatory protein production. Both activities of histones were found to be dependent on the strong cationic charge of these proteins. Proinflammatory responses to P. falciparum histones were were partially dependent on Toll-like receptor 2 (TLR2). Recombinant human activated protein C (rhAPC) cleaved parasite histones and abrogated the increases in endothelial permeability and IL-8 production. More importantly, levels of both parasite and human histones were markedly elevated in patients with severe malaria as compared to healthy controls, and patients with uncomplicated infection and bacterial sepsis. Together, these findings strongly suggest Src-family kinases and parasite histones as targets for adjunctive therapies in severe falciparum malaria.
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    Role of CD36 in endothelial activation by TLR2 ligands
    (2008) Kapadia, Roxna; Ho, May
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    The role of nitric oxide in Plasmodium falciparum cytoadherence
    (2002) Serirom, Supattra; Ho, May
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    The Role of NLRP3 in Shiga toxin Induced Inflammation
    (2018-01-08) Bondzi-Simpson, Nana Adom; Muruve, Daniel; Ho, May; Chadee, Krisendath; Armstrong, Glen D.
    Enterohemorrhagic Escherichia coli (EHEC) is a pathogen that causes severe colitis. Shiga toxins (Stx) are a major virulence factor for EHEC and Stx-induced inflammation and cell death play a critical role in the development of EHEC-related disease. Therefore, the goal of this project was to examine the mechanisms by which Stx activates proinflammatory cytokine IL-1β and cell death in human macrophages. Stx induced ROS-dependent IL-1β secretion and pyroptosis in human THP-1 macrophages but not murine macrophages that lacked the Stx receptor CD77. Stx triggered the assembly of NLRP3, ASC and caspase-1 containing inflammasomes and genetic deletion of NLRP3 abolished Stx-induced IL-1β maturation and pyroptosis. Stx preferentially induced expression the endoplasmic reticulum stress receptor IRE1α. Pharmacological inhibition of IRE1α significantly reduced Stx-induced mitochondrial ROS production, IL-1β, and pyroptosis. These data suggest that Stx activate the IRE1α arm of the ER stress pathway upstream of mitochondrial ROS to trigger the NLRP3 inflammasome.