Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72410/1/bjp.2008.204.pd

Child occupants and side-impact crashes : Commentary

Commentary piece. Side-impact crashes are more dangerous for children and represent a challenge to injury prevention efforts. A recent study found that significant injury occurred in 41% of side-impact crashes, 15% of frontal impacts, and 3% of rear impacts involving child occupants. In addition, other studies have reported child mortality rates of 30% for side-impact crashes and 17% for frontal-impact crashes. Because of the large size of the head in relation to the rest of the body, a child's head and neck are more vulnerable than those of an adult. Children have more head surface area and a lower-seated height, both of which increase the risk of contact with the interior door panel or pillars during side-impact crashes.Pediatrics, Department ofMedicine, Faculty ofOther UBCNon UBCReviewedFacult

Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells

Kit receptor and its ligand stem cell factor (SCF) are critical regulators of mast cell production, proliferation, degranulation, and chemotaxis. In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells displayed a striking defect in cell spreading and lamellipodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn−/− mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn−/− mast cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role upstream of PI3K and Rac GTPases to promote the reorganization of the cytoskeleton during mast cell spreading and chemotaxis

Factors affecting the avi-faunal distribution in the three lagoons (Malala, Embillakala and Bundala Lewaya) of Bundala National Park (A Ramsar Wetland) in Sri Lanka

Bundala National Park, covering an area of 6216 ha, is located about 250 Km Southeast of Colombo, in the Hambantota District. The shallow brackish water lagoons located within the park - Koholankala (390 ha), Malala (650 ha), Embilikala (430 ha) and Bundala (520 ha) form a complex wetland system that harbors a rich bird life, including several species of migratory waterfowl. This led to the declaration of Bundala as Sri Lanka's first Ramsar wetland - a wetland of international importance especially for migratory waterfowl, in 1990. Distribution and the composition of the aquatic bird species inhabiting these lagoons with respect to the habitat characters are poorly understood. Present study was conducted (December, 2000-December, 2001) in Malala, Embillakala and Bundala Lewaya lagoons with the objective of investigating the relationship between some lagoon parameters (salinity, perimeter, area) and water bird abundance and diversity. Data were collected weekly basis. Bird abundance and the composition significantly differ among lagoons. This study revealed the most abundant bird groups in each lagoon. Highest aquatic bird diversity was recorded in Embillakala. This high diversity in Embillakala lagoon can be partly attributed to its moderate salinity, water depth and abundance of aquatic macrophytes. Lowest aquatic bird diversity was recorded in Bundala Lewaya. This study also revealed that salinity, aquatic macrophytes and lagoon area were key determinants of aquatic bird abundance. Although these lagoons are in the same landscape, they vary each other physically and chemically so that different bird communities might be supported

Sperm maturation in vitro: co-culture of spermatozoa and epididymal epithelium

Sperm maturation involves an intimate interaction between spermatozoa and the epididymal epithelium. Aspects of this relationship can be examined by co-incubating epididymal spermatozoa with epididymal epithelium in vitro. Plaques of epididymal epithelium from a variety of species (for example rodents, dogs, humans) can be maintained in culture medium supplemented with growth factors and androgens. When co-incubated with these epithelial cultures, immature epididymal spermatozoa undergo maturation changes that lead to the acquisition of progressive motility, zona binding and, in some instances, fertilizing capacity in vitro. The use of such co-culture techniques for the understanding of sperm maturation in vitro and in vivo is reviewed with reference to recent experiments

Protein tyrosine phosphatase-a complexes with the IGF-I receptor and undergoes IGF-I-stimulated tyrosine phosphorylation that mediates cell migration

Protein tyrosine phosphatase-α (PTPα) is a widely expressed receptor-type phosphatase that functions in multiple signaling systems. The actions of PTPα can be regulated by its phosphorylation on serine and tyrosine residues, although little is known about the conditions that promote PTPα phosphorylation. In this study, we tested the ability of several extracellular factors to stimulate PTPα tyrosine phosphorylation. The growth factors IGF-I and acidic FGF induced the highest increase in PTPα phosphorylation at tyrosine 789, followed by PMA and lysophosphatidic acid, while EGF had little effect. Further investigation of IGF-I-induced PTPα tyrosine phosphorylation demonstrated that this occurs through a novel Src family kinase-independent mechanism that does not require focal adhesion kinase, phosphatidylinositol 3-kinase, or MEK. We also show that PTPα physically interacts with the IGF-I receptor. In contrast to IGF-I-induced PTPα phosphorylation, this association does not require IGF-I. The interaction of PTPα and the IGF-I receptor is independent of PTPα catalytic activity, and expression of exogenous PTPα does not promote IGF-I receptor tyrosine dephosphorylation, indicating that PTPα does not act as an IGF-I receptor phosphatase. However, PTPα mediates IGF-I signaling, because IGF-I-stimulated fibroblast migration was reduced by ∼50% in cells lacking PTPα or in cells with mutant PTPα lacking the tyrosine 789 phosphorylation site. Our results suggest that PTPα tyrosine phosphorylation can occur in response to diverse stimuli and can be mediated by various tyrosine kinases. In the case of IGF-I, we propose that IGF-I-induced tyrosine 789 phosphorylation of PTPα, possibly catalyzed by the PTPα-associated IGF-I receptor tyrosine kinase, is required for efficient cell migration in response to this growth factor

CD34 function in intracellular signaling and mucosal inflammatory disease development

Medicine, Faculty ofReviewedFacult