Invasive fungal rhinitis with adnexal involvement caused by Histoplasma capsulatum in a cat from a non-enzootic location.

CASE SUMMARY: This report describes a cat with a rare form of histoplasmosis: invasive rhinitis with adnexal involvement, mimicking disease more commonly caused by cryptococcosis or aspergillosis. This case is especially noteworthy as it was from an area where histoplasmosis is not enzootic. RELEVANCE AND NOVEL INFORMATION: Invasive fungal rhinitis causes significant morbidity in cats. Diagnostic investigation of more common pathogens includes detection of fungal antigen (Cryptococcus) or antifungal antibodies (Aspergillus). This case demonstrates that histoplasmosis can present as chronic nasal disease in cats. Histoplasma antigen testing provides a non-invasive diagnostic option. Moreover, this case serves as a reminder that histoplasmosis can affect cats anywhere, even in non-enzootic areas.

Osteoblast differentiation and migration are regulated by dynamin GTPase activity.

Bone formation is controlled by osteoblasts, but the signaling proteins that control osteoblast differentiation and function are still unclear. We examined if the dynamin GTPase, which is associated with actin remodeling and migration in other cells, plays a role in osteoblast differentiation and migration. Dynamin mRNA was expressed in primary osteoblasts throughout differentiation (0-21 days). However, alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was decreased in osteoblasts over-expressing dynamin. Conversely, ALP activity was increased following shRNA-mediated knockdown of dynamin and in osteoblasts treated with the dynamin inhibitor, dynasore. Dynasore also reduced c-fos and osterix expression, markers of early osteoblasts, suggesting a role for dynamin in pre-osteoblast to osteoblast differentiation. Since dynamin GTPase activity is regulated by tyrosine phosphorylation, we examined the mechanism of dynamin dephosphorylation in osteoblasts. Dynamin formed a protein complex with the tyrosine phosphatase PTP-PEST and inhibition of phosphatase activity increased the level of phosphorylated dynamin. Further, PTP-PEST blocked the Src-mediated increase in the phosphorylation and GTPase activity of wild-type dynamin but not the phosphorylation mutant dynY231F/Y597F. Although ALP activity was increased in osteoblasts expressing GTPase-defective dynK44A, and to a lesser extent dynY231F/Y597F, osteoblast migration was significantly inhibited by dynK44A and dynY231F/Y597F. These studies demonstrate a novel role for dynamin GTPase activity and phosphorylation in osteoblast differentiation and migration, which may be important for bone formation.