A potent inhibitor of α-mannosidase was isolated from Swainsona canescens. The inhibitor was
shown to be an indolizidinetriol by spectroscopic
techniques and the relative stereochemistry was defined as 8aβ-indolizidine-lα,2α,8β-triol.
An indolizidine alkaloid (swainsonine) was isolated from the plant Swainsona canescens. Swainsonine is a specific and potent inhibitor of alpha-mannosidase (EC 3.2.1.24) and when administered to animals produces a phenocopy of the genetically based lysosomal storage disease, mannosidosis. Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosomal alpha-mannosidase.
The role of CD40/CD154 interaction during infection has primarily focused on pathogens that drive inflammatory Th1 responses. In this study, we show that CD40/CD154 interaction is a fundamental requirement for Th2 response development to the parasitic helminth Schistosoma mansoni. Compared with infected wild-type mice, greatly reduced levels of Th2-associated cytokines were measured both in vitro and in vivo, and no IgE or IgG1 was detected in infected CD154−/− mice. In the absence of an overt Th2 response, no exaggerated Th1 response was mounted by CD154−/− mice. Infected CD154−/− mice suffered severe morbidity and mortality, even though parasitemias in wild-type and CD154−/− mice did not differ significantly. These data indicate that CD40/CD154 interaction is required to allow development of a Th2-dominated immune response to S. mansoni and support the view that failure to develop such a response can have fatal consequences.
Clinical and pathological findings are reported from a series of 12 cases of disseminated aspergillosis (A. terreus) in 11 German Shepherd dogs and one Dalmatian referred to Murdoch University Veterinary Hospital (MUVH) over the period 1980 to 1984. A preliminary study of humoral and cell mediated immune components and complement levels revealed no consistent abnormality in 9 dogs tested apart from raised IgG levels. Serum IgA levels were depressed in 30% of cases. Serial data from one extensively monitored case is presented. The unusual epidemiological and pathogenetic features of the disease are discussed.
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