Wiskott–Aldrich syndrome protein (WASP) is in a complex with WASP-interacting protein (WIP). WASP levels, but not mRNA levels, were severely diminished in T cells from WIP
−/−
mice and were increased by introduction of WIP in these cells. The WASP binding domain of WIP was shown to protect WASP from degradation by calpain
in vitro
. Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP
−/−
mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding. The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP
−/−
mice. Despite its ability to increase WASP levels proteasome inhibition did not correct the impaired IL-2 gene expression and low F-actin content in T cells from the R86H WAS patient. These results demonstrate that WIP stabilizes WASP and suggest that it may also be important for its function.
In order to determine the comparative sensitivity of two methods of detecting Blastocystis hominis and to investigate the seasonality of infection with this enteric protozoan parasite, the present study was conducted. In each of two 3-month periods representing winter, spring (February-April) and summer (July-September), 500 routine stool submissions were examined for B. hominis using microscopy following either formol-ether concentration or in vitro culture using Jones' medium. The organism was detected in 39 of the 1,000 samples investigated using the in vitro culture technique and in none of the samples using the formol-ether concentration technique. In 82% of the B. hominis-positive samples, no concurrent bacterial or parasitic pathogens were found, and diarrhoea was the most commonly recorded symptom among patients. Infection was more prevalent in summer than in winter/spring, occurring primarily in the 71-80-year age group. Cysts were detected in 20.5% of positive samples, but only following Ficoll-Paque concentration of formol-ether concentrates. Cyst excretion was more prevalent in summer than in winter/spring.
This paper elucidates the status of the different morphological forms of Blastocystis and reports the existence of thin- and thick-walled cysts in B. hominis on the basis of current experimental evidence. It is suggested that the thin-walled cysts are autoinfectious, leading to multiplication of the organism in the intestinal tract. The thick-walled cysts are responsible for external transmission via the faecal-oral route. A life cycle for B. hominis is postulated on the basis of these findings.
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