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Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet counts), immune deficiency, and bloody diarrhea (due to the low platelet counts). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. more...

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Signs and symptoms

WAS generally becomes symptomatic in children. Due to its mode of inheritance, the overwhelming majority are male. It is characterised by bruising caused by thrombocytopenia (low platelet counts), small platelet size on blood film, eczema, recurrent infections, and a propensity for autoimmune disorders and malignancies (mainly lymphoma and leukemia).

In Wiskott-Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts. Also, patients develop a type of itchy rash called eczema. Autoimmune disorders are also found in patients with WAS.

Diagnosis

The diagnosis is made on the basis of clinical parameters, the blood film and low immunoglobulin levels. Skin immunologic testing (allergy testing) may reveal hyposensitivity. It must be remembered that not all patients will have a family history, since they may be the first to harbor the gene mutation. Often, leukemia may initially be suspected on the basis of the low platelets and the infections, and bone marrow biopsy may be performed. Decreased levels of Wiskott-Aldrich syndrome protein and/or confirmation of a causative mutation provides the most definitive diagnosis.

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Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility
From International Journal of Leprosy and Other Mycobacterial Diseases, 6/1/04

Stamm, L. M., Morisaki, J. H., Gao, L. Y., Jeng, R. L., McDonald, K. L., Roth, R., Takeshita, S., Heuser, J., Welch, M. D., and Brown, E. J. Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility. J. Exp. Med. 198(9) (2003) 1361-1368.

Mycobacteria are responsible for a number of human and animal diseases and are classical intracellular pathogens, living inside macrophages rather than as free-living organisms during infection. Numerous intracellular pathogens, including Listeria monocytogenes, Shigellaflexneri, and Rickettsia rickettsii, exploit the host cytoskeleton by using actin-based motility for cell to cell spread during infection. Here we show that Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of actively inducing actin polymerization within macrophages. M. marinum that polymerized actin were free in the cytoplasm and propelled by actin-based motility into adjacent cells. Immunofluorescence demonstrated the presence of host cytoskeletal proteins, including the Arp2/3 complex and vasodilatorstimulated phosphoprotein, throughout the actin tails. In contrast, Wiskott-Aldrich syndrome protein localized exclusively at the actin-polymerizing pole of M. marinum. These findings show that M. marinum can escape into the cytoplasm of infected macrophages, where it can recruit host cell cytoskeletal factors to induce actin polymerization leading to direct cell to cell spread.-Authors' Abstract

Copyright International Leprosy Association Jun 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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