ABSTRACT
The most common cause of granulomatous lymphadenitis in countries like ours is mycobactrium tuberculosis followed by atypical mycobacterial infection, fungal infections, parasitic infection, cat scratch disease, lymphogranuloma venereum (inguinal lymphadenopathy), and leprosy Here, we present three cases of lymphadenopathy due to histoplasmosis in immunocompetent children. Two of them presented with fever, lymphadenopathy, initially diagnosed as granulomatous lymphadenitis consistent with tuberculosis on FNAC and were put on antitubercular drugs. However, their condition gradually became worse. As the patients continued to deteriorate, subsequent lymph node biopsies were done and diagnosed as histoplasmosis. Third case presented with acute loss of vision with hepatosplenomegaly and lymphadenopathy. Initially considered as acute leukemia, but eventually established as histoplasmosis. Histoplasmosis should be considered as one of the possible causes of granulomatous lymphadenitis in children.
Subject(s)
Histoplasmosis , Lymphadenitis , Lymphadenopathy , Tuberculosis , Granuloma/diagnosis , Histoplasmosis/diagnosis , Humans , Lymphadenopathy/diagnosis , Tuberculosis/diagnosisABSTRACT
The mammalian verprolin family of proteins, WIP (WASP Interacting Protein), CR16 (Corticoid Regulated) and WIRE (WIp-RElated) regulate the actin cytoskeleton through WASP/N-WASP (Wiskott Aldrich Syndrome Protein and Neural-WASP). In order to characterize the WASP/N-WASP-independent function of WIRE, we screened and identified IRSp53 (Insulin Receptor Substrate) as a WIRE interacting protein. Expression of IRSp53 with WIRE in N-WASP(-/-) mouse fibroblast cells induced filopodia while co-expression of IRSp53 with WIP did not. The induction of filopodia is dependent on WIRE-IRSp53 interaction as mutation in the SH3 domain of IRSp53 abolished WIRE-IRSp53 interaction as well as the ability to induce filopodia. Similarly, the Verprolin (V)-domain of WIRE is critical for IRSp53-WIRE interaction and for filopodia formation. The interaction between WIRE and IRSp53 is regulated by Cdc42 as mutations which abolish Cdc42-IRSp53 interaction lead to loss of IRSp53-WIRE interaction as shown by pull down assay. The plasma membrane localization of IRSp53 is dependent on Cdc42 and WIRE. Expression of Cdc42(G12V) (active mutant) with WIRE-IRSp53 caused significant increase in the number of filopodia per cell. Thus our results show that Cdc42 regulates the activity of IRSp53 by regulating the IRSp53-WIRE interaction as well as localization of the complex to plasma membrane to generate filopodia.
Subject(s)
Carrier Proteins/physiology , Nerve Tissue Proteins/metabolism , Pseudopodia , Wiskott-Aldrich Syndrome Protein, Neuronal , Animals , Carrier Proteins/metabolism , Cell Line , Fibroblasts/cytology , Fibroblasts/ultrastructure , Gene Knockdown Techniques , Humans , Mice , Microfilament Proteins , Protein Binding/physiology , RNA, Small Interfering/pharmacology , Transfection , cdc42 GTP-Binding Protein/metabolismABSTRACT
Dedifferentiated papillary carcinoma of thyroid shows combined histopathological features of classical papillary carcinoma and anaplastic carcinoma. This is a very rare tumour in adolescence. This prompted the authors to report this case.
