Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the involvement of cytotoxic granules in apoptosis of aplastic anaemia (AA), we analysed bone marrow clot sections of AA for apoptosis and perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) expression. Perforin, TIA-1 expression and apoptosis were significantly increased in AA patients compared with control subjects, but granzyme B was not. TIA-1 was significantly correlated with apoptotic cells of AA. No correlation was found between perforin and apoptotic cells of AA. These results suggest that perforin and TIA-1 play a role in the pathogenesis of AA. TIA-1 is implicated as an effector in the apoptosis of AA.
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PMID:Involvement of cytotoxic granules in the apoptosis of aplastic anaemia. 1261 21

Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural killer cells. Inherited perforin mutations account for 20% to 40% of familial hemophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by the absence of functional perforin. Aplastic anemia, the paradigm of immune-mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1 mutations among 5 unrelated patients were observed. Four of 5 patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. Natural killer (NK) cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1 genetic alterations help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure.
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PMID:Perforin gene mutations in patients with acquired aplastic anemia. 1731 87