Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors.
View Article and Find Full Text PDFThis unit provides information how to use short interfering RNA (siRNA) for sequence-specific gene silencing in mammalian cells. Several methods for siRNA generation and optimization, as well as recommendations for cell transfection and transduction, are presented.
View Article and Find Full Text PDFIntroduction: Crossed cerebellar diaschisis is a functional deficit in an area that is remote from that of a supratentorial brain lesion, although the two are anatomically and functionally connected. Deactivation of the contralateral cerebellar hemisphere occurs and is believed to be caused by a transneuronal metabolic depression of the cortico-ponto-cerebellar pathway. A reduction in the blood flow in the brain takes place and this gives rise to a diminished oxygenation of the cerebellar hemisphere.
View Article and Find Full Text PDFWe describe the natural history of lupus nephritis (LN) in a historical cohort of 190 white patients with the diagnosis of biopsy-proven LN followed in a single reference center.We evaluated 670 patients with systemic lupus erythematosus (SLE) consecutively followed in our department from 1970 until 2006. All patients fulfilled the 1997 revised criteria for the classification of SLE.
View Article and Find Full Text PDFObjective: To analyze the prevalence of neutropenia in a large cohort of patients with primary Sjögren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes.
Methods: The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (<2.
Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006.
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