The fusion protein PML-RARalpha, generated by the t(15;17)(q22;q11.2) translocation associated with acute promyelocytic leukemia (APL), initiates APL when expressed in the early myeloid compartment of transgenic mice. PML-RARalpha is cleaved in several positions by a neutral serine protease in a human myeloid cell line; purification revealed that the protease is neutrophil elastase (NE). Immuno...

Multiple Sclerosis (MS) is considered to be a T cell-mediated autoimmune disease. An attractive strategy to prevent activation of autoaggressive T cells in MS, is the use of altered peptide ligands (APL), which bind to major histocompatibility complex class II (MHC II) molecules. To be of clinical use, APL must be capable of resisting hostile environments including the proteolytic machinery of ...

The antiphospholipid syndrome (APS) is a disorder which is characterized by the presence of autoimmune antiphospholipid antibodies (APL) and increased risk of thrombosis and fetal loss. APL are associated with recurrent abortions in APS patients and participate in the pathogenesis of venous or arterial thrombosis, although the underlying mechanisms are poorly understood. Antigens that are targe...

Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications ...

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosomal translocation that yields the PML/RARA fusion gene. Clinically, besides chemotherapy, two drugs induce clinical remissions: retinoic acid (RA) and arsenic trioxide (As). Both agents directly target PML/RARA-mediated transcriptional repression and protein stability, inducing to various extent promyelocyte diff...

More effective treatments for acute promyelocytic leukemia (APL) are needed. APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARα, which is generated in APL by chromosomal translocation. The E1-like ubiquitin-activating enzyme (UBE1L) associates with interferon-stimulated gene ISG15 that ...

Background: The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor (PML-RARA) fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 (FMS-like tyrosine kinase 3) tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutat...

BACKGROUND This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intra-patient variability for each azole was determined. METHODS From July 2012 to July 2015, 806 APL of ITR, VOR, POS liquid (POS-Liq), and POS tabl...

An experimental programming language called APLGOL adds structured programming facilities to the existing framework of APL. The conventional semantics of APL is unaltered and only minor changes are incorporated in the syntax. The advantages of the proposed interstatement structuring and control are outlined. Programs designed and written using " structured " programming techniques have been dem...