[Peripheral and bone marrow plasmacytosis in dengue fever: report of a case]. / Plasmocytose sanguine et médullaire au cours de la dengue : une observation.

We report a case of dengue fever with plasma cells in the blood (3980 per cubic millimeter) and bone marrow (30%) in a 55-year-old woman hospitalized for fever, arthralgias and thrombocytopenia (66,000 per cubic millimeter) on returning from the West Indies. Serological testing confirmed the diagnosis. Plasmacytosis is rare in dengue fever and its frequency and correlation with the different forms of the disease remain to be determined.

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells.

Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (Delta Psi m), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial Delta Psi m and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspase-independent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.

[Allopurinol hypersensitivity. A possible cause of hepatitis and mucocutaneous eruptions in a patient undergoing antitubercular treatment]. / Hypersensibilité à l'allopurinol. Une cause possible d'hépatite et d'éruption cutanéo-muqueuse chez un patient sous antituberculeux.

The authors describe a case of drug-induced cytolytic hepatitis probably secondary to hypersensitivity to allopurinol which was prescribed incorrectly for secondary hyperuricaemia during treatment with pyrazinamide. The diagnosis was reviewed in view of the late occurrence of hepatitis in relation to the onset of the antituberculous treatment, the absence of a viral aetiology and the presence of clinical manifestations, biological and histological features which were compatible with hypersensitivity to allopurinol. The authors recalled that the type of uricaemia induced by pyrazinamide is most often asymptomatic and does not require any treatment with uric acid lowering drugs. Cessation of pyrazinamide is justified in cases of symptomatic hyperuricaemia but when the indications for pyrazinamide are imperative, treatment with an eliminator of uric acid is indicated. Allopurinol is contra-indicated in association with pyrazinamide on account of its inhibitory reaction to xanthine oxidase. Xanthine oxidase decreases the level pyrazinoic acid, a metabolite of pyrazinamide, which is responsible for the inhibition of the tubular secretion of uric acid.