On the expression of cytosolic calcium-independent phospholipase A2 (88kDa) in immature and mature myeloid cells and its role in leukotriene synthesis in human granulocytes.

The human calcium-independent phospholipase A2 (iPLA2; 88 kDa) has recently been cloned (Larsson, P.K.A., Claesson, H.-E. and Kennedy, B.P. (1998) J. Biol. Chem. 272, 207-214). Here we demonstrate the expression of the human iPLA2 mRNA and its splice variants in blood progenitor cells, immature leukemic cells and mature granulocytes. Chromatographical resolvable iPLA2 activity was found in the cytosolic fraction of granulocytes and the activity was inhibited by the iPLA2 inhibitor bromoenol lactone. This drug also inhibited leukotriene synthesis in human granulocytes, induced by low concentration of calcium ionophore A23187 (0.10-0.15 microM) or opsonized zymosan. These results suggest that iPLA2 is involved in the regulation of the pool of arachidonic acid destined for leukotriene synthesis in human granulocytes.

Successful intravenous immunoglobulin therapy for severe and persistent astrovirus gastroenteritis after fludarabine treatment in a patient with Waldenström's macroglobulinemia.

A 78-year-old male with Waldenström's macroglobulinemia was after 23 years of conservative treatment given fludarabine phosphate in 1993 because of disease progression. Three weeks after the third fludarabine course he presented with a 5-day-history of watery diarrhoea, nausea and vomiting. Stool cultures were negative but a semiquantitative electron microscopy method demonstrated massive amounts of astrovirus (> 10(14) particles/ml). Symptomatic treatment was given but since his condition deteriorated, high-dose intravenous immunoglobulin (IvIg) treatment, 0.4 g/kg for four days was initiated. Within twenty-four hours all symptoms disappeared and the patient was discharged after a few days. A stool sample collected after two weeks demonstrated 10(7) particles/ml and after four weeks no astrovirus could be detected. The association between fludarabine and this opportunistic infection and the potential role of high dose IvIg treatment are discussed.

Primary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study.

A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract and the liver developed ulcerative colitis, which was treated with glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL-amyloidosis was successfully treated with high-dose chemotherapy and autologous stem-cell transplantation. The patient was in good clinical condition for 18 months after treatment, until she developed diarrhea, which was found to be due to collagenous colitis. Two years after treatment of amyloidosis, the patient is in excellent condition, the symptoms of heart failure have stabilized and no adverse effects of the treatment regime have been observed. The bowel diseases are in clinical remission.

Diverse expression of cytosolic phospholipase A2, 5-lipoxygenase and prostaglandin H synthase 2 in acute pre-B-lymphocytic leukaemia cells.

Several lines of evidence suggest that phospholipases A2, leukotrienes and prostaglandins play a role in the proliferation of haemopoietic cells. The expression of genes involved in the biosynthesis of leukotrienes and prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight patients with acute pre-B-lymphocytic leukaemia (pre B-ALL). RT-PCR analysis demonstrated that four of the investigated pre-B-ALL clones expressed the gene coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5-lipoxygenase. In contrast, the remaining four pre-B-ALL clones expressed 5-lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of these two genes are different and that their cellular functions are not linked to each other. The capacity of pre B-ALL cells to produce LTB4 and to express the 5-lipoxygenase protein, correlated with the expression of 5-lipoxygenase mRNA. All pre-B-ALL clones expressed genes coding for 5-lipoxygenase activating protein (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the eight pre B-ALL clones expressed PGH synthase 2. In comparison, normal tonsillar B cells did not express cPLA2 or PGH synthase 2.

Liposomal amphotericin B and surgery in the successful treatment of invasive pulmonary mucormycosis in a patient with acute T-lymphoblastic leukemia.

Pulmonary mucormycosis is a usually fatal opportunistic infection in immunocompromised patients. We describe the first case of an adult patient with hematological malignancy and profound neutropenia to survive a disseminated pulmonary Rhizomucor pusillus infection. Early diagnostic procedures combined with high doses of liposomal amphotericin B and surgical resection may have contributed to the successful outcome.