Thrombomodulin has a central role in the regulation of coagulation through its abilities to promote generation of the potent anticoagulant activated protein C. Because little is known about monocyte thrombomodulin expression and its regulatory mechanism by lipopolysaccharide, we investigated the effect of lipopolysaccharide on monocyte's thrombomodulin expression. Lipopolysaccharide reduced the surface thrombomodulin expression of human peripheral blood monocytes in a dose-dependent and time-dependent manner, regardless of the addition of serum. The surface thrombomodulin activity was comparably decreased in monocytes incubated with lipopolysaccharide. Blocking nuclear factor-kappaB by MG132 or aurine tricarboxylic acid effectively inhibited the lipopolysaccharide-induced surface thrombomodulin down-regulation of monocytes. Lipopolysaccharide inactivation by polymyxin B in the supernatants from the lipopolysaccharide-stimulated cultures still reduced the surface thrombomodulin expression of monocytes, suggesting a role for soluble mediators in the down-regulation of thrombomodulin. The lipopolysaccharide-induced thrombomodulin surface expression and the mRNA levels of the monocytic leukemic cell line (THP-1) were decreased in serum-depleted culture, while they were increased in medium containing 10% serum. We conclude that lipopolysaccharide down-regulates the thrombomodulin expression of monocytes and that nuclear factor-kappaB is a critical mediator of the repression of thrombomodulin by lipopolysaccharide. Regulation of the THP-1 thrombomodulin expression by lipopolysaccharide depends on the presence of serum.

Summary. Translocations involving the MLL gene on the chromosome 11 (11q23) are frequently observed in acute leukaemia. The detection of this genetic change has a unique significance as a result of its implication of poor prognosis. To reveal the utility of fluorescence in situ hybridization (FISH) in detecting the MLL translocation, we analysed 289 consecutive Korean patients (children and adults) with acute leukaemias using both conventional cytogenetic analysis (CC) and FISH, placing an emphasis on the result discrepancies. Twenty-two of 289 patients (7AE6%) had the 11q23/MLL translocation. In nine of 22 patients (41%), only FISH detected the translocation. In eight of these 22 patients, a total of 19 follow-up examinations were performed, of which FISH detected a significant level of leukaemic cells harbouring the MLL translocation in five patients (26%) without cytogenetic evidence. In addition to the MLL translocation, FISH detected submicroscopic amplification, partial deletion of the MLL gene and trisomy 11 in 12 patients without cytogenetic evidence. In summary, up to 41% of the MLL translocations at initial work-up and 26% during follow-up were detected by FISH without cytogenetic evidence. Thus, we recommend that MLL FISH should be performed in the diagnosis and monitoring of acute leukaemias in combination with CC.Keywords: acute leukaemia, 11q23 translocation, MLL, cytogenetic analysis, fluorescence in situ hybridization.Human leukaemia is now recognized as an acquired genetic disease. A large number of consistent chromosomal changes have been identified and some of these have provided unique insights into the understanding of the pathogenesis of the disease (Heim & Mitelman, 1995;Look, 1997). Karyotypic analysis to identify chromosomal abnormalities is now part of the routine work-up for diagnostic and riskstratification studies for determining the appropriate therapy in newly diagnosed and relapsed leukaemia patients. Structural abnormalities involving the q23 band of chromosome 11 (11q23) are probably the most common of the many identified genetic abnormalities in haematological malignancies, and the majority of these involve the MLL (myeloid/lymphoid leukaemia or mixed lineage leukaemia) gene, which is also known as ALL-1, HRX and HTRX1 (Thirman et al, 1993). The MLL gene is located on 11q23 and contains more than 30 exons. Translocation involving this gene usually occurs between exons 5 and 11, which is known as the breakpoint cluster region (Djabali et al, 1992;Gu et al, 1992). The translocation of this gene occurs in approximately 5-8% of acute myeloid leukaemias (AML), 7-10% of acute lymphoblastic leukaemias (ALL) and in 60-70% of infant leukaemias, irrespective of the phenotype (Thirman et al, 1993;Pui et al, 1995). The 11q23/MLL translocation is known to be associated with acute leukaemia in infancy and with therapy-related leukaemia, and this translocation in acute leukaemia implies a poor prognosis although there is some disagreement on this issue (Cimino et al, 1995;Rubnitz et al, 1997)...

Although platelet count is a good parameter for the diagnosis of disseminated intravascular coagulation (DIC), a single measurement of platelet is not enough to reflect the ongoing platelet consumption because of compensatory synthesis of circulating platelet number. Increased thrombopoiesis owing to peripheral destruction is expected in patients with DIC. Reticulated platelet, measured as immature platelet fraction (IPF), and plasma thrombopoietin (TPO) are markers of platelet production. We investigated the potential usefulness of circulating IPF and TPO in 222 patients suspected of having DIC. Both IPF and TPO levels were significantly increased in overt DIC patients and well correlated with DIC score. IPF also correlated with fibrin-related marker such as fibrinogen degradation product and D-dimer. Both IPF and TPO showed better mortality prediction than platelet count with the multivariate logistic regression and Kaplan-Meier survival analysis. These results suggest that IPF and TPO are new potential candidates to detect the severity of DIC and to predict DIC mortality.

The authors conducted an investigation focusing mainly on the activities of the inhibitory factors of the coagulation and fibrinolysis processes in 35 normal adults and 72 liver cirrhosis and/or hepatoma patients. The activities of antithrombin III, protein C, and alpha 2-plasmin inhibitor were reduced to less than 50% in patients with decreased hepatic synthetic function while lupus anticoagulant was detected in more than 50% of patients with decreased hepatic synthetic function. Hemostatic abnormalities in advanced lived diseases may be caused partly by a decrease of coagulation and fibrinolysis inhibitors and the presence of lupus anticoagulant.

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