Yoko Kawai

Different roles of p38 MAPK and ERK in STI571‐induced multi‐lineage differentiation of K562 cells

STI571 is a specific tyrosine kinase inhibitor of Abl kinase. It was previously reported that STI571 induced hemoglobin synthesis in the chronic myelogenous leukemia (CML) cell line K562. However, its mechanisms remain unknown. In this study, we demonstrated that STI571 induced the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and dephosphorylation of extracellular signal‐regulated kinase (ERK) in K562 cells. In contrast, the phosphorylation of c‐Jun N‐terminal kinases (JNK) in K562 cells was not altered by STI571. We also found that STI571 induced all the myeloid (CD11b, CD13), megakaryocytic (CD41a, CD42), and erythroid (glycophorin‐A) markers on K562 cells. A p38 MAPK‐specific inhibitor, SB203580, inhibited the STI571‐induced multi‐lineage differentiation of K562 cells, indicating that p38 MAPK is crucial for this differentiation. In contrast, SB203580 did not overcome the inhibitory effect for proliferation of K562 cells, indicating that p38 MAPK activation by STI571 does not affect cell numbers. Among the hematopoietic transcription factors, the expression level of c‐myb mRNA was clearly downregulated after incubation with STI571 in K562 cells. STI571‐induced downregulation of c‐myb mRNA was prevented by the pretreatment of K562 cells by SB203580. Our data provides insights into how p38 MAPK and ERK pathways are involved in STI571‐induced differentiation of K562 cells. J. Cell. Physiol. 198: 370–376, 2004© 2003 Wiley‐Liss, Inc.

Clinical characteristics of thrombotic microangiopathy following ABO incompatible living donor liver transplantation

Thrombotic microangiopathy (TMA) may develop after living donor liver transplantation (LDLT), but the mechanism is not fully understood. We retrospectively analyzed all patients undergoing LDLT at our center, including TMA patients, to elucidate the clinical characteristics and presentation and to determine which patients have a higher risk of occurrence of TMA. In all, 57 adult patients were reviewed after LDLT at our institution. TMA was diagnosed by sudden and severe thrombocytopenia, followed by hemolytic anemia with fractionated erythrocytes in the blood smear. Clinical features were compared between the TMA group and the non‐TMA group. Of the 57 patients, 4 were diagnosed with posttransplantation TMA. ABO blood group (ABO)‐incompatibility, cyclophosphamide (CPA), and recipient blood group (type O) were closely correlated with the occurrence of TMA. Thrombocytopenia appeared 1 to 5 days before hemolytic anemia. Coagulative function markers stayed at the same level after TMA, while marked elevation was shown in fibrinolytic function markers such as plasminogen activator inhibitor type 1 (PAI‐1). TMA occurred at a higher prevalence in ABO‐incompatible graft recipients. Additional factors associated with ABO‐incompatible transplantation, such as an overdose of immunosuppressants, may affect the likelihood of TMA. Sudden and severe thrombocytopenia presented before hemolytic anemia and the serum levels of PAI‐1 correlated well with the clinical course of TMA. In conclusion, early recognition of thrombocytopenia and elevation of PAI‐1 is crucial to diagnose TMA especially in ABO‐incompatible LDLT. Liver Transpl 13:1455–1462, 2007.

Microbial production of (2R, 4R)-2,4-pentanediol by enatioselective reduction of acetylacetone and stereoinversion of 2,4-pentanediol

Summary(2R, 4R)-2,4-Pentanediol was obtained by the enatioselective reduction of acetylacetone (2,4-pentanedione) with the resting cells of methanol yeast,Candida boidinii KK912 (IFO 10574). (2R, 4R)-2,4-Pentanediol was also obtained by the stereoinversion of the isomeric mixture of 2,4-pentanediol.

Molecular Mechanism of Shear Stress-Induced Platelet Aggregation

Blood circulating in vessels is exposed to shear stress caused by the force necessary to produce flow; the difference in velocity between layers situated at varying distances from the vessel wall determines the shear rate, which is directly proportional to the shear force and inversely proportional to the viscosity of blood. Previous studies have demonstrated that exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists (1) (2). Under high shear stress, which may mimic the rheological situation existing in certain districts of the arterial circulation, von Willebrand factor (vWf) may have a crucial role in the formation of the irreversible platelet aggregates (3) (4) . However, the precise molecular mechanism of shear stress-induced platelet aggregation (SIPA) has yet to be clarified.