SummaryThrombopoietin (Tpo) regulates platelet production, but the mechanisms regulating the serum Tpo level and platelet count in circulation have been a subject of debate. Tpo was reported to be expressed mainly in liver and kidney, but we found that Tpo is expressed in all tissues examined: abundantly in liver, kidney, muscle, colon, brain and intestine, and moderately in bone marrow, spleen, lung, stomach, heart, thymus, ovary, and endothelial and leukemic cell lines. The levels of Tpo transcripts in major Tpo producing organs, liver and kidney, and in the platelet production sites bone marrow and spleen, were constant during acute thrombocytopenia induced by anti-platelet monoclonal antibody administration in mice, and during thrombocytosis induced by Tpo injection. Furthermore, we noticed that platelet count is not exactly inversely proportional to serum Tpo level. During acute thrombocytopenia, serum Tpo level transiently increased a few hours after antibody injection, and returned to the basal level just when matured megakaryocytes accumulated in bone marrow and spleen but the platelet count was still low. Matured megakaryocytes in bone marrow and spleen increased when the serum Tpo level decreased, and decreased when platelet count rebounded. Taken together with other observations, we propose here a modified version of Kuter and Rosenberg’s theory, that is, Tpo is constitutively expressed in a variety of organs throughout the body, even in acute thrombocytopenia and thrombocytosis, and that the serum Tpo level is not regulated by Tpo gene expression nor only by platelet counts in circulation, but by the total counts of both megakaryocytes in bone marrow and spleen and of platelets in circulation

Summary. To investigate the efficacy and safety of granulocyte colony‐stimulating factor (G‐CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G‐CSF or control groups after remission induction therapy. The G‐CSF group received G‐CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1·5 × 109/l. The control group did not receive G‐CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G‐CSF and control groups respectively). The complete remission rate was similar in the G‐CSF and control groups (80·8% versus 76·8%), as was the 5‐year probability of disease‐free survival (34·5% versus 33·6%) and overall survival (42·7% versus 35·6%). Neutrophil recovery was significantly faster in the G‐CSF group than in the control group (12 d versus 18 d, P = 0·0001). The median duration of febrile neutropenia was significantly shorter in the G‐CSF group than in the control group (3 d versus 4 d, P = 0·0001). In conclusion, prophylactic administration of G‐CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.

SummaryWe assayed serum thrombopoietin (TPO) levels in amegakaryocytic thrombocytopenia (AMT) and immune thrombocytopenic purpura (ITP) patients by using a newly established enzyme-linked immunosorbent assay (ELISA). TPO levels in AMT patients were quite high (mean ± SD = 13.7 ± 11.2 fmoles/ml, n = 4), whereas those in ITP patients were only slightly higher (1.25 ± 0.39, n = 12) than those of the healthy donors (0.55 ± 0.2, n = 20). Furthermore, in ITP patients no correlation was observed between platelet counts and serum TPO levels (correlation coefficient = 0.14). We further assayed serum TPO levels sequentially during steroid treatment in patients with AMT and ITP. In one AMT patient serum TPO levels started to decrease in accordance with the increase of megakaryocyte counts, which preceded the increase in platelet counts. However, in ITP patients serum TPO levels did not change significantly throughout the course of the treatment despite the recovery of platelet counts. Based on these findings, we conclude that serum TPO levels may be regulated at least in part by megakaryocyte counts.

Polarization change induced by directional electron transfer attracts considerable attention owing to its fast switching rate and potential light control. Here, we investigate electronic pyroelectricity in the crystal of a mononuclear complex, [Co(phendiox)(rac-cth)] (ClO 4)•0.5EtOH (1•0.5EtOH, H 2 phendiox = 9, 10-dihydroxyphenanthrene, rac-cth = racemic 5, 5, 7, 12, 12, 14-hexamethyl-1, 4, 8, 11-tetraazacyclotetradecane), which undergoes a twostep valence tautomerism (VT). Correspondingly, pyroelectric current exhibits double peaks in the same temperature domain with the polarization change consistent with the change in dipole moments during the VT process. Time-resolved Infrared (IR) spectroscopy shows that the photo-induced metastable state can be generated within 150 ps at 190 K. Such state can be trapped for tens of minutes at 7 K, showing that photo-induced polarization change can be realized in this system. These results directly demonstrate that a change in the molecular dipole moments induced by intramolecular electron transfer can introduce a macroscopic polarization change in VT compounds.

The contribution of an eosinophil granule protein, major basic protein (MBP), to the pathogenesis of thrombosis seen in patients with eosinophilia was investigated. The sera from eosinophilic patients containing elevated levels of MBP inhibited thrombomodulin (TM) function as a cofactor for the thrombin-catalysed activation of protein C more significantly than those from normal individuals (means 48.5% v 17.4%, respectively). It was suggested that the binding of mature MBP in the sera to TM was electrostatic, because mature MBP (pI 10.9) bound to TM, whereas pro-MBP (pI 6.2) did not. The inhibition of TM cofactor activity by eosinophil granule proteins was mainly attributed to the mature MBP, because MBP-depleted eosinophil granule proteins did not inhibit TM cofactor activity significantly. This inhibition seemed to be due to the specific thrombin-binding to TM being blocked. We concluded that eosinophil granule proteins, particularly MBP, potentially contribute to the hypercoagulation seen in some conditions of eosinophilia, at least because of the inhibition of TM function as a cofactor of the anticoagulation system.

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Structural alterations occur in the long arm of chromosome 3 in approximately 2% of patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). The major alterations are inv(3)(q21q26) and t(3:3)(q21;q26) and are often classified as the 3q21q26 syndrome. We previously reported that the EVI1 gene is transcriptionally activated in AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) and that the chromosomal breakpoints at 3q26 in the translocations were 5′ of the EVI1 gene, whereas the breakpoints in the inversion cases were 3′ of the gene. In these studies, four additional cases of AML with inv(3)(q21q26) are shown to express the EVI1 gene and to have breakpoints 3′ of the gene. To characterize the 3q21 breakpoint region, cosmid and phage clones were isolated that cover approximately 100 kb. At 3q21, the breakpoints for both AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) were found to cluster over a region of approximately 50 kb downstream of the Ribophorin I gene. The results indicate a common mechanism for the translocations and inversions and support the hypothesis that the transcriptional activation of the EVI1 gene is mediated by enhancer elements associated with the Ribophorin I gene.

Azo-crown ether-based photoswitching chiral phase transfer catalysts have been developed to control the catalytic activity by photoirradiation. Azobenzene binaphthyl crown ether (ABCE) can switch its reactivity and selectivity through structural transformation of the crown ether moiety induced by E/Z photoisomerization of azobenzene. (Z)-ABCE promoted enantioselective alkylation of the glycine Schiff base to afford chiral amino acid derivatives in good yields with high enantiomer ratios. In contrast, (E)-ABCE hindered the reaction progress under the same conditions.