Biomedical subjects
M Tozuka
Publications and source records attributed to M Tozuka.
Regulation of hepatic high density lipoprotein binding proteins after administration of simvastatin and cholestyramine to rats.
We investigated the regulation of putative high density lipoprotein (HDL) receptors in rat liver after cholesterol feeding and the administration of cholesterol-lowering drugs to rats. The expression of two plasma membrane HDL binding proteins (HB1 and HB2) were compared in control and treated livers by first separating membrane proteins on sodium dodecyl sulfate-polyacrylamide gels and quantitating HB1 and HB2 levels with a specific ligand blot assay. Of the various treatments used, only simvastatin or simvastatin plus cholestyramine produced significant changes, with reductions of up to 40% and 60%, respectively, for HB1 and HB2. The effect on the binding proteins was not associated with changes in serum cholesterol concentrations, which did not change significantly after either treatment, although a marked rise in liver cholesterol concentration after cholesterol was associated with a moderate increase in HB2 expression. We show evidence for regulation of the levels of hepatic HDL binding proteins and provide another important criterion for the acceptance of HB1 and HB2 as components of a functional HDL receptor.
Characterization of hypertriglyceridemia induced by L-asparaginase therapy for acute lymphoblastic leukemia and malignant lymphoma.
Plasma lipids and apolipoproteins were determined in 19 children with acute lymphoblastic leukemia (ALL) or malignant lymphoma (ML) who were treated by L-asparaginase with prednisolone and vincristine. Extreme hypertriglyceridemia, i.e., over 10,000 mg/l of the maximum serum triglyceride concentration, was induced in 8 patients; these concentrations were not over 10,000 mg/l in the remaining 11 patients. The possibility was raised that the apolipoprotein E (apoE) isoform apoE4 (epsilon 4) participated in the induction of extreme hypertriglyceridemia, since the frequency of the apoE4/E3 phenotype in the patients with extreme hypertriglyceridemia was higher compared to those in the patients without extreme hypertriglyceridemia and control subjects (n = 248). The acute and severe hypertriglyceridemia was induced at 8 to 14 days after the end of the L-asparaginase therapy, with an earlier remarkable increase in the apoCIII/apoCII ratio and an extreme decrease of fibrinogen concentrations (a marker of the protein productivity of the liver). It is well known that apoCII and apoCIII have possible functions as an activator and an inhibitor of lipoprotein lipase (LPL), respectively. The extreme increase in the apoCIII/apoCII ratio could be one of the reasons for the accumulation of triglyceride-rich lipoproteins in plasma.