We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 ,uU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20

Two recombinant mutants of porcine kidney D-amino acid oxidase [EC 1.4.3.3, DAO], in which Tyr(228) and His(307) are replaced with Phe and Leu, respectively, have been expressed in Escherichia coli and purified to apparent homogeneity. The molecular size and amino-terminal sequence of the two mutants were the same as those of the native DAO. Kinetic analysis revealed that the Michaelis constants of the Phe-228 and Leu-307 mutants for D-alanine were 71- and 10-fold and the inhibition constants for benzoate, a potent competitive inhibitor, were 1,189- and 18-fold greater than those of the native DAO, respectively. The maximum velocities of the Phe-228 and Leu-307 mutants were 66 and 58% that of the native DAO. The kinetically estimated dissociation constant of the Leu-307 mutant for FAD was 28-fold greater than that of the native DAO, whereas the value of the Phe-228 mutant was comparable to that of the native DAO. The Leu-307 mutant and the recombinant wild-type DAO were inactivated by D-propargylglycine (D-PG), a suicide substrate. However, the Phe-228 mutant was resistant to the inactivation. Absorption peaks of the Phe-228 mutant were blue-shifted about 10 nm from the corresponding peaks of the wild-type DAO, and the oxidized form was fully reduced by D-alanine without appearance of the purple intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of simvastatin on the lipid profile of hemodialysis patients.hibit dyslipidemia, which is thought to be one of the Background. Simvastatin, a 3-hydroxy 3-methylglutaryl co-

Rat gene for renin-binding protein (RnBP) was shown to be expressed in the kidney, adrenal gland, brain, lung, spleen, ovary, testis, and heart. On sodium depletion and captopril administration, the rat showed a marked increase in the adrenal RnBP mRNA level and a slight decrease in the kidney RnBP mRNA level. In two-kidney, one clip hypertensive rats, the RnBP mRNA levels of the clipped and contralateral kidneys were unchanged and also its adrenal mRNA level was maintained at the control level. The recombinant rat RnBP was synthesized in Escherichia coli cells and purified to apparent homogeneity. The RnBP existed as a homodimer and formed a heterodimer with rat renin to inhibit renin activity extensively. Intravenous injection of the RnBP into rats resulted in a rapid and strong inhibition of plasma renin activity, which persisted at least for 2 h. These results suggest that the expression of RnBP gene in the kidney and adrenal gland is regulated independently, and the function of RnBP is related to electrolyte homeostasis, probably through the interaction with renin.

One of the side effects by interferon ribavirin (I/R) treatment is haemolytic anemia, causing some patients to discontinue I/R treatment. The exact mechanism of I/R-induced anemia is unknown. The aim of this study is to evaluate the effects of I/R treatment on the serum lipid and red blood cell (RBC) membrane lipid profiles of patients with chronic hepatitis C (CHC) and the association between changes of RBC membrane lipids and haemolytic anemia by I/R treatment. Fourteen patients with CHC were treated with I/R and their serum lipid profiles were studied. In addition, in seven of the 14 patients, the RBC membrane lipid profiles were analysed. In the RBC membrane lipid composition, the total cholesterol, total phospholipids and cholesterol/phospholipids (C/PL) ratio were significantly increased. Phosphatidylcholine (PC) and the phosphatidylcholine/ sphingomyelin (PC/SM) ratio were significantly decreased and other phospholipid fractions were significantly increased. Changes in the serum lipids and RBC membrane lipid profiles of patients with CHC treated with I/R were shown. Especially, a decrease in the RBC deformability and membrane fluidity by changes in these RBC membrane lipids was supposed and it is suggested that those changes may result in haemolytic anemia by I/R treatment.