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S Nagano

Publications and source records attributed to S Nagano.

At least 73 records · Page 4Linked to original sources
PubMed1995

Putative hydrogen bond network in the heme distal site of horseradish peroxidase.

The N delta 1 atom of the distal His of several peroxidases is known to make a hydrogen bond with the side chain oxygen of Asn. Thus, a mutant horseradish peroxidase, in which Asn70 is replaced by Val, has been expressed in Esherichia coli to disrupt the putative hydrogen bond. Substitution of Asn70 to Val reduces the rate constant for the compound I formation from 1.6 x 10(7) (native) to 6 x 10(5) M-1s-1. The rate constant for reduction of compound I of N70V by guaiacol has been also reduced from 7.8 x 10(6) (native) to 1.2 x 10(5) M-1s-1. While compound I of N70V is stable and reduced to the resting state of the mutant without apparent formation of compound II at neutral pH, compound II of N70V is obtained as a stable intermediate at alkaline pH. Similar alteration of the reactivity has been observed in the reaction with guaiacol.

Amino Acid Sequence↗
PubMed1995

Similar to oleic acid, eicosapentaenoic acid stimulates apolipoprotein B secretion by inhibiting its intracellular degradation in Hep G2 cells.

We previously reported that oleic acid (OA) rapidly increased apolipoprotein (apo) B secretion by suppressing early intracellular degradation of nascent apo B in Hep G2 cells and suggested that the suppression of apo B degradation is associated with triglyceride (TG) biosynthesis from OA. To determine whether the inhibition of apo B degradation is associated with increased TG synthesis or is a direct effect of OA, we examined the effect of another fatty acid, eicosapentoenoic acid (EPA), on apo B kinetics in Hep G2 cells, since it is well known to have hypolipidemic action in clinical studies. The incorporation of [3H]glycerol into cellular TG was stimulated five-fold when Hep G2 cells were incubated for 2 h with EPA or OA (0.4 or 0.8 mM-1.5% bovine serum albumin (BSA) complex). The incorporation of [14C]acetic acid into cellular cholesteryl ester (CE) was significantly decreased by EPA treatment, whereas OA did not affect CE synthesis. Similar effects of these fatty acids on cellular lipid synthesis were observed in long-term incubation (24 h). Apo B was linearly secreted into the medium during 3 h, and EPA and OA doubled the rate of secretion. In long-term (24 h) incubations, both fatty acids significantly increased the incorporation of [3H]leucine into secreted apo B radioactivity or the accumulation of apo B mass in the medium. Pulse-chase studies revealed that both EPA and OA reduced intracellular apo B degradation to a similar degree. The inhibition of apo B degradation was also observed when the cells were preincubated with either EPA or OA for 24 h. These results suggest that increased TG synthesis leads to suppression of intracellular apo B degradation, which is independent of the source of exogenous fatty acid.

Apolipoproteins B↗
PubMed1995

Interferon alpha therapy for chronic active hepatitis type C after renal transplantation and allograft rejection.

An acute type rejection episode occurred in one of two patients treated with Interferon alpha (IFN alpha) for type C hepatitis (CHC). Histopathological examination of the graft kidney revealed focal cellular infiltration and chronic transplant glomerulopathy which showed acute or chronic type rejection. In spite of bolus administration of methyl-prednisolone, the elevation of serum creatinine level continued. After administration of anti-human lymphocyte globulin (AHLG), renal function improved, but urinary protein was still positive. Another patient had no episode of rejection during or after IFN alpha therapy.

Adult↗
PubMed1995

Radiographic study of bone loss of mandibular lingual cortical plate accompanied by third molar development.

OBJECTIVE: The purpose was to determine the features of mandibular lingual cortical bone loss around the root of the mandibular third molar. STUDY DESIGN: We examined occlusal radiographs in 2210 persons aged 11 to 78 years. RESULTS: Prominent increase of incidence of bone loss was evident in subjects in their third decade compared with those in their second decade. The incidence was not decreased into the sixties. The incidence of bone loss in men was significantly higher than that in women. The incidence was not influenced by inflammation around the tooth crown of the third molar, by tooth caries, or by metal fillings present in the third molar. CONCLUSIONS: The present observations suggest that bone loss is induced by physiologic processes that accompany root formation of the third molar after mandibular growth.

Adolescent↗
PubMed1995

Intracellular apoprotein B degradation is suppressed by decreased albumin concentration in Hep G2 cells.

It is generally accepted that hepatic secretion of apoprotein (apo) B-containing lipoproteins is substantially increased in nephrosis. To elucidate the mechanisms for the oversecretion of apo B, we investigated the effect of a various concentration of albumin on apo B kinetics in the absence or presence of oleate in Hep G2 cells. Hep G2 cells were labeled with [3H]-leucine in leucine-free medium containing 0, 1.5, 3.0 or 4.5% BSA for 180 minutes, and the secreted radiolabeled apo B, apo A1 and albumin were isolated by immunoprecipitation and counted. The secretions of apo B and albumin were suppressed by BSA (bovine serum albumin) in a dose-dependent manner, but the secretion of apo A1 was not suppressed significantly. Oleate (0.4 mM) increased the rate of apo B secretion by 2.5-fold when oleate was bound to 1.5% BSA, but at higher concentrations of BSA (3.0 or 4.5%), apo B secretion was less responsive to oleate. A pulse-chase study indicated that early apo B degradation was significantly suppressed in cells incubated with lower concentrations of BSA (0 or 1.5% BSA), thereby rapidly stimulating apo B secretion. Oleate (0.4 mM) potently inhibited apo B degradation when oleate was bound to 1.5% BSA, whereas the inhibition was not observed when oleate was bound to 4.5% BSA. Intracellular albumin synthesis was stimulated in BSA-free medium, but intracellular decay of albumin was essentially unaffected by concentration of BSA. Similar to BSA, a higher concentration of dextran (3.0 or 4.5%) reduced apo B secretion, and this was the result of increased early apo B degradation in the cells. These results indicate that reduced albumin suppresses intracellular apo B degradation, and the inhibition of apo B degradation by oleate is manifested only at a low concentration of albumin. Therefore, the present study suggests that free fatty acids bound to low concentration of albumin in the circulating plasma play an important role on hepatic oversecretion of apo B-containing lipoprotein in hypoalbuminemic state, such as nephrotic syndrome.

Apolipoprotein A-I↗
PubMed1995

Intra- and interindividual variation in the pharmacokinetics of tacrolimus (FK506) in kidney transplant recipients--importance of trough level as a practical indicator.

BACKGROUND: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. METHODS: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step immunoabsorption assay. Methylprednisolone was used as a concomitant immunosuppressive drug. RESULTS: The blood concentration-time curves showed remarkable interindividual variation. Intraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684), Cmax (r = 0.838) and AUC0-12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), Cmax (r = 0.270) or AUC0-12 (r = 0.355). tmax ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and Cmax or AUC0-12 was observed in both intraindividual (Cmax, r = 0.876; AUC0-12, r = 0.926) and interindividual (Cmax, r = 0.943; AUC0-12, r = 0.984) measurements. CONCLUSIONS: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.

Adult↗
PubMed1994

Hyperlipidemia in streptozocin-diabetic hamsters as a model for human insulin-deficient diabetes: comparison to streptozocin-diabetic rats.

Characteristics of the lipoprotein profile and metabolism of triglyceride-rich lipoproteins in diabetic hamsters were investigated to assess their suitability as a model for human diabetic hyperlipidemia. Diabetes was induced in the hamsters by intraperitoneal injection of streptozocin (30 mg/kg) for 3 days and compared with the results in streptozocin-diabetic rats (50 mg/kg intravenously). Similar degrees of hyperglycemia and hypoinsulinemia were observed 8 to 10 days after the final streptozocin injection in both groups. Fasting plasma lipid concentrations were about 2.5 times greater in hamsters than in rats. Plasma cholesterol was principally associated with high-density lipoprotein (HDL) in both rodents, although the distribution in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was significantly greater in hamsters (44%) than in rats (13%). Diabetes increased the concentrations of triglyceride, cholesterol, and phospholipid 5.6- to 7.8-fold in hamsters, whereas it increased them only 1.3- to 1.6-fold in rats. Diabetic hamsters have a plasma lipoprotein profile similar to that of diabetic man, ie, triglyceride-rich lipoproteins are increased and HDL cholesterol is decreased. The concentration of HDL cholesterol was inversely correlated with the severity of hypertriglyceridemia (r = .76, P < .005). This combination of events does not occur in diabetic rats. Hamsters had a low level of apoprotein B-48-containing triglyceride-rich lipoproteins, although diabetes increased the estimated concentration by fourfold. In rats apoprotein B-48 is the predominant form, but diabetes did not alter the relative proportion of apoprotein B isoforms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mechanism of hypertriglyceridemia in Dahl salt-sensitive rats, an animal model of spontaneous nephrotic syndrome.

It has been reported that focal and segmental glomerulosclerosis (FSGS) with pronounced proteinuria rapidly develop in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. We found that even when they are fed a standard rat chow (0.3% NaCl), DS rats, especially males, exhibit marked proteinuria, hypoalbuminemia, and hypertriglyceridemia without marked hypertension at 32 to 38 weeks of age. The nephrosis was associated with spontaneously developed FSGS. We therefore investigated the mechanism of hypertriglyceridemia in nephrotic animals. Plasma triglyceride (TG) and apoprotein (apo) B levels were markedly increased in DS rats compared with Sprague-Dawley (SD) rats, and this was mainly attributable to an increase in the concentration of very-low-density lipoprotein (VLDL). The TG secretion rate estimated by the Triton WR1339 method was significantly greater in DS rats. VLDL-TGs isolated from both the DS and SD rats were endogenously radiolabeled with different isotopes, and a mixture of these was then injected into DS and SD recipients. The half-life of VLDL-TG was about three times longer in DS recipients, regardless of the source of VLDL. In SD recipients, VLDL from DS rats was cleared at a slower rate than VLDL from SD rats. The activity of lipoprotein lipase in postheparin plasma was substantially decreased in DS rats. Isoelectric focusing gel electrophoresis (IEF) showed that the ratio of apo E/C or apo C-II/C-III in VLDL was markedly decreased and the ratio of apo E or apo C to apo A1 in high-density lipoprotein (HDL) was slightly decreased in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Laparoscopic study of peliosis hepatis and nodular transformation of the liver before and after renal transplantation: natural history and aetiology in follow-up cases.

Although peliosis hepatis and nodular transformation of the liver can occur after renal transplantation, their prevalence has not been well defined. To investigate the incidence of these complications, 137 laparoscopies were studied, 52 in 50 cases before and 85 in 66 cases after renal transplantation. To elucidate the aetiology and natural history of these diseases, cases were followed up by repeated laparoscopies. Peliosis was observed after transplantation (before: n = 1, after: n = 15 [22%], p < 0.005). Nodular transformation was seen only after transplantation (n = 5 [7%]), and was accompanied by peliosis (n = 4, p < 0.01). On observation before and after transplantation in the same cases, these diseases appeared after transplantation (peliosis: n = 9, p < 0.005; nodular transformation: n = 2). In follow-up cases, these diseases were confirmed after the discontinuation of or the controlled administration of immunosuppressants. The aetiology of the micronodular transformation which appeared following peliosis in a case treated without cyclosporin was shown to be azathioprine. However, the macronodular transformation observed in two cases treated with both azathioprine and cyclosporin seemed to be due to cyclosporin. This suggests that cases of peliosis hepatis and nodular transformation which appear after renal transplantation are associated with immunosuppressants, and that cyclosporin treatment may also affect the morphogenesis of nodular transformation.

Adult↗
PubMed1994

Long-term graft survival rate of zero-mismatch kidney transplants for HLA-DRB1.

The study of a two-locus association between HLA-B and -DRB 1 revealed a significant 43 linkage disequilibrium. Donor-recipient HLA-DRB1 was determined by these 43 linkages. Zero-mismatch for HLA-DRB1 had a significant effect on the graft survival rate in living related and cadaver transplants. The 5-year graft survival rate was 94% in the zero-mismatch group for HLA-DRB1, 96% for related transplants, 92% for cadaver cases, and 94% in HLA identical siblings. A statistically significant difference was found between the zero-mismatch group for HLA-DRB1 and mismatch groups for HLA-DRB1 or HLA-DR (P < 0.01). The zero-mismatch group for HLA-DRB1 had mismatches for HLA-A and/or HLA-B in 46 of 70 cases (66%). No significant differences in the rejection rate was observed between zero-mismatch and mismatch cases for HLA-A and/or -B in the zero-mismatch group for HLA-DRB1. In the second step, genotyping was conducted in 118 cases. The 5-year graft survival rate was 93% in the zero-mismatch group for HLA-DRB1 and 86% in mismatch group (not a significant difference). We concluded that zero-mismatch transplant for HLA-DRB1 had a better long-term graft survival rate regardless of HLA class I.

Cyclosporine↗