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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 145 records · Page 8Linked to original sources
PubMed1988

Evidence for the role of active oxygen in guanidine synthesis in haemodialysis patients and in vitro.

This study clarifies the correlation between guanidino compounds and other laboratory findings including peroxidative markers in the sera of patients undergoing regular haemodialysis. The concentration of guanidine, for example, correlates significantly with iron, ferritin, and malondialdehyde. Guanidine is synthesized from various guanidino compounds such as arginine, guanidinoacetic acid, creatinine, creatine, methylguanidine, guanidinosuccinic acid, and canavanine in vitro by the hydroxyl radical. These results suggest that guanidine is synthesized as a result of active oxygen, and demonstrates the importance of guanidine as an indicator of the peroxidative state in patients with uraemia.

Adult↗
PubMed1988

Serum binding and biliary excretion of bilirubin after bilirubin loading in Nagase analbuminemic rats and heterozygous (Jj) Gunn rats.

To elucidate the effects of albumin on the handling of serum bilirubin, hepatic metabolism and biliary excretion of bilirubin were examined during intravenous bilirubin infusion in Sprague-Dawley (SD) rats, Gunn (heterozygous, Jj) rats, and Nagase analbuminemic rats (NARs). Serum bilirubin was primarily bound to a protein fraction with a molecular weight of about 600 x 10(3) or more in NARs. About 39.2% +/- 12.5% of the serum bilirubin during infusion of bilirubin was bound to the same fraction in Gunn rats. Bilirubin was substantially taken up into the liver and excreted into the bile in NARs, suggesting the role of a high molecular protein, probably a lipoprotein, in its blood transport and the hepatic uptake process. In NARs, biliary bilirubin secretion reached the peak between 20 and 40 minutes after the initiation of bilirubin loading and decreased thereafter, whereas it continued to increase in SD rats and in NARs to which albumin was administered 20 minutes after the start of bilirubin loading. Biliary bilirubin fractions before bilirubin loading were similar in SD rats and NARs, whereas an increase in bilirubin monoglucuronide (BMG) and a decrease in bilirubin diglucuronide (BDG) were observed in Gunn rats. After the initiation of bilirubin loading, a decrease in biliary BDG and an increase in BMG and unconjugated bilirubin were observed in all groups of rats.

Animals↗
PubMed1987

Inter-organ metabolism and transport of a cysteine-S-conjugate of xenobiotics in normal and mutant analbuminemic rats.

Biosynthesis of N-acetylcysteine S-conjugates of toxic electrophiles, mercapturic acids, occurs via inter-organ metabolism and transport in which liver, small intestine and kidney play an important role. Since a mercapturic acid is a hydrophobic organic anion and strongly binds to plasma albumin in vitro, the ligand-albumin interaction may affect the metabolic fate of this final metabolite in vivo. To investigate the role of the circulating albumin in detoxication and elimination of a toxic electrophile, urinary occurrence of the final metabolite was determined in normal and mutant Nagase analbuminemic rats (NAR) after administration of S-benzylcysteine, a model compound of cysteine conjugates. S-Benzylcysteine intravenously administered was excreted rapidly into urine as its N-acetyl derivative in both animal groups. However, the urinary recovery of this mercapturic acid was significantly lower in NAR than in normal animals. The lower urinary recovery in NAR was due to a rapid and random distribution of the unbound metabolite in the circulation to extrarenal tissues. In contrast, no significant difference in the urinary recovery of the final metabolite was observed between the two animal groups if S-benzylcysteine was given orally. Kinetic analysis revealed that the major part of the orally administered S-benzylcysteine was transferred to the liver and acetylated predominantly in this organ in both animal groups; the mercapturic acid which was synthesized in the liver can be transferred to the kidney and excreted into urine even in the absence of the circulating albumin. These results indicate that albumin is important for a final elimination of a mercapturic acid when animals were extraorally challenged with a large dose of toxic electrophiles by which the rate of biosynthesis and the plasma level of the amphipathic metabolites were increased.

Acetylation↗
PubMed1987

A new radioimmunoassay of free thyroxine using 125I-labelled thyroxine-protein complex uninfluenced by albumin and thyroxine-binding globulin.

We describe a double-antibody solid phase radioimmunoassay for free thyroxine (FT4) in serum with use of 125I-labelled thyroxine-human chorionic gonadotropin conjugate. Since the labelled conjugate does not bind to thyroxine binding globulin (TBG) and albumin because of its large molecular weight, the method is uninfluenced by TBG or albumin. The measurable range of FT4 in serum was 2.0 to 128 ng/l. The mean coefficients of variation within and between assays were 4.6-8.6% and 6.3-11.6%, respectively. The FT4 values determined by the proposed method correlated well with those determined by commercial radioimmunoassay in subjects with normal albumin concentration (r = 0.98). The FT4 concentrations in serum as determined by this method were 9 to 17 ng/l for healthy adult subjects; high for patients with hyperthyroidism; low for patients with hypothyroidism; and within normal limits for pregnant women, and patients with high or low concentrations of thyroxine-binding globulin.

Albumins↗
PubMed1987

Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients.

To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of this diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.

Animals↗
PubMed1987

Conversion of androstenedione to 3 beta-hydroxy-5-androsten-17-one and 3 beta-hydroxy-4-androsten-17-one by the testicular microsomal fraction of Sprague-Dawley rats.

When androstenedione was incubated with testicular microsomes of Sprague-Dawley rats in the presence of reduced nicotinamide-adenine dinucleotide (NADH), unknown metabolites were produced, in addition to testosterone and 7 alpha-hydroxyandrostenedione. The metabolites were identified as 3 beta-hydroxy-4-androsten-17-one and 3 beta-hydroxy-5-androsten-17-one (3:1) by biochemical and radiochemical methods. These results confirmed the occurrence of the reverse reactions from androstenedione to 3 beta-hydroxy-4-androsten-17-one and 3 beta-hydroxy-5-androsten-17-one catalyzed by the 3 beta-hydroxysteroid dehydrogenase and 5-ene-4-ene isomerase in the microsomal fraction of Sprague-Dawley rat testes.

Acetylation↗
PubMed1987

A high level of transferrin mRNA in the liver of analbuminemic rats.

By means of immunological screening, a cDNA clone bearing the mRNA sequence for rat transferrin was isolated from a cDNA library of rat liver mRNA. The amounts of transferrin mRNA in livers of analbuminemic rats (NAR, Nagase analbuminemia rats) and normal rats were determined by RNA blot hybridization using a cloned transferrin cDNA probe. The level of transferrin mRNA in the NAR liver was about 1.7 times that in the normal rat liver. These findings suggest that the enhanced synthesis of transferrin in the NAR liver resulted from an increase in the transferrin mRNA level.

Animals↗
PubMed1987

Establishment and characteristics of five analbuminemic inbred strains of rats.

Five analbuminemic inbred strains of rats (AD/1, AD/2, AD/3, AD/4, AD/5) were established from Nagase analbuminemic rats (NAR). They showed no genetic differences in coat color, biochemical marker gene loci and skin grafting test. Their serum levels of total cholesterol, phospholipids, triglycerides, and beta-lipoproteins were compared with normal inbred strains (L) derived from Sprague-Dawley rats. Their plasma apoproteins were also examined. All inbred strains of analbuminemic rats showed hyperlipidemia progressing with age although there were slight variations in their lipid and apoprotein levels. These analbuminemic inbred strains of rats may be multigenic models of lipid metabolism abnormality.

Animals↗
PubMed1987

Sex differences in the effect of uric acid on the survival of analbuminemic rats exposed to cold: effects of gonadal hormones and uric acid.

When female analbuminemic rats were injected with 0.8 mg uric acid every 3 h, their survival time at 5 degrees C increased from 14 h to 28 h, but uric acid had no effect on analbuminemic male rats. When female rats were oophorectomized 1 week before cold exposure, the injection of uric acid had no effect on their survival. Furthermore, uric acid did not increase the survival of the female rats that were administered a pellet containing 5 mg testosterone 1 week before the cold exposure. When the male rats were castrated 1 week before cold exposure, their survival time decreased from 20 h to 14 h, and administrations of 5 mg estradiol pellet at the time of castration and 0.8 mg uric acid every 3 h during cold exposure increased their survival time to 23 h.

Animals↗
PubMed1987

Transplantation of putative preneoplastic hepatocytes of analbuminemic rats in the livers of Sprague-Dawley x analbuminemic hybrid rats.

As the analbuminemia of analbuminemic rats (NAR) is inherited as a recessive trait, the livers of F1 hybrids of Sprague-Dawley X NAR (SD X NAR) retain the capability to produce albumin. We induced albumin-negative hyperplastic nodules in the livers of NAR, isolated the nodule cells and transplanted them in the livers of SD X NAR by infusion into the mesenteric vein. When the hosts were treated with dietary 2-acetylaminofluorene plus a partial hepatectomy, numerous albumin(-) nodules of donor origin were formed within the albumin(+) livers of the hosts. This system should be useful to analyze sequential events during hepatocarcinogenesis by using a genotypic marker.

Animals↗
PubMed1987

[Research related to hormones in Nagase analbuminemic rats].

The levels of hormones in the anterior pituitary gland and serum in Nagase analbuminemic rats (NAR) were examined. For the anterior pituitary gland, the contents of prolactin, TSH, GH, LH and FSH in male NAR were lower than those of normal rats. In female NAR, prolactin and TSH levels were also lower than those in normal rats, whereas LH, FSH and GH were unchanged. In serum, the concentrations of TSH, T3, T4, estradiol, testosterone and prolactin (female only) were examined. The serum prolactin level in female NAR was lower than that of normal rats, whereas a higher level of serum TSH was seen in NAR. Male NAR had a higher T3 level and a lower T4 level. Although the estradiol concentration in male NAR was normal, the serum testosterone level was only a quarter of that in normal rats. We investigated the reason for the low level of serum testosterone in male NAR through biochemical studies on steroid metabolism. The results indicated that the low serum concentration of testosterone in NAR was mainly attributable to decreased biosynthesis of testosterone in the testes. Prolactin is the primary hormone for experimental mammary tumorigenesis. In association with the lower prolactin level in female NAR, induction of tumors by 7, 12-dimethylbenz (a) anthracene (DMBA) was studied. NAR showed a significantly lower mammary tumor response to DMBA. The incidences of spontaneous mammary tumor in NAR and normal rats after 2 years were also compared. The incidence was much lower in NAR than in the controls. Thus the lower mammary tumor induction in NAR could mostly be ascribed to the lower level of circulating prolactin.

9,10-Dimethyl-1,2-benzanthracene↗