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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 163 records · Page 9Linked to original sources
PubMed1987

A long-term cortical blindness after head trauma.

Here is a case of long-term cortical blindness after a head trauma. Its etiology is ascribed to the cerebral vascular occlusion caused by the head trauma. From the findings of both a computerized tomography (CT) and magnetic resonance image (MRI), the lesions of our case are assumed to be in the bilateral areas 17 (Brodmann), some part of the bilateral areas 18, 19 (Brodmann) and bilateral optic radiations. On determination of the areas of these lesions, the location of the lesion in the bilateral areas 17 has been especially done by using the MRI. The MRI findings in our case have a full significance on this point.

Adult↗
PubMed1986

Effect of albumin on hepatic uptake of warfarin in normal and analbuminemic mutant rats: analysis by multiple indicator dilution method.

Multiple indicator dilution studies of warfarin uptake were carried out on isolated perfused rat livers in the presence and absence of bovine serum albumin (BSA) in the perfusate using normal rats and Nagase analbuminemic rats (NAR). A distributed model was fitted to the dilution data and estimates of influx, efflux, and sequestration rate constants were obtained. In both groups of rats, the intrinsic clearance for unidirectional hepatic uptake (CLint,influx) of warfarin in the presence of 1.6 g/dl BSA was approximately 37-45% of that in the absence of BSA, while the unbound fraction of warfarin with 1.6 g/dl BSA in the perfusate was only 4.2% of that in the absence of BSA. Thus the degree of BSA-induced reduction of the value of CLint,influx and that of the unbound fraction are different. From these observations, it was found that the hepatic uptake of warfarin is not driven solely by the unbound concentration of warfarin, supporting the recent concepts of albumin-mediated transport for tightly albumin bound ligands as reported by Ockner et al. In addition, the fact that the same hepatic uptake mechanism of warfarin was also observed in NAR suggested that the hepatic uptake of warfarin may not necessarily require a special albumin receptor on the hepatocyte surface.

Animals↗
PubMed1986

Reduced activity of androgen biosynthesis in the testes of rats with analbuminemia.

Steroid metabolism in Nagase Analbuminemia Rats (NAR), a mutant strain established from Sprague-Dawley rats, was studied. NAR are characterized by lack of serum albumin and hyperlipidemia. Total testosterone concentration in the serum of NAR was lower than that of normal rats, while the serum free testosterone, LH and FSH concentrations were similar. The half lives of 14C-labeled testosterone administered intravenously in NAR and normal Sprague-Dawley (SD) rats were 4.4 and 4.1 min, respectively. The plasma clearance rates of testosterone in NAR and normal rats were 34.7 and 39.1 ml/min per kg body weight. On Sephadex G-100 chromatography, a mixture of [3H]testosterone and normal rat serum gave two protein peaks eluted in the void volume and the albumin fraction, and the radioactivity was eluted all in the albumin fraction. In contrast, a mixture of [3H]testosterone and NAR serum gave a single protein peak eluted in the void volume and the radioactivity was mainly eluted with this protein peak. The association constants of testosterone to NAR and normal rat sera were 1.25 and 2.24 X 10(4) M-1. Enzyme activities related to the synthesis of testosterone by the testicular microsomal fractions of NAR and normal rats were examined. The activities of 3 beta-hydroxysteroid dehydrogenase, 5-ene-4-ene isomerase, 17 alpha-hydroxylase, C-17-C-20 lyase and 17 beta-hydroxysteroid dehydrogenase were lower in NAR than in normal rats. The activity for synthesis of testosterone from pregnenolone by the testicular microsomal fraction of NAR was about 40% of that of normal rats. These findings indicate that the low serum concentration of testosterone in NAR is mainly attributable to decreased biosynthesis of testosterone in the testes.

Androgens↗
PubMed1986

Hepato-renal transport of phenolsulfonphthalein in analbuminemic rats: albumin is essential for hepatic compensatory elimination of a nephrophilic ligand in animals with renal dysfunction.

To investigate a possible function of plasma albumin in partitioning organic anions into bile and urine, phenolsulfonphthalein (PSP) was administered intravenously and its in vivo fate was studied in normal and analbuminemic mutant rats (NAR). No significant change in the rate of PSP disappearance was observed in bilaterally nephrectomized normal rats. However, biliary excretion of the injected dye increased remarkably in nephrectomized normal rats. Intravenously injected PSP disappeared very rapidly from the circulation of NAR. Thus, the plasma clearance and distribution volume of PSP were significantly larger in NAR than in normal rats. Bilateral nephrectomy also failed to decrease the plasma clearance and distribution volume of the dye in NAR. In striking contrast to the experiments in normal rats, bilateral nephrectomy did not increase the biliary secretion of PSP in NAR. When PSP bound to equimolar albumin was injected into bilaterally nephrectomized NAR, the biliary excretion of PSP increased significantly with concomitant decrease in both plasma clearance and distribution volume of the dye. These results indicate that, in cases of renal transport dysfunction, albumin plays a critical role in hepatic compensatory excretion of PSP, a nephrophilic organic anion, whose molecular weight (MW 354) is close to the threshold value for partitioning a ligand to the eliminatory routes in liver and kidney of a rodent.

Animals↗
PubMed1986

Lectin binding sites related with rat ascites hepatoma cell adhesion.

In order to elucidate the correlation between cell surface lectin binding sites and the degree of cell adhesiveness, quantitative lectin binding assays were performed using three types of rat ascites hepatoma cell lines (free cell, mixed cell, and island-forming cell types). The lectin binding site patterns showed no remarkable differences among the intact tumor cell lines, but treatment of the cells with L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK)-trypsin or neuraminidase induced remarkable differences in the modulation of the number of lectin binding sites. TPCK-trypsin treatment caused a marked decrease in the number of peanut agglutinin binding sites on the island-forming and mixed cell types, concomitant with disaggregation of the cells, showing that trypsin sensitive binding sites are involved in the cell-cell adhesion. Neuraminidase treatment caused a decrease in wheat germ agglutinin binding sites and an increase in castor bean agglutinin binding sites, and these effects were greater for the free cell type. These results indicated that alpha-sialyl-beta-D-galactosyl residues are more abundant on the cell surface of the free cell type than the other cell types. Therefore, it was suggested that electrostatic repulsion due to negative charges of the cell surface sialic acid contributes to the low cell adhesiveness of the free cell type.

Animals↗
PubMed1986

Active oxygen in methylguanidine synthesis.

Methylguanidine (MG), a toxin reported in uremia, is thought to be a product of creatinine oxidation. This study is designed to demonstrate the role of active oxygen in the oxidation of creatinine under conditions compatible with those found in uremia. MG synthesis is moderately stimulated by the superoxide radical derived from 3 mM hypoxanthine and 0.015 units/ml xanthine oxidase and inhibited by the addition of superoxide dismutase. This is increased markedly by the addition of 0.05% hydrogen peroxide and augmented to about 56,000 times the control rate in the presence of hydroxyl radicals derived from the reaction of 10 mM FeSO4 and 0.05% hydrogen peroxide. In addition, MG synthesis is inhibited by the addition of sorbitol, lactulose or ethanol, the scavengers of hydroxyl radicals. These results indicate that creatinine can be oxidized to MG by various species of active oxygen and that one of the mechanisms of MG synthesis is such oxidation. MG, therefore, may be a useful indicator of peroxidation in vivo.

Creatinine↗
PubMed1986

Reproductive activity of analbuminemic rats.

Long-term feeding and breeding in a conventional environment have been investigated in analbuminemic rats, a mutant strain established from Sprague-Dawley rats. Analbuminemic rats kept alive for over two years and maintained normal reproductive performance for over one year. The rotational system of one male and four females was better reproductive efficiency than the continuous pairing system of one male and one female. The litter size and weaning rate in analbuminemic rats were similar to those in Sprague-Dawley rats. Although we tried to establish a caesarean delivered SPF colony of analbuminemic rats, no changes in reproductive performance were recognized.

Animals↗
PubMed1986

Establishment and characteristics of three analbuminemic congenic strains of rats.

We have established three analbuminemic congenic strains of rats (ACI-alb, F344-alb, and SHR-alb) by repeated backcrossing with a progeny test or intercrossing. Some coat color and biochemical marker genes of each congenic strain agreed with those of the background inbred strain of rats, except for the alb gene locus. These established congenic strains were maintained by cross-intercrossing. Body weights, organ weights and serum lipid concentrations of each strain were measured up to 30 weeks of age. Body weights of ACI-alb congenic strains (alb/alb and alb/+) were similar to those of the original ACI(+/+) strain, but those of F344-alb and SHR-alb were heavier in the order of +/+, alb/+ and alb/alb. The liver and adrenal weights of all strains were higher in the order of alb/alb, alb/+ and +/+. Serum lipid concentrations were also higher in the same order. These three analbuminemic congenic strains originating from different inbred strains should be useful in studies of carcinogenesis and genetically modified mechanisms of albumin functions.

Adrenal Glands↗
PubMed1986

Frequent administration of uric acid extends survival of fasting analbuminemic rats under cold environment.

Analbuminemic rats died within 18 h after a rapid decrease of body temperature whereas control Charles River, Wistar, and Sprague Dawley rats survived for 40 h, when the animals were kept at 5 degrees C without food. Five low molecular weight fractions obtained from Sprague Dawley rat sera were administered to analbuminemic rats kept under these conditions. The duration of survival was extended by the administration of two of the fractions. Several characteristics of one of these fractions coincided with those of uric acid, and body temperature of analbuminemic and Sprague Dawley rats increased within 5 min after uric acid administration.

Animals↗
PubMed1986

Presence of albumin-positive cells in the liver of analbuminemic rats and their increase on treatment with hepatocarcinogens.

The analbuminemic rat is a mutant in which albumin mRNA processing is blocked owing to a seven-base-pair deletion in the 9th intron of the albumin gene. A small amount of albumin is detected in the serum of this rat. Production of serum albumin in the liver of this mutant rat was studied by an immunohistochemical method. The results showed that a few albumin-positive cells were present in the liver of the mutant rat, whereas all the hepatocytes in normal rat liver were albumin-positive. In the mutant the number of albumin-positive cells increased with age: their frequency was 10(-5) at birth and 6 X 10(-3) at 45 weeks of age. On administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 2-acetylaminofluorene, albumin-positive cells increased dramatically. Their numbers were 7 to 10 times those of untreated rats after 10 to 16 weeks of carcinogen treatment. The number of albumin-positive cells did not decrease after 3'-Me-DAB feeding was discontinued. In regenerating liver after partial hepatectomy, clusters of albumin-positive cells increased while the number of singlet albumin-positive cells decreased. These observations suggest that the appearance of albumin-positive cells in analbuminemic rat liver may be due to a somatic mutation of the hepatocytes.

2-Acetylaminofluorene↗
PubMed1986

High susceptibility of analbuminemic rats to gastric tumor induction by N-methyl-N'-nitro-N-nitrosoguanidine.

Analbuminemic rats were found to be highly susceptible to induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (67-83 micrograms/ml) given to the rats in drinking water for 32 weeks. The rats were sacrificed at experimental week 44. Gastric tumors were found in 12 of 17 analbuminemic rats (70%) and in 8 of 21 normal rats (38%). Intestinal tumors developed in 7 of 17 (41%) analbuminemic rats and in 9 of 21 (42%) normal rats.

Animals↗
PubMed1986

Urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine in an analbuminemic congenic strain of rats with an ACI genetic background.

An analbuminemic congenic strain of rats originating from ACI (ACI-alb) rats was established. The rats were found to be highly susceptible to induction of urinary bladder cancer by N-butyl-N-(4-hydroxy-butyl)nitrosamine. Bladder cancers were observed in all male ACI-alb and normal ACI rats treated with the compound, but the average weight of the bladder including tumors was more in ACI-alb rats than in ACI rats (0.63 +/- 0.24 g and 0.18 +/- 0.05 g, respectively; ratio, 3.5:1).

Animals↗
PubMed1985

Role of plasma albumin in renal elimination of a mercapturic acid. Analyses in normal and mutant analbuminemic rats.

Biosynthesis of N-acetylcysteine S-conjugates of xenobiotics (mercapturic acids) occurs via interorgan metabolism and the renal transtubular transport system plays an important role in elimination of the final metabolites from the organism. To assess the behavior of a mercapturic acid in the circulation, plasma clearance of radioactive S-benzyl-N-acetylcysteine and its interaction with plasma proteins were studied in normal and mutant analbuminemic rats (NAR). Intravenously injected S-benzyl-N-acetylcysteine rapidly disappeared from the circulation both in NAR and normal animals. However, its plasma clearance was significantly higher in NAR (45.7 ml kg-1 min-1) than in normal rats (25.2 ml kg-1 min-1). Ultrafiltration analysis revealed that 18.4% and 80.1% of the mercapturate bound to plasma protein(s) from NAR and normal rats, respectively, at 50 microM ligand concentration. The mercapturic acid bound to plasma albumin with an association constant of 2.24 X 10(5) M-1 and the number of binding sites was 1.18/mol albumin. The binding was competitively inhibited by probenecid and L-tryptophan. Concomitant administration of this mercapturic acid with equimolar amounts of albumin resulted in a marked decrease in the plasma clearance (26.2 ml kg-1 min-1) and an increase in the urinary secretion of this ligand in NAR. 30 min after injection of the mercapturic acid (10 mumol/kg body weight), 27.3% and 60.4% of the injected dose was recovered from urine and kidneys of NAR and normal rats respectively. About 41% of the dose was recovered in NAR urine when the ligand was injected bound to an equimolar amount of albumin. These results suggested that albumin is important for the renal accumulation and urinary elimination of the circulating mercapturic acid.

Acetylcysteine↗
PubMed1985

Transhepatic transport of taurocholic acid in normal and mutant analbuminemic rats.

To elucidate a possible function of plasma albumin in vectorial transport of various cholephilic organic anions, such as bile acids, plasma clearance and transhepatic transport of radioactive taurocholate were studied in vivo in normal and mutant analbuminemic rats. Intravenous administration of taurocholate was followed by its rapid disappearance from the circulation in both animal groups. However, plasma clearance of taurocholate was significantly larger in analbuminemic (68.3 ml/min per kg of body weight) than in normal rats (29.8 ml/min per kg of body weight) at a dose of 8 mumol/kg of body weight. The increased plasma clearance in analbuminemic rats was accompanied by a more prompt biliary secretion of the ligand than occurred in normal animals; 79 and 42% of the injected dose was recovered in analbuminemic and normal rat bile, respectively, within 10 min after administration. Ultrafiltration analysis revealed that the binding of taurocholate to serum protein(s) was significantly lower in analbuminemic rats as compared with that in normal rat serum; 24 and 76% of taurocholate bound to protein fractions of analbuminemic and normal rat serum, respectively, at 0.5-mM ligand concentration. Binding of taurocholate to cytosolic proteins of normal and analbuminemic liver were similar; 23 and 28% of taurocholate bound to protein fractions from analbuminemic and normal rat, respectively, at 10 mg protein/ml and 20-microM ligand concentration. These results indicate that plasma albumin does not play a role in directing circulating taurocholate to the liver and that transhepatic transport of the bile acid increases with the increase in concentration of unbound ligand in the circulation.

Animals↗