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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 181 records · Page 10Linked to original sources
PubMed1985

Bile acid profiles in analbuminemia rats.

Bile acid profiles in serum, urine and bile of Nagase analbuminemia rats (NAR) and Sprague-Dawley rats (SDR) were examined. Serum bile acid levels in NAR (2.02 + 0.51 micrograms/ml, n = 15, M +/- S.E.) were markedly decreased as compared with those in SDR (20.86 +/- 3.72 micrograms/ml, n = 10). The unbound fraction of acids in serum examined by equilibrium dialysis was about ten times higher in NAR than in SDR. In the profiles of urinary and biliary bile acids in NAR and SDR, as big differences as seen for serum bile acids were not observed. Low bile acid levels in serum of NAR may reflect low bile acid binding capacity of NAR serum because the absence of albumin was thought to be one of the major causes of low bile acid levels in serum of NAR.

Aging↗
PubMed1985

The role of albumin in the hepatic transport of bilirubin: studies in mutant analbuminemic rats.

Bilirubin and other cholephilic organic anions are bound to albumin in the circulation; their hepatic uptake involves a carrier-mediated process. To investigate the possible role of serum albumin in the transhepatic transport of a cholephilic ligand, plasma clearance of radioactive bilirubin and its biliary excretion as well as its interaction with plasma proteins were compared between normal and mutant analbuminemic rats (NAR). With a tracer amount of 3H-labeled bilirubin, its plasma clearance and biliary excretion were comparable in both animal groups. However, the plasma clearance of a loading dose of the ligand was significantly increased and its biliary recovery was low in NAR as compared with normal animals. In accord with these findings in vivo, gel permeation chromatographic analysis revealed that the bilirubin binding capacity of serum proteins was significantly lower in NAR than in control animals. When bilirubin was administered to NAR as a mixture with equimolar albumin, its plasma disappearance was considerably decreased and its biliary recovery was increased. Similar effects were observed when albumin was replaced by an equimolar amount of glutathione S-transferases (ligandins). These observations indicate that, although ligand-protein interaction in the circulation is important for directing bilirubin to the plasma membranes of the hepatocyte, this mechanism is not specific for albumin.

Animals↗
PubMed1985

Biosynthesis of methylguanidine in isolated rat hepatocytes and in vivo.

To clarify the organ in which methylguanidine is synthesized, high doses of creatinine, which is known to stimulate the synthesis of methylguanidine, were administered to male Wistar rats intraperitoneally. Various tissues of the rats were frozen by a freeze clamp method before and 1, 2 and 3 h after injection, and methylguanidine was determined by high-pressure liquid chromatography using 9,10-phenanthrenequinone for fluorometric determination. We found evidence that the liver, kidney, lung, muscle, red blood cells and gut flora synthesize methylguanidine. In addition, we measured the synthesis of methylguanidine in isolated hepatocytes prepared from normal rats following the addition of creatinine, arginine and guanidinoacetic acid to the incubation medium. Synthesis of methylguanidine was observed only in those incubations which contained creatinine, and was dependent on the concentration of creatinine in the media and on the incubation period. Isolated rat hepatocytes also synthesized guanidine in the presence of guanidinoacetic acid. These results indicate that the liver is one of the organs which synthesize methylguanidine and also that creatinine is the precursor.

Animals↗
PubMed1985

Low susceptibility of analbuminemic rats to induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

The susceptibility of analbuminemic rats (Nagase analbuminemic rats; NAR) to induction of bladder cancer by oral N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was studied. Male NAR and Sprague-Dawley rats (SD) were fed normal diet or normal diet supplemented with 0.2% FANFT for 10 weeks and killed in week 52. Bladder cancer was found in 5 of 24 SD (21%) but not in 18 NAR (0%). Proliferative lesions of the bladder epithelium, which are considered to be precancerous or more advanced than precancerous changes, were found in 16 of 24 SD (67%), but in only 4 of 18 NAR (22%). NAR showed lower susceptibility than control SD to induction of bladder cancer by FANFT.

Animals↗
PubMed1985

Renal secretion of phenolsulfonphthalein: analysis of its vectorial transport in normal and mutant analbuminemic rats.

Transtubular transport of many organic anions, such as p-aminohippuric acid and phenolsulfonphthalein (PSP), from plasma into urine is an important renal function. Most of these nephrophilic ligands strongly bind to albumin in the circulation. To investigate a possible function of plasma albumin in vectorial transport of these organic anions, plasma clearance and urinary excretion of PSP, on one hand, and its interaction with serum proteins, on the other, were studied in normal and mutant Nagase analbuminemic rats (NAR). Intravenously administered PSP rapidly disappeared from the circulation, followed by its urinary excretion in both NAR and normal rats. However, its plasma clearance was significantly larger in NAR (53.9 ml/min/kg body weight) than in normal animals (4.7 ml/min/kg body weight). Gel exclusion Sephadex G-100 chromatography and ultrafiltration analysis revealed that the PSP binding capacity of serum proteins was considerably lower in NAR than in normal rats; 32.0% and 12.5% of the ligand bound to NAR serum protein and 94.4% and 84.2% to normal rat serum protein (predominantly albumin) at 0.1 and 0.5 mmol/L ligand concentrations, respectively. Despite the greater PSP clearance in NAR, its urinary excretion was lower in NAR than in the normal animals; 20.9% +/- 2.5% and 46.0% +/- 12.6% of the administered dose appeared in NAR and normal rat urine, respectively, within 3 hours of administration. Injection of PSP with equimolar albumin resulted in a decrease in plasma clearance and an increase in urinary excretion of PSP in NAR; more than 31.4% +/- 3.3% of the injected dose appeared in the urine within 3 hours of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1984

Mammary tumor induction in analbuminemic rats by 7,12-dimethylbenz(a)anthracene.

Induction by 7,12-dimethylbenz(a)anthracene of mammary tumors was studied in analbuminemic rats, a mutant strain established from Sprague-Dawley rats which are characterized by the absence of serum albumin and hyperlipidemia. Twenty-three weeks after carcinogen administration, the incidence and average number of mammary tumors and the tumor weight per tumor-bearing rat were respectively 35.0%, 1.7 +/- 0.2 (S.E.) and 8.9 +/- 0.5 g in analbuminemic rats and 69.2%, 2.3 +/- 0.2 and 12.2 +/- 2.8 g in the controls. Associated with this lower mammary tumorigenic response, analbuminemic rats had significantly lower plasma prolactin levels than controls during proestrus at 7-8 weeks of age when carcinogen was given (176 +/- 62 vs 308 +/- 52 ng/ml).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Carcinogenic effects of 3-di(hydroxymethyl)-amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazine in the small intestine of Ishibashi and Wistar rats.

The carcinogenic effect of an oral administration of 3-di(hydroxymethyl)-amino-6-(5-nitro-2-furylethenyl)-1,2,4-triazin e (DHNT) was studied in two strains of rats. Ishibashi (IS) rats have a perpetual absorption disturbance while Wistar Imamichi (WI) rats have no such disturbance. Small intestinal carcinomas developed in 10 out of 15 (66.7%) IS rats and in all 8 (100%) Wistar rats given 3,500 ppm DHNT for 43 weeks. The total number of lesions in the small intestine was 24 in IS rats and 21 in WI rats. Histologically, the lesions consisted of 7 mucosal dysplasias, 4 adenomas and 12 tubular and 1 papillary adenocarcinoma in IS rats, and 3 mucosal dysplasias, 1 adenomas, and 15 tubular and 2 papillary adenocarcinomas in WI rats. The levels of plasma leucine aminopeptidase, copper and total protein were lower, while blood urea nitrogen was higher in both strains of rats given DHNT than in control rats.

Adenocarcinoma↗
PubMed1984

Purification and characterization of hyaluronic acid from the horny layer of guinea pigs.

Hyaluronic acid was purified from the horny layer of guinea pigs and its biochemical and physical properties were studied. The horny layer, obtained by applying n-hexadecane to guinea pig skin, was digested with pronase, and glycosaminoglycans in the digest were separated from UV-absorbing material by Sephadex G-75 chromatography (sample A, 17.5 mg). On DEAE-Sephadex chromatography, the fraction obtained with 0.5 M NaCl was found to contain 94% of the total uronic acid. This fraction, consisting mainly of hyaluronic acid, was dialyzed and lyophilized (sample B, 12.5 mg). Sample B, consisting of 26.1% uronic acid and 27.0% glucosamine on a dry weight basis, could be digested completely with Streptomyces hyaluronidase. Sample B had a low reduced viscosity which showed almost no concentration dependence. The intrinsic viscosity of sample B was 0.83 dl/g and its molecular weight, calculated from its viscosity, was 34,000. Sample B was eluted from Sepharose CL-6B as a broad peak between the void volume and the total column volume. The enzyme levels of hyaluronidase, beta-glucuronidase, and beta-N-acetylglucosaminidase in the n-hexadecane treated guinea pig skin increased to 1.7 to 2.5 fold those of controls after 6 days of the experiment. These results suggested that hyaluronic acid in the horny layer of n-hexadecane treated guinea pig skin might be degraded by hyaluronic acid degrading enzymes in the hyperkeratinized tissue.

Animals↗
PubMed1984

Penetration of bilirubin into the brain in albumin-deficient and jaundiced rats (AJR) and Nagase analbuminemic rats (NAR).

An albumin-deficient and jaundiced strain of rats (AJR) was established by crossing Nagase analbuminemic rats (NAR) with jaundiced Gunn rats. AJR have no serum albumin and die with kernicterus within 3 weeks after birth. Their serum bilirubin level was 25 per cent (20 micrograms/ml) of that of Gunn rats at 1-2 weeks of age, while their brain bilirubin content was 1.2-2.7 times (4-5 micrograms/g brain) that of Gunn rats. Binding of bilirubin to NAR plasma proteins was examined. The bilirubin binding protein in NAR plasma was found to be lipoprotein, showing an association constant of 6.7 X 10(6) M-1. Bilirubin-transport into the brain of postnatal NAR was investigated by intravenous infusion of bilirubin with taurocholate. The brain bilirubin level of NAR infused with free bilirubin was 1.6 times that of normal rats. In NAR, the brain level on infusion of lipoprotein-bound bilirubin was similar to that on infusion of free bilirubin, but albumin-bound bilirubin scarcely entered the brain. These findings suggest that lipoprotein-bound bilirubin can diffuse across the blood-brain barrier into the brain.

Aging↗
PubMed1984

Disposition of salicylic acid in analbuminemic rats.

To clarify the role of albumin in the dispositions of drugs by in vivo experiment, analbuminemic rats were used and plasma-level analyses and whole-body autoradiography following intravenous administration of 14C-salicylic acid were carried out. The distribution volume of salicylic acid in analbuminemic rats (650 +/- 33 ml/kg) was remarkably larger than that in normal rats (180 +/- 3 ml/kg) (p less than 0.01). Whole-body autoradiograms demonstrated that transfer of salicylic acid from the blood to the liver, muscle and brain, especially to the liver, may be increased in analbuminemic rats. The increased distribution may be explained by the lack of plasma albumin, since the distribution of salicylic acid depends in part on plasma albumin binding. The total body clearance of salicylic acid in analbuminemic rats (12.2 +/- 1.4 ml/min/kg) was about 3.2 times that in normal rats (3.8 +/- 0.1 ml/min/kg) (p less than 0.01), suggesting that metabolic clearance and/or renal clearance is enhanced in analbuminemic rats. Increased extraction by the liver and/or the kidney due to increased free fraction in total (bound and unbound) plasma salicylic acid assumed to be responsible for this result.

Animals↗
PubMed1984

Hormone levels of anterior pituitary gland and serum in Nagase analbuminemia rats.

The hormone levels in the anterior pituitary gland and serum in Nagase analbuminemia rats (NAR), a mutant strain established from Sprague-Dawley rats with hyperlipidemia, were examined. For the anterior pituitary gland, the prolactin, TSH, GH, LH and FSH contents in male NAR were significantly lower than those of normal rats. In female NAR, prolactin, TSH and LH levels were also lower than those in normal rats, whereas FSH and GH were normal. For the serum, the concentrations of TSH, total T3, total and free T4, estradiol-17 beta and testosterone were examined. The serum testosterone concentration in NAR was lower than that of normal rats. Histochemical examination of the hydroxysteroid dehydrogenase (HSD) activity of testes was made in relation to the serum testosterone level. NAR testes, which are rather small compared with those of normal rats, have lower HSD activity. A higher level of serum TSH was seen in NAR. Total and free T4 concentrations were low in the male NAR only. Estradiol-17 beta and T3 concentrations in NAR were unchanged. Changes in serum LH and FSH levels during the estrous cycle in NAR were also studied. Their patterns of change are normal.

Age Factors↗
PubMed1984

Establishment of an albumin-deficient and fatty strain of rats.

An albumin-deficient and fatty strain of rats (AFR) was established from crosses between albumin-deficient rats (NAR) and fatty Zucker rats. AFRs have double homozygous mutant genes (alb/alb, fa/fa). The AFRs are heavier than the fatty Zucker rats and they have enlarged livers and adrenal glands. In addition, AFRs show more severe hyperlipidemia than fatty Zucker rats. This strain of rats may serve as a model of human obesity and hyperlipidemia.

Animal Husbandry↗
PubMed1984

Anemia and potassium permeability of red blood cells in analbuminemic rats.

A mutant strain, Nagase analbuminemia rats (NAR), was established from Sprague-Dawley rats. Hematological evaluations were made on NAR of 4 to 52 weeks of age. NAR had an abnormally low number of red blood cells (RBC), a low hematocrit, a reduced hemoglobin concentration and an increased number of reticulocytes. Their plasma electrolyte level was normal. Osmotic fragility of RBC was slightly increased in the rats. Thus NAR shows a slight anemia. The in vitro experiments on RBC were performed. The incubation of blood showed a hemolytic tendency and elevated potassium efflux in the blood of NAR. In addition, an increased efflux of potassium was found in the RBC of NAR, when the RBC was washed with phosphate buffered saline and then was incubated with the saline containing CaCl2. This potassium efflux was prevented in the presence of rat albumin. These findings suggest that the deficiency of serum albumin may increase the permeability of potassium in erythrocyte membrane in NAR.

Anemia, Hemolytic↗
PubMed1984

[A problem on the uric acid value of rats for clinical evaluation].

Routine monitoring on levels of serum uric acid in the rats has been widely employed as an important factor in the nucleic acid metabolism, despite of the presence of the uricase in them. In this paper, it is confirmed that the levels of allantoin in serum and urine of the normal rats were higher than those of uric acid. Therefore, the concentration of allantoin in serum and urine of the rats with abnormal nucleic acid metabolism caused by adenine administration were measured. The results indicated that the value of serum allantoin was more sensitive to abnormal nucleic acid metabolism.

Adenine↗
PubMed1984

Age-related changes in the molecular weight of hyaluronic acid from rat skin.

Age-related changes in the molecular weight of hyaluronic acid from the skin of rats was studied using fetuses, newborn animals and rats 1, 2, 3, 4, 13, 26 and 52 weeks of age. Average values of the molecular weight of hyaluronic acid varied with age in three phases: 39 X 10(4) in fetuses and up to the age of one week, 55 X 10(4) in individuals aged to 26 weeks and 87 X 10(4) in individuals 52 weeks of age. The distribution of molecular weight was quite different between 4 weeks and 52 weeks of age. At 4 weeks of age, the molecular weight of hyaluronic acid was widely distributed, ranging from 18 X 10(4) to 79 X 10(4), while that from 52-week-old individuals was very high with a distribution ranging from 92 X 10(4) to 119 X 10(4).

Aging↗