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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 91 records · Page 5Linked to original sources
PubMed1994

Analbuminemia does not significantly influence hepatocarcinogenesis on comparing F344 rats and a congenic line carrying the analbuminemic mutation.

Analbuminemic rats differ from Sprague-Dawley rats (SD), their strain of origin, with respect to carcinogenic susceptibility of various organs. We compared hepatic changes after carcinogenic treatments in two kinds of analbuminemic rats with different genetic backgrounds (NAR isolated from outbred SD and F344-alb F344-congenic analbuminemic rats) as well as in their parent strains. After the rats were treated according to the Solt-Farber protocol [a single dose of diethylnitrosamine (DEN) followed by dietary 2-acetylaminofluorene (2-AAF) plus partial hepatectomy], F344 and F344-alb demonstrated similar numbers of much larger hyperplastic hepatic nodules (HPN) than SD or NAR, while in the latter two cases, sizes are approximately the same, NAR had a greater number of HPN. When HPN cells of F344 rats were infused into the portal vein of F344 and F344-alb, followed by treatment with the Solt-Farber protocol, the transplanted cells formed almost the same numbers of colonies of almost equal size within the livers in these two strains of rats. With continuous administration of a 2-acetylaminofluorene (2-AAF) diet, which can change the normally albumin-negative hepatocytes of analbuminemic rats to albumin-positive cells, this process occurred earlier in F344-alb than NAR, but almost the same numbers were reached after 30 days. The results demonstrate responses to significantly differ between NAR and F344-alb, with both resembling their parent strains to a large extent, indicating that genetic background has the major influence on susceptibility to hepatic carcinogenesis, rather than analbuminemia itself.

2-Acetylaminofluorene↗
PubMed1994

Biosynthesis of guanidine in isolated rat hepatocytes, perfused rat liver and intact animals.

Plasma levels of guanidine (G) are reported to be increased in uremic patients and are synthesized from various guanidino compounds via a chemical reaction involving the hydroxyl radical in vitro. To identify both the metabolic precursor and the synthesizing organ of G, we investigated the concentrations of G in various organs of rats administered several guanidino compounds and we attempted to synthesize G biologically using isolated rat hepatocytes or perfused rat liver. In addition, we investigated the effect of the peroxidative state on the G synthesis in isolated hepatocytes using various reagents which alter this condition. Results show that the concentration of G increased in the kidney, liver and muscle following the administration of L-canavanine. In addition, G increased in the kidney at 90 min after the administration of guanidinoacetic acid (GAA). Moreover, G is synthesized from L-canavanine in isolated rat hepatocytes and perfused rat liver, and G synthesis in hepatocytes is partially inhibited by the addition of superoxide dismutase, catalase, glutathione or ethylenediaminetetraacetic acid. These results suggest that L-canavanine is possibly a biological precursor and GAA is an endogenous precursor of G. Furthermore, it is suggested that these reactions are closely related to the peroxidative state.

Animals↗
PubMed1994

New steroidal saponins from the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae).

From the rhizome of Anemarrhena asphodeloides Bunge (Liliaceae), four new steroidal saponins named anemarrhenasaponins I-IV (1-4) were isolated, together with known saponins, timosaponin A-III (5), marcogenin diglycoside (6) and timosaponin B-II (7) and a xanthone C-glycoside, mangiferin. These saponins are coprostane type steroidal glycosides. Their structures were established on the basis of spectroscopic and chemical evidence.

Magnetic Resonance Spectroscopy↗
PubMed1994

Reversion of altered phenotype in primary cultured rat hepatocytes after intrahepatic and intrasplenic transplantation.

BACKGROUND: The phenotype of isolated rat hepatocytes changes during in vitro cultivation, but it is not clear whether this process turns back when the cells are returned to an in vivo milieu. Glutathione S-transferase placental form (GST-P), which is not expressed in hepatocytes in vivo, is induced within a few days of cultivation, whereas cytochrome P-450 constitutionally expressed in hepatocytes in vivo rapidly diminishes. We explored the dynamic nature of hepatocytic phenotypes using these two markers and intrahepatic and intrasplenic transplantation of cultured hepatocytes. EXPERIMENTAL DESIGN: Hepatocytes of F344 rats were isolated and cultured for 5 days to form spheroidal aggregates and then implanted into the livers and spleens of congenic analbuminemic rats. Expression of GST-P and P-450 was then examined immunocytochemically. In the intrahepatic case, the implanted hepatocytes could be distinguished from surrounding host hepatocytes by albumin immunostaining. RESULTS: The intrahepatically implanted hepatocytes turned GST-P-negative within 5 to 10 days, and re-expressed P-450 to a comparable level to that in surrounding host hepatocytes after 2 days. On the other hand, the hepatocytes implanted within spleens continued to express GST-P for 10 days, and started to express P-450 at extraordinarily high levels after 5 to 10 days. CONCLUSIONS: The phenotype of hepatocytes under in vivo and in vitro conditions has proven to be changeable from one to another.

Animals↗
PubMed1993

Elevation of serum albumin by intrahepatic transplantation of albumin-producing cells does not correct quantitative abnormalities of non-albumin proteins in analbuminemic rats.

Nagase analbuminemic rats (NAR) show quantitative abnormalities of non-albumin serum proteins which could represent a compensatory response to the analbuminemia, although total serum protein levels are normal. When hyperplastic hepatic nodule (HPN) cells of F344 rats, which produce albumin, were infused into the portal vein of congenic analbuminemic rats (F344-alb) followed by treatment with the Solt and Farber dietary regimen, the transplanted cells grew within the livers, occasionally developing into hepatocellular carcinomas (HCC). In the recipient F344-alb, while serum albumin was considerably elevated, the total serum protein was also increased. Moreover, the abnormal pattern of serum proteins in NAR was unchanged by the elevation of albumin. These results indicate that the unique pattern of serum proteins in NAR is constitutive and cannot be corrected by a continuous increase in albumin levels.

Animals↗
PubMed1993

Increase in albumin mRNA by repeated intrahepatic transplantation of F344 rat hepatocytes into the liver of congenic analbuminemic rats.

Hepatocytes of F344 rat were transplanted into the liver of congenic analbuminemic rats by infusion into the mesenteric vein from once to four times at one-week intervals. The transplantability was confirmed by the increase in the number of albumin-positive cells and appearance of normal albumin mRNA within the recipient liver, and the elevated serum albumin level. When the normal albumin mRNA was quantitated by reverse transcriptase polymerase chain reaction (RT-PCR) using the abnormally spliced albumin mRNA of analbuminemic rats as an internal standard, the increase in normal mRNA was in good agreement with the serum albumin level and the number of albumin positive hepatocytes within the liver. These three markers proportionally increased with the number of infusion times. Our results demonstrate that the number of intrahepatically transplanted hepatocytes is able to be increased by repeated infusion.

Animals↗
PubMed1993

Change of polyamine level in various tissues of male rats intoxicated with paraquat.

The effects of paraquat (PQ) on the contents of putrescine (PUT), spermidine (SPD) and spermine (SPM) in the various tissues and organs were examined by means of high-performance liquid chromatography in rats intoxicated with the toxin by three intraperitoneal infusions of PQ for 6 days on every other day. The contents of PUT, SPD and SPM in the large intestine per mg of wet weight showed statistically significant decreases of 39 (P < 0.01), 73 (P < 0.01) and 27% (P < 0.05), respectively. In the liver, however, they showed statistically significant increases of 214 (P < 0.01), 39 (P < 0.05) and 78% (P < 0.01).

Animals↗
PubMed1993

Pathological characteristics of mucopolysaccharidosis VI in the rat.

The histological and electron microscopical characteristics of the pathology of rats with arylsulphatase B-deficient mucopolysaccharidosis (mucopolysaccharidosis VI; MPS VI) were investigated. In affected animals, intracytoplasmic vacuoles were prominent in chondrocytes, the macrophage system, cardiac valve fibroblasts, cornea, connective tissues, vascular smooth muscle cells and uterine stromal cells. Tissues containing glucosaminoglycans stored in lysosomes were positive to Mowry's colloidal iron and alcian blue stains. By electron microscopy, the lysosomes were seen to be distended by electron lucent or fine fibrillary storage material, and lysosomal storage was also detected in the endothelial cells of the arteries and cornea. In the central and peripheral nervous system abnormalities were restricted to the connective tissue. Lesions in the affected rats resembled those described in human and feline mucopolysaccharidosis VI. These results indicate that MPS VI of the rat may be a useful animal model for human MPS VI (Maroteaux-Lamy syndrome).

Animals↗
PubMed1993

Recovery from changes in the blood and nasal cavity and/or lungs of rats caused by exposure to methanol-fueled engine exhaust.

One group of male, pathogen-free, Fischer 344 rats was exposed to about 17-fold diluted exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h, and then the rates of recovery from the resulting increased levels of plasma formaldehyde and carboxyhemoglobin in their erythrocytes were measured. The carboxyhemoglobin level in the erythrocytes was restored within 4 h, whereas the plasma formaldehyde level was still elevated after 4 h but was restored to the normal level within 8 h. No methanol or formic acid was detected in the plasma. Another group of rats was exposed to the same dilution of exhaust for 8 h/d for 7 d, and then the recovery from histopathological damage of the nasal cavity and lungs was also examined. Hyperplasia/squamous metaplasia and erosion of the respiratory epithelium lining the nasoturbinate, maxilloturbinate, or nasal septum, and infiltration of neutrophils into the submucosa at level 1 (level of the posterior edge of the upper incisor teeth) were observed immediately after the exposure period. Lesions of the respiratory epithelium at level 2 (incisive papilla) were less than those at level 1. Slight lesions at levels 1 or 2 were still noticed 1 wk after exposure, but not 4 wk after exposure. Just after exposure, decreases of Clara cells in the terminal bronchiolus and of cilia in the bronchial/bronchiolar epithelium were also observed. Moreover, focal hypertrophy of alveolar walls and increase of macrophages were observed in parts adjacent to respiratory bronchiolus. One week after the exposure period, these changes were no longer seen. These results indicate that changes in the blood and in the nasal cavity and lungs caused by methanol-fueled engine exhaust are reversible. However, complete recovery from damage of the nasal cavity caused by 7-d exposure to the exhaust takes 4 wk, and recovery from elevated plasma formaldehyde and erythrocyte carboxyhemoglobin levels caused by a single 8-h exposure takes 4-8 h.

Animals↗
PubMed1993

Polyamine increase in rat tissues treated with 1-beta-D-arabinosylcytosine and 5-fluorouracil.

The effects of 1-beta-D-arabinosylcytosine (ara-C) and 5-fluorouracil (5-FU) on body weight, and the contents of putrescine, spermidine and spermine in 14 different tissues were examined in rats given these drugs for 5 days. There were statistically significant increases in all three polyamines in the small intestine, in spermidine in the lung, and in spermine in the thymus, spleen and liver of rats treated with ara-C and 5-FU. Putrescine content in the spleen, heart, muscle and liver, and spermidine and spermine contents in the stomach of the 5-FU-treated rats also showed significant increases.

Animals↗
PubMed1993

Identification of F344 rat hepatocytes transplanted within the liver of congenic analbuminemic rats by the polymerase chain reaction.

Hepatocytes isolated from F344 rats were transplanted into the liver of congenic albumin-deficient rats (Nagase's analbuminemic rats NAR]) by infusion into the mesenteric vein. Both albumin-positive hepatocytes in the liver and the serum albumin level increased proportionally to the number of the infused F344 hepatocytes in the recipients. However, there was no such increase in the control rats which had received transplantation of NAR hepatocytes. After the polymerase chain reaction (PCR)-mediated analysis of cDNA and genomic DNA of the recipient livers, the implantation of the F344 hepatocytes was confirmed by the increase in normal albumin mRNA and the presence of 7 bp which are missing in the NAR albumin gene. Although treatment of NAR with the 2-acetylaminofluorene diet turned albumin-negative hepatocytes to positive ones, the sequence of the normal albumin gene could not be identified in the NAR liver. This study demonstrates that the hepatocytes infused into the portal vein are readily organized into the host liver parenchyma and continue to produce albumin.

Animals↗
PubMed1993

Arylsulfatase B-deficient mucopolysaccharidosis in rats.

A rat colony with mucopolysaccharidosis VI was established and the clinical, pathological, and biochemical features were characterized. Affected rats had facial dysmorphia, dysostosis multiplex, and increased urinary excretion of glucosaminoglycans (GAGs). Ultrastructural studies revealed storage of GAGs throughout the reticuloendothelial cells, cartilage, and other connective tissues, but no deposition was observed in the nervous system. Biochemical analyses demonstrated that the excreted GAG was dermatan sulfate and the activity of hepatic arylsulfatase B was < 5% of the normal mean value. Pedigree analysis showed that the phenotype was inherited as an autosomal recessive single trait. The availability of a rat model of human mucopolysaccharidosis VI should permit the development and evaluation of various strategies to treat the human disease.

Animals↗
PubMed1993

Modifying effects of chemicals on the development of liver preneoplastic placental glutathione S-transferase positive foci in analbuminemic and Sprague-Dawley rats.

Nagase analbuminemic rats (NARs) were compared to the Sprague-Dawley (SD) stock in a medium-term assay system for hepatocarcinogenesis regarding their susceptibilities to the influence of chemicals on the development of glutathione S-transferase, placental form, positive (GST-P+) foci. Two weeks after initiation with diethylnitrosamine (DEN), the animals were exposed alternatively to 0.06% 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB), 50 ppm DEN, 0.25% ethionine, 1% clofibrate, and 1% butylated hydroxyanisole (BHA) for a 6-wk period. Adequate controls included groups only initiated with DEN or treated with each test compound alone. For evaluation of the modifying potential of the chemicals, indices were generated by using the mean values obtained for number and area of GST-P+ foci after each treatment. Comparison between these indices suggests that SD rats were relatively more sensitive than NARs to the modifying effects of complete carcinogens (3'-Me-DAB and DEN). The strains were similarly-susceptible to the promoting influence of ethionine, a nongenotoxic carcinogen. The inhibitory influence of BHA was more intense in NARs, whereas in both strains clofibrate was associated to similarly reduced values for number and area of GST-P+ foci. The degree of susceptibility of each strain to the modifying influence of chemicals on foci development depended on the chemical agent investigated.

Acetylglucosaminidase↗
PubMed1993

[Effect of methamphetamine on the auditory system].

Four series of experiments were performed to evaluate the effects of methamphetamine on the auditory system of guinea pigs. Methamphetamine was administered to guinea pigs via intraperitoneal injection, and the time course of latencies of waves I, II, III, and IV, interpeak latencies of waves I-III, III-IV, and I-IV of the ABR, and the near-field potential of the inferior colliculus and cochlear nerve were measured. These physiological data were analyzed in comparison with the distribution of methamphetamine in the inferior colliculus and cochlea following its immunohistochemical staining, as well as the serum methamphetamine concentration. The following results were obtained; 1. The wave latencies and interpeak latencies of ABR decreased up to 120 minutes after the administration. 2. In the cochlear nerve recording, the amplitude of the response increased and the latency decreased up to 90 minutes after the administration. These changes in responses were, however more prominent in the inferior colliculus recording. 3. Immunohistochemical examination revealed that methamphetamine was present in the hair cells of the organ of Corti, spiral ligament, spiral ganglion cells and the inferior colliculus 30 minutes after the administration. 4. The serum concentration of methamphetamine rapidly reached its maximal level, and then dropped gradually, logarithmically, having become almost horizontal at a low level 6 hours later. These results suggest that methamphetamine does exert an effect on the peripheral auditory system, as well as on the central nervous system, which is generally regarded as the effector organ. It is assumed that the pharmacological effect of methamphetamine on the cochlea involves excitation of sensory cells, afferent nerve fibers and spiral ganglion cells.

Animals↗
PubMed1992

A novel note on the effect of ara-C on the polyamine content of the male accessory organs of the rat.

The effects of 1-beta-D-arabinosylcytosine (ara-C) given for 5 days on body weight, on the weights of the prostate, seminal vesicles and testis, and on the polyamine content (putrescine, put; spermidine, spd; spermine, spm) in these organs were examined in rats. The body weights of the ara-C-treated rats showed a decrease of 13% (P less than 0.01) and the weights of the prostate, seminal vesicles and testis were reduced by 20% (P less than 0.05), 13% and 5.0% (P less than 0.1), respectively. However, put, spd and spm contents in the ara-C-treated prostate were increased 1.2, 1.8 and 2.9 times, respectively. The contents of these polyamines in the ara-C-treated seminal vesicles increased about 40% for all polyamines. Both spd and spm in the treated testis showed a significant increase of about 20% (P less than 0.05) as compared with the control. In addition, the total polyamines in the whole organs increased significantly in both the prostate and testis.

Animals↗