Search PubMed⌕ Search

Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 127 records · Page 7Linked to original sources
PubMed1990

Characteristics and significance of albumin-positive hepatocytes in analbuminemic rats.

Analbuminemic rats (NAR) are a mutant strain in which splicing of the albumin mRNA is blocked due to a seven-base-pair deletion in an intron of the albumin gene. NAR liver contains a few hepatocytes that react with anti-rat albumin antibody (Alb+ hepatocytes), and these cells increase in number during aging and on treatment with hepatocarcinogens. To characterize these Alb+ hepatocytes, we examine their albumin mRNA, the biochemical specificity of their albumin, and its intracellular distribution. Signals of albumin mRNA were observed in a few hepatocytes by in situ hybridization. Moreover, a small amount of cytoplasmic albumin mRNA was detected by RNA blot analysis in the liver of aged NAR and NAR treated with 3'-methyl-4-diaminoazobenzene (DAB). Immunoelectron microscopic examination revealed the cisternae of the rough and smooth endoplasmic reticula, Golgi complexes, and secretory vesicles of the Alb+ hepatocyte of NAR being filled with material that reacted with anti-rat albumin antibody. These facts suggested that albumin was gradually synthesized in Alb+ hepatocytes but that its secretion was disturbed. The albumin-like proteins of NAR were shown by Western blot analysis to consist of three species of 68 kDa, 50 kDa, and 25 kDa proteins. The 50 kDa albumin was thought to be formed by exon-skipping splicing of the albumin mRNA precursor, which was recently reported by Shalaby and Shafritz (Proc. Natl. Acad. Sci. USA 87, 2652-2656 (1990)). The 25 kDa protein was suspected to be formed by fragmentation of the 50 kDa protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1989

Fluorometric assay for polyamines in urine and tissues using electrophoresis on Titan III cellulose acetate.

A simple, rapid assay method for polyamines (putrescine, spermidine, and spermine) in urine and tissues using electrophoresis on Titan III cellulose acetate was developed. In this procedure, polyamines are preliminarily extracted from a hydrolysate of urine or from supernatants of tissue homogenates by use of a Bio-Rex 70 minicolumn. After electrophoretic separation, polyamines are fluorometrically detected by the reaction with o-phthalaldehyde and 2-mercaptoethanol. Six extracts and two external standards of polyamines can be separated and detected in 11 min on a cellulose acetate strip. This method permits the determination of polyamines in a range of 0.1 mM (25 pmol) to 1.0 mM (250 pmol).

Animals↗
PubMed1989

Elevated activity of pancreatic type amylase in the urine as an early indicator of pancreatic tumors in hamsters.

Levels of amylase isozymes in the urine and serum of Syrian hamsters during pancreatic carcinogenesis, induced by N-nitrosobis(2-oxopropyl)amine (BOP), were investigated. BOP was injected subcutaneously (sc) into female Syrian golden hamsters at a dose of 10mg/kg once weekly for 6 wk and amylase activities in urine and serum samples were measured every other week from the first treatment of BOP. Although total amylase in the urine showed no remarkable changes, the pancreatic type isozyme demonstrated only very low levels for the first 6 wk and then from wk 8, became elevated showing continuously high levels in all animals thereafter. Animals were sacrificed at wk 10, 14, and 18. Dysplastic lesions of the pancreas developed in all the hamsters investigated. Furthermore, pancreatic adenocarcinomas were also observed in all animals sacrificed at wk 18. Thus, the results suggest that measurement of pancreatic isoamylase in the urine might allow early indication of pancreatic tumor development in hamsters.

Adenocarcinoma↗
PubMed1989

Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of rat hepatocarcinogenesis in a medium-term assay system: quantitation of glutathione S-transferase P-positive foci development.

Strain differences in susceptibility to promotion by the liver carcinogens 2-acetylaminofluorene (2-AAF) and phenobarbital (PB) were examined in the medium-term bioassay system initially developed in our laboratory using male F344 rats as the test animal and glutathione S-transferase placental form (GST-P)-positive foci as the lesion end-point. Numbers and areas per cm2 of induced GST-P-positive hepatocellular foci were compared in LEW, F344, NAR, SD, WBN, SHR, Wistar and ODS rats initiated with diethylnitrosamine (DEN) and subjected to partial hepatectomy during subsequent administration of 2-AAF or PB. LEW, SD, WBN, and F344 rats were most susceptible to hepatopromotion by both compounds, with a hundred fold increase in lesion area being observed for 2-AAF in the LEW case. NAR and SHR strains demonstrated an intermediate response, while Wistar and, in particular, the related ODS rats demonstrated very low susceptibilities. The obvious strain differences could be expressed in terms of comparative indices of promoting effects of 2-AAF and PB as well as DEN itself regarding each of the 8 strains tested. The use of F344 rats for the bioassay model was validated by the relatively high sensitivity to both DEN and 2-AAF initiation as well as second-stage promotion stimulus exhibited.

2-Acetylaminofluorene↗
PubMed1989

Tumor-associated expression of a serum protein, termed aX protein (alpha 1-inhibitor III), and its mRNA in rat liver.

A cDNA clone bearing the mRNA sequence for rat alpha X protein (alpha X) was isolated from a cDNA library constructed from rat liver mRNA. The nucleotide sequence of alpha X protein cDNA showed 97% homology with that of the 3'-proximal domain of alpha 1-inhibitor III cDNA. The amino acid sequence deduced from that of alpha X cDNA also exhibited high homology with the primary sequences of alpha 1-inhibitor III and alpha 2-macroglobulin. K231 ascites hepatoma cells were transplanted into male ACI rats, and the level of alpha X mRNA in the liver of the tumor-bearing rats was determined by RNA blot hybridization with the cDNA probe. The serum concentration of alpha X decreased to about 30% of the control value with time after transplantation. The amount of alpha X mRNA in the liver of tumor-bearing rats was proportional to the serum concentration of alpha X. The serum concentrations of transferrin and albumin in the tumor-bearing rats also decreased to about 30 and 60% of the normal levels, respectively. However, the amounts of mRNAs for transferrin and albumin in the liver of tumor-bearing rats did not decrease. These findings indicate that the mechanisms of tumor-associated decrease in the concentrations of different serum proteins in tumor-bearing rats may differ.

Acute-Phase Proteins↗
PubMed1989

Strain differences in susceptibility to 2-acetylaminofluorene and phenobarbital promotion of hepatocarcinogenesis: immunohistochemical analysis of cytochrome P-450 isozyme induction by 2-acetylaminofluorene and phenobarbital.

Strain differences in the expression of cytochrome P-450 isoenzymes (P-450s) during enhancement of hepatocarcinogenesis by 2-acetylaminofluorene (2-AAF) and phenobarbital (PB) were investigated immunohistochemically using monoclonal antibodies against phenobarbital (PB) (APF3) or 3-methylcholanthrene (3-MC) (APH8) inducible P-450s. LEW, SD, WBN, F344, SHR, NAR, Wistar and ODS rats were studied, the first five strains proving to be less susceptible to 2-AAF induction of APH8 while responding strongly to the promoting influence of this chemical, as reported previously. The other three strains, NAR, Wistar and ODS, demonstrated greater inducibility, this correlating with an observed resistance to promotion by 2-AAF. PB administration was not associated with any strain difference in APF3 cytochrome P-450 inducibility except in the ODS rat, in which its effects were minimal. The results provide direct evidence that differential expression of cytochrome P-450 species plays a major role in determining responsiveness to hepatocarcinogenesis-promoting agents such as 2-AAF.

2-Acetylaminofluorene↗
PubMed1989

A clinical case of Klinefelter's syndrome with various psychiatric symptoms.

We present here a clinical case of Klinefelter's syndrome with various psychiatric symptoms. A 60-year-old male showed delusions of persecution, poisoning, and reference, auditory, visual and somatic hallucinations, depressive state and memory disturbance. These clinical symptoms except for memory disturbance were the characteristic clinical features of psychiatric symptoms in some cases of Klinefelter's syndrome reported so far. There has been no reported case of Klinefelter's syndrome showing memory disturbance. The memory disturbance of the present case is regarded as an amnestic organic brain syndrome (DSM-III) due to Klinefelter's syndrome.

Delusions↗
PubMed1989

[Methylguanidine synthesis by active oxygen generated by stimulated human neutrophils].

In previous papers, we have reported that methylguanidine (MG), a known uremic toxin, was synthesized from creatinine (Cr) by active oxygen generated not only by chemical reagents but also by isolated rat hepatocytes. In this paper, we studied whether or not active oxygen generated by stimulated human neutrophils produces MG from Cr. MG was measured after incubating 2 x 10(6) human neutrophils for 2 h in 1 ml of Hanks' balanced salt solution (pH 7.4) containing 100 mg/dl Cr at 37 degrees C after the addition of phorbol myristate acetate (PMA). MG was measured by high pressure liquid chromatography followed by reaction with 9, 10-phenanthrenequinone. MG was synthesized by the stimulated neutrophils and not by the unstimulated ones. MG synthesis reached a plateau (1.11 +/- 0.03 nmol/120 min/2 x 10(6) cells) at a concentration of 0.125 microM PMA and reached a maximum value (1.95 +/- 0.03 nmol/120 min/2 x 10(6) cells) at a concentration of 100 mg/dl Cr. MG synthesis increased depending on the concentration of neutrophils between 1 and 8 x 10(6)/ml and increased depending on the duration of incubation up to 4 h. MG synthesis was strongly inhibited by superoxide dismutase, by the scavengers of hypochloride (taurine and methionine) and by sodium azide. Catalase and the scavenger of the hydroxyl radical (dimethyl sulfoxide) inhibited MG synthesis less effectively. The effects of the scavengers of active oxygen suggest the participation of active oxygen in MG synthesis from Cr in this system. Among the active oxygen species, superoxide anion and hypochloride play an important role in this system.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1988

Albumin-negative hepatocytes in Sprague-Dawley x analbuminemic F1 rats treated with hepatic carcinogens.

Analbuminemic rats (NAR) are a mutant breed with an inherent inability to synthesize albumin. However, heterozygous rats born of a pair of NAR and Sprague-Dawley (SD) rats can synthesize albumin. Immunohistochemical staining for albumin shows that, although the majority of hepatocytes of SD x NAR F1 (female SD x male NAR) rats are positive for albumin, a small number of hepatocytes are negative. These albumin-negative hepatocytes are frequently found in the form of clusters which appear cytologically normal. When the rats were given a dietary regimen of 2-acetyl-aminofluorene (2-AAF), there was a significant increase in the number of albumin-negative hepatocytes. On the other hand, diethylnitrosamine (DEN) or 5-azacytidine did not increase the number of albumin-negative hepatocytes. 2-AAF and DEN also induced enzyme-altered hepatocytes but the albumin-negative hepatocytes were of a completely different class from the enzyme-altered hepatocytes. The results of this study indicate that some kind(s) of carcinogens induce mutated hepatocytes which are probably not involved in carcinogenesis.

2-Acetylaminofluorene↗
PubMed1988

Lack of albumin as genotypic marker of preneoplastic analbuminemic rat hepatocytes transplanted within albumin-positive liver.

In analbuminemic rats, preneoplastic hepatocytes lack the capability to produce albumin. On the other hand, the hepatocytes of F1 hybrids born from parents of analbuminemic rats and normal rats retain their capability to produce albumin, since the analbuminemia is inherited as a recessive trait in rats. We isolated hyperplastic nodule cells from Nagase's analbuminemic rats and transplanted them into the livers of F1 hybrid rats by infusion into the mesenteric vein. The host rats were subjected to a short term dietary 2-acetylaminofluorene and underwent a two-thirds partial hepatectomy to promote the growth of preneoplastic hepatocytes. Within 10 to 13 days after transplantation, may albumin-negative hepatocytic nodules were formed in the albumin-positive host livers. Almost all the albumin-negative nodules expressed conventional biochemical markers for preneoplastic hepatocytes. Eight to 9 weeks after the transplantation, almost the same number of albumin-negative nodules were observed as on days 10-13. However, roughly a half of the albumin-negative nodules showed no biochemical markers. The results indicate that the majority of early preneoplastic lesions revert to become phenotypically normal after removal of the promoting stimuli.

Albumins↗
PubMed1988

Mapping of the hooded, Gc protein, and albumin gene loci in linkage group VI of the laboratory rat.

Crosses to determine the position of the three gene loci, h, Gc, and Alb, in the sixth linkage group of the rat used three strains, the TM strain, the ACI-alb analbuminemic congenic strain, and the abh-alb tester strain established by crossing the abh coat color tester strain and analbuminemic rats. Their genotypes were [C/C, h/h, GcB/GcB, Alb/Alb], [C/C, hi/hi, GcA/GcA, alb/alb] and [C/C, h/h, GcA/GcA, alb/alb], respectively. Determination of genotypes was performed by coat color and polyacrylamide gel electrophoresis (PAGE of serum protein for the Gc and albumin genes. The positions of the three gene loci in the VI linkage group were calculated from the recombination values from the phenotypes of progenies. According to this data, the three gene loci were in h-Gc-Alb tandem and the distances were 15.5 +/- 1.0% in h-Gc, 15.8 +/- 1.0% in h-Alb, and 0.32 +/- 0.16% in Gc-Alb. These data confirmed the relationship among the Gc, Alb, and Afp genes in the rat as well as in humans.

Animals↗
PubMed1988

Serum bilirubin fractions in analbuminemic rats after bile duct ligation. Albumin requirement in the formation of covalently protein-bound bilirubin.

To clarify the role of albumin in the production of covalently protein-bound bilirubin (delta bilirubin, B delta) in the blood and the pathophysiological relevance of B delta, changes in the serum bilirubin level and histological findings in the liver, kidneys and myocardium were studied in Sprague-Dawley (SD) rats and Nagase analbuminemic rats (NAR) after bile duct ligation (BDL). In SD rats, the serum bilirubin level increased until 3 days after BDL, and was followed by the appearance of B delta. The increase in serum bilirubin was smaller in NAR, and no serum B delta was noted. Albumin administration to NAR 1 day after BDL increased serum bilirubin with the appearance of B delta. Serum bilirubin decreased in both SD rats and NAR 7 days after BDL. Marked deposition of bile pigments was noted in NAR in the renal tubular epithelium. The renal bilirubin content was decreased after albumin administration. From these results it is concluded that albumin is necessary for the production of B delta, and that renal deposition of bile pigments progresses in the absence of albumin.

Animals↗
PubMed1988

Acute phase response of plasma proteins in analbuminemic rats.

In healthy Nagase analbuminemic rats (NAR), the highest degree of relative increase in serum protein concentration was found for alpha-2-macroglobulin, the most prominent acute phase protein in rats. Its levels were about 30- and 60-fold higher in males and females, respectively, than those in the control Sprague-Dawley (SD) rats. In terms of absolute concentration, however, alpha-1-inhibitor 3 (also called alpha-X-protein or murinoglobulin) showed the most conspicuous change, its levels being higher by about 7 mg/ml than those in SD. When the acute phase reaction was induced by subcutaneous injection of turpentine, the levels of alpha-1- and alpha-2-macroglobulins, alpha-1-cysteine proteinase inhibitor, alpha-1-antiproteinase, and alpha-1-inhibitor 3 in NAR changed in essentially the same way as in SD: alpha-1-inhibitor 3 decreased markedly while the rest increased further. These results suggest that mechanisms responsible for the elevation of serum globulins in healthy NAR are not directly related to those involved in the acute phase response. On the other hand, the antithrombin III levels in healthy NAR were about twice the control values and changed little during the inflammation. In contrast, this protein in SD doubled during the acute phase, its maximal levels being close to those in healthy or inflamed NAR. This suggests that the antithrombin III level in healthy NAR is regulated by a mechanism similar to that in SD maximally reacting to the acute phase stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1988

Strain differences in N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis in rats.

Differences in susceptibility of the urinary bladder epithelium to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in various strains were examined. In experiment 1, 5 strains of male rats were given 0.025% BBN in the drinking water for 8 weeks followed by drinking water without BBN for 32 weeks. Analbuminemic rats (NAR) and ACI rats had high incidences of urinary bladder lesions (papillary or nodular hyperplasia, papilloma and carcinoma), F344 and Wistar rats had low incidences, and Sprague-Dawley (SD) rats showed an intermediate incidence. Carcinoma area was largest in NAR rats followed in decreasing order by SD, ACI and F344 rats. The extent of tumor invasion was higher in NAR and ACI rats than in SD rats. In experiment 2, the 5 strains of male rats were administered 0.025% BBN in the drinking water. Some rats from each group were killed after each of weeks 4 and 8. The urinary bladder of ACI and NAR rats given BBN had the most marked lesions observed by scanning electron microscopy, with less marked changes in SD rats. F344 and Wistar rats showed the weakest response. Cytochrome P-450 content of the liver in ACI rats treated with BBN for 4 weeks was significantly higher than those of controls. Cytochrome P-450 and cytochrome b5 contents of the control and BBN-treated rats were significantly higher in ACI and SD rats than in Wistar, F344 or NAR rats. These results indicate that there are strain differences in the urinary bladder response to BBN.

Animals↗
PubMed1988

High susceptibility of an analbuminemic congenic strain of rats with an F344 genetic background to induced bladder cancer and its possible mechanism.

The susceptibility of an analbuminemic congenic strain of rats (F344-alb) originating from the F344 strain to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. F344-alb rats were found to be highly susceptible to induction of urinary bladder cancers. The incidences of bladder cancers in F344-alb and F344 rats were 94% (15/16) and 31% (5/16) in males and 100% (16/16) and 19% (3/16) in females. The bladder weights of these rats, including tumors, were 307 +/- 294 mg, 123 +/- 26 mg, 183 +/- 80 mg and 93 +/- 11 mg, respectively. Administration of 0.05%, 0.1% and 0.3% BBN in the drinking water for 2 weeks resulted in greater increases in the bladder content of N-butyl-N-(3-carboxypropyl)nitrosamine in F344-alb rats than in F344 rats. This increase was prevented by the presence of rat albumin.

Animals↗
PubMed1988

Alterations in the glomerulus in aminonucleoside nephrosis in analbuminemic rats.

Whether obliteration of glomerular epithelial foot processes and increases in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity are the consequence or the cause of proteinuria after administrations of the aminonucleoside of puromycin was examined using Nagase analbuminemic rats. The administration of puromycin aminonucleoside to Nagase analbuminemic rats did not induce proteinuria. However, the increase in urinary NAG activity and the degree of abnormality of foot processes in the glomerular cells were similar to those in control Sprague-Dawley rats. These findings suggest that NAG excretion and the morphological alterations of epithelial cells in nephrosis are not the consequence of massive proteinuria.

Acetylglucosaminidase↗