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Biomedical subjects

H Sone

Publications and source records attributed to H Sone.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effects of chronic administration of low doses of 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline on glutathione S-transferase placental form-positive foci development in the livers of rats fed a choline-deficient diet.

Effects of chronic administration of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) at the very low doses of 0.4 and 4 ppm, respectively 1000- and 100-fold less than the dose shown to be carcinogenic (400 ppm), on the liver of rats fed a choline-deficient (CD) diet were examined in terms of glutathione S-transferase placental form (GST-P)-positive foci. Male F344 rats were given CD diet containing 0, 0.4 or 4 ppm MeIQx for 20 or 40 weeks. As controls, rats received choline-supplemented (CS) diet in the same manner. MeIQx at 4 ppm in the CD diet significantly increased both the number and area of GST-P-positive foci, the values being 2.3- and 2.1-fold at 20 weeks and 2.0- and 3.3-fold at 40 weeks, respectively, compared with those observed for CD diet alone. MeIQx at 0.4 ppm in CD diet did not affect the development of GST-P-positive foci. No influence of the heterocyclic amine was found in the CS groups, where only very small numbers of minute lesions were observed. The level of MeIQx-DNA adducts in rats given the CD diet containing 4 ppm MeIQx was 2- to 3-fold lower than that in rats given the CS diet containing 4 ppm MeIQx at 20 and 40 weeks. This result indicates that DNA adduct formation and cell proliferation are both required for the increase of GST-P-positive foci in rats fed 4 ppm MeIQx in a CD diet. The above findings strongly suggest that MeIQx could be carcinogenic even at 4 ppm under CD conditions, where liver cell regeneration is continuously occurring.

Animals↗
PubMed1993

Hemodynamic effects of lipo-PGE1 on peripheral artery in patients with diabetic neuropathy: evaluated by two-dimensional color Doppler echography.

Twenty non-insulin-dependent diabetic patients were studied to evaluate the hemodynamic effects of lipo-PGE1 (prostaglandin E1 incorporated in lipid microspheres). Improvement of diabetic neuropathy was assessed on the basis of subjective symptoms such as pain, coldness, numbness and dysethesia (subjective) after intravenous administration of lipo-PGE1. After lipo-PGE1 treatment, the subjective symptoms were markedly improved. Hemodynamic effects of this drug on the dorsalis pedis artery were examined using new real-time two-dimensional color Doppler echography. After administration of lipo-PGE1, the cross-sectional area of the dorsalis pedis artery significantly increased from 2.6 +/- 0.2 mm2 to 3.5 +/- 0.2 mm2 (P < 0.01). Moreover, the blood flow index significantly increased from 40 +/- 7 to 61 +/- 11 (P < 0.05). The results of this study suggest that lipo-PGE1 may serve as a useful drug in improving diabetic neuropathy.

Adult↗
PubMed1992

Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats.

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.

Animals↗
PubMed1992

Enhanced stability of YEp plasmids in lager brewing yeasts is related to lager brewing yeast 2-microns DNA.

YEp plasmid stability in the presence of either Saccharomyces cerevisiae laboratory strain 2-microns DNA, or lager brewing yeast 2-microns DNA in the same genetic background, was compared under non-selective culture conditions. It was found that YEp plasmids were more stably maintained in the presence of lager 2-microns DNA under these conditions. By construction of laboratory-lager 2-microns DNA hybrid plasmids, an 867 bp StuI fragment of lager 2-microns DNA was shown to be responsible for the enhanced stability of the YEp plasmid. Nucleotide substitutions at two sites were found by sequencing this region. It was also confirmed that increasing cell ploidy enhanced YEp stability under non-selective conditions.

DNA, Fungal↗
PubMed1992

Induction of preneoplastic lesions by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the livers of rats treated with carbon tetrachloride.

The multifactorial nature of carcinogenesis in man has impelled us to study the effects of various chemicals and conditions in combination. In the present investigation, we examined the effects of low doses of 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) in combination with carbon tetrachloride (CCl4) on the formation of glutathione S-transferase placental form (GST-P)-positive foci in rat liver. Administration of diet containing MeIQx at 0.4, 4 or 40 p.p.m., representing one-thousandth, one-hundredth and one-tenth of the dose proved to induce hepatocellular carcinomas (400 p.p.m.), for 8 or 12 weeks did not induce GST-P-positive foci. However, 40 p.p.m. of MeIQx when co-administered with CCl4 (0.7 ml/kg, s.c. twice a week) induced preneoplastic lesions: 7- and 3-fold increases in the numbers and areas of GST-P positive foci in week 8, and 8- and 6-fold increases respectively in week 12, over those with CCl4 alone. Furthermore, a marked increase in the number of hyperplastic nodules was observed in this group of rats in week 12. No significant increases of GST-P-positive foci were observed at doses of 0.4 or 4 p.p.m. MeIQx in combination with CCl4. Thus, it is predicted that chronic exposure to 40 p.p.m. of MeIQx eventually results in induction of hepatocellular carcinomas in injured rat liver.

Animals↗
PubMed1991

Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats.

LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations were observed, suggesting that ras activation is not involved in spontaneous hepatocarcinogenesis in LEC rats. The expression of mRNAs for c-myc, Ha-ras, c-raf, and the protein phosphatase 2A alpha gene (PP-2A alpha) was also examined in the four HCCs by northern blot analysis. Three of the four HCCs had c-myc expression levels approximately 30-fold higher than that in the liver of control Long-Evans rats with an agouti coat color (LEA), a sibling line of LEC rats, while the remaining HCC had an expression level sevenfold higher than that of control. In contrast, the expression levels of the Ha-ras, c-raf, and PP-2A alpha genes were the same as those in the livers of control rats. Studies of c-myc expression and mitotic index in five other HCCs, two hyperplastic nodules, and two nontumorous portions of livers of HCC-bearing LEC rats that had chronic-phase hepatitis suggested that the high level of c-myc gene expression was not due only to increased cell proliferation but might possibly be more integrally involved in hepatocarcinogenesis.

Amino Acid Sequence↗
PubMed1991

Inhibitory effect of 2-O-octadecylascorbic acid in agglutination assay with concanavalin A; short-term examination of rat urinary bladder carcinogenesis.

A derivative of ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), is a strong scavenger of active oxygen species. We examined the effect of CV-3611 on a short-term test of bladder carcinogenesis, using concanavalin A (Con A)-dependent agglutination of isolated bladder epithelial cells. Rats were given 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for 1 week, and then 5% sodium saccharin or 2% DL-tryptophan or 0.01% BHBN alone or with 0.002, 0.006 or 0.02% CV-3611 for 3 weeks. Treatment with CV-3611 reduced the effects of the bladder tumor promoters sodium saccharin and DL-tryptophan by 48-86 and 65-87%, respectively. CV-3611 also reduced the number of aggregates of bladder epithelial cells from rats treated with BHBN for 4 weeks. These results suggest that CV-3611 has a suppressive effect on rat bladder carcinogenesis.

Agglutination Tests↗
PubMed1991

Relationship between the limited proteolysis of glycinin and its conformation.

The relationship between the limited proteolysis and conformation of native glycinin was studied by the following methods: analyses of the proteolytic digestion of chemically modified glycinin, circular dichroism (CD) measurements, a secondary structure prediction from the amino acid sequence and a hydropathy index analysis. The locations of tryptic fragments of glycinin were confirmed from the N-terminal amino acid sequences of the fragments. T fragments and P fragments were located at the N-terminal and central area of the acidic polypeptide chains, respectively. One of the cleavage sites was the Arg residue of around the 100th from the N-terminal side. The regions digested by limited trypsinolysis were presumed to be flexible, hydrophilic and near the surface of the molecule by prediction methods from the amino acid sequence. The other regions were predicted to be compact and beta-sheet in nature, almost 40-50% of the amino acid residues being predicted as beta-sheet from the amino acid sequence and from CD data.

Amino Acid Sequence↗
PubMed1990

Cloning and sequence analysis of the arginine deiminase gene from Mycoplasma arginini.

Arginine deiminase from Mycoplasma arginini was purified. The purified enzyme has a molecular weight of 46,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Its specific activity (20 units/mg protein) and amino acid composition showed a strong similarity to that of the Mycoplasma arthritidis arginine deiminase. The amino acid sequences of the N-terminal region and three internal peptides generated by enzymatic cleavage of the purified protein were determined. Using a synthetic oligonucleotide mixture complementary to part of the determined N-terminal amino acid sequence, the gene coding for arginine deiminase was isolated from a phage library. A nucleotide sequence of 2189 bp encoding the gene was determined. An open reading frame (ORF) contained the amino acid sequences corresponding to the determined N-terminal region and the three internal peptides of arginine deiminase. Thus it was concluded that this ORF encoded the arginine deiminase, a 385 amino acid polypeptide (mol.wt. 43,900 daltons). The three tryptophan residues in the sequenced peptides align with UGA codons in the nucleotide sequence, indicating that the nonsense codon UGA is used as a tryptophan codon in M. arginini.

Amino Acid Sequence↗
PubMed1990

Application of a ribosomal DNA integration vector in the construction of a brewer's yeast having alpha-acetolactate decarboxylase activity.

An integration plasmid, pIARL28, containing the ribosomal DNA gene as a homologous recombination sequence was constructed for introduction of the alpha-acetolactate decarboxylase gene into brewer's yeast. The transformation efficiency of pIARL28 was 20- to 50-fold higher than those of the other YIp vectors, as yeast cells had approximately 140 copies of the ribosomal DNA gene. All transformants showed very high alpha-acetolactate decarboxylase activity due to the multiple integrated copies of the plasmid. The transformants were grown in nonselective conditions, and segregants which had maintained the alpha-acetolactate decarboxylase expression cassette but no other vector sequences were isolated. Southern analysis showed that these marker-excised segregants contained more than 20 copies of the alpha-acetolactate decarboxylase gene and were stably maintained under nonselective conditions. Fermentation tests confirmed that the diacetyl concentration was considerably reduced in wort fermented by these marker-excised segregants. The degree of reduction was related to the copy number of the alpha-acetolactate decarboxylase gene.

Carboxy-Lyases↗
PubMed1990

Acute toxicity tests of mofezolac (N-22) in mice and rats.

Mofezolac (N-22) is a newly developed analgesic and anti-inflammatory agent. The acute toxicities of N-22 were investigated in ICR mice and Wistar rats in oral (p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. LD50 values of N-22 in mice were 1528 mg/kg (p.o.), 275 mg/kg (i.p.) and 612 mg/kg (s.c.) for males, and 1740 mg/kg (p.o.), 321 mg/kg (i.p.) and 545 mg/kg (s.c.) for females. Those in rats were 920 mg/kg (p.o.), 378 mg/kg (i.p.) and 572 mg/kg (s.c.) for males, and 887 mg/kg (p.o.), 342 mg/kg (i.p.) and 510 mg/kg (s.c.) for females. The sex difference was not clearly observed in mice and rats, but the species difference was observed in p.o. routes. As an initial toxic sign, the hypoactivity was observed in mice and rats of all routes, subsequently, paleness of skin, anemic conjunctiva, emaciation, stupor and/or coma were observed in mice and rats of p.o. and i.p. routes. In rats of those routes, tonic and/or asphyxial convulsion and dyspnea were also observed. In pathological examination of mice and rats, gastrointestinal disorders were observed in p.o. and i.p. routes, and changes of subcutaneous tissue at the injection site were observed in s.c. route.

Administration, Oral↗
PubMed1990

[Fifty two-week chronic oral toxicity study of mofezolac (N-22) in rats].

Fifty two-week oral toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in Wistar rats with dose levels of 5, 20, 60 and 120 mg/kg/day, and the 5-week withdrawal was followed for recovery study. Hematuria, blanching of the skin and suppression of body weight gain were observed in females given 120 mg/kg, and 9 of these prostrated and died from week 20 to week 52, or were euthanized when moribund. These symptoms were not seen in males at any dose levels. In 120 mg/kg group, increased positive cases of fecal occult blood were observed during the administration period, and the pathological examination revealed gastrointestinal lesions such as erosion, ulcer, hemorrhage and mucosal regeneration in the small intestine. Renal disorder was also involved mainly in females given 120 mg/kg, as shown by increase in urine volume with declined osmotic pressure and specific gravity, serum urea nitrogen, creatinine, inorganic phosphorus, and other related parameters. In addition to enlargement, rough surface and scar formation, dilated tubular lumen and papillary ducts of the kidney were observed as a main lesion. Incidental findings with those disorders, observed mainly in females given 120 mg/kg, included increase in leucocytes with high neutrophils ratio, and enlargement of the spleen, adrenals and mesenteric lymph node. There were some of the similar gastrointestinal and renal changes mainly in females given 60 mg/kg. Anemic findings were noted in both sexes of 120 mg/kg and in females of 60 mg/kg group, and mainly females given 120 mg/kg showed increase in platelets, reticulocytes and fibrinogen, shortening of blood coagulation time, as well as extramedullary or accented hematopoiesis of the liver, spleen and bone marrow. Other serum biochemical changes observed mainly in females given 120 mg/kg were decrease or decreasing trend in total protein, A/G ratio, and transaminase activity. Fine structure of the liver from females given 20 mg/kg or more revealed cisternal dilatation of smooth-surfaced endoplasmic reticulum of hepatocytes, and the increased liver weight was observed in females given 120 mg/kg. Accordingly, non-effective dose level of N-22 in 52-week chronic toxicity study was estimated to be 20 mg/kg for males and 5 mg/kg for females.

Administration, Oral↗
PubMed1989

Signalling pathway of tumor necrosis factor in normal and tumor cells.

Several aspects of the activity and effects of tumor necrosis factor (TNF) were investigated to gain further insight into its cytotoxic mechanism. The relation between number of TNF receptors and TNF susceptibility of both tumor cells and normal cells was studied, utilizing a specific binding assay. Among the tumor cells, a fairly close correlation (r = 0.855) was observed between receptor number and sensitivity to TNF. No cytotoxic effect by TNF was observed on any of the normal cells tested, even though TNF receptors were shown to be present, and cell proliferation was apparently stimulated by TNF in some cases. TNF internalization and intracellular distribution were studied by pulse-labelling and Percoll density gradient centrifugation. In L-M (murine tumorigenic fibroblasts, highly sensitive to TNF cytotoxicity) cells and HEL (human embryonic lung cells, non-sensitive to TNF cytotoxicity) cells, receptor-bound 125I-labelled recombinant human TNF was rapidly internalized and delivered to lysosomes within 15-30 min, and this was followed by degradation and release into the culture medium. The presence of either a cytoskeletal disrupting agent or a lysosomotropic agent was observed to inhibit the cytotoxic effect of TNF, thus also indicating that TNF internalization, followed by delivery to lysosomes, is essential in the cytolytic mechanism of TNF. As observed by [3H]uridine incorporation, TNF did not affect RNA synthesis in L-R cells (TNF-resistant cell lines derived from L-M cells) and HEL cells, but markedly stimulated (by 3.5 times) RNA synthesis in L-M cells.

Animals↗
PubMed1989

A sensitive thyroid stimulating hormone assay for screening of thyroid functional disorder in elderly Japanese.

The use of a screening test for thyroid functional disorder by sensitive thyroid stimulating hormone assay in the elderly was investigated. The basal thyroid stimulating hormone levels predicted the response of thyroid stimulating hormone to thyrotropin releasing hormone; it was suppressed in 99 (99.0%) of 100 hyperthyroid patients. Therefore, not only primary hypothyroidism but also hyperthyroidism can be excluded when the serum thyroid stimulating hormone levels are normal. An epidemiological study was then performed on 2,421 (76.7%) of the Japanese general population aged 40 or over recruited from the residents in Hisayama town and also in 122 residents between 20 and 40 years of age. Additional free T4 measurement was necessary in about 10% of the residents with abnormal TSH levels to confirm the diagnosis of hyperthyroidism or distinguish latent from overt hypothyroidism. There was a significant correlation between age and serum thyroid stimulating hormone levels after logarithmic conversion (r = 0.1533, P less than .001). The prevalence of thyroid dysfunction found in 1,026 males and in 1,395 females aged 40 or over was, respectively: hyperthyroidism, less than 0.1% and 0.2%, latent (subclinical) hypothyroidism, 3.2% and 5.5%, and overt hypothyroidism, 0.4% and 0.7%. We conclude that the screening with this sensitive thyroid stimulating hormone assay and additional free T4 measurement is useful for detection of patients with thyroid functional disorder.

Adult↗
PubMed1988

Induction of synthesis of tumor necrosis factor in human and murine cell lines by exogenous recombinant human tumor necrosis factor.

Treatment of sensitive human myosarcoma cells (KYM-S) with exogenous tumor necrosis factor (r-TNF) resulted in the production of TNF by the cells. The newly synthesized cellular TNF was identified immunologically on Western blots and as a single 1.8-kilobase band on Northern blots. TNF synthesis began within 2 h of administration of the exogenous TNF in a dose-dependent manner. r-TNF also induced TNF synthesis in mouse tumorigenic fibroblasts (L-M). Resistant sublines of these cells as well as TNF nonsensitive human diploid fibroblasts possessed TNF mRNA without pretreatment, indicating an inverse correlation between levels of TNF expressed and sensitivity to the cytotoxic effects of exogenous TNF. It is conceivable that the newly synthesized cellular TNF functions in some protective manner to block cytolytic effects of exogenous TNF.

Animals↗
PubMed1988

Continuous internalization of tumor necrosis factor receptors in a human myosarcoma cell line.

The cell dynamics of the receptor for tumor necrosis factor (TNF) were examined in TNF-sensitive KYM cells derived from human myosarcoma. With receptor synthesis inhibited by cycloheximide, the half-life of the surface TNF receptor was 2 h in the absence of TNF and 30 min in its presence, suggesting that the TNF receptor is non-recycling and that its internalization is accelerated by TNF. During cell incubation with TNF receptor degradation suppressed by chloroquine, the number of surface TNF receptors remained approximately constant, but the total number of surface and internal TNF receptors increased gradually, at 3 h reaching 1.5 times the initial number, thus suggesting continuous synthesis, externalization, internalization, and degradation of the TNF receptor in the absence of cycloheximide. On cell incubation with 125I-TNF, the intracellular quantity of the pulse-labeled TNF-receptor complex promptly increased, reaching a maximum at 20 min, and then gradually declined, thus confirming that the TNF receptor is internalized as a TNF-receptor complex in the presence of TNF. During incubations with protein synthesis suppressed by cycloheximide following surface TNF receptor digestion by trypsin, TNF receptors reappeared on the cell surface, increasing in number to a peak at 60 min and gradually decreasing, and cells previously exposed to cycloheximide with or without TNF showed no recurrence of surface TNF receptors, suggesting that the TNF receptor is non-recycling. The results of the study thus suggest that the TNF receptor is continuously internalized and degraded intracellularly by lysosomes without being recycled regardless of the presence or absence of TNF and, further, that its internalization is accelerated when it is part of the TNF-receptor complex.

Cell Line↗