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Biomedical subjects

A Nishikawa

Publications and source records attributed to A Nishikawa.

At least 127 records · Page 7Linked to original sources
PubMed1997

Enhancement of cell proliferation and prostaglandin biosynthesis by 1,8-dihydroxyanthraquinone in the rat large intestine.

The effects of 1,8-dihydroxyanthraquinone (DHAQ), a stimulant laxative named danthron, on cell kinetics and prostaglandin (PG) biosynthesis in the gastrointestinal tract were investigated in male 8-week-old F344 rats divided into three groups, each consisting of 10 animals. The animals in groups one, two and three were respectively given diets supplemented with 0%, 0.1% and 0.2% DHAQ for 24 days. PGE2 levels in the colorectal mucosa were significantly (P < 0.05 and 0.001) elevated after DHAQ treatment and showed some evidence of a dependence of DHAQ dose, consistent with the plasma PGE2 levels. BrdU-labeling indices in the large intestinal epithelium were also significantly (P < 0.01) increased, although the other portions of the gut such as the stomach and small intestine were not significantly affected. Excretion of the main urinary metabolite of PGE (PGE-MUM) was significantly (P < 0.001 or 0.01) increased whereas the urinary PGE2 concentration and total PGE2 excretion were not changed. Thus the results of the present study clearly indicate enhancement of cell proliferation by DHAQ in the large intestine epithelia, correlated with increased PGE2 levels in the large intestinal mucosa as well as the plasma, and possible support for the conclusion that quantitative analysis of urinary PGE-MUM, but not PGE2 itself, offer a useful approach for biomonitoring exposure to such stimulant laxatives.

Animals↗
PubMed1997

Partial sequences of large subunit ribosomal DNA of a new yeast species, Trichosporon domesticum and related species.

We determined the partial sequences of large subunit rDNA of a new yeast species, Trichosporon domesticum, which was isolated from the house of a summer-type hypersensitivity pneumonitis patient. Phylogenetically, T. domesticum was positioned in the taxonomic group containing T. montevideense and T. brassicae, which indicated an identical serotype. A phylogenetic relationship among all species of the genus Trichosporon which belong to the basidiomycetous yeast is clarified.

Alveolitis, Extrinsic Allergic↗
PubMed1997

Mechanistic insights into chemopreventive effects of phenethyl isothiocyanate in N-nitrosobis(2-oxopropyl)amine-treated hamsters.

The influence of phenethyl isothiocyanate (PEITC) on cell kinetics in the target organs of N-nitrosobis(2-oxopropyl)amine (BOP) tumorigenicity and on xenobiotic-metabolizing enzymes was investigated in hamsters. Female 5-week-old Syrian hamsters were given a single s.c. dose of 0, 20 or 50 mg/kg of BOP 2 h after receiving PEITC by gavage at a dose of 0, 100 or 250 mumol/animal (0, 16.3 or 40.8 mg/animal). Six and 22 h after the BOP administration, hamsters were killed and tissues were sampled. Proliferating cell nuclear antigen immunohistochemistry demonstrated significant reduction (P < 0.05-0.001) by PEITC of the labeling indices in the pancreatic acini and ducts, bronchioles, and renal tubules of the BOP-treated animals in a dose-dependent manner. In the lungs, the PEITC pretreatment significantly (P < 0.001) reduced the O6-methyldeoxyguanosine levels as compared to the BOP-alone value. Immunoblot analysis of liver cytochrome P450 isoenzymes showed CYP 2B1 to be mainly involved in the metabolic activation of BOP. PEITC significantly (P < 0.05) inhibited the induction of several isoenzymes, including CYP 2B1, while lowering the hepatic glutathione S-transferase activity as well as glutathione levels, regardless of BOP administration. Our results thus suggest that PEITC exerts its chemopreventive activity against BOP initiation of carcinogenesis in hamsters by decreasing cell turnover and DNA methylation in the target organs, and by influencing hepatic xenobiotic-metabolizing phase I enzymes, although the relationship, if any, of the latter with the former events remains to be investigated.

Animals↗
PubMed1997

The adenovirus E1A repression domain disrupts the interaction between the TATA binding protein and the TATA box in a manner reversible by TFIIB.

The human adenovirus E1A 243 amino acid oncoprotein possesses a transcription repression function that appears to be linked with its ability to induce cell cycle progression and to inhibit cell differentiation. The molecular mechanism of E1A repression has been poorly understood. Recently, we reported that the TATA binding protein (TBP) is a cellular target of E1A repression. Here we demonstrate that the interaction between TBP and the E1A repression domain is direct and specific. The TBP binding domain within E1A 243R maps to E1A N-terminal residues approximately 1 to 35 and is distinct from the TBP binding domain within conserved region 3 unique to the E1A 289R transactivator. An E1A protein fragment consisting of only the E1A N-terminal 80 amino acids (E1A 1-80) and containing the E1A repression function was found to block the interaction between TBP and the TATA box element as shown by gel mobility and DNase protection analysis. Interestingly, a preformed TBP-TATA box promoter complex can be dissociated by E1A 1-80. Further, TFIIB can prevent E1A disruption of TBP-TATA box interaction. TFIIB, like TBP, can overcome E1A repression of transcription in vitro. The ability of the E1A repression domain to block TBP interaction with the TATA box and the ability of TFIIB to reverse E1A disruption of the TBP-TATA box complex implies a mechanism for E1A repression distinct from those of known cellular repressors that target TBP.

Adenovirus E1A Proteins↗
PubMed1997

[Induction of cell differentiation and programmed cell death in amphibian metamorphosis].

Both the phenomena, the cell growth and differentiation, and the programmed cell death, are involved in the reconstruction of body from larval type to adult type during amphibian metamorphosis. Since all of metamorphic events are triggered by increase of plasma thyroid hormone level, the reconstruction of body during metamorphosis will provide useful biological system for analyzing the mechanism of hormonal induction of cell differentiation and programmed cell death. Induction of death of skein-type epidermal basal cells in tail skin of bullfrog tadpoles was involved in cell cycle arrest caused by triiodothyronine (T3). On the other hand, induction of adult type stratified and cornified epidermis was involved in T3-induction of the growth and differentiation of non-skein type epidermal basal cells in body skin. Developmental origin of these two different basal cells should be clarified. Analysis of adult type epidermal keratin expression during Xenopus metamorphosis revealed that enhanced transcription of adult type gene by synergism between T3 and glucocorticoid. Since receptors of these two hormones are belong to the same members of steroid receptor super family, interaction of hormones and hormone receptors should be studied for clarifying the molecular mechanism of the hormonal synergism at a transcription level. Programmed muscle cell death is important in tail degeneration as well as in the larval-to-adult conversion of the dorsal body muscle cell of Xenopus laevis during metamorphosis. In the tail, only death of larval type muscle cells occur. However, in the body, both the death of larval type muscle cells and new myogenesis (the growth and differentiation of adult type cells) occur to form adult skeletal muscles. The new myogenesis area expanded in a wave-like fashion with an anteroposterior gradient during metamorphic climax stage. The area of muscle cell death expanded like a wave from the base of the tail to the anterior and posterior side. Growth, differentiation and death of muscle cells were induced by T3. The origin of adult satellite cells for new myogenesis should be clarified in order to understand the mechanism of skeletal muscle development during metamorphosis.

Amphibians↗
PubMed1997

[Effects of 16-week dietary administration of 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline in rats].

2-Amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), a heterocyclic amine found in cooked meats, is carcinogenic in mice and rats at high doses. In order to examine the toxicity including preneoplastic changes at the lower doses, a total of 170 male Fischer 344 rats were administered MeIQx for 16 weeks at a dose of 100, 10, 1, 0.1, 0.01, 0.001 ppm or 0 ppm in the diet. The numbers of GST-P positive foci and BrdU-labeling indices in the liver were significantly increased by the dietary administration of 10 ppm and 1 ppm or more of MeIQx respectively, when compared with the basal diet-fed control rats. Aberrant cry p tfoci (ACF) were also significantly increased in the 100 ppm MeIQx group as compared to the control value. No histopathological changes indicating obvious toxicity of MeIQx were observed in the major organs other than the liver and large intestine. In conclusion, our results clearly indicate that MeIQx selectively targets the liver and large intestine of rats as organs for the toxicity, but dose not affect the other major organs at low doses.

Animals↗
PubMed1997

[Effects of dietary magnesium deficiency in the rat: with special reference to ultrastructural examination].

Epidemiologically, it has been suggested that dietary magnesium/calcium imbalance is associated with the risk of heart diseases. In the present study, the effects of magnesium deficiency and/or calcium over intake were investigated in rats. Male Sprague-Dawley rats were divided into 4 groups, and respectively fed basal diet (AIN-76) alone (Group 1), calcium-doubled AIN-76 diet (Group 2), magnesium-deficient AIN -76 diet (Group 3) and magnesium-deficient/calcium-doubled AIN-76 diet (Group 4) for 19 days. A biochemical assay using inductively coupled plasma showed that the magnesium concentrations of the femoral bone and serum were significantly (p < 0.001) lower in Groups 3 and 4 than in Group 1. The lipid peroxides of the heart in Group 4 and of the liver in Groups 3 and 4 were increased as compared to the Group 1 values although there was no statistical significance. Ultrastructurally, degenerative changes of organellas including mitochondria were observed in myocardial, liver and renal tubule cells of Groups 2-4. Severe degeneration such as disorganization, lysis and disarrangement of myofibrils was most evident in myocardial cells of Group 4. Our results thus suggest that dietary magnesium deficiency gives rise to retrogressive changes in some organs including the heart, and concurrent calcium overintake synergistically enhances the myocardial injury due to magnesium deficiency.

Animals↗
PubMed1996

Bafilomycin A1 induces apoptosis in PC12 cells independently of intracellular pH.

PC12 cells growth-arrested with bafilomycin A1 died showing apoptotic chromatin condensation in the nuclei. The bafilomycin A1-induced chromatin condensation was preceded by neurite outgrowth (NOG), required higher concentrations of bafilomycin A1 than NOG, and was suppressed by cycloheximide and aurintricarboxylic acid. NH4Cl (10 mM), another acidotropic pH perturbing agent, neither induced apoptotic chromatin condensation by itself nor suppressed that induced by bafilomycin A1, suggesting that bafilomycin A1-induced apoptosis occurs independently of intracellular pH in PC12 cells.

Ammonium Chloride↗
PubMed1996

Reappraisal of eight representative carcinogenic and non-carcinogenic compounds in a new medium-term rat liver bioassay using D-galactosamine.

The carcinogenic potential of eight different compounds was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a non-surgical method to induce regeneration in place of partial hepatectomy (PH). Male rats were initially given a single i.p. injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two i.p. injections of DGA (300 mg/kg) at the end of weeks 2 and 5. They were treated with one of the test compounds aflatoxin B1, benzo[a]pyrene, diethylstilbestrol, urethane, sodium saccharin, bucetin, D-mannitol and sodium chloride in the diet or basal diet alone for weeks 3-8. Carcinogenic potential was assessed by comparing the numbers and areas per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for the hepatocarcinogens aflatoxin B1, diethylstilbestrol or urethane, and for the non-liver carcinogen benzo[a]pyrene. Negative values were shown in rats treated with the non-carcinogens, D-mannitol and sodium chloride. The two other non-liver carcinogens sodium saccharin and bucetin, also did not exert positive effects in the system. The present data are consistent with findings in previous medium-term bioassays using PH. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive non-invasive method to screen large numbers of environmental carcinogens.

Animals↗
PubMed1996

Human N-acetylglucosaminyltransferase III gene is transcribed from multiple promoters.

We have isolated cDNA clones for the human N-acetylglucosaminyltransferase III (GlcNAc-transferase III) gene. Two of them, H15 and H20, contain 5' non-coding regions that are totally different from each other except for 8 bp adjacent to the putative initiation codon. Analysis of one of the genomic cosmid clones containing the GlcNAc-transferase III coding region, Hug3, revealed the 5' non-coding regions of H15 and H20 contain two and one exons, respectively, in addition to the exon containing the coding region (exon 1). These have arisen as the result of alternative splicing. The transcription-initiation sites were determined by primer-extension analysis and 5'-rapid amplification of cDNA ends (RACe). Both H15-specific and H20-specific primers gave cDNAs longer than those expected from the lengths of H15 and H20, and a primer complementary to the region around the intron/exon junction near the putative initiation codon also gave distinct signals. Promoter activities of the 5'-flanking regions of H15, H20 and exon 1 were measured in a human hepatoblastoma cell line, HuH-6 cells by luciferase assays. The 5'-flanking region of exon 1 was the most active, whilst that of H15 was several times less active, and that of H20 was inactive. Our study suggests that multiple promoters of the GlcNAc-transferase III gene contribute to the complex regulation of this gene.

Alternative Splicing↗
PubMed1996

Chemopreventive effects of 24R,25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The modifying effects of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], a vitamin D3 derivative, on glandular stomach carcinogenesis were investigated in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride exposure during the postinitiation phase. A total of 130 male 6-week-old rats was divided into five groups. Groups 1-3 (consisting of 30 rats/group) were given MNNG in drinking water at a concentration of 100 ppm and were simultaneously fed a diet supplemented with 10% NaCl for 8 weeks. They were fed a diet containing either 5.0 ppm (group 1) or 2.5 ppm (group 2) 24R,25(OH)2D3 or were kept on the basal diet alone (group 3) for the following 57 weeks. Rats in groups 4 and 5 were given 24R,25(OH)2D3, as were animals in groups 1 and 3, but did not receive the MNNG + NaCl treatment. The total incidence of combined atypical hyperplasias and adenocarcinomas in the glandular stomachs was significantly lower in group 1 (24%) than in group 3 (70%; P < 0.01). The mean numbers of atypical hyperplasias or adenocarcinomas of the glandular stomachs in groups 1 (0.31) and 2 (0.66) were also significantly decreased (P < 0.01 and P < 0.05, respectively) as compared to the group 3 value (1.21). Thus, the development of cancerous and precancerous lesions in the glandular stomach was decreased by exposure to 24R,25(OH)2D3 in a dose-dependent manner. Urinary calcium levels were increased by this vitamin D3 derivative (in line with the applied dose) when assayed at 10, 30, and 62 weeks, regardless of the MNNG + NaCl treatment The present results clearly indicate that 24,25(OH)2D3 exerts chemopreventive effects, possibly by influencing calcium pharmacodynamics, when given during the postinitiation phase of glandular stomach carcinogenesis in rats.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

Long-term toxicity/carcinogenicity study of L-histidine monohydrochloride in F344 rats.

The long-term toxicity and carcinogenicity of histidine, an essential amino acid for most animal species, were examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given L-histidine monohydrochloride (HMHC) in their diet at concentrations of 0 (control), 1.25 and 2.5% for 104 wk; these dose levels were selected on the basis of the results of a subchronic toxicity study, in which body weights were depressed and formation of sperm granulomas in the epididymis was histologically evident in males fed 5.0% HMHC. All surviving rats were killed at wk 107. Increases in red blood cell count, haemoglobin value and haematocrit level were observed in male rats given 2.5% HMHC. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumor was found in the treated groups of either sex. Thus, it was concluded that, under the present experimental conditions, HMHC is not carcinogenic in F344 rats.

Administration, Oral↗
PubMed1996

Inhibitory effects of the dietary antioxidants butylated hydroxyanisole and butylated hydroxytoluene on bronchioloalveolar cell proliferation during the bleomycin-induced pulmonary fibrosing process in hamsters.

The effects of dietary antioxidants on bleomycin (BLM)-induced pulmonary fibrosis were investigated in Syrian golden hamsters. In addition, the influence on cell proliferative activity in bronchioloalveolar hyperplastic lesions during the lung fibrosing process was evaluated in terms of argyrophil nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA). Male 6-wk-old hamsters were divided into six groups. Groups 1-3 were intratracheally instilled with BLM at a dose of 2.5 U/kg body weight on days 0 and 14, and then given a diet supplemented with 1% butylated hydroxyanisole (BHA), or 1% butylated hydroxytoluene (BHT), or basal diet alone for the following 41 days. Groups 4-6 were given 1% BHA, 1% BHT or basal diet without BLM treatment for the same time period as that in those of groups 1-3. The mortality rate of animals in group 1 (BLM/BHA) (one in 20; 5%) was lower than in those of groups 2 (BLM/BHT) (three in 20; 15%) and 3 (BLM alone) (four in 20; 20%). BHA and BHT treatments significantly inhibited lung weight gains by BLM (P < 0.05). Histopathologically, both BHA and BHT reduced BLM-induced pulmonary histopathological changes such as fibrosis, macrophage aggregation and epithelial proliferation, with a tendency for correlation with accumulation of type III collagen. In addition, antioxidant treatment significantly lowered the mean numbers of AgNORs (P < 0.01) and PCNA-labelling indices (P < 0.05) in the hyperplastic bronchioloalveolar lesions. The results thus indicate that these antioxidants exert inhibitory effects on proliferation of hyperplastic lesions associated with lung fibrosis.

Animals↗
PubMed1996

Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis(2-oxopropyl)amine-treated hamsters.

The chemopreventive effects of phenethyl isothiocyanate (PEITC) were investigated in N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. Female 5-week-old Syrian golden hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were given BOP by two subcutaneous injections 7 days apart at a dose of 20 mg/kg body weight, plus either 100, 10 or 0 micromol of PEITC in corn oil by gavage 2 h prior to each BOP treatment, respectively per group. Animals in groups 4 and 5, each consisting of 10 hamsters, were given 100 and 10 micromol of PEITC alone in corn oil, and 10 animals in group 6 served as a vehicle control. Animals were sacrificed 52 weeks after the first BOP injection. Both the incidences and multiplicities of lung adenomas and/or adenocarcinomas were significantly decreased in a dose-dependent manner by PEITC treatments (P < 0.01 or 0.05). The lung tumor incidences were inhibited by 100% with 100 micromol PEITC and by 82% with the 10 micromol dosage. In addition, the high dose of PEITC also significantly inhibited pancreatic carcinogenesis (P < 0.05) and showed a tendency to lower the incidences of liver and renal tumors, although these effects were not statistically significant. Under the present experimental conditions, PEITC itself did not cause any apparent toxicity. Our results thus indicate that PEITC is a remarkably effective chemopreventive agent for the BOP-induced lung and pancreatic tumors in hamsters.

Adenocarcinoma↗
PubMed1996

A fluorescent assay method for GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha 1-6fucosyltransferase activity, involving high performance liquid chromatography.

An assay method for GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha 1-6fucosyltransferase (alpha 1-6FucT; EC 2.4.1.68) activity has been developed, involving a fluorescent pyridylaminated substrate. A glycopeptide derived from bovine gamma-globulin was coupled with 4-(2-pyridylamino)butylamine (PABA) through the peptide bond, and the following substrate was obtained. [equation: see text] The substrate and guanosine diphospho-fucopyranoside (GDP-Fuc) were incubated with a crude enzyme extract for 2 h, and then the enzymatic product was separated by reversed phase HPLC. Quantitation of the product involved measurement of the fluorescence intensity of the fucosylated pyridylaminated sugar. The structures of both synthesized GnGn-bi-Asn-PABA (substrate), and synthesized GnGnF-bi-Asn-PABA (product) were analyzed by 1H NMR. The enzymatic product was also analyzed by 1H NMR and was found to have alpha 1-6fucose at the reducing end GlcNAc. This method is highly specific for alpha 1-6FucT and is applicable for various experiments, including purification and cell culture ones.

Animals↗
PubMed1996

Synthetic collagen-like domain derived from the macrophage scavenger receptor binds acetylated low-density lipoprotein in vitro.

The bovine macrophage scavenger receptor is a 70 kDa membrane protein that is trimerized on the macrophage cell surface. The receptor binds modified low-density lipoproteins (LDL). The core binding site is located within 22 residues at the C-terminus of the collagen-like domain of the receptor. The Lys residue at position 337 plays an important role in ligand binding. Here, the collagen-like domain was constructed using a peptide architecture technique, in which three collagenous peptide chains were crosslinked at their N-termini. The crosslinked peptide showed a collagen-like structure by circular dichroism and existed mainly in a monomeric triple helical form as shown by gel exclusion chromatography. The triple-stranded peptide was demonstrated to bind acetylated LDL (Ac-LDL) using regions derived from Gly323 to Lys340 of the natural bovine scavenger receptor. However, a single-stranded peptide with the same amino acid sequence did not bind Ac-LDL. Furthermore, a triple-stranded mutated peptide in which Lys corresponding to Lys337 in the mother protein was substituted with Ala showed no binding activity to Ac-LDL. These results, taken together, indicate that the synthetic collagen-like peptide has a similar structure to the binding site in the scavenger receptor, and support the view that the collagen-like domain of the natural scavenger receptor recognizes Ac-LDL.

Amino Acid Sequence↗