Search PubMed⌕ Search

Biomedical subjects

K Hiramoto

Publications and source records attributed to K Hiramoto.

At least 37 records · Page 2Linked to original sources
PubMed1998

Tissue differences in protein synthesis of the budgerigar (Melopsittacus undulatus).

In a series of experiment to elucidate the rule of amino acid requirements in the fowls from small to large ones, the fractional synthesis rates (FSR) of protein were determined to collect basal data on protein and amino acid metabolism in budgerigars as a small bird. Twenty young adult budgerigars were injected with 0.1 ml/10 g body weight containing 40 microCi/100 mumol phenylalanine/ml in a wing vein, and killed at 2 and 10 min after the injection. The FSR in the whole body, liver, proventriculs and gizzard, intestine and breast muscle were determined. The FSR were not the same in all tissues, and estimated values were highest in the liver (104.7), and followed by the intestines (68.0), whole body (55.2), proventriculs + Gizzard (46.8), heart (35.8) and breast muscle (26.9%/day).

Amino Acids↗
PubMed1997

DNA strand-breaking activity and mutagenicity of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), a Maillard reaction product of glucose and glycine.

Aqueous solution of glucose and glycine was heated under reflux for 4 h and extracted with ethyl acetate. Reversed phase HPLC of the extract revealed a new DNA strand-breaking substance, which was purified by repeated HPLC and identified as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP). DDMP induced DNA strand breaking in a dose- and time-dependent manner. It was active to break DNA strands at pH 7.4 and 9.4. Its pyranone skeleton was destroyed at the pH values. DNA strand breaking by DDMP was inhibited by superoxide dismutase, catalase, scavengers for hydroxyl radical, spin trapping agents and metal chelators, and the breaking was enhanced by Fe(III) ion. A mixture of DDMP and a spin trap DMPO gave electron spin resonance signals of a spin adduct DMPO-OH, indicating generation of hydroxyl radical. DDMP was found to be mutagenic to Salmonella typhimurium TA100 without metabolic activation. These results show DDMP generated active oxygen species to cause DNA strand breaking and mutagenesis.

Catalase↗
PubMed1997

beta-Carotene effectively scavenges toxic nitrogen oxides: nitrogen dioxide and peroxynitrous acid.

beta-Carotene absorbed 2 equimolar amounts of NO2 accompanying the complete destruction of beta-carotene. Electron spin resonance study using 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl revealed that no significant amounts of NO were released by the interaction. Nitrogen atoms derived from NO2 were tightly bound to the beta-carotene molecules. Destruction of beta-carotene was inhibited little by alpha-tocopherol and polyunsaturated fatty esters, and slightly by ascorbyl palmitate, indicating that beta-carotene was a more effective scavenger of NO2. ONOOH/ONOO- and 3-morpholinosydononimine similarly destroyed beta-carotene. The results suggest that beta-carotene contributes to the prevention of cytotoxicity and genotoxicity of NO2 and ONOOH/ONOO- derived from NO.

Amiloride↗
PubMed1997

Immunosuppression by ultraviolet B rays via eyes in mice.

Irradiation by ultraviolet B (UV-B; 280-320 nm) initiates suppression of contact hypersensitivity. Immunosuppression was induced in C57BL/6N Crj mice by exposure of the dorsal skin or the eyes to a 10 kJ/m2 dose of UV-B radiation from 20SE sunlamps, followed by sensitization with 0.5% fluorescein isothiocyanate (FITC). The degree of immunosuppression induced by UV-B eye irradiation was equal to that induced by UV-B skin irradiation. When mice were irradiated with UV-B into the eyes after the optic nerve had been cut, systemic immunosuppression was not induced.

Animals↗
PubMed1997

DNA single strand breaks by aromatic nitroso compounds in the presence of thiols.

Aromatic nitroso compounds, nitrosobenzene (NB), N,N-dimethyl-4-nitrosoaniline (DMNA) and 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), caused DNA single strand breaks in the presence of thiol compounds. The strand breaking was inhibited completely by free radical scavenger ethanol. Electron spin resonance (ESR) studies showed that hydronitroxyl (or sulfur-substituted nitroxyl) radicals were generated in the early stage of the interactions. Formation of these radicals was not inhibited by ethanol, indicating that these radicals did not directly contribute to the strand breaking. The DNA strand breaking was inhibited partially by superoxide dismutase and catalase under the limited conditions, but not by removal of oxygen from or addition of metal chelators to the reaction mixture. By ESR-spin trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), the DMPO-OH spin adduct was detected. Formation of the spin adduct was inhibited by superoxide dismutase and catalase. The hydronitroxyl (or the sulfur-substituted nitroxyl) radicals may reduce oxygen into active oxygen species and also transformed by themselves into other unidentified free radical species to cause the DNA strand breaks.

Animals↗
PubMed1997

Appearance of electron spin resonance signals in the interaction of dithiocarbamate-Fe(II) with nitrogen dioxide and nitrite.

Whether dithiocarbamate-Fe(II) complexes used in the electron spin resonance (ESR) studies are specific for the detection of NO was investigated. It was found that the typical ESR signals of dithiocarbamate-Fe(II)-NO spin adducts appeared in the interaction of N-methyl-D-glucaminedithiocarbamate (MGD)-, bis(hydroxyethyl) dithiocarbamate (HED)- and diethyldithiocarbamate (DED)-Fe(II) complexes with the NO-derived nitrogen oxides, nitrogen dioxide (NO2) and nitrite ion (NO2-) in a prolonged incubation. Under the conditions of prolonged incubation, appearance of the ESR signals of the dithiocarbamate-Fe(II)-NO spin adducts may indicate the presence of not only NO but NO2 and NO2-.

Chelating Agents↗
PubMed1997

Conversion of nitroxide radicals by phenolic and thiol antioxidants.

Nitrone/nitroso spin traps are often used for detection of unstable hydroxyl radical giving stable nitroxide radicals with characteristic electron spin resonance (ESR) signals. This technique may be useful only when the nitroxide radicals are kept stable in the reaction system. The aim of the present study is to clarify whether the nitroxide radicals are kept stable in the presence of the hydroxyl radical scavengers. Effect of hydroxyl radical scavengers on the ESR signals of nitroxide radicals, 2,2,6,6-tetramethyl-piperidine- N-oxyl (TEMPO) and the spin adduct (DMPO-OH) of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and hydroxyl radical, was examined. Although the ESR signals of TEMPO and the DMPO-OH spin adduct were unchanged on treatment with ethanol and dimethyl sulfoxide, their intensities were effectively decreased on treatment with 6-hydroxy-2,5,7, 8-tetra-methylchroman-2-carboxylic acid (Trolox), cysteine, glutathione, 2-mercaptoethanol and metallothionein. Hence, the results of the detection of hydroxyl radical in the presence of phenolic and thiol antioxidants by the ESR technique using nitrone/nitroso spin traps may be unreliable.

Antioxidants↗
PubMed1997

A novel variant of acquired epidermolysis bullosa with autoantibodies against the central triple-helical domain of type VII collagen.

Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are autoimmune bullous disorders, with tissue-bound and circulating autoantibodies reactive with the noncollagenous NC1 domain of type VII collagen (C-VII). Here, we describe a novel acquired bullous dermatosis with autoantibodies against the triple-helical domain of C-VII. Three patients, all Japanese children, presented with widespread inflammatory tense blisters. Histologically, subepidermal tissue separation was noted with inflammatory infiltrate in the superficial dermis. Direct immunofluorescence staining revealed linear IgG/C3 deposits along the dermal-epidermal junction. Circulating IgG anti-basement membrane zone autoantibodies stained the dermal side of normal skin separated with 1 M NaCl. Direct and indirect immunoelectron microscopy using colloidal gold labeling showed that patient sera reacted with anchoring fibrils. The gold particles were localized both near the lamina densa and on the central banded portion of the fibrils. The sera reacted with C-VII in immunoblots. Epitope analyses with natural and recombinant fragments of C-VII disclosed that the sera did not recognize the NC1 domain of C-VII, but the central triple-helical domain of this anchoring fibril protein. Thus, the present probands show a hitherto unrecognized variant of epidermolysis bullosa acquisita, with autoantibodies against epitopes in the collagenous domain of C-VII.

Autoantibodies↗
PubMed1996

DNA strand cleavage by tumor-inhibiting antibiotic 6-diazo-5-oxo-L-norleucine.

A tumor-inhibiting antibiotic, 6-diazo-5-oxo-L-norleucine (DON), caused DNA single-strand breaks. Thus, supercoiled plasmid DNA was transformed into an open circular relaxed form DNA by incubation with DON at pH 7.4. DNA strand cleavage by DON was not inhibited by superoxide dismutase, but inhibited by catalase. The inhibition by catalase may not be due to the destruction of hydrogen peroxide, but to the masking DON by the interaction with the heme moiety of the enzyme. DNA strand cleavage by DON was inhibited by azide, mannitol, ethanol, cysteine and 2-mercaptoethanol, suggesting the involvement of radical species in the cleavage. The cleavage, however, was not suppressed by removal of dissolved oxygen from the reaction mixture, indicating that no oxygen-derived radicals participated in the cleavage. Electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN) elucidated the generation of a carbon-centered radical from DON. Hence, the carbon-centered radical may participate in DNA strand cleavage by DON.

Antibiotics, Antineoplastic↗
PubMed1996

DNA breaking activity and mutagenicity of soy sauce: characterization of the active components and identification of 4-hydroxy-5-methyl-3(2H)-furanone.

Soy sauce is a seasoning consumed widely in Southeast Asia. When supercoiled DNA was incubated with soy sauce at pH7.4 and 37 degrees C, extensive breaking of DNA single-strands was caused. It was found that the breaking activity was due to multiple components with different molecular weight and polarity. One of the components with the breaking activity was purified successively by extraction with ethyl acetate, thin-layer chromatography and high performance liquid chromatography, and identified as 4-hydroxy-5-methyl-3(2H)-furanone (HMF), one of the fragrant components in soy sauce. Formation of this component was found due to Maillard reaction of pentoses/amino acids. HMF was readily degraded into the compound with an endiol-ketol structure and reducing activity. Using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in an electron spin resonance-spin trapping technique, generation of hydroxyl radical in an aqueous solution of HMF was confirmed. While DNA breaking by soy sauce was little inhibited by the scavengers of active oxygen radicals, the breaking by HMF was effectively inhibited by superoxide dismutase, catalase, hydroxyl radical scavengers, spin-trapping agents, thiol compounds and metal chelating agents. Hence, DNA breaking activity of HMF was found due to generation of active oxygen radicals. HMF was found mutagenic to Salmonella bacteria without metabolic activation, probably due to generation of active oxygen radicals.

DNA↗
PubMed1996

DNA strand break by 2,5-dimethyl-4-hydroxy-3(2H)-furanone, a fragrant compound in various foodstuffs.

2,5-Dimethyl-4-hydroxy-3(2 H)-furanone (DMHF), produced by Maillard reaction of sugar/amino acid and found in various foodstuffs, showed mutagenicity to Salmonella typhimurium TA100 strain with and without S9 mix, and induced micronucleated mouse peripheral reticulocytes. DNA strand breaking activity of the compound at pH 7.4 increased with the increasing dose of the compound and with the increasing incubation time. The breaking activity was inhibited in the presence of superoxide dismutase, catalase, hydroxyl radical scavengers, spin trapping agents, thiol compounds and metal chelators, and also by removal of dissolved oxygen from the incubation mixture. Addition of Fe(III) ion to the incubation mixture enhanced the breaking activity. Incubation of DMHF with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) gave electron spin resonance signals characteristic to DMPO-OH adduct, indicating generation of hydroxyl radical. It was found that DMHF generated hydroxyl radical with an aid of a trace amount of metal ions, and induced DNA strand breaking. Mutagenicity and induction of micronucleated reticulocytes by DMHF may be caused as a result of DNA modification via hydroxyl radical.

Animals↗
PubMed1996

Formation of the mutagenic/carcinogenic imidazoquinoxaline-type heterocyclic amines through the unstable free radical Maillard intermediates and its inhibition by phenolic antioxidants.

Generation of the imidazoquinoxaline-type heterocyclic amines in the heated model system composed of glucose/glycine/creatinine in aqueous diethylene glycol was effectively prevented by phenolic antioxidants, butylated hydroxyanisole (BHA), propyl gallate (PG), sesamol, esculetin and epigallocatechin gallate (EGCG) in a dose-dependent manner. Generation of the mutagens in heated-and-dried bonito meat was effectively prevented on pretreatment with EGCG or green tea extract. Electron spin resonance (ESR) studies showed that the heated model mixture of glucose/glycine generated the unstable pyrazine cation radical, and its formation was inhibited by BHA, sesamol and EGCG. ESR-spin trapping studies using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN) showed that the heated model mixture of glucose/glycine or glucose/glycine/creatinine generated unstable carbon-centred radical(s), and their formation was effectively inhibited by BHA, sesamol and EGCG. It is likely that the unstable free radical Maillard intermediates played an important role in the formation of the imidazoquinoxaline-type heterocyclic amines, and the phenolic antioxidants effectively scavenged the radical species to prevent the mutagen formation.

Anticarcinogenic Agents↗
PubMed1996

Abnormalities in behavior, learning ability, and the cholinergic system induced by long-term ultraviolet A irradiation of mice.

Behavioral abnormalities, jumping reaction, increase in spontaneous activity abnormal violence, and lethargy were observed in long-term ultraviolet A (UVA)-irradiated hairy male Crj:CD-1 mice. The learning ability of 6- and 12-months UVA-irradiated mice was significantly reduced compared to un-irradiated age-matched mice. Acetylcholine levels, acetylcholinesterase and choline acetyltransferase activities in the whole brains were decreased in both of 6- and 12-month irradiated mice. Only 1 of 6 mice irradiated for 12 months was histologically observed to have a drastic loss of bilateral hippocampal pyramidal cells in the CA1 field of Ammon's horn.

Animals↗
PubMed1996

Effect of plant phenolics on the formation of the spin-adduct of hydroxyl radical and the DNA strand breaking by hydroxyl radical.

The effect of plant phenolics, including flavonoids and green tea polyphenolics, on hydroxyl radical was examined by a common method using an electron spin resonance (ESR) technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. The intensity of the ESR signals of DMPO-OH adduct formed by the interaction of DMPO with Fenton reagent was reduced in the presence of each phenolic in a dose-dependent manner. However, the decrease in the intensity of the signals was due partly to the enhanced disappearance of the spin adduct by the phenolics, as has been previously shown. This spin trapping method was unreliable for evaluation of the effect of the phenolics against hydroxyl radical. Hydroxyl radical induced-DNA single-strand breaks may be a better index for evaluation of the activity of the phenolics regarding hydroxyl radical. The effect of the phenolics on DNA single-strand breaks induced by Fenton reagent was examined. While sesamol and esculetin were inhibitory, most polyphenolics, especially (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), were rather stimulatory. The results indicate that sesamol and esculetin scavenged hydroxyl radical, and EGC and EGCG generated hydroxyl radical under the conditions where hydroxyl radical was generating.

Catechin↗
PubMed1995

DNA strand breaking by the carbon-centered radical generated from 4-(hydroxymethyl) benzenediazonium salt, a carcinogen in mushroom Agaricus bisporus.

4-(Hydroxymethyl)benzenediazonium salt (HMBD), a carcinogen in mushroom Agaricus bisporus, was found to generate a carbon-centered radical, 4-(hydroxymethyl)phenyl radical, during incubation at pH 7.4 and 37 degrees C, when estimated by Electron Spin Resonance (ESR) spin-trapping technique using 5,5-dimethyl-1-pyrroline N-oxide (DMPO), N-tert-butylphenyl-alpha-nitrone (PBN) and 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS). Formation of a substantial amount of benzyl alcohol during incubation of HMBD in the presence of a hydrogen donor, ethanol, supported the generation of the carbon-centered radical. When plasmid supercoiled DNA was incubated with HMBD at pH 7.4 and 37 degrees C for 30 min, the supercoiled DNA was converted into a nicked circular relaxed form and subsequently into a linear form. Sequence analysis indicated that the compound cleaved the plasmid DNA strand non-specifically. The intracellular double stranded DNA of Escherichia coli was fragmented by the compound, which may be responsible for its cytotoxicity. The compound induced mouse micronucleated peripheral reticulocytes. The compound was active in breaking DNA strands in the absence of molecular oxygen and in the presence of superoxide dismutase and catalase, indicating that no oxygen-derived radicals participated in the breaking. DNA breaking was inhibited by hydrogen donors butyl hydroxyanisole and ethanol, thiol compounds L-cysteine and 2-mercaptoethanol, and spin-trapping agents DMPO and PBN, indicating the direct contribution of the carbon-centered radical to the breaking.

Agaricus↗
PubMed1995

DNA strand breaks induced through active oxygen radicals by fragrant component 4-hydroxy-2-hydroxymethyl-5-methyl-3(2H)-furanone in Maillard reaction of hexose/amino acid.

The Maillard reaction of glucose/amino acid produces components that induce strand breakage of supercoiled DNA. This study was designed to elucidate the structure of the active components and the mechanisms of their DNA strand breakage. When an aqueous mixture of glucose/glycine heated under reflux for 4 hr was extracted with ethyl acetate, the extract showed mutagenicity to Salmonella typhimurium TA100 and strand-breaking activity for supercoiled DNA. One of the components with DNA strand-breaking activity was isolated by repeated HPLC using a reverse phase column. The component was identified as 4-hydroxy-2-hydroxymethyl-5-methyl-3(2H)-furanone (HHMF), a fragrant component in the Maillard reaction mixture. HHMF was similarly produced in the reaction of glucose/alanine and fructose/glycine. DNA strand-breaking activity of the component at pH 7.4 increased with increasing dose of the component and with increasing incubation time. The strand-breaking activity of the component was greater at pH 7.4 than at pH 4.4 and 9.4; it was inhibited in the presence of superoxide dismutase, catalase, hydroxyl radical scavengers, spin-trapping agents, thiol compounds and metal chelators, and also by removal of dissolved oxygen from the reaction mixture. The strand-breaking activity was enhanced in the presence of ionic iron. Incubation of HHMF with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) gave electron spin resonance signals characteristics of the DMPO-OH adduct, indicating generation of the hydroxyl radical. HHMF generated superoxide, hydrogen peroxide and then hydroxyl radical with the aid of a trace amount of metal ions, which effectively cleaved the DNA strand.

Amino Acids↗
PubMed1995

Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3-b]indole.

To investigate the genotoxic properties of a food-derived carcinogen, 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), we have tested whether Trp-P-2 and its metabolically transformed products can induce DNA recombinations. Trp-P-2 is a strong mutagen and its activated form, the N-hydroxylated derivative, Trp-P-2(NHOH), is known to form DNA adducts and cause DNA chain cleavage. Using a system in which phage lambda undergoes recombination inside host Escherichia coli, we have found that Trp-P-2(NHOH), but not Trp-P-2 itself, can induce recombination. A nitroso derivative of Trp-P-2, Trp-P-2(NO), which can be reduced intracellularly to form Trp-P-2(NHOH), also induced recombination. Active oxygens are implicated in this recombinogenic action, since Trp-P-2(NHOH) is known to undergo spontaneous oxidative degradation, generating active oxygen radicals which can cause DNA chain cleavages. 4-Hydroxyaminoquinoline N-oxide and phenyl-hydroxylamine also showed recombinogenic actions in this assay system; hence, it is suspected that aromatic amine-type carcinogens have this property in common.

Bacteriophage lambda↗