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Biomedical subjects

Y Ohara

Publications and source records attributed to Y Ohara.

At least 145 records · Page 8Linked to original sources

N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity.

The reaction of cytidine with hydrazine to give N4-aminocytidine was greatly promoted by addition of a less-than-stoichiometric amount of bisulfite, and the product was isolated in a good yield. N4-Aminocytidine was strongly mutagenic to bacteria (Salmonella typhimurium TA100 and TA1535, and E. coli WP2 uvrA) and to phage (phi X174 am3). The activity did not require the presence of mammalian microsomal fraction in the system. The mutagenic potency of N4-aminocytidine in these systems was two orders of magnitude greater than that of N4-amino-2'-deoxycytidine, and more than two orders of magnitude greater than that of N4-hydroxycytidine. The greater activity of the riboside than the deoxyriboside was ascribed to the lack of deoxycytidine kinase in these cells. This compound may be useful as a powerful mutagen to induce a transition mutation in microorganisms.

Bacteriophage phi X 174↗

Mutagenicity of chalks. A case in which the test results led to the improvement of the quality of commercial goods.

Mutagenicity testing, of methanolic extracts of chalks, by the Salmonella/mammalian-microsome system revealed that the blue and the green chalks contained mutagens. A positive mutagenic response was observed on Salmonella typhimurium strain TA98, both in the presence and absence of the microsome system (S9). The source of the mutagenicity was traced to the blue pigment used for manufacturing these chalks. The pigment, copper phthalocyanine, a product of a Japanese chemical industrial company, was found to contain impurities that were mutagenic. The mutagenic principle giving positive response in the TA98 in the presence of S9 was purified 10(5)-fold from the original pigment. Although its structure is yet to be elucidated, this indirect frame-shift mutagen had a strong activity: 5700 His+ revertants per microgram. This information, delivered in the beginning of 1981, prompted the manufacturer to start supplying a mutagen-free product. As a result, the blue chalks on the market became no longer mutagenic in the summer of 1982.

Chromatography, High Pressure Liquid↗

Adsorption of mutagens to cotton bearing covalently bound trisulfo-copper-phthalocyanine.

A method for separating nonpolar mutagens from their dilute aqueous solutions is described. It utilizes the affinity of the mutagens to a phthalocyanine derivative attached to cotton through a covalent bond. For mutagens having 3 or more fused aromatic rings in their structures, efficient adsorption took place on soaking the cotton in their solutions. The mutagens adsorbed can be recovered by elution with ammoniacal methanol. Mutagenicity in smoker's urine, cooked beef, and river water was detected by use of this method.

Adsorption↗

Characterization of mutagenic fractions in beef extract and in cooked ground beef. Use of blue-cotton for efficient extraction.

Mutagenic components in commercial beef extract and in cooked ground beef were adsorbed from their aqueous solutions on cotton bearing covalently linked trisulfo-copper-phthalocyanine residues (blue-cotton). By repeating the adsorption and elution, efficient concentration of the mutagenic components with a satisfactory overall recovery was achieved. Carboxymethyl cellulose column chromatography was found to be an excellent means to separate 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) from 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), two strong mutagens that have previously been found in heated beef samples. Chromatography of the mutagenic components of beef extract on this column gave two mutagenic fractions which corresponded to MeIQx and IQ in elution profile. In reversed-phase high performance liquid chromatography, the major active component of the MeIQx fraction and that of the IQ fraction behaved identically with standard samples of MeIQx and IQ, respectively. The contents of these mutagens in a sample of Difco beef extract were estimated at 200-300 ng of MeIQx and 20-40 ng of IQ per gram. By the same fractionation procedures, mutagenic substances in the cooked beef were fractionated into MeIQx-type and IQ-type components. The activity distribution among these two fractions was similar to that found for beef extract.

Adsorption↗

Absence of Carp's agent in sera of patients with multiple sclerosis in Japan.

A study was devised to test for Carp's agent in the sera of Japanese patients with multiple sclerosis (MS). The sera were obtained from 17 patients with definite MS and six patients with possible MS. Strain C3H mice were given an intraperitoneal injection of 0.1 mL of each serum. One week before and 1, 3, and 6 weeks after inoculation, blood drops from tail tip were smeared and polymorphonuclear leukocytes (PMNLs) were counted. Although the experimental animals were kept under careful control, substantial fluctuation in the number of PMNLs occurred, and the variations of PMNL count in the experimental groups were all within the normal range. We conclude that there is no Carp's agent in the sera of patients with MS in Japan.

Animals↗

A solvent effect on the mutagenicity of tryptophan-pyrolysate mutagens in the Salmonella/mammalian microsome assay.

The effect of adding organic solvents to the pre-incubation mixture in the Salmonella/mammalian microsome assay was examined in tests of the tryptophan-pyrolysate mutagens, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Acetonitrile enhanced the mutagenic activity of Trp-P-1 and Trp-P-2 by an order of magnitude under optimal conditions. Strong enhancement of mutagenicity was also observed for the addition of ethanol, methanol, tetrahydrofurfuryl alcohol, tetrahydrofuran, 1,2-dimethoxyethane and N,N-dimethylformamide. The enhancing effect of acetonitrile on the mutagenicity of Trp-P-2 was found to be result of enrichment of the active metabolite in the assay system.

Acetonitriles↗

An aetiological study on spondylolysis from a biomechanical aspect.

The authors report clinical studies on lumbar disorders (clinical symptoms, X-ray findings) in athletes in various sports. The sport items were divided into three groups according to the main dynamic load applied to the lumbar region. As a result, over 60% of the athletes suffered from "lumbago", and among them spondylolysis reached the high rate of 27%. Arising from these clinical observations, we performed biomechanical laboratory analyses on human cadaver material, axial compression and rotational bending. Our results suggest that the incidence of spondylolysis depends upon the extent and direction of the loads.

Athletic Injuries↗

A sensitive assay for mutagenic activity of N-nitrosamines and its use for detection of modulators of the mutagenicity.

By carrying out the pre-incubation of bacteria with N-nitrosamines under acidic conditions, the mutagenicity of N-nitrosodimethylamine on Salmonella TA100 and E. coli WP2 try, hcr was detected with increased sensitivity, compared to usual assays in neutral buffers. Using this modified assay system, compounds have been screened for their modulating effects on N-nitrosamine-mediated mutagenesis and the following were found to be inhibitors: cysteine, cysteamine, bisulfite, n-propylamine, n-butylamine, n-hexylamine, n-octylamine, n-nonylamine, serotonine, tryptamine, epinephrine, norepinephrine and oleic acid. The mechanisms of inhibition are discussed.

Amines↗

Histopathological study on effects of potassium aspartate on the hypothalamus of rats.

Rats of various ages were treated orally or intraperitoneally with potassium aspartate. The dose required to induce hypothalamic lesion varied considerably by the age of animals and route of administration. Additional experiment, in which the animals were orally treated three times a day with potassium aspartate in dose levels between the maximum safety dose and minimum lesion-producing dose in the preceding single dose study, revealed no hypothalamic lesion at all in any animals of each age group. In this condition, the maximum safety dose was 3--5 times as large as that in single dosage administration experiment. Regarding the safety evaluation of potassium aspartate preparations, brief discussions on some points in extrapolation of the results of the present experimental study to the clinical use were made.

Administration, Oral↗

Rare occurrence of the tetratype tetrads in Saccharomycodes ludwigii.

Genetic data suggesting the absence of crossover in Saccharomycodes ludwigii have been described. Tetrad data obtained from 888 asci from 60 pairs of genes with 22 genetic markers showed the absence of tetratype asci, except for 5 asci in which a single pair of alleles showed tetratype segregation to the other genetic markers in each ascus. Spore arrays in the linear asci showed that the + - + - and + - - + (or - + + -) asci occurred at almost equal frequencies. The two coherent spores at each end of an ascus were always marked with different alleles of a gene.

Chromosomes↗