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Biomedical subjects

T Horiuchi

Publications and source records attributed to T Horiuchi.

At least 505 records · Page 28Linked to original sources

Studies on cis-trans isomerization of nitrofuran derivatives by bacterial nitroreductases.

cis-trans Isomerization of 3-(5-nitro-2-furyl)-2-(2-furyl)-acrylamide(AF-2) using Escherichia coli B/r and its two 5-nitro-2-furaldehyde semicarbazone (nitrofurazone)-resistant mutants was investigated. The isomerizing activity was detected in all three strains and markedly increased with acquiring resistance to nitro-furazone in intact cells and cell free extracts. Two distinct isomerases, nicotinamide adenine dinucleotide phosphate(NADPH)-dependent one with high activity and NAD(P)H-dependent with low activity were separated by Sephadex G-100 and Sepharose 4B columns. Both enzyme activities agreed with the nitrofurazone-reducing activity due to O2-sensitive nitroreductase as reported previously. Another nitroreductase, O2-insensitive one, was unable to isomerize cis AF-2 to trans form. These results suggest that bacterial cis-trans isomerases are not O2-insensitive nitroreductase, but O2-sensitive ones.

Bacteria↗

Infrared spectroscopic analysis of materials from calcified epithelioma.

An infrared spectrum of the calcified epithelioma excised from the eyelid of a three-year old girl was observed. Main absorption peaks were assigned as proteins and calcium phosphate. The crystallinity of calcium phosphate was 41%. The relative content of proteins and calcium phosphate was monitored as 7.4:1, reproducing the spectrum of the calcified epithelioma with a mixture of keratin and calcium phosphate. An epithelioma taken from the trunk of a 41-year-old man showed no calcification and the infrared spectrum of this epithelioma showed no absorption peaks of calcium phosphate.

Adult↗

Studies on olivoretins indicate a requirement for a free hydroxyl group for teleocidin B activity.

Three olivoretins, A, B and C (isolated from Streptoverticillium olivoreticuli), which are O-methylated teleocidin B isomers, were found to be biologically inactive. A fourth olivoretin, D, which has a free hydroxyl group and is identical to one of the four teleocidin B isomers, teleocidin B-4 (teleocidin B of Hirata) was biologically active. These findings indicate that the free primary hydroxyl group of teleocidin B isomers is necessary for activity. The effect on biological activity of the structural difference between des-O-methylolivoretin B (teleocidin B-1) and des-O-methylolivoretin C was also studied.

Animals↗

[Mode of action of fluoropyrimidines, in relation to their clinical application].

From results which we obtained in experiments on 5-fluoropyrimidine analogs, it was demonstrated that the mode of action of these compounds was as follows: In human cancer, in contrast to experimental animal tumors, it was demonstrated that thymidine phosphorylase (Thd Pase) activity was dominant compared to that of uridine phosphorylase (Urd Pase). This observation would indicate that 5-fluorouracil (5-FU) was mainly metabolized to produce 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), via 5-flu fluoro-2'-deoxyuridine(FdUR). FdUMP would inhibit DNA synthesis by blocking thymidilate synthetase activity, resulting in the death of cancer cells. Thd Pase activity by which 5-FU is converted to FdUR would participate greatly in the antitumor effect of the compounds because of the fact that FdUR has 1,000 times greater antitumor activity than 5-FU. Moreover, some of the fluoropyrimidines are activated by this enzyme to produce 5-FU. It should be emphasized that Thd Pase activity is higher in tumor tissue than in normal tissues. This finding would mean that the compounds would exert a selective (antitumor) activity on cancer cells. In addition, a clinical trial of fluoropyrimidines showed them to be effective when administered to patients in order to maintain a lower effective level of 5-FU in tumor tissues for a longer period of time. Such experiences would also lend more weight the possible of the mode of action of the of fluoropyrimidines mentioned above.

Animals↗

[Valve replacement for congenital valvular disease].

Among 365 cases of mitral and aortic valve replacement (MVR, AVR) done in our institute during the period between 1968 and 1983, there were 20 congenital cases (5.5%), who were pointed out to have valvular disease since birth or early childhood and had no evident history of infectious disease. Mean ages at operation of MVR and AVR groups were 5.6 +/- 3.6 and 22.4 +/- 6.0 years respectively. Predominant pathology of mitral valve was regurgitation in 9 and stenosis in 2 cases. Seven cases were associated with other cardiac anomalies. Cumulative follow-up period was 34.3 patient-years (p-y). There were 3 late deaths resulted from xenograft calcification. In AVR group, predominant pathology of the valve was regurgitation in 8 cases and stenoregurgitation in one case. All cases were associated with other cardiac anomalies. There were 2 late deaths within the cumulative follow-up period of 39.5 p-y. Cumulative survival rates at 15 years, both in MVR and AVR groups were lower in congenital group than in the group of acquired disease. The incidences of prosthesis malfunction, prosthesis related complication and late death in the both MVR and AVR groups were higher in congenital group, when compared to that in the group of acquired disease.

Adolescent↗

A dominant (mutD5) and a recessive (dnaQ49) mutator of Escherichia coli.

The two known strong mutators of Escherichia coli K12, mutD5 (Degnen & Cox, 1974) and dnaQ49 (Horiuchi et al., 1978), are located at almost the same position, at five minutes on the linkage map. To clarify the genetical and functional relationships between these two mutators, we have constructed hybrid plasmids and phages carrying dnaQ+ or mutD5 by using in vivo and in vitro recombination techniques and examined their effect on the phenotype of wild-type or mutant bacteria. The results indicated that the mutD5 mutator is dominant over the wild-type allele whereas dnaQ49 is recessive. Thus, mutD5 plasmid or mutD5 transducing lambda phage can be used to convert a wild-type strain to a highly mutable strain. Both dnaQ+ and mutD5 plasmids carried a 1.5 X 10(3) base DNA fragment derived from the E. coli chromosome and they were indistinguishable from each other by restriction enzyme analysis. Moreover, specific labeling of the plasmid-encoded proteins by the maxicell method revealed that the mutD5 plasmid codes for two proteins, one whose molecular weight is 25,000 and the other whose molecular weight is 21,000, which correspond to the dnaQ protein and RNase H, respectively. Insertion of the gamma delta sequence into the mutD gene of the plasmid resulted in disappearance of the 25,000 Mr protein. These results suggested that the dnaQ49 and mutD5 mutator are mutations that have arisen in a single gene, though they differ in many respects.

Bacteriophage lambda↗

Quantitative analysis of pulmonary vascular disease in simple cardiac anomalies with the Down syndrome.

Intimal changes and medial thickness of small pulmonary arteries were morphometrically examined in 21 cases of simple cardiac anomalies with the Down syndrome, and their correlations with age and with pulmonary arterial peak pressure were then compared with those of 20 cases of simple cardiac anomalies without the Down syndrome and 17 cases of complete transposition of the great arteries (TGA). Results indicate that (1) intimal changes developed at an earlier age in patients with simple cardiac anomalies and the Down syndrome than in those without the Down syndrome, (2) the intimal changes were more severe than those in simple cardiac anomalies without the Down syndrome at the same level of pulmonary arterial pressure and milder than those in TGA, and (3) the media of small pulmonary arteries in simple cardiac anomalies with the Down syndrome was thinner than the media in cases without the syndrome at the same radius and the same level of pulmonary arterial pressure but thicker than the media in TGA. Retarded development of medial hypertrophy in the Down syndrome or TGA in response to pulmonary hypertension appears to make the pulmonary arteries susceptible to even moderate pressure load and appears to be responsible for early development of severe intimal changes.

Adolescent↗

An amber replication mutant of F plasmid mapped in the minimal replication region.

We have constructed a mini-F derivative (pKP1013) consisting of a 5.4 kilobase pairs (kb) segment (44.0 to 49.4 kb) of mini-F and fragments carrying the chloramphenicol and spectinomycin resistance genes that originated from the R plasmid NR1. The plasmid pKP1013 replicates autonomously in a manner indistinguishable from that of the parental mini-F. An amber mutant defective in replication has been isolated from pKP1013 by localized mutagenesis using N-methyl-N'-nitro-N-nitrosoguanidine. The virtual absence of incorporation of [3H]-thymidine into the plasmid DNA as well as the kinetics of appearance of plasmid-free segregants suggest that plasmid DNA synthesis is primarily affected under nonpermissive conditions. The amber mutation has been mapped within the 530 base pairs (bp) region that extends from 45.25 (XmaI) to 45.78 Kb (PstI) by extensive analysis of in vitro recombinants constructed from rep+ and rep- plasmids.

Chromosome Mapping↗