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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 361 records · Page 20Linked to original sources

Hemoglobin Sendagi (beta 42 Phe----Val): a new unstable hemoglobin variant having an amino acid substitution at CD1 of the beta-chain.

Hb Sendagi, a new unstable hemoglobin variant, was found in a Japanese male and his daughter, who have a moderate hemolytic anemia. The variant showed decreased stability upon heat and isopropanol precipitation tests. The variant did not separate from hemoglobin A by electrophoresis, but the abnormal beta-chain emerged ahead of the normal beta-chain on reverse-phase HPLC. Structural analyses revealed that the phenylalanine beta 42 (CD1), one of the critical amino acid residues in the heme pocket, had been replaced by valine. Oxygen equilibrium studies of the patient's hemolysates indicated that Hb Sendagi had a lowered oxygen affinity and a normal response to 2,3-diphosphoglycerate. Hb Hammersmith (beta 42 Phe----Ser) and Hb Louisville (Bucuresti) (beta 42 Phe----Leu) have previously been reported to have varying degrees of molecular instability and altered oxygen binding function. Hb Sendagi provides an additional model for elucidation of the role of the phenylalanine beta CD1 on the structure and function of hemoglobin.

Anemia, Hemolytic↗

Enzymatic conversion of 7-hydroxyguanine to its nucleosides.

7-Hydroxyguanine, an antitumor purine-analog, reacted with ribose (or deoxyribose)-1-phosphate in the presence of purine nucleoside phosphorylase. We prepared 7-hydroxyguanine riboside and deoxyriboside using purine nucleoside phosphorylase from bovine spleen. Each nucleoside exhibits antitumor activity against mouse leukemia L1210 cells. The therapeutic effect of 7-hydroxyguanine deoxyriboside is superior to those of 7-hydroxyguanine and 7-hydroxyguanine riboside.

Animals↗

Propioxatins A and B, new enkephalinase B inhibitors. I. Taxonomy, fermentation, isolation and biological properties.

A soil isolate of actinomycete, strain SANK 60684, was found to produce new enkephalinase B inhibitors, propioxatins A and B. The presence of both LL- and meso-2,6-diaminopimelic acid, glycine and galactose in the cell wall assigned this strain to genus Kitasatosporia. From the morphological, cultural and physiological characteristics, this strain was determined to be Kitasatosporia setae. The Ki values of propioxatins A and B were 1.3 X 10(-8)M and 1.1 X 10(-7)M, respectively, for enkephalinase B. All other proteases examined except aminopeptidases, which were slightly inhibited, were not inhibited by these two compounds.

Actinomycetales↗

[Bacteriological and clinical study of ciprofloxacin in gonococcal urethritis].

The purpose of this study was to determine the susceptibility of Neisseria gonorrhoeae to ciprofloxacin (CPFX). The MIC's of CPFX against 50 clinical isolates of N. gonorrhoeae was examined and they were between less than or equal to 0.003 microgram/ml and 0.006 microgram/ml including 8 beta-lactamase producing strains. The CPFX was administered orally to 3 groups of 10 cases with gonococcal urethritis, groups being determined by 3 dose levels: a group with 200 mg b.i.d. for 3 days (a total of 1,200 mg), another with 400 mg b.i.d. (a total of 800 mg) and the final group with single administration of 400 mg. The effect of CPFX in the 1,200 mg-administered group was excellent in 3 and good in 7. The effect of the drug in the 800 mg-administered group was excellent in 2 and good in 8. The effect in the 400 mg-administered group was all good. Therefore, the overall cure rate was 100% including 5 patients with beta-lactamase producing gonococcic infection. Side effects were not observed in the 30 cases.

Administration, Oral↗

Role of intracellular calcium ion in human promyelocytic leukemia HL-60 cell differentiation.

The relationship between calcium ions and the differentiation of human promyelocytic leukemia HL-60 cells was investigated. Proliferation of HL-60 cells incubated in calcium-free medium was inhibited without cell differentiation. On the other hand, incubation with 100 microM verapamil markedly inhibited cell proliferation and caused slight cell differentiation into monocytes. Both calcium-free medium and 100 microM verapamil enhanced HL-60 cell differentiation after treatment with 1 nM 1 alpha,25-dihydroxyvitamin D3, 1 nM beta-all-trans-retinoic acid, or 0.75% dimethyl sulfoxide. However, no enhancement was obtained by treatment with 1 nM 12-O-tetradecanoylphorbol-13-acetate. The free cytosolic calcium concentration was measured by the intracellularly trappable fluorescent calcium indicator, quin 2. The increase of intracellular calcium induced by 250 nM ionomycin was completely blocked by 100 microM verapamil in calcium-free medium, suggesting that the high concentration of verapamil (100 microM) blocks the intracellular calcium mobilization in HL-60 cells. Therefore, the enhancing effect of calcium deprivation or verapamil of HL-60 cell differentiation seemed to be closely related to the inhibition of intracellular calcium mobilization. This speculation is supported by the finding that 50 microM 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, an intracellular calcium antagonist, also enhanced HL-60 cell differentiation induced by 1 alpha,25-dihydroxyvitamin D3, beta-all-trans-retinoic acid, or dimethyl sulfoxide.

Calcitriol↗

[Treatment of atypical leukemia].

Treatment of atypical leukemia is reviewed with emphasis on the establishment of the concept of atypical leukemia and the treatment of this disease is discussed on a historical basis. Furthermore, a recent approach to this disease based on induction of differentiation of leukemia cells by low-dose cytosine arabinoside is discussed.

Aged↗

The distribution and properties of RNA primed initiation sites of DNA synthesis at the replication origin of Escherichia coli chromosome.

RNA-linked DNA molecules were obtained from E. coli dnaCts cells synchronously initiating a new round of chromosome replication. The deoxynucleotides at the transition from primer RNA to DNA were 32P-labeled, and their positions were located on the nucleotide sequence of 1.4 kb genomic region (position -906 to +493) including the oriC and its leftside flanking region. In the r-strand (the counterclockwise strand), many strong transition sites were mapped in the left half portion of the oriC and a few weak sites in the left outside region. In the 1-strand (the clockwise strand), no transition sites were found inside the oriC but many weak sites were found in the left outside region. The results support the initiation mechanism in which the first leading strand synthesis starts with the r-strand counterclockwise from the oriC that is followed by the 1-strand synthesis on the displaced template strand on the left of oriC. Primer RNA molecules attached to the strong r-strand transition sites were only a few residues in length. Properties of the transition sites were discussed.

Base Sequence↗

Alkali-labile structures linked to the 5' ends of Bacillus subtilis short DNA chains.

Alkali-labile portion covalently linked to the 5' ends of Bacillus subtilis short DNA chains, the putative primer RNA for discontinuous DNA synthesis, was isolated and analyzed using a temperature sensitive DNA polymerase I mutant, which accumulates nascent DNA fragments at a restrictive temperature. A novel oligonucleotide structure as well as mono- to triribonucleotide stretches were isolated at the 5' end of the short DNA chains. A structure for the novel oligonucleotide is proposed to be p5' X3' pp5' rN, where X represents unidentified nucleoside with a peculiar property. Possible metabolic relationship between these molecules and primer RNA has been discussed.

Alkaline Phosphatase↗

Evidence that discontinuous DNA replication in Escherichia coli is primed by approximately 10 to 12 residues of RNA starting with a purine.

Intact primer RNA for discontinuous DNA replication of Escherichia coli has been detected by specific labeling in vitro of its 5'-terminal tri- (or di-) phosphate group with vaccinia guanylyltransferase and [alpha-32P]GTP. A mutant defective either in RNase H or in both RNase H and DNA polymerase I accumulated about 10 or 30 times more intact primer RNA, respectively, than wild-type cells. The primers started with purine in an A to G ratio of 5 and the most abundant 5'-terminal dinucleotide sequence was (p)ppA-Pu. The chain length of the intact primer RNA was approximately 10 to 12 nucleotide residues. The structural properties of the E. coli primer RNa resemble those of the eukaryotic primer RNA.

Base Sequence↗