Biomedical subjects
Publications and source records attributed to Y Mizukami.
The nucleotide sequence of Bacillus phage Nf gene F has been determined. The deduced amino acid sequence of gpF is very similar to that of gp4, the transcriptional activator of phage phi 29. Both proteins contain the consensus structure that is conserved for the DNA-protein interacting domain of DNA-binding proteins such as the repressor, Cro and CII proteins of phage lambda.
Immunohistochemical and electron microscopic examinations were made of a carcinosarcoma of the esophagus in an 80-year-old man. An immunohistochemical examination showed that sarcomatous spindle cells were vimentin-positive, whereas squamous carcinoma cells were keratin-positive. No coexistence of vimentin and keratin in a single tumor cell was found. Electron microscopically, the sarcomatous spindle cells were characterized by well-developed rough endoplasmic reticulum, abundant intermediate filaments, and the occasional presence of peripheral aggregates of microfilaments. No definite desmosomes were identified among these cells. These results appear to indicate that most of the spindle-shaped tumor cells assume fibroblastic cellular features and synthesize the intermediate filament protein usually expressed in mesenchymal cells, even though such tumor cells could be epithelial in origin.
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The bioavailability and pharmacokinetics of theophylline after a single intravenous administration of theophylline and multiple oral administration of a sustained-release theophylline tablet formation were studied in dogs. In addition, the pharmacokinetics of theophylline after multiple oral doses of the drug was also studied in asthmatic patients. In the intravenous administration of theophylline (5 mg/kg) to dogs, the theophylline half-life was 4.0 +/- 0.2 h. The apparent volume of distribution (Vd) and plasma theophylline clearance (CL) were 0.734 +/- 0.019 l/kg and 126.7 +/- 3.4 ml/kg/h, respectively. In the multiple oral doses of the drug in amounts ranging from 7.52 to 9.09 mg/kg, the Vd and CL were 0.765 +/- 0.021 l/kg and 111.0 +/- 2.4 ml/kg/h, respectively. The mean oral absorption rate constant (ka) was calculated to be 0.355 +/- 0.035 h-1 and the mean elimination rate constant (kel) was 0.146 +/- 0.007 h-1. The absolute bioavailability of the drug calculated by a computer fitting method was 1.08 +/- 0.07. The result suggests that the drug has complete absorption. On the other hand, the pharmacokinetic parameters in the asthmatic patients were 0.337 +/- 0.055 l/kg for the Vd, 32.55 +/- 3.48 ml/kg/h for the CL, 0.222 +/- 0.058 h-1 for the ka and 0.105 +/- 0.016 h-1 for the kel, respectively. This study indicated that the dog may be useful to predict bioavailability of a sustained-release theophylline tablet formulation in humans. However, it showed that there are differences between dogs and humans in the pharmacokinetic parameters.
The gene structure of cytochrome P-450b, a major form of phenobarbital-inducible cytochrome P-450 in rat livers was elucidated by sequence analysis of the cloned genomic DNAs and was compared with the previously determined gene structures of cytochrome P-450e, a minor form of phenobarbital-inducible cytochrome P-450 and two forms of 3-methylcholanthrene-inducible cytochrome P-450 (P-450c and -d). The gene for cytochrome P-450b is 23 kilobase pairs (kb) long and is separated into 9 exons by 8 intervening sequences. This gene structure is very similar to that of cytochrome P-450e except for the first intron, the first intron being much longer in cytochrome P-450b gene (approximately 12 kb) than in cytochrome P-450e gene (3.2 kb), but differs greatly from the gene structures of two 3-methylcholanthrene-inducible cytochrome P-450s as pointed out previously (Sogawa, K., Gotoh, O., Kawajiri, K. & Fujii-Kuriyama, Y. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5066-5070). The nucleotide sequences in all 9 exons and their flanking regions in introns show very close homology between the two phenobarbital-inducible cytochrome P-450 genes. Forty base substitutions are found in approximately 1900 nucleotides of all exonic sequences, and 15 of them result in 14 amino acid replacements. These base substitutions occur in relatively limited regions of the gene sequences. Most of them are found in exons 6, 7, 8, and 9, most frequently in exon 7 as described previously (Mizukami, Y., Sogawa, K., Suwa, Y., Muramatsu, M. & Fujii-Kuriyama, Y. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3958-3962). The close sequence homology between the two phenobarbital-inducible cytochrome P-450 genes is also found to extend to the promoter region with one notable exception. The simple repeated sequences of (CA)n which is present at -254 position in cytochrome P-450e gene is also observed at the equivalent position in cytochrome P-450b gene, but the repetitiveness is greatly reduced in cytochrome P-450b gene ((CA)5 for P-450b versus (CA)19 for P-450e), and this may somehow be related to the difference in the level of cytochrome P-450b and P-450e in the inductive phase of phenobarbital administration.
The distribution of endogenous peroxidase and hydrogen-peroxide-producing NAD(P)H-oxidase, which are essential enzymes for the iodination of thyroglobulin, was cytochemically determined in the thyroid follicular cells of propylthiouracil (PTU)-treated rats. Peroxidase activity was determined using the diaminobenzidine technique. The presence of NAD(P)H-oxidase was determined using H2O2 generated by the enzyme; the reaction requires NAD(P)H as a substrate and cerous ions for the formation of an electron-dense precipitate. Peroxidase activity was found in the developed rough endoplasmic reticulum (rER) and Golgi apparatus, but it was also associated with the apical plasma membrane; NAD(P)H-oxidase activity was localized on the apical plasma membrane. The presence of both enzymes on the apical plasma membrane implies that the iodination of thyroglobulin occurs at the apical surface of the follicular cell in the TSH-stimulated state which follows PTU treatment.
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An extremely rare mucoepidermoid carcinoma of the thyroid gland was found in a 44-year-old woman. By light microscopic examination, the tumor consisted of mucous cells and squamoid cells, and was similar to that occurring in any other organs. By electron microscopic examination, the mucous cells displayed prominent mucous droplets, and showed no evidence of colloid production in their cytoplasms. Abundant tonofilaments in aggregates were observed in the squamoid cells. Biochemically, thyroxine (T4) and triiodothyronine (T3) were not detectable in the tissue of this tumor. These findings indicate that this mucoepidermoid carcinoma does not retain the functional properties of thyroid follicular cells; namely, no evidence was found to substantiate a follicular epithelial origin of this tumor.
A multicopy plasmid, 2.1 kb in size, was isolated from Shigella sonnei and named pKYM. This plasmid is cryptic and isolated along with pKY-1, a ColE1-like plasmid. In this paper, we report the physical map of pKYM and some characters required for its multiplication. The replication of the plasmid DNA does not require DNA polymerase I but depends on protein(s) produced by itself. The plasmid is poorly mobilized by the F factor.
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