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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 289 records · Page 16Linked to original sources

Inherited primary hypothyroidism with thyrotrophin resistance in Japanese cats.

Mutant cats were developed with non-goitrous primary hypothyroidism. They were clinically characterized by severely retarded growth, mild anaemia and high mortality in the young. They responded markedly to thyroid hormone replacement. Thyroid glands in the mutants were normal in position but slightly reduced in size. Laboratory studies revealed low serum concentrations of thyroxine (T4) and tri-iodothyronine (T3), and increased serum concentrations of TSH. Administration of TRH induced no further increase in TSH. Administration of exogenous TSH after suppression of endogenous TSH by T3 did not increase the serum concentration of T4 in the mutants, in sharp contrast with the threefold increase in serum T4 observed in the normal litter-mates. These findings suggest that the underlying pathogenesis of this disorder is unresponsive to TSH. Moreover, we found that the mutants were transmitted in an autosomal recessive manner.

Animals↗

Multilineage antigen expression and possible autocrine secretion of an interleukin 1 by Ph1-positive leukemic cell line KOPM-28.

A newly established Ph1-positive cell line, KOPM-28 was analyzed for immunological phenotype and the release of biological substance. The surface marker analysis revealed myelomonocytoid antigens, erythroid antigens and megakaryocyte-platelet antigens. Also, the cells could be induced for hemoglobin synthesis by the addition of hemin. The conditioned medium of this cell line showed the presence of interleukin 1 (IL-1) activity but not interleukin 2. Exogenous IL-1 and the conditioned medium stimulated the DNA synthesis of the cells themselves. Consequently, the yield substance works on the growth of original cells as an autocrine fashion, and might act on other normal cells as a paracrine factor.

Antigens, Neoplasm↗

Helvecardins A and B, novel glycopeptide antibiotics. I. Taxonomy, fermentation, isolation and physico-chemical properties.

A strain of actinomycetes identified as Pseudonocardia compacta subsp. helvetica produced new glycopeptide antibiotics, helvecardins A and B. They were isolated from culture broth mainly by affinity chromatography of D-alanyl-D-alanine and preparative HPLC. The physico-chemical properties of helvecardins A and B showed that they resemble each other. Though helvecardin A was structurally related to beta-avoparcin, it clearly differed in the presence of an O-methyl moiety in its NMR spectrum.

Aminoglycosides↗

Hydantocidin: a new compound with herbicidal activity from Streptomyces hygroscopicus.

Hydantocidin, a new compound with potent non-selective herbicidal activity, was found in a submerged culture of Streptomyces hygroscopicus SANK 63584. It was isolated from the culture filtrate by the following successive treatments comprised of activated carbon, Diaion HP-20, Dowex 50WX4, and Avicel column chromatographies. Finally it was crystallized as colorless needles from acetone. The molecular formula, C7H10N2O6, was determined by analyses of HRFAB mass spectrum in conjunction with 13C NMR spectrometry. The structural elucidation revealed that it has a unique structure with a spiro-bond between ribose and hydantoin moieties in the molecule. The characteristic herbicidal activities against annuals as well as perennials, including monocotyledonous and dicotyledonous weeds, were observed.

Animals↗

[A case report of neurinoma originating from the recurrent nerve].

A 55-year-old man was admitted to hospital because of an abnormal shadow on his chest X-ray film. On examination, the patient appeared healthy. CT scan, magnetic resonance imaging, and ultrasonography showed evidence of a tumor. At operation, a tumor was found originating from the left recurrent nerve, and it was removed together with the vagus nerve. The patient had a favorable postoperative course except for hoarseness, and was discharged on the 31st postoperative day. Mediastinal neurinoma originating from the recurrent nerve is rare, and only 20 cases have been reported in Japan.

Cranial Nerve Neoplasms↗

Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.

The treatment of HL-60 myelocytic leukemia cells with 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in the activation of a neutral sphingomyelinase and in sphingomyelin turnover (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). In this paper, the effects of 1,25-(OH)2D3 on the product of sphingomyelin hydrolysis, ceramide, and the possible function of ceramide as a lipid mediator of the effects of 1,25-(OH)2D3 on HL-60 cell differentiation were investigated. Treatment of HL-60 cells with 1,25-(OH)2D3 resulted in a time- and dose-dependent increase in ceramide mass levels. Ceramide levels peaked at 2 h following treatment of HL-60 cells with 100 nM 1,25-(OH)2D3 with an increase of 41% over base line. The mass of generated ceramide (13 +/- 2 pmol/nmol of phospholipid) agreed with the mass of hydrolyzed sphingomyelin (17 +/- 4 pmol/nmol of phospholipid). Cell-permeable ceramides with shorter N-acyl chains induced HL-60 cell differentiation at subthreshold concentrations of 1,25-(OH)2D3. Higher concentrations of cell-permeable ceramides potently induced HL-60 cell differentiation independent of 1,25-(OH)2D3. A 2-h exposure of HL-60 cells to N-acetyl-sphingosine was sufficient to cause differentiation. Morphologically, N-acetylsphingosine caused a similar monocytic differentiation of HL-60 cells as did 1,25-(OH)2D3. Exogenous ceramide was further metabolized to sphingomyelin and other sphingolipids, but no conversion to sphingosine was detected. Moreover, sphingosine and its analogs failed to affect monocytic differentiation of HL-60 cells in response to subthreshold 1,25-(OH)2D3, indicating that the effect of ceramide was independent of sphingosine generation. These studies demonstrate that ceramide is a lipid mediator that may transduce the action of 1,25-(OH)2D3 on HL-60 cell differentiation.

Calcitriol↗

Isolation and characterization of the two distinct genes for human glutamate dehydrogenase.

Two genomic clones containing a part of the glutamate dehydrogenase gene were isolated from a human genomic library. The restriction map of both clones were distinctly different from one another, although the nucleotide sequences of the three exons that they contained were virtually the same in each clone. Southern blotting analysis of the genomic DNAs from several unrelated human individuals revealed that in every case the probe hybridized with at least two DNA fragments of different sizes, each characteristic to one of the two clones. These results strongly suggest that the two clones presently obtained do not result from polymorphism but are generated from two different gene loci for glutamate dehydrogenase on the human chromosome.

Amino Acid Sequence↗

Structural organization of the rat cytochrome c oxidase subunit IV gene.

We have isolated two overlapping clones covering the entire length of the gene of nuclear-encoded sub-unit IV of cytochrome c oxidase (COXIV) from a rat genomic library in Charon 4A and determined the structural organization of the gene. The gene spans approximately 7.0 kilobases and contains five exons interrupted by four introns. Of these exons, exon 2 codes for a whole length of the presequence of the rat COXIV precursor protein, while exons 3 to 5 encode three distinct structural domains of the mature protein. The 5'-flanking region of the gene lacks conventional TATA and CAAT boxes, but has a high G + C content and contains two putative binding sites for transcription factor SP1 and a sequence resembling the AP-4 responsive element. These results indicate that the promoter region of the rat COXIV gene possesses characteristic features common in housekeeping genes. The chloramphenicol acetyltransferase assay performed by constructing an improved phagemid, pBlueCAT3, revealed that a 773-base pair DNA fragment immediately preceding the cap site has a strong promoter activity. An octanucleotide sequence, -TTCTTGGT-, which is very close to the yeast HAP2/HAP3 responsive element, is located in the 5'-upstream region of the present gene.

Amino Acid Sequence↗

Transcriptional regulation of protein kinase C by 1,25-dihydroxyvitamin D3 in HL-60 cells.

Vitamin D3 treatment of the human promyelocytic cell line, HL-60, is accompanied by an increase in phorbol ester receptor number (Martell, R. E., Simpson, R. U., and Taylor, J. M. (1987) J. Biol. Chem. 262, 5570-5575). In this study, the mechanism and significance of vitamin D3-induced changes in protein kinase C levels were investigated. Treatment of HL-60 cells with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) resulted in a 2-3-fold increase in phorbol dibutyrate binding at 24 h. This was accompanied by a 4.2-fold increase in steady state mRNA levels for the beta isoenzyme of protein kinase C and by a 3.8-fold increase in its transcriptional rate as determined from nuclear run-off studies. Protein kinase C alpha mRNA, which was approximately 15% of the beta isoenzyme levels, showed similar increases in mRNA and transcriptional rates in response to 1,25-(OH)2D3. Protein kinase C gamma mRNA was not detected. The increases in protein kinase C levels were accompanied by increases in activation of the enzyme by phorbol esters. More importantly, 1,25-(OH)2D3 caused a 1.5-2.0-fold increase in the endogenous phosphorylation of protein kinase C substrates independent of exogenous activators or endogenous formation of diacylglycerol. This is the first report of transcriptional activation of protein kinase C. This mechanism of up-regulation of protein kinase C may explain the increased activity of protein kinase C in vitamin D3-treated HL-60 cells, and may constitute an important mechanism for the long term modulation of the protein kinase C pathway of cell regulation independent of diacylglycerol generation.

Caenorhabditis elegans Proteins↗

Purification and characterization of NADPH-dependent methemoglobin reductase from the nucleated erythrocytes of bullfrog, Rana catesbeiana.

Two protein components having a NADPH-dependent methemoglobin reductase activity were purified to electrophoretic homogeneity from the erythrocytes of the bullfrog, Rana catesbeiana. Their molecular properties were investigated. The components were separated by isoelectric focusing, having discrete bands of pI 5.0 and 7.5, respectively. The pI 5.0 component, designated F-5.0, was faint yellow, with a broad absorption in the range of 400-450 nm, while the pI 7.5 component, designated F-7.5, was colorless and did not absorb in that range. The molecular weight was estimated to be 22,000 for both components by gel filtration and SDS-PAGE. When F-5.0 was subjected to isoelectric focusing repeatedly, the protein part of that component gradually moved to and refocused at pH 7.5, leaving a yellow color at acidic pH. Both F-5.0 and F-7.5 were highly specific for NADPH and had the same kinetic properties in catalyzing the reduction of MB, DCPIP, FMN, or FAD, and that of methemoglobin or cytochrome c in the presence of a certain dye. They were also indistinguishable from one another in their amino acid compositions and were completely identical in the N-terminal sequence of 24 amino acid residues. These findings strongly suggest that the two components can be attributed to the same enzyme molecule, carrying an identical protein moiety but interacting differently with some unidentified biological pigments, and that they are equivalent in their molecular and kinetic properties to the NADPH-dependent enzyme(s) occurring in human erythrocytes.

Amino Acid Sequence↗

[Detection of African type penicillinase-producing Neisseria gonorrhoeae in Japan].

The Plasmid DNA patterns of 22 penicillinase-producing Neisseria gonorrhoeae (PPNG) strains isolated from male patients with gonococcal urethritis in 1988 at Tokyo Metropolitan Taito Hospital were determined. The 3.3 megadalton plasmid, the so called the African type plasmid, was present in 3 isolates out of 22 PPNGs, all of which occurred with a conjugative 24.5 megadalton plasmid. 4.4 megadalton plasmid was present in 19 isolates out of 22 PPNGs, 5 of which occurred with a conjugative 24.5 megadalton plasmid. The infective sources of the 3 cases of the African type PPNGs were found as 1 from philippines and 2 from prostitutes, so called Soap Land Girl in Japan. And they suggests that the African type PPNGs are already common in Japan.

Adult↗

Percutaneous treatments for biliary diseases.

Percutaneous treatment of biliary disease was administered in 173 cases, mainly among high-risk or elderly patients. Diagnosis was acute cholecystitis in 32 cases, acute cholangitis in 16, hepatic abscess in five, gallbladder stones in 28, common bile duct stones in 11, intrahepatic stones in five, malignant obstructive jaundice in 61, and benign biliary stenosis in 15. The treatment was successful in 158 of 173 cases (91.3%). Complications were encountered in 17 (9.8%). Most of these occurred during the initial period and were mild and controllable with conservative treatments. There were two deaths (1.2% of patients); one was not related to the procedure. These data suggest that percutaneous treatments are safe and effective even among elderly or high-risk patients with biliary diseases.

Adult↗

Studies on the biosynthesis of corrinoids and porphyrinoids. II. The origin of nitrogen of vitamin B12.

To clarify the origin of nitrogen of vitamin B12, 15N-labeled aminolevulinic acid (ALA) was prepared and administered to Propionibacterium shermanii. Vitamin B12 thus isolated showed four signals in the nitrogen-15 nuclear magnetic resonance (15N-NMR) spectrum. The nitrogen of [5-15N]riboflavine was incorporated into the benzimidazole part of vitamin B12. Hydroxycobalamin was transformed into cyanocobalamin by treatment with [15N]potassium cyanide, and the 15N-NMR spectrum was measured. The results of these experiments revealed the origin of the nitrogen atoms of vitamin B12, and allowed the 15N-NMR signals to be assigned.

Chemical Phenomena↗