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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 343 records · Page 19Linked to original sources

Cloning of the p53-dependent origin of cellular DNA replication.

We have recently reported that the c-myc protein may promote cellular DNA replication by binding to the origin of DNA replication (ori) and that an origin of human DNA replication which can autonomously replicate in human cells was cloned as a binding sequence of c-myc protein (Iguchi-Ariga et al., 1987). Here we report that cellular tumor antigen p53 may also participate in cellular DNA replication and another origin of DNA replication was cloned as a possible p53-binding sequence. The sequence could autonomously replicate in Raji cells which express p53 at a high level but not in HL-60 cells in which the coding gene for p53 is largely deleted. Little homology of the sequences was found between c-myc protein-binding ori and p53-binding ori. This suggests that c-myc protein and p53 may independently recognize different ori in chromosomal DNA.

Animals↗

[Efficacy of ofloxacin in sexually transmitted male urethritis and cervicitis].

Efficacy and safety of ofloxacin (OFLX), a new quinolone antibacterial agent, were investigated in cases of sexually transmitted male urethritis and cervicitis. Chlamydial infections occupied a large part of the patients enrolled. This study was conducted in 29 institutions. A total of 1,126 patients with gonococcal, chlamydial or non-gonococcal non-chlamydial infections were enrolled in the study. The general dosing regimen of oral OFLX was 100 mg t.i.d. or 200 mg t.i.d. for 14 consecutive days. Along with the clinical efficacy evaluated by doctors in charge, therapeutic and clinical efficacies were determined according to standardized evaluation criteria. The evaluation of therapeutic efficacy was based on bacterial eradication. On the other hand, clinical efficacy was determined upon the improvement in causative bacteria, WBC counts in smear (or initial urine) specimens and urethra/cervical discharges. Clinical efficacy was determined on 7 and 14 days after starting the medication, except for gonococcal infections for which the efficacy was determined on Day 3 and Day 7. The results obtained are summarized as follows. 1. Efficacy evaluation by standardized criteria Therapeutic efficacy rates in gonococcal infections were 97.9% (93/95) on Day 3 and 100% (119/119) on Day 7. In chlamydial infections, the rates were 77.7% (363/467) on Day 7 and 93.6% (392/419) on Day 14. Chlamydial urethritis rated 94.8% (239/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in gonococcal infections were 63.2% (60/95) on Day 3 and 95.8% (114/119) on Day 7. In chlamydial infections, they were 70.0% (327/467) on Day 7 and 89.7% (376/419) on Day 14. Chlamydial urethritis rated 88.5% (223/252) and cervicitis 91.6% (153/167) on Day 14. Clinical efficacy rates in non-gonococcal non-chlamydial infections were 93.3% (97/104) for male urethritis and 65.9% (27/41) for cervicitis on Day 14. 2. Clinical efficacy determined by doctors in charge A total of 1,028 cases, 752 urethritis and 276 cervicitis cases, was evaluated by doctors in charge. Clinical efficacy rates were 90.3% for urethritis and 92.4% for cervicitis. 3. Safety Safety evaluations was conducted in 1,087 patients. Side effects were observed in 23 patients among them (2.12%). None of them were deemed serious. General laboratory examinations were conducted for 169 patients. Abnormal findings were seen in 11 patients (6.51%) or 13 cases, all of which were minor. The results of this multi-center clinical trial demonstrated that OFLX is effective and well tolerated in the treatment of sexually transmitted disease (STD), both gonococcal and chlamydial infections.

Adult↗

[Allergic granulomatous angiitis with subarachnoid hemorrhage--a case report].

A case of allergic granulomatous angiitis showing various symptoms of the central nervous system is reported. A 29-year-old female was admitted to our hospital because of severe headache and urinary incontinence. Consciousness was drowsy, and right IIIrd cranial nerve palsy was observed. CT scan revealed subarachnoid hemorrhage, hydrocephalus and arachnoid cyst. Since no aneurysm or arteriovenous malformation was detected by angiography, continuous ventricular drainage was performed. Marked hypertension due to renal vascular origin was suggested by means of laboratory data about serum renin etc., so renal as well as cerebral angiography was carried out by Seldinger's method. There revealed aneurysms of the left renal artery and a branch of the left anterior cerebral artery. Then, ventriculo-peritoneal shunt and resection of left frontal aneurysm were done. Microscopic finding of the excised aneurysm was necrotizing angiitis with infiltration of eosinophil. Six days after the operation, CT scan showed asymptomatic subcortical hematoma at the right occipital lobe. The patient was in good condition and had no cerebral or other complication following steroid therapy. The present case was considered as a very rare one because no case with subarachnoid hemorrhage and cerebral aneurysm due to allergic granulomatous angiitis was reported in the previous literature.

Adult↗

Molecular cloning and sequence analysis of two rat major globin cDNAs.

Two cDNA clones for globins of the adult Wistar rat were isolated from a reticulocyte cDNA library and the nucleotide sequences of the inserts were determined. One clone contained a cDNA insert consisting of 556 bp and the other contained one of 577 bp, both covering the entire coding sequences for rat globins. Comparisons of their predicted amino acid sequences with known sequences of rat globins revealed that these cDNAs coded for a rat major alpha- and a major beta-globin, I alpha and II beta, respectively. The cause of diversity of rat globins was discussed in terms of the nucleotide sequences of cDNAs and known amino acid sequences of globins.

Amino Acid Sequence↗

Purification and properties of the manganese superoxide dismutase from the liver of bullfrog, Rana catesbeiana.

A manganese superoxide dismutase (Mn-SOD) from the liver of bullfrog, Rana catesbeiana, was purified to electrophoretic homogeneity. The enzyme has a molecular weight of about 84,000 and is composed of four identical subunits, each containing one manganese atom. The amino acid composition of the enzyme is similar to that of Mn-SODs isolated from human and chicken livers, but differs considerably from that of the Escherichia coli enzyme (D. Barra et al. (1984) J. Biol. Chem. 259, 12595-12601; R. A. Weisiger and I. Fridovich (1973) J. Biol. Chem. 248, 3582-3592; H. M. Steinman (1978) J. Biol. Chem. 253, 8708-8720). The N-terminal amino acid is lysine. The sequence of 23 amino acid residues in the N-terminal region was determined. It shows excellent homologies with those of the human and chicken enzymes (H. M. Steinmam and R. L. Hill (1973) Proc. Natl. Acad. Sci. USA 70, 3725-3729; C. Ditlow et al. (1982) Carlsberg Res. Commun. 47, 81-91). The frog liver enzyme is also located exclusively in the mitochondrial matrix. Immunologically the same enzyme is also found in the tadpole liver, in an amount of about one-half of that in the adult bullfrog.

Amino Acid Sequence↗

Magnesium deprivation inhibits the expression of differentiation-related phenotypes in human promyelocytic leukemia HL-60 cells.

The role of magnesium ions in the differentiation of human promyelocytic leukemia HL-60 cells was investigated. When HL-60 extracellular magnesium was deficient (less than 0.01 mM), the total intracellular magnesium content and [3H] leucine incorporation rates decreased to 61 and 28%, respectively, on day 3. When the cells were treated with various inducers (100 nM 1 alpha, 25 dihydroxyitamine D3 (1,25(OH)2D3), 100 nM beta-all-trans retinoic acid (RA), 20 nM 12-o-tetradecanoyl phorbol-13-acetate (TPA), 1.25% dimethylsulfoxide (DMSO) and 30 nM aclacinomycin (AcM] in magnesium-deficient medium, the expression of differentiation-related phenotypes (nitroblue tetrazolium (NBT) reducing ability, nonspecific esterase (NSE) activity and monoclonal antibody, OKM1 binding activity) was almost completely inhibited. After a 2-day treatment with 100 nM 1,25(OH)2D3 in magnesium-deficient medium, the expression of differentiation-related phenotypes was restored by further incubation in the absence of inducer in standard magnesium medium (0.4 mM). These results suggested that magnesium deprivation inhibited the expression of HL-60 differentiation-related phenotypes but not their commitment to differentiation. These phenotypes were expressed without inducer in standard magnesium medium after a 2-day simultaneous treatment with 1,25(OH)2D3 and cyclohexamide (protein synthesis inhibitor) in magnesium-deficient medium, but not after simultaneous pretreatment with 1,25(OH)2D3 and alpha-amanitin (RNA synthesis inhibitor). Thus, it was suggested that the magnesium-requiring step in HL-60 cell differentiation is in protein but not mRNA synthesis. This conclusion is supported by the findings that changes in c-myc and c-fms mRNA levels in HL-60 cells treated with 100 nM 1,25(OH)2D3 in magnesium-deficient medium and those in standard magnesium medium were the same. In addition, dibutyryl cyclic adenosine monophosphate (dbc AMP) could restore expression of differentiation-related phenotypes inhibited by magnesium deprivation but not those inhibited by cyclohexamide, even though magnesium deprivation inhibited protein synthesis as much as did cyclohexamide. This suggests that magnesium-requiring step in HL-60 cell differentiation is different from that inhibited by cyclohexamide.

Aclarubicin↗

Relative roles of T7 RNA polymerase and gene 4 primase for the initiation of T7 phage DNA replication in vivo.

Initiation sites of T7 phage DNA replication in the presence and absence of T7 phage gene 4 primase have been analyzed by using Escherichia coli cells infected with T7 phage amber mutants, T73,6 and T73,4,6, respectively. Restriction analysis of the [3H]thymidine-labeled DNA, synthesized by the T73,4,6 phage-infected cells in the presence of 2',3'-dideoxy-3'-azidothymidine, has shown that only the light (L) strand of T7 DNA has been synthesized from the primary origin area to the right. Transition sites from RNA to DNA have been located precisely in the primary origin region of the T7 phage genome. In the gene 4- condition, greater than 20 transition sites have been detected only in the L strand. They scattered widely downstream from the phi 1.1 promoters and mostly downstream from the phi 1.3 promoter. The same transition sites have been detected in the gene 4+ condition, suggesting that the transcripts started from these promoters are used as primers of the rightward L-strand DNA synthesis in the gene 4+ condition. In addition, many heavy (H)- and L-strand transition sites have been detected at gene 4 primase sites in the gene 4+ condition. The relative roles of T7 phage RNA polymerase and primase at the primary origin have been discussed.

Base Sequence↗

Variation among mouse ribosomal RNA genes within and between chromosomes.

We compared nucleotide sequences of the transcription-initiation region of five mouse ribosomal DNA (rDNA) clones. Two clones were isolated from Japanese wild mice, Mus musculus molossinus, and the other three from BALB/c mice originating in M. m. domesticus. Two BALB/c clones that are derived from the same chromosome are very similar, suggesting the occurrence of intrachromosomal homogenization of rDNA repeats. However, the other clone of BALB/c was approximately as different from the former two clones as from the rDNA clones of M. m. molossinus. These results suggest that, compared with intrachromosomal homogenization, homogenization among rDNA repeats on nonhomologous chromosomes occurs relatively infrequently after the mouse subspecies separation.

Animals↗

A possible relationship between cord blood transferrin and birth length in infants.

Cord blood levels of transferrin (Tf) and insulin-like growth factor I (IGF-1) were measured in 33 normal and 12 preterm infants. Tf was measured by the single radial immunodiffusion technique, while IGF-1 was measured by specific RIA. Tf levels in normal term infants (195 +/- 27 mg/dl) were significantly below normal adult levels (261 +/- 12 mg/dl). Tf levels in preterm infants (159 +/- 30 mg/dl) were lower than those in normal term infants. Tf levels showed a positive correlation with birth length, weight, gestational age and albumin levels in all infants. There was no correlation between Tf and IGF-1 levels in term and preterm infants.

Birth Weight↗

Effects of ingested 4000ppm aluminum on the essential metals, especially zinc, in intact and ethanol treated mice.

The effects of ingested Al on the essential metals were investigated using mice. Animals were divided into 4 groups: 1) Control, 2) Al, 3) EtOH and 4) Al+EtOH groups. Powdered commercial food, containing 1.26% P, 1.36% Ca, 70ppm Zn, 15ppm Cu, 200ppm Fe and 3.1ppm Al, was used to prepare the diets. For Al-treated groups, Al(AlCl3) was added to powdered food at a concentration of 4000ppm. The co-existing effect of EtOH which is known to affect the essential metals, was also investigated as a possible modulater of Al toxicity at a concentration of 5% for 22 days, followed by 10% for 36 days in the drinking water. After 58 days feeding with food containing Al and / or EtOH containing water, the Al effects on serum and femur P and Ca were found to be slight except for a significant decrease of serum P concentration in the Al+EtOH group. In this group, femur weight was less and femur Al concentration was more compared with the Al group. The effects on Fe and Cu were little. We observed a significant decrease of serum Zn concentration with 4000ppm Al diet in both the Al-treated groups. The fact that serum ALPase activity, a Zn enzyme, increased in disregard of a significant decrease of serum Zn concentration suggested the enzyme release from injures tissues. It is noticeable that a significant decrease of serum Zn concentration was observed when dietary Zn was sufficient. It is reported that the dietary intake of Zn is under the recommended allowance for many people. Since Al compounds are widely used as drugs, food additives and a conditioned latent Zn deficiency is rather common in human diseases, the effects of Al on the Zn metabolism are to be investigated further.

Aluminum↗

Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. I. Taxonomy of producing organism.

Strain SANK 60983, an actinomycete isolated from a soil sample, was found to produce the new glycopeptide antibiotics, chloropolysporins A, B and C. Short chains of spores occur in the both aerial and substrate hyphae. meso-Diaminopimelic acid is present in the cell wall and galactose and arabinose in the whole-cell hydrolysate. Mycolic acid is absent. On the basis of the morphological, cultural and physiological characteristics, this strain was determined to be a new species of Faenia designated Faenia interjecta sp. nov. The type strain of F. interjecta Okazaki and Enokita is SANK 60983.

Anti-Bacterial Agents↗

[Bacteriological and clinical evaluation of norfloxacin in male gonorrheal urethritis].

Thirty male patients with gonorrheal urethritis were treated with norfloxacin (NFLX) at our urological ward between May and July, 1984, and clinically evaluated. Thirty-nine strains of Neisseria gonorrhoeae isolated from the clinical specimens of these patients were bacteriologically studied. Of the 39 strains, 3 (7.7%) were PPNG strains and the other 36 strains were non-PPNG strains. The minimum inhibitory concentration (MIC) of penicillin G, PCG to the 3 PPNG strains was 6.25-25 micrograms/ml and that to the 36 non-PPNG strains was 0.05-3.13 micrograms/ml. The MIC of NFLX to the PPNG strains was 0.025-0.1 microgram/ml and that to the non-PPNG strains was less than or equal to 0.0125-0.2 microgram/ml. The patients with gonorrheal urethritis were given NFLX orally for 3 days at a daily dose of 600 mg. The clinical efficacy rate was 100%: excellent in 12 and good in 18 cases. All 3 patients with gonorrheal urethritis caused by PPNGs were cured. No subjective side effects were found.

Adolescent↗