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Biomedical subjects

N Okada

Publications and source records attributed to N Okada.

At least 559 records · Page 31Linked to original sources

Detection of unique tRNA species in tumor tissues by Escherichia coli guanine insertion enzyme.

The guanine insertion enzyme from Escherichia coli catalyzes exchange of guanine located at the first position of the anticodon of tRNA with radioactive guanine (N. Okada and S. Nishimura, unpublished data). tRNA isolated from various tumors, including slowly growing Morris hepatoma 7794A, incorporated considerable guanine with E. coli guanine insertion enzyme, whereas tRNA isolated from all normal tissues so far tested, except regenerating rat liver, incorporated scarcely any. In the rat ascites hepatoma AH7974, the guanine was mostly incorporated into minor isoaccepting species of tRNAAsp that contained the guanine residue instead of Q base in the first position of the anticodon. This is a sensitive and easy method for identifying unique tRNA species in tumor tissues.

Animals↗

Structure determination of a nucleoside Q precursor isolated from E. coli tRNA: 7-(aminomethyl)-7-deazaguanosine.

A precursor of modified nucleoside Q isolated from E. coli methyl-deficient tRNA was determined to be 7-(aminomethyl)-7-deazaguanosine. The structure was deduced by means of its chromatographic and electrophoretic mobilities, and UV and mass spectra, in addition to comparison with the synthesized authentic compound. The same molecule is also found in tRNA of an E. coli mutant selected for deficient synthesis of modified nucleosides.

Chromatography, Thin Layer↗

Bactericidal activity of cephalosporins in an in vitro model simulating serum levels.

The bactericidal activity of cefazolin, cephaloridine, and cephalothin in a simulated intramuscular study (500 mg) and a simulated intravenous drip infusion study (2 g/2 h) is reported. In both model systems, the bactericidal activity of cefazolin surpassed that of cephalothin, and there were certain differences between cefazolin and cephaloridine in the simulated intramuscular study when human serum was used as a medium. In a routine reference static system, the drug levels were constant at the simulated peak level of each cephalosporin by both routes. In this system the three cephalosporins were equal in activity. In a third experiment, the effect of drug concentrations and exposure time on bactericidal activity of the cephalosporins was studied. The bactericidal activity of cephaloridine was the strongest of the three drugs when exposure time was 2 h and drug concentration was less than four times the minimal inhibitory concentration. At concentrations above four times the minimum inhibitory concentration, all three cephalosporins were equal in activity when the exposure time was 2 h.

Bacteria↗

Surveillance and follow-up of patients with implanted cardiac pacemaker by telephone transmission.

A follow-up study on pacemaker function in 15 patients with implanted cardiac pacemaker has been performed by telephone transmission. The transmitting set consisting of electrocardiograph, pacemaker pulse modulator and acoustic coupler was manipulated by the patients themselves. ECG, pacemaker pulse, and pulse rate were simultaneously transmitted through 1 channel to the receiver in our clinic. Of 56 patients with pacemaker, 15 patients were surveyed by telephone transmission. In these patients battery exhaustion was detected in 3, competition in 2, and lead fracture in 1. The fact that surveillance and follow-up of the patients with implanted cardiac pacemaker could be carried out by telephone transmission as well as by clinic visitation tells us that the telephone transmission is a useful method and plays an important role in a pacemaker clinic. Moreover our study established its further usefulness in the patient's preference due to difficulties in travelling to the pacemaker clinic and in reducing patient's anxiety.

Adolescent↗

Detection of nucleoside Q precursor in methyl-deficient E.coli tRNA.

32P-Labeled tRNAAsn was isolated from methyl-deficient E. coli tRNA. Nucleotide sequence analysis showed that tRNAAsn contains three derivatives of the Q nucleoside, possibly Q precursors, in addition to guanosine in the first position of the anticodon. One of the Q precursors was isolated on a large scale. Its UV spectra were identical with those of normal Q, indicating that 7-deazaguanosine structure having a side chain at position C-7 is complete in the Q precursor. No radioactivity was incorporated into Q or Q precursors from either [methyl-14C]methionine, [1-14C]methionine or [U-14C]methionine, showing that methionine was not directly involved in the formation of Q.

Asparagine↗

Isolation of mammalian tRNAAsp and tRNATyr by lectin-Sepharose affinity column chromatography.

tRNAAsp from rabbit liver, rat liver and rat ascites hepatoma was readily isolated by concanavalin A-Sepharose (Con A-Sepharose) affinity column chromatography. tRNATyr from these sources was extensively purified by Ricinus communis lectin-Sepharose column chromatography. These results, together with the chromatographic behaviour of four tRNAs (tRNATyr, tRNAHis, tRNAAsn and tRNAAsp) on acetylated DBAE-cellulose column chromatography suggested that tRNAAsp contains a Q nucleoside species having a mannose moiety while tRNATyr contains Q nucleoside with galactose. The sugars attached in 4-position of cyclopentene diol in the Q molecule are therefore not present at random in the four tRNAs, but present only in each specific tRNA. This is the first case which shows that plant agglutinin interacts with nucleic Acid as well as polysaccharide and glycoproteins.

Animals↗

Enzymatic synthesis of Q nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver.

The Q nucleosides isolated from rabbit liver tRNA are known to have sugars (mannose or galactose) linked to their cyclopentene diol moiety. A Q nucleoside containing mannose (manQ) was synthesized by a cell-free system from rat liver, using purified E. coli tRNAAsp as an acceptor and GDP-mannose as a donor molecule. The novel mannosyltransferase catalyzing this reaction was purified from a particulate-free soluble enzyme fraction and found to be strictly specific for tRNAAsp. These results, together with the anomeric configuration of mannose in Q nucleoside, indicate that no lipid intermediate is involved in the biosynthesis of Q nucleoside.

Animals↗

Laboratory evaluation of FR10024 a new cephalosporin derivative.

FR10024 is a broad-spectrum antibiotic. The in vitro antibacterial activity of FR10024 against clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis is greater than that of any of the cephalosporins developed to date. Indole-positive Proteus, Enterobacter, and Citrobacter are resistant to FR10024, as is true for the other cephalosporins. However, more than half of the strains of Enterobacter and Citrobacter tested were susceptible to FR10024 at an inoculum of 10(6) cells/ml. A single subcutaneous injection of FR10024 to mice with peritoneal infections due to S. aureus and several species of gram-negative bacilli gave a protective effect inferior to that of cefazolin but appeared to be superior to that of cephalothin. When given in two divided doses, however, the protective effect of FR10024 was enhanced and almost equaled that of cefazolin. The serum levels and rates of urinary recovery of FR10024 varied in different animal species. The mean peak serum level of FR10024 in humans after a single intramuscular injection of 500 mg was two times higher than that of cephalothin. The serum half-life after intramuscular injections of 250 and 500 mg was slightly shorter than that of cephalothin. After receiving 250 mg of FR10024 intramuscularly the urinary recovery rate was 87.7% in healthy volunteers. The biliary excretion rate of FR10024 was particularly high. The 24-h excretion of FR10024 in rats was 63.3%, this being six to seven times higher than that for cefazolin, which has the highest biliary excretion of the other known cephalosporins. When FR10024 was injected intramuscularly (20 mg/kg), it was found that the hepatic levels of FR10024 in rats were the highest of all the cephalosporins, including cefazolin, but the levels of FR10024 in other tissues were not as high as those of cefazolin.

Adult↗

Enterohepatic circulation of a new oral cephalosporin, FR10612, and its effect on serum and tissue levels in rats.

Serum levels of FR10612 given orally to rats persisted significantly longer than did those of cephalexin. Since the elucidation of this phenomenon observed in rats is considered to be pertinent to the understanding of the drug kinetics of FR10612 in other animals including man, the present study was undertaken. From the dose-response curve of the serum levels of FR10612 in rats, it is apparent that the maximum oral absorption is obtained in the range of 100-400 mg/kg. Even when the doses were increased from 100 to 1,000 mg/kg, the tissue levels with the exception of the kidneys, did not increase significantly. However, the persistence of the tissue levels was enhanced. The serum and tissue levels of FR10612 in rats after repeated massive dosings did not increase accumulatively. From the experimental results of FR10612 in rats with ligated bile ducts and the results obtained after intravenous injection, it seems clear that the prolonged in vivo levels of FR10612 in rats after oral dosing are closely related to its enterohepatic circulation.

Administration, Oral↗