Biomedical subjects
Publications and source records attributed to I Fujii.
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Explore the source record for details and available documents.
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Explore the source record for details and available documents.
The recent development of molecular cloning systems in Streptomyces has made possible the isolation of biosynthetic genes for some of the many antibiotics produced by members of this important genus of bacteria. Such clones can now be used to test the idea that novel antibiotics could arise through the transfer of biosynthetic genes between streptomycetes producing different antibiotics. The likelihood of a 'hybrid' compound being produced must depend on the substrate specificities of the biosynthetic enzymes, about which little is known. In attempts to demonstrate hybrid antibiotic production, we therefore began with strains producing different members of the same chemical class of compounds in order to maximize the chance of success. Here we report the production of novel compounds by gene transfer between strains producing the isochromanequinone antibiotics actinorhodin, granaticin and medermycin. These experiments were made possible by the recent cloning of the whole set of genes for the biosynthetic pathway of actinorhodin from Streptomyces coelicolor A3(2) (ref. 8). We believe that this represents the first report of the production of hybrid antibiotics by genetic engineering.
Two new 9,10-seco-cycloartanes, named sphaerophyside SC (1) and sphaerophyside SD (2), together with four known compounds (3-6), were obtained from the ethanol extract of the seeds of Sphaerophysa salsula. The structures of these compounds were elucidated on the basis of spectral and chemical evidences. Compounds 3-6 were isolated from the plant for the first time.
To elucidate the relation of hematocrit (Hct) to the incidence of cerebral infarction, a prospective follow-up study of 16 years (1965-81) was performed in a general population sample of 1220 Hisayama residents aged 44 and over, of both sexes. Most of the subjects who died during the follow-up period were autopsied, the rate being 89.0%. Hct decreased with advancing age in men, but not in women. The average value for Hct was significantly lower in women than in men. According to the mean value +/- 1 SD of Hct, the subjects were grouped into 3, in each sex as follows: low (less than 35%), normal (35-45%) and high (greater than or equal to 45%) for men, and, low (less than 30%), normal (30-40%) and high (greater than or equal to 40%) for women. During the follow-up period, cerebral infarction occurred in 117 patients. The cumulative incidence of cerebral infarction in the low Hct group for men was the lowest, even after adjustments for age and blood pressure. Conversely, the incidence in the low Hct group of women was significantly higher than that in the normal Hct group and was consistently increased with time during 2-5 years of the follow-up. After the 6th year or later, however, the incidence was gradually but significantly increased in the high Hct group, compared with the normal Hct group. Since Hct levels were related with other variables such as serum total cholesterol, serum total protein, Quetelet index and prevalence of hypertension in both sexes, heavy alcohol consumption in men, and glucose intolerance in women, such variables were taken into account using Cox's proportional hazards regression model.(ABSTRACT TRUNCATED AT 250 WORDS)
Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine (AcS-morphine) were studied. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation. AcS-morphine, however, was 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. It is interesting that 6 beta-isomer of AcS-morphine is 5 times as potent as 6 alpha-OH isomer of morphine in the analgesic action, because 6 alpha-OH isomer of morphine is much more potent than that of 6 beta-OH isomer. The effects of AcS-morphine on the specific binding of [3H]-naloxone, [3H]-ethylketocyclazocine and [3H]-D-Ala2-D-Leu5-enkephalin to the membrane fractions from the rat brain were tested. AcS-morphine was about 5 times as potent as morphine in its interactions with opioid receptors, as determined by the binding assay. AcS-morphine, as well as morphine, had a selectively high affinity to mu-receptors. The "sodium effect" and the "GTP effect" of AcS-morphine were almost the same as those of morphine. The dependence liability of AcS-morphine was preliminary tested in the guinea-pig ileal preparations treated with a high concentration of AcS-morphine for 24 hr. Results suggested that AcS-morphine is weaker than morphine in its dependence liability, though it seems almost certain that AcS-morphine does have this liability.