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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 739 records · Page 41Linked to original sources

Effects of amphotericin B and its methyl ester on plasma membranes of Candida albicans and erythrocytes as examined by freeze-fracture electron microscopy.

Freeze-fracture electron microscopy of the plasma membranes of Candida albicans yeast cells and red blood cells treated with amphotericin methyl ester and amphotericin B showed that amphotericin B (50 micrograms ml-1) caused extreme aggregation of intramembranous particles on the protoplasmic fracture face of the C. albicans membrane, and a marked reduction of the density of intramembranous particles. On the other hand, the rearrangement of intramembranous particles induced by amphotericin methyl ester (50 micrograms ml-1) produced elevations of the particle-free membrane domains toward the outside of the cells, so that the particles were aggregated in linear furrows surrounding these elevations on the protoplasmic fracture face, and the corresponding ridges on the exoplasmic fracture face. The density of intramembranous particles was greatly reduced on the protoplasmic fracture face. Both polyenes produced only small changes in the erythrocyte membranes at the same concentration. These results suggest that amphotericin methyl ester affects the ergosterol-containing membranes more than amphotericin B, and that ergosterol has a higher sensitivity for these two polyene antibiotics than cholesterol.

Amphotericin B↗

Within-person variability of nutrient intake in a group of Hawaiian men of Japanese ancestry.

Within-person variability of nutrient intake is examined using data on 7 consecutive days for 329 men. The variability of nutrient intake within persons differs for the nutrients examined. Some nutrients, such as starch, have small within-person components of variance and are therefore highly reliable even using a single 24-h recall. Others, such a polyunsaturated fatty acids, have large within-person components of variance and are thus less reliable. Within-person variability affects the power of a study to detect differences in nutrient intake between groups and also affects the magnitude of calculated correlation coefficients. For the least reliable nutrient it is estimated that the correlation would be attenuated to two-thirds its true size. Eating patterns in the cohort appear to be nonrandom. Using this nonrandomness of nutrient intake it may be possible to reduce the within-person component of variance using less recalls than is suggested if random eating patterns are assumed.

Cholesterol↗

Acculturation and coronary heart disease among Japanese men in Hawaii.

A cohort of 4653 men of Japanese ancestry living in Hawaii, with traditional Japanese social and cultural lifestyles, were studied for the association of the prevalence and incidence of coronary heart disease (Honolulu Heart Program, 1971-1979). Two of four scales of acculturation were significantly associated with coronary heart disease prevalence independently of 11 other risk factors, but none of the acculturation scales were associated with incidence appeared to be mostly due to the inclusion of fatal cases in the incidence data, although other explanations are possible. Measures of acculturation were also significantly associated wih many of the other coronary heart disease risk factors in such a way that the more traditional Japanese men had lower serum cholesterol and uric acid, were less obese, more physically active, and smoked fewer cigarettes than the more westernized men. A comparison of bivariate and multivariate analyses indicated that some of acculturation scales were indirectly associated with coronary heart disease because of the confounding association with the other risk factors.

Acculturation↗

Biochemical characterization of secreted proteases during growth in Tetrahymena pyriformis WH-14: comparison of extracellular with intracellular proteases.

Tetrahymena pyriformis strain WH-14 secreted large quantities of intracellular proteases into its culture medium during growth. Extracellular enzymes were purified to homogeneity from cell-free medium by ammonium sulfate precipitation, CM-Sephadex column chromatography, gel filtration, and DEAE-cellulose column chromatography. The DEAE-cellulose eluates were separated into four peaks (P-I, P-II, P-III, and P-IV), each of which exhibited a different specific activity toward azocasein and alpha-N-benzoyl-DL-arginine-rho-nitroanilide (Bz-Arg-Nan). These four forms of the protease showed similarity in amino acid composition, molecular weight (21,000-24,000), and antigenic reactivity. They had pH optima at neutral range. P-I showed the highest specificity to azocasein whereas P-IV was most effective toward the synthetic substrates. The Km values for hydrolysis of Bz-Arg-Nan were 2.4, 1.6, 1.3 and 1.4 mM for P-I, P-II, P-III, and P-IV, respectively, and the corresponding Kcat/Km values were 5.0, 9.4, 28.5, and 114.3 S-1 . M-1. These properties of secreted proteases were compared with those of intracellular proteases purified by the same procedure except for the initial Triton X-100 extraction. There were similarities in specific activity toward two substrates, molecular weight, Km, pH optima, and antigenic reactivity between the proteases from two sources, providing evidence that the intracellular proteases may be secreted into the extracellular medium without modification.

Amino Acids↗

Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys.

The pharmacokinetics of SM-1652 were studied in mice, rats, rabbits, dogs, and rhesus monkeys. The plasma half-lives of SM-1652, administered intravenously at a dose of 20 mg/kg, were 11.0 min in mice, 26.0 min in rats, 65.8 min in rabbits, 72.6 min in dogs, and 150.9 min in monkeys. The 24-h urinary excretion of SM-1652 was 30 to 35% of the dose in mice and rats, 70 to 75% in rabbits and dogs, and 45% in monkeys. Biliary excretion of the antibiotic over a 24-h period was 60 and 19% in rats and rabbits, respectively; it was 19% in dogs over a 9-h period after SM-1652 administration. Approximately 95% of the intravenous dose of SM-1652 was recovered as the unchanged form in the urine and bile of rats and rabbits. The binding of SM-1652 to serum protein was 44.0% in mice, 46.0% in rats, 90.4% in rabbits, 93.2% in monkeys, 30.0% in dogs, and 96.3% in humans.

Animals↗

Pharmacokinetics of cefotetan (YM09330) in humans.

The pharmacokinetics and safety of cefotetan (YM09330) were examined after intravenous administration of single and multiple doses to normal volunteers. Cefotetan was well tolerated in single doses of 500 to 3,000 mg and in multiple doses of 500 and 1,000 mg at 12-h intervals for 1 and 3 days. These doses produced high plasma levels. The half-life (3 h) of cefotetan was longer than that of cefazolin. There was no evidence of drug accumulation in the plasma in the multiple-dose study. Mean recoveries of cefotetan in urine within a 24-h period were 74.5 to 88.4% of the dose, regardless of the route of administration and the dosage. The tautomer of cefotetan accounted for approximately 5% of the dose excreted in the urine. No tautomer was detected in plasma. Concentrations of drug in plasma and urine measured by microbiological assay were in good agreement with those measured by high-pressure liquid chromatography.

Adult↗

Phenanthrene-degrading phenotype of Alcaligenes faecalis AFK2.

A phenanthrene-degrading bacterium that assimilated a wide range of organic compounds was isolated from a soil sample and identified as Alcaligenes faecalis strain AFK2. The strain degraded phenanthrene through protocatechuate, but did not utilize naphthalene. The phenanthrene-degrading phenotype (Phn+) of AFK2 disappeared after 20 successive subcultures in a mineral salts medium containing o-phthalate or after subculture in nutrient broth containing mitomycin C. The results suggested that the Phn+ phenotype of this strain might be encoded by extrachromosomal genes.

Alcaligenes↗

Evidence for predominance of phospholipase A2 in release of arachidonic acid in thrombin-activated platelets: phosphatidylinositol-specific phospholipase C may play a minor role in arachidonate liberation.

Human platelets prelabeled with [3H]glycerol exhibited a trasient increase in radioactivity (1.5-fold gain) in 1,2-diacylglycerol when they were exposed to thrombin. An alteration in radioactivity in monoacylglycerol which is derived from diacylglycerol by diacylglycerol lipase, however, was not observed during the whole period of incubation with thrombin. Lysophosphatidylcholine and lysophosphatidylethanolamine gained radioactivity. By contrast, the level of lysophosphatidylinositol plus lysophosphatidylserine did not show any change. When the effects of thrombin on platelet lipids were examined for [3H]arachidonate-labeled platelets, thrombin-activation induced a 15-fold increase in radioactivity in 1,2-diacylglycerol, a subsequent decrease of which was accompanied by accumulation of radioactivity in phosphatidic acid. There was a concurrent release of free arachidonic acid. These findings, taken together with phospholipid alteration analyzed by phosphorus assay upon thrombin-activation, indicate evidence than newly produced diacyglycerol in thrombin-activated platelets may be immediately converted to phophatidic acid by a diacylglycerol kinase rather than metabolized to monoacylglycerol or arachidonic acid by diacylglycerol lipase, and also that arachidonic acid would be mainly released from phosphatidylcholine and phosphatidylethanolamine by a phospholipase A2 activity.

Arachidonic Acid↗

[Distribution of 67Ga-citrate in 3'-methyl-4-dimethylaminoazobenzene-induced hepatoma of rats].

The distribution of 67Ga-citrate in the hepatoma of rat induced by 3'-methyl-4-dimethylaminoazobenzene was studied. 67Ga uptake ratio resected specimen, autoradiography and histological specimen were compared each other. 67Ga uptake ratio of the tumor was increased 1.6 to 7.2 times (average 4.4) to control group. Regardless of the size of the tumor, macroautoradiographically observed distribution of 67Ga-citrate in the hepatoma was higher in the peripheral zone than in the central zone. Histologically the degeneration of tumor cell was low or absent in the peripheral zone of tumor, whereas it was intense in the central zone. 67Ga-citrate was highly accumulated in the zone which the degeneration was low or absent. We, however, could not demonstrate the site where 67Ga-citrate was incorporated.

Animals↗

Comparison of Tl-201 chloride and Ga-67 citrate scintigraphy in the diagnosis of thyroid tumor: concise communication.

Twenty-five patients with thyroid tumors were scintigraphed with both Tl-201 chloride and Ga-67 citrate. All cases showed a focal area of decreased activity with I-131 or pertechnetate (Tc-99m), and each had a histological diagnosis after surgery or excisional biopsy. From the data we conclude the following: (1) Tumors giving a positive scan with Tl-201 chloride but negative results using Ga-67 citrate prove to be differentiated carcinoma or poorly differentiated adenoma. (2) All tumors that are positive with Ga-67 are highly malignant types, and if these tumors are negative by Tl-201, undifferentiated carcinoma is suggested. (3) Ga-67 citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy on undifferentiated carcinoma.

Adenocarcinoma↗

[Cefotetan, a new cephamycin antibiotic: in vitro and in vivo antibacterial activities (author's transl)].

Cefotetan (CTT) is a new parenteral semisynthetic cephamycin-type antibiotic with a broad antibacterial spectrum against both Gram-positive and Gram-negative bacteria. Against wide varieties of Gram-negative bacteria, particularly including indole positive Proteus, S. marcescens, Enterobacter sp. and C. freundii CTT was more highly active than cefmetazole, cefoxitin and cefazolin. The 50% inhibition doses (ID50) of CTT against E. coli, K. pneumoniae, P. mirabilis, indole positive Proteus and S. marcescens were by far superior to those of the 3 other antibiotics. The antibacterial activities of CTT were bactericidal and were little affected by addition of horse serum and by variation in pH of the medium, in inoculum size and in type of culture media. Model infections in mice against Gram-positive and Gram-negative bacteria were studied. The therapeutic effects after subcutaneous injection of CTT against various Gram-negative bacterial infections were superior to those of cefmetazole, cefoxitin and cefazolin.

Animals↗

[Pharmacokinetics of cefotetan and an aminoglycoside preparation in combined administration. 1. Individual quantification of cefotetan and sisomicin by bioassay and their absorption, distribution, and excretion in rats when given together].

The beta-lactam and aminoglycoside groups of antibiotics are often used in combination. This paper reports a bioassay method for each of cefotetan and sisomicin concentration in body fluids, and pharmacokinetics of both drugs following intravenous administration of cefotetan and intramuscular administration of sisomicin alone and in combination to rats. As to cefotetan determination, a previously reported bioassay method was modified by increasing the NaCl concentration in the sensitivity test agar from 0 to 6%, using Bacillus subtilis ATCC 6633 as the test organism. To assay for sisomicin in the presence of cefotetan, Pseudomonas aeruginosa ATCC 8689, resistant to the beta-lactam antibiotic, was used. Cefotetan (20 mg/kg intravenous) and sisomicin (10 mg/kg intramuscular) were administered concomitantly to rats. The mean plasma concentrations of cefotetan and sisomicin were 16.3 microgram/ml and 16.1 microgram/ml, at 30 minutes after administration respectively. The concentrations were declined to 2.20 microgram/ml for cefotetan and 2.53 microgram/ml for sisomicin at 90 minutes after dosing administration. The calculated plasma half-lives (T 1/2 beta) were 21.3 minutes for cefotetan and 22.2 minutes for sisomicin. The plasma and tissue concentrations of cefotetan administered in combination with sisomicin were nearly the same as those of cefotetan alone. Urinary excretion of cefotetan and sisomicin in the concomitant administration was carried out in rats. Recoveries in urine were 45.9% of the dose for cefotetan and 85.6% of the dose for sisomicin for a period of 24 hours. When each drug was administered alone to rats, cefotetan and sisomicin were recovered 49.8% and 81.6%, respectively, of the dose in the 24-hour urine.

Absorption↗

[Pharmacokinetics of a cefotetan and an aminoglycoside preparation in combined administration. 2. Absorption and exercise of cefotetan and sisomicin in dogs when the two are given together].

Cefotetan (20 mg/kg i.v.) and sisomicin (10 mg/kg i.m.) were administered alone or in combination to Beagle dogs. The mean plasma concentrations of cefotetan administered in combination with sisomicin at the above dosages were 98.0 microgram/ml at 5 minutes, 45.7 microgram/ml at 30 minutes and 3.46 microgram/ml at 4 hours. These plasma concentrations of cefotetan were similar to those of cefotetan administered alone to the corresponding dogs. The calculated plasma half-lives (T 1/2 beta) of cefotetan were 53.9 minutes in combination with sisomicin and 57.4 minutes alone. The excretion of cefotetan in dog urine were 52.4% and 50.2% of the dose after administration in combination with sisomicin and alone, respectively, during 24 hours. The results indicate that there were no significant differences in the pharmacokinetics of cefotetan alone or in combination with sisomicin in dogs. The maximum concentrations of sisomicin in dogs administered in combination with cefotetan were 20.2 microgram/ml at 30 minutes after dosing. The concentrations of 11.7 microgram/ml at 2 hours and 3.13 microgram/ml at 4 hours of administration were maintained in plasma. The calculated plasma half-lives of sisomicin were 68.8 minutes in combination with cefotetan and 86.4 minutes alone. The urinary rcoveries of sisomicin were 79.3% and 76.1% in combination with cefotetan and alone, respectively, during 24 hours. There were no significant differences in the pharmacokinetics of sisomicin alone and in combination with cefotetan in dogs.

Absorption↗

[Comparison of 201T1-chloride and 67Ga-citrate in thyroid tumor scintigraphy].

Twenty-five patients with thyroid tumors were examined by 201T1-chloride and 67Ga-citrate scintigraphy heterochronously in our department. All cases showed the cold nodule with 131I or 99mTc-pertechnetate thyroid scintigraphy and each one was given a histological diagnosis after surgery or excisional biopsy. In 15 cases of thyroid carcinoma, 12 (80%) were positive by 201T1-chloride; 4 (26.7%) were positive by 67Ga-citrate. In examining each histological type, 8 of 9 cases of papillary carcinoma (88.9%) were positive by 201T1-chloride. In 1 negative case the tumor was almost completely encysted; however, they were all negative by 67Ga-citrate. In 2 patients with follicular carcinoma, both of them revealed a positive figure by 201T1-chloride, and one of these with oxyphilic cell carcinoma showed a positive figure by 67Ga-citrate. In 1 case of medullary carcinoma there was slight accumulation with 201T1-chloride, but there was no accumulation with 67Ga-citrate. In 3 cases of undifferentiated carcinoma, 2 patients with small carcinoma showed a negative figure by 201T1-chloride. However, they all showed a positive figure using 67Ga-citrate and this medium also disclosed distant metastases of undifferentiated carcinoma. In 10 patients with thyroid adenoma, 3 (30%) showed a positive figure by 201T1-chloride. Histologically, these were all tubular adenoma, but in all cases of thyroid adenoma 67Ga-citrate revealed a negative figure. From the above mentioned results, the following conclusion were reached. Tumors showing a positive figure by 201T1-chloride that elicited negative results using 67Ga-citrate proved to be differentiated carcinoma or low differentiated types of adenoma. Surgery is indicated in these cases. All of the tumors revealing a positive figure by 67Ga-citrate were highly malignant types. If these tumors showed a negative figure when 201T1-chloride was used, undifferentiated carcinoma was suggested. In undifferentiated carcinoma, 67Ga-citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy.

Adenocarcinoma↗

[Morphological alterations in Escherichia coli and Serratia marcescens induced by cefotetan (author's transl)].

The effects of cefotetan (CTT, YM09330) and cefmetazole (CMZ) on the morphological changes of Escherichia coli NY-17 and Serratia marcescens IID 620 were examined with scanning electron microscope. 1) CTT and caused E. Coli NY-17 filamentous forms at 0.024 microgram/ml but CMZ showed same morphological changes at 0.2 microgram/ml which is about 10 fold higher concentration than that of CTT. Spheroplast like structures and cell lysis were observed at lower concentrations than those of CMZ. 2) In case of Serratia marcescens IID 620, filamentous forms, spheroplast like structures and cell lysis were also observed at lower concentrations than those of CMZ. The action of CTT against the both strains was bactericidal.

Anti-Bacterial Agents↗