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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 703 records · Page 39Linked to original sources

Interrelationship between tumorigenicity and the chemical nature of N-methyl-N'-aryl-N-nitrosoureas.

The tumorigenic activity of a series of N-methyl-N'-aryl-N-nitrosoureas (I-X) on mouse skin was investigated in comparison with that of N-methyl-N-nitrosourea (MNU). The tumorigenic potency of I-X was less than that of MNU, although the former are much stronger mutagens; and no correlations were found between the tumorigenicity of I-X and their mutagenicity. The major tumors induced by the methoxy and methyl derivatives, both of which have high lipophilicity, were sarcomas (fibrosarcomas and fibroanaplastic, anaplastic, and pleomorphic cell sarcomas) in contrast to the fact that squamous cell carcinomas were the major tumors induced by MNU. Although the nitrosoureas were not administered intragastrically to the animals, squamous cell carcinomas were observed in the forestomachs of mice treated with I-X, but no tumors were produced in the stomachs by MNU. Adenocarcinomas were found in the lungs of mice treated with all the nitrosoureas. Hyperplastic nodules were observed in the livers of mice treated with methoxy and hydrogen derivatives, while cysts were found with methyl derivatives.

Alkylation↗

Delayed secondary immune response in mice immunized with Toxoplasma antigens and its effect for protection against Toxoplasma gondii.

Primary immune response by mice immunized with Toxoplasma peritoneal exudate (PE) was produced slowly at a low level. To induce high Toxoplasma antibodies, mice should be boostered after the primary immune response reached the peak in 4 weeks or later. Immunization of mice with PE alone in 4 weeks could suppress the growth of Toxoplasma but could not accomplish protection. Two of 9 mice immunized with PE in complete Freund's adjuvant (CFA), and 16 of 27 mice immunized with PE containing Toxoplasma ( ToxoPE ) in CFA were protected against a challenge of 1 X 10(3) Toxoplasma, RH strain. The mice surviving to the challenge showed complete protection against a rechallenge of higher dose, 1 X 10(6) RH strain. Their ascites were very high in LA titer and would be a great source for obtaining high titer antibodies to Toxoplasma without contamination of host serum components. Biological characters of Toxoplasma, RH strain, in chronic infection of mice are discussed.

Animals↗

Coupling of polyphosphoinositide breakdown with calcium efflux in formyl-methionyl-leucyl-phenylalanine-stimulated rabbit neutrophils.

Exposure of rabbit neutrophils to formyl-methionyl-leucyl-phenylalanine (FMLP) induced the efflux of 45Ca2+ from pre-labeled cells which was almost complete within 30 s. On the other hand, FMLP-induced 45Ca2+ influx did not become apparent until 60 s after stimulation. When [3H]arachidonic acid-labeled neutrophils were stimulated with FMLP, the radioactivities in phosphatidylinositol 4,5-biphosphate (TPI) and phosphatidylinositol 4-phosphate (DPI) significantly decreased in parallel with the induction of 45Ca2+ efflux. In contrast, degradation of polyphosphoinositides in [3H]glycerol-labeled neutrophils was not significant until 60 s. Taken together, these results indicate that the early degradation of polyphosphoinositides, especially of those rich in arachidonic acid is closely associated with the initial efflux of calcium in FMLP-stimulated rabbit neutrophils. The study of resynthesis of polyphosphoinositides by measuring 32Pi incorporation into these lipids is also presented.

Animals↗

Thiazide effect on the mineral content of bone.

The thiazide diuretics are known to cause calcium retention. In order to study the effect of thiazides on bone mineralization, we have measured the mineral content of bone at five sites (the distal radius, the distal ulna, the proximal radius, the proximal ulna, and the os calcis) in 1368 men with a mean age of 68 years, including 323 who were taking thiazides for hypertension. The results were adjusted for age and body-mass index. Thiazide users had significantly more bone mineral content at all five sites than did non-users. Untreated hypertensive patients and persons without hypertension had comparable bone mineral content, indicating that the higher mineral content found among thiazide users is related to the drug and not to the underlying hypertension. These findings suggest the possibility of a preventive or therapeutic role for thiazides in osteoporosis.

Aged↗

Modification of positional distribution of fatty acids in phosphatidylinositol of rabbit neutrophils stimulated with formylmethionyl-leucyl-phenylalanine.

The effects of formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) on the positional distribution of fatty acids in phosphatidylinositol (PI), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were investigated with rabbit neutrophils. The proportion of arachidonate at the C-2 position of PI was 35.0% in resting neutrophils and declined to 30.8% after 5 min stimulation with the peptide at a concentration of 10(-7) M. In contrast, the profiles of the positional distribution of fatty acids in PC and PE were not affected upon stimulation with fMet-Leu-Phe. The phospholipid composition of rabbit neutrophils was examined at different time intervals following the addition of fMet-Leu-Phe. PI and PC, but no other phospholipids, exhibited significant changes in their quantities. The quantity of PC decreased at 5 min with a concurrent increase in that of lysophosphatidylcholine (lysoPC), suggesting a phospholipase A2 action on PC. The quantity of PI, on the other hand, decreased at 1 min with an accompanying increase in phosphatidic acid when the profile of the positional distribution of fatty acids in PI remained unchanged. No lysophosphatidylinositol (lysoPI) was detected. This indicates the enhancement of the PI cycle in the fMet-Leu-Phe-stimulated neutrophils. The augmented PI cycle in response to fMet-Leu-Phe was further supported by the finding that [3H]arachidonyl-diacylglycerol and -phosphatidic acid accumulated at the expense of [3H]arachidonylPI in rabbit neutrophils prelabelled with [3H]arachidonate. Restoration of the content of PI to the higher than the original level at 5 min after stimulation with fMet-Leu-Phe, however, leads to the suggestion that de novo synthesis of PI as well as PI resynthesis along the closed cycle of PI has occurred at 5 min and that this newly synthesized PI, via a de novo pathway with a different pattern of the positional fatty acyl composition, is the cause of the decreased proportion of arachidonate.

Animals↗

Purification and characterization of a secreted protease from Tetrahymena pyriformis.

A simple major protease, secreted into the medium during growth of Tetrahymena pyriformis strain W, has been purified about 4000-fold by (NH4)2SO4 precipitation, ion-exchange chromatography, gel filtration and affinity chromatography on organomercurial-Sepharose. The purified protease was homogeneous as judged by polyacrylamide gel electrophoresis and was a monomeric protein with a molecular weight of 22 000-23 000. Amino acid analysis showed that the enzyme was rich in acidic amino acids. In addition, the purified Tetrahymena protease consists of multiple forms with isoelectric point between pH 5.3 and 6.3. Optimum activity of the purified enzyme was in the pH range 6.5-8.0 with alpha-N-benzoyl-DL-arginine-p-nitroanilide and with azocasein, while it was in the lower pH range (4.5-5.5) for denatured hemoglobins. The purified enzyme was inhibited by compounds effective against thiol proteases. Leupeptin and chymostatin were potent inhibitors but pepstatin was without effect. This enzyme is similar to cathepsin B and appears to be a major proteolytic enzyme in Tetrahymena.

Amino Acids↗

Plasmid involvement in the degradation of polycyclic aromatic hydrocarbons by a Beijerinckia species.

A Beijerinckia species, capable of oxidizing phenanthrene, biphenyl and other polycyclic aromatic hydrocarbons, was shown to contain two plasmids that were designated pKGl and pKG2. The molecular masses of plasmids pKG1 and pKG2, as determined by electron microscopy, were approximately 147 X 10(6) and 20.8 X 10(6) daltons, respectively. Growth of the organism on benzoate led to the isolation of strains that had lost the ability to grow with phenanthrene and biphenyl. All of the Phn-, Bph- strains had also lost the smaller plasmid, pKG2. The results presented suggest that plasmid pKG2 is responsible for the synthesis of enzymes involved in the degradation of phenanthrene and biphenyl.

Azotobacter↗

Trends of coronary heart disease among men of Japanese ancestry in Hawaii.

The 15-year prospective study of cardiovascular disease among a cohort of Japanese men in Hawaii provided an opportunity to examine the temporal trends of coronary heart disease (CHD) incidence and mortality rates and to compare them with Hawaii State CHD mortality rates. The State mortality records showed a decline in CHD mortality from 1968 to 1978 which was similar to the national trends. For more than 11,000 men of Japanese ancestry under surveillance, there was no evidence of declining rates for either CHD deaths or for total CHD incidence. There was also no change in case-fatality rates during this time. An explanation for these differences could not be provided but there was a suggestion that it involved changes in classification of some groups of cardiovascular disease and stroke.

Adult↗

Postmenopausal bone loss at multiple skeletal sites: relationship to estrogen use.

Bone mineral content (BMC) was measured in the distal radius, proximal radius, and os calcis in 608 postmenopausal women, and the values were compared to vertebral osteoporosis and compression fractures determined radiographically, as well as to history of estrogen use. Current estrogen users had significantly higher BMC at all appendicular sites as compared to non-users. Prior estrogen users had lower appendicular BMC's than current users, but they were still significantly higher than non-users. However, radiographic assessment of the lumbar spine showed no difference in osteoporosis or compression fracture prevalence between prior users and non-users of estrogen, whereas current estrogen users had a significantly lower prevalence of osteoporosis in the spine. These findings suggest that estrogen effect on trabecular bone in the os calcis may be more transient than on cortical, appendicular bone. They also suggest that long term or permanent estrogen replacement is required to prevent spinal compression fractures.

Adult↗

The impact of elevated blood pressure upon 10-year mortality among Japanese men in Hawaii: the Honolulu Heart Program.

The impact of blood pressure upon total and cause-specific mortality during 10 years of follow-up was studied for 7610 Japanese men in Hawaii, aged 45-68 at baseline examination. The age adjusted rate of total mortality for men with definite hypertension (WHO criteria) was twice that for normotensive men. The relative risk of mortality was five for all cardiovascular diseases (CVD), four for coronary heart disease (CHD), and six for stroke. Men with borderline hypertension also had significantly high mortality rates intermediate between the definite hypertensives and the normotensives. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were the most important independent predictors of total, CVD, CHD and stroke mortality in multivariate analysis, taking account of 11 other known risk factors. However, SBP was more strongly related to total, CVD and CHD mortality than was DBP, whereas the reverse was true for stroke mortality. There was no significant association of either SBP or DBP with cancer and other non-cardiovascular mortality in multivariate analysis. Men who were receiving antihypertensive medication at baseline examination had a higher mortality from CVD, CHD and stroke as compared to untreated men in every category of blood pressure status. This apparently paradoxical finding probably reflects more advanced status of hypertension existing before treatment rather than adverse effects of drugs per se; however, this latter possibility cannot be dismissed.

Aged↗

Cloning of a LEU gene and an ARS site of Candida maltosa.

Gene libraries of DNA from an n-alkane-assimilating yeast strain, Candida maltosa IAM12247, were constructed, using Escherichia coli plasmid vector pBR322. A LEU gene from C. maltosa was cloned, and found to complement leu- mutations in E. coli and Saccharomyces cerevisiae. In E. coli, the LEU gene in the cloned yeast DNA fragment was efficiently expressed when inserted into the vector in one orientation, while in the other orientation, it was expressed only weakly. In S. cerevisiae, the Candida LEU gene was efficiently expressed when inserted into a shuttle vector pRC3 in both orientations, suggesting that the isolated Candida DNA fragment contains a promoter sequence of Candida in front of the LEU gene, which is operative in S. cerevisiae but not in E. coli. In addition, our data suggest that the cloned LEU fragment also contains an ARS (autonomously replicating sequence) site of C. maltosa.

Candida↗

Animal pharmacokinetics and toxicology of cefotetan--a new cephamycin antibiotic.

In animal pharmacokinetic studies the biological half-lives of cefotetan were 13.0 min in mice, 15.9 min in rats, 30.5 min in rabbits, 55.5 min in dogs and 77.9 min in rhesus monkeys. The acute intravenous LD50 values (g/kg) were 6.4 and 5.0 in male and female mice, respectively, and 8.5 and 6.8 in male and female rats, respectively. Six-month repeated dose studies of 30 to 1000 mg/kg per day intraperitoneally in rats and 100 to 600 mg/kg per day intravenously in rhesus monkeys showed no notable organ toxicity. A teratogenicity study in rats indicated that cefotetan had no adverse effects on fetal and postnatal development. The nephrotoxicity of cefotetan in rabbits was considerably less than that of cefazolin.

Abnormalities, Drug-Induced↗

Social networks and coronary heart disease among Japanese men in Hawaii.

A group of 4653 men of Japanese ancestry living in Hawaii were studied for the association of measures of social networks with both the prevalence and incidence rates of coronary heart disease (Honolulu Heart Program, 1971-1979). Prevalence rates for myocardial infarction, angina, and total coronary heart disease were inversely associated with the social network scales in bivariate analyses with age, and in multivariate analyses including 12 other risk factors. With the incidence data, the associations were less evident. Bivariate analysis with age revealed inverse associations for nonfatal myocardial infarction and total coronary heart disease with only one of the social network scales. With multivariate analyses, there was no significant association of any subgroup of coronary heart disease with any scale, although there was a borderline association (p = 0.08) of nonfatal myocardial infarction with one scale. No individual question was significantly associated with either prevalence or incidence rates for coronary heart disease. There was also little evidence of reduced risk of incident coronary heart disease associated with the social network scale for men in high risk categories of serum cholesterol, blood pressure, and cigarette smoking.

Aged↗

In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity.

SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.

Anti-Bacterial Agents↗

Detection of DR antigen on leukemic cells from a patient suffering from adult T-cell leukemia and progressive systemic sclerosis.

This report concerns an unusual case of adult T cell leukemia (ATL) complicated with progressive systemic sclerosis (PSS). The surface markers of peripheral blood mononuclear cells (PBM) and lymph node cells, both of which mainly consisted of leukemic cells, were examined. The effect of these cells on the pokeweed mitogen (PWM)-induced IgG synthesis by normal PBM also was studied. The leukemic cells formed rosettes with sheep red blood cells (SRBC; E) and expressed T cell antigen, Leu-1, and DR antigen. The detection of cell surface antigens was carried out by employing monoclonal antibodies against these antigens. We diagnosed this case as DR positive ATL. In terms of the immunoregulatory function of these leukemic cells, the co-culture experiments showed that these cells had some suppressive effect on the PWM-induced IgG production by allogeneic normal PBM.

Female↗

Characteristics of joggers among Japanese men in Hawaii.

In a population-based cohort of Japanese American men in Hawaii, the 450 joggers differed from 6,171 nonjoggers in being younger, taller, heavier, and more obese; in having larger vital capacity, higher socioeconomic status, and a higher prevalence of certain electrocardiographic abnormalities; and in being more health conscious as demonstrated by less smoking and a higher frequency of special diets. Blood pressure, serum total cholesterol, hematocrit and high density lipoprotein cholesterol (HDL-C) did not differ significantly between the two groups. Multiple regression analysis showed HDL-C to be inversely related to obesity and cigarettes, and directly related to alcohol consumption but to have no relationship to jogging or age. Temporal analyses suggested that initiation of jogging was followed by a reduction in heart rate, but there was no significant change in other measured parameters. Coronary heart disease (CHD) prevalence was increased in joggers, perhaps because the diagnosis of CHD predisposes to this activity. We conclude that jogging has probably had little impact on the health of this cohort.

Aged↗