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K Yazawa

Publications and source records attributed to K Yazawa.

At least 181 records · Page 10Linked to original sources
PubMed1984

Structure-activity relationships of saframycins.

In vitro antitumor activities of 13 saframycins, including the potent antitumor component, saframycin A, were determined with the highly sensitive established cell line of L1210 mouse leukemia to investigate structure-activity relationships. Saframycins which lack the alpha-cyanoamine group or the alpha-carbinolamine group exhibited much lower cytotoxic activity than saframycin A. The modification of active saframycins either at the C-14 position on the basic skeleton or at the C-25 position on the side chain with bulky substituents resulted in a decrease in cytotoxic activity. These structure-activity relationships corroborated the proposed major mechanism of action for the antitumor activity of saframycin A and supported our proposed model for the saframycin A-DNA adduct.

Animals↗
PubMed1983

Syndrome of inappropriate secretion of antidiuretic hormone caused by vincristine therapy: a case report of the neuropathology.

The syndrome of inappropriate secretion of antidiuretic hormone is a rare but well-recognized neurotoxic side effect of vincristine therapy. The first neuropathological report of a case is presented. A 6-month-old boy with skin leukemia developed inappropriate secretion of antidiuretic hormone caused by vincristine. Postmortem examination revealed axonal spheroids in the ansa lenticularis and the area surrounded by the substantia innominata, amygdala and supraoptic nucleus. The lesion was confined to that area and the neurosecretory neurons were intact with well preserved neurophysin. The pathological findings suggest that these fibers play a role in the development of inappropriate secretion of antidiuretic hormone caused by vincristine therapy.

Humans↗
PubMed1981

Binding of saframycin A, a heterocyclic quinone anti-tumor antibiotic to DNA as revealed by the use of the antibiotic labeled with [14C]tyrosine or [14C]cyanide.

Saframycin A is antitumor antibiotic structurally characterized by twin heterocyclic quinone skeletons and alpha-cyanoamine moiety. The binding of saframycin A to DNA was investigated using the antibiotic labeled at different positions. Heterocyclic quinone skeletons were biosynthetically labeled with [14C]tyrosine. The cyano residue of saframycin A was specifically labeled as a result of the reaction of [14C]cyanide with a derivative of saframycins, decyanosaframycin A, in the culture filtrate. When calf thymus DNA was incubated with [14C]tyrosine-labeled saframycin A in the presence of dithiothreitol, radioactivities were progressively recovered from DNA fraction. In contrast, saframycin A in the absence of dithiothreitol was completely devoid of reactivity toward DNA. When [14C]cyanide-labeled saframycin A was reacted with DNA, however, none of the radioactivity was associated with DNA. The release of cyano residue from the antibiotic was triggered by the reduction. Thus, conversion of quinone to hydroquinone skeletons as well as conversion of alpha-cyanoamine to immonium or alpha-carbinolamine is the consequence of the reduction. The fact that dithiothreitol-inducible binding of saframycin A to DNA was blocked by the addition of excess cyanide indicates that immonium or alpha-carbinolamine is the actual species involved in the interaction with DNA. The striking similarities between saframycin A and anthramycin in regard to the mode of binding to DNA are discussed.

Animals↗
PubMed1981

Intestinal microflora and aging: age-related change of enzymes in the liver and the small intestine of germ-free and conventional rats.

The activities of various enzymes involved in detoxication and carbohydrate metabolism in the liver and the gastrointestinal tract of germfree (GF) and conventional (CV) rats, 8 and 40 weeks' old, were measured in relationship to intestinal microflora and aging. In 8-week-old rats, the activities of nitroreductase (NR) and aniline hydroxylase (AH) in the liver, and of alkaline phosphatase (ALP), maltase and lactase in the duodenum were higher in GF than in CV rats, but the activities of arginosuccinate synthetase (ASS) and lactate dehydrogenase (LDH) in the liver were higher in CV than in GF rats. In 40-week-old rats, the activities of NR and glucose-6-phosphatase dehydrogenase (G-6-PDH) of the liver and ALP, maltase and lactase of the duodenum were higher in GF than in CV rats, but those of ASS, UDP-glucuronyl transferase (UDP-GT), AH, beta-glucuronidase, and LDH of the liver were higher in CV than in GF rats. Compared between 8- and 40-week-old rats the activities of NR, beta-glucuronidase, LDH, and acid phosphatase increased with aging in both GF and CV rats. The specific activities of ASS in CV and UDP-GT and AH in GF rats decreased with aging. The total activities of ASS and AH in GF rats also decreased with aging. The activities of ALP, maltase and lactase decreased with aging in both GF and CV rats. Thus, these data suggested that there are influences of indigenous intestinal microflora and aging on the activities of various enzymes in the liver and gastrointestinal tract.

Acid Phosphatase↗
PubMed1981

Intestinal microflora and aging: age-related change of lipid metabolism in germ-free and conventional rats.

The influence of intestinal microflora and aging on the lipid metabolism in germ-free (GF) and conventional (CV) rats, 8 and 40 weeks old, was investigated. Serum cholesterol at the age of 8 and 40 weeks and serum triglyceride (TG) at the age of 40 weeks was higher in GF than in CV rats. Serum cholesterol decreased and serum TG and corticosterone tended to increase in both GF and CV rats with aging. In the rats 40 weeks of age, lipase activity of the pancreas and the duodenal, jejunal, and colorectal contents in GF rats increased, but that of the ileal and cecal contents in GF and CV rats decreased. Intestinal microflora tended to depress the age-related increase of serum TG and lipase activity of the pancreas and the duodenal and jejunal contents. Lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities of the epididymal adipose tissue were higher in CV than in GF rats at both 8 to 40 weeks of age. The LPL activity increased and the HSL activity decreased in both GF and CV rats with aging. The concentration of cholesterol increased and that of bile acids decreased in the cecal contents of 40-week-old GF rats.

Aging↗
PubMed1981

Effect of lactobacilli on urinary indican excretion in gnotobiotic rats and in man.

The effect of Lactobacillus species on urinary indican excretion in two types of gnotobiotic rats (GBH-9 and GB-5) and in man was studied. L. salivarius, L. plantarum and L. casei colonized in the cecum and colon of both types of rats at levels of 10(7) to 10(8) per gram of contents following one-dose oral administration and caused a significant reduction in urinary indican excretion, whereas two strains of L. acidophilus which colonized at low levels (10(4) to 10(5)/g) did not reduce indican excretion. Daily feeding of Lactobacillus concentrates caused a further significant reduction in indican excretion which was corrected by tryptophan intake, even in the case of L. acidophilus. There was a clear relationship between fecal lactobacillus counts and urinary indican. A significant reduction of indican secretion was obtained only when the fecal counts of lactobacilli exceeded 10(7).4/g in rats. L. casei also had an effect in man, reducing urinary excretion of indican and p-cresol. Reduction in indican excretion seems to be accompanied by decreasing fecal tryptophanase activity in rats and man. A negative correlation was also obtained between fecal resident lactobacilli and urinary indican in man (r = -0.532, n = 28, p less than 0.01). Subjects with lactobacilli at a level of 10(6)/g or more excreted less indican than those harboring the bacteria at levels below 10(5)/g.

Adult↗
PubMed1981

Properties of the biotin transport system in Bifidobacterium breve N4.

Binding of biotin to resting cells of Bifidobacterium breve N4, which grew in a biotin-deficient medium, was independent of pH from 1 to 9 and of temperature below 50 C. It was not inhibited by metabolic inhibitors including sulfhydryl reagents, but it was inhibited by treatment with 80% ethanol or 5% trichloroacetic acid. It was also competitively inhibited by biotin-sulfone, but not by tetrahydrothiophene nor dethiobiotin. The binding constant was calculated to be 3.3 X 10(8) M--1. The amount of biotin unextractable with hot water, representing part of the transported biotin, increased gradually for 20 min, this increase was inhibited by NaF, hydroxylamine and low temperature. 14C-biotin on the cells was displaced by cold biotin and biotin-sulfone; the displacement was not inhibited by metabolic inhibitors, but it was dependent on temperature. A few minutes after binding, the biotin was released to the medium. The release was dependent on pH and temperature, was affected by energy sources and was inhibited by metabolic inhibitors, e.g. NaF, p-chloromercuribenzoic acid and hydroxylamine. It could be stopped at any time by cooling to 0 C or by adding NaF, and the amount of accumulated biotin did not increase under those conditions. These results suggest that the binding sites on the cell surface decreased in number or in their binding affinity for biotin through an energy-dependent process.

Actinomycetaceae↗
PubMed1981

Effect and fate of orally administered lactic acid in rats.

We investigated the effect and the fate of an extremely high amount of orally administered lactic acid in rats. The dosed amount of lactic acid, 390 mg per 200 g body weight (30 times higher than that normally detected in the stomach of rats), was determined from the results of observation of acute toxicity of lactic acid in rats. Six hours after the administration of excess lactic acid together with 10 muCi of L-[U-14C]Lactic acid and 10 muCi of D-[U-14C]lactic acid, rats were sacrificed and the pH of the blood, the amount of lactic acid in each organ, L-lactate dehydrogenase (LDH) and some other enzyme activities and incorporation of radioactivities in each fraction of certain organs were measured. The control rats were given the labeled lactic acid and the same volume of water in place of cold lactic acid. Significant decrease of blood pH (delta- pH = 0.14) and increase of blood lactic acid concentration (2-fold) were observed. However, these differences were no longer observed at 24hr after the administration. The amount of lactic acid degraded to expired CO2 was 42.4% in the experimental group, whereas it was 61.3% in the control group. Radioactivities incorporated into protein and lipid fractions in the experimental group were higher than those in the control group, 3.8 and 4.9 times, respectively. It was suggested that an extremely high amount of orally administered lactic acid was utilized as an energy source, and that an excess of lactic acid was incorporated into protein and lipid in addition to degradation into CO2.

Administration, Oral↗