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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 937 records · Page 52Linked to original sources

Esophageal and gastric cancers with metastases induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.

Three 6-month-old male beagle dogs were given a solution of 150 microng N-ethyl-N'-nitrosoguanidine (ENNG)/ml to drink ad libitum for 9 months. They all developed esophageal squamous cell carcinomas and gastric adenocarcinomas. The stomach adenocarcinomas were mostly in the antrum along the lesser curvature and were either well differentiated or poorly differentiated, with or without signet ring cells. The well-differentiated adenocarcinomas metastasized to the liver, and the poorly differentiated ones metastasized to the lymph nodes. The gastric mucosa in the antrum was atrophic, and the muscularis mucosae was fibrotic. Esophageal lesions were multicentric moderately differentiated squamous cell carcinomas, and they developed without diffuse hyperplastic changes of the epithelium. One dog with a large ulcerated carcinoma of the esophagus had metastases in the lung, liver, peritoneum, and abdominal lymph nodes. One dog also had a hemangiosarcoma with hepatic metastasis and spindle cell sarcoma in the stomach and duodenum, respectively.

Adenocarcinoma↗

Further studies on the effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of a microbial protease inhibitor, leupeptin, on the induction of urinary bladder tumors in W rats by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Three groups of animals were given 0.01% BBN in their drinking water for 12 weeks. A basal powder diet supplemented with 0.1% leupeptin was given to group A throughout the experiment and to group B when BBN administration was stopped. Group C was given the basal diet without leupeptin throughout the study. The total preservation period was 40 weeks. Results clearly showed that when leupeptin was given during the promotion step of bladder carcinogenesis (as in group B), it increased the size of tumors and the incidences of cancer and invasion. When leupeptin was given throughout the experiments, its effect was counteracted (as in group A).

Animals↗

Interactions of norharman and harman with DNA.

The interactions of norharman (9H-pyrido [3,4-b] indole) and harman (1-methyl-9H-pyrido [3,4-b] indole) with DNA were studied. DNA caused remarkable fluorescence quenching and change in the absorption spectra of the dyes. Scatchard plots obtained by optical titration gave Kd values of 2.2 X 10(-5)M and 7.7 X 10(-6)M, and apparent numbers of binding sites of 0.13/base and 0.12/base for norharman and harman, respectively. Agarose gel electrophoresis of circular DNA, closed in the presence or absence of norharman revealed that the dye intercalates DNA, thereby causing 17 +/- 3 degrees unwinding of the double helix.

Alkaloids↗

A 13C NMR study of poly(adenosine diphosphate ribose) and its monomers: evidence of alpha-(1'' leads to 2') ribofuranosy1 ribofuranoside risidue.

The 13C NMR spectra of poly(adenosine diphosphate ribose), ribosyl adenosine 5', 5''-bis(phosphate) and related compounds were analyzed. The structure of the ribose-ribose linkage was determined as alpha-(1'' leads to 2')ribofuranosyl ribofuranoside, from the 13C chemical shifts of methyl-alpha- and methyl-beta-D-ribofuranosides, and from the downfield displacements of 13C NMR signals by glycosidic bond formation.

Adenosine Diphosphate Sugars↗

Natural occurence of a biopolymer, poly (adenosine diphosphate ribose).

Evidence for the natural occurrence of poly(adenosine diphosphate ribose) in vivo was obtained using a sensitive radioimmunoassay and poly(adenosine diphosphate ribose) glycohydrolase, which specifically hydrolyzes poly(adenosine diphosphate ribose). Calf thymus, liver, kidney, brain, pancreas and spleen contained poly(adenosine diphosphate ribose). Naturally occurring poly(adenosine diphosphate ribose) in calf thymus is composed of molecules of various chain lengths, like that synthesized by an in vitro system. Calf thymus was estimated to contain about 0.02 microgram/mg DNA of poly(adenosine diphosphate ribose).

Animals↗

Effect of leupeptin on induction of lymphoblastic leukemia in mice by N-nitrosobutylurea.

The effect of leupeptin on the induction of lymphoblastic leukemia in ICR/JCL female mice by N-nitrosobutylurea (NBU) was investigated. NBU was given as a 0.02% solution in drinking water for 10 weeks. A 0.1% concentration of leupeptin was given in the diet. Group A was fed on the leupeptin diet from the beginning, Group B received it after the end of NBU treatment, and Group C was fed on a leupeptin-free control diet throughout. The average periods in the appearance of leukemia in groups A, B, and C were 115+/-50, 112+/-43, and 100+/-17 days (mean+/-SD), respectively, and there was a significant difference between groups A and B and Group C at P less than 0.001. In regard to this point, leupeptin might have the effect of retarding the rpocess of leukemogenesis. However, leupeptin showed no effect on the incidence and histopathological finding of leukemia.

Animals↗

Isolation of transitional epithelial cells from the rat urinary bladder.

A method was developed to isolate transitional cells from the mucous lining of the rat urinary bladder by treatment with ethylene diaminetetraacetic acid and sonication. The isolated cells were examined by phase contrast microscopy, Giemsa staining, and scanning electron microscopy. Two types of isolated cells were distinguished: large ones which were characterized as superficial cells and smaller ones which seemed to be intermediate basal cells.

Animals↗

A novel phosphodiesterase from cultured tobacco cells.

A novel phosphodiesterase was purified from cultured tobacco cells to a state which appeared homogeneous on polyacrylamide gel electrophoresis. The enzyme hydrolyzed various phosphodiester and pyrophosphate bonds, including p-nitrophenyl thymidine 5'-phosphate, p-nitrophenyl thymidine 3'-phosphate, cyclic nucleotides, ATP, NAD+, inorganic pyrophosphate, dinucleotides, and poly(adenosine diphosphate ribose), which is a polymer synthesized from NAD+. However, it did not hydrolyze highly polymerized polynucleotides. The molecular weight of the native enzyme was estimated as 270 000 to 280 000 by gel filtration on Sephadex G-200 and Bio-Gel A-5m. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the enzyme was composed of subunits with molecular weights calculated to be 75 000. The enzyme did not require divalent cations for activity being fully active in the presence of ethylenediaminetetraacetic acid. The pH optimum for the enzyme was approximately 6 with p-ni-trophenyl thymidine 5'-phosphate or adenosine cyclic 3',5'monophosphate, and 5.3 with NAD+. Double reciprocal plots of the initial velocity against the concentration of p-nitrophenyl thymidine 5'-phosphate gave two apparent Km values of 0.17 and 1.3 mM, suggesting the presence of at least two active sites.

Hydrogen-Ion Concentration↗

Mutagenicities of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid.

Many nitrofuran derivatives are known to be mutagenic on Escherichia coli WP2 but not on Salmonella typhimurium TA1535, TA1536, TA1537 or TA1538. Ames and coworkers recently obtained a new tester strain of S. typhimurium, TA100, by putting an R factor plasmid, pKM101, into TA1535. We found that all mutagenic nitrofuran derivatives previously found to be mutagenic on E. coli WP2 were mutagenic on this new strain (TA100).

Drug Resistance, Microbial↗

Effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by n-butyl-n-(4-hydroxybutyl)nitrosamine.

Leupeptin, isolated from Actinomycetes, is a potent and specific inhibitor of proteases. We found that the administration of leupeptin enhanced that size of urinary bladder tumors induced in rats by the oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). BBN was given as a 0.05% solution in the drinking water for 6 weeks, and then animals were fed a diet with or without 0.1% leupeptin for 30 weeks. The average weight of the bladders with tumors in rats fed a leupeptin diet was about eight times that of rats on a diet without leupeptin, though the incidences and average numbers of tumors in the bladders were similar in the two groups.

Animals↗