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Biomedical subjects

T Takano

Publications and source records attributed to T Takano.

At least 649 records · Page 36Linked to original sources

Sequential changes in tumor development induced by 1,4-dinitrosopiperazine in the nasal cavity of F344 rats.

Tumor development was examined sequentially in the nasal cavity of male F344 rats given 0.01% 1,4-dinitrosopiperazine (DNP) in their drinking water for various periods. Rats were sacrificed at 10-week intervals for up to Week 50. On continuous DNP administration, simple hyperplasia of the nasal cavity epithelium was observed from Week 10, papillary hyperplasia, nodular hyperplasia, and papilloma was observed from Week 20, and carcinoma was observed from Week 30. Carcinoma was observed in 100% of the animals given DNP for 50 weeks. The carcinomas were adenocarcinomas (86%), adenosquamous cell carcinomas (10%), and undifferentiated carcinomas (4%). Simple hyperplasia was distributed evenly in the nasal cavity. Seventy % of the nodular hyperplasias and 81% of the carcinomas were located in the ethmoturbinate and about 75% of the papillary hyperplasias and papillomas were located in the nasoturbinate and maxilloturbinate. These findings suggest that nodular hyperplasia is very important as a precursor of carcinoma in the nasal cavity of rats treated with DNP and that papilloma is less important in relation to carcinoma development.

Animals↗

Structure of the baboon endogenous virus genome: nucleotide sequences of the long terminal repeat.

The entire nucleotide sequence of the long terminal repeat (LTR) of baboon endogenous virus (BaEV) M7 was determined, which consisted of 554 base pairs (bp). At both ends of the LTR, 13 bp sequences, AAATGAAAAGTAA and TGATTCTAACATC, were detected to be inverted repeats. The structure with these inverted repeats resembles those of other retroviruses and transposable elements. a Hogness box, TATAAAA, and a putative poly(A)-addition signal, AGTAAA, were present within the right-hand half of the LTR, where the initiation and termination of the viral RNA synthesis seems to occur in the integrated BaEV genome. The primer-binding site of at least 14 bp long was found just outside of the LTR where the strong stop DNA started, and the primer for reverse transcription in BaEV seemed to be tRNAPro. Several structural features are commonly detected in the LTRs of BaEV and other retroviruses. Our studies suggest that BaEV has evolved from a common ancestor with other mammalian type C viruses. Close relationships between BaEV and a feline endogenous virus, RD114, are demonstrated.

Cloning, Molecular↗

Purification and properties of rabbit liver acid-lipase (4-methylumbelliferyl oleate hydrolase).

An acid lipase was purified from rabbit liver lysosomes by, in sequence, osmotic treatment of the lysosomal fraction, Sephadex LH-20, DEAE-Sephadex A-50, Bio-Gel A-5m, hydroxyapatite and, finally, Sephadex G-200 column chromatography. The substrate was 4-methylumbelliferyl oleate. The enzyme was solubilized by Sephadex LH-20 column chromatography instead of detergents and organic solvents, to obtain an intrinsic macromolecule. 4-Methylumbelliferyl oleate hydrolase, osmotically released from lysosomal particles, had a very high molecular weight (greater than 800 000) which was reduced by gel filtration on a Sephadex LH-20 column; the final molecular weight of the purified enzyme was 58 000. The specific activity of 4-methylumbelliferyl oleate hydrolase increased at almost the same rate as acid cholesterol esterase and triacylglycerol lipase after Sephadex LH-20 column chromatography; the thermal stability of the activity of the three enzymes was almost identical. We also discuss the properties of the enzyme molecule and the interaction between the enzyme and the lysosomal membrane.

Animals↗

Structure of the baboon endogenous virus genome: cloning of circular virus DNA in bacteriophage lambda.

Linear, small and large circular forms of unintegrated viral DNAs were detected in Hirt supernatant fraction of human cultured cells infected with baboon endogenous virus M7. The circular M7 DNAs were cloned in bacteriophage lambda, Charon 28. Seventeen independent clones were isolated and analyzed by restriction endonuclease mapping. Nine clones were carrying a viral sequence of 8.6 kilobase pairs (kb) with two tandem repeats of 0.6 kb, which correspond to the large circular form of the unintegrated M7 DNA. Eight other clones had the viral insert of 8.0 kb, i. e., the small circular form, and were deleted one of the repeated sequences. The repeated sequences correspond to the long terminal repeats of 0.6 kb, located at both ends of the linear M7 DNA of 8.6 kb. One of the recombinants of the large circular M7 DNA had an inversion of 2.5 kb. One end of the inverted sequence was near the terminus of the long terminal repeats and the other in the gag gene region. The inversion seems to be occurred by integration of a viral DNA within itself during early periods of infection. The mechanism of the processes leading to integration is discussed from the structure of these unintegrated M7 DNAs as the precursors.

Bacteriophage lambda↗

Effects of parathyroid hormone and cyclic AMP analogues on the activity of ornithine decarboxylase and expression of the differentiated phenotype of chondrocytes in culture.

Parathyroid hormone (PTH) greatly increased the level of adenosine 3', 5' cyclic monophosphate (cAMP) in rabbit costal chondrocytes in culture 2 minutes after its addition. PTH, as well as N6 O2' dibutyryl adenosine 3', 5' cyclic monophosphate (DBcAMP) and 8 Bromo adenosine 3', 5' cyclic monophosphate (8 Br-cAMP) induced ornithine decarboxylase (ODC; L-ornithine carboxylyase; EC 4.1.1.17), which reached a maximum 4 hours after their addition. Neither cAMP, N6 O2' dibutyryl guanosine 3', 5' cyclic monophosphate (DBcGMP), nor sodium butyrate increased the activity of the enzyme. PTH had no effect on DNA synthesis, while DBcAMP and 8 Br-cAMP decreased DNA synthesis. Expression of the differentiated phenotype of chondrocytes in culture was also induced by PTH, DBcAMP, and 8 Br-cAMP, but not by cAMP, DBcGMP, or sodium butyrate, as judged by morphological change. Glycosaminoglycan synthesis, a characteristic of the cartilage phenotype, began to increase 8 hours after addition of PTH or DBcAMP, reaching a plateau 32 hours after their addition. These findings suggest that PTH induces increase of ODC activity and expression of the differentiated phenotype of chondrocytes through increase of cAMP and that induction of OCD is closely related to expression of the differentiated phenotype of chondrocytes.

Animals↗

Direct effects of carbon monoxide on cardiac function.

The direct effects of carbon monoxide (CO) on cardiac function were investigated in hemoglobin-free living rabbits treated with perfluorochemical blood substitutes. After exchange transfusion with a perfluorochemical emulsion, the erythrocyte count was below 10 X 10(4)/mm3 in each animal. Gas mixtures of oxygen with 5%, 10%, and 20% of CO or nitrogen were administered via a respirator. The results showed that the cardiac effects of CO and nitrogen were significantly different as regards changes in arterial pressure, pulse pressure, heart rate, and the product of heart rate and systolic arterial pressure in spite of the same oxygen tension in the inhaled gases. It was concluded that there was a direct effect of CO not mediated by hemoglobin.

Animals↗

Dose responses of five hepatocarcinogens for the initiation of rat hepatocarcinogenesis.

Using the Solt and Farber model (Nature, 263 (1976) 701), dose-response relationships between initiating agents and the induction of hyperplastic nodules in rat liver were investigated. Male Fischer 344 rats were initiated by a single application of 1 of 5 carcinogens at 3 doses: 200.0, 50.0 and 12.5 mg/kg of diethylnitrosamine (DEN); 1.00, 0.25 and 0.062 mg/kg of aflatoxin B1 (Af-B1); 60.0, 15.0 and 3.75 mg/kg of N-2-fluorenylacetamide (2-FAA); 600.0, 150.0 and 37.5 mg/kg of 3'-methyl-4-dimethylaminobenzene (3'-me-DAB); 40.0, 10.0 and 2.5 mg/kg of dimethylnitrosamine (DMN) and their vehicles. Two weeks after initiation, animals were placed on a 0.02% 2-FAA diet for 2 weeks. Partial hepatectomy was performed at the end of the third week of the experiment. All rats were killed 4 weeks after the initiation, and the hyperplastic nodules of the liver were counted and their areas measured. Dose responses were observed in both numbers and areas of hyperplastic nodules per unit area of sections with all of the 5 carcinogens examined.

2-Acetylaminofluorene↗

Structure of a B-DNA dodecamer: conformation and dynamics.

The crystal structure of the synthetic DNA dodecamer d(CpGpCpGpApApTpTpCpGpCpG) has been refined to a residual error of R = 17.8% at 1.9-A resolution (two-sigma data). The molecule forms slightly more than one complete turn of right-handed double-stranded B helix. The two ends of the helix overlap and interlock minor grooves with neighboring molecules up and down a 2(1) screw axis, producing a 19 degrees bend in helix axis over the 11-base-pair steps of the dodecamer. In the center of the molecule, where perturbation is least, the helix has a mean rotation of 36.9 degrees per step, or 9.8 base pairs per turn. The mean propeller twist (total dihedral angle between base planes) between A . T base pairs in the center of the molecule is 17.3 degrees, and that between C . G pairs on the two ends averages 11.5 degrees. Individual deoxyribose ring conformations as measured by the C5'-C4'-C3'-O3' torsion angle delta, exhibit an approximately Gaussian distribution centered around the C1'-exo position with delta avg = 123 degrees and a range of 79 degrees to 157 degrees. Purine sugars cluster at high delta values, and pyrimidine sugars cluster at lower delta. A tendency toward 2-fold symmetry in sugar conformation about the center of the molecule is detectable in spite of the destruction of ideal 2-fold symmetry by the molecular bending. More strikingly, sugar conformations of paired based appear to follow a "principle of anticorrelation," with delta values lying approximately the same distance to either side of the center value, delta = 123 degrees. This same anticorrelation is also observed in other DNA and DNA . RNA structures.

Deoxyribose↗

Role of polyamines in expression of the differentiated phenotype of chondrocytes in culture.

Addition of putrescine to cultures of rabbit costal chondrocytes during the log-phase stimulated expression of their differentiated phenotype, as judged by increase in the synthesis of glycosaminoglycans and of metachromasia with toluidine blue staining. Putrescine stimulated glycosaminoglycan synthesis maximally at a concentration of 10(-7) M, and spermidine and spermine were also effective at similar concentration. These polyamines had little effect on DNA synthesis, RNA synthesis, DNA accumulation, or protein accumulation. These findings suggest that polyamines may be important in the expression of the differentiated phenotype of chondrocytes in culture.

Animals↗