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Biomedical subjects

T Ushijima

Publications and source records attributed to T Ushijima.

201 records · Page 12Linked to original sources

Mutation induction by okadaic acid, a protein phosphatase inhibitor, in CHL cells, but not in S. typhimurium.

Okadaic acid (OA) is a specific and strong inhibitor of protein phosphatases 1 and 2A present in eukaryotes, and a potent promoter of carcinogenesis in mouse skin. In this study, we examined the mutagenicity of OA. OA did not induce mutations in S. typhimurium TA100 and TA98, with or without a microsomal metabolic activation system. However, it was strongly mutagenic to Chinese hamster lung (CHL) cells without a microsomal activation system, as shown using diphtheria toxin (DT) resistance (DTr) as a selective marker. Treatment of CHL cells with OA at 17.5 ng/ml induced 164 DTr mutants per 10(6) survivors. A plot of the mutation frequency against the OA concentration gave a concave curve, and the mutant frequency was calculated to be 5500/10(6) survivors/micrograms, with OA in the dose range of 10-15 ng/ml. This value was about 680 times that of ethyl methanesulfonate (EMS), and comparable to that of 2-amino-N6-hydroxyadenine, one of the strongest known mutagens. Elongation factor 2 (EF-2) obtained from 4 DTr clones was not ADP-ribosylated by DT fragment A. PCR-direct sequencing revealed that the hot spot of EF-2 for EMS mutagenesis in CHO-K1 cells, the first letter of codon 717, was not a hot spot for OA mutagenesis in CHL cells.

Animals↗

Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs.

The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1--34)] and natural bovine PTH containing 84 amino acids [PTH-(1--84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24--34) containing 11 amino acids. PTH-(24--28) containing 5 amino acids, and PTH-(25--27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.

Animals↗

A new experimental model for simultaneous evaluation of aortic and pulmonary allograft performance in a composite graft.

A model was developed in pigs for simultaneous evaluation of aortic and pulmonary allograft performance in a composite graft. The composite graft consisted of vascular prosthesis and aortic and pulmonary allografts. Following antibiotic preservation, it was anastomosed to the recipient's thoracic descending aorta by an extrapleural approach without using cardiopulmonary bypass. Aortic blood flow was completely diverted into the composite graft. All 12 recipient pigs recovered well, 4 of which were assigned for the initial study to design the suitable experimental schedule. Calcification readily occurred in the aortic allografts and aneurysmal dilatation without calcification developed in the pulmonary allografts. These morphological findings were consistent with those of previous reports. This model has several benefits. First, aortic and pulmonary allograft conduits can be implanted and evaluated simultaneously under the same conditions by making a composite graft. Second, the magnitude of the operation is minimum, and postoperative circulatory and respiratory management is uncomplicated. Third, wound infection rarely occurs, because the skin incision is made on the back. These preliminary studies suggest that this model will allow future study concerning aortic and pulmonary allograft conduits under different conditions.

Aneurysm↗