Biomedical subjects

A Fujihara

Publications and source records attributed to A Fujihara.

At least 19 recordsLinked to original sources

PubMed2000

Requirement of transfer-messenger RNA for the growth of Bacillus subtilis under stresses.

BACKGROUND: Bacterial transfer-messenger RNA (tmRNA, 10Sa RNA) is involved in a trans-translation reaction which contributes to the degradation of incompletely synthesized peptides and to the recycling of stalled ribosomes. However, its physiological role in the cell remains elusive. In this study, an efficient system for controlling the expression of the gene for tmRNA (ssrA), as well as a tmRNA gene-defective strain (ssrA:cat), were constructed in Bacillus subtilis. The effects of tmRNA on the growth of the cells were investigated under various physiological culture conditions using these strains. RESULTS: The cells were viable in the absence of ssrA expression under the usual culture conditions. However, the growth rate of cells without tmRNA expression, relative to that of the expressed cells, decreased with elevating temperature (> 45 degrees C), and at 52 degrees C, the highest temperature for growth of the wild-type, cells grew depending on the expression level of tmRNA. Furthermore, the transcription level of the ssrA from the authentic promoter at a high temperature (51 degrees C) was about 10-fold higher than that at a lower temperature (37 degrees C). tmRNA-dependent growth and an increase in tmRNA amount were also observed in cells under other stresses, such as high concentrations of ethanol or cadmium chloride. It is also shown that alanylated tmRNA rather than tmRNA-mediated proteolysis is required for growth at high temperature. CONCLUSION: The expression of tmRNA gene (ssrA) is required for the efficient growth of B. subtilis under several strong stresses. The transcription of ssrA increases under several stressful conditions, suggesting that it is a stress-response gene. Alanyl-tmRNA, probably via its ability of recycling stalled ribosomes via trans-translation, is involved in the stress tolerance of bacteria.

Alanine↗

PubMed1996

Antitumor activity of zinostatin stimalamer (YM881) in human hepatoma cell lines and VX2 liver tumor-bearing rabbits.

Antitumor activities of zinostatin stimalamer (YM881) were examined in human hepatoma cell lines (SK-Hep1 and HuH2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 causing a 50% inhibition of growth of SK-Hep1 and HuH2 cells were 6.7 and 27 nM, respectively. In VX2 tumor-bearing rabbits, administration of YM881 suspended in Lipiodol, an iodinated fatty acid ethylester of poppyseed oil, (YM881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs. sham-operated and Lipiodol-treated groups) inhibitory effects on tumor growth and histopathological changes at 1 and 2 weeks after administration. In contrast, Lipiodol (0.2 ml/body) tended to inhibit the growth of VX2 tumor (p < 0.1, vs. sham-operated group) at 1 week after administration, but showed only moderate effects at 2 weeks after administration. Minimal necrosis was observed at 1 and 2 weeks after administration of Lipiodol, and histopathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM881/Lipiodol suspension showed antitumor activity in VX2 tumor-bearing rabbits presumably due to the inhibition of the growth of hepatoma cells by YM881 itself. Lipiodol, on the other hand, is considered to augment the antitumor activity of YM881 by maintaining high YM881 concentrations in tumor tissue.

Animals↗

PubMed1994

[Intra-arterial combination chemotherapy using both regimen selected by chemosensitivity test and caffeine to increase effect for osteosarcoma in extremity].

We treated three patients with osteosarcoma in extremity with intra-arterial combination chemotherapy using a regimen selected by succinate dehydrogenase inhibition chemosensitivity test, and used caffeine to enhance its effect. In two patients with osteosarcoma in distal diametaphysis of the radius and extraskeletal osteosarcoma in sole of the foot, the effect of intra-arterial combination chemotherapy was increased and followed by the functional limb salvage procedure. But in one patient with osteosarcoma in the proximal tibia, the effect of pre-operative intra-arterial combination chemotherapy could not be increased, so amputation was required. He was changed to a post-operative intra-venous combination chemotherapy regimen selected by chemosensitivity test of the surgical material. All patients have been continuously disease-free at five to twelve months after surgery.

Adolescent↗

PubMed1994

[Anti-tumor activity of zinostatin stimalamer (YM 881) examined by human hepatoma cells in vitro and VX2 liver tumor in vivo].

Anti-tumor activities of zinostatin stimalamer (YM 881) were examined using human hepatoma cell lines (SK-Hep1 and HuH 2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 against SK-Hep 1 and HuH 2 cells were 6.7 and 27 mM, respectively. In VX2 tumor-bearing rabbits, administration of YM 881 suspended in iodinated fatty acid ethylesters of poppyseed oil (YM 881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs sham-operated and Lipiodol-treated groups) inhibitory effects on the growth and pathological changes 1 and 2 weeks after administration. On the other hand, Lipiodol (0.2 ml/body) showed a tendency to inhibit the growth of VX2 tumor (p < 0.1, vs sham-operated group) 1 week after administration, but it showed only moderate effects on the VX2 tumor growth 2 weeks after administration. Minimal necrosis was observed 1 and 2 weeks after administration of Lipiodol, and these pathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM 881/Lipiodol suspension showed the anti-tumor activity against VX2 tumor-bearing rabbits, presumably due to the inhibition of the growth of hepatoma cell by YM 881 per se. On the other hand, Lipiodol is considered to augment the anti-tumor activity by maintaining high YM881 concentrations in tumor tissue.

Animals↗

PubMed1993

Antisecretory effects of a novel and long-lasting histamine H2-receptor antagonist, YM-14471, in rats and dogs.

We investigated some properties of YM-14471 (2-2(-[2-(diaminomethyleneamino)thiazol-4-yl]methylthio)ethy l-5-[3- (diethylamino)propyl]-6-methyl-pyrimidine-4-one trihydrochloride), a new H2-receptor antagonist, in comparison with those of famotidine, cimetidine and omeprazole. In guinea pig atria, famotidine and cimetidine produced a competitive dose-dependent displacement of histamine-induced tachycardia. In contrast, low concentrations of YM-14471 showed competitive inhibition of tachycardia, whereas high concentrations were irreversible or slowly dissociable. In pylorus-ligated rats, intravenous YM-14471, famotidine and cimetidine dose-dependently inhibited basal gastric secretion with ED50 values of 0.04, 0.43 and 31.2 mg/kg, respectively. ED50 values for oral YM-14471, famotidine, cimetidine and omeprazole were 0.81, 0.42, 28.9 and 7.7 mg/kg when given at 1 hr before ligation, and 5.7, 26.7, 1639.5 and 18.6 mg/kg at 5 hr before ligation. In anesthetized dogs, intravenous YM-14471, famotidine, cimetidine and omeprazole also dose-dependently inhibited histamine (160 micrograms/kg.hr)-induced acid secretion with ED50 values of 13.7, 8.7, 333.3 and 65.3 micrograms/kg, respectively. In Heidenhain pouch dogs, YM-14471 inhibited histamine (40 micrograms/kg.hr)-induced acid secretion by both intravenous (0.02 mg/kg) and oral administration (0.3 mg/kg). Moreover, the inhibitory effect of YM-14471 was more prolonged than those of famotidine and cimetidine by either route, and it was as long as that of omeprazole dosed orally. These results suggest that YM-14471 is an irreversible or slowly dissociable H2-receptor antagonist, and has long antisecretory effect.

Animals↗

PubMed1990

Selective and competitive histamine H2-receptor blocking effect of famotidine on the blood pressure response in dogs and the acid secretory response in rats.

Famotidine has been already demonstrated to be a competitive H2-receptor antagonist in the stomachs of dogs and cats. The present experiments were carried out to examine the effects of famotidine on changes in blood pressure induced by dimaprit and several other agonists in vagotomized, anesthetized dogs and on changes in gastric acid secretion induced by histamine in stomach-perfused, anesthetized rats. Famotidine caused a parallel displacement of the dimaprit dose-response curve to the right with a DR10 value of 0.059 mumols/kg, indicating that famotidine is 166 times more potent than cimetidine in vascular H2-blocking activity. On the contrary, famotidine did not affect the depressor responses to 2-pyridylethylamine and histamine that were antagonized by mepyramine. The histamine dose-response curve was displaced to the right more markedly after simultaneous administration of mepyramine and famotidine than after mepyramine alone. The effects of methacholine, phenylephrine and isoproterenol on blood pressure were not influenced by famotidine in doses up to 720 nmol/kg. In rats, famotidine also caused a parallel displacement of the acid dose-response curve to histamine to the right with a DR3 value of 24 mumols/kg/hr in stomach-perfused rats anesthetized with pentobarbital, exhibiting a potency 108 times greater than that of cimetidine. Analysis of the acid dose-response curve with the Edie-Hofstee transformation showed that famotidine, like cimetidine, was a competitive H2-receptor antagonist.

Anesthesia↗

PubMed1990

Cardiovascular and bronchial actions of famotidine in anesthetized dogs.

The effects of famotidine (Gaster; CAS 76824-35-6) and cimetidine on cardiovascular and bronchial functions were investigated in anesthetized dogs. Famotidine did not affect heart rate, blood pressure, left ventricular pressure (LVP), max. dLVP/dt, cardiac output or coronary blood flow at i.v. doses of 1 to 30 mg/kg in open-chest dogs anesthetized with pentobarbital or a combination of nitrous oxide, oxygen and halothane (GOF). No hemodynamic changes were either observed after famotidine in pentobarbital anesthetized dogs whose cardiac function was depressed by propranolol (1 mg/kg i.v.). On the contrary, cimetidine dose-dependently decreased heart rate and blood pressure at doses greater than 3 mg/kg, and left ventricular pressure, cardiac output and coronary blood flow at the dose of 30 mg/kg. Regarding the electrocardiogram (ECG), famotidine did not produce any remarkable change at doses up to 30 mg/kg with the exception of a transient increase or decrease in the T-wave amplitude at a dose of 30 mg/kg. Cimetidine prolonged Q-T intervals of ECG in addition to changing the T-wave at a dose of 30 mg/kg. Neither famotidine nor cimetidine showed any effect on resting and histamine-increased bronchoresistance at doses up to 30 mg/kg. It is concluded that famotidine is superior to cimetidine with regard to safety because famotidine has no significant effects on cardiovascular functions in anesthetized dogs.

Airway Resistance↗

PubMed1989