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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 505 records · Page 28Linked to original sources

Effect of continuous intravesical infusion of low-concentrated mitomycin-C on bladder carcinogenesis in rats treated with N-butyl-N-4-hydroxybutyl-nitrosamine.

In the first experiment, histological changes of urinary bladder after long-term transvesical catheterization were evaluated in normal rats. No malignant changes of the bladder epithelium were detected in the two and four-week catheterization groups. However incidences of papilloma and papillary carcinoma developed in three of the five rats (60%) in the eight-week group. In a second experiment the therapeutic effect of continuous or intermittent administration of MMC on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. MMC at a total dose of four mg. was administered for two weeks in both therapeutic groups. Continuous infusion was performed transvesically using an osmotic pump and a silicone catheter, on the basis that preliminary examination revealed the urinary delivery rate of MMC was constant for two weeks. In the intermittent group, MMC solution was instilled transurethrally with a venural catheter twice a week. The continuous infusion of low concentrated MMC reduced significantly (p less than 0.02) the incidence of tumor development in spite of extended catheterization (for eight weeks) into the bladder. However, the intermittent instillation of high concentrated MMC hardly inhibited the development of bladder tumors. We should consider the optimal concentration and time of a drug in intravesical chemotherapy based on the above findings.

Administration, Intravesical↗

Isolation of virus-producing transformants from human gastric cancer cell line, HGC-27, infected with human T-cell leukemia virus type I.

A human anaplastic gastric cancer cell line, HGC-27, showed marked degeneration with formation of multinucleated syncytia and cell detachment of nearly all cells which began 24 hr after and reached a maximum 2 to 3 days after co-cultivation with X-irradiated MT-2 cells, HTLV-I producing human cord leukocytes. Less severe degeneration without formation of syncytia was also observed in the cultures inoculated with cell-free MT-2 culture media. Morphologically altered cells began to proliferate and formed piled up colonies in some of the cultures co-cultivated with X-irradiated MT-2 cells after a long culture period. The two clones designated HGC/MT2 (Cl-1) and HGC/MT2 (Cl-2) were separated by cell cloning. HGC/MT2 (Cl-1) and HGC/MT2 (Cl-2) cells were positive for HTLV-I gag proteins (p19 and p24) and pX gene products, p40x, as demonstrated by immunohistochemistry and immunoblotting analysis, contained HTLV-I provirus DNA, and consistently produced type C virus particles.

Cell Transformation, Viral↗

Effect of pentobarbital on gastric acid secretion elicited by secretagogues or electrical vagal stimulation in rats under urethane anesthesia.

The effect of pentobarbital, which stimulates gastric acid secretion in urethane-anesthetized rats, on secretagogue-stimulated or electrically stimulated acid secretion was studied in the rat perfused stomach. 2-Deoxy-D-glucose (2-DG)-stimulated gastric acid secretion was markedly depressed by intravenous injection of pentobarbital, but was definitely increased by lateral cerebroventricular injection and was unaffected by injection into the fourth cerebroventricle. Bethanechol-stimulated secretion was augmented by intravenous injection of pentobarbital. In vagotomized rats, pentobarbital did not affect the bethanechol-stimulated or electrically vagally stimulated secretion. These findings indicate that pentobarbital produces both stimulatory and inhibitory effects on gastric acid secretion through a central mechanism, especially in the forebrain. It was proposed that the inhibitory response would result from some interaction of intravenous 2-DG and pentobarbital in the central regulatory system of gastric secretion.

Animals↗

Structure specificities of yohimbine and indoloquinolizidine derivatives in blocking alpha-adrenoceptor and calcium channel.

1,12b-Cis-1-p-nitrobenzoyloxyindoloquinolizidine as well as 14 beta-p-nitrobenzoyloxyyohimbine possessed potent calcium channel blocking activities in the isolated rat perfused mesenteric vascular bed. Introduction of the bulky substituents to C-14 of yohimbine or to C-1 of indoloquinolizidine resulted in enhancement of the calcium channel blocking activities. By comparison of chemical structures between yohimbine and indoloquinolizidine, it was found that the E ring of yohimbine had no association with the calcium channel blocking activities. On the other hand, alpha 1- and alpha 2-adrenoceptor antagonistic activities which were tested in the rat mesenteric vascular bed and in the rat vas deferens, respectively, were markedly reduced by such introduction of the bulky substituents to yohimbine and indoloquinolizidine. From these results, it is expected that chemical modifications of indoloquinolizidine at the C-1 position provide new types of agents with calcium channel blocking activities.

Adrenergic alpha-Antagonists↗

Synergistic therapeutic effect of combination therapy with OK-432 and interferon-alpha or -gamma on Meth-A ascites tumor in BALB/c mice.

A synergistic therapeutic effect on Meth-A ascites tumor was obtained in BALB/c mice by the simultaneous i.p. injection of OK-432 and interferon alpha A/D (IFN-alpha). BALB/c mice that were cured of their Meth-A tumors showed significant tumor-specific rechallenge resistance. Combined therapeutic effect was significantly weaker in nude mice than in haired mice. The stimulation of host T-cell immunity was indicated to be crucially important for obtaining cured mice. Natural killer activity of peritoneal exudate cells was enhanced and peaked on day 1 with IFN-alpha, on day 3 with OK-432, and was sustained for up to 5 days with combination therapy. Macrophage activity assayed by in vivo resistance to the challenge of Listeria monocytogenes was stronger in order of OK-432 greater than OK-432 + IFN-alpha greater than IFN-alpha. Cytotoxic T-lymphocyte activity induced by immunization with the allogeneic tumor was enhanced most strongly by OK-432 plus IFN-alpha treatment. Each of the agents had tumor inhibitory activity on the growth of Meth-A cells in vitro, and there was a slight additive effect when two agents were used together. These findings suggest that the synergistic therapeutic effect of OK-432 plus IFN-alpha treatment on Meth-A ascites tumor was partly due to the direct antitumor activity of these two agents, but was also due in part to the beneficial antitumor immune responses that were induced. A similar synergism on Meth-A tumor was also observed by OK-432 plus interferon gamma treatment. However, this combination therapy was not effective on MH-134 ascites tumor in C3H mice.

Animals↗

[Left and right ventricular cardiac outputs in early neonatal periods examined using Doppler echocardiography].

To evaluate early neonatal circulatory adaptation, left and right ventricular cardiac outputs were examined in 10 normal neonates using Doppler echocardiography. Serial examinations were performed until ductal closure was confirmed. Two-dimensional echocardiography and Doppler echocardiography were used to evaluate structures of the heart and great vessels and flow within them. Then, the diameters of the ascending aorta (dAo) and pulmonary artery (dPA) were measured using M-mode echocardiography. The flow velocity patterns of the ascending aorta and pulmonary artery were recorded, measuring mean aortic (VAo) and pulmonary artery velocities (VPA). Left (LVCO) and right ventricular cardiac outputs (RVCO) were calculated as follows: LVCO = (dAo)2/4 x pi x VAo x 60, RVCO = (dPA)2/4 x pi x VPA x 60. 1. Patency of the ductus arteriosus was confirmed by the shunt through it in all neonates initially examined. The initial velocity pattern of the ductal shunts was bidirectional (9/10) or continuous left-to-right (1/10). The flow velocity pattern changed to continuous left-to-right in most neonates, and spontaneous closure of the ductus was confirmed at the age of 13 to 64.5 (mean 31.4) hrs. 2. Left-to-right shunt through the stretched foramen ovale was noted in six neonates temporarily. 3. As for the arterial diameter, dAo did not change, but dPA decreased at the time of spontaneous closure of the ductus. 4. Concerning mean aortic velocity, VAo increased when a continuous ductal left-to-right shunt was initially suspected, while VPA increased when spontaneous closure of the ductus was confirmed. 5. For cardiac output, LVCO (ml/min) changed from 618.4----718.3----562.7, while RVCO showed no change (576.1----546.5----557.8) according to a ductal flow change from bidirectional to continuous left-to-right and finally to no shunt. The LVCO/RVCO ratio increased with increasing age and (in 7/9) the maximal rate was noted when the continuous left-to-right ductal shunt was confirmed. The increased LVCO contributed to the increased LVCO/RVCO ratio. Using this method, serial evaluations of two ventricular cardiac outputs could be made.

Aorta↗

Effect of drug administration on experimental renal glomerular thrombosis.

Experimental thrombosis which developed exclusively in glomerular capillary walls was induced in rats by the combined injection of nephrotoxic antiserum (0.2 ml of pooled material) as a preparatory agent and 20 micrograms or more of lipopolysaccharide as a provoking agent. Effects of some antiplatelet and anticoagulant drugs on the glomerular lesions were tested in this experimental glomerular thrombosis. With administration of 2000 units/kg or more of heparin at the time of provoking injection, coagulation time was prolonged for over 5 hr, and the glomerular thrombosis was adequately prevented. Prolongation of prothrombin time (PT) for over 60 sec to prevent thrombosis required warfarin, but with this drug there was only a narrow margin between an effective dose and that which produced a fatal hemorrhage. Low levels of fibrinogen (less than 50 mg/dl) induced by batroxobin seemed to protect partially and high doses of urokinase did not seem to protect from glomerular thrombosis. OP-41483, a derivative of prostacyclin which is about five times more active than PGE1 in inhibiting platelet aggregation, and other anti-platelet drugs except for ticlopidine were not effective in preventing glomerular thrombosis. These findings were in accordance with the fact that thrombocytopenia induced by antiplatelet antiserum did not prevent glomerular thrombosis. Ticlopidine may have a unique and valuable therapeutic potential for the control of this condition.

Animals↗

[An autopsied case of pulmonary carcinoma with perforation peritonitis due to metastatic tumor necrosis at the jejunum caused by chemotherapy].

A 76-year-old man with lung carcinoma, who was undergoing both radiotherapy and chemotherapy (CDDP + ADR) suddenly died with the onset of abdominal symptoms. Autopsy disclosed that the main cause of death was suppurative panperitonitis, caused by a perforation of a metastatic lesion at the jejunum. A histological examination revealed extensive tumor necrosis in the metastatic liver lesions as well as in the jejunal lesions. Neither inflammatory nor circulatory damage was observed in the perforated lesion. Therefore, the cause of this perforation was considered to be chemotherapy that had brought on tumor necrosis. No similar reports of lung cancer deaths have been found in the literature in which the microscopic details were described. Accordingly, this case is reported for future reference with regard to cancer chemotherapy.

Adenocarcinoma↗

Stimulation of gastric acid secretion by microinjection of pentobarbital into the ventromedial hypothalamus.

Sites of stimulatory action of pentobarbital on gastric acid secretion were studied in rats anesthetized with urethane. Intracerebroventricular injection of pentobarbital dose-dependently stimulated gastric secretion. When injections of pentobarbital into the ventromedial hypothalamus were repeated with an interval of 30 min, the second and third consecutive injections produced a small but significant increase in gastric acid secretion. We propose that the ventromedial hypothalamus is involved in the stimulatory effect of pentobarbital on gastric acid secretion.

Animals↗

Morphine inhibits the gastric acid secretion stimulated by 2-deoxy-D-glucose via a central mechanism in anesthetized rats.

The effect of morphine on the gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was investigated in the perfused stomach of anesthetized rats. The intravenous infusion of morphine (0.01-1.0 mg/kg per h for 2 h) dose dependently suppressed the gastric acid secretion stimulated by 2-DG. This inhibitory effect of morphine was completely reversed by naloxone (1.0 mg/kg i.v.) pretreatment. On the other hand, even the higher dose of morphine (1.0 mg/kg per h for 70 min) had no effect on the gastric acid secretion evoked peripherally by electrical stimulation of the vagus nerve. These observations indicate that morphine suppressed the 2-DG-induced gastric acid secretion via a central mechanism(s), probably mediated by the opiate receptor(s).

Anesthesia↗

Effects of poly I: poly C on rat pulmonary and hepatic cytochromes P-450 and b5.

Interferon inducing agents such as poly I:poly C have been shown to reduce the hepatic hemoproteins cytochromes P-450 and b5 along with the associated monooxygenase activities [el Azhary and Mannering, Molec. Pharmac. 15, 698 (1979)]. In a previous study [Kikkawa et al., Lab. Invest. 50, 62 (1984)], we demonstrated that the interferon inducing agent poly I:poly C reduces pulmonary microsomal hemoprotein by 50% when administered to rats. The current investigation was conducted to characterize these changes in more detail and compare them to analogous changes in the liver. Compared to controls, cytochrome P-450 in both the lungs and livers of poly I:poly C treated rats declined by 40% at 24 hr and 55% at 48 hr (P less than 0.01). By 72 hr the decline was only 25%. In contrast, cytochrome b5 levels declined by less than 30% of control values during the first 48 hr following poly I:poly C injection (P less than 0.01) and returned to control levels by 72 hr. These changes in both cytochrome P-450 and b5 were reflected in decreases in pulmonary microsomal hemoprotein. Benzphetamine-N-demethylase activity declined by 45% in lung microsomes at 48 hr (P less than 0.01) after injection of poly I:poly C, while 7-ethoxycoumarin-O-deethylase (P less than 0.05) and 7-ethoxyresorufin-O-deethylase activities declined by approximately 41%. In the liver from these same poly I:poly C treated groups, benzphetamine-N-demethylase declined by 66% (P less than 0.05), while 7-ethoxycoumarin-O-deethylase and 7-ethoxyresorufin-O-deethylase activities declined by 60% (P less than 0.02 and P less than 0.05 respectively).

Animals↗

Antioxidant enzymes and survival of normal and simian virus 40-transformed mouse embryo cells after hyperthermia.

Relative cell survival and activity of the free radical scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase were measured in cloned normal (MEA) and SV40-transformed (SVMEA) mouse embryo cells exposed at 44 degrees C for 0-3 h. At 37 degrees C, all three enzymes were 2-5 times higher in MEA than in SVMEA. Hyperthermia did not significantly alter enzyme levels in either cell line but selectively reduced transformed cell survival to less than 5% while relative survival of normal cells remained above 75%. The latter, however, could be reduced to 25% when normal cells were pretreated with 3 mM diethyldithiocarbamate, an inhibitor of copper- and zinc-containing superoxide dismutase. Similar treatment rendered SVMEA extremely thermosensitive. On the other hand, sublethal heat treatment (15 min at 45 degrees C) of cultured cells resulted in a relative thermal resistance upon subsequent exposure to 45 degrees C for 1-4 h. This induced thermotolerance was associated with a rise in antioxidant enzyme levels and both became significant only 4-6 h after the initial heat treatment. Induced enzyme and thermotolerance levels in transformed cells remained, nonetheless, far below those of normal cells. The data show that inherent (in MEA) as well as induced (in SVMEA) thermotolerance is associated with high antioxidant enzyme levels while the reverse is true in the case of inherent (in SVMEA) and induced (in MEA) thermosensitivity. These findings suggest that increased production of oxygen free radicals may be involved in hyperthermic cell injury, which then becomes a function of basal or inducible levels of antioxidant enzymes. Induction of the latter by hyperthermia is apparently inefficient in transformed cells making them more vulnerable. Enzyme induction seems also to require a lag period of 4-6 h suggesting the possible involvement of an intermediate inducer(s) at molecular level. The so-called heat shock proteins may be candidates for such a role.

Animals↗