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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 739 records · Page 41Linked to original sources

Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation.

The efficacy of denopamine, an orally active beta 1-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118 +/- 28 mg; mean value +/- SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10-300 micrograms) in a dose-dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.

Animals↗

The association of imperforate anus and Hirschsprung's disease in siblings.

The recognition of Hirschsprung's disease is often delayed in children with imperforate anus. Two siblings with imperforate anus who were born of consanguineous parents had persistent constipation after the repair of the anorectal malformation. Subsequently colon biopsy confirmed that each had long segment aganglionosis beginning at the splenic flexure. A suspicion that these two disorders may coexist is mandatory for early correct diagnosis.

Anus, Imperforate↗

DNA topoisomerase II is required at the time of mitosis in yeast.

We have constructed five new temperature-sensitive DNA topoisomerase II mutations and have analyzed their physiological consequences in yeast. Several lines of evidence suggest that the activity of topoisomerase II is required specifically at the time of miosis. First, top2 mutations cause dramatic lethality at the restrictive temperature, but only if the mutant cells are actively traversing the cell cycle. Second, temperature-shift experiments with synchronized cultures show that the onset of inviability coincides with the time of mitosis. Third, fluorescence microscopy reveals that the normal progression of mitosis is disturbed in mutant cells at the restrictive temperature. Finally, inviability at the restrictive temperature is prevented by nocodazole, an inhibitor of tubulin polymerization that prevents formation of the mitotic spindle. These results are consistent with the hypothesis that the essential function of topoisomerase II is to allow the separation of intertwined chromosomal DNA molecules during mitosis.

Benzimidazoles↗

Cloning of yeast TOP1, the gene encoding DNA topoisomerase I, and construction of mutants defective in both DNA topoisomerase I and DNA topoisomerase II.

Rabbit antibodies specific to yeast DNA topoisomerase I were used in immunological screening of a Saccharomyces cerevisiae genomic DNA library in Escherichia coli. One of the clones identified by its expression of antigenic determinants of the yeast enzyme is shown to contain the coding sequence of the enzyme: no active DNA topoisomerase I is detectable in cell extracts when insertion or deletion mutations are introduced into a 2-kilobase-pair (kb) region of the sequence in a haploid yeast genome. Blot hybridizations show that there is a single copy of the cloned sequence per haploid and that the sequence is transcribed to give a 2.7-kb poly(A)+ message. Mutants in which 1.7 kb of the sequence is deleted are viable. Temperature-shift experiments using synchronously grown cells of a delta top1 top2 temperature-sensitive (ts) double mutant and its isogenic top2 ts strain show that, whereas mitotic blocks can prevent killing of the top2 ts mutant at a nonpermissive temperature, the same treatments are ineffective in preventing cell death of the delta top1 top2 ts double mutant. These experiments suggest that in yeast DNA topoisomerase I serves a role auxiliary to DNA topoisomerase II.

Base Sequence↗

Quantification of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in beef extracts by liquid chromatography with electrochemical detection (LCEC).

A simple and sensitive method was developed for quantification of mutagenic/carcinogenic aminoimidazoquinoline and aminoimidazoquinoxaline compounds in heated materials. Samples were partially purified by blue-cotton treatment, 0.1 N HCl-methylene dichloride partition and separation in a SEP-PAK silica cartridge. The recoveries of aminoimidazoquinoline and aminoimidazoquinoxaline compounds at the step of partial purification were estimated by spiking with 14C-labeled compounds. The compounds in partially purified materials were analyzed by liquid chromatography with electrochemical detection using a combination of two columns of octadecyl silane and cation exchange. Bacteriological-grade beef extract was found to contain 41.6 and 58.7 ng/g of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), respectively. MeIQx was also detected at a level of 3.1 ng per g in food-grade beef extract.

Animals↗

Bay K 8644, a dihydropyridine calcium agonist, augments vasoconstrictor responses to endogenous and exogenous noradrenaline in the peripheral vasculature of the dog.

The effect of Bay K 8644 (a substance known to increase calcium influx through the voltage-dependent calcium channel) on vasoconstrictor responses of resistance vessels to endogenous and exogenous noradrenaline (NA) was investigated in pentobarbitone-anaesthetized dogs which had also undergone spinal anaesthesia and bilateral vagotomy and received atropine. In these dogs the saphenous arterial bed was perfused at fixed flow rates with autologous blood to give perfusion pressure close to the systemic blood pressure. Electrical stimulation (3-30 Hz) of the saphenous nerve and single intra-arterial (i.a.) injections of noradrenaline (NA, 0.03-3 micrograms) produced an increase in perfusion pressure (vasoconstriction) in a frequency- and a dose-dependent manner, respectively. Intra-arterial infusions of Bay K 8644 (3 and 10 micrograms min-1) per se produced no significant change in perfusion pressure. However, these infusions augmented vasoconstrictor responses to both saphenous nerve stimulation (endogenous NA) and i.a. NA (exogenous NA). These results suggest that augmentation by Bay K 8644 of vasoconstrictor responses of resistance vessels to endogenous and exogenous NA is probably due to promotion of the calcium influx through calcium channels closely associated with alpha-adrenoceptors in smooth muscle cells there.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Amelioration of heart failure by MDL 17043 and MDL 19205, novel positive inotropic drugs, in dog heart-lung preparations.

The efficacies of MDL 17043 and MDL 19205 in ameliorating heart failure were assessed in dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. Six preparations were used for each drug. Both drugs in doses of 1-30 mumol similarly improved cardiac function in a dose-dependent manner and at 30 mumol improved it beyond control values. AV conduction impaired by pentobarbital was restored by 30 mumol of the 2 drugs. In these doses, however, neither of the drugs produced a significant increase in heart rate or arrhythmias. These results indicate that the 2 drugs would be of use in the treatment of heart failure.

Animals↗

Active, inactive and total renin concentrations in plasma of hypertensive patients.

To assess the role of inactive renin in hypertensive patients, active, inactive and total renin concentrations (ARC, IRC and TRC) were measured in 37 patients with hypertension of various etiologies. Inactive renin was activated by trypsin and renin concentration was measured using an excess of sheep substrate. Mean values of ARC, IRC, TRC and active renin ratio (AR ratio = ARC/TRC) were higher in 6 cases of renovascular hypertension, and lower in 6 cases of primary aldosteronism and 1 case of idiopathic hyperaldosteronism, when compared with 59 cases of normal subjects. Between ARC and IRC, a slightly positive correlation was observed. Moreover, between ARC and TRC as well as between ARC and AR ratio, close positive correlations were observed. Exceptionally, in a case of juxtaglomerular cell tumor, AR ratio was low in spite of the extremely high value of ARC. Our data suggest that the increase in circulating active renin is due to both the enhancement of the release of renin from the kidney and the increase in the activation of inactive renin, and vice versa.

Adolescent↗

Studies of an immunomodulator, swainsonine. II. Effect of swainsonine on mouse immunodeficient system and experimental murine tumor.

We examined the effect of swainsonine on antibody response to sheep red blood cells (SRBC) in immunodeficient mice which were treated with immunosuppressive factor or antitumor drugs, or inoculated with sarcoma 180 ascites tumor. The administration of swainsonine restored the capacities of the immunodeficient mice to produce antibody against SRBC. Furthermore, swainsonine inhibited completely the growth of sarcoma 180 ascites tumor in mice. Swainsonine also reduced lung metastases of B16 melanoma in mice. These results suggest that swainsonine has potential as an immunomodulator for the treatment of immunocompromised hosts.

Adjuvants, Immunologic↗

[Combination chemotherapy with cis-dichlorodiammineplatinum (11) (CDDP) and bleomycin BLM in advanced esophageal carcinoma].

Five patients with advanced carcinoma of the esophagus were treated with a combination chemotherapy employing CDDP and BLM. One cycle of chemotherapy consisted of CDDP, 50 mg/m2, on day 1 and BLM, 15 mg/patient on days, 1, 7 and 14. Two partial remission and 2 minor responses were obtained. Overall response rates, ths, were 80%. The most adverse effect was nausea. No significant elevation in the serum creatinine or BUN was recognized. Furthermore, the method of CDDP administration was studied on the serum level by 15 minutes' infusion and by 24 hours continuous infusion. The CDDP levels in the serum and tissue were determined by flameless atomic absorption spectrophotometry. The CDDP level in the serum by 15 minutes' infusion was higher than that by 24 hours continuous infusion. These results suggest that combination chemotherapy with CDDP and BLM may be a useful method for the treatment of advanced esophageal carcinoma.

Aged↗