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Biomedical subjects

T Sano

Publications and source records attributed to T Sano.

At least 811 records · Page 45Linked to original sources

Induction of intestinal metaplasia in the stomachs of rats by N-methyl-N'-nitro-N-nitrosoguanidine.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered orally to male Wistar rats at a concentration of 83 microgram/ml in the drinking water for 2, 4, 5, and 7 months; the rats were killed at about month 15. Intestinal metaplasia was found in the stomachs of 80-100% of the rats treated with MNNG for 4 or more months, of 37.5% treated with MNNG for 2 months, and of 10% of the controls. Metaplastic glands, composed of goblet cells and columnar cells with striated borders, were found in the pyloric region. Paneth's cells were found at the bottom of metaplastic glands in a rat treated with MNNG for 4 months. The incidence of well-differentiated adenocarcinomas of the stomach was 63-90% in rats treated with MNNG for 4 or more months and 25% in those treated with MNNG for 2 months.

Adenocarcinoma↗

Mechanism of rhythm determination among pacemaker cells of the mammalian sinus node.

The isolated rabbit sinus node was partly divided into two parts by a cut in the middle portion. Microelectrode recording near the bridge connecting the two parts revealed an interference between action potentials from the two parts. Comparison of microelectrode recordings from the two parts taken near the bridge suggested that an induced peculiar rhythm change in one part was probably induced by the electrotonic effects of the action potentials of the other part. To prove this, a subthreshold depolarizing square-wave pulse was applied extracellularly to the isolated uncut sinus node. When the pulse was applied in the early portion of slow diastolic depolarization, diastole was prolonged, and when it was applied in the later portion, diastole was shortened. These findings can explain the observed peculiar thythm and suggest that in the mammalian sinus node, pacemaker cells accelerate or decelerate mutually by the electrotonic effects of their action potentials, depending on the phase of application of the effects. In particular, for some time the faster pacemaker cells could be influenced by dragging effects from the neighboring slower pacemaker cells and the slower pacemaker cells by pulling effects from the neighboring faster pacemaker cells.

Action Potentials↗

Comparison of carcinogenicity of N-alkyl-N'-nitro-N-nitroso-guanidines.

Carcinogenicity of seven homologs of N-alkyl-N'-nitrosoguanidine (N-alkyl-NNG), namely, N-methyl-NNG, N-propyl-NNG, N-butyl-NNG, N-isobutyl-NNG, N-pentyl-NNG, and N-hexyl-NNG, was examined by injecting the compounds subcutaneously into rats. All of them except N-isobutyl-NNG and N-hexyl-NNG were carcinogenic, but N-ethyl-NNG followed by N-methyl-NNG were stronger carcinogens than those with longer alkyl chains.

Animals↗

Carcinogenicity of a food additive, AF-2, in hamsters and mice.

The carcinogenicity of a food additive, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (trade name, AF-2), was studied. A diet containing AF-2 at a rate of 0.25% was administered to male golden hamsters and male ddY mice. The hamsters developed squamous cell carcinomas in the forestomach after the 49th day from the start of administration. In mice fed a AF-2 diet for 308 days, squamous cell carcinoma was observed in the forestomach after the 381th day from the start of the experiment; in some cases the carcinoma metastasized to the lung and liver.

Animals↗

Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention.

A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points: 1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment. 2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positve significant correlations between the values obtained by these three methods. 3. It was proved to be highly reproducible and is thought to be useful clinically. By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.

3',5'-Cyclic-AMP Phosphodiesterases↗

Induction of liver tumors in rats by sodium nitrite and methylguanidine.

The carcinogenicity of sodium nitrite and methylguanidine singly and together were examined in rats. A hepatocellular carcinoma, a hemangiosarcoma and a spindle cell sarcoma were found in 3 of 15 rats fed continuously on pellet diet containing 0.16% sodium nitrite and 0.16% methylguanidine. Hemangiomas and bile duct adenomas of the liver were also found in 6 and 8, respectively, of the 15 rats in this group. Hemangiomas and bile ducts adenomas of the liver were found in 2 and 3, respectively, of the 4 rats fed on pellet diet containing 0.16% sodium nitrite. Only 1 of 5 rats fed on pellet diet containing 0.16% methylguanidine developed a hemangioma. No tumor was found in the control group. All the tumors were found in rats that survived for over 12 months. No significant changes were detected in the esophagus or stomach.

Adenoma, Bile Duct↗

Demonstration of bidirectional dual A-V nodal pathways in the same patient.

In a patient with documented paroxysmal junctional tachycardia (PJT) electrophysiologic studies were performed using an extrastimulus technique. At an A1-A2 interval of 360 msec, atrial extrastimulus revealed sudden prolongation of an A2-H2 interval from 370 to 540 msec and PJT ensued. This finding was consistent with antegrade dual A-V nodal pathways. On the other hand, at a V1-V2 interval of 540 msec, ventricular estrastimulus showed a jump in ventriculo-atrial (V-A) conduction time with evidence of delay in the A-V node from 285 to 565 msec and a ventricular echo followed. This finding was consistent with retrograde dual A-V nodal pathways. Mechanisms of bidirectional dual A-V nodal pathways are discussed.

Aged↗

Esophageal and gastric cancers with metastases induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.

Three 6-month-old male beagle dogs were given a solution of 150 microng N-ethyl-N'-nitrosoguanidine (ENNG)/ml to drink ad libitum for 9 months. They all developed esophageal squamous cell carcinomas and gastric adenocarcinomas. The stomach adenocarcinomas were mostly in the antrum along the lesser curvature and were either well differentiated or poorly differentiated, with or without signet ring cells. The well-differentiated adenocarcinomas metastasized to the liver, and the poorly differentiated ones metastasized to the lymph nodes. The gastric mucosa in the antrum was atrophic, and the muscularis mucosae was fibrotic. Esophageal lesions were multicentric moderately differentiated squamous cell carcinomas, and they developed without diffuse hyperplastic changes of the epithelium. One dog with a large ulcerated carcinoma of the esophagus had metastases in the lung, liver, peritoneum, and abdominal lymph nodes. One dog also had a hemangiosarcoma with hepatic metastasis and spindle cell sarcoma in the stomach and duodenum, respectively.

Adenocarcinoma↗

Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment.

The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease.

3',5'-Cyclic-AMP Phosphodiesterases↗

Paroxysmal supraventricular tachycardia with unusual induction. Concealed reentry or automaticity?

In a patient with documented paroxysmal supraventricular tachycardia, earlier atrial extrastimuli consistently induced His-ventricle (H-V) block and "atrioventricular junctional" beats, which were always followed by an echo or paroxysmal supraventricular tachycardia. In "atrioventricular junctional" beats, a V wave was preceded by an H deflection with the same intervals as that of the sinus beat. As for the underlying mechanism of paroxysmal supraventricular tachycardia, two possibilities were considered: (1) concealed atrioventricular nodal reentry, and (2) "triggered automaticity."

Adult↗

Demonstration of two anomalous bypasses in concealed Wolff-Parkinson-White syndrome.

Two patients with a history of paroxysmal supraventricular tachycardia but no evidence of the Wolff-Parkinson-White syndrome in the conventional electrocardiograms were studied utilizing atrial and ventricular extrastimuli. The evidence obtained in these patients was consistent with a concealed Wolff-Parkinson-White syndrome. In one patient, ventricular extrastimuli revealed three different responses in the curve of ventriculoatrial conduction, depending upon the interval of stimulus. In the other patient, intracardiac recordings, including the left atrial potential, showed that paroxysmal supraventricular tachycardia was induced by an impulse via an anomalous bypass which diverged from the main bypass or stemmed independently from the left ventricle and was maintained by impulses via the main bypass which lay between the left ventricle and the left atrium. The mechanisms for initiation of the paroxysmal supraventricular tachycardia were discussed.

Adult↗

Effect of leupeptin on induction of lymphoblastic leukemia in mice by N-nitrosobutylurea.

The effect of leupeptin on the induction of lymphoblastic leukemia in ICR/JCL female mice by N-nitrosobutylurea (NBU) was investigated. NBU was given as a 0.02% solution in drinking water for 10 weeks. A 0.1% concentration of leupeptin was given in the diet. Group A was fed on the leupeptin diet from the beginning, Group B received it after the end of NBU treatment, and Group C was fed on a leupeptin-free control diet throughout. The average periods in the appearance of leukemia in groups A, B, and C were 115+/-50, 112+/-43, and 100+/-17 days (mean+/-SD), respectively, and there was a significant difference between groups A and B and Group C at P less than 0.001. In regard to this point, leupeptin might have the effect of retarding the rpocess of leukemogenesis. However, leupeptin showed no effect on the incidence and histopathological finding of leukemia.

Animals↗