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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 595 records · Page 33Linked to original sources
PubMed1984

Lung injury and delayed toxicity produced by O,S,S-trimethyl phosphorodithioate, an impurity of malathion.

O,S,S,-Trimethyl phosphorodithioate (OSS-Me), an impurity present in organophosphorus insecticides, produced morphological alteration of rat and mouse terminal nonciliated bronchiolar epithelial (Clara) cells. The effects of OSS-Me on pulmonary and hepatic microsomal enzymes were studied following its po administration to rats. Oral 28-day LD50 of OSS-Me for rats was 67 mg/kg. The animals were treated with OSS-Me at 40, 100, and 160 mg/kg and killed 24 hr later. The relative lung weights were not affected at this time. Pulmonary microsomal benzo[a]pyrene hydroxylase decreased significantly; activities were less than 36% of control at the lowest dose. In contrast, the effect of OSS-Me treatment on hepatic monooxygenase activity was moderate. Benzo[a]pyrene hydroxylase, p-nitroanisole demethylase, or 7-ethoxycoumarin deethylase were not affected by OSS-Me treatment at any dose. Pulmonary and hepatic malathion carboxylesterase activities decreased following OSS-Me treatment. The decrease was more marked in liver. Time course effects of OSS-Me treatment on these parameters were examined by treating rats at 40 mg/kg, and the animals were killed at 6, 12, 24, and 72 hr after treatment. The lung relative wet weight was increased markedly at 72 hr. The benzo[a]pyrene hydroxylase activity of pulmonary microsomes was decreased at 24 and 72 hr after treatment, the maximum decrease being observed at 72 hr. At this time, glutathione of the lungs was depleted markedly. Significant decreases were not observed in hepatic monooxygenase activities. Liver glutathione content was not reduced at 72 hr. Pulmonary and hepatic malathion carboxylesterase activities decreased throughout the time course. OSS-Me selectively inhibited benzo[a]pyrene hydroxylase activity, depleted glutathione, and caused morphological alteration of Clara cells in lungs of rats. Although the toxic mechanism(s) produced by OSS-Me remains unknown, these results support the view that the lung is a target organ of OSS-Me-induced delayed toxicity.

Administration, Oral↗
PubMed1984

Role of metabolic activation, covalent binding, and glutathione depletion in pulmonary toxicity produced by an impurity of malathion.

O,O,S-Trimethyl phosphorothioate (OOS-TMP) is an impurity present in widely used organophosphorus insecticides such as malathion. Oral treatment of rats with the compound produces prominent bronchiolar epithelial necrosis. Following the administration of [3H]OOS-TMP to rats, substantial amounts of radiolabeled material were covalently bound to lung with a concomitant depletion of glutathione (GSH). Other organs showing significant covalently bound radioactivity were liver, kidneys, and ileum. The maximal accumulation occurred in the tissues within 6 hr, and reached a plateau between 6 and 12 hr. Pretreatment of rats with either phenobarbital or piperonyl butoxide decreased the level of radiolabeled material bound in lung, GSH depletion, and the toxicity of OOS-TMP. These results suggest that the covalent binding is due to a metabolite(s) of OOS-TMP and that the metabolite(s) is involved in the mechanism of toxicity of OOS-TMP. Pulmonary GSH may play a protective role against OOS-TMP induced lung toxicity.

Administration, Oral↗
PubMed1984

Elimination of unstable angina by diltiazem under temporary pacing.

We describe two patients in whom spontaneous angina following acute myocardial infarction (postinfarction angina caused by coronary artery spasm) and worsening angina were successfully eliminated after clinical dosage of oral diltiazem, while marked sinus node suppression developed and temporary pacing was performed. The patients were females (one was 67 years and one was 64 years old), and had no history of sinus node dysfunction. The occurrence of the adverse effect was not during angina, and the intervals between the initiation of diltiazem and the occurrence were 6 days after 120 mg/day in one patient, and 4 h after a single administration of 60 mg in the other. Diltiazem is also efficacious in the elimination of unstable angina, however one should note that diltiazem may remarkably suppress not only atrioventricular node activity but also sinus node activity in some patients.

Aged↗
PubMed1984

Sequential and dose-dependent alterations in rat bronchiolar epithelium during O,O,S-trimethyl phosphorothioate induced delayed toxicity.

The sequential and dose-dependent effects of O,O,S-trimethyl phosphorothioate (OOS-Me) on rat lung bronchiolar epithelium were investigated using scanning electron microscopy. At 12 h after oral treatment (20 mg/kg), there was a small increase in debris in the bronchioles and, by 24 h, there was much debris as well as phagocytic cells in the bronchioles. After 3 days, there was a decrease in the number of bronchiolar Clara cells as determined by the loss of their characteristic apical bulges. Concomitantly, there was a significant increase in lactate dehydrogenase activity in bronchopulmonary lavage fluid. By day 7, the Clara cells appeared to be reforming and, by day 14, the morphology of bronchiolar epithelium had returned to normal. Dose-dependent studies revealed a threshold dose level of OOS-Me between 10 and 20 mg/kg which produced the observed effects in Clara cells. Both sequential and dose-dependent effects of OOS-Me on Clara cells were correlated with changes in bronchopulmonary lavage lactate dehydrogenase activity.

Animals↗
PubMed1984

Morphological alterations of rat lung bronchiolar epithelium produced by various trialkyl phosphorothioates.

A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alkyl phosphorothioate esters, which induce delayed toxicity, were examined for their effect on rat bronchiolar epithelium. The structural analogues synthesized and tested include O, O-dimethyl S-ethyl phosphorothioate, O,O-dimethyl S-isopropyl phosphorothioate, O,O,S-triethyl phosphorothioate, and O,O-diethyl S-methyl phosphorothioate. The present investigation demonstrated that these analogues of OOS-Me which cause delayed toxicity produce body weight loss, accompanied by morphological alterations of terminal bronchiolar epithelium, i.e. loss of the apical bulge of non-ciliated Clara cells. Another impurity which produces delayed toxicity, O,S,S-trimethyl phosphorodithioate, was also capable of producing similar effects at near the LD50 level.

Administration, Oral↗
PubMed1984

Hereditary spherocytosis associated with a variant of band 3 protein in the erythrocyte membrane.

A 17-year-old woman with hereditary spherocytosis was found to be heterozygous for an unusual variant of the band 3 protein in erythrocyte membranes. The variant had a molecular weight of 95,000 daltons which was larger by about 3,000 daltons than the 92,000 m.w. normal band 3, and was phosphorylated less efficiently when intact cells were incubated with 32P-inorganic phosphate. It is discussed that this variant may affect the integrity of the membrane skeletons.

Adolescent↗
PubMed1984

Guinea pig plasma kallikrein as a vascular permeability enhancement factor. Its dependence on kinin generation and regulation mechanisms in vivo.

Plasma kallikrein (mol wt 80,000) was purified from guinea pig plasma, and it caused vascular permeability enhancement when injected into guinea pig skin. The activity had a linear relationship to the logarithm of kallikrein concentrations from 5 X 10(-9) M to 5 X 10(-6) M and was blocked by immunopurified anti-prekallikrein F(ab')2 rabbit antibody and soybean trypsin inhibitor. Carboxypeptidase B(1.7 units), a kinin-destructive enzyme, decreased the permeability activity to 1/20, while SQ 20,881 (10(-6) M), an inhibitor to a kinin-destructive enzyme, augmented the activity 5.4-fold. These results suggested that the permeability activity of kallikrein was performed finally through kinin generation in the skin. The permeability activity was short-lasting, and was completely blocked by a kallikrein inhibitor purified from guinea pig plasma, suggesting the presence of a down-regulation system for the permeability activity in vivo. Prostaglandin E2 (25 ng), a hyperemia inducer in microcirculation, augmented the permeability activity 12-fold, suggesting the presence of an up-regulation system in vivo. Accordingly, it was assumed that kallikrein-kinin system might play a role as a vascular permeability enhancement system in guinea pig skin.

Animals↗
PubMed1984

Permeation and deposition of fibrinogen and low-density lipoprotein in the aorta and cerebral artery of rabbits--immuno-electron microscopic study.

The localization of fibrinogen and low-density lipoprotein (LDL) in the arterial wall has been studied to determine whether they mediate the effects of hypertension and/or hypercholesteraemia on atherogenesis. In untreated control rabbits, fibrinogen was localized in the caveolae and vesicles of the endothelial cells and in the subendothelial spaces of the aorta. No fibrinogen was found in the subendothelial spaces of the cerebral artery. Hypertension or hypercholesteraemia was accompanied by enhanced insudation of fibrinogen into the subendothelial spaces of the aorta and cerebral artery, and fibrinogen deposition was most prominent in the hypercholesteraemic rabbits with induced renovascular hypertension. The insudation of fibrinogen appeared to occur by way of vesicular transport, and to some extent by junctional transport. In the untreated control rabbits, LDL was localized only in the caveolae and vesicles of endothelial cells in both aorta and cerebral artery. LDL was deposited in the subendothelial space of the aorta of hypercholesteraemic rabbits with or without hypertension, and in the cerebral artery of hypercholesteraemic rabbits with hypertension. These findings suggest that fibrinogen insudates into the intima of the aorta and cerebral artery both during hypertension and hypercholesteraemia, and that LDL insudation into the intima of the aorta in hypercholesteraemia is accentuated by hypertension. LDL insudated into the intima of the cerebral artery in the presence of hypercholesteraemia linked to hypertension. Thus, hypertension plays a significant role in the pathogenesis of cerebral atherosclerosis.

Animals↗
PubMed1983

Selective inhibition of rat pulmonary monooxygenase by O,O,S-trimethyl phosphorothioate treatment.

The effects of oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, were studied using pulmonary and hepatic microsomal enzymes of rats. The animals were treated with OOS at 10,20 and 40 mg/kg, and were killed on day 3 after treatment. Their relative lung weights increased markedly at 20 and 40 mg/kg, increasing 94% at the highest dose, whereas the weight of liver decreased. At 20 mg/kg OOS, the cytochrome P-450 content of the lung and liver decreased to 83 and 80% of the control levels respectively. Pulmonary microsomal 7-ethoxycoumarin (7-Ec) O-deethylase decreased in a dose-dependent manner; activities were less than 10% of control at the 40 mg/kg dose. The activity of pulmonary coumarin hydroxylase also decreased following OOS treatment, but the decrease was not dose-dependent since no activity was detectable at doses over 10 mg/kg. In contrast, the effect of OOS treatment on hepatic monooxygenase activity was moderate. 7-Ec deethylase activity was not affected by OOS treatment at any dose level, while p-nitroanisole (p-NA) demethylase activity was decreased only at the 40 mg/kg dose of OOS. Pulmonary malathion carboxylesterase activity was not affected by OOS treatment. In contrast, a dose-dependent decrease was observed in the liver carboxylesterase. Time course effects of OOS treatment on these parameters were examined by treating rats at 20 mg/kg. The animals were killed 0.5, 1,3 and 7 days after the treatment. The 7-Ec deethylase activity of pulmonary microsomes was decreased on days 0.5, 1 and 3 after treatment, the maximum decrease being observed on day 1. Significant decreases were not observed in hepatic microsomal activities of 7-Ec deethylase or p-nitroanisole demethylase throughout the experimental period; rather, these activities were higher on day 7. Hepatic microsomal malathion carboxylesterase was lower on days 0.5, 1 and 3 after OOS treatment.

Animals↗