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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 613 records · Page 34Linked to original sources

Effect of drug metabolism inducer and inhibitor on O,O,S-trimethyl phosphorothioate-induced delayed toxicity in rats.

Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity present in widely used organophosphorus insecticides, causes delayed toxicity in rats, i.e., death occurring as late as 28 days after the treatment. The signs of toxicity include body weight loss (maximum on day 3), red staining around the nose, mouth and eyes, and an increased level of lactate dehydrogenase (LDH) in bronchopulmonary lavage fluid accompanied by morphological alteration of non-ciliated bronchiolar epithelial Clara cells. Pretreatment with phenobarbital, piperonyl butoxide (2 h), SKF 525-A, or small multiple doses of OOS protected against the OOS-induced elevated level of bronchopulmonary lavage LDH, and the other signs of delayed toxicity including morphological alteration of Clara cells. These studies support the view that OOS-induced delayed toxicity is mediated by the cytochrome P-450 dependent metabolism of OOS, and the lung may be the major target organ of delayed toxicity produced by OOS.

Animals↗

Acquired B antigen and polyagglutination in a patient with gastric cancer.

Erythrocytes from a patient with blood type of A1 became nongenetically reactive with A (anti-B) serum, following the development of gastric cancer. Transient polyagglutinability was also apparent. The in vitro acetylation of the erythrocyte antigens abolished both the acquired B antigen and the polyagglutination. Although incubation of the heterologous type A1 erythrocytes with the patient's serum did not produce B antigen, deacetylase activity in the serum seems to relate to the acquired B antigen. In this case, either ileus as a result of metastatic adenocarcinoma of the stomach, or urinary tract infections could be the cause of the acquired B antigen.

ABO Blood-Group System↗

Effects of hypertension and hypercholesteremia on the permeability of fibrinogen and low density lipoprotein in the coronary artery of rabbits. Immunoelectron-microscopic study.

In an attempt to elucidate the effects of hypertension and/or hypercholesteremia on atherogenesis, with special reference to permeation and deposition of fibrinogen and low density lipoprotein (LDL) in the coronary artery, we studied electron-microscopically the localization of fibrinogen and LDL. In the untreated control rabbits, fibrinogen was localized in the caveolae and vesicles of the endothelial cells and in very small amounts in the subendothelial spaces of the coronary artery. Hypertension or hypercholesteremia was related to an enhanced insudation of fibrinogen into the subendothelial spaces of the coronary artery. The insudation of fibrinogen seemed to have occurred by way of vesicular transport and, to some extent, by junctional transport. LDL was localized only in the caveolae and vesicles of the endothelial cells of the coronary artery in the untreated control rabbits. LDL was deposited in the subendothelial space of the hypercholesteremic rabbits, with or without hypertension. Despite the lack of clear-cut and direct evidence, the insudation of LDL into the intima appeared to be enhanced by way of vesicular transport.

Animals↗

Malathion and phenthoate carboxylesterase activities in pulmonary alveolar macrophages as indicators of lung injury.

Malathion and phenthoate carboxylesterase activities were investigated in pulmonary alveolar macrophages (PAM) in Sprague-Dawley rats. PAM was found to be capable of hydrolyzing phenthoate at a faster rate than malathion. Oral administration to rats with O,O,S-trimethyl phosphorothioate (OOS-Me), a pneumotoxic impurity present in technical grades of malathion and phenthoate, increased the activities of these esterases in PAM without affecting an activity in lung microsomal carboxylesterase. The time course study indicated that this increase was maximal on Day 1 following treatment with OOS-Me at 20 and 40 mg/kg of doses. To assess the usefulness of measuring these esterases in PAM as an indicator of lung damage, paraquat and bromobenzene were administered to rats with treatment regimens which have been shown previously to result in histopathologically demonstrable pneumotoxicity. Malathion and phenthoate carboxylesterase activities in PAM were increased by two- to threefold following treatment with paraquat or bromobenzene. These treatments also increased lung microsomal malathion carboxylesterase activity by threefold. Furthermore, infection of rats with Pseudomonas aeruginosa by intratracheal inoculation increased malathion and phenthoate carboxylesterase activities in PAM by two- to threefold without increasing these activities in lung microsomes. These results indicate that PAM may play a significant role in detoxifying airborne malathion and phenthoate when inhaled. Furthermore, the activities of malathion and phenthoate carboxylesterases may be useful for detecting lung injury produced by pneumotoxic chemicals as well as bacterial infection.

Animals↗

An impurity of malathion alters the morphology of rat lung bronchiolar epithelium.

Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity in technical malathion, caused morphological changes in the bronchiolar epithelium of rat lungs. OOS-treated rat lungs had fewer but larger Clara (non-ciliated) cells than lungs from control rats given either corn oil or purified malathion. Moreover, lactate dehydrogenase (LDH) activity in bronchopulmonary lavage fluid was significantly higher in OOS than in control rats. We interpret these data to mean that OOS, and/or its metabolite(s) causes a lesion in the lung. Because of the widespread agricultural use of technical malathion, future work should address the significance of our findings and the possible toxic effect of OOS on lung tissue.

Animals↗

Kinetics of hydrolysis of Na-benzoyl-p-guanidino-L-phenylalanine p-nitroanilide by trypsin.

A new chromogenic substrate, Na-benzoyl-p-guanidino-L-phenylalanine p-nitroanilide (Bz-GPA-pNA), was synthesized. This compound is a good substrate for bovine trypsin (Km = 1.56 X 10(-5) M, kcat = 0.081 s -1, at pH 8.2) and was hydrolyzed as fast as Na-benzoyl-L-arginine p-nitroanilide (Bz-Arg-pNA) with much the same kcat/Km values. But the values are two orders of magnitude smaller than those for ester substrates, Na-benzoyl-p-guanidino-L-phenylalanine ethyl ester (Bz-GPA-OEt) and Na-benzoyl-L-arginine ethyl ester (Bz-Arg-OEt). Substrate activation behavior was observed on tryptic hydrolysis of this new substrate in a substrate concentration range higher than about 5.0 X 10(-4) M in analogy with the trypsin-Bz-Arg-pNA system.

Hydrolysis↗

Porcine liver aminopeptidase. Further characterization of its sulfhydryl groups.

Porcine liver aminopeptidase was inactivated by various sulfhydryl-reactive reagents, whose inactivation rates were in the order: p-chloromercuribenzoate(PCMB) greater than HgCl2 greater than 2,2'-dithiodipyridine greater than 5,5'-dithiobis(2-nitrobenzoic acid)(DTNB). The processes of inactivation by these reagents did not follow pseudo-first-order kinetics, and prolonged incubation did not alter the level of maximum inactivation. The substrates provided no protection against the inactivation by DTNB, and the numbers of sulfhydryl groups titrated with the reagent were not influenced by the presence or absence of puromycin (a competitive inhibitor). The modification of sulfhydryl groups caused a slight increase in the Km value for the enzyme and a significant decrease of the Vmax value. There are two ionizable groups (pKe, 6.2; 7.8 and pKes, 6.0; 7.8) in the catalytic action of the enzyme. From the pKi vs. pH profile of inhibition with PCMB, the pK value of 7.8 does not correspond to the ionization of a sulfhydryl group. The thiol-modified enzyme was activated by cobalt ion, as was the native enzyme (Kawata, S., et al. (1982) J. Biochem. 92, 1093-1101). But in contrast with the native enzyme, the thiol-modified enzyme was activated about 2.5-fold and the maximum activation remained almost constant during prolonged incubation with cobalt ion. These results suggest that the sulfhydryl groups of the enzyme are located apart from the binding site of cobalt ion and do not participate directly in the catalytic process.

Aminopeptidases↗

Molecular weights of acetylcholine receptor subunits from Narke japonica.

The molecular weights of acetylcholine receptor subunits from Narke japonica were determined by use of a combination of high-performance gel chromatography and low angle laser light scattering measurement. The molecular weights of the protein moieties of the alpha, beta, gamma, and delta-subunits were obtained as 39,000, 46,000, 47,000, and 48,000, respectively. Taking into account the carbohydrate contents of the subunits, the molecular weights were estimated to be 41,000, 49,000, 49,000, and 51,000. These values are considerably smaller than those estimated from SDS-polyacrylamide gel electrophoresis. However, these values agree approximately with those estimated from the elution volumes on high-performance gel chromatography in SDS solutions.

Animals↗

Branched chain fatty acids in phospholipids of guinea pig Harderian gland.

Fatty acid compositions of phosphatidyl ethanolamine and phosphatidyl choline extracted from the guinea pig Harderian gland were examined by gas chromatography and gas chromatography-mass spectrometry. Oleic acid was the major component of both phospholipids, but a large amount of saturated branched chain fatty acids was found: 34.5% in phosphatidyl ethanolamine, and 42.9% in phosphatidyl choline. On the other hand, linolenic and arachidonic acids were not found in these phospholipids. At the 1-position of phosphatidyl choline and phosphatidyl ethanolamine, 54.3% and 40.9% of fatty acids, respectively, had methyl branches. These methyl branches were located at the even-numbered carbon atoms. Branched chain fatty acids were also found at the 2-position of both lipids: 36.2% in phosphatidyl choline and 31.2% in phosphatidyl ethanolamine. The fatty acids of phosphatidyl ethanolamine and phosphatidyl choline from liver, cerebrum, cerebellum, erythrocytes, and plasma of the same animal were also analyzed. Saturated and unsaturated fatty acids, including arachidonic acid, were the major components. Branched chain fatty acids were also found in these lipids, but in very small amounts.

Animals↗

Incidence and clinicopathological significance of DIC in autopsy cases.

Disseminated intravascular coagulation (DIC) was examined pathologically in 4906 consecutive autopsy cases during the last 11 years. The cases having pathologically confirmed DIC showing microthrombi in three or more organs were 88. Of the underlying diseases for these cases, malignant tumor was found in 40 cases and diseases of hematopoietic organs in 19. Of the cases with malignant tumor, 11 had gastric cancer, 7 had lung cancer, and 4 had pancreatic cancer. Thirty-three of the 40 cases with malignant tumor showed metastasis in two or more organs. Cases with pathologically confirmed or suspected DIC that had microthrombi in one or more organs were 319. As for the incidence of pathologically suggestive DIC in each disease, the incidence of malignant tumor was 7.3% and that for diseases of the hematopoietic organ was 10.6%. Infection is an important underlying condition, especially gram-negative bacillus septicemia which may play an important role in the development of DIC. An increase in the number of white blood cells appears to be one of the causative conditions of DIC. Kidney is involved most frequently by the deposition of microthrombi, and 27 out of 88 cases show ischemic lesions induced by intravascular coagulation. There were 109 cases having clinically diagnosed or suspected DIC, but 67 cases showed no microthrombus formation. On the other hand, 63 among 4,797 cases with clinically unsuspected DIC revealed microthrombus formation in three or more organs by the postmortem examination.

Adolescent↗

High yields from microcarrier cultures by medium perfusion.

A culture perfusion system is described for the growth of anchorage-dependent cells on microcarriers. The critical component of this system is a column separator, which removes medium while allowing the microcarriers to remain in the culture. Amino acids and ammonia were analysed during cell growth of the perfusion culture. None of the amino acids was completely utilized. The accumulation of ammonia to 2.3 mM was observed and may be responsible for, or coincident with, events limiting further cell growth. It is suggested that oxygen deprivation and growth inhibitor accumulation, rather than nutrient depletion, are the major factors in limiting even higher cell yields.

Amino Acids↗

A new family with beta-thalassemia intermedia.

In a Japanese family several members in three generations had, on hemoglobin analysis, typical findings of heterozygous beta-thalassemia. However, hemoglobin concentrations, red cell morphology, splenic size and clinical histories indicated that the disorder was more severe than in the usual beta-thalassemia trait. From the previous and the present studies folic acid supplements appeared to be beneficial in ameliorating the anemia. The findings may provide an apparent pathophysiologic and genetic explanations for the more severe anemia and red-cell abnormalities present in a small proportion of families with beta-thalassemia trait.

Hemoglobins↗