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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,711 records · Page 95Linked to original sources

Metabolic fate of n-methyl-N-dodecylnitrosamine in the rat, in relation to its carcinogenicity to the urinary bladder.

The metabolic fate of N-methyl-N-dodecylnitrosamine (MDN) was investigated in the rat, in order to elucidate a possible correlation between urinary metabolites and organotropic carcinogenicity to the urinary bladder of this N-nitrosamine. MDN was extensively metabolized in the rat, no unchanged MDN being found in the urine. The urinary metabolites identified were N-methyl-N-(3-carboxypropyl) nitrosamine (MCPN), N-methyl-N-(2-hydroxy-3-carboxy-propyl) nitrosamine, N-methyl-N-(carboxymethyl) nitrosamine, and N-methyl-N-(2-oxopropyl) nitrosamine. Thus the metabolic pattern of MDN was essentially similar to that of N-methyl-N-(4-hydroxybutyl) nitrosamine, a potent bladder carcinogen, in the rat. A possible important role of MCPN in the induction of bladder tumors by MDN is discussed.

Animals↗

Metabolic fate of asymmetric N,N-dialkylnitrosamines having butyl group in the rat.

The metabolic fate of N-alkyl-N-butylnitrosamines (alkyl=ethyl, propyl, and pentyl), which induce tumors in the liver and esophagus but do not induce bladder tumors, was investigated in the rat, in order to elucidate any possible correlation between metabolism and the noncarcinogenicity to the urinary bladder of these N-nitrosamines. They were extensively metabolized in the rat, no unchanged compounds being found in the urine. The metabolic pattern of these N-nitrosamines having a butyl chain was essentially similar to that of N,N-dibutyl-nitrosamine, which induces tumors in the bladder as well as in the liver and esophagus. They were mainly metabolized via omega-oxidation followed by beta-oxidation and/or (omega-1)-oxidation of either of the two alkyl chains. Thus the N-alkyl-N-(3-carboxypropyl)nitrosamine and/or the N-alkyl-N-(2-carboxyethyl)nitrosamine were identified as the principal urinary metabolites. Possible important factors concerned with the induction of bladder tumors by N,N-dialkylnitrosamines are discussed from the metabolic point of view.

Animals↗

Distribution of post-proline cleaving enzyme in human brain and the peripheral tissues.

We have studied the distribution of post-propline cleaving enzyme activity in the various tissues in humans using 7-(succinyl-Gly-Pro)-4-methylcoumarinamide as substrate. The post-propline cleaving enzyme activity was high in muscle, testes, kidney and submandibular gland, but was low in the heart, mesenterium and aorta. In the brain, relatively high post-propline cleaving enzyme activity was observed in the cerebral cortex, but other brain regions showed a very low enzyme activity. On Sephadex G-100 column chromatography, enzyme activity in human kidney showed a major peak and a minor peak. The major peak coincided with the enzyme in human cerebral cortex, but was different from human serum enzyme. Diisopropylfluorophosphate, a serine protease inhibitor, strongly inhibited the enzyme activity of each active fraction. The enzyme in the cerebral cortex and kidney was inhibited by heavy metals and thiol blocking agents. However, inhibition of enzyme activity in the serum was not observed with such inhibitors. Therefore, we suppose that post-proline cleaving enzyme activity in the brain is similar, if not identical, to that in the kidney.

Brain↗

Cooperativity of albumin and aggrexons A and B for ADP-induced-aggregation of platelets.

Using extensively washed bovine platelets and a chemically defined medium instead of whole plasma, it was demonstrated that aggregation to a near normal extent was induced by ADP only in the presence of at least the following three components from plasma; albumin, Aggrexon A and Aggrexon B. These three proteins apparently acted cooperatively; the elimination of any one of the above mentioned plasma components from the system resulted in marked reduction of the aggregation.

Adenosine Diphosphate↗

The regional difference in the responses of the guinea pig gastric muscles to gastrin.

The responses to gastrin were studied in the circular muscles of guinea pig stomach. The muscle strips were prepared from the three different regions of the stomach; the pylorus, the antrum and the upper body. The responses to gastrin, which were concentration dependent contractions, appeared only in the preparations from the upper body. The contractile response of the upper body was observed not by the cumulative application of gastrin, but by the one show applications between which interval was 30 minutes. In contrast, any response to gastrin was not obtained in the other two regions. The contractile response to gastrin in the upper body was not affected by any antagonist, mepyramine 10(-6)g/ml, atropine 10(-6)g/ml, cimetidine 3 X 10(-5)g/ml or tetrodotoxin 10(-7)g/ml. In conclusion, it is reasonable that gastrin may act on the circular muscle of the upper body and cause the concentration dependent contraction by its direct effect.

Animals↗

Present state of fungal infections in autopsy cases in Japan.

In order to clarify the present state of opportunistic fungal infections increasing in incidence in autopsy cases, all autopsy cases from 1966 to 1975 reported in the Annual of Pathological Autopsy Cases in Japan were reviewed. Of the total 233,130 autopsy cases, mycoses were present in 4,340 (1.86%). The incidence of mycoses has strikingly increased during the recent five-year period. In Japan, the mycoses most frequently occurring in autopsy cases were candidiasis (32.28%), aspergillosis (23.08%), cryptococcosis (9.63%), and mucormycosis (2.90%). These occurred more frequently in younger persons and were most commonly secondary and deep-seated infections (95.78%). Among the primary diseases associated with mycoses, aplastic anemia (14.36%), leukemia (9.89%), malignant lymphoma (5.73%), multiple myeloma (4.68%), and systemic lupus erythematosus (4.62%) were most frequent. The incidence of the primary diseases associated with mycoses is increasing extraordinarily, and this seems to be strongly related to the modern therapy of using high doses of anticancer or immunosuppressive agents.

Adolescent↗

Mode of inactivation of putrescine oxidase by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide or metal ions.

1. Putrescine oxidase [EC 1.4.3.10] was partially inactivated by reaction with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), rapidly. The activity of the modified enzyme toward putrescine was 5.6% of that of the native enzyme. Moreover, the optimal pH and Km value of the modified enzyme for putrescine changed from 9.0 to 10.5 and from 0.23 to 3.4 mM, respectively. This modified enzyme showed activity toward monoamines such as n-butylamine, n-hexylamine, and n-octylamine, which are not substrates of the native enzyme. 2. Heavy metal ions inactivated putrescine oxidase completely. Hg2+ had the stronger ability to inactivate it. This inactivation was due to the dissociation of FAD from the enzyme molecule. The Fad-free enzyme had no ability to reassociate FAD, in contrast to the apoenzyme. The enzyme treated with Hg2+ showed characteristic behavior on SDS-polyacrylamide gel electrophoresis. 3. From the results of chemical modification it was deduced that a carboxyl group plays an important role in binding the substrate.

Apoenzymes↗

Mesothelioma with lung cancer complicating asbestosis.

The patient had been employed in an asbestos factory for four years from the age of 16. Five years ago, she complained of sputum and cough, and she was treated for chronic bronchitis. From March, 1977, when she was 53 years old, hydrothorax and ascites increased, her weight decreased and she was hospitalized for cachexia. The clinical diagnosis of malignant diffuse mesothelioma was made on the presence of atypical cells in the effusions. Atypical cells showed a positive colloidal iron staining test and positive hyaluronidase digestion test. Asbestos bodies were found in the sputum. The patient died on February 1978. Postmortem confirmed asbestosia and mesothelioma which was scattered over the pleura, pericardial sac, diaphragma, peritoneum and pancreas. In addition, bronchiolo-alveolar cell type lung cancer was found localized in the lower lobe of the left lung. The electron beam diffraction disclosed the asbestos as amosite (brown asbestos).

Asbestosis↗