Effect of polyamines on prostaglandin synthesis in various cell-free systems.
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Biomedical subjects
Publications and source records attributed to M Kitada.
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The follow up study on rheumatic heart disease was carried out over a 20 year period by the questionaire method. Two hundreds and seventy-nine patients were analyzed and the following results were obtained. 1) Sixteen cases (5.5%) died, 20 cases (6.8%) showed deterioration, 155 cases (53.1%) were unchanged, 35 cases (12.0%) were improved, 12 cases (4.1%) were announced that their valvular lesions disappeared and 22 cases (7.2%) underwent cardiac surgery. The more severe the findings at the final examination under our program, the poorer the courses. 2) The cases having a severe status index showed a tendency for poor prognoses. Mitral steno-regurgitation revealed the poorest prognoses. 3) 84.3 per cent of the living cases were found to be leading normal daily lives without any restriction. 4) The average death rate was 1.0% per year during the 20 years between 1958 and 1978. The death rate for age group between 9 and 17 years old was the highest (1.34% per year). 5) The leading cause of death in every group including all the cases under our program was a recurrence of rheumatic fever. However in groups older than 18 years of age chronic congestive heart failure and unsuccessful cardiac surgery were leading causes.
Fukuda ECP-100 computer assisted ECG analysis system was introduced into the heart disease program for school children and high school students in Osaka City in 1979. This analysis system was used as screening tool and 39,532 of 4th graders of primary schools were examined during the first year. To evaluate and improve this analysis system a "pilot study" was organized and 52 school physicians and 10 specialists made up a "working group". "Urgent reference codes" were set to be printed out so that the limitation of the present system of the Heart Disease Program should be compensated. Problems of the ECG analysis system were as follows. The Q wave registered too wide and there were same difficulties in recognizing the end point of the T wave. Recognition ot tiny "r" wave seemed to be impossible and base line sway seemed responsible for numerous erroneous outputs. Some cases corresponding to code "4-n-n" were found to be normal after further examination. This system can be said to be useful as a screening tool. Using this system at least 4 cases of serious lesion were newly detected, one case of myocarditis and 3 cases of myocardial diseases.
1. The metabolism of tripamide, N-(4-aza-endo-tricyclo[5.2.1.0(2.6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide, has been studied with rat liver microsomal preparations. 2. Hydrolysis of tripamide was induced by phenobarbitone pretreatment and inhibited by O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN), a classical inhibitor of hepatic microsomal arylamidase. The hydrolysis was also catalysed by partially purified rabbit liver microsomal arylamidase. 3. The hydroxylation of tripamide was induced by 3-methylcholanthrene and inhibited by CO. 4. Inhibition of the hydroxylation of tripamide by antibodies of cytochrome P-450 and P-448 was studied. The 8-hydroxylation was inhibited by both antibodies, but 3-hydroxylation was inhibited by neither.
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The rate of malondialdehyde formation in rat liver microsomes decreased as concentration of spermine added to the reaction mixture was increased. Inhibitory effect on lipid peroxidation was observed even when spermine was added at 15 min after the onset of reaction. Microsomal lipid peroxidation was markedly increased when extracted lipids were added to the reaction mixture. It was, moreover, found that in the presence of exogeneous microsomal lipids, spermine inhibition was weakened. The character of spermine inhibition with respect to the amounts of exogeneous and endogeneous lipids was shown to be competitive. From these results, it was suggested that spermine interaction with microsomal lipids may be responsible for the inhibition of lipid peroxidation.
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Alkalophilic Bacillus No. 8-1 and No. 10A-2, isolated on alkaline media containing NaHCO3 and K2CO3, respectively, required Na+ specifically for the uptake of alpha-aminoisobutyric acid (AIB) into the cells. The K+ added to the uptake medium inhibited the accumulation of AIB in the cells of Bacillus No, 8-1, acting as a competitive inhibitor of the system. Sodium ion prevented the release of AIB from pre-loaded cells. Both potassium and lithium ions had the effect of retaining the AIB pool. The Vmax value for transport increased about five-fold when the pH value of medium was raised from 7 to 9, whereas the Km value decreased with the increase of concentration of sodium ion in the medium of pH 7 or 9. Sodium ion gradient across the membrane caused transient uptake by AIB by membrane vesicles of Bacillus No. 8-1.
Membrane vesicles were isolated from alkalophilic Bacillus No. 8-1, and the active transport of amino acids was studied. The transport of amino acids was dependent upon substrate oxidation and the presence of Na+. Concentrative uptake of amino acids was stimulated by the addition of an artificial electron donor system, ascorbate-phenazine methosulfate (PMS), and to a lesser extent by NADH, while succinate, L-lactate, and alpha-glycerol-phosphate did not stimulate the uptake. N,N,N',N'-Tetramethyl-p-phenylenediamine (TMPD) and cytochrome c were able to replace PMS, and reduced forms of these compounds were also very efficient electron donors. Amino acid transport was dependent on electron transfer, and inhibition of NADH oxidation by cyanide, 2-heptyl-4-hydroxyquinoline-N-oxide (HOQNO), and sodium azide directly prohibited serine transport. The pH optima for serine transport lay between pH 8 and 9 for all energy sources. Sodium ion stimulated serine transport in the presence of NADH, NADH plus cytochrome c or succinate plus PMS, but had no stimulatory effect on the corresponding dehydrogenase activities. Sodium ion was also required for accumulation of serine in response to an artificial membrane potential where the respiratory chain was not operative. These results indicated that the stimulatory effect of Na+ on amino acid uptake was on the transport process itself.
Effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on the components of rat liver microsomal electron transport system was investigated by comparison with those of phenobarbital, 3-methylcholanthrene and polychlorinated biphenyl. When NKK-105 was administered to rats at a dose of 250 mg/kg/day for 7 days, cytochrome b5 content and NADPH-cytochrome c reductase activity were significantly increased but cytochrome P-450 content to the lesser extent. Three inducers of the drug metabolizing enzymes remarkably increased cytochrome P-450 content but increased cytochrome b5 content to a lesser extent.
The rate for sudden unexpected death among the male school children and high school student was 3.4 per 100,000, and among the female was 2.0 per 100,000. The rate showed the tendency to increase with age among the male, but not in the female. Most of the sudden deaths occurred during day time while they were awake and the death during sleep occurred in 9.2%. The sudden death in the school occurred in 26.5%. Concerning the causes of the death, in 20.5% of the cases it was unknown (even though acute heart failure was the terminal symptoms). In 18.1% basal heart disease was responsible, in 15.7% asthmatic spell and in 10.8% cerebral hemorrhage. It was found that 38.6% of the sudden death cases were as usual in the condition preceding to the onset of the symptom, 18.1% of cases had been complaining of tiredness or overwork and 9.6% had been with symptoms of respiratory infection. The sudden death of handicapped children was occupying 25.3% of the deaths encountered in the present study.
The time course linearity of ethylmorphine N-demethylation was improved by the addition of polyamines to the reaction mixture. The most remarkable effect on the time course linearity of ethylmorphine N-demethylation was observed when spermine was used. The apparent stimulatory effect of spermine was decreased remarkably by the simultaneous addition of EDTA to inhibit lipid peroxidation. Similar results were observed when an additional lipid peroxidation inhibitor such as Co2+, Mn2+ or 2,2'-bipyridine was used in place of EDTA. Hydrogen peroxide-dependent ethylmorphine N-demethylation activity in rat liver microsomes was not influenced by the addition of spermine. In addition, neither lipid peroxides formation nor the stimulatory effects of polyamines on ethylmorphine N-demethylation was observed in the reconstituted monooxygenase system. These results suggest that the inhibitory effects of polyamines on lipid peroxidation might be responsible for the stimulatory effects on drug oxidations.
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