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Biomedical subjects

F Hirata

Publications and source records attributed to F Hirata.

At least 127 records · Page 7Linked to original sources
PubMed1981

Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells.

The role of phospholipid methylation and phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) in natural killer (NK) function by human peripheral blood mononuclear cells was studied. Pretreatment of effector cells with a methyltransferase inhibitor, 3-deazaadenosine, in the presence of homocysteine thiolactone, reduced cytotoxicity in a dose-dependent fashion. This effect was closely associated with inhibition of methylation of lipids but not of nucleic acids or proteins. The suggestion for a role of phospholipid methylation was supported by the observation that the interaction between NK-susceptible tumor targets and peripheral blood mononuclear cells caused increased phospholipid methylation only when susceptible target cells were used. Phospholipase A2 was also implicated in human NK activity. Inhibitors of the enzyme such as tetracaine, mepacrine, Rosenthal's inhibitor, and corticosteroids impaired NK function. Rosenthal's inhibitor was also shown to exert an inhibitory effect on a purified NK-cell population obtained by the isolation of large granular lymphocytes on Percoll gradients. Peripheral blood mononuclear cells were also directly shown to display phospholipase A2-like activity, as measured by the decrease in radioactive arachidonate from prelabeled phospholipids, specifically phosphatidylcholine, in effector cells. These data suggest that enhanced phospholipid methylation occurs during the recognition function of NK cells. Consequent activation of phospholipase A2 might be involved in the mechanisms leading to lytic events within the target cell.

Adrenal Cortex Hormones↗
PubMed1981

Adrenoceptor desensitization after immobilization stress or repeated injection of isoproterenol.

Immobilization stress (2.5 h daily) or repeated injection of isoproterenol (1 mg/kg, 3 times daily) for 1 wk caused a subsensitivity to the chronotropic and pressor effect of epinephrine in pithed rats. Propranolol (1 mg/kg) inhibited, to a greater extent in control than in immobilized rats, the chronotropic effect of epinephrine. The residual heart rates did not differ significantly among control, immobilized, and isoproterenol-treated rats. Practolol (1 mg/kg) but not butoxamine (5 mg/kg) mimicked the effect of propranolol. The subsensitivity in the blood pressure responses was not abolished by injection of either of the beta-adrenoceptor blockers. Butoxamine or propranolol shifted the epinephrine dose-blood pressure response curves to the left. The degree of shift was similar in control and immobilized or isoproterenol-treated rats. Daily injection of quinacrine (16 mg/kg), an antimalarial agent that inhibits phospholipase A2, blocked the subsensitivity to the chronotropic effect of epinephrine, but not that to the pressor effect of epinephrine. These observations suggest that immobilization stress causes desensitization of alpha- and beta 1-receptors but not beta 2-receptors. The mechanism of desensitization of beta 1-receptors by immobilization appears to be similar to that after isoproterenol treatment, possibly due to increased turnover of phospholipids.

Adrenergic beta-Antagonists↗
PubMed1981

Effect of pyridoxal 5-phosphate on the activity of GOT isozyme in plasma from patients with Duchenne muscular dystrophy.

GOT isozyme (soluble GOT, s-GOT and mitochondrial GOT, m-GOT) activities with and without reactivation by the co-enzyme pyridoxal 5-phosphate (PALP) in plasma from 42 patients with Duchenne muscular dystrophy (DMD), and 11 normal controls were investigated. The magnitude of the enzyme activities in patients at the early stage of DMD greatly exceeded those of controls. As the disease progressed, the levels gradually declined, but late stage values were still higher than the control values except s-GOT with PALP. At the mid stage as well as the late stage, the increase in m-GOT activity was approximately to double the unstimulated activity, indicating that, in these patients, as much as half the m-GOT in the circulation was in the inactive apoenzyme form, whereas s-GOT showed negligible increase following PALP addition at any stage.

Adolescent↗
PubMed1981

Quinacrine-blocked desensitization of adrenoceptors after immobilization stress or repeated injection of isoproterenol in rats.

Repeated forced immobilization or repeated administration of isoproterenol reduces the number of beta adrenoceptors in the heart and spleen of rats. Isoproterenol, but not immobilization, reduced the number of beta receptors in the lung. These changes in beta adrenoceptors were prevented by administration of quinacrine, a phospholipase A2 inhibitor, although the drug had no effect on beta adrenoceptors when given alone. Immobilization, but not isoproterenol, reduced the number of alpha-1 adrenoceptors in the heart but had no effect on the lung. Quinacrine treatment decreased the number of alpha-1 receptors in heart and lung but increased alpha-2 receptors in the spleen. The changes in receptor number attending exposure to agonists are usually consistent with the expected changes. The effects of quinacrine on such changes suggest that phospholipids are involved in modulating the changes in number of receptors or their availability to interact with ligands.

Animals↗
PubMed1981

Regulation of the beta-adrenergic receptor by methylation of membrane phospholipids.

Stimulation of the beta-adrenergic receptor increases the enzymatic methylation of membrane phospholipids. Increased synthesis of phosphatidyl-N-monomethylethanolamine by methyltransferase I increases fluidity and enhances the ability of the beta-adrenergic receptor to couple with adenylate cyclase. The number of beta-adrenergic receptors can be regulated by the rate of synthesis and of degradation of phosphatidylcholine formed by transmethylation.

Animals↗
PubMed1981

Phospholipid methylation: a possible mechanism of signal transduction across biomembranes.

The conversion of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is catalyzed by two methyltransferases with S-adenosylmethionine as the methyl donor. PC formed by transmethylation is further metabolized by phospholipase A2. The synthesis and degradation of methylated phospholipids are involved in regulating the number of the beta-adrenergic receptors and their coupling to adenylate cyclase in rat reticulocytes, HeLa cells, and rat astrocytoma cells. Methylation of the phospholipids in these cells is stimulated by binding of agonists to the beta-adrenergic receptors. Accumulation of phosphatidyl-N-monomethylethanolamine causes an increase in membrane fluidity and enhances the coupling of the receptors to adenylate cyclase. Agents that inhibit phospholipid methylation decrease the number of receptors in intact HeLa cells, while increased phospholipid methylation unmasks cryptic receptors. Conversely, the degradation of methylated phospholipids appears to be closely associated with the desensitization of the beta-adrenergic receptors following prolonged stimulation with isoproterenol. Inhibition and stimulation of phospholipase A2 causes inhibition and stimulation of this desensitization process.

Adenylyl Cyclases↗
PubMed1981

[Heart sounds and heart murmurs in progressive muscular dystrophy of Duchenne type (author's transl)].

Phonocardiographic and echocardiographic investigation was performed in patients with progressive muscular dystrophy of Duchenne type (PMD). The clinical materials consisted of 90 patients with PMD (aged 8 to 21 yrs, a mean of 14.5), and 90 normal subjects (aged 6 to 19 yrs, a mean of 11.7). The patients with PMD were classified into 8 stages from the mildest, S(1), to the severest, S(8), according to Swinyard-Deaver' criteria. In the 90 normal subjects the diminished first heart sound was noted in 12 cases (13.3%), presystolic murmurs in 4 cases (4.4%), and diastolic rumbles in 9 cases (10%), whereas, in the patients with PMD the diminished first heart sound was noted in 47 cases (52.2%), presystolic murmurs in 41 cases (45.6%), and diastolic rumbles in 44 cases (48.9%). There was a significant difference in the incidence of the above-mentioned three phonocardiographic findings between the PMD patients and the normal subjects. But there was no significant difference in the incidence of a systolic click between these two groups. The incidence of the diminished first heart sound increased with the progress of Swinyard-Deaver' classification. A presystolic murmur was observed with the highest incidence in the stage of S(8). The incidence of a rumble was also augmented with increasing severity of the disorder from the stages of S(1) to S(7), but decreased in S(8). Another attenpt was made to relate the phonocardiographic findings to those of the echocardiogram. In the cases with anterior mitral leaflet fluttering, there were diastolic rumble in 69% whereas 16.7% of the patients without anterior mitral leaflet fluttering had diastolic rumbles. In two-dimensional echocardiography, the anterior and posterior mitral leaflets looked like pennants fluttering in the wind. All these observations positively indicate that anterior mitral leaflet fluttering was closely associated with the genesis of rumbles. Consequently, it can be concluded that the diminished first heart sound, presystolic murmurs and diastolic rumbles might be useful clinical signs in the assessment of the myocardial involvement in PMD.

Adolescent↗
PubMed1980

Phospholipid methylation and biological signal transmission.

Many types of cells methylate phospholipids using two methyltransferase enzymes that are asymmetrically distributed in membranes. As the phospholipids are successively methylated, they are translocated from the inside to the outside of the membrane. When catecholamine neurotransmitters, lectins, immunoglobulins or chemotaxic peptides bind to the cell surface, they stimulate the methyltransferase enzymes and reduce membrane viscosity. The methylation of phospholipids is coupled to Ca2+ influx and the release of arachidonic acid, lysophosphatidylcholine, and prostaglandins. These closely associated biochemical changes facilitate the transmission of many signals through membranes, resulting in the generation of adenosine 3',5'-monophophate in many cell types, release of histamine in mast cells and basophils, mitogenesis in lymphocytes, and chemotaxis in neutrophils.

Adrenal Medulla↗
PubMed1980

Phospholipid methyltransferase asymmetry in synaptosomal membranes.

The sequential methylation of phosphatidylethanolamine to form phosphatidylcholine is carried out by two methyltransferases in rat brain synaptosomes. The first enzyme methylates phosphatidylethanolamine to form phosphatidylmonomethylethanolamine. The second enzyme methylates the monomethylated phospholipid two additional times, forming phosphatidylcholine. Experiments comparing the rate of methylation between intact and lysed synaptosomes indicate that synaptosomes accumulate S-adenosyl-L-methionine and that the first methylation takes place on the cytoplasmic side of the membrane. Studies comparing trypsin digestion of proteins in intact and lysed synaptosomes indicate that the first enzyme is localized on the cytoplasmic side of the membrane and the second enzyme faces the external surface. Phospholipase C hydrolyzed phosphatidylcholine formed by methylation, suggesting its localization in the external layer of the phospholipid bilayer. A mechanism for an enzyme-mediated flip-flop of phospholipids from the cytoplasmic side to the outer surface of the synaptosomal plasma membrane is presented.

Animals↗