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Biomedical subjects

F Hirata

Publications and source records attributed to F Hirata.

At least 109 records · Page 6Linked to original sources
PubMed1982

Variants of the rat basophilic leukemia cell line for the study of histamine release.

Cloning of the rat basophilic leukemia (RBL) cell lines demonstrates variability in cell chromosome number (approximately 44-70) and in their capacity to release histamine following an IgE- or Ca2+-ionophore stimulus. After IgE activation there is increased phospholipid methylation, Ca2+ influx, arachidonic acid, and histamine release. On Ca2+ ionophore A23187 stimulation, phospholipid methylation is not increased, but Ca2+ influx, arachidonic acid, and histamine release occur. Variants of the RBL-cloned sublines defective at different stages in the release process were obtained and used to sequence the different events in the release process: IgE activation is followed by methylation, Ca2+ influx, arachidonic acid, and histamine release. However, there are other variants with defects in intermediate steps in the pathway, e.g., increased phospholipid methylation that is not followed by Ca2+ influx or arachidonic acid release not followed by histamine release. Isolating variants carrying drug-resistance markers made hybridization (reconstitution) experiments possible. Two variants were recognized, each of which was deficient in one of the two phospholipid methyltransferase enzymes. Neither of these two variants released histamine; hybrids formed by fusion of these two cell lines have both phospholipid methyltransferase enzymes and release histamine. By other complementation experiments, groups of variants with defects at different steps in the histamine release sequence were recognized. Clearly, these basophilic leukemia cell lines provide a unique system for the study of the mechanism of histamine release.

Animals↗
PubMed1982

Biochemical analysis of glucocorticoid-induced inhibition of IgE-mediated histamine release from mouse mast cells.

Pretreatment of mouse mast cells with 10(-7) to 10(-6) M dexamethasone (DM) during overnight sensitization with mouse IgE antibody resulted in inhibition of antigen-induced histamine release and degranulation. The inhibition of both degranulation and histamine release increased linearly with the duration of the treatment; maximal inhibition was obtained after approximately 16 hr with DM. The addition of DM to sensitized mast cells immediately before antigen challenge did not affect the antigen-induced histamine release. DM interacted directly with mast cells by binding to DM-specific cytoplasmic receptors. The treatment of mast cells with DM did not affect the binding of IgE to mast cells or intracellular cAMP levels. Bridging of cell-bound IgE anti-DNP antibody on mouse mast cells either by multivalent DNP-HSA or by anti-IgE induced phospholipid methylation at the plasma membrane and Ca++ influx into the cells. Pretreatment of mast cells with DM inhibited the antigen-induced phospholipid methylation and Ca++ uptake but failed to affect histamine release by Ca++ ionophore A23187. The results suggest that DM treatment inhibits histamine release by the inhibition of the early stage of biochemical processes leading to opening Ca++ channels but does not affect the process distal to Ca++ influx or the binding of IgE molecules to IgE receptors.

Animals↗
PubMed1982

[Evaluation of poor R wave progression by cross-sectional echocardiography with wall motion index].

Poor R wave progression (PRWP) in the precordial leads on the electrocardiogram in an often used but ill-defined electrocardiographic finding of antero-septal myocardial infarction. In view of the fact that the cross-sectional echocardiogram (CSE) provides a reliable method for detecting the presence and location of regional asynergy associated with acute myocardial infarction, 47 patients (myocardial infarction; 27, other disease; 20) with PRWP were selected to investigate whether or not CSE could be useful for differentiating the cases showing PRWP with myocardial infarction from those without myocardial infarction. On CSE, the left ventricle was divided into 9 segments, and to grade the severity of segmental asynergy, each segment was assigned a numerical score based upon the type of wall motion. These scores were assigned as follows; hyperkinesis: -1, normal: 0, hypokinesis: +1, akin sis: +2, and dyskinesis: +3 (Heger, 1979). The total wall motion index (WMI) was obtained by summing the scores for each of the 9 segments. And the antero-septal WMI was also obtained by summing the scores for each of the antero-septal segments. The antero-septal WMI in patients with myocardial infarction (4.45 +/- 2.59) was significantly greater than that in patients with other diseases (-0.1 +/- 2.38) (p less than 0.001). The antero-septal WMI equal to or more than +3 was found to be the most useful parameter in identifying the cases with myocardial infarction (sensitivity: 81.5%, specificity: 85.0%). Consequently, it can be concluded that CSE is quite useful for differentiation of PRWP between the cases with or without myocardial infarction.

Adult↗
PubMed1981

The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation.

Lipomodulin, purified to near homogeneity from rabbit peritoneal neutrophils, was phosphorylated by cyclic AMP-dependent protein kinase from bovine heart with concomitant loss of its ability to inhibit phospholipase A2 from porcine pancreas. Phosphorylation of lipomodulin was confirmed by the incorporation of 32P from [gamma-32P]ATP. To demonstrate that lipomodulin undergoes phosphorylation in vivo, rabbit peritoneal neutrophils were incubated with 32P and lipomoculin was isolated by immunoprecipitation with serum from a patient with systemic lupus erythematosus which has anti-lipomodulin antibody. Analysis of 32P-labeled immunoprecipitates by sodium dodecyl sulfate electrophoresis revealed a single peak of radioactivity that comigrated with [35S]methionine-labeled lipomodulin. The administration of a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine to intact rabbit neutrophils, resulted in a marked increase in arachidonate release from the cells and an increase in 32P incorporation into lipomodulin. A close correlation was found between the extent of phosphorylation of lipomodulin and the rate of arachidonate release. Phosphorylation of lipomodulin in neutrophils gradually returned to the control level with corresponding cessation of arachidonate release. In contrast to the in vitro system, phosphorylation of lipomodulin and release of arachidonic acid from peptide-stimulated neutrophils required Ca2+ entry into the cells. These results suggest that the phosphorylation-dephosphorylation of lipomodulin, phospholipase inhibitory protein, is an important mechanism for chemotactic receptor-mediated regulation of arachidonic acid release in rabbit neutrophils.

Animals↗
PubMed1981

Mepacrine treatment prevents immobilization-induced desensitization of beta-adrenergic receptors in rat hypothalamus and brain stem.

Forced immobilization is a severe stress in rats which diminishes levels of epinephrine in specific nuclei in the hypothalamus and brain stem, suggesting that release of epinephrine is stimulated to a rate which exceeds the rate of its replacement. In the pineal gland, frog erythrocytes, C6 astrocytoma cells and rat brain, beta-adrenoceptor agonists appear to regulate the number of their receptors. Exposure to high concentrations of an agonist leads to apparent decrease in receptors reflected by a decrease in maximal specific binding of antagonists. The apparent decreases in receptors have been shown to be attended by decreases in physiologic responsiveness. In C6 astrocytoma cells, beta-agonists stimulate methylation of phosphatidylethanolamine to increase formation of membrane phosphatidylcholine which in turn appears to enhance activation of adenyl cyclase. Interference with the metabolism of phospholipids by exposure to phospholipase A2 inhibitor, mepacrine (quinacrine), prevents agonist-induced desensitization of beta-adrenoceptors in astrocytoma cells. In the present study repeated immobilization stress has been found to decrease significantly the number of beta-adrenoceptors in hypothalamus and brain stem while increasing the number of alpha 2-adrenoceptors. The desensitization of beta-adrenoceptors was prevented by treatment with mepacrine.

Animals↗
PubMed1981

Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx, and histamine release: reconstitution by hybridization.

Variants of the rat basophilic leukemia (RBL) cell line were isolated and screened for phospholipid methyltransferase I and II activities, enzymes that convert phosphatidylethanolamine to phosphatidylcholine. Two variants were found that had decreased phospholipid methyltransferase enzyme levels and were unable to cause an influx of Ca2+ or release histamine in an IgE-mediated reaction. However, these cells were able to release histamine through an ionophore-induced reaction, indicating that the releasing mechanism distal to the Ca2+ channel was intact. One cell line, 1C1.B1, had low specific activity for phospholipid methyltransferase I. A second variant, 2H3.B6, had reduced phospholipid methyltransferase II activity. Although both variants were unable to incorporate label from [methyl-3H]methionine or [3H]serine into phosphatidylcholine, they were able to incorporate [methyl-3H]choline and myo-[2-3H(N)]inositol into phospholipids. Fusion of the two cell lines and isolation on selective media resulted in the growth of eight independent hybrids. All eight had an increased number of chromosomes and normal phospholipid methyltransferase activities. Stimulation of the hybrids with IgE resulted in CA2+ influx and histamine release. These results indicate that phospholipid methylation precedes and is necessary for Ca2+ influx, and they further support the hypothesis that methylation is a necessary early step in the IgE-mediated histamine release reaction in RBL cells.

Animals↗
PubMed1981

Bridging of IgE receptors activates phospholipid methylation and adenylate cyclase in mast cell plasma membranes.

Bridging of IgE receptors on normal rat mast cells by divalent anti-receptor antibodies induced phospholipid methylation and an increase in intracellular cyclic AMP within 15 sec after the receptor bridging. These biochemical events were followed by Ca2+ influx and histamine release. When IgE receptors on isolated plasma membranes were bridged by the antibody, both the increase in the incorporation of [3H]methyl into lipid fraction and the synthesis of cyclic AMP were demonstrated. The synthesis of cyclic AMP in this system was enhanced in the presence of GTP. The results indicated that the bridged IgE receptors are linked to both methyltransferases and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in the plasma membrane. An increase in cyclic AMP prior to receptor bridging suppressed phospholipid methylation in the plasma membrane, Ca2+ uptake, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazaadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are e, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are e, and subsequent histamine release. On the other hand, inhibition of phospholipid methylation by (S)-isobutyryl-3-deazadenosine resulted in the suppression of cyclic AMP synthesis in the plasma membrane. These findings suggest that the activation of phospholipid methylation and the activation of adenylate cyclase are mutually regulated.

Adenylyl Cyclases↗
PubMed1981

Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases.

The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.

Animals↗