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Biomedical subjects

S Nakashima

Publications and source records attributed to S Nakashima.

At least 235 records · Page 13Linked to original sources
PubMed1989

Evidence of Ca2+ mobilizing action of arachidonic acid in human platelets.

The addition of arachidonic acid induced a rapid release of 45Ca2+ from human platelet membrane vesicles which accumulated 45Ca2+ in the presence of ATP. Docosahexaenoic acid, eicosapentaenoic acid, linolenic acid and linoleic acid were less active than arachidonic acid. In contrast, oleic acid, myristic acid and palmitic acid were without effect. The thromboxane A2 analogue induced no 45Ca2+ release. The cyclooxygenase/lipoxygenase inhibitor failed to suppress arachidonic acid-induced 45Ca2+ release at the concentration which inhibited the production of lipid peroxides. These data indicate that the activity of arachidonic acid may be due to fatty acid itself and not to its metabolites. The combination of arachidonic acid and inositol 1,4,5-trisphosphate (IP3) resulted in a greater 45Ca2+ release from platelet membrane vesicles than either compound alone. When the intracellular free Ca2+ concentration ([Ca2+]i) was measured using fura-2, the thrombin-induced [Ca2+]i increase was reduced in platelets which had been treated with a phospholipase A2 inhibitor, ONO-RS-082 (2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid). These results provide evidence that arachidonic acid alone may cause Ca2+ increase and also may induce an additional Ca2+ mobilization to IP3-induced Ca2+ release in human platelets.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Primary role of calcium ions in arachidonic acid release from rat platelet membranes. Comparison with human platelet membranes.

The liberation of arachidonic acid (AA) was investigated in platelet membranes prelabelled with [3H]AA. In rat platelet membranes, Ca2+ at concentrations over several hundred nanomolar induced [3H]AA release, with a concurrent decrease in 3H radioactivity of phosphatidylethanolamine and phosphatidylcholine. Some 4-6% of total radioactivity incorporated into platelet membrane lipids was released at 1-10 microM-Ca2+, which is nearly equivalent to that attained in agonist-stimulated platelets. Formation of lysophospholipids in [3H]glycerol-labelled membranes and decrease in [3H]AA liberated by the phospholipase A2 inhibitors mepacrine and ONO-RS-082 suggest that [3H]AA release is mainly catalysed by phospholipase A2. In intact platelets agonist-stimulated [3H]AA release was markedly decreased in the absence of extracellular Ca2+ or in the presence of the intracellular Ca2+ chelator quin 2. These results indicate that in rat platelets the rise of intracellular Ca2+ plays a primary role in the activation of phospholipase A2. In contrast, Ca2+ even at high millimolar concentrations did not effectively stimulate [3H]AA release in human platelet membranes. Thus factor(s) additional to or independent of Ca2+ is required for the liberation of AA in human platelets.

Animals↗
PubMed1989

Accumulation of diacylgylcerol in platelet phosphoinositide turnover in schizophrenia: a biological marker of good prognosis?

Phosphoinositide (PI) turnover was examined by measuring phosphatidic acid (PA) and diacylglycerol (DG) production following thrombin stimulation in platelet membranes from 20 schizophrenic patients, 10 patients with other mental disorders, and 9 normal controls. In 6 of 13 acute schizophrenic patients, DG was not transformed into phosphatidic acid (PA), but accumulated in the platelets instead. The abnormal findings persisted for at least 2 months, but then reversed over a long period. Three years later, the patients with abnormal PI turnover had a significantly better outcome than other acute schizophrenic patients.

Adolescent↗
PubMed1989

[Geometrical investigation on mechanism and movement of Gysi Simplex OU articulator].

Gysi Simplex OU articulator was constructed by modifying Gysi Simplex 1914, and has been used for students' practice of complete denture construction at 18 Japanese dental schools. Therefore, the mechanism and movement of the articulator should be explained and understood clearly from the educational standpoint of view. In this study, the movement was analyzed by geometrical drawing after Ishiwara-Suetsugu's simplified method. The following results were obtained: 1. Sagittal inclination of incisal guidance acted as an important role for location and inclination of lateral axis. 2. Accessory working condylar guide, which is located behind the condyle post, is another important mechanism as one of determinants of the movement. 3. The lateral wall of balancing condylar guide should be forced to touch always the balancing condyle. 4. It was clarified that the movement of Gysi Simplex OU followed the Gysi's axis theory.

Dental Articulators↗
PubMed1989

[Phosphoinositide turnover and Ca2+ mobilization during phagocytosis in cultured chick retinal pigment epithelial cells].

Ca2+ mobilization and phosphoinositide turnover were examined during phagocytosis of latex particles in cultured chick retinal pigment epithelial cells (RPE cells). Ca2+ influx into cells and Ca2+ efflux from the cells were enhanced by about 1.5-fold and 3-fold compared to control cells, respectively. A high content of Ca2+ in RPE cells has been reported. Therefore, the Ca2+ efflux observed here may be a reflection of Ca2+ release into cytosol from the intracellular storage site(s). In [3H] inositol-prelabeled RPE cells, addition of latex particles elicited decreases in phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol with the concomitant formation of inositol phosphates including inositol trisphosphate, indicating the hydrolysis of phosphoinositides by phospholipase C. These results suggest that phosphoinositide turnover may be closely coupled with Ca2+ mobilization during phagocytosis in RPE cells.

Animals↗
PubMed1989

[Enhancement of membrane phospholipid breakdown and synthesis during phagocytosis in cultured chick retinal pigment epithelial cells].

In chick cultured retinal pigment epithelial cells (RPE cells) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are major membrane phospholipid constituents. The synthesis of these phospholipids occurred gradually, compared to rapid synthesis of phosphatidic acid (PA) and phosphatidylinositol (PI). Exposure of RPE cells to latex particles elicited active phagocytosis. In [3H] glycerol- or [3H] arachidonic acid-prelabeled cells, a transient decrease in PI was observed without increases in the level of either diacylglycerol (DG) or PA. However, the radioactivity of PC and PE significantly increased. The enhancement of de novo synthesis of phospholipids, measured by the incorporation of [3H] glycerol, was not stimulated within 2 hours after the addition of latex particles. The transient increase in the ratio of [14C] choline/[3H] glycerol in PC may indicate the accelerated synthesis of PC but not via a de novo synthetic pathway. The results obtained in the present study indicate that DG, produced by PI breakdown, may be utilized in PC synthesis for the replenishment of membrane lost during phagocytosis.

Animals↗
PubMed1988

Stimulation of arachidonic acid release by guanine nucleotide in saponin-permeabilized neutrophils: evidence for involvement of GTP-binding protein in phospholipase A2 activation.

Addition of a guanine nucleotide analog, guanosine 5'-O-(thiotriphosphate) (GTP gamma S)(1-100 microM) induced release of [3H]arachidonic acid from [3H]arachidonate-prelabeled rabbit neutrophils permeabilized with saponin. The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced arachidonate release was enhanced by GTP gamma S, Ca2+, or their combination. Ca2+ alone (up to 100 microM) did not effectively stimulate lipid turnover. However, the combination of fMLP plus GTP gamma S elicited greater than additional effects in the presence of resting level of free Ca2+. The addition of 100 microM of GTP gamma S reduced the Ca2+ requirement for arachidonic acid liberation induced by fMLP. Pretreatment of neutrophils with pertussis toxin resulted in the abolition of arachidonate release and diacylglycerol formation. Neomycin (1 mM) caused no significant reduction of arachidonate release. In contrast, about 40% of GTP gamma S-induced arachidonate release was inhibited by a diacylglycerol lipase inhibitor, RHC 80267 (30 microM). These observations indicate that liberation of arachidonic acid is mediated by phospholipase A2 and also by phospholipase C/diacylglycerol lipase pathways. Fluoride, which bypasses the receptor and directly activates G proteins, induced arachidonic acid release and diacylglycerol formation. The fluoride-induced arachidonate release also appeared to be mediated by these two pathways. The loss of [3H]arachidonate was seen in phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine. These data indicate that a G protein is involved between the binding of fMLP to its receptor and activation of phospholipase A2, and also that the arachidonic acid release is mediated by both phospholipase A2 and phospholipase C/diacylglycerol lipase.

Animals↗
PubMed1988

Hereditary dentatorubral-pallidoluysian atrophy: clinical and pathologic variants in a family.

We describe a family showing dentatorubral-pallidoluysian atrophy. Three patients appeared through three successive generations and displayed a wide variety of clinical pictures. The male proband with onset in childhood showed progressive myoclonus epilepsy syndrome. The father experienced cerebellar ataxia, myoclonus, and mild dementia starting in middle age; the paternal grandmother had progressive symptoms of cerebellar ataxia, choreiform movements, and dementia, but neither myoclonus nor epilepsy in senescence. Neuropathologic examination of two patients, the proband and the paternal grandmother, revealed combined degeneration of the dentatorubral and pallidoluysian systems and obvious degeneration involving the striatum in the proband and the cerebellar cortex in the grandmother. The present study indicates that this disease can include many clinical and pathologic variants even in the same family.

Adolescent↗
PubMed1987

Differential sensitivity of arachidonic acid release and 1,2-diacylglycerol formation to pertussis toxin, GDP beta S and NaF in saponin-permeabilized human platelets: possible evidence for distinct GTP-binding proteins involving phospholipase C and A2 activation.

Human platelets labeled with [3H]arachidonic acid and permeabilized with saponin produced [3H]1,2-diacylglycerol (DG) by phospholipase C and released [3H]arachidonate by phospholipase A2, when activated with thrombin. Thrombin-induced arachidonate liberation was almost completely inhibited with pretreatment of pertussis toxin (10 micrograms/ml), whereas DG formation was decreased by only 20-40% in the toxin-treated platelets. Although guanosine 5'-o-(2-thiodiphosphate) (GDP beta S) suppressed arachidonate release and DG production in a dose-dependent manner, the half maximal inhibition required less than 10 microM for arachidonate release but more than 100 microM for DG production. Moreover, the dose-response effects of NaF on arachidonate release and DG formation were different. These results indicate that arachidonate release and DG formation are differently affected by these agents acting on guanine nucleotide binding proteins (G-proteins), suggesting that the distinct G proteins modulate the activity of phospholipase C and phospholipase A2.

Arachidonic Acid↗
PubMed1987

Neomycin is a potent agent for arachidonic acid release in human platelets.

Neomycin (10 microM - 1 mM) was found to induce considerable release of [3H]arachidonic acid from phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine in saponin-permeabilized human platelets prelabeled with [3H]arachidonic acid. The magnitude of arachidonate liberation was almost equal to that induced by A23187 (400 nM) or even greater than that caused by thrombin (1 U/ml). Moreover, neomycin enhanced arachidonic acid release induced by thrombin. Since no significant formation of diacylglycerol and phosphatidic acid via phospholipase C was observed, the arachidonate liberation was considered to be mainly catalyzed by phospholipase A2 action. Addition of neomycin (100 microM) to 45Ca2+-preloaded platelets elicited 45Ca2+ mobilization from intracellular stores. These results indicate evidence that neomycin evokes Ca2+ mobilization from internal stores, which leads to activation of phospholipase A2 to release arachidonic acid in human platelets.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

A role of diacylglycerol kinase in stimulus-secretion coupling of human platelets. Dissociation of serotonin secretion from Ca2+ mobilization.

The addition of diacylglycerol kinase inhibitor, R 59 022 (6-[2-[4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl]-7-methyl - 5H-thiazolo[3,2-alpha]pyrimidin-5-one) resulted in a marked accumulation of diacylglycerol in thrombin-stimulated platelets. Release of arachidonic acid induced by thrombin was not affected by the inhibitor. In intact platelets, the conversion of exogenously added 1-oleoyl-2-acetylglycerol to 1-oleoyl-2-acetylphosphatidic acid also was inhibited by the inhibitor. We further investigated the effects of the inhibitor on serotonin secretion and Ca2+ mobilization in thrombin-activated platelets. R 59 022 potentiated serotonin secretion induced by thrombin or 1-oleoyl-2-acetylglycerol. On the other hand, the thrombin-induced increase in cytosolic free Ca2+ concentration measured with aequorin or Quin2 was found to be depressed by R 59 022. These results indicate that diacylglycerol kinase has an important role in regulation of serotonin secretion and that Ca2+ mobilization may not be tightly coupled to serotonin secretion.

Aminoquinolines↗
PubMed1987

Paragangliomas of the craniocervical region. An immunohistochemical study on tyrosine hydroxylase.

An immunohistochemical study on tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine synthesizing pathway, was made on three craniocervical region paragangliomas, two of which showed metastases to the cervical lymph nodes. In all of the original tumors, the majority of tumor cells showed positive immunostaining for TH of variable intensity in their cytoplasm regardless of their cytological features such as cellular and nuclear pleomorphism. The finding suggests that most tumor cells are capable of production of catecholamines and are derived from chief cells in the normal paraganglia. In cervical lymph nodes, however, no positive immunostaining for TH was observed in metastatic tumor cells, in contrast with the findings in the original tumors. The absence of TH immunoreactivity in metastatic tumor cells appears to be noteworthy in considering their malignant potential. Application of the TH immunohistochemistry to further cases appears important for the better understanding of this neoplasm, a catecholamine-producing tumor.

Adult↗
PubMed1987

Guanine nucleotides stimulate arachidonic acid release by phospholipase A2 in saponin-permeabilized human platelets.

GTP or GTP gamma S alone caused low but significant liberation of arachidonic acid in saponin-permeabilized human platelets but not in intact platelets. GTP or GTP gamma S also enhanced thrombin-induced [3H]arachidonic acid release in permeabilized platelets. Inhibitors of the phospholipase C (neomycin)/diacylglycerol lipase (RHC 80267) pathway for arachidonate liberation did not reduce the [3H]arachidonic acid release. The loss of [3H]arachidonate radioactivity from phosphatidylcholine was almost equivalent to the increase in released [3H]arachidonic acid, suggesting the hydrolysis of phosphatidylcholine by phospholipase A2. The effect of GTP gamma S was greater at lower Ca2+ concentrations. These data indicate that the release of arachidonic acid by phospholipase A2 in saponin-treated platelets may be linked to a GTP-binding protein.

Arachidonic Acid↗
PubMed1986

GTP and GDP will stimulate platelet cytosolic phospholipase C independently of Ca2+.

The hydrolysis of [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) by cytosolic phospholipase C from human platelets was determined. Cytosolic fractions were prepared from platelets that had or had not been preactivated with thrombin. Thrombin pretreatment did not affect cytosolic phospholipase C activity. In both cytosolic fractions, phospholipase C was activated by GTP and GTP gamma S. This action is observed in the presence of 2 mM EGTA. GDP was as effective as GTP in stimulating cytosolic phospholipase C in the presence of Ca2+ or EGTA. Partially purified phospholipase C obtained from platelet cytosol is activated by GTP, but not by GTP gamma S, in the presence of 2 mM EGTA. However, in the presence of 6 microM Ca2+, both GTP and GTP gamma S stimulated the partially purified phospholipase C. Our present information indicates that GTP and GDP have a direct effect on the cytosolic phospholipase C.

Blood Platelets↗