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Biomedical subjects

S Nojima

Publications and source records attributed to S Nojima.

At least 37 records · Page 2Linked to original sources
PubMed1995

Clear differences in ceramide metabolism between glycosphingolipids and sphingomyelin in a human promyelocytic leukemia cell line HL-60 stimulated by a differentiation inducer.

Although the ceramide components of both glycosphingolipids (GSLs) and sphingomyelin (SM) in HL-60 cells were identical, the molecular species of the ceramides preferentially used in biosynthesis were quite different in GSLs and SM. When HL-60 cells were stimulated to differentiate into macrophage-like cells by phorbol ester after their sphingolipids had been metabolically labeled with L-[3-14C]serine to saturation point, marked changes in the radioactivities of the ceramide residues were observed in GSLs, showing the activation of a biosynthetic pathway of ganglioside GM3. No significant changes were, however, observed in the ceramide residues of SM. These results indicate that it is necessary to consider the overall metabolism of ceramides, including their origin, when investigating the functions of ceramides in signal transduction systems.

Cell Differentiation↗
PubMed1995

Platelet-activating factor (PAF) and the formation of chronic subdural haematoma. Measurement of plasma PAF levels and anti-PAF immunoglobulin titers.

In order to estimate the contribution of platelet-activating factor (PAF) to the formation of chronic subdural haematomas (CSH), we measured plasma PAF and anti-PAF antibody levels in head-injured patients with and without CSH and normal volunteers. Plasma PAF and anti-PAF IgG levels were higher in patients with CSH than in patients without CSH or in normal volunteers. Furthermore, plasma PAF and anti-PAF IgG levels increased in a time-dependent manner over the first 35 days following head injury. These data suggest that PAF may be involved in the generation of CSH.

Adult↗
PubMed1995

Selective inhibition of human TNF-alpha action by flecainide acetate, an antiarrhythmic drug.

It is now generally accepted that human tumor necrosis factor-alpha (hTNF-alpha) affects not only tumor cells but also normal cells, providing critical tissue damage. hTNF-alpha also enhanced the response of polymorphonuclear neutrophils (PMN) by its priming action and resulted in the increased generation of active oxygen which in turn may be responsible for the tissue injury. Seeking a conventional drug to attenuate the cytolytic activity of tumor necrosis factor (TNF-alpha) and thereby prevent excessive tissue injury, we focused on the cytolytic action of hTNF-alpha against L929 cells, which are sensitive to TNF-alpha, and found that flecainide acetate [N-(2-piperidylmethyl) 1,5-bis-(2,2,2-trifluoroethoxy) benzamide acetate] inhibited specifically the cytolytic action of hTNF-alpha against L929 cells. Flecainide acetate also specifically inhibited the priming action of hTNF-alpha which enhance the formylmethionyl-leucyl-phenylalanine (FMLP)-induced receptor-mediated superoxide (O.2-) generation of human peripheral polymorphonuclear neutrophils (hPMN). The ID50 values for hTNF-alpha induced cytotoxicity in L929 cells and hTNF-alpha primed FMLP-induced O.2- generation of hPMN were 30 and 50-60 microM, respectively. However, the drug does not inhibit the FMLP- or phorbol myristate acetate (PMA)-induced O.2- generation of nonprimed hPMN and has a weak cytotoxic effect on L929 cells. From these results, it is concluded that flecainide acetate suppressed specifically the action of hTNF-alpha.

Animals↗
PubMed1994

Platelet-activating factor (PAF) and the development of chronic subdural haematoma.

Platelet activating factor (PAF) content and PAF-acetylhydrolase (PAFAH) activity were measured in the plasma and haematoma of 34 chronic subdural haematoma (CSH) patients. The plasma PAF level in patients with CSH was higher than that in healthy controls. Although there was no correlation between the plasma PAF levels and the interval between the onset of symptoms and the day of sampling, namely, the interval after bleeding, the haematoma PAF level gradually decreased according to the interval after the onset of symptoms. There was no difference between plasma PAFAH activity in patients with CSH and that in healthy controls, and haematoma enzyme activity gradually increased correlated with the interval between the onset of symptoms and surgery. In addition, the localization of PAF in haematoma capsules was histochemically determined. PAF was solely localized to the peri-sinusoidal vessels in the outer membrane of haematoma capsules. Based on these biochemical and histochemical studies, we speculated that PAF may play a role in the development of chronic subdural haematomas.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

Differences related to the production of arachidonic acid between collagen- and thrombin-stimulated human platelets.

The effects of collagen and thrombin on the liberation of free arachidonic acid were investigated in human platelets by fluorometric high-performance liquid chromatography. Collagen induced a concentration-dependent increase in the extent of platelet aggregation, as well as an accumulation of arachidonic acid in human platelets. By contrast, thrombin effectively provoked a potent aggregation at relatively low concentration without any accumulation of free arachidonic acid, although the accumulation of arachidonic acid was detected at a high concentration of thrombin (> 0.1 U/ml) that induced full aggregation. The selective liberation of arachidonic acid was found in thrombin-stimulated platelets. Non-selective liberation of fatty acids occurred in platelets that had been stimulated with a high concentration of collagen (10 micrograms/ml), as well as in platelets stimulated with A23187. The net amount of free arachidonic acid in collagen-stimulated platelets was estimated by use of eicosatetraenoic acid (ETYA), which is an inhibitor of both cyclooxygenase and lipoxygenase. ETYA markedly potentiated the accumulation of free arachidonic acid in collagen-stimulated platelets without changing the amounts of other fatty acids in the cell.

Arachidonic Acid↗
PubMed1994

Accumulation of platelet-activating factor acetylhydrolase in the peritoneal cavity of guinea pig after endotoxin shock.

We examined the production of PAF, a mediator of shock, and LysoPAF, an inactive metabolite of PAF, in the guinea pig peritoneal cavity after i.p. administration of Escherichia coli LPS. Within 1 h of LPS administration, the level of PAF in the peritoneal fluid increased from 4.9 to 37.2 pmol/animal and decreased to the control value thereafter. In contrast, the level of lysoPAF gradually rose from 63.5 to 268 pmol/animal for up to 6 h. The activity of acetylhydrolase, which converts PAF to lysoPAF, in the peritoneal cavity increased in parallel with the increase in the lysoPAF level. The enzyme was distinguishable from phospholipase A2, because p-bromophenacylbromide (p-BPB), Ca2+, and ethylenediaminetetraacetic acid (EDTA) did not affect its enzymatic activity. In addition, this acetylhydrolase revealed similar biochemical properties to that detected in plasma. Both acetylhydrolases were resistant to trypsin treatment and had the same apparent molecular weight, as shown by gel-filtration column chromatography. These results suggest that the acetylhydrolase, which accumulates in the peritoneal cavity, infiltrates from the plasma in response to LPS, and then participates in the exclusion of PAF during endotoxin shock.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

Purification and characterization of platelet-activating factor acetylhydrolase from peritoneal fluid obtained from guinea pigs after endotoxin shock.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) acetyl-hydrolase is an enzyme that hydrolyzes the acetyl ester of PAF. We purified this enzyme, which accumulated in the peritoneal cavity during endotoxin shock, by ammonium sulfate precipitation, and sequential use of butyl-Toyopearl, heparin-Sepharose, Con A-Sepharose, chelating-Sepharose, and MonoQ column chromatographies. We identified a monomeric polypeptide with a molecular weight of approximately 63 kDa on SDS-PAGE. This molecular weight differs from those of previously described acetylhydrolases. The purified enzyme did not degrade phospholipids with a long chain fatty acyl group at the sn-2 position. In addition, the enzyme activity was not inhibited by either pBPB or quinacrine. Accordingly, this enzyme is distinct from phospholipase A2. In addition, this enzyme also hydrolyzed some oxidatively fragmented phospholipids with PAF-like biological activities such as 1-O-hexadecyl-2-glutaroyl-sn-glycero-3-phosphocholine and 1-O-hexadecyl-2-succinoyl-sn-glycero-3-phosphocholine.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

[The relationship between the family system and the family coping among families with a chronically ill child].

The purposes of this study were to identify the family coping strategies among families with chronically ill children and to explore the relationship between the family system (variables), the family burden and the family coping. One hundred fifty-two families with chronically ill children were studied. The Japanese version of Family Adaptability and Cohesion Evaluation Scales II and the Family Coping Behavior Inventory II were used. The result were 1) the family cohesion and adaptability in families with a chronically ill child tended to be lower than normal families; 2) the integration coping pattern was positively related with family cohesion and the family burden; 3) the problem solving coping pattern was positively related with the family burden; 4) the normalization coping pattern was negatively related with the family burden and positively related with the family cohesion; 5) the crisis response coping pattern was positively related with the family burden and negatively related with the family cohesion.

Adaptation, Psychological↗
PubMed1993

Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage.

This study examines whether platelet-activating factor (PAF) is involved in the occurrence of vasospasm after subarachnoid hemorrhage (SAH). A vasospasm model was produced in rabbits, with animals in six experimental groups receiving two subarachnoid injections of autologous arterial blood with the addition of one of the following; saline (Control Group 1), 25% dimethyl sulfoxide (Control Group 2), PAF (1, 2.5, 5, or 10 micrograms), CV6209 (10 or 100 micrograms), BN52021 (10 or 100 micrograms), or anti-PAF immunoglobulin G (IgG, 50 or 500 micrograms). No significant differences were detected between Control Groups 1 and 2 with regard to neurological deterioration and basilar artery constriction after SAH was induced. Administration of PAF together with autologous blood aggravated neurological deficits in a dose-dependent manner (r = 0.724, p < 0.001) and produced basilar artery constriction at two doses each of 2.5 micrograms (p < 0.05), 5 micrograms (p < 0.01), and 10 micrograms (p < 0.01). Neurological deterioration was prevented in rabbits receiving an intracisternal administration of either PAF antagonist CV6209 or BN52021 or anti-PAF IgG (p < 0.01 at a total dose of 20 micrograms and p < 0.05 at a total dose of 200 micrograms CV6209, p < 0.01 at total doses of 20 and 200 micrograms BN52021, and p < 0.01 at total doses of 100 and 1000 micrograms anti-PAF IgG). A reduction in basilar artery constriction was achieved by the injection of anti-PAF IgG (p < 0.05 at total doses of 100 and 1000 micrograms). Histological examination at autopsy on Days 14 to 21 showed mainly ischemic changes in the brain, including selective neuronal necrosis and cerebral infarction. The control and PAF groups showed marked ischemic changes. On the other hand, no ischemic changes were noted in the anti-PAF IgG group, and only 9% of animals in the CV6209 group and 25% in the BN52021 group demonstrated selective neuronal necrosis or infarction. This study thus provides evidence to support the role of PAF in the pathogenesis of vasospasm after SAH.

Animals↗
PubMed1993

Immunofluorescent localization of platelet-activating factor (PAF) in the rat.

An immunofluorescent staining method for detecting platelet-activating factor (PAF) is described. This method employs a polyclonal anti-PAF rabbit antibody. When rat brain, heart, lung, liver or kidney tissue was stained using this method, the heart, lung and kidney exhibited PAF-specific staining. Analysis of the amount of PAF in different organs, either by immunofluorescence or by bioassay, showed that kidney tissue contains the greatest amount of PAF.

Animals↗
PubMed1992

Possible influence of lysophospholipase on the production of 1-acyl-2-acetylglycerophosphocholine in macrophages.

The rate of production of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (acylPAF) was measured in macrophages following the incorporation of [3H]acetate. Upon activation by A23187, guinea pig alveolar macrophages incorporated [3H]acetate into PAF, but a little radioactivity was found in acylPAF. However, labeling of acylPAF and PAF with [3H]acetate was greatly enhanced in A23187-stimulated alveolar macrophages that had been pretreated with phenylmethanesulphonyl fluoride (PMSF). [3H]PAF was predominantly converted to 1-[3H]alkyl-2-acyl glycerophosphocholine, but [14C]acylPAF rapidly hydrolyzed to 14C-labeled free fatty acid by the incubation with lysates prepared from macrophages. The deacetylation of [14C]acylPAF and [3H]PAF by acetylhydrolase and also the hydrolysis of [14C]lysoPC by lysophospholipase were strongly inhibited in macrophages that had been pretreated with PMSF, while PMSF failed to inhibit the activities of acetyltransferase and acyltransferase. The relative proportions of PAF and acylPAF were quite different in different types of cells. In contrast to alveolar macrophages, peritoneal macrophages, neutrophils and spleen cells from guinea pigs incorporated 2-4 times more [3H]acetate into acylPAF than into PAF. The presence of high levels of acylPAF in peritoneal macrophages was confirmed by GLC-MS analysis. The activities of lysophospholipase, acetylhydrolase and acetyltransferase were measured in alveolar and peritoneal macrophages to determine whether the preferential formation of acylPAF as compared to PAF in peritoneal macrophages was due to differences in these activities between alveolar and peritoneal macrophages. The activity of acetylhydrolase of peritoneal macrophages was almost the same as that in alveolar macrophages. The activity of acetyltransferase in peritoneal macrophages was about half of that in alveolar macrophages. However, the activity of lysophospholipase in peritoneal macrophages was one-sixth of that in alveolar macrophages. These results suggest that lysophospholipase is one of the primary factors involved in the control of the production of acylPAF in activated cells, and that it acts by modulating the availability of lysoPC for the synthesis of acylPAF. Furthermore, high levels of activity of lysophospholipase allow the preferential formation of PAF, via the rapid hydrolysis of lysoPC which would act as a competitive inhibitor of the incorporation of acetate into lysoPAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1991

Specific binding of antibodies to platelet-activating factor (PAF) as demonstrated by thin-layer chromatography/immunostaining.

The specificity of rabbit antibodies produced by injection of 1-O-(15'-carboxypentadecyl)-2-N,N-dimethylcarbamoyl-sn-glycero-3- phosphocholine bovine serum albumin (BSA) conjugates was examined by a thin-layer chromatography (TLC/immunostaining method. Phosphatidylcholine (PC), lysophosphatidylcholine (lysoPC), lyso platelet-activating factor (lysoPAF), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM), phosphatidylinositol (PI), phosphatidic acid (PA) and cardiolipin (CL) were not immunostained. Among several synthetic PAF-related compounds, the antibodies only bound to PAF agonists which have the activity to induce washed rabbit platelet aggregation. The results suggest that the binding sites of the antibodies on the PAF molecule are the acetyl group at the sn-2 position and the choline moiety at the sn-3 position of glycerol, both of which are essential for exerting the biological function of PAF and for binding to the PAF receptors located on cellular membranes.

Animals↗