[Mechanism of morphological changes of platelets upon exposure to cold].
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Blood Platelets↗
Biomedical subjects
M Higashihara
Publications and source records attributed to M Higashihara.
Rapid potentiation of DNA binding activities of particular transcription factors with leucine-zipper motifs in discrete brain structures of the gerbil with transient forebrain ischemia.
Binding of radiolabeled double stranded oligonucleotide probes for nuclear transcription factors with leucine-zipper motifs, such as activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and Myc, was unevenly distributed in gerbil brain in a manner peculiar to each factor. Among 3 different hippocampal subfields examined, the dentate gyrus had the highest basal DNA binding activities of AP1 with progressively less potent binding in the CA3 and CA1 subfields. Similarly, the dentate gyrus was highest in the basal binding of probes for both CREB and Myc among the 3 distinct hippocampal subregions. However, transient forebrain ischemia for 5 min induced more potent enhancement of the AP1 binding in the CA1 subfield 4 h after the insult than in the CA3 subfield and dentate gyrus. In contrast, the ischemic injury similarly tripled DNA binding activities of CREB without markedly affecting those of Myc in hippocampal CA1 and CA3 subfields. Binding of the probe for AP1 was also markedly potentiated following ischemia in the thalamus, caudate putamen, frontal cortex and cerebellar cortex in a rank order of decreasing magnitude, while the ischemic insult induced slight but statistically significant potentiation of both CREB and Myc binding in the thalamus without affecting that in other discrete brain regions. These results suggest that expression of AP1 may be a determinant of unique vulnerability and/or resistance to an ischemic insult in the gerbil hippocampus.
Animals↗
A case of POEMS syndrome with thrombocytopenia and biliverdinaemia.
This report describes a case of POEMS syndrome with extremely rare complications of thrombocytopenia and biliverdinaemia. The thrombocytopenia appeared to be due to immunopathogenesis. Steroid treatment resulted in complete disappearance of the biliverdinaemia in this patient as well as symptoms and signs of POEMS syndrome, suggesting that the biliverdinaemia was related to POEMS syndrome.
Biliverdine↗
Okadaic acid induces marked shape change of human platelets.
Okadaic acid (OA) induced marked shape changes of human platelets but neither granule secretion nor increase in [Ca2+]i occurred. Morphological changes induced by OA were unique and different from those observed with thrombin mainly in two respects. One is that the pseudopods formed by OA treatment were longer and straighter than those by thrombin. The other is that no granule centralization was observed with OA-treatment, although central condensation of cytofilaments was observed as was with thrombin. The immunocytochemical analysis employing anti-myosin antibody revealed that myosin was distributed in the elongated pseudopods. Since OA induced phosphorylation of the 20-kDa myosin light chain (MLC20) corresponding to the change in shape of platelets but did not induce phosphorylation of the 47-kDa protein (pleckstrin) (Higashihara M. et al. FEBS Lett. 307:206-210, 1992), these results suggest that phosphorylation of MLC20 plays an important role in OA-induced unique morphological changes of platelets.
Blood Platelets↗
Effects of the prior activation of protein kinase C on human platelet activation induced by thrombin.
Effects of the prior activation of protein kinase C (PKC) on the responses induced by thrombin were studied using human blood platelets, in which PKC is abundantly expressed. At a concentration of 25 nM, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) induced little aggregation or release by itself but selectively elicited PKC activation in a time-dependent manner, as monitored by 47-kDa protein phosphorylation. Increases in the intracellular Ca2+ concentration of human platelets caused by thrombin, at any concentration, were markedly inhibited by the prior addition of 25 nM TPA in a time-dependent manner. However, the effects of TPA on platelet aggregation and secretion induced by thrombin varied, depending upon the agonist concentration; the PKC activator markedly enhanced the aggregation and secretion induced by lower concentrations of thrombin but had a tendency to weakly inhibit those induced by higher concentrations of thrombin. TPA enhanced the ionomycin effect upon aggregation and release without obvious effects on the ionophore-induced Ca2+ mobilization, suggesting that PKC potentiates platelet function by increasing intracellular sensitivity to Ca2+. There was a good time-dependent correlation of the TPA effects among the three parameters, namely, the phosphorylation of the 47-kDa protein, inhibition of the [Ca2+]i increase induced by thrombin, and enhanced ionomycin effects in aggregation and release. It is most likely that the final responses of agonist-activated platelets depend upon the balance of two factors induced by PKC; inhibition of Ca2+ signals and enhancement of intracellular sensitivity to Ca2+.
Blood Platelets↗
Increased secretion of interleukin-6 in malignant mesothelioma cells from a patient with marked thrombocytosis.
BACKGROUND: A high prevalence of thrombocytosis in malignant mesothelioma has been reported, although its pathogenesis remains unknown. METHODS: The case of a patient with marked thrombocytosis in peritoneal malignant mesothelioma is reported. To investigate the cytokines responsible for thrombocytosis in this patient, enzyme-linked immunosorbent assay and immunohistochemical analysis were used. RESULTS: Tumor cells produced large amounts of interleukin-6 (IL-6) and small amounts of granulocyte macrophage colony stimulating factor (GM-CSF) and monocyte colony stimulating factor (M-CSF). Immunocytochemical staining of tumor cells showed strong positivity for IL-6. CONCLUSIONS: These results indicated that persistent secretion of IL-6 promoted thrombogenesis in this patient.
Humans↗
The inhibitory effects of okadaic acid on platelet function.
Okadaic acid (OA), a potent inhibitor of protein phosphatases type 1 and type 2A, inhibited thrombin-induced platelet aggregation (IC50 = 0.8 microM), [14C]serotonin release and increase in intracellular Ca2+ ([Ca2+]i) in the same dose dependence. In the absence of thrombin OA increased the phosphorylation of 50-kDa protein and 20-kDa myosin light chain (MLC20). The 50-kDa protein phosphorylation was accomplished within a shorter time period and at a lower concentration than was the MLC20. OA decreased the thrombin-induced phosphorylation of 47-kDa protein and MLC20, although phosphorylation of MLC20 reincreased at higher concentrations of OA (5-10 microM). Since type 2A phosphatase is more sensitive to OA than type 1, these results suggest that type 2A phosphatases are involved in the regulation of Ca2+ signaling in thrombin-induced platelet activation.
Blood Platelets↗
Natural interferon-alfa for basophilia.
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Basophils↗
[Amplification and inhibition of platelet function by serum lipoproteins].
Low-density lipoprotein (LDL) at a concentration of 100 micrograms/mL, which is near the dissociation constant (Kd) of LDL-binding, had a maximal stimulatory effect on agonist-induced platelet aggregation. Anti-LDL receptor monoclonal antibody (C-7), like native LDL, induces a transient increase in intracellular Ca2+ and a shape change of human platelets. On the other hand, high-density lipoprotein (HDL) inhibited platelet function. ApoE-rich HDL, as well as, apoE.DMPC potently inhibited platelet aggregation in a dose-dependent manner. ApoE.DMPC stimulated the release of cholesterol into the supernatant, suggesting that apoE plays a major role in the inhibitory effect of apoE-rich HDL in platelet function, presumably due to the release of cholesterol from the plasma membrane.
Apolipoproteins E↗
Inhibition of platelet function by high-density lipoprotein from a patient with apolipoprotein E deficiency.
Apolipoprotein E-(apoE-) rich high-density lipoprotein (HDL) of normal subjects showed marked inhibitory effects on platelet aggregation and ATP release as compared with apoE-poor HDL, suggesting that apoE has inhibitory effects on platelet function (Desai et al. J. Lipid Res. 30:831, 1989; Higashihara et al. FEBS Lett. 282:82, 1991). A patient with apoE deficiency showed evidence of decreased platelet aggregability in platelet-rich plasma, but normal aggregability in washed platelets. Both patient's plasma and HDL fraction inhibited platelet aggregation of normal subjects. Patient's HDL reconstituted with recombinant apoE showed further inhibitory effects on platelet function. These results suggest that apoE is a potent, but not unique, inhibitory factor for HDL.
Adenosine Diphosphate↗
Effect of phosphorylation of myosin light chain by myosin light chain kinase and protein kinase C on conformational change and ATPase activities of human platelet myosin.
Human platelet myosin forms 10S and 6S conformations, and its Ca(2+)- and Mg(2+)-ATPase activities are parallel with the transition between 10S and 6S conformation, as judged by the gel filtration, intrinsic fluorescence, and viscosity methods. The 20,000-dalton myosin light chain (LC20) is phosphorylated by both myosin light chain kinase (MLC kinase) and Ca2+, phospholipid-dependent protein kinase (protein kinase C [PKC]). The phosphorylation (1 mol of phosphate/mol of LC20) by MLC kinase shifts the equilibrium toward the 6S conformation, but that by PKC does not. The prephosphorylation of myosin by PKC prevents the effect of phosphorylation by MLC kinase on actin-activated Mg(2+)-ATPase activity, but not the effect on conformational change. Inhibition of actin-activated ATPase activity by PKC is due to a decreased affinity of myosin for actin, and no change in Vmax is observed. These results suggest that sequential phosphorylation of myosin by both kinases plays an important role in the ATPase activities of human platelet myosin.
Actins↗
Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s.
MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.
Adenylate Cyclase Toxin↗
Two-step mobilization of arachidonic acid in platelet activation induced by low concentrations of TP 82, a monoclonal antibody against CD9 antigen.
Arachidonic acid mobilization in platelets activated by low concentrations (less than or equal to 1.6 micrograms/ml) of TP 82, a monoclonal antibody against CD9, appears to consist of two distinct phases. In the first phase, limited arachidonic acid release occurs concomitantly with a shape change induced by TP 82. This appears to be dependent upon phospholipase A2 activation, since it is well preserved in the presence of aspirin, which completely blocked both intracellular Ca2+ elevation and phosphatidic acid formation which would indicate phospholipase C activation. The Na+ Exchange was also found to participate in the first phase of arachidonic acid mobilization, since extracellular Na+ depletion and ethylisopropylamiloride, a specific inhibitor of the Na+/H+ exchanger, effectively blocked this limited mobilization of arachidonic acid. The second, much larger, phase of arachidonic acid mobilization occurs with the beginning of platelet aggregation. A limited amount of thromboxane A2 formed during the first phase of arachidonic acid release plays an important role in induction of the massive arachidonic mobilization in the second phase. Factors, as yet unidentified, also appear to work synergistically with thromboxane A2 to induce the full picture of arachidonic acid mobilization.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
The role of apoE in inhibitory effects of apoE-rich HDL on platelet function.
Apolipoprotein E- (ApoE-) rich high-density lipoprotein (HDL), which was prepared from the bound fraction of normolipemic volunteers on heparin-Sepharose and from a hyperalphalipoproteinemic patient, potently inhibited aggregation of human platelets in a dose-dependent fashion. Dimyristoyl phosphatidylcholine liposome with apoE (apoE.DMPC) also inhibited platelet aggregation, and incubation of washed platelets with apoE.DMPC resulted in the release of cholesterol into the supernatant in a time- and dose-dependent manner. These results suggest that apoE plays a major role in the inhibitory effect of apoE-rich HDL in platelet function, presumably due to the release of cholesterol from the plasma membrane.
Adenosine Triphosphate↗
Immunosuppressive effect of infectious bursal disease virus strains of variable virulence for chickens.
Infection of chicks with attenuated Lp and Sp clones of the RF-1 strain of infectious bursal disease virus was shown to exert no immunosuppressive effect, whereas the parent strain RF-1tc and the original virulent strain RF-1wt were immunosuppressive. One-day-old chicks infected with Lp and Sp clones showed no suppression of immunological response to live Newcastle disease vaccines B1 and TCND, and to bivalent infectious coryza vaccine. On the other hand, infection with RF-1tc or RF-1wt strains was immunosuppressive for these vaccines. The immunosuppressive effect of RF-1tc and RF-1wt strains was more pronounced for infectious coryza vaccine and B1 vaccine than for TCND vaccine. The immunosuppressive effect of RF-1tc and RF-1wt strains was lower when chicks were infected with these strains at the age of 21 days than when they were infected at one day of age.
Animals↗
[Lipid metabolism of platelet membrane].
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Arachidonic Acid↗
[Acute leukemia successfully treated with natural interferon-alpha].
Natural interferon-alpha (IFN-alpha) alone was administered to a 42-year-old man with acute leukemia, whose bone marrow revealed hypocellularity (NCC = 6 X 10(4)/microliters) and a 50% increase in blasts. Initial chemotherapy regimens, including BHAC-DMP or low dose Ara-C were ineffective. One month after starting nIFN-alpha therapy, the blasts in his bone marrow decreased below 3% and peripheral blood cell counts became normal. He has been in remission for at least 7 months.
Acute Disease↗
Effects of various inhibitors on platelet activation induced by TP 82, a CD 9 monoclonal antibody.
TP 82, a monoclonal antibody against CD 9 antigen, induced human platelet activation at concentrations higher than 0.4 microgram/mL in terms of aggregation, release of intracellular granule contents, production of arachidonic acid metabolites, and elevation of the intracellular Ca2+ concentration. The effects of a competitive inhibitor of ADP, acetylsalicylic acid, EGTA, and GRGDSP which blocks fibrinogen binding to IIb/IIIa complex suggested that each of released ADP, thromboxane A2, extracellular Ca2+, and close cell contact acts together to potentiate platelet activation induced by TP 82. While each of these inhibitors severely suppressed platelet activation induced by lower concentrations of the antibody (less than or equal to 0.8 microgram/mL), that induced by higher concentrations (greater than or equal to 3.2 micrograms/mL) was only partially blocked. Intracellular Ca2+ elevation was totally dependent upon the production of thromboxane A2, regardless of the antibody concentrations.
Adenosine Diphosphate↗